Genetic switch behind pregnancy discovered: Key to solving IVF failures and miscarriages

Women on an IVF journey or other infertility treatments often spend a lot of time wondering the how, when and why of getting pregnant. It's not easy to deal with their bodies that play hard to get, especially while on multiple hormone injections. Now, the Indian Council of Medical Research (ICMR) has found something that might finally answer many of its questions. The researchers found a fundamental biological switch in women's wombs that controls embryo implantation. It was published in the international journal Cell Death Discovery, said PTI. 

What the study uncovered
Dr Deepak Modi, ICMR-NIRRCH scientist and corresponding author of the study, said that two genes, HOXA10 and TWIST2, open or close a 'gate' in the womb walls to allow pregnancy. Apparently, the interior of a uterus is like a fortress that prevents anything from entering. If an implantation should succeed, this fortress should briefly open where the embryo arrives, says the study. HOXA10 ensures the uterus walls remain guarded. Dr Mohit Jolly of IISc, Bengaluru, said, "When an embryo comes in contact with the lining, HOXA10 temporarily switches off at that location. This short 'switch-off' allows another gene, TWIST2, to act. The activation of TWIST2 opens the gate by making the uterine cells soft and flexible, allowing them to move slightly and let the embryo in."

The study was conducted by the Indian Council of Medical Research, National Institute for Research in Reproductive and Child Health (ICMR-NIRRCH), Mumbai; Banaras Hindu University (BHU), Varanasi, and the Indian Institute of Science (IISc), Bengaluru. It had experts in molecular biology, genomics and mathematical modelling.

The challenges
The extent to which the uterine wall opens is also a significant factor in whether pregnancy occurs. If it opens very little, an embryo cannot implant. But if it opens too much, the pregnancy cannot be sustained. Controlling the balance between HOXA10 and TWIST2 could guide new strategies to improve IVF (in vitro fertilisation) success rates in future. The process was studied in mice, hamsters, monkeys, and human cells, and it was found that this HOXA10-TWIST2 switch occurs across species, as reported. 

Dr Geetanjali Sachdeva, Director of ICMR-NIRRCH, said, "Understanding this biological switch will explain why some women face repeated implantation failures or very early pregnancy loss, even with healthy embryos."