Genetic Causes of Male Infertility
Condition: Male Infertility
MeSH terms: Infertility; Infertility, Male
Study type: Observational

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.
      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.
    

Keywords: Genotypes; Mutation; Folate; Male Infertility; Nutrition