Effects of vitamin D supplementation on ovulation and pregnancy in women with polycystic ovary syndrome: a systematic review and meta-analysis

Abstract

ObjectiveTo evaluate the effect of vitamin D supplementation on pregnancy and ovulation in patients with polycystic ovary syndrome.MethodWe searched Pubmed, Medline (via Ovid, 1974 to 2020), EMBASE (via Ovid, 1974 to 2020), Cochrane Central Register of Controlled Trials (via Ovid), Web of Science, CNKI, WangFang and the Vip database from inception until April 2021. Two researchers independently screened articles, collected data and evaluated the quality, with Review manager 5.3 for meta-analysis.ResultsTotally 20 randomized controlled studies with 1961 subjects were included. Meta analysis showed that pregnancy rate [RR=1.44 (1.28, 1.62), p<0.00,001], ovulation rate [RR=1.42 (1.14, 1.78), p=0.002] and matured oocytes rate [RR=1.08 (1.03, 1.13), p=0.002] of vitamin D supplementation group were significantly higher than those of control group. Meanwhile, early miscarriage rate [RR=0.44 (0.30, 0.66), p<0.00,001], androgen level [MD=-2.31 (-3.51, -1.11), p=0.0002], luteinizing hormone [MD=-1.47 (-2.57, -0.36), p=0.009], follicle stimulating hormone [MD=-0.15 (-0.24, -0.05), p=0.002], and premature delivery rate [RR=0.38, 95% CI (0.21, 0.70), p=0.002] were declined significantly than the controls. However, only one article suggested that the progesterone [MD=6.52 (4.52, 8.52), p<0.05] in the vitamin D intervention group was increased. There was no notable difference in the biochemical pregnancy rate [RR=0.95 (0.55, 1.63), p=0.84], gestational hypertension rate [RR=0.40, 95% CI (0.15, 1.11), p=0.08], gestational diabetes mellitus rate [RR=0.27, 95% CI (0.05, 1.39), p=0.11], fertilization rate [RR=1.05 (1.00, 1.10), p=0.04], cleavage rate [RR=1.03 (0.99, 1.06), p=0.17], high-quality embryo rate [RR=1.08 (0.98, 1.20), p=0.10], endometrial thickness [MD=0.10], 77 (-0.23, 1.77), p=0.13], estrogen level [MD=-0.34 (-1.55, 0.87), p=0.59], LH/FSH [MD=-0.14, 95% CI (-0.48, 0.20), p=1.00] and anti-Mullerian hormone [MD=-0.22 (-0.65, 0.21), p=0.32].ConclusionVitamin D supplementation contribute to the higher pregnancy and ovulation rates, and lower androgen, LH, FSH and early miscarriage rates in women with PCOS, regardless of the use of ovulation induction drugs or assisted reproductive technologies. However, no significant improvement was observed in fertilization rate or cleavage rate. Due to the limitation in quality of involved studies, more high-quality RCTs are needed for further validation.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42021250284.

Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study

“…The mechanism by which serum VD ultimately contributes to the development of PCOS by affecting testosterone remains unclear, but possible explanation has been proposed. Serum VD heightens the activity of aromatase within the ovary, thereby fostering the conversion of androgens to estrogens, ultimately culminating in diminished androgens production [ 53 ]. Kinuta et al demonstrated a marked reduction in aromatase activity within the ovaries of VDR knockout mice in contrast to the control group [ 54 ].…”

“…Yasmine et al have reported that endometrial thickness of PCOS patients maybe improved after VD administration [ 60 ]. A recent meta-analysis has shown that VD supplementation to PCOS women could decrease the occurrence rates of early miscarriage and premature delivery [ 53 ]. The nuclear receptor of VD (VDR) and 1,25(OH)2D3 membrane binding protein are expressed in both ovarian granulosa and theca cells [ 61 , 62 ].…”