Infertility Clinical Trial
Official title:
Development of Clinical Tests to Predict the Success of Assisted Reproductive Techniques in a Fertility Clinic
NCT number | NCT02437578 |
Other study ID # | CBG study3 |
Secondary ID | |
Status | Completed |
Phase | |
First received | |
Last updated | |
Start date | May 2015 |
Est. completion date | March 2019 |
Verified date | March 2019 |
Source | Rigshospitalet, Denmark |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
Status | Completed |
Enrollment | 542 |
Est. completion date | March 2019 |
Est. primary completion date | October 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 43 Years |
Eligibility |
Inclusion Criteria: - part of an infertile couple - > 18 years of age Exclusion Criteria: - women >43 years of age - men with sperm concentration < 0.1 million/ml |
Country | Name | City | State |
---|---|---|---|
Denmark | Dansk Fertilitetsklinik | Frederiksberg |
Lead Sponsor | Collaborator |
---|---|
Martin Blomberg Jensen | Dansk Fertilitetsklinik |
Denmark,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | CYP24A1 expression in sperm as a positive predictive marker of the number of pregnancies and live births following IVF/ICSI | CYP24A1 expression is evaluated in the semen sample used for IVF/ICSI | 9 months after semen analysis | |
Secondary | CYP24A1 expression in sperm as a positive predictive marker of the fertilization rate and blastocyst/4cell quality following IVF/ICSI | CYP24A1 expression is evaluated in the semen sample used for IVF/ICSI | within 28-35 days from CYP24A1 expression | |
Secondary | CYP24A1 expression as a better predictor of success by using IUI, IVF and ICSI than semen analysis | CYP24A1 expression is evaluated in the semen sample used for IUI/IVF/ICSI | One month after semen analysis | |
Secondary | VDR expression in sperm as a positive predictive marker of the number of pregnancies and/or live births following IUI, IVF, ICSI | VDR expression is evaluated in the semen sample used for IUI/IVF/ICSI | 9 months after semen analysis | |
Secondary | VDR expression in sperm as a positive predictive marker of the number of pregnancies and/or live births following IUI, IVF, ICSI | VDR expression is evaluated in the semen sample used for IUI/IVF/ICSI N300 | 9 months after semen analysis | |
Secondary | RANKL expression in sperm as a positive predictive marker of the number of pregnancies and/or live births following IUI, IVF, ICSI | VDR expression is evaluated in the semen sample used for IUI/IVF/ICSI N300 | 9 months after semen analysis | |
Secondary | Expression of a vitamin D regulated gene in sperm as a positive predictive marker of the number of pregnancies and/or live births following IUI, IVF, ICSI | Expression of a vitamin D regulated gene will be evaluated in the semen sample used for IUI/IVF/ICSI N300 | 9 months after semen analysis | |
Secondary | Combined expression of CYP24A1, VDR and RANKL in sperm as a positive predictive marker of the number of pregnancies and/or live births following IUI, IVF, ICSI | Expression the selected genes will be evaluated in the semen sample used for IUI/IVF/ICSI N300 | 9 months after semen analysis | |
Secondary | CYP24A1, VDR and RANKL as markers for good quality sperm and progressive motile sperm. | CYP24A1 and semen quality | day 1 | |
Secondary | Serum vitamin D determine expression of CYP24A1, VDR and RANKL in sperm | associations between local expression and serum vitamin D | day 1 | |
Secondary | Serum levels of vitamin D metabolites as markers of good semen quality and higher chance of pregnancies and/or live births following IUI, IVF, ICSI | 9 months after semen analysis | ||
Secondary | High serum level of OPG as markers of good semen quality and more pregnancies and/or live births following IUI, IVF, ICSI | 9 months after semen analysis | ||
Secondary | Serum level of RANKL as markers of low semen quality and low chance of pregnancies and/or live births following IUI, IVF, ICSI | 9 months after semen analysis | ||
Secondary | Serum level of FGF23 and or Klotho as positive predictors of semen quality and the number of pregnancies and/or live births following IUI, IVF, ICSI | 9 months after semen analysis | ||
Secondary | Serum level of LHCGRas a negative predictor of semen quality and the number of pregnancies and/or live births following IUI, IVF, ICSI | 9 months after semen analysis | ||
Secondary | Serum level of total, undercarboxylated or matrix osteocalcin as markers of semen quality and the number of pregnancies and/or live births following IUI, IVF, ICSI | 9 months after semen analysis | ||
Secondary | Serum levels of vitamin D regulated genes as markers of semen quality and the number of pregnancies and/or live births following IUI, IVF, ICSI | 9 months after semen analysis | ||
Secondary | Serum levels of calcium and phosphate and semen quality and the number of pregnancies and/or live births following IUI, IVF, ICSI | 9 months after semen analysis | ||
Secondary | vitamin D metabolites in follicular fluid as a positive predictive marker of oocyte quality, fertilisationrate, implantation, pregnancy and/or live births following IVF/ICSInumber of pregnancies and/or live births following IUI, IVF, ICSI | 1 and 9 months after semen analysis | ||
Secondary | Concentration of calcium and phosphate in follicular fluid as a positive predictive marker of oocyte quality, fertilisationrate, implantation, pregnancy and/or live births following IVF/ICSI | 1 and 9 months after semen analysis | ||
Secondary | Concentration of 1,25 dihydroxyvitamin D in follicular fluid as a positive predictive marker of the probability of the CYP24A1 positive sperm to fertilize the oocyte and/or live births following IVF/ICSI | within 1 month after semen analysis and 9 months after semen analysis | ||
Secondary | Concentration of reproductive factors in follicular fluid as a positive predictive marker of with oocyte quality, fertilisationrate, implantation, pregnancy and/or live births following IVF/ICSI | Klotho, LHCGR TRAP5, calcium, phosphat, | 1 and 9 months after semen analysis | |
Secondary | Concentration of selected bone factors in follicular fluid as a positive predictive marker of with oocyte quality, fertilisationrate, implantation, pregnancy and/or live births following IVF/ICSI | RANKL, OPG, RANK, FGF23, Osteocalcin, MGP, DKK, calcitonin, PTHrP, SOST, Capthepsin K | 1 and 9 months after semen analysis | |
Secondary | Polymorphisms in the selected vitamin D regulated genes and semen quality, male reproductive hormone levels or pregnancy and/or live births following IUI/IVF/ICSI | VDR, CYP24A1, CYP2R1, RANKL, TRPV6, TRPV5, CatSper, CaSR, Osteocalcin, MGP, or other vitamin D regulated genes | 1 and 9 months after semen analysis | |
Secondary | Polymorphisms in the selected bone-gonadal genes and semen quality, male reproductive hormone levels or pregnancy and/or live births following IUI/IVF/ICSI | RANK, OPG, LHCGR, FGF23, Klotho, GPRC6a, PHEX, MEPE, DMP1,DKK1,PTHR, calcitonin, PTHrP, SOST, Capthepsin K, FSH, FSHR, SLC34A1-3, PIT1-2 | 1 and 9 months after semen analysis | |
Secondary | Polymorphisms in selected gonadal genes and oocyte quality, AMH levels, female reproductive hormone levels or pregnancy and/or live births following IUI/IVF/ICSI | VDR, CYP24A1, CYP2R1, LHCGR, TRPV6, TRPV5, CatSper, GPRC6a, LHCGR, PHEX, MEPE, DMP1,DKK1,PTHR, PTHrP, FSH, FSHR, SLC34A1-3, PIT1-2 or other vitamin D regulated genes | 1 and 9 months after semen analysis | |
Secondary | Polymorphisms in selected bone genes and oocyte quality, AMH levels, female reproductive hormone levels or pregnancy and/or live births following IUI/IVF/ICSI | RANKL, OPG, FGF23, Klotho, CaSR, RANK, Osteocalcin, MGP, calcitonin, PTHrP, SOST, Capthepsin K | 1 and 9 months after semen analysis | |
Secondary | FSH signalling polymorhisms and reproductive function in women and men | Single nucleotide polymorphisms (SNPs) related to genes encoding the FSHß subunit (FSHB) and the FSH receptor (FSHR) affect FSH production (FSHB c.-211 G>T) and sensitivity/expression of its receptor in vitro (FSHR c.2039A>G & FSHR c.-29G>A) FSHR c.2039A>G, but not FSHR c.-29G>A, is associated with increased FSH levels in adult women, while there are conflicting results on FSHB c.-211 G>T. | 1 and 9 months after semen analysis | |
Secondary | Endocrine disrupting chemicals in serum, follicular fluid, seminal fluid as predictive markers of semen quality, pregnancies and live birth rate following IUI, IVF, ICSI | p,p'-DDE Nonylphenol Triclosan Homosalate Benzyl butyl phthalate OD-PABA Di-iso-butyl phthalate Dibutyl phthalate 4-Methylbenzophenone Octyl methoxycinnamate Benzophenone-3 Perfluorooctanoic acid |
1 and 9 months after semen analysis | |
Secondary | LHCGR i follicular fluid and serum as predictors of serum levels of sex hormones and gonadotropins | LHCGR measured in serum and follicular fluid from women undergoing IVF and ICSI | at the time for oocyte retrieval | |
Secondary | LHCGR as predictors of a responsiveness (number of follicles, collected oocytes, fertilisation, number of 2 and 4 cell embryos, and implantation) to hormonal treatment given during ART (hCG, Lh, FSH) | LHCGR measured in serum and follicular fluid from women undergoing IVF and ICSI. | LHCGR at the time for oocyte retrieval and outcomes determined i the following week | |
Secondary | LHCGR i follicular fluid and serum as predictors of oocyte quality, abortion rate and live birth rate | LHCGR measured in serum and follicular fluid from women undergoing IVF and ICSI | at the time for oocyte retrieval and up to nine months later |
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