Comparative Effectiveness of Recombinant Human Follicle-Stimulating Hormone:Recombinant Human Luteinizing Hormone in a 2:1 Ratio versus Highly Purified Human Menopausal Gonadotropin Alone in Ovarian Stimulation for Medically Assisted Reproduction Treatment Using in vitro Fertilization/Intracytoplasmic Sperm Injection: A Systematic Review and Meta-Analysis.

Investigation of the number of oocytes recovered from different ovarian stimulation (OS) protocols is essential, as oocyte number is positively associated with the number of good-quality embryos obtained; however, there are few data comparing the number of oocytes retrieved following OS with recombinant or urinary gonadotropins. A systematic review and meta-analysis of published evidence was performed to compare the number of oocytes retrieved with recombinant human follicle-stimulating hormone:recombinant human luteinizing hormone (r-hFSH:r-hLH) in a 2:1 ratio versus highly purified human menopausal gonadotropin (HP-hMG) alone from day 1 of OS. The literature search was conducted according to PRISMA guidelines (<ext-link ext-link-type="uri" xlink:href="https://www.prisma-statement.org/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.prisma-statement.org/</ext-link>) using Medline, EMBASE, Biosis, SciSearch, and TOXCENTER on STN. Studies were included if they reported on r-hFSH:r-hLH in a 2:1 ratio versus HP-hMG alone, both administered from day 1 of OS, and the results for the number of oocytes retrieved were presented for both interventions. Data were extracted from the full articles independently by two reviewers (J.-E.S. and B.H.). Results were analyzed using a random-effects meta-analysis model. Any potential risk of bias was assessed using the ROBINS-I tool. Secondary outcomes were the number of mature (MII) oocytes, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. Six studies were included in the meta-analysis (5,287 cycles): four non-interventional studies, one non-interventional cross-over study, and one randomized controlled trial. The number of oocytes per cycle was significantly higher in women treated with r-hFSH:r-hLH 2:1 compared with those treated with HP-hMG alone (mean difference 1.43, 95% confidence interval [CI]: 0.18-2.69; p = 0.025). Clinical pregnancy rate per started cycle was significantly higher with r-hFSH:r-hLH 2:1 compared with HP-hMG (rate ratio 1.18, 95% CI: 1.06-1.33; p = 0.004; five studies). There were insufficient data to draw any firm conclusions on the other secondary outcomes. The higher number of oocytes retrieved with r-hFSH:r-hLH is a pertinent finding, owing to the well-established positive association between oocyte number and reproductive outcomes. Although we report a higher clinical pregnancy rate for r-hFSH:r-hLH 2:1, limited data prevented us from drawing firm conclusions regarding live birth outcomes.