Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology

Abstract

Objective

To assess the correlation between the levels of vitamin D in follicular fluid and serum, and to determine whether the level of 25-hydroxyvitamin D (25OH-D) in follicular fluid of infertile women undergoing assisted reproductive technology (ART) is associated with the outcome.

Study design

Eighty-two infertile women undergoing ART at an academic tertiary care centre were recruited for a prospective cohort study. Levels of 25OH-D in follicular fluid and serum were measured. Standardized regimens for pituitary downregulation and controlled ovarian hyperstimulation were employed. Patient and cycle parameters, and clinical pregnancy (defined as evidence of intra-uterine gestation sac plus heart rate on ultrasound) were determined.

Results

A significant correlation was found between the levels of vitamin D in follicular fluid and serum (r = 0.767, p = 0.001). The overall rates of chemical, clinical and ongoing pregnancy were 35.5% (n = 29), 29.3% (n = 24) and 23.2% (n = 19), respectively. No significant difference was found in these pregnancy rates between the tertiles of 25OH-D level in follicular fluid (p = 0.959, 0.995 and 0.604, respectively). The median serum level of vitamin D was 8.13 (range 5.37–13.62) ng/ml in the clinically pregnant group and 8.29 (range 5.93–21.23) ng/ml in the non-pregnant group (p = 0.235). Interestingly, the median level of vitamin D in follicular fluid was 9.19 (range 5.25–19.51) ng/ml in the clinically pregnant group and 10.34 (range 5.89–29.69) ng/ml in the non-pregnant group (p = 0.433). The fertilization rate decreased significantly and the implantation rate increased (not significantly) with increasing tertiles of 25OH-D level in follicular fluid.

Conclusions

The level of 25OH-D in follicular fluid is reflective of body stores of vitamin D. Most subjects in this study were deficient in vitamin D, but this study found that vitamin D deficiency does not play a pivotal role in the outcome of ART.

Introduction

The well-established function of the steroid hormone vitamin D is to maintain calcium and phosphorus homeostasis, and to promote bone mineralization. Since this vitamin can have a significant influence on the growth and differentiation of a variety of tissues, and decreases the risk of many chronic illnesses including common cancers, autoimmune diseases, infectious diseases and cardiovascular disease [1], [2], [3], [4], [5], [6], [7], it has become the focus of many studies in recent years. The discovery that most tissues and cells in the body have a vitamin D receptor has provided new insights into the function of this vitamin [1]. Reduced fertility rates and fertility capacity, diminished mating success, impaired neonatal growth, increased pregnancy complications, gonadal insufficiency, reduced aromatase gene expression, low aromatase activity, hypogonadism, bone malformations, uterine hypoplasia, impaired folliculogenesis and infertility have been reported in vitamin-D-deficient animal models [8], [9], [10]. Also, it has been reported that vitamin D affects placental steroidogenesis, placental calcium transport, expression of placental lactogen and decidualization of the endometrium [2], [11], [12].

Although the biological actions of vitamin D are mediated through a member of the steroid nuclear hormone receptor superfamily but there is a debate about the mechanism of reproductive function of this vitamin [10], [13], [14], [15]. While some attributed the direct effect of vitamin D but others realize that hypocalcemia associated with vitamin D deficiency is responsible for reduced fertility in vitamin D–deficient animals [16].

Due to limited specific human data in this regard and the epidemic of vitamin D deficiency in Iran [17], this study was undertaken to evaluate the predictive value of the level of vitamin D in follicular fluid on assisted reproductive technology (ART) outcome in infertile patients.