Investigating the regulation of male fertility
Research type
Research Study
Full title
Investigating the regulation of male fertility
IRAS ID
156160
Contact name
CN Jayasena
Contact email
Research summary
Research Summary
Infertility is a devastating condition. Ten percent of couples suffer infertility, and nearly half of these cases are due to sperm abnormalities in the male partner (‘male infertility’). Little is known about the underlying causes of male infertility. No drugs are available which have proven benefit for male infertility. The only effective treatment for male infertility is testicular sperm extraction (TESE). TESE is a surgical technique, which aims to retrieve sperm directly from biopsies of testicular tissue under general anaesthetic; however, TESE is an invasive procedure, requires a highly skilled surgeon to perform the procedure, and has limited availability in the NHS. There is therefore a major need to learn more about the mechanisms causing male infertility in order to improve the treatment of men with this condition.
We propose to perform an observational study investigating the underlying causes of male infertility in men who are already undergoing a clinically requested diagnostic semen analysis (DSA, i.e. 'sperm count') in the Andrology Unit of Hammersmith Hospital. Participants would be invited to complete a questionnaire, undergo testicular size measurement (a simple and routine procedure), and give a blood sample to measure levels of reproductive hormones and to perform genomic analysis (analyse their DNA). In addition, semen collected as part of their routine care would be frozen later genomic analysis.
All information from the study would be confidential, and have no health implications for participants, but could be invaluable for future patients with male infertility. Studying the hormonal and genetic causes of male infertility may be greatly beneficial to improve the treatment of men with infertility. Specifically, this work could lead to novel treatments for male infertility, reduce the need for surgical procedures such as TESE, and improve the quality of information we can give to patients about their condition.
Summary of Results
Infertility is a devastating condition for couples wishing to have a baby. Around 1 in 10 couples suffer from infertility and nearly half of these cases are due to problems with sperm in the male partner (“male infertility”). In some cases we are unable to find a cause for the infertility in men and there may be an underlying genetic cause.
Firstly, we looked at men who were being investigated for male infertility, who had no sperm and no other cause has been found. We performed genetic testing to look for changes in the genes which are involved sperm production. We found alterations in the sequence of genes called FKBP6, MEIOB and YBX2, which would be predicted to affect function of their respective proteins that are highly specifically located in the testes. As a result of this study, further research has found that alterations in the sequence of the gene FKBP6 is shown to be associated with male infertility. Testing for this gene in men with unknown causes of male infertility may be a useful diagnostic test. This work was published in 2022 (DOI: 10.1016/j.ajhg.2022.09.002).
Secondly, we look at the semen of men whose female partners had recurrent pregnancy loss. Recurrent pregnancy loss affects 1-2% of couples and is when a woman has three or more miscarriages before 20 weeks. We studied the semen of these men to look for DNA damage and reactive oxygen species (ROS). ROS are very small molecules found within the body, needed for the body to work normally. In large amounts however they can cause damage to DNA. Our study found that the male partners of women with recurrent pregnancy loss had a higher amount of ROS and DNA damage in semen compared with healthy men. Investigating the male partner in women who have recurrent pregnancy loss may be useful as part of the clinical assessment. This work was published in 2019 (DOI: 10.1373/clinchem.2018.289348).
REC name
London - West London & GTAC Research Ethics Committee
REC reference
14/LO/1038
Date of REC Opinion
15 Jul 2014
REC opinion
Further Information Favourable Opinion