Mild ovarian stimulation and poor ovarian response.

One of the most frustrating problems in IVF today is the low pregnancy rate in women with poor ovarian response. Poor responders are estimated to comprise approximately 9-24% of IVF/ICSI patients .Various stimulation protocols have been tried to improve pregnancy outcomes in poor responder women (Shanbhag et al., 2007). Since most studies included small numbers of patients and used different definitions of poor response, the best stimulation protocol is still unknown. Most treatment comparisons include high doses of gonadotropins and only vary in their means of ovarian suppression ie GnRH agonist versus antagonist or no downregulation at all. High doses of gonadotropins did not result in higher pregnancy rates although this treatment regime appears to be the standard treatment worldwide in poor responder patients. Such a demanding protocol is more burdensome to the patient, costly and may result in embryos of lower quality.



Mild stimulation using a GnRH antagonist and a low dose of gonadotrophins may present a good alternative. Mild stimulation protocols have been shown to reduce the mean number of days of stimulation, the total amount of gonadotrophins used and the mean number of oocytes retrieved. The proportion of high quality and euploid embryos seems to be higher compared with conventional stimulation protocols and the pregnancy rate per embryo transfer is comparable. Moreover, the expected reduced costs, better tolerability for patients and shorter time needed to complete an IVF cycle make a mild approache an interesting treatment option.



Therefore, 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.

Most treatment comparisons include high doses of gonadotropins and only vary in their means of ovarian suppression ie GnRH agonist versus antagonist or no downregulation at all. High doses of gonadotropins did not result in higher pregnancy rates although this treatment regime appears to be the standard treatment worldwide in poor responder patients. Such a demanding protocol is more burdensome to the patient, costly and may result in embryos of lower quality.



The mild stimulation using a GnRH antagonist and a low dose of gonadotrophins may present a good alternative. Mild stimulation protocols have been shown to reduce the mean number of days of stimulation, the total amount of gonadotrophins used and the mean number of oocytes retrieved. The proportion of high quality and euploid embryos seems to be higher compared with conventional stimulation protocols and the pregnancy rate per embryo transfer is comparable. Moreover, the expected reduced costs, better tolerability for patients and shorter time needed to complete an IVF cycle make a mild approache an interesting treatment option.

N/A

Couples will be 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 will be performed by computer at a central randomisation center at the IVF center.