ovarian stimulation- back to basics


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ovarian stimulation- back to basics

  1. 1. Ovarian Stimulation Back to Basics Dr Parul Sehgal Incharge IVF, Maharaja Agrasen Infertility and ART centre Maharja Agrasen Hospital, Punjabi Bagh, New Delhi-26
  2. 2. Road to Infertility can be Tough and Tiring
  3. 3. Treatment may involve advanced infrastructure delicate hormone balancing careful handling of gametes
  4. 4. But in the end once inside the mothers body nature take over
  6. 6. 1 +1
  7. 7. 1 +2
  8. 8. INFERTILITY FACTS <ul><li>1 in 7 couple suffer from infertility </li></ul><ul><li>For past few decades more and more nulligravid females are now infertile </li></ul><ul><li>Time is critically important factors for couples as AGE is the single most important prognosticator for success </li></ul><ul><li>Chance of spontaneous pregnancy in a healthy couple is 30 % in a cycle. </li></ul><ul><li>In subfertile couple during the three years after first infertility consultation , chance of spontaneous conception followed by live birth is 25-40%, so in a cycle, fecundity rate is 0.7 – 1%. This drops further by 0.5 if other factors like tubal disease, endometriosis or abnormal sperm parameters are present. </li></ul>
  9. 9. <ul><li>Normally , no ART procedure should be used in a woman below 20 years </li></ul><ul><li>No ART procedure shall be done without husbands consent </li></ul><ul><li>For a sperm donor , accepted age shall be between 21 and 45 years </li></ul>
  10. 10. To look for the cause <ul><li>Female Factor Male Factor </li></ul><ul><li>Anovulatory </li></ul><ul><ul><li>Tubal </li></ul></ul><ul><li>Endometrial Adhesions </li></ul><ul><li>Medical factors </li></ul><ul><li>Psychological factors </li></ul>
  11. 11. Anovulatory Infertility WHO CRITERIA <ul><li>GP I :- FSH, LH Dysfunction at the level of hypth. & Pit </li></ul><ul><li>GP II :- (N) FSH </li></ul><ul><li> (N) E2 </li></ul><ul><li>GP III :- Ovarian Failure FSH </li></ul><ul><li> E2 </li></ul><ul><li>GP IV :- Prolactin </li></ul><ul><li>GP V :- Out flow tract defect. </li></ul>
  12. 12. WHO GP II <ul><li> Most commonly found </li></ul><ul><li>All PCOS present with this type of anovulation </li></ul><ul><li>Oligo Ovulation:- Ovulation once in 35-180 days </li></ul><ul><li>2) Anovulation:- No ovulation for 6 months </li></ul><ul><li>3) Hyper androgenism :- Clinical signs </li></ul><ul><li> blood test for S.Testosterone </li></ul><ul><li> Androstenedione </li></ul><ul><li> Free androgen Index </li></ul><ul><li>4) Oligo menorrhea </li></ul><ul><li>5) Amenorrhea </li></ul>
  14. 14. Basics of ovarian stimulation <ul><li>Age </li></ul><ul><li>BMI </li></ul><ul><li>Baseline FSH :- (Blood Test) </li></ul><ul><li>Antral follicular count (USG) </li></ul><ul><li>AMH </li></ul>
  15. 15. <ul><li>FSH >10-20 Poor Response </li></ul><ul><li>LH >10 Poor Response </li></ul><ul><li>E2 >60-75 Poor quality OOcyte </li></ul><ul><li>Insulin B normal 45pg/ml </li></ul><ul><li> <45 pg/ml-Low reserve </li></ul><ul><li>USG : Antral follicle count more practical & direct approach. </li></ul><ul><li>Superier to chronological age & endocrine markers </li></ul><ul><li>-Eijkemans et al </li></ul><ul><li>B/L Ovarian <10 Follicles - Poor Response </li></ul>Contd…) On the D2/3 of cycle
  16. 16. Normally follicular size at D2=3-5mm <ul><li> If Follicle </li></ul><ul><li>>15mm >15mm </li></ul><ul><li>E2 high E2 Low </li></ul><ul><li>Functioning Ovarian cyst Non Functioning ovarian cyst </li></ul><ul><li>Rest the Cycle You can proceed </li></ul><ul><ul><ul><ul><li> cyst may regress OR Poor ovarian response New follocle may develop </li></ul></ul></ul></ul>
  17. 17. Ovarian stimulation <ul><li>CLOMIPHENE LETRAZOLE </li></ul><ul><li>GONADOTROPINS </li></ul>
  18. 18. CLOMIPHENE <ul><li>Dose for normal women 50-100 mg/day </li></ul><ul><li>less sensitiveUpto 250 mg/day </li></ul><ul><li>Extremely sensitive 25 mg/ day </li></ul><ul><li>No advantage in using dose > 150 mg </li></ul><ul><li>Start with 100 mg will reduce the Tt time </li></ul><ul><li>75% of pregnancies occur with in first 3 cycles </li></ul><ul><li>80% will ovulate </li></ul><ul><li>30-45% will get pregnant </li></ul><ul><li>20-25% will not respond at all </li></ul><ul><li>Can be started on Day 2/3/4/5 </li></ul><ul><li>does not influence results </li></ul>
  19. 19. Clomiphene as a choice <ul><li>Mainly in Irregular ovulation WHO type II , PCOS </li></ul><ul><li>Anovulatory Infertiliy </li></ul><ul><li>In ovulating women with Unexplained Infertility </li></ul><ul><li>CC+ IUI – Increase pregnancy rates </li></ul><ul><li>CC may overcome subtle defects in ovulatory functions, inc the no. of mature follicles. </li></ul>
  20. 20. Why my patient did not respond to CC <ul><li>Obese BMI high </li></ul><ul><li>Insulin resistant </li></ul><ul><li>Hyper androgenic </li></ul><ul><li>LH high </li></ul><ul><li>Persisting luteal cyst </li></ul><ul><li>WHO gp I anovulation- Abn Hypoth./Pituitary </li></ul><ul><li>WHO gp III anov - premature ovarian failure </li></ul><ul><li>WHO gp IV anov - High prolactin </li></ul>
  21. 21. What can be done <ul><li>Extended Clomiphene </li></ul><ul><li>Insulin sensitizing agents-Metformin </li></ul><ul><li>Addition of Cabergoline/bromocriptene </li></ul><ul><li>Gonadotropin </li></ul><ul><li>Sequential CC + Gonadotropin </li></ul><ul><li>Ovarian drilling </li></ul><ul><li>Aggressive weight loss </li></ul>
  22. 22. Extended Clomiphene therapy stair step protocol <ul><li>Day 3-7 Begin CC 50 mg/day </li></ul><ul><li>Day 7-14 USG Follicular study </li></ul><ul><li>Day 14 Small Follicles </li></ul><ul><li>Day14-18 CC 100 mg/day </li></ul><ul><li>Day 19 USG Follicular Study </li></ul><ul><li>Day 22-26 CC 150 mg/day </li></ul><ul><li>USG </li></ul><ul><li>Total time stairstep protocol 28 days </li></ul><ul><li>Traditional protocol 88 days </li></ul>
  23. 23. Side effects of Clomiphene <ul><li>Multiple follicles </li></ul><ul><li>Multiple pregnancies </li></ul><ul><li>Bloating & abdominal distension </li></ul><ul><li>Ovarian cyst formation </li></ul><ul><li>Hot flashes( DISTURBED SLEEP) 10% </li></ul><ul><li>Visual disturbances 5% </li></ul><ul><li>blurred vision , flashes of light </li></ul>
  24. 24. LETRAZOLE <ul><li>Dose 2.5 to 5mg/day for 5 days </li></ul><ul><li>Start on cycle day 3/4/5 </li></ul><ul><li>No effect on cervical mucus or endometrium </li></ul><ul><li>Monofollicular ovulation </li></ul><ul><li>Many trial have proved letrazole giving more pregnancies when used alone or with gonadotropins </li></ul><ul><li>Still evidence–based medicine is needed to use it as first line of treatment </li></ul>
  25. 25. Stimulated with CC/Letrazole IUI Anovulation/ Irregularovulation For Better Results
  26. 26. STIMULATED IUI <ul><li>Indication : Women with regular (25- 32days) ovulatory cycles & patent Fallopian tubes. </li></ul><ul><li>Male partner must not have severe male infertility <5X106 motile sperm/ml. Mild to moderate male factor is not excluded &these couples often conceive readily. </li></ul>(Contd…)
  27. 27. Not meant for: <ul><li>Women >38yrs. </li></ul><ul><li>Women with short cycle (<25 days) & FSH >12 iu/l </li></ul><ul><li>Women with Normal FSH but LH 10 iu/l </li></ul><ul><li>Woman with irregular cycles & severe anovulation </li></ul><ul><li>Women with raised basal FSH & LH >8iu/l </li></ul><ul><li>Women with H/o severe endometriosis </li></ul><ul><li>Women with H/o abdominal surgery </li></ul><ul><li>Women with partner with severe male factor unless using donor sperm. </li></ul>
  28. 28. HOW DOES IUI HELP <ul><li>Treatment is designed to </li></ul><ul><li>Synchronise the timing of ovulation & sperm deposition </li></ul><ul><li>Marginally increase the number of oocytes available for fertilisation </li></ul><ul><li>Place the sperm in a closer approximation to the oocyte </li></ul>
  29. 29. Over response with ovarian stimulation for IUI
  30. 30. <ul><li>>3 FOLLICLES >16 mm </li></ul><ul><li>Cycles Cancelled </li></ul><ul><li>OR </li></ul><ul><li> </li></ul><ul><li>follicle reduction / cont. to IVF </li></ul><ul><li>Next attempt IVF: Long protocol </li></ul>
  31. 31. IUI IN OLDER AGE GROUPS <ul><li># Older women needs more aggressive stimulation >39. </li></ul><ul><li># Although occasional pregnancies will occur if older women are treated with SIUI, this will waste critical time for the majority. </li></ul>
  32. 32. Case 1 <ul><li>27yrs old female. </li></ul><ul><li>Married for 3 years </li></ul><ul><li>Attempting for 16months. </li></ul><ul><li>No. contraception taken </li></ul><ul><li>Regular menses , mild dysmenorrhea that responds to NSAIDS. </li></ul><ul><li>Physical ex:- no cervical/adnexal tenderness. </li></ul><ul><li>Vaginal/ semen culture- negative for infection. </li></ul><ul><li> Priliminary test Day 3 :- FSH,LH </li></ul><ul><ul><ul><ul><ul><li> E2 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li> Semen analysis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li> </li></ul></ul></ul></ul></ul>
  33. 33. What other test <ul><li>HSG Why? </li></ul><ul><li> Infertility 3yrs </li></ul><ul><li> without OC </li></ul><ul><li> Young age </li></ul><ul><li>Rt. Sided proximal tubal obstr. </li></ul><ul><li>Lt. sided patent Tube. </li></ul><ul><li>Cause </li></ul><ul><li>1) Spasm </li></ul><ul><li>2) Tubal Obstr </li></ul><ul><li>Tubal flushing Saline Sonography IUI </li></ul><ul><li>+ </li></ul><ul><li>with gonadotrophins </li></ul><ul><li>6 Cycles of Clomiphene citrate </li></ul><ul><li>+ IUI </li></ul>
  34. 34. Failed to Conceive <ul><ul><li> </li></ul></ul><ul><ul><li> Laparoscopy IUI with gonadotropins </li></ul></ul><ul><li>Reveals ext. Adhesion with endometriosis. </li></ul><ul><li>IVF </li></ul><ul><li>Laprotomy with With severe endomertriosis </li></ul><ul><li>Lyses of adhesion & ext. adhesion IVF-ET offers </li></ul><ul><li>& resection/ablation best pregnancy rates & </li></ul><ul><li>Of endometiosis avoid risk of surgery . </li></ul>
  35. 35. Case 2 <ul><li>37yrs old </li></ul><ul><li>P1+Ao </li></ul><ul><li>2 yrs of sec. Infertility </li></ul><ul><li>O.C for 5 yrs </li></ul><ul><li>Stopped O.C 2yrs ago. </li></ul><ul><li> She presented to her gynecologist </li></ul><ul><li>5 months ago with c/o infertility. </li></ul><ul><li>Test offered: D3 :- FSH </li></ul><ul><li> E2 </li></ul><ul><li> Semen Analysis </li></ul>(Contd…)
  36. 36. Aggressive workup needed considering (her age) <ul><ul><li>2 cycle of CC with timed intercourse </li></ul></ul><ul><li> Now What? </li></ul><ul><li>Do you encourage CC with Gonadotropin HSG/ </li></ul><ul><li>More cycle of CC IUI With IUI Laparoscopy </li></ul><ul><li>With timed intercourse? </li></ul>
  37. 37. 3 more cycle of IUI with CC <ul><ul><ul><ul><ul><li>Failed to become pregnant. </li></ul></ul></ul></ul></ul><ul><li>HSG Laparoscopy Gonadotropinc </li></ul><ul><li> with IUI </li></ul><ul><ul><ul><ul><ul><li> HSG Done </li></ul></ul></ul></ul></ul><ul><li> B/L patent tube with no intrauterine fllling defect. </li></ul><ul><li>Gonadotropins </li></ul><ul><li> + </li></ul><ul><li> IUI </li></ul><ul><li>Patient became pregnant in the second cycle of IUI </li></ul>
  38. 38. Case -3 <ul><li>Pts Age 44yrs Male partner-49 yrs </li></ul><ul><li>ML 17 years </li></ul><ul><li>P0A1 last abortion 7 years back, 5wks gestation </li></ul><ul><li>HSA Tmc 70 million, 43 % Am </li></ul><ul><li>HSG (2007) B/l tubes patent </li></ul><ul><li>FSH 28 mIU/ml </li></ul><ul><li>LH 12 mIU/ml </li></ul><ul><li>She has had 3 IUI’S IN THE LAST 6 MONTHS </li></ul><ul><li>Few Laparoscopy IVF-ET </li></ul><ul><li>more and with </li></ul><ul><li>IUI’s hysteroscopy donor Oocyte/ Embryo </li></ul><ul><li>+ IUI + Gonadotropins </li></ul><ul><li>Gonadotropins </li></ul>
  39. 39. As treatment revolves around these basic parameters,we have answers for all our failures and as we work on our patient, we know <ul><li>Age </li></ul><ul><li>Weight </li></ul><ul><li>Duration of Infertiliy </li></ul><ul><li>Previous treatments offererd for infertility </li></ul>
  40. 40. Poetry of reproduction will go on….. Thank you