The Association Between Pre-cycle Maternal Vitamin D Status and Reproductive Outcomes in Frozen-Thawed Embryo...

Area of Science:

• Reproductive Endocrinology
• Nutritional Science
• Infertility Research

Background:

• Vitamin D is increasingly recognized for its role in reproductive health, specifically endometrial receptivity and implantation.
• The precise impact of maternal vitamin D status on frozen embryo transfer (FET) outcomes remains under investigation.
• Endometrial receptivity is a critical factor in successful implantation during assisted reproductive technologies.

Purpose of the Study:

• To systematically review and meta-analyze the association between maternal vitamin D concentrations and reproductive success in FET cycles.
• To evaluate the impact of vitamin D status on clinical pregnancy rates (CPR) and live birth rates (LBR).
• To focus on the role of endometrial receptivity in the context of vitamin D levels and FET outcomes.

Main Methods:

• Systematic search of CENTRAL, Embase, MEDLINE, and Scopus databases up to November 2025.
• Inclusion of observational studies comparing reproductive outcomes in women with low versus normal serum 25-hydroxyvitamin D (25(OH)D) levels before autologous FET.
• Data pooling using a random-effects model and risk of bias assessment using the Newcastle-Ottawa Scale (NOS).

Main Results:

• Four cohort studies (2,061 FET cycles) were included. Overall analysis showed low vitamin D associated with lower CPR, but not statistically significant (OR: 0.37, 95% CI: 0.12-1.08) due to high heterogeneity (I²=92.7%).
• Analysis restricted to high-quality studies (1,769 cycles) eliminated heterogeneity (I²=0%) and revealed a significant reduction in CPR for vitamin D deficient patients (OR: 0.80, 95% CI: 0.65-0.99; p=0.03).
• Pooled analysis of live birth rates showed a borderline, non-significant reduction in the low vitamin D group (OR: 0.79, 95% CI: 0.60-1.04; p=0.08).

Conclusions:

• Vitamin D deficiency appears linked to adverse reproductive outcomes in FET cycles, particularly evident in high-quality data.
• Low vitamin D levels may serve as a prognostic marker for poorer FET outcomes.
• High-quality randomized controlled trials are necessary to confirm these findings and establish definitive recommendations for vitamin D screening and supplementation in FET protocols.