Sub-fertility Causes &Management

1. Sub-fertilityCauses &Management Dr. Yousef Gadmour Professor, Al-fateh university Senior consultant, Al-Jalla Hospital Tripoli , Libya

2. Definitions: • Sub fertility- Involuntary failure to conceive within 12 months of commencing unprotected sexual intercourse. • Primary infertility - No previous pregnancy. • Secondary infertility- previous pregnancy. (whatever the outcome)

3. Causes(and approximate incidence) 1. Idiopathic - 25 per cent 2. Sperm defects or functional disorder - 25 per cent 3. Ovulation failure - 20 per cent 4. Tubal damage - 15 per cent 5. Endometriosis - 5 per cent 6. Coital failure - 5 per cent 7. Cervical mucus defect - 3 per cent 8. Obstruction of sperm ducts - 2 per cent

4. Principles of management: • Deal with the sub fertile couple together. • No one is at fault or to blame. • Give good explanations of causes , prognosis and outline of treatment of sub fertility. • Carry out investigations and treatments consistency in proper sequence.

5. 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, dysparunia • Contraceptive history

6. History - Male • Infections; gonorrhea , tuberculosis. • Radiation, toxic exposures ,drugs. • Mumps orchitis. • Testicular injury/surgery. • occupation (Excessive heat exposure). • Smoking. • Diabetes mellitus.

7. History - Female • Detailed menstrual history ; Irregular menses, amenorrhea. • Hirsutism. • Galactorrhoea. • Previous pregnancies and mode of deliveries. • Ectopic pregnancy history. • PID.

8. History - Female • Appendicitis. • IUCD use. • Endometriosis. • Stress. • Weight changes. • Excessive exercise. • Cervical and uterine surgery.

9. Physical Examination - Male • Weight & Height (BMI). • Size of testicles (orchidometry). • Testicular descent. • Varicocele. • Outflow abnormalities (hypospadias, etc). • General look- Klinefelter syndrome (47XXY). • Weight & Height (BMI). • Size of testicles (orchidometry). • Testicular descent. • Varicocele. • Outflow abnormalities (hypospadias, etc). • General look- Klinefelter syndrome (47XXY). • Kallmann syndrome (hypothalamichypogonadism) (delayed puberty ,normal stature, no smell ).

10. Physical Examination - Female • Weight & Height (BMI) • Hirsutism • Thyroid examination • Abdominal examination • Speculum examination - HVS, endocervical swap • Vaginal examination- Uterosacral nodularity, Uterine mobility • USS-(Vaginal)

11. General laboratory investigations: Female • FBS(GTT). • TFT. • chlamydial antibody titer. • Rubella antibody titer (If negative, immunize and advise not to try for pregnancy for 3 months). • HIV,HBV,HCV.

12. General laboratory investigations: Female • Day 2 FSH, LH. • Serum prolactin (fasting). • Day 21 serum progesterone.

13. General laboratory investigations: Male • HIV,HBV,HCV. • FBS (GTT). • TFT. • Serum Testosterone, FSH, PRL levels.

14. Routine investigation in the female Assessment of Ovulation • Basal body temperature • Mid luteal serum progesterone • Endometrial biopsy • Ultrasound monitoring of ovulation

15. BBT Cheap and easy, but… • Inconsistent results. • Provides evidence after the fact. • May delay timely diagnosis and treatment; 98% of women will ovulate within 3 days of the nadir. • Biphasic profiles can also be seen with LUF syndrome.

16. Luteal Phase Progesterone • Pulsatile release, thus single level may not be useful unless elevated. • Performed 7 days after presumptive ovulation ( day 21 ). • If done properly , level >15 ng/ml consistent with ovulation.

17. Endometrial Biopsy • Invasive, but the only reliable way to diagnose luteal phase defect (LPD). • Performed 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. • Controversy exists over the relevance of luteal phase defect as a cause of infertility and the accuracy of the endometrial biopsy in assessing the delay.

18. Postcoital test (PK tests) • Scheduled around 1-2d before ovulation (increased estrogen effect) • 48hours of male abstinence before test • No lubricants • Evaluate 8-12h after coitus (overnight is ok!) • Remove mucus from cervix (forceps, syringe)

19. Postcoital test (PK test) • PK (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)

20. 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.

21. Tubal Function • Evaluate tubal patency whenever there is a history of PID, endometriosis or other adhesiogenic condition. • Tests: • HSG • Laparoscopy • Falloposcopy (not widely available)

22. Hysterosalpingography (HSG) • Can be uncomfortable. • Done at the end of menses. • Can detect intrauterine and tubal disorders but not always definitive.

23. Laparoscopy • Invasive; requires OT 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 • Test of tubal patency by dye test

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

25. Assessment of uterine cavity Hysteroscopy • It is advisable to assess the uterine cavity pathology as submucous fibroid, polyps, uterine malformation, and others . • Outpatient hysteroscopy, hysterosalpingography are equivalent regarding evaluation of uterine cavity pathology

26. Routine investigation in the male Semen analysis • Test after (~3) days abstinence from intercourse. • If abnormal parameters, repeat twice, 2 weeks apart • Normal values: Volume: 2 to 6 ml Density: 20 to 250 million /ml Motility: > 50 % with forward motion within 2 hours Morphology: > 50 % normal sperm

27. Other Male Investigation • Doppler USS (varicocele). • Testicular Biopsy.

28. Treatment Options

29. Ovarian Disorders Anovulation • Clomiphene Citrate (CC) ± hCG • Human Menopausal Gonadotropin (hMG) • Pure FSH Central amenorrhea • CC first, then hMG • Pulsatile GnRH

30. Ovarian Disorders Hyperprolactinaemia: • Drugs :Bromocriptin, Carbegoline(Dostinex), Quinagolide (Norprolac) • Surgery if macroadenoma Premature ovarian failure : • ? high-dose hMG (not very effective) Luteal phase defect: • Progesterone suppositories during luteal phase • CC ± hCG

31. Ovulation Induction • Clomiphene Citrate • Compete with natural oestrogens by blocking receptors in target organs including the pituitary, leading to increased FHS levels. • 70% induction rate, ~40% pregnancy rate. • Patients should typically be normoestrogenic. • Induce menses and start on day 2 for 5 days. • With high dosages, antiestrogen effect dominate. • Multiple pregnancy rates 5-10%. • Monitor effects with USS & D21 progesterone.

32. hMG • LH +FSH (also FSH alone = Metrodin) • For patients with hypogonadotrophic hypoestrogenism or normal FSH and E2 levels • Close monitoring essential, including estradiol levels & USS • 60-80% pregnancy rates overall, lower for PCOS patients • 10-15% multiple pregnancy rate

33. CC Vasomotor symptoms Ovarian enlargement Multiple gestation NO risk of malformations hMG Multiple gestation OHSS (~1%) Can often be managed as outpatient Diuresis Severe cases fatal if untreated in ICU setting Risks

34. Fallopian Tubes • Tuboplasty • IVF

35. Corpus • Asherman syndrome • Hysteroscopic Lysis of adhesions (scissor) • Postop. ; IUCD, E2 • Fibroids (rarely need treatment) • Myomectomy ( hysteroscopic, laparoscopic, open) • ??Uterine artery embolization. • Uterine anomalies (rarely need treatment) • Metroplasty.

36. Peritoneum (Endometriosis) • From a fertility standpoint, excision beats medical management (Laser therapy ). • Lysis of adhesions. • GnRH-a (Not a cure and has side effects & expensive). • Danazol (side effects, cost). • Continuous OCP’s ( poor fertility rates ). • Chances of pregnancy highest within 6 -12 months after treatment.

37. Male Factor • Hypogonadotrophism • hMG • GnRH • CC, hCG ( results poor ) • Varicocoele • Ligation? ( No definitive data yet ) • Retrograde ejaculation • Ephedrine, imipramine • AIH with recovered sperm

38. Male Factor • Idiopathic oligospermia • No effective medical treatment • IVF (in-vitro fertilization) • ICSI ( Intra- cytoplasmic sperm injection ) • TESE( Testicular Sperm Extraction ) • MESA(Microsurgical Epididymal Sperm Aspiration) • ?? donor insemination

39. Unexplained Infertility • 15-20% of couples • Consider PRL, laparoscopy, other hormonal tests, cultures, Antisperm Abs. testing, sperm penetration assay if not done. • Review previous tests for validity. • Empirical treatment: • Ovulation induction • IUI • Consider IVF and its variants • Adoption

40. Summary • Sub fertility is a common problem. • Sub fertility is a disease of couples. • Evaluation must be thorough, but individualized. • Treatment is available, including IVF, but can be expensive, invasive, and of limited efficacy in some cases. • Consultation with a reproductive endocrinologist is advisable.

41. Thanks