Vitamin D Deficiency and Pregnancy Rates in Women Undergoing Frozen Embryo Transfer

Vitamin D Deficiency and Pregnancy Rates in Women Undergoing Frozen Embryo Transfer. A Prospective Cohort Study

Vitamin D receptors are present and differently expressed in murine endometrium and ovary throughout the estrous cycle , whereas knock-out experiments have shown that vitamin D receptor null mice experience uterine hypoplasia and impaired folliculogenesis.

Only few retrospective studies examining the role of vitamin D levels in infertile patients have been published up to date, whereas results are strongly contradictory, with some supporting that maternal vitamin D deficiency is associated with lower pregnancy rates and others demonstrating that vitamin D deficiency does not affect final reproductive outcome.

Finally, a recent retrospective study postulated that vitamin D deficiency may negatively affect pregnancy rates with an effect mediated through the endometrium, given that vitamin D deficiency was not correlated with ovarian stimulation characteristics or with markers of embryo quality in this study.

In order to examine a potential negative effect of vitamin D deficiency on pregnancy rates, mediated through the endometrium, the aim of the current study was to examine the impact of vitamin D levels on pregnancy rates only in an infertile population undergoing embryo transfer of frozen-thawed embryos.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Procedure: Frozen embryo transfer

• Study Type: Observational
• Enrollment (Actual): 280

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Centre for Reproductive Medicine UZ Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Infertile women undergoing a frozen ET with 1 or 2 Day 5 (blastocyst stage) embryo

Description

Inclusion Criteria:

• All women undergoing a frozen ET with 1 or 2 Day 5 (blastocyst stage) embryo
• Age 18-39

Exclusion Criteria:

• Women > or = 40 years old
• IVM ET
• Uterine abnormalities

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vitamin D deficient patients; Serum 25-OH Vitamin D levels <20ng/L undergoing Frozen embryo transfer (vitamin D levels are measured on the day of embryo transfer)	Procedure: Frozen embryo transfer; Embryo transfer of frozen/thawed embryos after IVF/ICSI
Vitamin D sufficient patients; Serum 25-OH Vitamin D levels >20ng/L undergoing Frozen embryo transfer (vitamin D levels are measured on the day of embryo transfer)	Procedure: Frozen embryo transfer; Embryo transfer of frozen/thawed embryos after IVF/ICSI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy	The presence of intrauterine gestational sac at 7 weeks of gestation	4 weeks after embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical pregnancy	Positive pregnancy test 2 weeks after embryo transfer	2 weeks after embryo transfer

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Nikolaos P. Polyzos, MD PhD, Universitair Ziekenhuis Brussel; Principal Investigator: Arne Van de Vijver, MD, UZBrussel

Publications and helpful links

General Publications

• Ozkan S, Jindal S, Greenseid K, Shu J, Zeitlian G, Hickmon C, Pal L. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril. 2010 Sep;94(4):1314-1319. doi: 10.1016/j.fertnstert.2009.05.019. Epub 2009 Jul 8.
• Anifandis GM, Dafopoulos K, Messini CI, Chalvatzas N, Liakos N, Pournaras S, Messinis IE. Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome. Reprod Biol Endocrinol. 2010 Jul 28;8:91. doi: 10.1186/1477-7827-8-91.
• Aleyasin A, Hosseini MA, Mahdavi A, Safdarian L, Fallahi P, Mohajeri MR, Abbasi M, Esfahani F. Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology. Eur J Obstet Gynecol Reprod Biol. 2011 Nov;159(1):132-7. doi: 10.1016/j.ejogrb.2011.07.006. Epub 2011 Aug 10.
• Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K. Characterizing the influence of vitamin D levels on IVF outcomes. Hum Reprod. 2012 Nov;27(11):3321-7. doi: 10.1093/humrep/des280. Epub 2012 Aug 21.
• Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, Kawakami T, Arioka K, Sato H, Uchiyama Y, Masushige S, Fukamizu A, Matsumoto T, Kato S. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet. 1997 Aug;16(4):391-6. doi: 10.1038/ng0897-391.
• Zarnani AH, Shahbazi M, Salek-Moghaddam A, Zareie M, Tavakoli M, Ghasemi J, Rezania S, Moravej A, Torkabadi E, Rabbani H, Jeddi-Tehrani M. Vitamin D3 receptor is expressed in the endometrium of cycling mice throughout the estrous cycle. Fertil Steril. 2010 May 15;93(8):2738-43. doi: 10.1016/j.fertnstert.2009.09.045. Epub 2009 Nov 6.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: November 10, 2013
• First Submitted That Met QC Criteria: November 10, 2013
• First Posted (Estimate): November 15, 2013

Study Record Updates

• Last Update Posted (Estimate): August 6, 2015
• Last Update Submitted That Met QC Criteria: August 5, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Infertility
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Infertility; Vitamin D Deficiency
• Other Study ID Numbers: 2013/181; B.U.N. 143201317807