Gonadotropin releasing hormone analogue as an adjunct to gonadotropin therapy for clomiphene‐resistant PCOS

BACKGROUND: Elevation of endogenous LH levels may result in premature luteinization. This may also be associated with the increased rate of spontaneous abortion. Gonadotropin releasing hormone analogue (GnRHa) used prior to human menopausal gonadotropin (hMG/FSH) administration may improve the outcome of ovulation induction. OBJECTIVES: To assess if GnRHa pre-treatment plus FSH/hMG increase the rate of clinical pregnancy and/or decrease the rate of spontaneous abortion in women with WHO group 2 ovulatory dysfunction, compared with hMG/FSH alone. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: All relevant published and unpublished RCTs were selected. Three RCTs were identified comparing these two approaches. DATA COLLECTION AND ANALYSIS: DATA EXTRACTION: A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. DATA SYNTHESIS: 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2. MAIN RESULTS: Studies were clinically and statistically homogenous. Common odds ratios for pregnancy per treatment cycle and moderate to severe ovarian hyperstimulation syndrome (OHSS) were 1.50 (0.72-3.12) and 1.40 (0.5-3.92) respectively. REVIEWER'S CONCLUSIONS: These studies are too small to clearly demonstrate clinically significant differences in pregnancy rate between the two approaches. However, data from IVF studies suggest that there may be an increased risk of OHSS associated with GnRHa use. In the absence of evidence suggesting a benefit of GnRHa augmentation for PCOS, it should not be recommended as a standard treatment for this patient group. Further studies assessing live birth and OHSS rates are warranted.