INFERTILITY

1. INFERTILITY

2. Fertilization

3. Terminology • Infertility; it is failure to achieve pregnancy after 1 year of effort. It can be primary or secondary. The period in definition may be extended to 2 years in young patient and shortened to 6 months in older one. • Sterility; it is absolute infertility. • Fecundity rate; monthly pregnancy rate. • Cumulative pregnancy rate; ratio of pregnant women to all treated women.

4. Statistics • 80% of couples will conceive within 1 year of unprotected intercourse • ~86% will conceive within 2 years

5. Etiologies • Sperm disorders 30.6% • Anovulation/oligo-ovulation 30% • Tubal disease 16% • Unexplained 13.4% • Cx factors 5.2% • Peritoneal factors 4.8%

6. Infertility increases with aging • Aging • Less ovulation • More LPD • Less uterine receptivity 5 10 15 20 25 30 Infertility per cent 25-29 30-34 35-39 40-44 years Average incidence of infertility is 10%

7. Associated Factors • PID • Endometriosis • Ovarian aging • Spermatic varicocele • Toxins • Previous abdominal surgery (adhesions) • Cervical/uterine abnormalities • Cervical/uterine surgery • Fibroids

8. Overview of Evaluation • Female • Ovary • Tube • Corpus • Cervix • Peritoneum • Male • Sperm count and function • Ejaculate characteristics, immunology • Anatomic anomalies

9. The Most Important Factor in the Evaluation of the Infertile Couple Is:

10. HISTORY

11. History-General • Both couples should be present • Age • Previous pregnancies by each partner • Length of time without pregnancy • Sexual history • Frequency and timing of intercourse • Use of lubricants • Impotence, anorgasmia, dyspareunia • Contraceptive history

12. History-Male • History of pelvic infection • Radiation, toxic exposures (include drugs) • Mumps • Testicular surgery/injury • Excessive heat exposure (spermicidal)

13. History-Female • Previous female pelvic surgery • PID • Appendicitis • IUD use • Ectopic pregnancy history • DES (?relation to infertility) • Endometriosis

14. History-Female • Irregular menses, amenorrhea, detailed menstrual history • Vasomotor symptoms • Stress • Weight changes • Exercise • Cervical and uterine surgery

15. When Not to Pursue an Infertility Evaluation • Patient not sexually-active • Patient not in long-term relationship? • Patient declines treatment at this time • Couple does not meet the definition of an infertile couple

16. Physical Exam-Male • Size of testicles • Testicular descent • Varicocele • Outflow abnormalities (hypospadias, etc)

17. Physical Exam-Female • Pelvic masses • Uterosacral nodularity • Abdomino-pelvic tenderness • Uterine enlargement • Thyroid exam • Uterine mobility • Cervical abnormalities

18. Overall Guidelines for Work-up • Timeliness of testing-w/u can usually be accomplished in 1-2 cycles • Timing of tests • Don’t over test • Cut to the chase, i.e. proceed with laparoscopy if adhesive disease is likely

20. Work-up by Organ Unit

21. Ovary

22. Ovarian Function • Document ovulation: • BBT • Luteal phase progesterone • LH surge • Endometrial secretory phase biopsy • If Premature Ovarian Failure suspected, perform FSH • FSH, LH, Testosterone & Androstenedione>> pco • TSH, PRL, adrenal functions if indicated • Karyotyping if suspected • The only convincing proof of ovulation is pregnancy

23. Ovarian Function • Three main types of dysfunction • Hypogonadotropic, hypoestrogenic (central) • Normogonadotrophic, normoestrogenic (e.g. PCOS) • Hypergonadotropic, hypoestrogenic (POF)

24. BBT • Cheap and easy, but… • Inconsistent results • May delay timely diagnosis and treatment • 98% of women will ovulate within 3 days of the nadir • No correlation with increased pregnancy rate

25. Luteal Phase Progesterone • Pulsatile release, thus single level may not be useful unless elevated • Performed 7 days after presumptive ovulation • Done properly, >15 ng/ml consistent with ovulation

26. Urinary LH Kits • Very sensitive and accurate • Positive test precedes ovulation by ~24 hours, so useful for timing intercourse • Downside: price, obsession with timing of intercourse

27. Endometrial Biopsy • Invasive, but the only reliable way to diagnose LPD • ??Is LPD a genuine disorder??? • Pregnancy loss rate <1% • Perform around 2 days before expected menstruation (= day 28 by definition) • Lag of >2 days is consistent with LPD • Must be done in two different cycles to confirm diagnosis of LPD

28. Fallopian Tubes

29. Tubal Function • Evaluate tubal patency whenever there is a history of PID, endometriosis or other adhesiogenic condition • Kartagener’s syndrome can be associated with decreased tubal motility • Tests • HSG • Laparoscopy • HyCoSy • Falloposcopy (not widely available)

30. Hysterosalpingography (HSG) • Radiologic procedure requiring contrast • Performed optimally in early proliferative phase (avoids pregnancy) • Low risk of PID except if previous history of PID (give prophylactic doxycycline or consider laparoscopy) • Oil-based contrast • Higher risk of anaphylaxis than H2O-based • May be associated with fertility rates

31. Hysterosalpingography (HSG) • Can be uncomfortable • Pregnancy test is advisable • Can detect intrauterine and tubal disorders but not always definitive

32. Laparoscopy • Invasive; requires OR or office setting • Can offer diagnosis and treatment in one sitting • Not necessary in all patients • Uses (examples): • Lysis of adhesions • Diagnosis and excision of endometriosis • Myomectomy • Tubal reconstructive surgery

33. HyCoSy

34. Falloposcopy • Hysteroscopic procedure with cannulation of the Fallopian tubes • Can be useful for diagnosis of intraluminal pathology • Promising technique but not yet widespread

35. Uterine Corpus

36. Corpus • Asherman Syndrome • Diagnosis by HSG or hysteroscopy • Associated with hypo/amenorrhea, recurrent miscarriage • Fibroids, Uterine Anomalies • Rarely associated with infertility • Work-up: • Ultrasound • Hysteroscopy • Laparoscopy

37. Cervix

38. Cervical Function • Infection • Ureaplasma suspected • Stenosis • S/P LEEP, Cryosurgery, Cone biopsy (probably overstated) • Immunologic Factors • Sperm-mucus interaction

39. Cervical Function • Tests: • Culture for suspected pathogens • Postcoital test (PK tests) • Scheduled around 1-2d before ovulation (increased estrogen effect) • 480 of male abstinence before test • No lubricants • Evaluate 8-12h after coitus (overnight is ok!) • Remove mucus from cervix (forceps, syringe)

40. Cervical Function • PK, continued (normal values in yellow) • Quantity (very subjective) • Quality (spinnbarkeit) (>8 cm) • Clarity (clear) • Ferning (branched) • Viscosity (thin) • WBC’s (~0) • # progressively motile sperm/hpf (5-10/hpf) • Gross sperm morphology (WNL) Male factors

41. Problems with the PK test • Subjective • Timing varies; may need to be repeated • In some studies, “infertile” couples with an abnormal PK conceived successfully during that same cycle

42. Peritoneum

43. Peritoneal Factors • Endometriosis • 2x relative risk of infertility • Diagnosis (and best treatment) by laparoscopy • Can be familial; can occur in adolescents • Etiology unknown but likely multiple ones • Retrograde menstruation • Immunologic factors • Genetics • Bad karma • Medical options remain suboptimal

44. Male Factors

45. Male Factors-Semen Analysis • Sample collected after 3-days abstinence • Sample should be produced manually, no lubricants • Sample should not be chilled on transport • Rapid delivery of sample to the lab. • Two semen analysis 3-months apart • Do not say azoo without centrifugation

47. Semen analysisMacleod criteria • Volume; 2-4 ml • Count; > 20 million/ml • Motility; > 50% progressive • Morphology; > 30% normal • Oval head • Acrosomal cap • Single tail • Pus cells; < 1 million/ml • FSH, PRL, karyotype

48. Grading of sperm motilityMacleod scale • 0; immotile • Living immotile (Asthenospermia) • Dead immotile (Necrosprmia) • 1; sluggish non-linear • 2; sluggish linear • 4; rapid linear (progressive)

49. Male Factors • Serum T, FSH, PRL levels • Semen analysis • Testicular biopsy • Sperm penetration assay (SPA)