Mild ovarian stimulation in women with poor ovarian response undergoing IVF and ICSI.

To compare mild ovarian stimulation IVF versus the standard IVF followed by replacement embryos one cycle cryopreserved embryo in poor responders women. Couples are allocated 1:1 to a treatment consisting of one cycle of mild ovarian stimulation IVF-ET plus subsequent cryo-cycles or one cycle of conventional controlled ovarian hyperstimulation IVF-ET followed by plus subsequent cryo-cycles. The randomisation is performed by computer at a central randomisation center at the IVF center.

the aim of this study is to compare two strategies that present a large contrast in the stimulation dosage, i.e. a high dosage of stimulation versus a low dosage of stimulation. Our study is designed to objectively compare the ongoing pregnancy rate of mild stimulation, i.e. a GnRH antagonist short protocol with 150 IU FSH preceded by OCP (mild ovarian stimulation IVF) to a long GnRH agonist protocol with 450 IU HMG,(standard IVF), followed by replacement of two embryos in expected and non expected poor responder women. Subsequent cryopreserved transfer cycles will be included in the analysis. Expected and unexpected poor responder women will be analysed separately

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Group (1) will be pre-treated with oral contraceptive pills (OCP) started on cycle day 2-3 of the preceding cycle for a variable period of 14-21 days. The date of the last OC intake will be decided by the investigator , then a fixed dose of 150IU/day HP/rec FSH, sc will be initiated on day 5 after the last OCP after establishing ovarian and uterine quiescence using vaginal ultrasound. GnRH antagonist will be commenced on stimulation day 6 (Fixed protocol).


Group (2) will be treated with the GnRH agonist triptoreline starting 1 wk before the expected menses (usually cycle d 21). After down-regulation is achieved [serum estradiol (E2), 150 pmol/liter], ovarian stimulation will be commenced with a fixed daily dose of 450 IU/day HMG. After establishing ovarian and uterine quiescence using vaginal ultrasound, Triptoreline and GnRH agonist will be continued up to and including the day of human chorionic gonadotropin (HCG) administration. When the leading follicle reaches a diameter of 18 mm or more and at least two follicles reach a diameter of 15 mm or more, HP/rec FSH will be stopped, and a single sc bolus of 10,000 IU hCG (Pregnyl, NV Organon, Oss, The Netherlands) will be administered 35 h before the planned time of oocyte retrieval. All follicles 12 mm or larger will be aspirated. Subsequently, IVF with or without ICSI will be performed, after that the DET will be performed 3,5 d thereafter. TET is allowed in case of patients are more than 40 years or in patients with poor embryo quality. Any remaining good-quality embryos are cryopreserved using slow-cooling on day 4 and transferred in subsequent cycles until pregnancy is achieved or all embryos have been used. Luteal support in the form of intravaginal progesterone (P; Progestan, Organon; 200 mg, three times daily) will be given from the day of oocyte retrieval until a urine pregnancy test will be performed 17 d later. In case of a positive pregnancy test women will be monitored using ultrasound visualisation during their pregnancy. Monitoring will take place at 5 to 8 weeks of amenorrhea to check whether an intrauterine gestational sac is present, i.e. a clinical pregnancy. Subsequently monitoring will take place at 11 to 12 weeks amenorrhea to register the presence of an intrauterine gestational sac with fetal heart beat, i.e. an ongoing pregnancy.