Genotype-Guided Fertility Treatment Enhances Pregnancy Outcomes, reveals study
Researchers have found in a new study that a genotype-guided approach significantly improves the chances of pregnancy and live birth. Specifically, women who are S-carriers benefit more from urinary FSH (uFSH), whereas those with the NN genotype respond better to recombinant FSH (rFSH).
About 15 per cent of all couples of reproductive age are involuntarily childless. A major reason why so many need assisted reproduction is that nowadays more and more people are putting off starting a family.
“This is a global trend that is expected to increase in the coming years. In Europe alone, one million IVF treatments are carried out each year; in Sweden, the corresponding number is 25,000,” says Yvonne Lundberg Giwercman, professor at Lund University who led the research. She has been researching fertility in both men and women for many years.
IVF treatment involves stimulating the woman’s ovaries to mature many eggs, which are then retrieved and fertilised with sperm in the laboratory before being returned to the uterus. There are two different types of hormone treatments to choose from for egg maturation: biological or synthetic. But the powerful hormone therapy also carries the risk of serious side effects, sometimes requiring women to go into intensive care – and many attempts at IVF fail. In Sweden, the government subsidises up to three IVF cycles.
“There is an over-reliance on IVF treatments. Around 75 per cent of all attempts fail and up to 20 per cent of women experience side effects, some serious enough to require emergency treatment. The choice of hormone therapy is a contributing factor, and a major challenge is that healthcare today to some extent has to guess which treatment is best for the woman,” says Ida Hjelmér, PhD and laboratory researcher at Lund University and first author of the study.
To find out who responds best to which hormone treatment, the researchers turned to genetics. A total of 1,466 women undergoing IVF treatment at the Reproductive Medicine Centre at Skåne University Hospital in Malmö, Sweden were included in the study. Women with endometriosis or polycystic ovary syndrome (PCOS) were excluded. Of the 1,466 women, 475 were randomised to two different hormone treatments while the rest were controls. One candidate gene that is involved in fertilisation by mediating the action of follicle-stimulating hormone (FSH), which is known to play an important role in egg maturation, was of particular interest and mapped by gene sequencing.
The study identified that women with a particular variant of the FSH receptor (FSHR) gene that mediates the action of the hormone responded best to the biological hormone treatment, while others benefited from receiving the synthetic type of hormone. By knowing the woman’s genetic profile in advance, we can increase the number of successful pregnancies, says Yvonne Lundberg Giwercman.
“We see an increase in the number of pregnancies and a relative number of 38% more babies born among women who received hormone therapy that matched their gene variation compared with those who did not. This means that for every 1,000 women undergoing IVF treatment, the equivalent of four more school classes are born: 110 more babies,” says Yvonne Lundberg Giwercman.
But mapping genes is costly and takes time. That is why the researchers have now developed a simple oral swab test, which within an hour shows which hormone therapy is most suitable. The result can be seen with the naked eye as a pink or yellow coulour.
The researchers have applied for a patent for the test, set up the company Dx4Life AB and are supported in the process by LU Innovation, LU Ventures and the SmiLe Incubator with a view to commercialising the product.
“Our hope is that this will reduce the risk of suffering for women, increase the number of successful treatments and cut costs for taxpayers. Our goal is for the test to be available by the start of 2026,” says Yvonne Lundberg Giwercman, who is also the CEO of the company that developed the oral swab test.
Reference:
Ida Hjelmér, FSH receptor N680S genotype-guided gonadotropin choice increases cumulative pregnancy and live birth rates after in vitro fertilization, Frontiers in Endocrinology, https://doi.org/10.3389/fendo.2025.1576090
