Clinical Tests to Predict the Success of Assisted Reproductive Techniques

NCT02437578 | Completed DMC

• 1 other identifier: CBG study3
• Study Type: observational
• Target: 542
• Locations: 1 country
• Sites: 1

Brief Summary

Today, it is evident that vitamin D has more widespread effects than the classical actions related to bone mineralization and calcium homeostasis. Vitamin D deficiency results in impaired reproductive performance in various species of animals, and recently the investigators have shown that the Vitamin D receptor (VDR), activating (CYP2R1, CYP27A1, CYP27B1) and inactivating (CYP24A1) enzymes are expressed in the human testis, epididymis, seminal vesicle, prostate and spermatozoa. Functional studies showed that activated vitamin D increases intracellular calcium and sperm motility in mature spermatozoa, and hence may be important not only for spermatogenesis but also for sperm function. Any test that might assist in guiding the treatment of the infertile couple would be beneficial both for most infertile couples and the society in general. The fact that vitamin D may play a role for human semen quality are now being tested clinically. If vitamin D supplementation proves efficient this opens for the first time for a causal, safe and cheap treatment of at least some cases of "idiopathic" impaired semen quality. This may also have consequences in the in vitro setting as activated vitamin D may be used to select high quality sperm during assisted reproductive techniques. The presence of the vitamin D receptor and vitamin D metabolizing enzyme CYP24A1 in particular is able to discriminate spermatozoa from normal and infertile men. CYP24A1 is expressed at the annulus of normal sperm, but it is virtually absent from spermatozoa from infertile men. This indicates that CYP24A1 expression may assist in predicting the chance of success by using insemination (IUI), IVF or ICSI. CYP24A1 expression is induced by activated vitamin D, which indicates that other VDR activated genes also may serve as positive predictive markers of fertility. In addition, vitamin D metabolites and other factors in the female reproductive tract will be measured to determine if they alone or in combination with other markers can determine whether the best solution for the infertile couple would be to do IUI, IVF, or ICSI. The suggested clinical trial may therefore be able to evaluate several secondary endpoints in addition to CYP24A1 in our search for predictive markers for fertilization. For instance several biomarkers in serum, seminal plasma or follicular fluid in conjunction with genetic polymorphisms in several genes important for reproductive function.

Conditions

Infertility

Keywords

vitamin d; fertility; markers; endocrine disruption; reproduction

Outcome Measures

Primary Outcomes (1)

• CYP24A1 expression in sperm as a positive predictive marker of the number of pregnancies and live births following IUI

  CYP24A1 expression is evaluated in the semen sample used for IUI

  9 months after semen analysis

Secondary Outcomes (32)

• CYP24A1 expression in sperm as a positive predictive marker of the number of pregnancies and live births following IVF/ICSI

  9 months after semen analysis

• CYP24A1 expression in sperm as a positive predictive marker of the fertilization rate and blastocyst/4cell quality following IVF/ICSI

  within 28-35 days from CYP24A1 expression

• CYP24A1 expression as a better predictor of success by using IUI, IVF and ICSI than semen analysis

  One month after semen analysis

• VDR expression in sperm as a positive predictive marker of the number of pregnancies and/or live births following IUI, IVF, ICSI

  9 months after semen analysis

• VDR expression in sperm as a positive predictive marker of the number of pregnancies and/or live births following IUI, IVF, ICSI

  9 months after semen analysis

Study Arms (1)

Infertile couples

Infertile couples referred to Dansk fertilitetsklinik (Danish Fertility clinic) for IUI, IVF and ICSI treatment

Eligibility Criteria

• Age: 18 Years - 43 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

All infertile couples referred to Dansk Fertilitetsklinik will be invited to participate. Anticipated 800-1000 IUI and 400 IVF/ICSI will be conducted during the planned study period. The investigators assume that up to 600 IUI and 200 IVF/ICSI wish to participate. Thus 600-800 treatments is the estimated target for inclusion in this study. The investigators expect a small retraction rate (\< 20) because of high motivation and no adverse effects.

You may qualify if:

• part of an infertile couple
• \> 18 years of age

You may not qualify if:

• women \>43 years of age
• men with sperm concentration \< 0.1 million/ml

Sponsors & Collaborators

• Martin Blomberg Jensen: lead
• Dansk Fertilitetsklinik: collaborator

Study Sites (1)

Dansk Fertilitetsklinik

Frederiksberg, 2000, Denmark

Location

Related Publications (1)

• Wulff SM, Jorsal MJ, Kooij I, Krog H, Bentin-Ley U, Blomberg Jensen M, Yahyavi SK. Phosphate concentrations in follicular fluid during assisted reproductive treatment: relevance for ovarian function and fertility outcomes. Reprod Biol Endocrinol. 2025 May 14;23(1):69. doi: 10.1186/s12958-025-01408-w.

  PMID: 40369590 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Not number of subject but number of cycles/treatments Serum Seminal plasma follicular fluid DNA granulosa cells

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Martin B Jensen, MD, DMSc

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, DMSc

Study Record Dates

• First Submitted: April 16, 2015
• First Posted: May 7, 2015
• Study Start: May 1, 2015
• Primary Completion: October 1, 2018
• Study Completion: March 1, 2019
• Last Updated: March 26, 2019

Record last verified: 2019-03

Locations

DK (1)