Management of poor ovarian response
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Management of poor ovarian response

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

  • Management of Poor Ovarian response
  • Definition
    • No universal definition
    • General consensus: women with poor response to ovarian stimulation
    • OR
    • those with low ovarian reserve
  • Normal ovarian response DAYS FROM LH PEAK LH FSH 10 15 20 25 0 5 10 15
    • FSH stimulates follicle growth
    • LH surge induces ovulation
  • Reserve
    • Usually, ovarian function goes hand in hand with age, and as a woman becomes older, her ovarian response starts declining.
    • 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.
    • The infertility specialist is really not interested in the woman's calendar (or chronological age), but rather her biological age - or how many eggs are left in her ovaries.
  • Poor response
    • OI (monofollicular )
    • Superovulation (multifollicular)
  • Poor response & Monofollicular induction
  • Gold Standard: Clomiphene Citrate
    • Dose:
    • 50-150 mg./day.
    • starting day 2,3,4 or 5 for 5 days.
    • Monitoring:
    • ultrasound
    • menstrual pattern
    • BBT, LH kits
    • day 21 progesterone.
  • Expected conception rate on clomiphene citrate
    • 40% of patients ultimately conceive.
    • 80% can be expected to ovulate.
    • (Hancock 1973)
  • Clomiphene citrate failure
    • Total lack of response (anovulatory).
    • Partial lack of response:
      • No complete growth of follicles.
      • No LH rise.
    • Conception failure: After 4-6 months of ovulation.
  • CC Resistant
    • If still anovulatory after 6 months of continuous use the case is considered “clomiphene resistant”
  • No ovulation:
    • dose.
    • duration of treatment (10 days).
    • add hMG.
  • The Aromatase Inhibitors
    • Letrozole (Fimara 2.5 mg)
    • effective.
    • It has the following advantages:
    • 1- It reduce E2 level.
    • 2- It avoids the unfavorable effects on the endometrium frequently seen with CC
  • Prolactin Reducing Medications
    • Bromocryptine, Lisuride
    • Causes:
    • - Pituitary adenoma (prolactinoma)
    • - Hyperactive lactotrophs.
    • - Medications: tranquilizers, hallucinogens, painkillers, alcohol,..
  • Metformin
    • The addition of metformin in the CC-resistant patient is highly effective in achieving ovulation induction.
    • Meta-analysis by Siebert et al, 2006
  • gonadotrophins
    • Conventional protocol:
    • 150 IU for five days, then dose is adjusted.
    • OR
    • Fixed low dose protocol 75 IU for 10 days, then adjusted.
  • Ovarian Drilling
    • There is no evidence that one modality of drilling is superior to the other.
    • It is suggested that the resumption of ovulation is temporary in many patients after drilling.
    • The incidence of adhesions varies from zero to 100% following drilling.
  • Cochrane Review
    • no significant difference in pregnancy rates between laparoscopic ovarian drilling and gonadotrophins after 6–12 months follow up. But caution about ovarian reserve in LOD (Farquhar,2005)
  • Poor response & Multifollicular induction IVF/ICSI
  • 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
  • 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
  • What to do
    • Increasing gonadotrophin in the same cycle does not result in significant improvement in the number of oocytes, embryos or pregnancies obtained
  • 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
  • Prediction
    • age
    • FSH
    • Estradiol
    • Inhibin
    • anti-Müllerian hormone
    • ovarian volume
    • antral follicle count
    • 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
  • Poor response TI/IUI Gonadotrophins Modified natural cycle ” Antagonist “ IVM” IVF