Effect of growth hormone cotreatment in sub-fertile women ≥ 40 years: a meta-analysis

Treatment of sub-fertile women aged ≥ 40 years old (advanced maternal age (AMA)) is challenging. Co-treatment with growth hormone (GH) is suggested to improve reproductive outcomes in poor responders. However, few studies, and with conflicting results, focused on women of AMA. A systematic review and meta-analysis of randomized controlled trials (RCTs) and comparative retrospective trials (CRTs) of GH cotreatment in AMA women undergoing in vitro fertilization or intracytoplasmic injection treatment using their autologous oocytes was performed. The search included studies published in English up to the end of 2021. The primary outcome was the clinical pregnancy rate per embryo transfer. Secondary outcomes were the number of mature and retrieved oocytes and the rate of live birth. A total of 406 studies were found. The final analysis included 3 RCTs and 4 CRTs with 481 patients who used GH and 400 patients who did not. Clinical pregnancy and live birth rates were significantly higher in the GH cotreatment group compared to the placebo as well as the group without GH co-treatment, (odds ratio (OR): 2.2; 95% CI: 1.34–3.61 and OR: 4.12; 95% CI: 1.82–9.32, respectively). Intriguingly, the subgroup analysis showed that poor-responder patients did not benefit from co-treatment with GH. There were no statistically significant differences in the number of mature or retrieved oocytes. GH cotreatment in a subgroup of women of AMA improves clinical pregnancy and live birth per fresh embryo transfer. However, this conclusion must be taken with caution and further research is needed. The review is registered in the PROSPERO database (www.crd.york.ac.uk/prospero/; CRD42021252618). LAY SUMMARY: Women over 40 years undergoing in vitro fertilization (IVF) treatment commonly require high doses of injectable medications to stimulate their ovaries. Co-treatment with growth hormone (GH) has been shown to enhance the ovarian response and improve the outcome. The investigators found seven studies that compared 881 women over 40 years of age who had undergone IVF treatment with or without GH cotreatment. Statistical analysis of data from these studies showed that some of these women may benefit from adding a GH to their ovarian stimulation medications. The benefit was evident in those with good ovarian reserve. Women over 40 years with a good ovarian reserve can increase their chance of pregnancy by 4–20% when using GH during ovarian stimulation. However, this finding requires confirmation in a well-designed study with large sample size. Furthermore, the optimal dose, regimen, safety, and cost-effectiveness of GH cotreatment should be clarified.