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Infertility

Infertility

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Infertility

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  1. Infertility Edward Illions, M.D. Associate Professor Division of Reproductive Endocrinology & Infertility Department of Obstetrics, Gynecology & Women’s Health Albert Einstein College of Medicine

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

  3. Epidemiology of Infertility • Affects 10-15% of couples of reproductive age.

  4. Terminology Fecundability: Probability of achieving pregnancy within one menstrual cycle-approximately 25% Fecundity: The ability to achieve a live birth within one menstrual cycle

  5. 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 161:855, 1956.

  6. Female Reproductive Anatomy

  7. 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

  8. Integral Components to Fertility

  9. 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

  10. Male Infertility- etiology

  11. 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 (>14% Kruger) Head/neck piece/tail WBC’s < 1 million/ml

  12. Male Infertility-Terminology Oligospermia <20 Million per ml Asthenospermia <50% motile sperm Teratospermia >70% abnormal sperm Oligo-astheno-teratospermia Azoospermia No sperm seen Obstructive Cystic Fibrosis/Infections Non-Obstructive Kleinfelter’s Syndrome (47 XXY) Sertoli Cell Only Syndrome

  13. 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

  14. 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

  15. Female Infertility- etiology

  16. Female Infertility

  17. 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

  18. 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

  19. 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 < 10 ng/mL associated lower pregnancy rate BBT (basal body temperature) Endometrial biopsy in luteal phase Urinary LH surge monitoring Serial ultrasound follicular tracking

  20. Basal Body Temperature (BBT) Chart

  21. 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

  22. 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

  23. Ovulatory Disorders- Hyperprolactinemia Prolactin (normal <20 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 < 10mm Macroadenomas >10mm

  24. Ovulatory Disorders- Hypothalamic amenorrhea Anorexia nervosa Excessive exercise Ballet dancers Competitive athletes Stress Chronic illness Exogenous opiods

  25. Female Infertility- cervical hospitality testing Post coital test (PCT) 8 - 12 hrs post coitus Mid follicular cervical mucus Clarity Spinbarkeit (stretchability) 8-10 cm Ferning Sperm - > 10 motile sperm per HPF Shaking phenomenon-antisperm antibodies

  26. Post-coital test

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

  28. 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)

  29. Female Infertility- tubal factor testing:Hysterosalpingogram (HSG) Early follicular phase of cycle Rule out STD’s 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

  30. Assessment of tubal patency Hysterosalpingogram (HSG)

  31. Hysterosalpingogram (HSG)

  32. Evaluating uterine cavity by HSG Filling defects

  33. 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

  34. Sonohysterogram (HSN)

  35. Sonohysterogram (HSN)

  36. Female Infertility- fertilization and embryo development testing With treatment by IVF (in vitro fertilization) and/or ICSI (intracytoplasmic sperm injection)

  37. 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

  38. 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

  39. Evaluation of the Infertile Couple History FemaleMale Menstrual - Medical Dietary - Sexual Medical - Occupational Gyn/Ob - Family Sexual Family

  40. Physical exam Female Height Sexual Development Breasts/Galactorrhea Thyroid Hirsutism Acanthosis nigricans Anosmia Male Height Sexual Development Breasts Genitalia Thyroid Anosmia

  41. 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

  42. 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

  43. Mid cycle cervical mucus smear demonstrates a “ferning” pattern on drying

  44. Management……. Male factor Intrauterine insemination (IUI) Intracytoplasmic sperm injection (ICSI) Donor sperm

  45. 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

  46. 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

  47. 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

  48. THANK YOU!