Male InfertilityNCT00341120
Genetic Causes of Male Infertility
An observational study of Male Infertility, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in Sweden.
Trial summary
This study is being conducted at the University Hospital of Lund University in Malmo, Sweden, in collaboration with the U.S. National Institute of Child Health and Human Development. The study will try to identify genetic causes of impaired sperm production and male infertility. Read more about this study
- Who is it for?
- Ages 20 to 45 years, men only
- Conditions the study is for
- Male Infertility
- How many people
- 400 participants
- Where
- 1 siteSweden
- Study dates
- 2 Jan 2003to 29 Aug 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 45 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Referred to the Scanian Andrology Centre.
- Age 20-45.
- Partner age less than 40.
- Having had regular sexual intercourse without contraception for a year or more without achieving a pregnancy.
- Partner attending Lund University prenatal clinic.
- Age 20-45.
Show all 10Show fewer
- Partner age less than 40.
- Having fathered one or more pregnancies.
- Having stopped birth control to achieve present pregnancy.
- Having achieved present pregnancy in less than 12 months of unprotected intercourse.
Who cannot join
- Klinefelters syndrome.
- Hypogondotropic hypogonadism.
- Y-chromosome microdeletion or abnormality.
- Other genetic cause for infertility.
- Obstructive azoospermia.
- Partner with salpingitis.
Show all 19Show fewer
- Partner with polycystic ovarian syndrome.
- Partner with disturbance of ovulation.
- Partner with endometriosis.
- History of cancer.
- History of treatment with cytotoxic drugs, irradiation, or sulfasalazopyrine.
- History of cryptorchidism.
- History of mumps orchitis.
- History of vasectomy.
- History of cancer.
- History of treatment with cytotoxic drugs, irradiation, or sulfasalazopyrine.
- History of cryptorchidism.
- History of mumps orchitis.
- Having sought or partner having sought treatment or investigation for fertility.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Methylenetetrahydrofolate Reductase C677T Mutation, Other Variant Genotypes, and Male Infertility
This study is being conducted at the University Hospital of Lund University in Malmo, Sweden, in collaboration with the U.S. National Institute of Child Health and Human Development. The study will try to identify genetic causes of impaired sperm production and male infertility. It will focus on the possible role of the MTHFR and CBS genes, which regulate absorption and metabolism of the vitamin, folate in infertility. If the nutritional intake or metabolism of this vitamin is related to male infertility, then this cause of infertility would be potentially curable.
Fertile and infertile men between 20 and 45 years of age may be eligible for this study. Criteria include the following:
Read more
- Fertile men: men whose partners are younger than age 40 and are attending Lund University prenatal clinic; who have fathered one or more pregnancies and who stopped birth control to achieve the present pregnancy; who achieved the present pregnancy in less than 12 months of unprotected intercourse.
- Infertile men: men referred to the Scandian Andrology Centre whose infertility is unexplained, whose partners are younger than age 40 and who have had regular sexual intercourse without contraception for at least 12 months without achieving a pregnancy.
All participants will have the following tests and procedures:
- Complete a questionnaire providing information about their reproductive and medical history and recent dietary history;
- Provide blood samples for analysis of red cell folate, plasma folate, plasma homocysteine, plasma B12, and for genetic evaluation;
- Provide a semen sample for routine analysis, including volume, sperm concentration, sperm motility, and sperm morphology.
In addition, infertile men will undergo a physical examination and review of their medical records.
Read the detailed description
It is evident that genetic variation plays a substantial role in the etiology of male infertility. Studies of children fathered through intracytoplasmic sperm injection or ICSI have revealed mutations on the AZF region of the Y chromosome linked to male infertility. Mutations of other genes may also be involved. Candidates would include genes for the androgen receptor, follicle-stimulating hormone, and luteinizing hormone, and genes involved in the regulation of spermatogenesis and sperm motility. Mutations in mitochondrial DNA have been linked to poor sperm motility and raise the possibility that some types of male subfertility may be inherited only through the female line.
We propose to assess the role of folate/homocysteine status and MTHFR and CBS gene variants in infertile men in Sweden with no known cause for their infertility and whose wives/partners appear to be fertile. We propose to perform the study in Sweden since Sweden, unlike the U.S., at present does not mandate the enrichment of flour or other foodstuffs with folate.
- Conditions
- Male Infertility
- Keywords
- Genotypes, Mutation, Folate, Male Infertility, Nutrition
- Medical subject headings
- Infertility, Male
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start2 Jan 2003
- Study completion29 Aug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Male InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Investigators
- Richard J Levine, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00341120
- Sponsor's protocol ID
- 999903076
- Other IDs
- 03-CH-N076
- Status last verified
- 29 Aug 2012
- First submitted
- 19 Jun 2006
- Last updated
- 5 Apr 2018
- Results posted
- No
Publications
Ma K, Mallidis C, Bhasin S. The role of Y chromosome deletions in male infertility. Eur J Endocrinol. 2000 May;142(5):418-30. doi: 10.1530/eje.0.1420418.
PubMed 10802517Ford WC. Biological mechanisms of male infertility. Lancet. 2001 Apr 21;357(9264):1223-4. doi: 10.1016/s0140-6736(00)04452-4. No abstract available.
PubMed 11418145Ruiz-Pesini E, Lapena AC, Diez-Sanchez C, Perez-Martos A, Montoya J, Alvarez E, Diaz M, Urries A, Montoro L, Lopez-Perez MJ, Enriquez JA. Human mtDNA haplogroups associated with high or reduced spermatozoa motility. Am J Hum Genet. 2000 Sep;67(3):682-96. doi: 10.1086/303040. Epub 2000 Aug 9.
PubMed 10936107
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methylenetetrahydrofolate Reductase C677T Mutation, Other Variant Genotypes, and Male Infertility
- ClinicalTrials.gov ID
- NCT00341120
- Acronym / sponsor ID
- 999903076
- Conditions
- Male Infertility
- Keywords
- Genotypes, Mutation, Folate, Male Infertility, Nutrition
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 2 Jan 2003
- Study completion
- 29 Aug 2012
- First posted
- 21 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being conducted at the University Hospital of Lund University in Malmo, Sweden, in collaboration with the U.S. National Institute of Child Health and Human Development. The study will try to identify genetic causes of impaired sperm production and male infertility. It will focus on the possible role of the MTHFR and CBS genes, which regulate absorption and metabolism of the vitamin, folate in infertility. If the nutritional intake or metabolism of this vitamin is related to male infertility, then this cause of infertility would be potentially curable.
Fertile and infertile men between 20 and 45 years of age may be eligible for this study. Criteria include the following:
- Fertile men: men whose partners are younger than age 40 and are attending Lund University prenatal clinic; who have fathered one or more pregnancies and who stopped birth control to achieve the present pregnancy; who achieved the present pregnancy in less than 12 months of unprotected intercourse.
- Infertile men: men referred to the Scandian Andrology Centre whose infertility is unexplained, whose partners are younger than age 40 and who have had regular sexual intercourse without contraception for at least 12 months without achieving a pregnancy.
All participants will have the following tests and procedures:
- Complete a questionnaire providing information about their reproductive and medical history and recent dietary history;
- Provide blood samples for analysis of red cell folate, plasma folate, plasma homocysteine, plasma B12, and for genetic evaluation;
- Provide a semen sample for routine analysis, including volume, sperm concentration, sperm motility, and sperm morphology.
In addition, infertile men will undergo a physical examination and review of their medical records.
Detailed description
It is evident that genetic variation plays a substantial role in the etiology of male infertility. Studies of children fathered through intracytoplasmic sperm injection or ICSI have revealed mutations on the AZF region of the Y chromosome linked to male infertility. Mutations of other genes may also be involved. Candidates would include genes for the androgen receptor, follicle-stimulating hormone, and luteinizing hormone, and genes involved in the regulation of spermatogenesis and sperm motility. Mutations in mitochondrial DNA have been linked to poor sperm motility and raise the possibility that some types of male subfertility may be inherited only through the female line.
We propose to assess the role of folate/homocysteine status and MTHFR and CBS gene variants in infertile men in Sweden with no known cause for their infertility and whose wives/partners appear to be fertile. We propose to perform the study in Sweden since Sweden, unlike the U.S., at present does not mandate the enrichment of flour or other foodstuffs with folate.
Study design
Who may qualify
- Ages
- 20 to 45 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Referred to the Scanian Andrology Centre.
- Age 20-45.
- Partner age less than 40.
- Having had regular sexual intercourse without contraception for a year or more without achieving a pregnancy.
- Partner attending Lund University prenatal clinic.
Key exclusion criteria (19 listed)
- Klinefelters syndrome.
- Hypogondotropic hypogonadism.
- Y-chromosome microdeletion or abnormality.
- Other genetic cause for infertility.
- Obstructive azoospermia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Background: PubMed 10802517Ma K, Mallidis C, Bhasin S. The role of Y chromosome deletions in male infertility. Eur J Endocrinol. 2000 May;142(5):418-30. doi: 10.1530/eje.0.1420418.
- Background: PubMed 11418145Ford WC. Biological mechanisms of male infertility. Lancet. 2001 Apr 21;357(9264):1223-4. doi: 10.1016/s0140-6736(00)04452-4. No abstract available.
- Background: PubMed 10936107Ruiz-Pesini E, Lapena AC, Diez-Sanchez C, Perez-Martos A, Montoya J, Alvarez E, Diaz M, Urries A, Montoro L, Lopez-Perez MJ, Enriquez JA. Human mtDNA haplogroups associated with high or reduced spermatozoa motility. Am J Hum Genet. 2000 Sep;67(3):682-96. doi: 10.1086/303040. Epub 2000 Aug 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard J Levine, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Male Infertility, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00341120, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2018.