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Infertility

Infertility. Chairman of the Indian College of Obstetricians & Gynecologists (ICOG) Past President of the Federation of Obstetric & Gynecological Societies of India (FOGSI) 2006 Honorary Fellow of the Royal College of Obstetricians & Gynecologists

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Infertility

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  1. Infertility

  2. Chairman of the Indian College of Obstetricians & Gynecologists (ICOG) • Past President of the Federation of Obstetric & Gynecological Societies of India (FOGSI) 2006 • Honorary Fellow of the Royal College of Obstetricians & Gynecologists • Prof. and Cons. Obs. & Gyn,Breach Candy Hospital, Jaslok Hospital, Sir H.N. Hospital Mumbai, India.

  3. Causes of Infertility Couples (Speroff & Fritz, 2005)

  4. Causes of Infertility(Continued) Women (Speroff & Fritz, 2005)

  5. Introduction • Primary infertility The inability to conceive after 1 year of unprotected intercourse for a woman younger than 35, or after 6 months of unprotected intercourse for a woman 35 or older (Speroff & Fritz, 2005). • Secondary infertility The inability of a woman to conceive who previously was able to do so (Speroff & Fritz, 2005).

  6. Unexplained Infertility Clinical Definition : Absence of a definable cause fora couple’s failure to achieve pregnancy after 12 months of attempting conception despite a thorough evaluation Sub-fertility :Any form of reduced fertility withprolonged time of unwantednon-conception.

  7. First visit • Have both come to all visits • Get a complete history • Sexual history • Educate

  8. Visit 1: Male History Past medical history • Fathered previous pregnancies within 3 years • Genital trauma or surgery • Genital infections; GC, Chlamydia, mumps • Environmental heat: spa, pants, sitting time Coital factors • Coital frequency • Coital technique, esp ejaculation factors

  9. Visit 1: Male History Current exposures • Drugs: b-blockers, Ca channel blockers,cimetidine, HMG-CoAreductase inhibitors • Toxic chemicals, esp. metals and dyes • Street drug and alcohol use • Cigarette smoking

  10. Visit 1: Male Examination Utility is controversial • “Preferable” to do exam, but little contribution If semen analysis is normal Male examination • Masculine traits • Varicocoele • Hypospadias • Urethral discharge • Prostatitis

  11. Visit 1: Female History • Prior infertility; evaluation, treatments • Hx of PID; postpartum/ postTB infection • Pelvic pain, dysmenorrhea; endometriosis • Medical: diabetes, thyroid; pelvic surgery • Medications, alcohol, street drugs Contd….

  12. Visit 1: Female History • Cigarette smoking • Galactorrhea • Menstrual patterns • Cycle length range (best 25-35 days apart) • Moliminal symptoms (if present, ovulating)

  13. Visit 1: Female Examination • Weight, BMI, waist circumference (PCOS) • Skin: axial hirsuitism, acne, male-pattern balding (PCOS) • Breasts: galactorrhea ( ▲prolactin) • Cervix: mucus, friability (infection) • Uterine corpus • Size, shape (fibroids, uterine anomalies) • Corpus tenderness (PID) • Fixed retroflexion (EM) • Adnexa: tenderness (PID, EM), mass (EM, tumor)

  14. Visit 1: Pelvic Ultrasound • Diagnostic pelvic ultrasound • >10 to 12 follicles per ovary (PCOS) • Persistent hemorrhagic cysts with low-level echoes (endometriosis) • Anatomical conditions: fibroids, polyps, and • Müllerian anomalies (uterine septum) • Decreased ovarian volume and reduced antral follicle count associated with reduced fertility • Serial TV ultrasound used to document ovulation

  15. Visit 1: Laboratory Women • CBC, ESR • TSH, prolactin • Ovarian reserve testing (if indicated) • Screen for gonorrhea, chlamydia (if indicated) • Microscopy of cervical mucus

  16. Visit 1: Laboratory Men • Semen analysis if has not fathered children • Fresh sample (to lab within 30 mins.) –most sperm in initial ejaculate • Male should be abstinent for 48 to 72 hours

  17. Visit 1: Counseling • Time intercourse just before ovulation • Use menstrual calendar to predict ovulation • Shortest cycle length minus 14 days • Ovulation prediction kit to confirm ovulation

  18. Coital frequency and Technique • Every other day intercourse starting 4-5 days before expected ovulation • Lay supine with knees up x 20 minutes after intercourse • No sperm-toxic lubricants

  19. Visit 1: Counseling • Stop smoking (both partners) • If BMI > 30, recommend/assist with weight loss • Preconceptional care Folic acid 400 mcg PO per day Rubella serology; immunize if seronegative Contd…..

  20. Visit 1: Counseling • Change medications to safer FDA pregnancy category »Antihypertensives »Anti-epileptic drugs • Blood glucose control in diabetics

  21. Sperm Count • Fresh sample (to lab within 30 mins.) –most sperm in initial ejaculate • Male should be abstinent for 48 to 72 hours

  22. Sperm Analysis • Volume - : 2.0ml or more • pH : 7.2- 8.0 • sperm concentration : 20 x 10 spermatozoa/ml or more • total sperm count : 40 x 10 spermatozoa per ejaculate or more • motility : 50% or more with forward progression (categories a and b) or 25% or more with ra (category a ) within 60 minutes of ejaculation Contd.....

  23. Sperm Analysis • Morphology : 30% or more with normal forms • Vitality : 75% or more live, ie. Excluding dye • White blood cells : fewer that 1 x 106/ ml • Immunobead test : fewer than 20% spermatozoa with adherent particles • MAR test : fewer than 10% spermatozoa with adherent particles

  24. Normozoospermia Normal ejaculate Asthenozoospermia Teratozoospermia Azoospermia Aspermia Normal ejaculate Sperm concentration <20 × 106 /ml <50% spermatozoa with forward progression <30% spermatozoa with normal morphology No spermatozoa in the ejaculate No ejaculate Sperm Terms

  25. Tests for the lady • Thyroid • Midcycle progesterone level &/or luteal phase progesterone level • FSH/ LH • Cortisol • Hystersalpingogram • Laporoscopy/hysteroscopy • Postcoital Test

  26. Markers Of Ovarian Reserve • Baseline hormones- FSH - Estradiol - Inhibin B - Antimullerian hormone • Ultrasound parameters- Antral follicle count- Ovarian volume- Ovarian Stromal Blood Flow Contd..

  27. Markers Of Ovarian Reserve • Dynamic tests.-Clomiphene citrate challenge test (CCCT)- Exogenous FSH ovarian reserve test (EFFORT)- GnRH agonist stimulation test (GAST)

  28. Clomiphene Citrate Challenge Test Clomiphene citrate ( 100mg OD ) from D – 5 to D – 9 of the cycle FSH measured on Day – 3 and Day – 10 An abnormally high value ( cut – off point 10 – 26 mIU / ml ) indicates diminished ovarian reserve

  29. Exogenous FSH Ovarian Reserve Test ( EFORT ) Day 3 – Inhibin B to be done ( Pre ) Administer 300 IU FSH After 24 hrs – Inhibin B to be repeated ( Post ) EFORT Values= Post Inhibin B – Pre Inhibin B < 78.6 : patient is poor responder 78.6 – 110.4 : patient is borderline > 110.4 : patient is good responder

  30. GnRH Agonist Stimulation Test ( GAST ) GnRH agonist down regulation Administration of 100 mcg baserelin every 4 hrs for a total daily dose of 1200mcg OR Every 6 hrs for a total dose of 800mcg S – FSH and S – estradiol to be measured before and after 24 hrs of treatment Change in estradiol less than 180 pg/ml and / or FSH 9.5 IU/L predicts poor oocyte response

  31. Documentation of Ovulation • Regular menstrual cycles with molimia • Mid-luteal phase progesterone > 9 ng/ml • BBT • LH surge: positive ovulation prediction kit • Pelvic ultrasound evidence of ovulation • Secretoryendometrium on endometrial biopsy

  32. Tests of Tubal Patency • Hysterosalpingography • Hydrohysterosonography • Sonosalpingography • Hydrogynecography or sion procedure • Redionucleide HSG • Selective salpingography • Hysterosalpingographic fallopian tube recanalization.

  33. Role of Laparoscopy Controversial as to whether to include it in the basic evaluation or not Studies indicate that it may demonstrate previously undetected stage I or II endometriosis, periovarian or peritubal adhesions Contd…..

  34. Role of Laparoscopy This may alter treatment plans such as surgery for endometriosis or directly IVF for peritubal adhesion Can be avoided in women with a normal HSG in patients who may need IVF

  35. Laproscopy findings • Uterus ---- fibroids uterine anamoly • Tubes --- patency hydrosalpinx • Ovaries --- PCOS chocolate cyst • POD --- endometriosis adhesions

  36. Hysteroscopy findings • Cervical canal --- polyps • Uterine cavity --- adhesions polyps fibroids uterine anamoly • Endometrium --- proliferative/ hyperplastic • Tubal ostium --- visualised or not

  37. Post coital test Technique • No longer routine, since subjective interpretation and poor correlation with pregnancy rates • Evaluates sperm-cervical mucus interaction • Schedule 1-3 days before expected ovulation • Abstain x 48o, then intercourse 2-8 hrs before PCT • Retrieve mucus with cytobrush or cannula

  38. Post coital test Normal findings • Quant (+4), clarity (clear) , SBK (>8 cm), fern (+4) • Mucus WBC count (<5 wbc/ HPF) • Sperm quantity ( > 20/ HPF correlates >20 million/ cc) • Sperm motility (> 1-3 progressively motile/ HPF)

  39. Fertility Treatment: Goals • To ensure patient safety • To help a couple experience a healthy pregnancy and birth or an alternative way to build a family • To use as little of a couple’s resources as necessary

  40. Fertility Treatment: Options • Correct ovulatory dysfunction • Correct tubal or uterine abnormalities • Overcome subfertile sperm parameters • ART

  41. Serum TSH Serum Prolactin Anovulatory Ovulatory Specific treatment Prog C.T. Dysovulatory Infertility Negative Positive Unexplained Infertility Serum FSH N LPD Pre Luteinasation LH surge Absent PCOD No PCOD Low High CC CC + HMG HMG/FSH Brom/cabergolin Corticosteroids Metformin (Insulin sensitizers) Letrozol (Aromatase inhibitor) Surgical treatment (Ovarian Drilling) Hypo pit. hypogonadism POF Superovulation IUI CC CC + HMG HMG/FSH HMG OC GnRHa + HMG No success Associated tubal / male factor ART Ovulation Induction CC GnRH + HMG CC+HMG/FSH

  42. Clomiphene Citrate + HMG / FSH OR CC 100mg D5 to D9 CC 100mg D3 to D7 Inj. HCG 10,000 IU 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Clomiphene Citrate dose Day of cycle Contd...

  43. Clomiphene Citrate Antiestrogenic effect on hypothalamus Increase in GnRh Increase in LH & FSH Development of follicles Increase in E2 Increase in LH OVULATION

  44. Letrozole Letrozole 2.5mg bd D3 to D7 Inj. HCG 10,000 IU 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Letrozole dose Day of cycle Contd...

  45. Tamoxifen Taxomifen 50 – 100mg / day Inj. HCG 10,000 IU 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Tamoxifen dose Day of cycle Contd...

  46. CC + Gonadotropins FSH + HMG CC Inj. HCG 10,000 IU 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 18 Tamoxifen Day of cycle Contd...

  47. HMG / FSH Ampoules / day 3 2 1 0 5 10 15 Gonadotropins (Step up Regimen) Day of cycle

  48. Gonadotropins (Step down Regimen) HMG / FSH Ampoules / day 3 225 IU 150 IU 2 75 IU 1 2 10 12 14 16 0 4 8 6 Day of cycle

  49. GnRH Agonist Short Protocol HMG 225 IU HMG 150 IU HMG 75 IU Inj. HCG 10,000 IU Lupride 1mg 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 18 Day of cycle Contd...

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