Spontaneous Reduction in ART-Conceived Twin Pregnancies: Risk Factors, Perinatal Outcomes, and a Prediction Model
DOI:
https://doi.org/10.71321/mapcd847Keywords:
Assisted reproductive technology, Twin pregnancy, Spontaneous reduction, Logistic regression, Prediction modelAbstract
Objective: To investigate the risk factors for spontaneous reduction (SR) in assisted reproductive technology (ART)-conceived twin pregnancies and compare perinatal outcomes between SR and non-SR pregnancies, and to develop and validate an SR risk prediction model in the dizygotic twin (DZT) cohort.
Methods: This single-center retrospective cohort study enrolled patients who achieved clinical twin pregnancies following ART at the Reproductive Center of the First Affiliated Hospital of Anhui Medical University between January 2015 and December 2024. Participants were classified into monozygotic twins (MZT, n=505) and dizygotic twins (DZT, n=3,263) based on the number of gestational sacs and fetal heartbeats detected on early pregnancy ultrasound, and each cohort was further divided into SR and Non-SR groups. Baseline characteristics, treatment parameters, and perinatal outcomes were compared between groups. Univariable and multivariable logistic regression analyses were performed with SR as the dependent variable, incorporating nine core predictors. A predictive model for SR was constructed in the DZT cohort and internally validated; model performance was evaluated using the receiver operating characteristic (ROC) curve with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis (DCA). Risk stratification was performed by tertiles of predicted probability.
Results: In the DZT cohort, the SR group had significantly older maternal age, a higher proportion of advanced maternal age (≥35 years), and higher rates of blastocyst-stage transfer, intracytoplasmic sperm injection (ICSI), and frozen-thawed embryo transfer cycles than the Non-SR group (all P<0.05). No statistically significant differences were observed in any of these characteristics in the MZT cohort. Perinatal outcome trends were consistent across both cohorts: the SR group had later gestational age at delivery, lower rates of preterm birth and low birth weight, but higher rates of glucose metabolism abnormalities and lower rates of premature rupture of membranes. Multivariable logistic regression identified advanced maternal age (aOR=3.00), history of previous miscarriage (aOR=1.32), blastocyst-stage transfer (aOR=3.05), non-good-quality embryos (aOR=1.79), ICSI (aOR=1.56), and frozen-thawed cycles (aOR=3.33) as independent risk factors for SR, whereas secondary infertility (aOR=0.67) and transfer of ≥2 embryos (aOR=0.53) were associated with a reduced risk. The DZT-SR prediction model achieved an AUC of 0.857 on internal validation, with acceptable calibration and favorable net clinical benefit on DCA. SR incidence increased progressively across low-, intermediate-, and high-risk strata at 8.3%, 28.7%, and 77.9%, respectively.
Conclusion: SR in ART-conceived twin pregnancies is closely associated with maternal age and multiple embryo- and cycle-related factors. The DZT-SR prediction model, built on nine routinely available clinical variables, demonstrated good internal validation performance and may serve as a practical tool for early pregnancy risk stratification and individualized follow-up planning.
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