Evaluation of the relationship between serum 25-hidroxy vitamin D levels and dominant follicle size and formation time in women undergoing ovulation induction

Objective: Infertiliy has been defined as the inability of a couple to achieve pregnancy despite regular and unprotected sexual intercourse for one year long period. Ovulatory dysfunction (20-40%), tubal and peritoneal diseases (30-40%), male factor (30-40%) and uterus factor have been identified as the causes of infertility. Ovulation induction has been designated as the use of pharmacological agents for triggering monofollicular development and ovulation in couples diagnosed with anovulation. This thesis study aims to evaluate the relationship among serum concentrations of vitamin D, size of dominant follicle and the time to acquire dominant follicle in women undergoing ovulation induction for infertility. Materials and Methods: This is a cross-sectional review of 101 couples that were diagnosed with infertility and underwent ovulation induction for infertility at the department of obstetrics and gynecology in Afyonkarahisar Health Sciences University Hospital between January 2020 and January 2022. All women aged younger than 40 years, all men aged younger than 40 years and all couples who had an indication for ovulation induction and intrauterine insemination (IUI) were included. All women aged older than 39 years, all men aged younger than 39 years and all couples who had an indication for in vitro fertilization (IVF) were excluded. Data related with age, marital duration, obstetric history, body mass index, basal hormone profile, medical and surgical history, infertility type, duration and cause, antral follicle count, spermiogram, previous and current ovulation induction cycles were recorded. Results: The mean female age was 26.5 years, the mean male age was 29.4 years, the mean marital duration was 4.4 years and the mean infertility duration was 2.6 years for 101 couples with infertility. Primary infertility was diagnosed in 56 couples (55.4%) while 45 couples (44.6%) had secondary infertility. BMI >30 was found in 38 (37.6%) of 101 patients. The most frequent causes of infertility were anovulation (n=64, 63.4%), hyperprolactinemia (n=21, 20.8%), male factor (n=15, 14.9%) and uterine factor (n=14, 13.9%). Polycystic ovaries were detected in 44.6% of infertile women (n=45) and there was oligospermy in 15.5% of infertile men (n=17). Ovulation induction was performed by administering clomiphene citrate in 41 women (40.6%), letrozole in 6 women (5.9%) and gonadotropins in 54 women (53.5%). The mean serum concentration of vitamin D was 13.52±5.93 mg/l (range: 1.88-27.74 mg/l) at the day of human chorionic gonadotropin (HCG) administration. Clinical pregnancy was achieved in 48 women out of 101 women who underwent ovulation induction (47.5%), there was ongoing pregnancy in 33 women (32.7%) and 7 women (6.9%) delivered live-born infants. When compared to couples that failed to achieve pregnancy by ovulation induction, the couples who were able to achieve pregnancy by ovulation induction had significantly higher female age (p=0.003), higher male age (p=0.012), longer marital duration (p=0.036), higher frequency of surgery (p=0.001) and cesarean delivery (p=0.003). The couples that failed to achieve pregnancy and the couples who were able to achieve pregnancy by ovulation induction were found to be have statistically similar serum concentrations of vitamin D (13.9±6.0 mg/l vs 13.2±5.9 mg/l, p=0.584). Similarly, ongoing pregnancies by ovulation induction and the remaining pregnancies were statistically similar with respect to serum levels of vitamin D (14.9±5.4 mg/l vs 11.5±6.7 mg/l, p=0.064). A statistically significant positive correlation was detected between basal prolactin levels and serum concentration of vitamin D at the day of HCG administration (r=0.282, p=0.004). There was a statististically significant negative correlation between basal thyroid stimulating hormone levels and serum concentrations of vitamin D at the day of HCG concentration (r=-0.263, p=0.008). Based on logistic regression analysis, female age, male age, marital duration and surgical history were identifid as independent prognostic factors for achieving clinical pregnancy (respectively p=0.040, p=0.013, p=0.040 and p=0.001). Vitamin D level was not defined as an independent prognostic factor for achieving either clinical pregnancy or ongoing pregnancy. Conclusion: This study concludes that serum concentrations of vitamin D do not exert significant effects on the success of ovulation induction cycles. However, this conclusion should be evaluated carefully and confirmed by studies with similar samples and designs before this conclusion has been addressed as a clinical practice point. The major reason for this recommendation is the existence of power limiting factors which are relatively small sample size, inability to draw a receiver operating curve, absence of longitudinal data and lack of data related with seasonal change of vitamin D concentrations. The inclusion of all patients who received different pharmacological agents and all patients who underwent IUI might lead to heterogeneity. Large scale and prospective studies with well planned design and standardization should be conducted to clarify the effects of serum vitamin D concentrations on clinical pregnancy and live birth ratios in infertile women undergoing ovulation induction.