Vitamin D deficiency and pregnancy rates following frozen-thawed embryo transfer: a prospective cohort study

Abstract

Study question: What is the effect of vitamin D deficiency on the pregnancy rates following frozen embryo transfer (FET)?.

Summary answer: Vitamin D deficiency does not affect pregnancy rates in FET cycles.

What is known already: Although there is evidence that the potential impact of vitamin D deficiency on reproductive outcome may be mediated through a detrimental effect on oocyte or embryo quality, the rationale of our design was based on evidence derived from basic science, suggesting that vitamin D may have a key role in endometrial receptivity and implantation. Only few retrospective clinical studies have been published to date with conflicting results.

Study design, size, duration: This study is the first prospective observational cohort study from the Centre for Reproductive Medicine at the University Hospital of Brussels. The duration of the study was 1 year.

Participants/materials, setting, methods: A total of 280 consecutive patients, who had at least one blastocyst frozen and were planned for a FET, were enrolled in the study following detailed information and signing of a written informed consent. Serum analysis of 25-OH vitamin D was measured on the day of embryo transfer, and the impact of vitamin deficiency was investigated on reproductive outcomes.

Main results and the role of chance: Among all patients, 45.3% (n = 127) had vitamin D deficiency (<20 ng/ml), and 54.6% (n = 153) had vitamin D levels ≥20 ng/ml. Positive human chorionic gonadotrophin rates were similar among patients with vitamin D deficiency and women with total serum 25-OH vitamin D levels ≥20 ng/ml (40.9 versus 48.3%, P = 0.2). Similarly, no difference was found in clinical pregnancy rates in women with vitamin D deficiency [32.2% (41/127)] compared with those with higher vitamin D levels [37.9% (58/153)]; P = 0.3. When analyzing the results according to different thresholds, as proposed by the Endocrine Society, clinical pregnancy rates were comparable between vitamin D deficient (<20 ng/ml), vitamin D insufficient (20-30 ng/ml) and vitamin D replete women (≥30 ng/ml) [32.3% (41/127) versus 39.5% (36/91) versus 35.5% (22/62), respectively, P = 0.54]. Multivariate logistic regression analysis showed that vitamin D status is not related to pregnancy outcome.

Limitations, reasons for caution: Ethnicity in relation to vitamin D status was not assessed, given that the vast majority of patients included in our study were Caucasian, whereas we did only assess 25-OH vitamin D levels and not bioavailable vitamin D. Furthermore, although we failed to find a difference between vitamin D deficient women and women with vitamin D levels ≥20 ng/ml, we need to underscore that our study was powered to detect a difference of 15% in clinical pregnancy rates.

Wider implications of the findings: Vitamin D deficiency does not significantly impair pregnancy rates among infertile women undergoing frozen-thawed cycles. The measurement of vitamin D levels in this population should not be routinely recommended.

Study funding/competing interests: No external funding was used for this study. No conflicts of interest are declared.

Keywords: blastocyst; frozen embryo transfer; implantation; pregnancy rate; vitamin D.