Hopes and facts about mild ovarian stimulation.

Over the last two decades, easier and less expensive stimulation treatments have been largely replaced by more complex and more demanding protocols. Since the mid-nineties, long-term gonadotrophin-releasing hormone agonist stimulation protocols have been widely used. Such lengthy expensive regimens are not free from short- and long-term risks and complications. Mild stimulation protocols 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 reduced costs, the better tolerability for patients and the less time needed to complete an IVF cycle make mild approaches clinically and cost-effective over a given period of time. However, further prospective randomized studies are needed to compare cumulative pregnancy rates between the two protocols. Natural cycle IVF, with minimal stimulation, has been recently proposed as an alternative to conventional stimulation protocols in normo- and poor responder patients. Although acceptable results have been reported, further large prospective randomized studies are needed to better evaluate the efficacy of these minimal regimens compared with conventional stimulation approaches.

GnRH antagonists in ovarian stimulation for ICSI with oocyte restriction: a matched, controlled study.

Italian legislation regarding reproductive medicine limits the number of embryos transferred per attempt to three. Thus, in order to achieve pregnancy, more IVF cycles may be required, generating a need for methods of ovarian stimulation with fewer side effects. The gonadotrophin-releasing hormone (GnRH) antagonists have several advantages in this respect, but there is a debate regarding a possible lower pregnancy rate from resulting cycles. This study evaluated the clinical applicability of GnRH antagonists for ovarian stimulation in young women undergoing intracytoplasmic sperm injection (ICSI) in which only three oocytes can be fertilized. The 200 women treated with GnRH antagonist had a significantly shorter stimulation and lower gonadotrophin consumption, oestradiol concentration, total and mature oocyte recovery as compared with 200 matched controls treated with GnRH agonist. No differences were found between the groups in the number of normal zygotes, total cleaved, transferred and high quality embryos, or in the clinical outcomes. Thus, the previously reported lower pregnancy rate in GnRH antagonist cycles may be related to the oocyte characteristics. Finally, under conditions of oocyte number restriction, the GnRH antagonist-based cycles may be proposed as an efficacious, safe and minimally invasive alternative to GnRH agonist in a standard long protocol.