TY - JOUR
T1 - Vitamin D Deficiency Is Associated with Poor Ovarian Stimulation Outcome in PCOS but Not Unexplained Infertility
AU - Butts, Samantha F.
AU - Seifer, David B.
AU - Koelper, Nathanael
AU - Senapati, Suneeta
AU - Sammel, Mary D.
AU - Hoofnagle, Andrew N.
AU - Kelly, Andrea
AU - Krawetz, Steven A.
AU - Santoro, Nanette
AU - Zhang, Heping
AU - Diamond, Michael P.
AU - Legro, Richard S.
N1 - Funding Information:
Financial Support: This study was supported by the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant U10 HD27049 (to C. Coutifaris, University of Pennsylvania), Grant U10 HD38992 (to R.S.L.); Grant U10 HD055925 (to H.Z.); Grant U10 HD39005 (to M.P. D.); Grant U10 HD38998 (to W. Schlaff and R. Alvero, University of Colorado); Grant U10 HD055936 (to G. Christman, University of Florida); Grant U10 HD055942 (to R. Brzyski and R. Robinson, University of Texas Health Science Center at San Antonio); Grant U10 HD055944 (to P. Casson, University of Vermont); Grant U54 HD068157 (to S.F.B); and U54-HD29834 to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. S.F.B. is supported by the Penn Presbyterian Harrison Fund. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or the National Institutes of Health. Both the Pregnancy in Polycystic Ovary Syndrome II (NCT00719186) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation trials (NCT01044862) from which data were derived for this study were registered with ClinicalTrials.gov.
Funding Information:
This study was supported by the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant U10 HD27049 (to C. Coutifaris, University of Pennsylvania), Grant U10 HD38992 (to R.S.L.); Grant U10 HD055925 (to H.Z.); Grant U10 HD39005 (to M.P. D.); Grant U10 HD38998 (to W. Schlaff and R. Alvero, University of Colorado); Grant U10 HD055936 (to G. Christman, University of Florida); Grant U10 HD055942 (to R. Brzyski and R. Robinson, University of Texas Health Science Center at San Antonio); Grant U10 HD055944 (to P. Casson, University of Vermont); GrantU54HD068157(to S.F.B); and U54-HD29834 to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core of the Specialized Cooperative Centers Program in Reproduction and Infertility Research
Funding Information:
The primary hypothesis of this study was that vitamin D deficiency is an important modifiable contributor to diminished treatment success in women with either PCOS or unexplained infertility undergoing ovarian stimulation (which, going forward, represents either oral ovulation induction or oral/injectable ovarian stimulation). To test this hypothesis, we performed an assessment of vitamin D status in stored sera from completed randomized controlled trials conducted by the Reproductive Medicine Network (RMN): (i) The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (10) and (ii) The Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation (AMIGOS) trial (19). The RMN is funded by the National Institute of Child Health and Human Development as a cooperative effort of seven clinical sites charged with conducting high-quality clinical studies in reproductive medicine.
Funding Information:
Disclosure Summary: D.B.S. is co-inventor of using anti-Müllerian hormone as a means of accessing ovarian reserve and receives royalties from a license agreement between Rutgers Medical School/Massachusetts General Hospital and Beckman-Coulter. M.P.D. is a board member and advanced reproductive care consultant for Halt Medical, Genzyme, Auxogyn, Actamax, and ZSX Medical; an investigator for Abbvie, Novartis, Boeringher Ingelheim, Ferring, EMD Serono, and Biosante. R.S.L. is a speaker for Ferring Pharmaceuticals. A.N.H. receives grant funding from Waters, a mass spectrometry company, and is a consultant for Roche. S.A.K. receives support from the Merck 2016 Grant for Fertility Innovation and EIC Systems Biology in Reproductive Medicine. The remaining authors have nothing to disclose.
Publisher Copyright:
© Copyright 2019 Endocrine Society.
PY - 2018/11/9
Y1 - 2018/11/9
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2018-00750
DO - 10.1210/jc.2018-00750
M3 - Article
C2 - 30085176
AN - SCOPUS:85052810878
SN - 0021-972X
VL - 104
SP - 369
EP - 378
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -