How vitamin D level influences in vitro fertilization outcomes: results of a systematic review and meta-analysis

Objective: To investigate the impact of serum vitamin D level on in vitro fertilization (IVF) outcomes.

Design: Systematic review and meta-analysis.

Setting: Not applicable.

Patients: Infertile women undergoing conventional IVF or intracytoplasmic sperm injection (ICSI).

Interventions: Systematic search of PubMed, MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database, and Web of Science from inception until July 2019 with cross-checking of references from relevant articles in English. Vitamin D levels were categorized into three groups: deficient (<20 ng/mL), insufficient (20-30 ng/mL), and replete (>30 ng/mL). Before starting the data extraction, we registered the review protocol in PROSPERO (CRD42019134258).

Main outcome measures: We consider clinical pregnancy rate (CPR), live birth rate (LBR), and/or ongoing pregnancy rate (OPR) as primary outcomes. Likewise, the miscarriage rate was considered as a secondary outcome.

Results: Primary analysis showed that women with a replete level of vitamin D had higher CPR and LBR/OPR compared to those with a deficient of insufficient level of vitamin D. However, sensitivity analysis led to non-significant differences between the comparators for CPR (odds ratio 0.71, 95% confidence interval 0.47-1.08, I2 = 61%) and OPR/LBR (odds ratio 0.78, 95% confidence interval 0.56-1.08], I2 = 61%). Also, for miscarriage a statistically different rate was not reached.

Conclusion: Serum vitamin D levels do not influence IVF outcomes in terms of CPR, LBR/OPR, and miscarriage rate. Future large cohort studies are warranted to determine whether the threshold of vitamin D affects reproductive outcomes. Currently, there is a lack of consensus between the appropriate vitamin D threshold to predict reproductive outcomes compared to the one established for bone health.

Prospero number: CRD42019134258.