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Investigation of Infertility – An
Initial Approach
Jason A Hitkari, MD, FRCSC
Medical Director, Olive Fertility Centre
Vancouver
Clinical 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 Commercial
Support
• 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.
CFPC CoI Templates: Slide 2
Mitigating Potential Bias
• There is an inherent bias in being a Medical Director
of Olive Fertility Centre and speaking about fertility
• In the pharmaceuticals discussed, I have no direct
financial interest
• In the testing discussed, I have no direct financial
interest
CFPC CoI Templates: Slide 3

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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 to
practice
• To review new options for patients (egg
freezing)
Work Up Of Infertility
FEMALE 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 and
Development (OECD)

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From: Organization for Economic Co-operation and Development
(OECD)
Change in the mean age of women at the birth
of the first child

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Cumulative Fertility and Maternal
Age
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/Investigate
After Trying
12 mos. 9 mos. 6 mos.

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Abortion Risk by Maternal Age
Maternal age (yrs)
15-24
25-29
30-34
35-39
40-44
>45
Abortion rate
9.5%
10.0%
11.7%
17.7%
33.8%
52.2%
CARTR 2011
Pregnancy by Female Age

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PGS Data (2012, based on 4600 embryos)
MATERNAL AGE-RELATED ANEUPLOIDY RATES WHEN ALL
CHROMOSOMES
ARE EVALUATED IN DAY 5 HUMAN IVF EMBRYOS
B Pettersen1, K Merrion1, J Keller1, G Gemelos1, M Rabinowitz1
Table 1: Day 5 Aneuploid Rates
Maternal Age # of blastomeres
Tested (# 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 children
conceived with IVF. She then underwent
two IVF cycles without success and then
underwent comprehensive chromosome
testing”

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Assessing Ovarian Reserve is
Critical
Lower ovarian reserve
Higher aneuploidy rates
Lower chance of conception
Less time
Panic!

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How Do You Assess Ovarian
Reserve?
• Day 3 FSH and estradiol
Problems with FSH
1. Fluctuates from month-to-month
2. Is dependent upon day of the month
3. Can be falsely alarming
4. 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 into
your practice.
• Realize that it is our BEST marker of
ovarian reserve
• Consider it in patients who:
– Have concerning FSH levels
– Patients >40
– Everyone struggling with fertility?
– Future role in PCOS diagnosis?
Work Up Of Infertility
FEMALE 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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Hysterosalpingogram
• Still our “go to” test to evaluate both
tubes and uterus
• Sonohysterogram is an alternative
• Not always accessible
Work Up Of Infertility
FEMALE 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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Work Up Of Infertility
FEMALE 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
Pelvic Ultrasound
PROS CONS
Will inform you about fibroids No information on fallopian tubes
Will identify ovarian pathology (ex
endometrioma)
Limited information on intra-cavity
bumps (ie polyps)
Limited information on ovarian
reserve

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Work Up Of Infertility
FEMALE 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
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 of
this result as binary – YES OR NO

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Work Up Of Infertility
FEMALE 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
Semen Analysis Tips
• Morphology is of limited value in
predicting 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 Per
month/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 Andrology
Society

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Odds And Ends….
EMPIRIC CLOMID
“in couples whose infertility remains
unexplained…empiric treatment with
clomiphene citrate combined with
intercourse 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 of
unexplained infertility generally need
more intervention
jhitkari@olivefertility.com