A study led by researchers from the University of Oxford’s Big Data Institute has identified 25 genetic variants linked to infertility and 269 that are linked to hormones that can affect fertility.
The study, published in Nature Genetics, is the first comprehensive view of the relationships between genes and infertility. The results may lead to improved diagnosis and treatments for fertility-related conditions.
Infertility, defined as the inability to achieve pregnancy within 12 months of regular unprotected sexual intercourse, is thought to affect one in six couples around the world. It is associated with a wide range of social, environmental, and genetic factors but the exact cause is not known for up to 28% of couples and 40% of women.
Previous studies have suggested that infertility may be caused by problems with reproductive hormones and obesity but so far there has been limited evidence on how our genes affect fertility.
Key findings:
- 25 genetic variants for infertility were identified, 22 in women and three in men;
- 269 genetic variants were found to be associated with hormones that can affect fertility, including follicle-stimulating hormone (which has different functions depending on sex and age), luteinising hormone (which triggers ovulation in women and sperm production in men), oestradiol (the main oestrogen found in women), and testosterone. However, no genetic association was found between female infertility and reproductive hormones;
- Three genetic variants were found to be associated with male infertility. One of the three variations is near ENO4, a gene linked to sperm movement. When this gene is removed in male mice, it causes infertility;
- Endometriosis was found to be genetically associated with all-cause female infertility and polycystic ovarian syndrome (PCOS) was found to be genetically associated with anovulatory infertility;
- Just three of the eight genetic variants linked to anovulatory infertility (when an egg has not been released as part of a regular menstrual cycle) were also linked to PCOS, suggesting that there may be other conditions that are contributing to genetic causes of anovulatory infertility that require specific treatment;
- The study found no genetic association between obesity and infertility, supporting previously published evidence that found no fertility-related benefits as a result of short-term weight loss in overweight and obese women. The study did find evidence that the causal link between obesity and anovulatory infertility is bidirectional, meaning that each condition worsens the other.
Cecilia Lindgren, Professor of Genomic Endocrinology & Metabolism at Oxford Population Health and the Big Data Institute, said ‘Our results suggest that while individual genes associated with hormone regulation may be relevant for fertility, there is limited genetic evidence for correlation between reproductive hormones and infertility. However, our findings suggest that there may be individual genes associated with hormones that can have an effect on fertility and that must be explored.
‘Infertility is a growing concern, due to factors like age, lifestyle, and environmental exposures. Our results are a huge step forward in unravelling the complex biology behind fertility, but we need to explore other genetic and non-genetic avenues to be able to identify the underlying causes of infertility and provide better answers to those suffering from the condition.’
The researchers looked at genetic data from more than one million participants in seven large-scale population studies around the world. Among these participants, the researchers looked for cases of female infertility that were the result of any cause, anatomical differences, anovulation, and unknown causes that were either linked to a known fertility condition such as PCOS or endometriosis or completely unknown. The researchers also looked at male infertility as a result of any cause. The study is the largest of its kind to date.