Gab Kovacs International Medical Director Monash IVF Hawthorn Victoria Australia

Declared speakers fees from MSD and Bayer being a stakeholder in Monash IVF ISIS FERTILITY ACT

L1 In vitro fertilization and factors affecting success Professor Gab Kovacs AM International Medical Director Monash IVF

Date Footer

Date Footer

Date Footer

How to improve your ART

success rates

bull Based on an ldquoEvidence Based Reviewrdquo

bull 48 Chapters- each written by a leading expert

bull Written in late 2010

bull Published by Cambridge University Press

Possible factors

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

L1 In vitro fertilization and factors affecting success Professor Gab Kovacs AM International Medical Director Monash IVF

Date Footer

Date Footer

Date Footer

How to improve your ART

success rates

bull Based on an ldquoEvidence Based Reviewrdquo

bull 48 Chapters- each written by a leading expert

bull Written in late 2010

bull Published by Cambridge University Press

Possible factors

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Date Footer

Date Footer

Date Footer

How to improve your ART

success rates

bull Based on an ldquoEvidence Based Reviewrdquo

bull 48 Chapters- each written by a leading expert

bull Written in late 2010

bull Published by Cambridge University Press

Possible factors

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Date Footer

Date Footer

How to improve your ART

success rates

bull Based on an ldquoEvidence Based Reviewrdquo

bull 48 Chapters- each written by a leading expert

bull Written in late 2010

bull Published by Cambridge University Press

Possible factors

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Date Footer

How to improve your ART

success rates

bull Based on an ldquoEvidence Based Reviewrdquo

bull 48 Chapters- each written by a leading expert

bull Written in late 2010

bull Published by Cambridge University Press

Possible factors

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

How to improve your ART

success rates

bull Based on an ldquoEvidence Based Reviewrdquo

bull 48 Chapters- each written by a leading expert

bull Written in late 2010

bull Published by Cambridge University Press

Possible factors

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Possible factors

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Patient preparation (1)- Hormonal screening and Ultrasound

bull AMH- ndash predicts ovarian response

ndash Warns of likely OHSS

ndash Can be measured any time in cycle

bull Thyroid screening

bull Pelvic ultrasound ndash Antral follicle count (AFC)

ndash Uterine abnormalities- fibroids polyps senechiae

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected

bull Fibroids- ndash Submucous ndash Definite

ndash Intramural- Maybe

ndash Subserous- no

bull Laparoscopy- not routinely ndash If hydrosalpinges present

bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates

ndash Endometrioma Dermoids

bull May be beneficial to remove

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Patient preparation (3)- Vitamins and other nutrients

bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy

bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Patient Preparation (4) Weight control

bull Thinness and obesity have a negative impact on reproduction

bull Not just for getting pregnant but staying pregnant and having a healthy child

bull Weight control andor reduction will improve chances of success

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Patient preparation (5)-Thrombophilia screening

bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Patient preparation (6)-Immunological Screening

bull Antinuclear factor

bull Antithyroid antibodies

bull Anti gastric parietal cell antibodies

bull Antigliadin transglutaminase

bull Antiovarian antibodies

bull Natural Killer Cells (NKC)

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Patient preparation (7) Immunological Screening NK

Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile

bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)

bull Can be tested in Blood or Endometrium-

ndash What is ldquonormalrdquo

bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells

bull No conclusive evidence for any benefit

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Conclusion Immunological Thrombophilia

bull No good evidence that these factors are significant

bull No definite evidence that treatment of any of these factors improves outcomes

bull (steroids anticoagulants albumin intralipid)

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Patient Preparation (7)- Metformin in PCOS

bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist

protocol

ndash as adjunct to the short antagonist protocol requires further clarification

bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Stimulation Regimens

bull No significant difference between Agonist and Antagonist

bull Marginal benefits for hMG vs rFSH

bull Pretreatment with OC

ndash Benefits exceed disadvantages

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Stimulation regimens- poor responders

bull DHEA-

bull Limited evidence that DHEA may improve oocyte numbers quality

bull LH addback-

bull Maybe some subgroups

bull Growth Hormone

bull Some evidence for benefit RCT in progress

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Rationale for using LH ldquoadd-backrdquo

bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and

then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle

bull With the use of

ndash rFSH

ndash Agonistantagonist protocols levels of LH very low (lt12IUL)

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is

needed for normal healthy follicular development and oocyte maturation

bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits

bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following

ndash women aged ge35 years and

ndash women who are hyporesponsive to FSH

The latter group of women may be further identified by specific genetic

biomarkers that are currently being investigated

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Monitoring

bull optimized by adopting an individualized patient-

centred approach to COH

bull selection of ndash appropriate COH protocol

ndash close monitoring of follicle growth and serum E2 levels

ndash adjustment of gonadotrophin dose to avoid hyper-response

ndash individualized timing of hCG injection

bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates

ndash minimizes the risk of OHSS

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Monitoring

bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndash Assisted hatching

ndash PGD

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Sperm preparation

bull Only use ICSI if indicated

bull Use most viable motile functional spermatozoa- IMSI Feldberg

bull Discontinuous gradient centrifugation or a new electrophoretic approach

bull Select least damaged DNA containing

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Laboratory aspects ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Metabolomics

ndash morphokinetics

ndash Assisted hatching

ndash PGD

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Addition of Co-factors

bull Has the potential to improve the development of zygotes to the blastocyst stage

bull Might mimic the autocrine and paracrine factors

bull Perhaps the use of microfluidic culture systems would be more applicable

bull Much research and controlled studies are required before these co factors can be routinely used

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Embryo Transfer- cleavage or blastocyst

bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later

bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes

bull Day 5 ET the preferred option with increasing move to single embryo transfer

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

Metabolomics-

bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability

bull determine more subtle embryo characteristics

bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

bull Theory the differences between viable and sub-viable

embryos are reflected by metabolism activity

bull Take a small sample of the culture medium where the

embryo has been growing and measure amino acids etc

bull Eg glucose pyruvate amino amino acids

bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)

bull Expected time-frame for commercial availability 1-2 years

Laboratory aspects

ndash Sperm preparation and selection

ndash Culture media and culture of embryos

ndash Extended culture

ndash Embryo selection

bull Metabolomics

bull Morphokinetics

ndashAssisted hatching

ndash PGD

Embryoscope

PRIMO VISION EVO

Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-

t2 and s2 = t4-t3

Meseguer M et al Hum Reprod 2011262658-2671

copy The Author 2011 Published by Oxford University Press on behalf of the European Society of

Human Reproduction and Embryology All rights reserved For Permissions please email

journalspermissionsoupcom

Could time-lapse embryo imaging reduce the need for biopsy and

PGS Swain JE J Assist Reprod Genet 2013 Jul 11

Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy

Embryoscope

PRIMO VISION EVO

Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-

t2 and s2 = t4-t3

Meseguer M et al Hum Reprod 2011262658-2671

copy The Author 2011 Published by Oxford University Press on behalf of the European Society of

Human Reproduction and Embryology All rights reserved For Permissions please email

journalspermissionsoupcom

Could time-lapse embryo imaging reduce the need for biopsy and

PGS Swain JE J Assist Reprod Genet 2013 Jul 11

Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy

PRIMO VISION EVO

Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-

t2 and s2 = t4-t3

Meseguer M et al Hum Reprod 2011262658-2671

copy The Author 2011 Published by Oxford University Press on behalf of the European Society of

Human Reproduction and Embryology All rights reserved For Permissions please email

journalspermissionsoupcom

Could time-lapse embryo imaging reduce the need for biopsy and

PGS Swain JE J Assist Reprod Genet 2013 Jul 11

Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy

Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-

t2 and s2 = t4-t3

Meseguer M et al Hum Reprod 2011262658-2671

copy The Author 2011 Published by Oxford University Press on behalf of the European Society of

Human Reproduction and Embryology All rights reserved For Permissions please email

journalspermissionsoupcom

Could time-lapse embryo imaging reduce the need for biopsy and

PGS Swain JE J Assist Reprod Genet 2013 Jul 11

Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy

Could time-lapse embryo imaging reduce the need for biopsy and

PGS Swain JE J Assist Reprod Genet 2013 Jul 11

Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy

Possible factors

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Embryo transfer

bull Dummy transfer beneficial

bull Position-mid fundus

bull Ultrasound monitoring

bull Catheter soft but malleable

bull Bed rest- no help

bull Intercourse may help

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Ancillary treatments

bull Heparin Aspirin

bull Hormones ndash Estrogen

ndash Progestogens

ndash DHEA

bull Immunotherapy ndash Steroids

ndash IVIG Humira

bull Adjuvants ndash Chinese herbs

ndash Sidenafil

ndash Hyperbaric oxygen

ndash Acupuncture

Immunological Thrombophilia

bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure

Hormone Supplements

bull On the basis of the currently best available evidence

bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles

ndash excluding antagonist trigger

Prednisolone

bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle

bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial

Challenges 2011

bull Poor responders

bull Implantation failure ndash Embryo quality

bull Genetic

bull Developmental

ndash Endometrial receptivity

bull Hormonal

bull Immunological

bull Haematological

Embryo transfer

bull Dummy transfer beneficial

bull Position-mid fundus

bull Ultrasound monitoring

bull Catheter soft but malleable

bull Bed rest- no help

bull Intercourse may help

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Ancillary treatments

bull Heparin Aspirin

bull Hormones ndash Estrogen

ndash Progestogens

ndash DHEA

bull Immunotherapy ndash Steroids

ndash IVIG Humira

bull Adjuvants ndash Chinese herbs

ndash Sidenafil

ndash Hyperbaric oxygen

ndash Acupuncture

Immunological Thrombophilia

bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure

Hormone Supplements

bull On the basis of the currently best available evidence

bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles

ndash excluding antagonist trigger

Prednisolone

bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle

bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial

Challenges 2011

bull Poor responders

bull Implantation failure ndash Embryo quality

bull Genetic

bull Developmental

ndash Endometrial receptivity

bull Hormonal

bull Immunological

bull Haematological

bull Patient preparation

bull Stimulation Regimens

bull Monitoring

bull Laboratory aspects

bull Embryo transfer

bull Ancillary treatment

Ancillary treatments

bull Heparin Aspirin

bull Hormones ndash Estrogen

ndash Progestogens

ndash DHEA

bull Immunotherapy ndash Steroids

ndash IVIG Humira

bull Adjuvants ndash Chinese herbs

ndash Sidenafil

ndash Hyperbaric oxygen

ndash Acupuncture

Immunological Thrombophilia

bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure

Hormone Supplements

bull On the basis of the currently best available evidence

bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles

ndash excluding antagonist trigger

Prednisolone

bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle

bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial

Challenges 2011

bull Poor responders

bull Implantation failure ndash Embryo quality

bull Genetic

bull Developmental

ndash Endometrial receptivity

bull Hormonal

bull Immunological

bull Haematological

Ancillary treatments

bull Heparin Aspirin

bull Hormones ndash Estrogen

ndash Progestogens

ndash DHEA

bull Immunotherapy ndash Steroids

ndash IVIG Humira

bull Adjuvants ndash Chinese herbs

ndash Sidenafil

ndash Hyperbaric oxygen

ndash Acupuncture

Immunological Thrombophilia

bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure

Hormone Supplements

bull On the basis of the currently best available evidence

bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles

ndash excluding antagonist trigger

Prednisolone

bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle

bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial

Challenges 2011

bull Poor responders

bull Implantation failure ndash Embryo quality

bull Genetic

bull Developmental

ndash Endometrial receptivity

bull Hormonal

bull Immunological

bull Haematological

Immunological Thrombophilia

bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure

Hormone Supplements

bull On the basis of the currently best available evidence

bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles

ndash excluding antagonist trigger

Prednisolone

bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle

bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial

Challenges 2011

bull Poor responders

bull Implantation failure ndash Embryo quality

bull Genetic

bull Developmental

ndash Endometrial receptivity

bull Hormonal

bull Immunological

bull Haematological

Hormone Supplements

bull On the basis of the currently best available evidence

bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles

ndash excluding antagonist trigger

Prednisolone

bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle

bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial

Challenges 2011

bull Poor responders

bull Implantation failure ndash Embryo quality

bull Genetic

bull Developmental

ndash Endometrial receptivity

bull Hormonal

bull Immunological

bull Haematological

Prednisolone

bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle

bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial

Challenges 2011

bull Poor responders

bull Implantation failure ndash Embryo quality

bull Genetic

bull Developmental

ndash Endometrial receptivity

bull Hormonal

bull Immunological

bull Haematological

Challenges 2011

bull Poor responders

bull Implantation failure ndash Embryo quality

bull Genetic

bull Developmental

ndash Endometrial receptivity

bull Hormonal

bull Immunological

bull Haematological