Infertility
Edward Illions, M.D.
Associate Professor
Division of Reproductive Endocrinology & Infertility
Department of Obstetrics, Gynecology & Women’s
Health
Albert Einstein College of Medicine
4/9/2015
Definition
• Failure to conceive after 12 months of
regular coital activity in the absence of
contraception.
• Classification :
– Primary
– Secondary
4/9/2015
Epidemiology of Infertility
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4/9/2015
Affects 10-15% of couples of reproductive age.
Terminology
• Fecundability: Probability of achieving
pregnancy within one menstrual cycleapproximately 25%
• Fecundity: The ability to achieve a live
birth within one menstrual cycle
4/9/2015
Natural Fertility
Time Required for Conception
Time of Exposure
% Pregnant
1 month
3 months
6 months
1 year
2 years
30%
57%
72%
85%
93%
Guttmacher AF, Factors affecting normal expectancy of conception, JAMA 161:855, 1956.
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Female Reproductive Anatomy
4/9/2015
Integral Components to
Fertility
• Gamete availability
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– Production
– Deposition
Sperm transport
Cervical hospitality
Patency of fallopian tubes
Fertilization
Normal embryonic development and cleavage
Endometrial receptivity
Implantation
Embryonic growth and development
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Integral Components to
Fertility
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Etiology of Infertility
• Male factors
• Female factor/s
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Tubal factor
Ovulatory disturbances
Unexplained infertility
Miscellaneous
– Uterine factor
– Cervical factor
4/9/2015
35%
55%
40%
40%
10%
10%
Male Infertility- etiology
4/9/2015
Male Infertility-diagnostic
tests
• Semen Analysis-WHO criteria
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Volume
Viscosity
Color
Sperm count
Motility
Morphology
2-5ml
viscous/liquefies in 30 min.
opalescent
20 million/ml
50% motile (≥20µm/sec)
30% normal (>14% Kruger)
– Head/neck piece/tail
– WBC’s
4/9/2015
< 1 million/ml
Male Infertility-Terminology
• Oligospermia
• Asthenospermia
• Teratospermia
<20 Million per ml
<50% motile sperm
>70% abnormal
sperm
• Oligo-astheno-teratospermia
• Azoospermia
No sperm seen
• Obstructive
• Non-Obstructive
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Cystic Fibrosis/Infections
Kleinfelter’s Syndrome (47 XXY)
Sertoli Cell Only Syndrome
Male Infertility-diagnostic
tests
• Karyotype
– Klinefelter syndrome (1:500 males)
• Y microdeletion
– AZFa, AZFb, AZFc (= DAZ)
• Cystic Fibrosis
– Congenital bilateral absence of vas
deferens (1-2% infertile males)
– 5T allelle
4/9/2015
Male Infertility-diagnostic
tests
• NOT utilized anymore (really)
– Sperm Penetration Assay
– Human Zona Binding Assay/Hemizona Assay
– Hypo-osmotic Swelling Test
• Hypo-osmotic sodium citrate and fructose
solution
– Sperm Antibodies
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Female Infertility- etiology
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Female Infertility
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Female Infertility- ovarian
reserve testing
Cycle Day 3 FSH / Estradiol (E2)
FSH > 10 IU/L associated with
poor pregnancy rates with IVF
E2 > 80 pg/mL
Clomiphene Challenge Test (CCCT)
FSH > 10 IU/L on CD3 or CD10
Ultrasound ovarian volume
4/9/2015
Female Infertility- ovulation testing
• Average menstrual cycle – approximately 28
days (range is 21-35 days).
• Ovulation occurs approximately the 14th day
of a 28 day cycle.
• Ovulatory disorders
– Oligo-ovulation and Oligomenorrhea
– Anovulation and amenorrhea
• Missed periods for 6 months OR for a 3 cycles
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Female Infertility- ovulation testing
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Menstrual history (cycle length)
Symptoms consistent with ovulation
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Mid-luteal serum progesterone ≥ 3ng/mL
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BBT (basal body temperature)
Endometrial biopsy in luteal phase
Urinary LH surge monitoring
Serial ultrasound follicular tracking
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Mid cycle mucus changes
Pre-menstrual molimina
Mittleschmertz
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< 10 ng/mL associated lower pregnancy rate
4/9/2015
Basal Body Temperature (BBT)
Chart
4/9/2015
Pulsatility of GnRH secretion, the frequency
as well as amplitude, are critical for effects
on pituitary gonadotrophs
Frequency and
amplitude of GnRH
pulses change during
the course of menstrual
cycle.
FP: 1 in 60-90min
LP: 1 in 2-6 hours
4/9/2015
Ovulatory disorders- PCOS
– 5-10% reproductive aged women
– Oligo-anovulation and Hyperandrogenism.
– Features of hyperandrogenism
– Hirsuitism
– Acne
– Android obesity
– Metabolic profile
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Insulin resistance
Obesity
Metabolic syndrome – Hyperlipidemia, hypertension
Increased risk for type II diabetes mellitus
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Ovulatory DisordersHyperprolactinemia
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Prolactin (normal <20 ng/ml)
– Diurnal variation-highest during sleep
– Increase seen with:
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Food intake
Sleep
Stress
Coitus/pelvic exam
Breast stimulation
» Thoracic lesions/dermatological disorders
Iatrogenic
– Psychotropic medications
– Dopamine antagonists, phenothiazines, etc
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Hypothyroidism
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Pituitary adenomas
– Microadenomas
– Macroadenomas
4/9/2015
– Secondary to TRH
< 10mm
>10mm
Ovulatory Disorders-
Hypothalamic amenorrhea
– Anorexia nervosa
– Excessive exercise
• Ballet dancers
• Competitive athletes
– Stress
– Chronic illness
– Exogenous opiods
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Female Infertility- cervical
hospitality testing
• Post coital test (PCT)
– 8 - 12 hrs post coitus
– Mid follicular cervical mucus
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Clarity
Spinbarkeit (stretchability) 8-10 cm
Ferning
Sperm - > 10 motile sperm per HPF
– Shaking phenomenon-antisperm antibodies
4/9/2015
Post-coital test
4/9/2015
Post-coital test
NOT DONE ANYMORE
(rare exceptions)
4/9/2015
Female Infertility- tubal factor
– Pelvic Inflammatory Disease (PID)
– Pathogens-Gonorrhea, Chlamydia, Anaerobes
– Pelvic adhesive disease
– Endometriosis
– Post-surgical adhesions
– Ruptured appendix
– Pelvic Tuberculosis
– Salpingitis Isthimica Nodosa (SIN)
– In-Utero-exposure to DES
(diethylstylbesterol)
4/9/2015
Female Infertility- tubal factor testing:
Hysterosalpingogram (HSG)
– Early follicular phase of cycle
• Rule out STD’s
– Advantages:
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Outpatient procedure
Reveals contour of the uterine cavity and tubal patency.
May provide information regarding peritubal disease.
May be therapeutic-especially using oil based media.
– Disadvantages:
• Risk of PID-1%
• False positive –air bubbles/tubal spasm
• Discomfort
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Assessment of tubal patency
Hysterosalpingogram (HSG)
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Hysterosalpingogram (HSG)
4/9/2015
Evaluating uterine cavity by HSG
Filling defects
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Female Infertility-
endometrial receptivity testing
• Luteal Phase Endometrial Biopsy
– Luteal phase defect
• >2 day lag on >1 biopsy
– Chronic endometritis
• presence of plasma cells in the endometrium
– Endometrial function test (EFT)
(NOT REALLY DONE ANYMORE, with specific exceptions)
• Anatomical abnormalities evaluation
(Fibroids/polyps/adhesions-Asherman’s Syndrome)
= HSG, HSN, Hysteroscopy
4/9/2015
Sonohysterogram (HSN)
4/9/2015
Sonohysterogram (HSN)
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Female Infertility- fertilization and
embryo development testing
• With treatment by IVF (in vitro
fertilization) and/or ICSI
(intracytoplasmic sperm injection)
4/9/2015
Female Infertility- some
additional tests…
• Thrombophilia screening
– Family or personal history of thrombosis
– Recurrent pregnancy loss
• Screening for medical disorders:
– Diabetes, renal disease,anemia
– STD’s
4/9/2015
All tests negative???
Unexplained Infertility
• No obvious etiology unmasked by
conventional assessment
• 70% of patients with unexplained
infertility will conceive over 2 years
• Fecundity is reduced to 1-3% in the
remainder
• Still treatment options
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Evaluation of the Infertile Couple
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Female
Menstrual
Dietary
Medical
Gyn/Ob
Sexual
Family
4/9/2015
History
Male
- Medical
- Sexual
- Occupational
- Family
Physical exam
Female
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Height
Sexual Development
Breasts/Galactorrhea
Thyroid
Hirsutism
Acanthosis nigricans
Anosmia
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Male
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Height
Sexual Development
Breasts
Genitalia
Thyroid
Anosmia
Investigations
1. Semen analysis
2. Ovulatory status
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Menstrual history
Symptoms consistent with ovulation
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Luteal serum progesterone ≥ 6ng/ml
BBT (basal body temperature)
Endometrial biopsy in luteal phase
Urinary LH surge monitoring
Serial ultrasound follicular tracking
4/9/2015
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Mid cycle mucus changes
Pre-menstrual molimina
Mittleschmertz
Assessment of Tubal Patency by
Laparoscopy
– Advantages
• Direct exam of pelvic structures and tubal
patency
• Other diagnoses-endometriosis/pelvic
adhesions
• Opportunity for correction of anatomical
abnormalities
– Lysis of adhesions/endometriosis ablation or
resection
– Disavantages:
• Risks of surgery
• Uterine cavity not assessed
4/9/2015
Mid cycle cervical mucus smear
demonstrates a “ferning” pattern
on drying
4/9/2015
Management…….
Male factor
– Intrauterine insemination (IUI)
– Intracytoplasmic sperm injection (ICSI)
– Donor sperm
4/9/2015
Management…….
Ovulation disorders
• Hyperprolactinemia
– Medical therapy
– Treat hypothyroidism
• PCOS
– Ovulation induction
• Medical
– Clomid
– Gonadotrophins
• Surgical
– Ovarian drilling
– Wedge resection
• Insulin sensitizers
– Metformin
– Weight loss and life-style modifications
4/9/2015
Management…….
• Tubal disease:
– Surgical- tuboplasty; lysis of adhesions
– IVF (in-vitro fertilization)
• Uterine factors:
– Correct anatomical distortions
– Treatment of LPD with progesterone
supplementation, clomiphene, gonadotropins
• IVF may be diagnostic for some couples!
• IVF with donor eggs
4/9/2015
Additional tests for infertile
couples anticipating fertility
treatment
• Screening tests offered to high risk
populations:
– Cystic Fibrosis
– Ashkenazi Jews
• Bloom syndrome, Canavan disease, Gaucher
disease, Niemann-Pick disease, Tay-Sachs
disease, Fanconi anemia, Familial dysautonomia,
Cystic fibrosis, Mucolipidosis Type IV
– Hemoglobin electrophoresis
4/9/2015
THANK YOU!
4/9/2015