sat 1420-infertility- -garibaldi

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Investigation of Infertility – AnInitial Approach

Jason A Hitkari, MD, FRCSCMedical Director, Olive Fertility Centre

VancouverClinical Associate Professor, UBC

Faculty/Presenter Disclosure

• Faculty: Jason Hitkari

• Relationships with commercial interests:– Grants/Research Support: Ferring Canada, Serono

Canada, Merck Canada– Speakers Bureau/Honoraria: UBC, Canadian Fertility and

Andrology Society– Consulting Fees: N/A– Other: Medical Director of Olive Fertility Centre

CFPC CoI Templates: Slide 1

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Disclosure of CommercialSupport

• This program has received financial support from no one.• This program has received in-kind support from no one.

• Potential for conflict(s) of interest:– I have not received any financial benefit from doing this session.


Mitigating Potential Bias

• There is an inherent bias in being a Medical Directorof Olive Fertility Centre and speaking about fertility

• In the pharmaceuticals discussed, I have no directfinancial interest

• In the testing discussed, I have no direct financialinterest


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Objectives

• To review the impact age has on fertility• To discuss the initial work up but with

specific focus on aspects relevant topractice

• To review new options for patients (eggfreezing)

Work Up Of InfertilityFEMALE MALE

Ovarian Reserve Testing – Day 3 FSH and estradiol Semen analysis

Hysterosalpingogram (or hysterosonogram)

TSH and Prolactin

Prenatal screening blood work

Pelvic ultrasound

Luteal phase progesterone

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Concerns on History…

• Patient not cycling regularly• Pelvic infection/surgery• Significant dysmenorrhea• Erectile dysfunction• Genital injury (male)

Average age at first birth

From: Organization for Economic Co-operation andDevelopment (OECD)

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From: Organization for Economic Co-operation and Development(OECD)

Change in the mean age of women at the birthof the first child

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Cumulative Fertility and MaternalAge

Age Group % Conceiving Within 1 Year

20-24 86

25-29 78

30-34 63

35-39 52

Impact of Female Age on Fertility

Canadian Fertility And Andrology Society

Refer/InvestigateAfter Trying

12 mos. 9 mos. 6 mos.

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Abortion Risk by Maternal Age

Maternal age (yrs)15-2425-2930-3435-3940-44>45

Abortion rate9.5%10.0%11.7%17.7%33.8%52.2%

CARTR 2011Pregnancy by Female Age

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PGS Data (2012, based on 4600 embryos)

MATERNAL AGE-RELATED ANEUPLOIDY RATES WHEN ALLCHROMOSOMES

ARE EVALUATED IN DAY 5 HUMAN IVF EMBRYOSB Pettersen1, K Merrion1, J Keller1, G Gemelos1, M Rabinowitz1

Table 1: Day 5 Aneuploid Rates

Maternal Age # of blastomeresTested (# Cycles)

Aneuploid Results

<30 years 16 (3) 31.2% + 11.6 %

30-34 years 250 (35) 35.6% + 3.0%

35-39 years 424 (76) 50.0% + 2.4 %

40+ years 171 (43) 68.4% + 3.5%

OVERALL 861 (157) 49.1% + 1.7 %

NSGC-2011

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Clinical Vignette

“42 year old woman with two childrenconceived with IVF. She then underwenttwo IVF cycles without success and thenunderwent comprehensive chromosome

testing”

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Assessing Ovarian Reserve isCritical

Lower ovarian reserve

Higher aneuploidy rates

Lower chance of conception

Less time

Panic!

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How Do You Assess OvarianReserve?

• Day 3 FSH and estradiol

Problems with FSH

1. Fluctuates from month-to-month2. Is dependent upon day of the month3. Can be falsely alarming4. Can be falsely reassuring (20% of the

time in infertile patients!)*

* Leader et al, Fertil Steril, 2012

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ANTI-MULLERIAN HORMONE ASSAY

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How to incorporate AMH intoyour practice.

• Realize that it is our BEST marker ofovarian reserve

• Consider it in patients who:– Have concerning FSH levels– Patients >40– Everyone struggling with fertility?– Future role in PCOS diagnosis?




TSH and Prolactin


Pelvic ultrasound


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Hysterosalpingogram

• Still our “go to” test to evaluate bothtubes and uterus

• Sonohysterogram is an alternative• Not always accessible




TSH and Prolactin


Pelvic ultrasound


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TSH and Prolactin


Pelvic ultrasound


Pelvic UltrasoundPROS CONS

Will inform you about fibroids No information on fallopian tubes

Will identify ovarian pathology (exendometrioma)

Limited information on intra-cavitybumps (ie polyps)

Limited information on ovarianreserve

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TSH and Prolactin


Pelvic ultrasound


Luteal Phase Progesterone

• >95% of patients with a regular cycle are ovulating• Good for monitoring response to ovulation induction

(ie PCOS)• Good if you are really uncertain if they are ovulating

• Looking at the absolute value is limited so think ofthis result as binary – YES OR NO

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TSH and Prolactin


Pelvic ultrasound


Semen Analysis Tips

• Morphology is of limited value inpredicting pregnancy rates

• Repeat abnormal results• Persistently abnormal in repeat testing –

consider referal

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What Could Be Wrong??

Important to recognize the limitation of our testing.

Unexplained Infertility

Age Permonth/year 1

First year Per month/year 2

< 35 15-20% 60-85% 4%35-39 10-15% 4%40 6% ?> 43 <1% ?

Canadian Fertility And AndrologySociety

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Odds And Ends….EMPIRIC CLOMID

“in couples whose infertility remainsunexplained…empiric treatment with

clomiphene citrate combined withintercourse is no better than expectant

management”

ASRM, Committee Opinion, 2013

Other Fertility Situations

• Same-sex couples• Single women• Egg donation• Gestational

Carriers• PGD• Oocyte Freezing

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Egg Freezing

• Works “relatively” well

Impaired Ovarian Reserve

Egg Freezing

• Consider in patients < 35• Consider discussing with single patients• AMH is a critical part of assessment

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SUMMARY

• Aneuploidy!• We need an accurate assessment of

ovarian reserve in ALL patients– Anti-mullerian Hormone

• Patients with longstanding histories ofunexplained infertility generally needmore intervention

[email protected]

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