Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles

Abstract

Gonadotrophin-releasing hormone agonist (GnRHa) has been widely used in cycles of in vitro fertilization (IVF). Among the various types of GnRHa ovarian stimulation protocols, the long protocol presents the best clinical pregnancy rates per cycle initiated (GnRHa administration until the suppression of ovarian activity is evident, within approximately 14 days). There are two types of GnRHa administration that can be used to lead to hypophysis desensitization in the IVF cycle in the long protocol: one consisting of daily GnRHa low doses, and another with the administration of analogues in higher long-acting doses (depot). There are controversies in the data as far as the number of ampoules to be used in the cycles with the depot GnRHa treatment, as well as regarding the number of follicles made available, the number of oocytes, fertilization, implantation and pregnancy rates. The objective of this study is to compare the use of a single long-acting depot dose to that of daily GnRHa doses in in vitro fertilization cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched 15 April 2004), Cochrane Central Register of Controlled Trials (Issue 2, 2004), MEDLINE (1984 to April 2004), EMBASE (1984 to June 2003), LILACS (1984 to April 2004) and reference lists of articles. Types of studies: RCTs comparing depot and daily administration of GnRHa for long protocols in IVF treatment cycles. Couples with any cause of infertility. Types of interventions: Ovarian stimulation with human follicle stimulating hormone (hFSH) and/or human menopausal gonadotropin (hMG) and/or recombinant follicle stimulating hormone (rFSH) in IVF treatment cycles. Types of outcome measures: Clinical pregnancy rates per woman, per oocyte retrieval procedure, per embryo transfer, number of oocytes retrieved, oocyte fertilization rates, ongoing/delivered pregnancy rates per cycle started, abortion rates, multiple pregnancy rates, number of ampoules of gonadotropin employed, ovarian hyperstimulation syndrome (OHSS) incidence rates, cost analysis and patient convenience. The reviewers evaluated allocation concealment, classified as adequate, uncertain or inadequate. Two reviewers extracted the data independently. All analyses were performed according to the intention-to-treat method. Six studies, with a total of 552 women, were included and analysed. The studies do not indicate that there is statistically significant difference between the use of depot GnRHa or daily GnRHa in the primary outcome, clinical pregnancy rates per woman (OR 0.94, 95% CI 0.65 to 1.37). However, there was sufficient evidence that the use of depot GnRHa for pituitary desensitization in IVF cycles increased the number of gonadotrophins ampoules (WMD 3.30, 95% CI 1.27 to 5.34) and the duration of the ovarian stimulation (WMD 0.56, 95% CI 0.31 to 0.81), as compared with daily GnRHa. Although we recognise that the clinical pregnancy rates per woman are not the ideal primary outcome, we found no evidence of differences between the long protocol using depot or daily GnRHa for IVF cycles. However, the use of depot GnRHa is associated with increased requirements for gonadotrophins and a longer time required for ovarian stimulation. If these differences could be shown to translate into economic benefit, depot GnRHa should increase the overall costs of IVF treatment.