Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

Abstract

Purpose: To review the current literature regarding the role of vitamin D status in pregnancy outcomes in women undergoing assisted reproductive technology (ART) and to assess cost-effectiveness of routine vitamin D deficiency screening and repletion prior to initiation of ART.

Methods: A systematic literature review was conducted using PubMed. Relevant study outcomes were compared among the selected studies. A cost-benefit analysis was performed using a decision tree mathematical model with sensitivity analyses from the perspective of direct societal cost. Published data were used to estimate probabilities and costs in 2014 US dollars.

Results: Thirty-four articles were retrieved, of which eight met inclusion criteria. One study demonstrated a negative relationship between vitamin D status and ART outcomes, while two studies showed no association. The remaining five studies concluded that ART outcomes improved after vitamin D repletion.

Conclusion: The majority of reviewed studies reported a decrement in ART outcomes in patients with vitamin D deficiency. Cost-benefit analyses suggested that screening and supplementing vitamin D prior to ART might be cost effective, but further evidence is needed. Given the absence of Level I evidence regarding vitamin D status and ART outcomes, full endorsement of routine vitamin D screening and supplementation prior to ART is premature.

Fig. 1

Synthesis of vitamin D and its effects on reproduction and pregnancy. D3 cholecalciferol, GDM gestational diabetes, PCOS polycystic ovarian syndrome, SAB spontaneous abortion, VDR vitamin D receptor

Fig. 2

Flow diagram of study selection

Fig. 3

Decision tree mathematical model for women with initial screen showing vitamin D deficiency. Women in the treatment strategy assumed to be replete before initiation of first cycle. CP clinical pregnancy, OP ongoing pregnancy, SAB spontaneous abortion

Fig. 4

Cost-benefit sensitivity analysis varying the ongoing pregnancy rate of an ART cycle with screening and treatment with vitamin D supplementation. The ongoing pregnancy rate of an untreated ART cycle was set at 38 %. Solid black line, treatment strategy; dashed gray line, no treatment strategy. X-axis, ongoing pregnancy rate (OPR); Y-axis, cost per ongoing pregnancy (2014 USD)

Fig. 5

Cost-benefit sensitivity analysis varying the cost of single ART cycle with vitamin D supplementation included. The cost for a single ART untreated cycle was set at $14,794. Solid black line, treatment strategy; dashed gray line, no treatment strategy. X-axis, cost per treated cycle (2014 USD), Y-axis, cost per ongoing pregnancy (2014 USD)