Reproductive success linked to 25-(OH)D concentrations in PCOS

Measures of reproductive success in women with polycystic ovary syndrome after ovulation induction may be independently predicted by serum 25-hydroxyvitamin D levels, according to study data.

“Our current study reaffirms a relevance of adequate 25-(OH)D for procreative success in women with PCOS undergoing [ovulation induction],” the researchers wrote. “Beyond reaffirming a consistency in directionality of the previously observed associations, we have additionally noted that this association becomes apparent at serum 25-(OH)D levels that are well beyond the threshold of 30 ng/mL that is currently deemed as a target ‘normal’ level.”

Lubna Pal, MBBS, F RCOG, FACOG, associate chair of education in the department of gynecology and reproductive sciences at Yale School of Medicine, and colleagues evaluated data from the Pregnancy in Polycystic Ovary Syndrome (PPOS I) randomized controlled trial on 540 women (mean age, 28 years) with PCOS to determine whether any links exist between vitamin D status and ovulation induction outcomes.

Primary outcome was live birth, and secondary outcomes included ovulation and pregnancy loss after ovulation induction. Vitamin D status was defined as sufficient ( 30 ng/mL), inadequate (20-29.9 ng/mL), deficient (< 20 ng/mL) or severely deficient (< 10 ng/mL).

During the 6-month trial duration, 74% of participants had evidence of ovulation. Compared with participants with 25-(OH)D levels of at least 20 ng/mL, those with 25-(OH)D deficiency were less likely to achieve ovulation (P = .006).

Live birth rate was nearly 19% overall. Compared with participants who did not deliver a live birth, serum 25-(OH)D was higher in those who did (P = .046). The likelihood of live birth was increased by 2% with each 1 ng/mL increase in 25-(OH)D (OR = 1.02; 95% CI, 1-1.04). Participants who were vitamin D sufficient had a 26% live birth rate, whereas the likelihood of live birth decreased in participants with vitamin D insufficiency (OR = 0.74; 95% CI, 0.57-0.96), vitamin D deficiency (OR = 0.61; 95% CI, 0.35-1.08) and vitamin D severe deficiency (OR = 0.48; 95% CI, 0.19-1.23).

Participants with vitamin D levels greater than 45 ng/mL had a fourfold increased likelihood of live birth (OR = 4.5; 95% CI, 1.27-15.72), whereas there was a 44% reduction in likelihood of live birth among participants with 25-(OH)D levels less than 30 ng/mL (OR = 0.58; 95% CI, 0.35-0.92). There were progressive improvements in the odds for live birth at 25-(OH)D thresholds of at least 38 ng/mL (OR = 1.42; 95% CI, 1.08-1.8) and at least 40 ng/mL (OR = 1.51; 95% CI, 1.05-2.17).

Twenty-nine percent of positive pregnancy tests were followed by pregnancy loss, and there was an 82% reduced likelihood of pregnancy loss with serum 25-(OH)D levels of at least 38 ng/mL compared with lower levels (OR = 0.18; 95% CI, 0.02-0.9).

“Our data suggest that for infertile women with PCOS, [vitamin D] status, as reflected by serum levels of 25-(OH)D, is relevant for procreative success,” the researchers wrote. “We hypothesize that decline in circulating 25-(OH)D below the [lower reproductive threshold] may be contributory to ovulatory dysfunction, whereas at levels at and above an [upper reproductive threshold], achieved through supplementation, may result in improved endometrial receptivity, as has been previously suggested, thus yielding improved treatment [live birth] rates and reduce risk of [pregnancy loss] in women with PCOS, a population that is already an enhanced risk for pregnancy wastage.” – by Amber Cox