Interventions for 'poor responders' to controlled ovarian hyperstimulation (COH) in in-vitro fertilisation (IVF)

BACKGROUND: The success of in-vitro fertilisation (IVF) treatment depends on adequate follicle recruitment by using controlled ovarian stimulation with gonadotrophins. Failure to recruit adequate follicles is called 'poor response'. Various treatment protocols have been proposed that are targeted at this cohort of women, aiming to increase their ovarian response. OBJECTIVES: To compare the effectiveness of different treatment interventions in women who have poor response to controlled ovarian hyperstimulation (are poor responders) in the context of in vitro fertilisation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials (MDSG), the Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library 2003, Issue 1), MEDLINE (1966 to August 2006), EMBASE (1980 to August 2006) and The National Research Register (NRR). The citation lists of relevant publications, review articles, abstracts of scientific meetings and included studies were also searched. The authors were contacted to identify or clarify data that were unclear from the trial reports. SELECTION CRITERIA: Only randomised controlled trials (RCTs) comparing one type of intervention versus another for controlled ovarian stimulation of poor responders to a previous IVF treatment, using a standard long protocol were included. DATA COLLECTION AND ANALYSIS: Two review authors independently scanned the abstracts, identified relevant papers, assessed inclusion and trial quality and extracted relevant data. Validity was assessed in terms of method of randomisation, completeness of treatment cycle and co-intervention. Where possible, data were pooled for analysis. MAIN RESULTS: Nine trials involving six different comparison groups have been included in this review. Only one trial reported live birth rates. Four groups compared the long protocol with another intervention. Only one comparison group (bromocryptine versus long protocol) reported a higher clinical pregnancy rate per cycle, in the bromocryptine arm (OR 5.60, 95% CI 1.40 to 22.47). Two comparison groups showed a lower number of oocytes in the long protocol group (versus stop and gonadotrophin releasing hormone (GnRH) antagonist protocols). However, two comparison groups also showed lower cancellation rates in the long protocol treatment group (versus stop and GnRHa flare-up protocols). None reported any evident difference in the adverse effects. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of any particular intervention either for pituitary downregulation, ovarian stimulation or adjuvant therapy in the management of poor responders to controlled ovarian stimulation in IVF. More robust data from good quality RCTs with relevant outcomes are needed.