Erratum: Is intracrinology of endometriosis relevant in clinical practice? A systematic review on estrogen metabolism

Identification of predictors of the ovarian response to clomiphene citrate in infertile women with polycystic ovary syndrome: A post-hoc analysis of a randomized controlled trial

Liu Y et al., 2026·Frontiers in endocrinology

Clomiphene citrate (CC) is the first-line medication for inducing ovulation in women with polycystic ovary syndrome (PCOS). However, approximately 20% of patients with PCOS are resistant to CC. This study aims to identify reliable baseline predictors of CC resistance in infertile women with PCOS. A post-hoc analysis of a large, multicenter randomized controlled trial (PCOSAct trial) conducted in China. The current analysis comprised the 471 participants who were randomized to the active CC arm and completed the requisite follow-up. To identify potential candidate variables, we employed multivariable logistic and LASSO regression analyses. Within the framework of a multivariable logistic regression model, we also estimated the independent associations between the identified candidate variables and resistance to CC. Additionally, we plotted the Receiver Operating Characteristic (ROC) curve and utilized the DeLong method to compare the statistical differences in the area under the curve (AUC). Finally, we constructed a restricted cubic spline (RCS) logistic regression model to illustrate the dose-response relationship between continuous predictor variables and CC resistance. CC resistance was identified in 32 (6.8%) participants. Body Mass Index (BMI), Total Testosterone (TT), and Anti-Müllerian Hormone (AMH) were useful predictors of ovarian response to CC. The "T+BMI" dual-factor model demonstrated high discriminative power (AUC = 0.801) and was statistically comparable to the three-factor model including AMH (AUC = 0.818; P = 0.347). TT was the strongest individual predictor (OR = 2.73 per 1-unit), while BMI was the most significant modifiable risk factor (OR = 2.49 per 1-SD). A simplified "T + BMI" assessment provides comparable prognostic utility without the need for AMH testing. For patients at high risk of CC resistance, we recommend upfront use of aromatase inhibitors or low-dose gonadotropins. This strategy avoids ineffective treatment cycles and enables personalized ovulation induction. The study was registered on ClinicalTrials.gov under the identification number NCT01573858 on July 6, 2012.

Clinical, metabolomic, and proteomic profiles associated with reproductive outcomes in unexplained recurrent pregnancy loss

Song Z et al., 2026·Frontiers in endocrinology

To identify preconception clinical and multi-omics factors associated with conception and early pregnancy loss in women with unexplained recurrent pregnancy loss (URPL). In this prospective cohort study, 149 women with URPL selected from 420 outpatients based on guideline-recommended criteria were enrolled between November 2024 and May 2025 and followed-up for 12 months. Preconception fasting plasma was analyzed for clinical biomarkers, untargeted metabolomics, and data-independent acquisition proteomics. Outcomes included conception, ongoing pregnancy beyond 12 weeks and early pregnancy loss before 12 weeks. Multivariable logistic regression was used to evaluate the associations of clinical and multi-omics factors with reproductive outcomes, adjusting for maternal age, body mass index, number of prior losses, and use of assisted reproductive technology. Of 149 women, 99 conceived (66.4%) during the follow-up. By 12 weeks of gestation, 67 (67.7%) had ongoing pregnancies and 32 (32.3%) experienced early pregnancy loss. Higher testosterone was associated with lower probability of conception (adjusted odds ratio [aOR] 0.50, 95% confidence interval [CI] 0.28-0.89, p = 0.019). Women who conceived showed higher levels of progesterone-related metabolites, including 17-hydroxyprogesterone (fold change, FC = 3.89), pregnanediol 3-O-glucuronide (FC = 2.37), and pregnanetriol 3α-O-β-D-glucuronide (FC = 2.39). Among women who conceived, higher prolactin was associated with higher odds of early pregnancy loss (aOR 1.09, 95% CI 1.01-1.18, p = 0.036), and anti-phosphatidylserine/prothrombin showed a borderline association (aOR 1.07, 95% CI 1.00-1.14, p = 0.052). Early pregnancy loss was characterized by lower bile acid-related metabolites and higher caffeine and methylxanthine metabolites. Proteomic analysis showed enrichment of bile acid biosynthetic process. After adjustment, higher 7α,12α-dihydroxy-3-oxocholest-4-en-27-oic acid was associated with lower odds of early pregnancy loss (aOR 0.64, 95% CI 0.44-0.95, p = 0.025). Higher testosterone was associated with lower odds of conception. Among women who conceived, early pregnancy loss was associated with higher prolactin, borderline higher anti-PS/PT, lower bile acid-related metabolites, and higher caffeine-related metabolites, with 7α,12α-dihydroxy-3-oxocholest-4-en-27-oic acid identified as an exploratory metabolomic candidate. These findings suggest that potential androgen-related biology, prolactin, non-criteria antiphospholipid antibodies, and bile acid metabolism may be associated with reproductive outcomes in URPL, warranting validation in independent cohorts.

Network meta-analysis on the efficacy of different interventions for treating thin endometrium

Unnamed record, 2025·Frontiers in Endocrinology

Editorial: Nervous system and reproduction: a highly integrative partnership

Lara HE et al., 2025·Frontiers in endocrinology

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.