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Age-dependent effects of low-molecular-weight heparin in recurrent implantation failure: A retrospective cohort study
Wenjing Wan1, Yujia Ren1, Yan Zhao2
1The Second Hospital, State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250012, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong 250012, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China.
Abstract:
This study aims to evaluate the effect of low molecular weight heparin (LMWH) on pregnancy outcomes in recurrent implantation failure (RIF) women without thrombophilia undergoing freeze-thaw embryo transfer (FET) cycles. A total of 392 FET cycles conducted between January 2021 and November 2024 were included in the study. Patients were divided into two groups: the LMWH group, receiving daily subcutaneous injections of 4000 AxaIU LMWH starting on the day of embryo transfer, and the control group, following the standard luteal phase support protocol without LMWH administration. Baseline characteristics and reproductive outcomes of the patients were systematically collected. Generalized estimating equation (GEE) models incorporating logistic regression were applied to adjust for potential confounding factors. Additional subgroup analyses were performed to assess the association between maternal age and pregnancy outcomes. After adjusting for confounding variables, no statistically significant differences were observed between the two groups in the rates of ongoing pregnancy (p = 0.729), biochemical pregnancy (p = 0.487), clinical pregnancy (p = 0.068) and miscarriage (p = 0.122) between the two groups. However, subgroup analysis revealed that among women over 35 years of age, the LMWH group exhibited significantly higher rates of clinical pregnancy (p = 0.016) and ongoing pregnancy (p = 0.039) compared to the control group. Although LMWH does not demonstrate improve pregnancy o utcomes in the general population of women with RIF, it may offer benefits for women of advanced maternal age. Considering these potential advantages in older women, further research is warranted to clarify the role of LMWH, particularly within the subgroup of women over 35 years of age.
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