Impact of Vitamin D Supplementation on IVF Outcomes in Vitamin D-Deficient Poor Responders: a Randomized Controlled Trial.

OBJECTIVE

This study aimed to evaluate the effect of vitamin D supplementation on in vitro fertilization (IVF) outcomes in poor responder women with vitamin D deficiency, focusing on fertilization rates, oocyte quality, and pregnancy rates.

METHODS

A randomized, double-blinded, placebo-controlled trial was conducted at a tertiary referral center (February 2022–2024). Seventy poor responder women (POSEIDON groups 3–4) with serum vitamin D levels < 30 ng/mL were randomized to receive either weekly 50,000 IU vitamin D (n = 33) or placebo (n = 35) for 6–8 weeks before IVF. Both groups underwent a GnRH-antagonist protocol. Primary outcomes included fertilization rate (2PN oocytes) and oocyte maturity (germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages). Secondary outcomes were chemical pregnancy rate (β-hCG > 50 IU/L), follicular fluid vitamin D levels, and embryo quality. Data were analyzed via Intention-to-Treat (ITT) and per-protocol approaches using SPSS v21.

RESULTS

Baseline characteristics (age, BMI, AMH, infertility duration) were comparable between groups (p > 0.05). Post-intervention, serum vitamin D levels were significantly higher in the supplementation group (40.95 ± 15.22 ng/mL vs. 25.07 ± 7.45 ng/mL, p < 0.001), but follicular fluid levels did not differ significantly (33.57 ± 23.59 vs. 25.49 ± 21.23 ng/mL, p = 0.12). IVF outcomes showed no significant differences in fertilization rate (0.50 ± 0.47 vs. 0.80 ± 1.66, p = 0.38), oocyte maturity, or embryo transfer cancellation rates (69.7% vs. 68.6%, p = 0.72). Both groups ' chemical pregnancy rates were similarly low (3.0% vs. 5.7%, p = 0.72). Per-protocol analysis yielded consistent results.

CONCLUSION

Vitamin D supplementation did not improve IVF outcomes in poor responders despite significantly increasing serum vitamin D levels. The lack of effect may reflect insufficient ovarian uptake of vitamin D or the inherently low prognosis of this population. Routine supplementation for IVF success in poor responders is not supported, though monitoring deficiency remains important for general health.