Background Luteinizing hormone (LH) activity plays a crucial role in follicular development, endometrial decidualization, and embryo implantation. We aimed to compare the efficacy and safety of gonadotropins with LH activity versus recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation (COS). Methods We included randomized clinical trials (RCTs) assessing gonadotropins with LH activity with or without rFSH versus rFSH, or comparing different sources of LH activity, or different doses. Participants were women undergoing COS. The outcomes were live births , ongoing pregnancies , oocytes recovered per woman , metaphase II (MII) oocytes per woman , and occurrence of ovarian hyperstimulation syndrome (OHSS) . We searched the MEDLINE, Embase, and CENTRAL databases. We calculated the mean differences (MDs) and risk ratios (RRs) for continuous and dichotomous outcomes, respectively. Results We included 56 RCTs with 14,034 women. The evidence of gonadotropins with LH activity (±rFSH) when compared with rFSH alone probably results in little to no difference in live birth (RR = 1.07, 95%CI = 0.96–1.18; 17 studies, moderate certainty of evidence) and ongoing pregnancy (RR = 1.03, 95%CI = 0.95–1.12; 19 studies, moderate certainty of evidence), may result in a slight reduction in the number of oocytes retrieved (MD = −0.50, 95%CI = −0.88 to −0.12, I 2 = 81.1%; 46 studies, low certainty of evidence), and is very uncertain in the number of MII oocytes (MD = −0.49, 95%CI = −0.93 to −0.05, I 2 = 86%; 30 studies, very low certainty of evidence). However, it probably does not increase OHSS compared with rFSH alone (RR = 0.80, 95%CI = 0.61–1.03, I 2 = 17.1%; 19 studies, moderate certainty of evidence). Subgroup analysis by downregulation protocol, ovarian reserve, and age showed some differences in the effects between the compared groups. Conclusions The evidence of gonadotropins with LH activity (±rFSH) when compared with rFSH alone probably results in little to no difference in live birth and ongoing pregnancy. However, there is a slight reduction in the number of oocytes retrieved. Moreover, they are safer than rFSH alone because they probably do not increase OHSS. Therefore, based on our review, the benefit–risk balance favors the addition of an LH-active gonadotropin for the prevention of OHSS. More studies are needed to determine the effects in specific populations. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42024572731 , identifier CRD42024572731.
Espinós et al. (Wed,) studied this question.