by Catherine M Windrim, Daniel Kane, Grainne Kelleher, Edgar Mocanu
International Journal of Obstetrics & Gynaecology Vol. 170; Issue 3. September 2025. Open access.
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Abstract
Objective
To evaluate the burden of vitamin D deficiency in female patients attending a fertility clinic in a tertiary referral center, assess temporal trends—including the potential impact of COVID-19 lockdowns—and explore socioeconomic disparities in vitamin D levels.
Methods
This retrospective cohort study analyzed vitamin D measurements from 765 female patients (mean age 35.7 ± 5.8 years) attending a fertility clinic between March 2010 and May 2022. Vitamin D status was categorized as deficient (<30 nmol/L), insufficient (30–50 nmol/L), or normal (>50 nmol/L). Comparative analyses examined pre- and post-COVID periods and healthcare funding status.
Results
Overall, 39.9% (n = 305) of patients exhibited sub-optimal vitamin D levels, with 8.8% (n = 67) deficient and 31.1% (n = 238) insufficient. Mean serum 25(OH)D was 62.8 ± 27.4 nmol/L. No statistically significant difference was observed between pre-COVID (44.2% sub-optimal) and post-COVID (38.1% suboptimal) periods (OR 0.78, 95% CI: 0.57–1.06, P = 0.110). However, marked seasonal variation was identified, with winter values significantly lower than summer values (45.3 ± 24.6 vs. 72.1 ± 28.3 nmol/L, P < 0.001). Furthermore, state-funded patients had a significantly higher rate of sub-optimal vitamin D status (50.2%, n = 107) compared to self-funded patients (35.9%, n = 198, P < 0.001).
Conclusion
Our findings demonstrate a high prevalence of sub-optimal vitamin D levels in a sub-fertility population, with significant seasonal fluctuations and notable socio-economic disparities. Despite initial concerns, COVID-19 lockdown measures did not appear to adversely affect overall vitamin D status. These results support the incorporation of routine vitamin D screening in infertility evaluations and the implementation of targeted supplementation, particularly in economically vulnerable groups and during winter months.
Introduction
Vitamin D has emerged as a critical factor in reproductive health, influencing both fertility and pregnancy outcomes. Beyond its well-known role in calcium metabolism and bone health, vitamin D is now recognized as a key regulator of ovarian function, implantation, and pregnancy maintenance. Vitamin D receptors (VDRs) are expressed in reproductive tissues, including the ovaries, endometrium, and placenta, suggesting a direct role in female fertility and pregnancy.
During pregnancy, maternal vitamin D in its active form, 1,25-dihydroxyvitamin D3 or calcitriol, levels rise 2–3 times above non-pregnant levels, driven by increased activity of 1α-hydroxylase mostly within the maternal kidney but also placental activation. Vitamin D deficiency disrupts this balance and has been implicated in adverse pregnancy outcomes, including pre-eclampsia, spontaneous preterm birth, and fetal growth restriction. Importantly, maternal vitamin D status directly influences fetal vitamin D stores, as 25-hydroxyvitamin D, 25(OH)D or calcifediol, freely crosses the placenta and serves as the primary source for the developing fetus.
A growing body of literature highlights the impact of vitamin D status on reproductive outcomes. Recent systematic reviews and meta-analyses have shown that vitamin D supplementation significantly improves clinical pregnancy rates among infertile women undergoing assisted reproductive technologies (ART) and reduces adverse pregnancy outcomes. For instance, Meng et al. found that vitamin D supplementation improved clinical pregnancy rates among infertile women undergoing ART with an odds ratio of 1.70 (95% confidence interval [CI]: 1.24–2.34, P = 0.001). Additionally, vitamin D deficiency (<50 nmol/L) is associated with a significantly increased risk of preterm birth (odds ratio [OR] = 1.28, 95% CI: 1.08–1.52), gestational diabetes (OR = 1.38, 95% CI: 1.22–1.57), small-for-gestational-age infants (OR = 1.43, 95% CI: 1.08–1.91), and recurrent miscarriage (OR = 4.02, 95% CI: 2.23–7.25). Conversely, vitamin D supplementation (>400 IU/day) has been linked to a reduction in pre-eclampsia (OR = 0.29, 95% CI: 0.09–0.95), miscarriage (OR = 1.60, 95% CI: 1.11–2.30), and fetal or neonatal mortality (RR = 0.69, 95% CI: 0.482–0.985). These findings underscore the importance of maintaining adequate vitamin D levels for improving both fertility and perinatal outcomes.
In addition, a systematic review and meta-analysis by Guang et al. found that vitamin D supplementation during pregnancy significantly reduced the risk of small-for-gestational-age (SGA) infants (RR = 0.72, 95% CI: 0.52–0.99) and increased birth weight by an average of 75.38 g (95% CI: 22.88–127.88 g). Moreover, neonates whose mothers received prenatal vitamin D supplementation had higher 25(OH)D levels (MD = 13.50 ng/mL, 95% CI: 10.12–16.87 ng/mL), underscoring the essential role of maternal vitamin D sufficiency in optimizing fetal growth. Notably, vitamin D supplementation at doses ≤2000 IU/day was associated with a 65% reduction in fetal or neonatal mortality (RR = 0.35, 95% CI: 0.15–0.80), further supporting the need for adequate vitamin D intake during pregnancy.
Given these findings, our study aimed to assess the prevalence of vitamin D insufficiency and deficiency in patients presenting to a tertiary fertility clinic. We conducted a retrospective cohort analysis examining temporal trends in vitamin D status, with a particular focus on differences before and after the COVID-19 pandemic, variations by season and age group, and disparities based on payer status (self-funded vs. state-funded).
SEE ALSO: Vitamin D deficiency is common among pregnant women in rural Victoria. Australian and New Zealand Journal of Obstetrics and Gynaecology and
High prevalence of vitamin D deficiency in Pakistani mothers and their newborns. International Journal of Gynecology & Obstetrics