Effects of vitamin D supplementation on semen quality, reproductive hormones and live birth rate: a randomized clinical trial

Context: Animal models and cross-sectional cohort studies have suggested a beneficial role for vitamin D in male reproduction.

Objective: Determine the effect of vitamin D and calcium supplementation on semen quality in infertile men with serum 25-hydroxyvitamin-D (25OHD)≤ 50 nmol/l.

Design: A single centre, triple-blinded, randomized clinical trial.

Participants: 1427 infertile men were screened to include 330. 1002 men did not meet inclusion criteria and 95 did not wish to participate.

Intervention: The active group received cholecalciferol 300,000IU initially followed by 1400IU + 500mg calcium daily for 150 days, while the other group received placebo.

Results: Serum concentrations of 25-OHD and 1,25OH2D3 were significantly higher in men treated with vitamin D + calcium for 150 days compared with placebo. Vitamin D supplementation was not associated with changes in semen parameters although spontaneous pregnancies tended to be higher 7.3% vs 2.4%,Δ5.0% [-0.6%;10.5%]. Vitamin D treatment in a subgroup of oligozoospermic men increased the chance for a live birth compared with placebo 35.6% vs 18.3%,Δ17.3% [1.6%; 32.9%]. Moreover, serum inhibin B was higher in vitamin D deficient men randomized to vitamin D 193pg/ml vs 143pg/ml, Δ49pg/ml [8;91pg/ml], however, the increase in sperm concentration was not significantly higher than placebo (p=0.07).

Conclusions: High dose vitamin D supplementation did not improve semen quality in vitamin D insufficient infertile men. The positive impact of vitamin D supplementation on live birth rate and serum inhibin B in oligozoospermic and vitamin D deficient men may be of clinical importance and warrant verification by others.

Trial ID: NCT01304927.