Effect of vitamin D supplementation on frozen embryo transfer cycle outcomes

The role of serum 25-OH D3 (D3) in the physiology and regulation of the female genital system has gained significant research interest. Recent data have suggested that sufficient D3 levels are associated with improved outcomes of in vitro fertilization (IVF), although other studies failed to confirm so. Screening for D3 levels before IVF is becoming common practice in many IVF centres, and D3 insufficiency is treated with supplements before treatment. However, little is known about the effect of this intervention on D3 levels during endometrial preparation for frozen-embryo transfer (FET) cycles, especially regarding clinical outcomes. To examine the effect of vitamin D supplementation and the impact of vitamin D status in women undergoing FET cycles, a prospective study of infertile women undergoing FET cycles was carried out. Initial screening of D3 levels was performed in 252 infertile women before a FET cycle, and where insufficiency was found (<30 ng/mL) [115 (45.6%)], supplements were prescribed according to a standardized protocol. Serum D3 levels were measured at three distinct time-points: at the initiation of endometrial preparation (T1), embryo transfer (T2), and beta-hCG testing (T3). We found no significant difference in ongoing pregnancy [40 (34.8%) vs. 51 (37.2%); odds ratio (OR) 0.90, 95% confidence interval (CI) 0.54-1.51; adjusted OR 1.04, 95% CI 0.58-1.83], live birth, positive β-hCG, clinical pregnancy, miscarriage, and ectopic pregnancy rates between D3-insufficient participants at T1 receiving vitamin D and D3-replete ones not receiving any supplementation (p-values >0.05). We also found no significant difference in ongoing pregnancy [21 (30.9%) vs. 66 (40.2%), and 17 (34.0%) vs. 51 (41.5%)] and the rest of the outcomes between D3-insufficient and replete participants at T2 and T3, respectively (p-values >0.05). In conclusion, this prospective cohort study of women undergoing FET cycles found no significant difference in ongoing pregnancy rates between D3-insufficient participants receiving supplementation at the beginning of endometrial preparation and replete ones receiving no supplementation. Large, high-quality trials are required to further investigate this hypothesis and compare the IVF outcomes between replete participants, insufficient participants receiving no supplementation, and insufficient participants receiving supplementation.