VITAMIN D DEFICIENCY AND UNEXPLAINED SUBFERTILITY: A PROSPECTIVE COHORT STUDY AT A TERTIARY HOSPITAL

Abstract

Background: Vitamin D's effect on fertility is uncertain, but its importance in reproductive health is growing. Unknown causes of infertility impact a considerable number of couples. Ovarian function and endometrial receptivity are affected by vitamin D deficiency in many reproductive-age women, which may reduce fertility [1]. Objective: To examine how blood vitamin D levels affect conception rates and reproductive hormone profiles in unexplained subfertility. Methods: From September 24, 2024, to March 20, 2025, the Combined Military Hospital (CMH) Lahore conducted this 6-month prospective cohort study. A consecutive non-probability sample of 100 subfertile women aged 18–36 with unexplained infertility (normal ovulatory function, patent fallopian tubes, and normal partner semen tests) was included. Women with pelvic inflammatory disease, genital TB, prior pelvic surgery, endometriosis, chronic medical conditions (e.g. diabetes or hypertension), or outside the age range were excluded. Standardized tests examined baseline serum 25-hydroxyvitamin D [25(OH)D] and essential fertility hormones: FSH, LH, TSH, prolactin, estrogen, and AMH. Participants were classified as vitamin D deficient (<20 ng/mL) or non-deficient (≥20 ng/mL). Conceptions were tracked for 6 months. Vitamin D deficiency vs. sufficient women's natural conception rate was the major outcome; hormone profile changes were secondary. All participants gave informed consent and ethical approval. Results: Participants had a mean age of 28.4±4.5 years and a mean infertile duration of 2.6±1.1 years Vitamin D deficiency was common, with 60% having 25(OH)D < 20 ng/mL and 40% having ≥ ≥20 ng/mL. Increased vitamin D levels were positively connected with AMH and inversely correlated with FSH (r = +0.30 and –0.22, respectively; p < 0.05), indicating improved ovarian reserve [3]. In the 6-month follow-up, 15 women (15%) got pregnant. Vitamin D-non-deficient women had a 25.0% cumulative pregnancy rate compared to 8.3% for deficient women (p = 0.02). Vitamin D-deficient women exhibited lower AMH levels (3.1±1.4 vs 4.0±1.6 ng/mL, p = 0.01) and somewhat higher day-3 FSH (7.8±2.0 vs 6.9±1.8 mIU/mL, p = 0.04) than vitamin D-sufficient women. Groups had equivalent LH, prolactin, TSH, and estradiol levels (p > 0.1). Figure 1 depicts vitamin D status-related conception rates, and Figure 2 shows pregnancy outcome distributions. Adverse effects were absent. Conclusion: Vitamin D deficiency was related to reduced conception rates and mild ovarian reserve marker abnormalities in this real-world sample of unexplained subfertility. Over six months, vitamin D-deficient women had one-third the pregnancy rate of vitamin D-sufficient women. These findings suggest vitamin D insufficiency contributes to female subfertility. Screening and addressing vitamin D insufficiency in subfertile women may enhance fertility, but intervention trials are needed to verify causality. Vitamin D supplementation may improve natural conception rates in unexplained infertility. More randomized studies are needed.