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Management of poor ovarian response

Management of poor ovarian response






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    Management of poor ovarian response Management of poor ovarian response Presentation Transcript

    • Management of Poor Or Hyper Ovarian response
    • Ovarian Reserve
      • Every girl is born with a finite number of eggs, and their number progressively declines with age.
      • A measure of the remaining number of eggs in the ovary is called the "ovarian reserve"; and as the woman ages, her ovarian reserve gets depleted.
    • 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
    • Prediction
      • age
      • History of previous poor response
      • History of previous OHSS
      • FSH
      • Estradiol
      • Inhibin
      • anti-Müllerian hormone
      • PCOS
      • antral follicle count
    • Pregnancy rate
      • The use of a wide range of tests suggests that no single test provides a sufficiently accurate result
    • AMH
      • If kits are available, AMH measurement could be the most useful in the prediction of ovarian response in anovulatory women.
      • It is done at any day of cycle
      • It is too expensive
      • Exact normal levels not yet well agreed upon
    • During Induction?
      • Careful monitoring of ovarian response:
          • US
          • E2
    • Poor Response
      • No universal definition
      • General consensus: women with poor response to ovarian stimulation
      • OR
      • those with low ovarian reserve
    • What is poor response in IVF
      • Less than 5 follicles from both ovaries
      • Oocyte quality is not related to number of oocytes but to women age
      • Young women with poor response has good quality embryos and better chance of getting pregnant
      • 1) Elderly patients with an abnormal
      • endocrinological profile.
      • 2) Young patients with an altered
      • endocrinological profile.
      • 3) Young patients with a normal basal
      • hormonal profile.
    • What to do
      • Increasing gonadotrophin in the same cycle does not result in significant improvement in the number of oocytes, embryos or pregnancies
    • Cancellation
      • Is a very good option in this cycle
      • Based on counselling the couples
      • Decision to continue is still valid especially with advanced age (more than 38 years old women)
    • In subsequent cycles
      • 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
      • What should be the maximum FSH dose in IVF/ICSI in poor responders
      • 450IU/day
    • 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
    • Protocols for poor responders
      • Long protocol with large doses of gonadotropins
      • Short protocol.
      • Minidose of GnRH agonist protocol
      • Clomiphene / hMG protocol
      • Large doses of clomiphene protocol without hMG
      • GnRH antagonist protocols.
      • GnRh antagonist protocol are associated with lower total dose and shorter duration of stimulation when compared with standard long protocol
      • But no difference regarding pregnancy rate
    • Short (flare up protocol):
      • GnRH-a is started on day one or two of the cycle.
      • Exogenous FSH administration, then is started on day 3 of the cycle to continue follicular stimulation, meanwhile complete pituitary desensitization occur.
    • Ultra-short protocol
      • GnRHa is given for only three days with the flare up technique
      • LH could be suppressed till the mid cycle
      • This protocol will help to retrieve more oocytes with a minimal risk of premature LH surge.
      • lower cancellation rates in the long protocol treatment group (versus stop and GnRHa flare-up protocols).
    • Growth hormone
      • Growth hormone may improve the number of oocytes but no difference in pregnancy rate
      • However, they are expensive and routine use can not be justified
    • NC
      • Minimal stimulation and natural cycle protocols are gaining interests in low responders
      • The have comparable results with standard IVF ovarian stimulation
      • They are simple and cheaper
      • There is no single best protocol that can transform a low responder into a high responders
      • The expectations should be discussed with the patients.
      • It is preferable to opt for a simpler and less expensive regimen for ovarian stimulation (Sunkara et al, 2007)
      • the efficacy of natural cycle IVF is hampered by high cancellation rates mainly due to untimely LH surge
    • Poor response TI/IUI Gonadotrophins Modified natural cycle ” Antagonist “ IVM” IVF
    • 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
      • Stop hMG and continue down regulation. This is the only complete prevention.
      • (Navot et al., 1992; Rizk and Aboulghar 1999; Aboulghar and Mansour, 2003)
      • Coasting:
      • HCG dose and other alternatives
      • Luteal phase : progesterone only.
    • 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%)
      • Coasting
      • Clinical and practical aspects
      • The Egyptian IVF-ET Center Experience
      • When to stop gonadotropins?
              • When the leading follicles reach 16mm
      • how many days?
              • Till the E2 drops to < 3000 pg/ml
              • (Sher et al., 1995; Benavida et al., 1997; Tortoriello et al., 1998;
              • Egbase et al., 1999; Fluker et al., 2000; Ohata et al., 2000)
      • Dose of hCG?
              • 5000 IU is enough
      • Special laboratory aspects?
              • Extra time to identify the oocytes from the follicular fluid
    • 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.
    • Novel Approach
      • Coasting + Antagonist
      • If E2 >6000 Pg/ml
      • Reduce duration of coasting
      • Extremely efficient
      • Allow for continuing hMG at minimal dose
      • Oocyte quality is high