The Association Between Pre-cycle Maternal Vitamin D Status and Reproductive Outcomes in Frozen-Thawed Embryo Transfer: A Systematic Review and Meta-Analysis

Vitamin D has been increasingly recognized for its potential role in reproductive physiology, particularly in endometrial receptivity and implantation. Despite growing interest, the impact of serum vitamin D status on outcomes of frozen embryo transfer (FET) cycles remains debated. The objective of this systematic review and meta-analysis was to assess the association between maternal vitamin D concentrations and reproductive success, specifically clinical pregnancy (CPR) and live birth rates (LBR), during frozen-thawed embryo transfer cycles, effectively focusing on the role of endometrial receptivity A systematic search was conducted in CENTRAL, Embase, MEDLINE, and Scopus for observational studies published until November 2025. Eligible studies compared reproductive outcomes in women with low versus normal serum 25-hydroxyvitamin D (25(OH)D) levels before autologous FET. The women were categorized as vitamin D insufficient if the level was <20 ng/ml and <30 ng/ml in different studies. The primary outcomes were the clinical pregnancy rate (CPR) and live birth rate (LBR). Data were pooled using a random-effects model, and the risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Four cohort studies comprising 2,061 FET cycles were included in the analysis. In the overall pooled analysis, low vitamin D levels were associated with lower odds of clinical pregnancy; however, this association did not reach statistical significance (OR: 0.37, 95% CI: 0.12-1.08), likely due to substantial heterogeneity among studies (I²=92.7%). When the analysis was restricted to high-quality research (involving 1,769 cycles), heterogeneity was eliminated (I²=0%), demonstrating a significant reduction in the likelihood of clinical pregnancy for patients with vitamin D deficiency (OR: 0.80, 95% CI: 0.65-0.99; p=0.03). Similarly, pooled analysis of live birth outcomes demonstrated a borderline reduction in live birth rates in the low vitamin D group, although this finding did not reach statistical significance (OR: 0.79, 95% CI: 0.60-1.04; p=0.08). Vitamin D deficiency appears to be associated with adverse reproductive outcomes in FET cycles, particularly when analyzing high-quality data. These findings suggest that low vitamin D levels are associated with adverse FET outcomes. However, as this review was limited to observational studies, these results identify deficiency as a prognostic marker rather than proving that screening and repletion directly optimize implantation and pregnancy success. Therefore, vitamin D sufficiency appears to be associated with poorer reproductive outcomes in (FET) cycles, but high-quality randomized trials are needed to establish definitive recommendations.