Addition of growth hormone to gonadotrophins in ovarian stimulation of poor responders treated by in-vitro fertilization: A systematic review and meta-analysis

Background: Whether the addition of growth hormone (GH) can improve the probability of pregnancy in poor responders undergoing ovarian stimulation for in-vitro fertilization (IVF) has been examined to date by several underpowered studies, which have not provided solid conclusions. Methods: A computerized literature search in MEDLINE, EMBASE, CENTRAL and randomized controlled trial (RCT) registries was performed independently by two reviewers, aiming to identify RCTs that evaluated the following research question: does GH addition increase the probability of pregnancy in poor responders undergoing ovarian stimulation with gonadotrophin releasing hormone (GnRH) analogues and gonadotrophins for IVF?. Results: Six relevant RCTs were identified, including a total of 169 patients. GH addition significantly increased clinical pregnancy (rate difference: +16%, 95% CI: +4 to +28; fixed effects model) (number-needed-to-treat (NNT) = 6, 95% CI: 4-25) and live birth rates (rate difference: +17%, 95% CI: +5 to +30; fixed effects model) (NNT = 6; 95% CI: 3-20). Furthermore, GH addition was associated with a significantly higher proportion of patients reaching embryo transfer (rate difference: +22%, 95% CI: +7 to +36; fixed effects model). Conclusions: The present meta-analysis provides evidence that GH addition increases the probability of clinical pregnancy and live birth in poor responders undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF. However, the total number of patients analyzed is small and thus further RCTs are warranted to prove or disprove this finding.