ivm/ivf in pcos (pco-like ovaries)

The Women’s Clinic

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IVM/IVF in PCOS (PCO-Like Ovaries)

Milton Ka Hong Leong MDCM DSc(McGill)

FRCS(C) FRCOG FACOG FHKCOGDirector, IVF Centre HK Sanatorium & Hospitals

Specialist in Reproductive MedicineAdjunct Professor, Department Obstetrics & Gynecology

McGill University,Montreal, CANADA


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PCOS

• Commonest endocrine disorder in women• May be 80% anovulatory infertility?• Ovulation induction required• Most are clomiphene responsive• Cumulative pregnancy rates lower than non-PCOS patients

• Balen 2002 2004


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PCOS

• Ovulation Induction:

• Low dose - reduced response• Higher dose - over-response• Leading to multiple pregnancies• Higher risk OHSS


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PCOS and IVF

• IVF is an effective, may be preferred choice of therapy because of the problems associated with ovulation induction

• Significantly more oocytes• Lower fertilization rate

• Dor et al, Homburg et al Kodama et al


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PCOS and IVF

• Pregnancies were comparable to non-PCOS patients• Increased miscarriage rate• FSH requirement leads to under or over response• Higher cancellation rate• Much higher chance of OHSS


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OHSS in IVF• Prevalent Factors:

• Age -younger• BMI - thinner• PCOS• PCO-like ovaries >10 follicles• Ovarian volume > 10 cu mm• LH/FSH > 2• Hyperandrogenism


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OHSS in IVF

• Preventive Measures

• Identify Risks - Low(er) FSH? No Help• Use GnRh-ant - ? 50%• Coasting E > 3000pg/ml but preg rate oocyte quality• Cancel cycle - patient reluctant• No hCG - use GnRH-a• No transfer - cryo-preservation• Albumin, hydroxyaethyl starch solution• High Dose Progesterone, no Luteal hCG


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PCOS, OHSS and IVF

• Risk up 5-30 fold (6-30%)• Estradiol >3000pg/ml• # Follicles >20


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OHSS in PCOS Undergoing IVF

• Preventive Measures:

• Pre-treat with laparoscopic drilling• Use GnRH-ant then GnRH-a to trigger• Metformin (as short as 28 days)• No Transfer, Cryopreservation• Early Aspiration of Follicles - 2 operations

• Conversion to IVM• IVM with and/or without stimulation


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Role of Metformin in PCOS Patients

In Clomiphene responsive pts, no difference in LBRIn Clomiphene resistant patients:Higher LBR when metformin added to Clomiphene to Laparoscopic drilling in IVF casesIn IVF patients add metformin reduces OHSS


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Progress in IVM Edwards 1965 : 1st in vitro matured oocyte

Veeck 1983 : 1st IVM pregnancy from an ovum derived from a stimulated cycle

Cha et al. 1991 : the first pregnancy from in-vitro matured oocytes derived from a caesarean section donor

Trounson et al. 1994: IVM in women with PCOS

improvements in culture condition and transfer techniques have demonstrated that IVM is an effective treatment for women with PCO or PCOS.

In general, clinical pregnancy and implantation rates for infertile women with PCO or PCOS have reached approximately 30-35% and 10-15%, respectively, (Chian et al., 2004).


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IVM/IVF in PCOS


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Advantages of IVM

• No/minimal stimulation: less OHSS less long term effect safety factor – cancer patients• Flexible start time, no preparation• Cancer patients no theoretical and actual risk (esp br ca)

can treat anytime


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IVM/IVF

• Best candidates • under 35• PCOS or PCO-like ovaries

To stimulate or not to stimulate, that is the question………………


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IVM/IVF vs IVF for PCOS

Child TJ, et al,2002


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Over responders

• Risk of OHSS• Treatment options

a) Cancel cycleb) Coastingc) No embryo transferd) Convert to IVM


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Over responders

Prolonged Coasting• Aim: To prevent hyperstimulation• Practice: Coast till E2 ≤ 3000 pg/mL• Sher, 1995 Start when 30% follices > 15

mm• Nilsson, 1999 When 3 follicles > 17mm


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IVM stimulation


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IVM/IVF in PCOS/PCO-Like Pts 2007

PCOS PCO-Like

# 8 10

Age 26-35(32.3)

29-38(33.4)

# Eggs 178(22.2)

126(12.6)

% matured/Fert 73%67.4%

76%78.2%

# ET 21(2.1)

14(1.75)

Pregnancies 3(37.5%)

5(50%)

% Implant 4/21(19%)

7/14(50%)


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FSH Priming or Not?


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Du AL,et al ,2005

Biological data and birth reports after in vitro maturation from unstimulated cycles in polycystic ovarian syndrome patients


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Natural cycle IVM results (McGill University)


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McGill Seoul Maria Sun Yat-sen HKSH Total

No of cycles 35 128 13 17 193Mean age 33.1±3.4 29 35.1±4.4Oocytes collected 284 1043 207 166 1700Maturation rates(%) 226 (80%) 733(70.3%) 104(50.3%) 110(66.3%) 1173 (69%)Fertilizaiton rates(%) 188 (83%) 580(79.1%) 87(83.8%) 89(80.9%) 944 (80.5%)Embryo transferred 2.5±8.6 4.0±1.6 4.6±2.5 2.3±1.0 No of ET cycles 35 123 13 17 188Clinical PR(%) 14(40%) 36(29.3%) 2(19.5%) 4(23.5%) 56 (29.8%)

Natural cycle IVM (summary)


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FSH priming for obtaining more oocytes or enhancing oocyte maturation(Mikkelsen et al., 1999; 2001; Suikkari et al., 2000).

However, the results were conflicting


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IVM stimulation


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Table . Number of oocytes obtained for in vitro maturation and rates of maturation, fertilization, cleavage and pregnancy in women inunstimulated and FSH-primed groups

Mikkelsen AL et al,2001


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NO FSH + FSH P

No of cycles 13 30 OPU day folic(mm) 6.4 ±0.7 8.1 ±1.9 <0.001 Oocytes collected 15.9 ±7.3 18.5 ±6.7 >0.05No. of MTII 8.0 ± 3.9 11.1 ±5.2 0.065No. of Fertilized 6.7 ±3.5 8.3 ±3.6 >0.05Embryo transferred 4.6±2.5 4.6 ±2.0 >0.05 Clinical PR(%) 2(19.5%) 11(36.7%) 0.132

In-vitro maturation outcomes between the FSH-primed and no FSH treatment groups

Sun Yat-sen University 2006


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Clinical variables and outcome of FSH-primed (Group A) and non-FSH-primed (Group B)

(PCOS)

Lin YH et al 2003


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IVF CENTRE (HKSH) data 2004-2005

FSH primed Non-stimulated P

No. of cycles 21 17

age 35.0± 4.0 35.1 ±4.4 0.93

E2/HCG day(pg/ml) 760.8 ± 816.2 130.3 ± 129.5 0.06

No. of oocytes 225 166

MTII ooyctes(%) 157 (69.8%) 110 (66.3%) 0.46

Fertilized (%) 129 (82.2%) 89 (80.9%) 0.79

No. of embryos transferred/ET

2.6 ± 0.9 2.3 ± 1.0 0.32

PR 29.8%(6/21) 23.5%(4/17) 0.73

IR 12.7% 12.8% 0.99


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Conclusions• PCOS poses as a problem in ovulation induction• IVF may be treatment of choice for PCOS, but OHSS has

to be controlled• IVM/IVF can circumvent problems with ovulation

induction• Stimulated or not, it is safe, effective• More studies have to be done, especially in follow-up of

children

IVM/IVF SHOULD BE TREATMENT OF CHOICE


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HCG priming or not ?


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How to improve pregnancy rate in IVM

Dr Milton Ka Hong Leong MDCM DSC (McGill)FRCS(C) FRCOG FACOG FHKCOGSpecialist in Reproductive MedicineAdjunct Professor,Department of Obstetrics & GynecologyMcGill University


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The advantages of IVM


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How to improve the pregnancy rate in IVM?


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•The percentage of oocytes achieving maturation at 48 h was significantly higher in the HCG-primed group than in the non-HCG-primed group.

•Ooycte maturation was hastened in the HCG-primed group.

•There were no significant differences in the rates of ooycte fertilization and cleavage in these two groups.

Chian RC,et al. 2000


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Stimulation protocolBest candidates: women under 35 years of age who

have polycystic-like ovaries

Stimulate or not

With or without HCG priming


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http://humrep.oxfordjournals.org/content/vol15/issue1/images/large/h013103.jpeg


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http://humrep.oxfordjournals.org/content/vol15/issue1/images/large/h013104.jpeg


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Is ICSI essential for IVM?


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Reports of insemination of human in vitro-matured oocytes are scarce.

In the study by Barnes et al. (1996), 43% of mature oocytes from normal ovaries and 26% of in vitro matured oocytes from PCOS women fertilized after insemination.

The reason for poor fertilization rates after standard insemination has been thought to depend on altered characteristics of zona pellucida as a result of the longer culture time before insemination.


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Comparison of outcomes between IVM-IVF and IVM-ICSI in all patients without hormonal priming

Viveca Hum Reprod 2005


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Comparison of outcomes between IVM-IVF and IVM-ICSI in women with presumed ovulatory, regular cycles

Viveca Hum Reprod 2005


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Ooycte-secreted factors enhance oocyte developmental

competence during IVM


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Hussein TS,et al.2006


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Selection Method


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Natural IVF with IVM(Seoul Maria)

Group1: Succeed to collect oocytes from Leading FollicleGroup2: Failed to collect ooyctes from Leading Follicle


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Distribution of Patients according to LF size at HCG injection (N=128)


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Proportion of OPU from a leading follicle in groups classified by the size of follicles at HCG injection (N=128)


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Comparison of Outcomes in IVF/M, IVM and COH


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REGISTRY • We have already set up a registry to collectively gather

information so that we can prove natural cycle or minimally stimulated cycle IVF with or without IVM can be an acceptable alternate, or even the preferred method.

• We would like to invite anyone and everyone to join in so we can reach a significant number faster, for patients’ sake

• A registry will speak louder than rhetoric• Register through: http//www.ivf.com.hk, or c/o Dr

Milton Leong, [email protected] until we get our specific website up


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IVM Registry• ART center• Patient's IVF#• Wife age• Husband age• Indication (pcos=1,cancer=2,tubal=3,endometriosis=4,unexplained=5, male factor=6,others=7)• Gn used or not (1= natural cycle,2= Gn used)• HCG used or not (1=used,0=no used)• No. of ooyctes collected• No. of Matured• No. of fertilized• No. of cleaved• ET day( D2/D3/D4/D5)• No. of embryos transferred• Pregnancy (clinical PR =1 )• Multiple pregnancy (2/3/4)• Abortion %• Pregnancy outcome (if known)


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REGISTRY

• Register through: http://www.ivf.com.hkor email [email protected]

• At least get in touch• Once our website is launched you will be contacted• Then join us for this worthwhile project


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Registry’s Current Member Groups

• Milton Leong, IVF Centre, Hong Kong• Yoshiharu Morrimoto, Namba IVF, Osaka, Japan• J-H Lim, Maria Fertility Hospital, Seoul and Beijing• Ri-Cheng/SL Tan, McGill Centre for Reproductive Medicine,

Montreal, Canada• XY Liang, Suen Yat-sen University, Guangzhou, China• JY Liu, Nanjing University, China• YY Cao, University of Anhui, China• JK Chen, Tsingtao IVF, China

Everyone’s Welcome to Join!Thank you.


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We are friends let’s join hands

Our goal is to provide the safest cost-effective treatment to our patients. Above all this should be provided with the least stress - physically, mentally and financially.

Thank you for listening.

ivm/ivf in pcos (pco-like ovaries)

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