Impact of adding r-LH to r-FSH during ovarian stimulation on reproductive outcomes of women with polyendocrine metabolic ovarian syndrome undergoing in vitro fertilization

Abstract

Background Polyendocrine Metabolic Ovarian Syndrome (PMOS) is a common endocrine disorder and a leading cause of anovulatory infertility. In women with PMOS, controlled ovarian stimulation (COS) often results in heterogeneous responses, with many oocytes of poor quality and lower fertilization rates. The combined use of recombinant Luteinizing Hormone (r-LH) and recombinant Follicle-Stimulating Hormone (r-FSH) has shown potential to improve Assisted Reproductive Technology (ART) outcomes in specific populations, such as women with hypogonadotropic hypogonadism or advanced age. However, its benefits in women with PMOS remain uncertain. This retrospective cohort study explores whether adding r-LH to r-FSH during COS improves reproductive outcomes in women with PMOS undergoing ART. Results The study included 156 women diagnosed with PMOS according to Rotterdam criteria, undergoing COS at a single tertiary center. After propensity score matching for age, body mass index (BMI), anti-Müllerian hormone (AMH), LH, and LH/FSH ratio, 106 women were divided into two groups: 53 received r-LH/r-FSH, and 53 received r-FSH alone. Baseline data, stimulation parameters, and ART outcomes were analyzed. Women in the r-LH/r-FSH group required a higher cumulative FSH dose (2932 ± 848 vs. 2455 ± 588IU, p<0.002), produced more follicles on trigger day (13.91 ± 7.45 vs. 10.09 ± 5.55, p=0.014), and had more oocytes injected (13.81 ± 8.01 vs. 11.66 ± 5.57, p=0.0499). Multivariate analysis confirmed r-LH/r-FSH was independently associated with increased follicular recruitment, regardless of AMH levels. However, stimulation protocol was not a significant predictor of oocyte count; age and AMH remained the primary factors. Total FSH dose was not associated with follicle number. No significant differences were observed in cumulative live birth rate; however, clinical pregnancy rate (CPR) after frozen embryo transfer (FET) was higher in the control group (54.5% vs. 25.0%, p=0.043). Conclusion Adding r-LH to r-FSH during COS in women with PMOS was associated with increased follicular recruitment but did not improve live birth or overall pregnancy rates. Notably, CPR after FET was lower with r-LH/r-FSH. These findings suggest r-LH may modulate ovarian response, but further research is needed to clarify its role in ART protocols. Due to the retrospective, non-randomized design, these results are hypothesis-generating, and routine use of r-LH in this setting cannot currently be recommended.