Low-molecular-weight heparin for frozen-thawed embryo transfer in women with adenomyosis: a parallel randomized pilot study

Adenomyosis is a gynecological disease caused infertility in woman of bearing age and there aren’t any effective treatments for it right now. This study aims to assess feasibility and provide preliminary clinical evidence regarding post‑implantation low‑molecular‑weight heparin (LMWH) and clinical pregnancy rates in women with adenomyosis undergoing in vitro fertilization (IVF). In this prospective, single-center, open-label, parallel, randomized pilot study, a total of 132 infertile women with adenomyosis diagnosed by the modified Morphological Uterus Sonographic Assessment (MUSA) criteria undergoing frozen-thawed embryo transfer (FET) were enrolled between January 2024 and November 2024 in department of Reproductive Medicine, the Second Qilu Hospital of Shandong University. Participants were randomly assigned in a 1:1 ratio using a computer-generated permuted-block randomization sequence to receive either subcutaneous enoxaparin sodium (LMWH group) for 14 days following embryo transfer or no LMWH intervention (control group). The primary exploratory outcome was the clinical pregnancy rate. Secondary outcomes included biochemical pregnancy rate, miscarriage rate, and live birth rate (blinded outcome assessment). In this exploratory analysis, all 132 patients who met the inclusion criteria were randomized evenly distributed into two groups. The clinical pregnancy rate in the LMWH group was higher than that in the control group (63.64% (42/66) versus 46.97% (31/66); RR: 1.355; 95% confidence interval (CI): 0.989–1.856; P = 0.054). Results remained consistent across logistic regression analysis. LMWH was associated with a higher odds of clinical pregnancy in both univariate (OR: 1.976; 95% confidence interval (CI): 0.985–3.965; P = 0.055) and multivariate models. However, the association remained statistically non-significant after adjustment for age and endometrial thickness prior to progesterone exposure (OR: 1.944; 95% confidence interval (CI): 0.952–3.968; P = 0.068). No study-related serious adverse events were observed. Despite the lack of statistical significance, the over 15% increase in the clinical pregnancy rate may represent a clinically meaningful trend, warranting further investigation of adjunctive post-transfer LMWH therapy in women with adenomyosis undergoing FET. These findings support a potential beneficial role for LMWH in this population and provide rationale for designing larger, adequately powered randomized controlled trials to confirm these preliminary observations and further evaluate its impact on live birth rate. The trial was prospectively registered at ClinicalTrials.gov under registration number ChiCTR2300079150 on 26 December 2023.