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Objective: To propose a new gene expression signature that identifies endometrial disruptions independent of endometrial luteal phase timing and predicts if patients are at risk of endometrial failure., Design: Multicentric, prospective study., Setting: Reproductive medicine research department in a public hospital affiliated with private fertility clinics and a reproductive genetics laboratory., Patients: Caucasian women (n = 281; 39.4 ± 4.8 years old with a body mass index of 22.9 ± 3.5 kg/m 2 ) undergoing hormone replacement therapy between July 2018 and July 2021. Endometrial samples from 217 patients met RNA quality criteria for signature discovery and analysis., Intervention(s): Endometrial biopsies collected in the mid-secretory phase., Main Outcome Measure(s): Endometrial luteal phase timing-corrected expression of 404 genes and reproductive outcomes of the first single embryo transfer (SET) after biopsy collection to identify prognostic biomarkers of endometrial failure., Results: Removal of endometrial timing variation from gene expression data allowed patients to be stratified into poor (n = 137) or good (n = 49) endometrial prognosis groups on the basis of their clinical and transcriptomic profiles. Significant differences were found between endometrial prognosis groups in terms of reproductive rates: pregnancy (44.6% vs. 79.6%), live birth (25.6% vs. 77.6%), clinical miscarriage (22.2% vs. 2.6%), and biochemical miscarriage (20.4% vs. 0%). The relative risk of endometrial failure for patients predicted as a poor endometrial prognosis was 3.3 times higher than those with a good prognosis. The differences in gene expression between both profiles were proposed as a biomarker, coined the endometrial failure risk (EFR) signature. Poor prognosis profiles were characterized by 59 upregulated and 63 downregulated genes mainly involved in regulation (17.0%), metabolism (8.4%), immune response, and inflammation (7.8%). This EFR signature had a median accuracy of 0.92 (min = 0.88, max = 0.94), median sensitivity of 0.96 (min = 0.91, max = 0.98), and median specificity of 0.84 (min = 0.77, max = 0.88), positioning itself as a promising biomarker for endometrial evaluation., Conclusion(s): The EFR signature revealed a novel endometrial disruption, independent of endometrial luteal phase timing, present in 73.7% of patients. This EFR signature stratified patients into 2 significantly distinct and clinically relevant prognosis profiles providing opportunities for personalized therapy. Nevertheless, further validations are needed before implementing this gene signature as an artificial intelligence (AI)-based tool to reduce the risk of patients experiencing endometrial failure., Competing Interests: Declaration of Interests P.D.-G., P.S.-L., and A.P. report planned European patent IVI RMA GLOBAL. K.S. has nothing to disclose. D.M.-G. has nothing to disclose. J.M.S.-R. has nothing to disclose. M.D.C.V. has nothing to disclose. A.D.-P. has nothing to disclose. I.S.-R. has nothing to disclose. A.M.-M. has nothing to disclose. N.P. has nothing to disclose. D.W. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the effectiveness of cerclage in twin pregnancies with a short cervix., Study Design: Retrospective cohort study performed in two University Institutions in Valencia (Spain) with two different protocols for the management of asymptomatic dichorionic diamniotic twin pregnancies with mid-trimester cervical length ≤ 25 mm: treatment with indomethacin, antibiotics and cerclage (cerclage group) (N = 43) versus expectant management (control group) (N = 37)., Results: The initial cervical length was similar in both groups but detection of a short cervix was performed earlier in the cerclage group (21.6 vs 24.1 weeks, p < 0.001). Women with cerclage had a greater pregnancy latency (12.5 vs. 7.7 weeks, p < 0.001); higher gestational age at delivery (34.1 vs. 31.8 weeks, p < 0.04); less spontaneous preterm birth (SPB) < 28 weeks (11.6 % vs 37.8 %, p < 0.009); higher birthweight (2145 vs 1733 g, p < 0.001); lower birthweight < 1500 g (12.5 % vs 40.0 %, p < 0.001); less admissions to the neonatal intensive care unit (NICU) (24.1 % vs 43.3 %, p < 0.03); shorter stay at NICU (25.6 vs 49.4 days, p < 0.02); lower respiratory distress requiring mechanical ventilation (14.9 % vs 36.5 %, p < 0.02); fewer patent ductus arteriosus (8.9 % vs 26.9 %, p < 0.008); and lower composite adverse neonatal outcome (26.6 % vs. 44.8 %, p < 0.03). Cerclage and gestational age at diagnosis were the only independent predictors of SPB < 32 and < 28 weeks by multivariate analysis. The cumulative data in the literature show promising beneficial effects of cerclage., Conclusion: Our data suggest that cerclage in asymptomatic twin pregnancies with a short cervix may reduce the earliest SPB and may improve neonatal outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)