efficacy of ovarian stimulation based on fshr genotype status

Conditions: Sterility

Summary: available data from in vitro studies and clinical trials indicate that genetic factors play a significant role in the success of controlled ovarian stimulation (cos) prior to in vitro fertilization - embryo trandfer (ivf-et). women with the fshr ser680asn ser/ser genotype make up between 13% and 26% of women undergoing ivf-et and are characterised by higher basal fsh serum concentrations, the need for a higher amount of fsh for cos, and a higher risk of poor response to cos and cycle cancellation. the investigators therefore intend to perform a study to investigate whether a dose-intensified cos protocol based on fshr genotype status in women with the fshr ser680asn ser/ser genotype is more effective than routine management in terms of * the mean number of follicles * the mean number of embryos * the rate of poor responders * the rate of women with cycle cancellations, and v) the clinical pregnancy rates. eligible women will be randomized to a stimulation protocol characterised by a longer duration and increased dosage of fsh stimulation (group a) or a standard stimulation protocol (group b).

women in group a will undergo controlled ovarian stimulation according to the following protocol: pituitary down-regulation will be achieved using buserelin (suprefact®, hoechst, frankfurt, germany) at a fixed daily dose of 200 mg s.c., according to a long agonist protocol, starting on day 2 of the normal menstrual cycle. treatment with r-hfsh (gonal-f®, serono austria gmbh, vienna, austria) will be started in women with serum e2 concentrations \ 15 mm in diameter or ovarian cysts on ultrasonographic examination. the initial r-hfsh dose will be 250 iu s.c. daily for 5 days, after which the dose will be increased to a maximum of 450 iu per day using a step-up protocol with steps of 50 iu/day. once the leading follicle has reached a diameter of 14 mm, patients will receive r-hlh (lutropin alfa; luveris®, serono austria gmbh, vienna, austria) at a dose of 75 iu s.c. for a maximum of 10 days. a dose of 75 iu lh per day was chosen based on findings from a controlled, prospective, dose-finding study in gonadotrophin-deficient women (who i classification) (7). ovulation will be induced by administration of hcg (profasi®, serono austria gmbh, vienna, austria), 10 000 iu i.m. or s.c., when at least two follicles have reached a diameter of \>17 mm. oocyte retrieval will be performed by ultrasound-guided follicular aspiration techniques 34-38 h after administration of hcg. ivf will be performed according to standard practices at our institution. a maximum of three embryos will be transferred 48 h after oocyte retrieval (eshre committee on good clinical and laboratory practice, 1995 ). patients will receive micronized progesterone, 600 mg/day, by vaginal administration for at least the first 3 weeks of pregnancy, beginning on the day of embryo transfer. women in group b will undergo ovarian hyperstimulation according to the following protocol: no pituitary down-regulation will be performed. treatment with r-hfsh (gonal-f®, serono austria gmbh, vienna, austria) will be started in women with serum e2 concentrations \ 15 mm in diameter or ovarian cysts on ultrasonographic examination. the r-hfsh dose will be 150 iu s.c. daily for 11 consecutive days. once the leading follicle has reached a diameter of 14 mm, patients will receive r-hlh (lutropin alfa; luveris®, serono austria gmbh, vienna, austria) at a dose of 75 iu s.c. for a maximum of 10 days. a dose of 75 iu lh per day was chosen based on findings from a controlled, prospective, dose-finding study in gonadotrophin-deficient women (who i classification) (european recombinant human lh study group, 1998 ). ovulation will be induced by administration of hcg (profasi®, serono austria gmbh, vienna, austria), 10 000 iu i.m. or s.c., when at least two follicles have reached a diameter of \>17 mm. oocyte retrieval will be performed by ultrasound-guided follicular aspiration techniques 34-38 h after administration of hcg. ivf will be performed according to standard practices at our institution. a maximum of three embryos will be transferred 48 h after oocyte retrieval (eshre committee on good clinical and laboratory practice, 1995 ). patients will receive micronized progesterone, 600 mg/day, by vaginal administration for at least the first 3 weeks of pregnancy, beginning on the day of embryo transfer.

Eligibility criteria:
inclusion criteria: * age between 18 and 40 * informed consent * indication for ivf-et exclusion criteria: * inability to understand written informed consent form * personal history of ovarian hyperstimulation syndrome

Keywords: ovarian stimulation fsh genotyping polymorphism