Low-molecular-weight heparin in thrombophilic women receiving in vitro fertilization/intracytoplasmic sperm injection: A meta-analysis

Abstract

Introduction: This meta-analysis aimed to evaluate the efficacy and safety of low-molecular-weight heparin (LMWH) on pregnancy outcomes in thrombophilic women receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).

Material and methods: A systematic literature search of PubMed, EMBASE, the Cochrane Library, and China National Knowledge Infrastructure was performed to identify randomized controlled trials (RCTs) comparing LMWH with no treatment or placebo published from database inception until February 19, 2023. Primary outcomes were the clinical pregnancy rate and implantation rate, and secondary outcomes were the live birth rate, miscarriage rate, and the risk of bleeding events. The certainty of the evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Meta-analysis was conducted using STATA 14.0.

Results: Five RCTs involving 1094 thrombophilic women receiving IVF/ICSI were finally included. Administration of LMWH was associated with statistically higher clinical pregnancy rate (4 RCTs, risk ratio [RR] 1.50, 95% confidence interval [CI] 1.23-1.82, p < 0.001, low certainty evidence), implantation rate (5 RCTs, RR 1.49, 95% CI 1.25-1.78, p < 0.001, very low certainty evidence), and live birth rate (2 RCTs, RR 2.15, 95% CI 1.60-2.89, p < 0.001, very low certainty evidence), but with statistically lower miscarriage rate (2 RCTs, RR 0.36, 95% CI 0.15-0.86, p = 0.021, very low certainty evidence). However, using LMWH was linked to a higher risk of bleeding events (2 RCTs, RR 2.36, 95% CI 1.49-3.74, p < 0.001, very low certainty evidence).

Conclusions: Very low certainty evidence suggests that administration of LMWH may benefit pregnancy outcomes in thrombophilic women receiving IVF/ICSI treatment, although it may also increase the risk of bleeding events. However, before putting our findings into practice, healthcare professionals should conduct an in-depth evaluation of the available evidence and specific patient situations. Furthermore, due to the low methodological quality of the included studies, more high-quality studies are needed to validate our findings in the future.

Keywords: in vitro fertilization; intracytoplasmic sperm injection; low-molecular-weight heparin; pregnancy outcomes; thrombophilia.