Infertility

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Infertility

• Staci E. Pollack, M.D.
• Assistant Professor
• Division of Reproductive Endocrinology
  Infertility
• Department of Obstetrics, Gynecology Womens
  Health
• Albert Einstein College of Medicine

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Definition

• Failure to conceive after 12 months of regular
  coital activity in the absence of contraception.
• Classification
• Primary
• Secondary

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Epidemiology of Infertility

• Affects 10-15 of couples of reproductive age.

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Terminology

• Fecundability Probability of achieving pregnancy
  within one menstrual cycle-approximately 25
• Fecundity The ability to achieve a live birth
  within one menstrual cycle

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Natural Fertility

• Time Required for Conception
• Time of Exposure Pregnant
• 1 month 30
• 3 months 57
• 6 months 72
• 1 year 85
• 2 years 93
• Guttmacher AF, Factors affecting normal
  expectancy of conception, JAMA 161855, 1956.

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Female Reproductive Anatomy
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Integral Components to Fertility

• Gamete availability
• 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 35
• Female factor/s 55
• Tubal factor 40
• Ovulatory disturbances 40
• Unexplained infertility 10
• Miscellaneous 10
• Uterine factor
• Cervical factor

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Male Infertility- etiology
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Male Infertility-diagnostic tests

• Semen Analysis-WHO criteria
• Volume 2-5ml
• Viscosity viscous/liquefies in 30 min.
• Color opalescent
• Sperm count 20 million/ml
• Motility 50 motile (20µm/sec)
• Morphology 30 normal (gt14 Kruger)
• Head/neck piece/tail
• WBCs lt 1 million/ml

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Male Infertility-Terminology

• Oligospermia lt20 Million per ml
• Asthenospermia lt50 motile sperm
• Teratospermia gt70 abnormal sperm
• Oligo-astheno-teratospermia
• Azoospermia No sperm seen
• Obstructive Cystic Fibrosis/Infections
• Non-Obstructive Kleinfelters Syndrome (47 XXY)
• Sertoli Cell Only Syndrome

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Male Infertility-diagnostic tests

• Karyotype
• Klinefelter syndrome (1500 males)
• Y microdeletion
• AZFa, AZFb, AZFc ( DAZ)
• Cystic Fibrosis
• Congenital bilateral absence of vas deferens
  (1-2 infertile males)
• 5T allelle

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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 gt 10 IU/L associated with poor pregnancy
  rates with IVF
• E2 gt 80 pg/mL
• Clomiphene Challenge Test (CCCT)
• FSH gt 10 IU/L on CD3 or CD10
• Ultrasound ovarian volume

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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

• Menstrual history (cycle length)
• Symptoms consistent with ovulation
• Mid cycle mucus changes
• Pre-menstrual molimina
• Mittleschmertz
• Mid-luteal serum progesterone 3ng/mL
• lt 10 ng/mL associated lower pregnancy rate
• BBT (basal body temperature)
• Endometrial biopsy in luteal phase
• Urinary LH surge monitoring
• Serial ultrasound follicular tracking

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Basal Body Temperature (BBT) Chart
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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
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Ovulatory disorders- PCOS

• 5-10 reproductive aged women
• Oligo-anovulation and Hyperandrogenism.
• Features of hyperandrogenism
• Hirsuitism
• Acne
• Android obesity
• Metabolic profile
• Insulin resistance
• Obesity
• Metabolic syndrome Hyperlipidemia, hypertension
• Increased risk for type II diabetes mellitus

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Ovulatory Disorders- Hyperprolactinemia

• Prolactin (normal lt20 ng/ml)
• Diurnal variation-highest during sleep
• Increase seen with
• Food intake
• Sleep
• Stress
• Coitus/pelvic exam
• Breast stimulation
• Thoracic lesions/dermatological disorders
• Iatrogenic
• Psychotropic medications
• Dopamine antagonists, phenothiazines, etc
• Hypothyroidism
• Secondary to TRH
• Pituitary adenomas
• Microadenomas lt 10mm
• Macroadenomas gt10mm

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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)
• 2-8 hrs post coitus
• Mid follicular cervical mucus
• Clarity
• Spinbarkeit (stretchability) 8-10 cm
• Ferning
• Sperm - gt 10 motile sperm per HPF
• Shaking phenomenon-antisperm antibodies

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Post-coital test
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Post-coital test
NOT DONE ANYMORE (rare exceptions)
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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)

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Female Infertility- tubal factor testing
Hysterosalpingogram (HSG)

• Early follicular phase of cycle
• Rule out STDs
• Advantages
• 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)
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Evaluating uterine cavity by HSG
Filling defects
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Female Infertility- endometrial receptivity
testing

• Luteal Phase Endometrial Biopsy
• Luteal phase defect
• gt2 day lag on gt1 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-Ashermans Syndrome)
• HSG, HSN, Hysteroscopy

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Sonohysterogram (HSN)
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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)

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Female Infertility- some additional tests

• Thrombophilia screening
• Family or personal history of thrombosis
• Recurrent pregnancy loss
• Screening for medical disorders
• Diabetes, renal disease,anemia
• STDs

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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

• History
• Female Male
• Menstrual - Medical
• Dietary - Sexual
• Medical - Occupational
• Gyn/Ob - Family
• Sexual
• Family

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Physical exam

• Female
• Height
• Sexual Development
• Breasts/Galactorrhea
• Thyroid
• Hirsutism
• Acanthosis nigricans
• Anosmia

• Male
• Height
• Sexual Development
• Breasts
• Genitalia
• Thyroid
• Hair
• Anosmia

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Investigations

• Semen analysis
• Ovulatory status
• Menstrual history
• Symptoms consistent with ovulation
• Mid cycle mucus changes
• Pre-menstrual molimina
• Mittleschmertz
• Luteal serum progesterone 6ng/ml
• BBT (basal body temperature)
• Endometrial biopsy in luteal phase
• Urinary LH surge monitoring
• Serial ultrasound follicular tracking

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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
• GA/risks of surgery
• Uterine cavity not assessed

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Mid cycle cervical mucus smear demonstrates a
ferning pattern on drying
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Management. Male factor

• Intrauterine insemination (IUI)
• Intracytoplasmic sperm injection (ICSI)
• Donor sperm

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Management. Ovulation disorders

• Hyperprolactinemia
• Medical therapy
• Treat hypothyroidism
• PCOS
• Ovulation induction
• Medical
• Clomid
• Gonadotrophins
• Surgical
• Ovarian drilling
• Wedge resection
• Insulin sensitizers
• Metformin
• Weight loss

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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

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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

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• THANK YOU!