Purpose: This systematic review and meta-analysis aimed to compare the short-term reproductive and long-term obstetric outcomes after endometrial preparations by ovarian stimulation protocols and hormone replacement therapy (HRT) in women with polycystic ovary syndrome (PCOS) prior to frozen embryo transfer (FET). Method: PubMed, EMBASE, Web of Science and the Cochrane Library were searched to identify relevant studies. Primary outcome was live birth rate, secondary outcomes included the rates of clinical pregnancy, miscarriage, implantation and hCG-postive, cycle cancellation, ectopic pregnancy, preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus and abnormal placentation. Results: Nine studies, including 8327 patients with PCOS, were identified. Live birth rate was significantly higher (RR = 1.11, 95% CI = 1.03–1.19) and miscarriage rate (RR = 0.60, 95% CI = 0.46–0.78) was significantly lower in stimulated protocol compared to the rates in HRT. While the rates of ongoing pregnancy, clinical pregnancy, implantation, hCG-positive, cycle cancellation and ectopic pregnancy showed no significant difference between the two protocols. Compared HRT with different stimulation protocols, significantly higher clinical pregnancy rate (RR = 1.54, 95% CI = 1.20–1.98) were found in letrozole group, but not in the other subgroups. For the obstetric outcomes, the preterm birth and preeclampsia rates were significantly lower in the stimulated group compared to that in the HRT group (RR = 0.85, 95% CI = 0.74–0.98; RR = 0.57, 95% CI = 0.40–0.82, respectively), while gestational hypertension, gestational diabetes mellitus and abnormal placentation rates showed no significant difference. Conclusions: The present data suggest that ovarian stimulation protocol as an endometrial preparation regimen prior to FET might be superior to HRT protocol with a significantly higher rate of live birth, lower risk of miscarriage, preterm birth and preeclampsia. Our study showed stimulated protocol is better than HRT regimen as an endometrial preparation for women with PCOS. However, quality of the evidence is low, more well-designed RCT studies are still needed to confirm the results before clinical recommendation, particularly direct comparisons between letrozole and other stimulated regimens.

Understanding metabolic changes in reproductive failure, including early miscarriage (EM), recurrent miscarriage (RM), and repeated implantation failure (RIF), may be beneficial to understand the pathophysiology, thus improving pregnancy outcomes. Nine metabolomic profiling studies in women with reproductive failures (4 for EM, 3 for RM, and 2 for RIF) were included for systematic review. In total 78, 75, and 25 significant metabolites were identified and 40, 40, and 34 metabolic pathways were enriched in EM, RM, and RIF, respectively. Among them, 7 and 11 metabolites, and 28 and 28 pathways were shared between EM and RM and between RM and RIF, respectively. Notably, histidine metabolism has the highest impact in EM; phenylalanine, tyrosine, and tryptophan biosynthesis. Ubiquinone and other terpenoid–quinone biosynthesis metabolism have the highest impact factor in RM; alanine, aspartate, and glutamate metabolism have the highest impact factor in RIF. This study not only summarized the common and distinct metabolites and metabolic pathways in different reproductive failures but also summarized limitations of the study designs and methodologies. Hence, further investigations and validations of these metabolites are still urgently needed to understand the underlying metabolic mechanism for the development and treatment of reproductive failures.