Management of poor ovarian responsePresentation Transcript
Management of Poor Or Hyper Ovarian response
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
History of previous poor response
History of previous OHSS
antral follicle count
The use of a wide range of tests suggests that no single test provides a sufficiently accurate result
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
Careful monitoring of ovarian response:
No universal definition
General consensus: women with poor response to ovarian stimulation
those with low ovarian reserve
PREGNANCY RATE ACCORDING TO AGE AND NUMBER OF OOCYTES RETRIEVED
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
LOW RESPONDERS CLASSIFICATION
1) Elderly patients with an abnormal
2) Young patients with an altered
3) Young patients with a normal basal
What to do
Increasing gonadotrophin in the same cycle does not result in significant improvement in the number of oocytes, embryos or pregnancies
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
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
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.
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 may improve the number of oocytes but no difference in pregnancy rate
However, they are expensive and routine use can not be justified
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
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)
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%)
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.