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Management of poor ovarian response

  1. 1. Management of Poor Or Hyper Ovarian response
  2. 2. Ovarian Reserve <ul><li>Every girl is born with a finite number of eggs, and their number progressively declines with age. </li></ul><ul><li>A measure of the remaining number of eggs in the ovary is called the &quot;ovarian reserve&quot;; and as the woman ages, her ovarian reserve gets depleted. </li></ul>
  3. 3. No. of Primordial Follicles Erickson GF 2000, Adashi EY (ed) N. Y. 31-48 Gougheon A, (2004) in Leung PK et al., (ed) San Diego 25-43. No. of oocytes 7 th Month of gestation 7.000.000 At Birth 2.000.000 Age of seven year 300.000 Puberty 40.000 Released by ovulation 400 – 500
  4. 4. Prediction <ul><li>age </li></ul><ul><li>History of previous poor response </li></ul><ul><li>History of previous OHSS </li></ul><ul><li>FSH </li></ul><ul><li>Estradiol </li></ul><ul><li>Inhibin </li></ul><ul><li>anti-Müllerian hormone </li></ul><ul><li>PCOS </li></ul><ul><li>antral follicle count </li></ul>
  5. 5. Pregnancy rate
  6. 6. <ul><li>The use of a wide range of tests suggests that no single test provides a sufficiently accurate result </li></ul>
  7. 7. AMH <ul><li>If kits are available, AMH measurement could be the most useful in the prediction of ovarian response in anovulatory women. </li></ul><ul><li>It is done at any day of cycle </li></ul><ul><li>It is too expensive </li></ul><ul><li>Exact normal levels not yet well agreed upon </li></ul>
  8. 8. During Induction? <ul><li>Careful monitoring of ovarian response: </li></ul><ul><ul><ul><li>US </li></ul></ul></ul><ul><ul><ul><li>E2 </li></ul></ul></ul>
  9. 9. Poor Response <ul><li>No universal definition </li></ul><ul><li>General consensus: women with poor response to ovarian stimulation </li></ul><ul><li>OR </li></ul><ul><li>those with low ovarian reserve </li></ul>
  10. 10. PREGNANCY RATE ACCORDING TO AGE AND NUMBER OF OOCYTES RETRIEVED
  11. 11. What is poor response in IVF <ul><li>Less than 5 follicles from both ovaries </li></ul><ul><li>Oocyte quality is not related to number of oocytes but to women age </li></ul><ul><li>Young women with poor response has good quality embryos and better chance of getting pregnant </li></ul>
  12. 12. LOW RESPONDERS CLASSIFICATION <ul><li>1) Elderly patients with an abnormal </li></ul><ul><li>endocrinological profile. </li></ul><ul><li>2) Young patients with an altered </li></ul><ul><li>endocrinological profile. </li></ul><ul><li>3) Young patients with a normal basal </li></ul><ul><li>hormonal profile. </li></ul>
  13. 13. What to do <ul><li>Increasing gonadotrophin in the same cycle does not result in significant improvement in the number of oocytes, embryos or pregnancies </li></ul>
  14. 14. Cancellation <ul><li>Is a very good option in this cycle </li></ul><ul><li>Based on counselling the couples </li></ul><ul><li>Decision to continue is still valid especially with advanced age (more than 38 years old women) </li></ul>
  15. 15. In subsequent cycles <ul><li>Increasing gonadotrophin in the subsequent cycle does not seem to result in significant improvement in the number of pregnancies obtained but may improve number of ooctes </li></ul>
  16. 16. <ul><li>What should be the maximum FSH dose in IVF/ICSI in poor responders </li></ul><ul><li>450IU/day </li></ul>
  17. 17. Protocols for IVF GnRH Antagonist Protocols GnRH Agonist Protocols 225 IU per day (150 IU Europe) Individualized Dosing of FSH/HMG 250  g per day antagonist Individualized Dosing of FSH/HMG GnRHa 1.0 mg per day up to 21 days 0.5 mg per day of GnRHa 225 IU per day (150 IU Europe) Day 6 of FSH/HMG Day of hCG Day 1 of FSH/HMG Day 6 of FSH/HMG Day of hCG 7 – 8 days after estimated ovulation Down regulation Day 2 or 3 of menses Day 1 FSH/HMG OCP
  18. 18. Protocols for poor responders <ul><li>Long protocol with large doses of gonadotropins </li></ul><ul><li>Short protocol. </li></ul><ul><li>Minidose of GnRH agonist protocol </li></ul><ul><li>Clomiphene / hMG protocol </li></ul><ul><li>Large doses of clomiphene protocol without hMG </li></ul><ul><li>GnRH antagonist protocols. </li></ul>
  19. 19. <ul><li>GnRh antagonist protocol are associated with lower total dose and shorter duration of stimulation when compared with standard long protocol </li></ul><ul><li>But no difference regarding pregnancy rate </li></ul>
  20. 20. Short (flare up protocol): <ul><li>GnRH-a is started on day one or two of the cycle. </li></ul><ul><li>Exogenous FSH administration, then is started on day 3 of the cycle to continue follicular stimulation, meanwhile complete pituitary desensitization occur. </li></ul>
  21. 21. Ultra-short protocol <ul><li>GnRHa is given for only three days with the flare up technique </li></ul><ul><li>LH could be suppressed till the mid cycle </li></ul><ul><li>This protocol will help to retrieve more oocytes with a minimal risk of premature LH surge. </li></ul>
  22. 22. <ul><li>lower cancellation rates in the long protocol treatment group (versus stop and GnRHa flare-up protocols). </li></ul>
  23. 23. Growth hormone <ul><li>Growth hormone may improve the number of oocytes but no difference in pregnancy rate </li></ul><ul><li>However, they are expensive and routine use can not be justified </li></ul>
  24. 24. NC <ul><li>Minimal stimulation and natural cycle protocols are gaining interests in low responders </li></ul><ul><li>The have comparable results with standard IVF ovarian stimulation </li></ul><ul><li>They are simple and cheaper </li></ul>
  25. 25. <ul><li>There is no single best protocol that can transform a low responder into a high responders </li></ul><ul><li>The expectations should be discussed with the patients. </li></ul><ul><li>It is preferable to opt for a simpler and less expensive regimen for ovarian stimulation (Sunkara et al, 2007) </li></ul>
  26. 26. <ul><li>the efficacy of natural cycle IVF is hampered by high cancellation rates mainly due to untimely LH surge </li></ul>
  27. 27. Poor response TI/IUI Gonadotrophins Modified natural cycle ” Antagonist “ IVM” IVF
  28. 28. Hyperresponse In its severest forms, it is complicated by hemoconcentration, venous thrombosis, electrolyte imbalance and renal and hepatic failure. Shenker and Weinstein, 1978; Navot et al., 1992; Aboulghar et al., 1993
  29. 29. <ul><li>Stop hMG and continue down regulation. This is the only complete prevention. </li></ul><ul><li>(Navot et al., 1992; Rizk and Aboulghar 1999; Aboulghar and Mansour, 2003) </li></ul><ul><li>Coasting: </li></ul><ul><li>HCG dose and other alternatives </li></ul><ul><li>Luteal phase : progesterone only. </li></ul>
  30. 30. Coasting is a routine practice at The Egyptian IVF-ET Center (May 2001 – May 2003) No. of Cycles 4969 No. of Coasting 560 Mean E 2 on hCG day 3742 + 1074 Days of Coasting 2 – 6 No. of Oocytes 18 + 7 No. of Cancelled ET (cryopreservation of all embryos) 3 OHSS (%) 6 (1.2 per 1000) Clinical Pregnancy (%) 265 (47.32%)
  31. 31. <ul><li>Coasting </li></ul><ul><li>Clinical and practical aspects </li></ul><ul><li>The Egyptian IVF-ET Center Experience </li></ul><ul><li>When to stop gonadotropins? </li></ul><ul><ul><ul><ul><ul><li>When the leading follicles reach 16mm </li></ul></ul></ul></ul></ul><ul><li>how many days? </li></ul><ul><ul><ul><ul><ul><li>Till the E2 drops to < 3000 pg/ml </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>(Sher et al., 1995; Benavida et al., 1997; Tortoriello et al., 1998; </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Egbase et al., 1999; Fluker et al., 2000; Ohata et al., 2000) </li></ul></ul></ul></ul></ul><ul><li>Dose of hCG? </li></ul><ul><ul><ul><ul><ul><li>5000 IU is enough </li></ul></ul></ul></ul></ul><ul><li>Special laboratory aspects? </li></ul><ul><ul><ul><ul><ul><li>Extra time to identify the oocytes from the follicular fluid </li></ul></ul></ul></ul></ul>
  32. 32. GnRH antagonist In a Cochrane review by Al-Inany , Abousetta and Aboulghar (2005) comparing agonist and antagonist, significant difference in the incidence of OHSS was found.
  33. 33. Novel Approach <ul><li>Coasting + Antagonist </li></ul><ul><li>If E2 >6000 Pg/ml </li></ul><ul><li>Reduce duration of coasting </li></ul><ul><li>Extremely efficient </li></ul><ul><li>Allow for continuing hMG at minimal dose </li></ul><ul><li>Oocyte quality is high </li></ul>
  34. 34. THANK YOU
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