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Lifestyle and Environment · Nutrition and Metabolic Health

Influence of Vitamin D supplementation on reproductive outcomes of infertile patients: a systematic review and meta-analysis

Meng X, Zhang J, Wan Q, Huang J, Han T, Qu T, Yu LL

Published February 3, 2023 Reproductive biology and endocrinology : RB&E, 21(1), 17
DOI 10.1186/s12958-023-01068-8 PMID 36737817 PMC PMC9896710

RRM Academy Synopsis

Pooled studies link vitamin D to higher clinical pregnancy in IVF

A pooled analysis of 12 studies in women undergoing IVF found that women given vitamin D had a higher clinical pregnancy rate than controls (odds ratio 1.70). Nine studies were randomized trials and three were cohort studies. Implantation, biochemical pregnancy and miscarriage rates showed no significant difference.

Key Findings

  • Across 12 studies (1235 women in vitamin D groups, 1117 controls), clinical pregnancy was higher with vitamin D (OR 1.70, 95% CI 1.24–2.34; I2 = 63%, P = 0.001).
  • Clinical pregnancy was higher in randomized trials (OR 1.49, 95% CI 1.05–2.11), cohort studies (OR 2.21, 95% CI 1.42–3.44) and studies of low pretreatment vitamin D (OR 2.06, 95% CI 1.32–3.22).
  • Implantation (OR 1.86, 95% CI 1.00–3.47), biochemical pregnancy (OR 1.49, 95% CI 0.98–2.26) and miscarriage (OR 0.98, 95% CI 0.63–1.53) showed no significant difference.
  • Clinical pregnancy was higher with multicomponent supplements (OR 1.75, 95% CI 1.18–2.59) but not with vitamin D alone (OR 1.67, 95% CI 0.98–2.82).
  • Omitting Somigliana 2021 gave OR 1.84 (95% CI 1.39–2.43) and cut heterogeneity from 63% to 36%; the same sensitivity analysis in the vitamin D-only subgroup gave OR 1.97 (95% CI 1.26–3.09).

Interpretation

The review pools nine randomized trials and three nonrandomized cohort studies. The review included infertile women undergoing ART (IVF, ICSI, fresh or frozen embryo transfer). Pooled outcomes were implantation, biochemical pregnancy, clinical pregnancy, miscarriage and multiple pregnancy; live birth was not pooled. The authors note small samples, high heterogeneity, and differences between studies in ethnicity, vitamin D status, length of supplementation and cause of infertility. The subgroup results split a small set of studies into smaller groups.

RRM Context

Restorative reproductive medicine seeks the underlying causes of infertility in both partners. Nutrition is one place an evaluation can look. The women in these studies were already undergoing IVF, which proceeds without finding why conception has not occurred. The authors cite earlier work finding vitamin D receptors in the pregnant uterine lining (decidua) and a role for vitamin D in regulating a gene key to implantation. They call for larger randomized trials.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Low vitamin D status has been associated with an increased risk for infertility. Recent evidence regarding the efficacy of vitamin D supplementation in improving reproductive outcomes is inconsistent. Therefore, this systematic review was conducted to investigate whether vitamin D supplementation could improve the reproductive outcomes of infertile patients and evaluate how the parameters of vitamin D supplementation affected the clinical pregnancy rate.

Methods

We searched seven electronic databases (CNKI, Cqvip, Wanfang, PubMed, Medline, Embase, and Cochrane Library) up to March 2022. Randomized and cohort studies were collected to assess the reproductive outcomes difference between the intervention (vitamin D) vs. the control (placebo or none). Mantel-Haenszel random effects models were used. Effects were reported as odds ratio (OR) and their 95% confidence interval (CI).

Systematic Review Registration

CRD42022304018.

Results

Twelve eligible studies (n = 2352) were included: 9 randomized controlled trials (RCTs, n = 1677) and 3 cohort studies (n = 675). Pooled results indicated that infertile women treated with vitamin D had a significantly increased clinical pregnancy rate compared with the control group (OR: 1.70, 95% CI: 1.24-2.34; I2 = 63%, P = 0.001). However, the implantation, biochemical pregnancy, miscarriage, and multiple pregnancy rates had no significant difference (OR: 1.86, 95% CI: 1.00-3.47; I2 = 85%, P = 0.05; OR: 1.49; 0.98-2.26; I2 = 63%, P = 0.06; OR: 0.98, 95% CI: 0.63-1.53; I2 = 0%, P = 0.94 and OR: 3.64, 95% CI: 0.58-11.98; I2 = 68%, P = 0.21). The improvement of clinical pregnancy rate in the intervention group was influenced by the vitamin D level of patients, drug type, the total vitamin D dosage, the duration, administration frequency, and daily dosage of vitamin D supplementation. The infertile women (vitamin D level < 30 ng/mL) treated with the multicomponent drugs including vitamin D (10,000-50,000 IU or 50,000-500,000 IU), or got vitamin D 1000-10,000 IU daily, lasting for 30-60 days could achieve better pregnancy outcome.

Conclusion

To the best of our knowledge, this is the first meta-analysis systematically investigated that moderate daily dosing of vitamin D supplementation could improve the clinical pregnancy rate of infertile women and reported the effects of vitamin D supplementation parameters on pregnancy outcomes. A larger sample size and high-quality RCTs are necessary to optimize the parameters of vitamin D supplementation to help more infertile patients benefit from this therapy.

Topics

Related research

Lifestyle and Environment › Nutrition and Metabolic Health › Dietary Patterns · Therapeutics › Supplements and Botanicals › Vitamins and Minerals
Xiangqian Meng, Jiayao Zhang, Qi Wan, Jihua Huang, Tingting Han, Ting Qu, Lin-Lin Yu
X Meng, J Zhang, Q Wan, J Huang, T Han, T Qu, L Yu
PMID 36737817 36737817 DOI 10.1186/s12958-023-01068-8 10.1186/s12958-023-01068-8 Meng et al. 2023, Meng 2023

Keywords

Clinical pregnancy rate, Infertile women, Reproductive outcomes, Supplementation, Vitamin D

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