Study Reveals Potential Cause of Female Infertility Linked to PCOS
Understanding Polycystic Ovary Syndrome (PCOS)
A recent study published in Nature Medicine sheds light on a possible cause of female infertility associated with polycystic ovary syndrome (PCOS). This hormonal disorder affects approximately 10-18% of women of reproductive age globally. Women with PCOS typically exhibit enlarged ovaries that contain numerous immature follicles. Alongside symptoms such as excessive hair growth, acne, and irregular menstruation, PCOS is a significant contributor to female infertility. The condition has a strong genetic basis, often passed from mother to daughter. However, genetic factors account for only about 50% of cases, prompting researchers to explore additional contributing factors.
AMH Levels in Women with PCOS
Women diagnosed with PCOS generally have an increased number of follicles, resulting in two to three times higher levels of anti-Müllerian hormone (AMH), which is produced by ovarian follicles. In women without fertility issues, AMH levels typically decline during pregnancy due to reduced ovarian activity. However, a French research team discovered that AMH levels were significantly elevated in pregnant women with PCOS compared to those without infertility complications. Notably, while age did not influence AMH levels, lean women with PCOS exhibited higher AMH levels than their lean counterparts. Interestingly, AMH levels were similar between obese women with PCOS and obese controls, although the reasons for this similarity remain unclear.
Impact of AMH on Fetal Development
The research team investigated the effects of elevated AMH levels on fetal development by administering AMH injections to pregnant mice. The results indicated that the female offspring displayed reproductive symptoms consistent with PCOS, such as irregular ovulation and fertility challenges. Additionally, these offspring exhibited neuroendocrine symptoms typical of PCOS, including elevated testosterone and luteinizing hormone levels, as well as masculinization of brain regions responsible for reproductive regulation.
Mechanism of AMH-Induced Symptoms
The study traced these symptoms back to gonadotropin-releasing hormone (GnRH), which is produced in the pituitary gland and responsible for triggering luteinizing hormone release. The researchers hypothesized that elevated AMH levels hyperactivate GnRH, leading to continuous luteinizing hormone release. In women with PCOS, persistently high luteinizing hormone levels hinder ovulation and increase testosterone production.
Reversing AMH-Induced Symptoms
The researchers sought to determine whether they could reverse the symptoms associated with elevated AMH levels. They aimed to identify an antagonist that would prevent AMH from binding to GnRH. Treatment of the offspring with this antagonist successfully reversed all AMH-induced infertility issues and normalized the associated neuroendocrine problems.
Future Directions in Treating Female Infertility
While gonadotropin-releasing hormone antagonists have been safely used in other contexts, their application for treating female infertility remains distant. Although the antagonist used in this study showed promising results, it is important to note that the research was conducted in mice, leaving the applicability to humans uncertain. Additionally, due to potential risks associated with hormonal alterations during pregnancy, the research team plans to explore alternative treatment strategies.
References
1. Couzin-Frankel J. Scientists may be closer to understanding a mysterious but common cause of female infertility. Retrieved from http://www.sciencemag.org/news/2018/05/scientists-may-be-closer-understanding-mysterious-common-cause-female-infertility, accessed 27 August 2018.
2. PCOS. Retrieved from https://jeanhailes.org.au/health-a-z/pcos/symptoms-causes, accessed 27 August 2018.
3. Tata B et al. Elevated prenatal anti-Mullerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nature Medicine. 2018; 24:834-846.