Vitamin D Deficiency Is Associated with Poor Ovarian Stimulation Outcome in PCOS but Not Unexplained Infertility

Samantha F. Butts, David B. Seifer, Nathanael Koelper, Suneeta Senapati, Mary D. Sammel, Andrew N. Hoofnagle, Andrea Kelly, Steven A. Krawetz, Nanette Santoro, Heping Zhang, Michael P. Diamond, Richard S. Legro

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Context The impact of vitamin D deficiency on the success of ovarian stimulation according to underlying infertility diagnosis has not been investigated. Objective To evaluate the relationship between vitamin D deficiency and reproductive outcomes after ovarian stimulation in women with either polycystic ovary syndrome (PCOS) or unexplained infertility. Design Retrospective cohort study. Setting Analysis of randomized controlled trial (RCT) data. Participants Participants from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) RCT (n = 607); participants from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) RCT of unexplained infertility (n = 647). Interventions Serum 25(OH)D levels measured in banked sera. Main Outcome Measures Primary: live birth; secondary: ovulation (PPCOS II), pregnancy, and early pregnancy loss. Results In PPCOS II, subjects with vitamin D deficiency [25(OH)D < 20 ng/mL or 50 nmol/L] were less likely to ovulate (adjusted OR, 0.82; 95% CI, 0.68 to 0.99; P = 0.04) and experienced a 40% lower chance of live birth (adjusted OR, 0.63; 95% CI, 0.41 to 0.98; P = 0.04) than those not deficient. In AMIGOS, no significant association between vitamin D deficiency and live birth was noted. In pregnant subjects from both studies, vitamin D deficiency was associated with elevated risk of early pregnancy loss (OR, 1.6; 95% CI, 1.0 to 2.6; P = 0.05). Conclusions In this investigation of women pursuing ovarian stimulation, the association between vitamin D deficiency and diminished live birth relied on carrying the diagnosis of PCOS and was not observed in unexplained infertility. Given the generally modest success of ovarian stimulation, addressing vitamin D deficiency may prove an important treatment adjunct for many infertile women.

Original languageEnglish (US)
Pages (from-to)369-378
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - Nov 9 2018

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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