A new preclinical study using human tissue grafted into mice has indicated that high levels of anti-Müllerian hormone (AMH) may contribute to fertility problems and other symptoms associated with polycystic ovary syndrome (PCOS).
The study, published in Science Advances, found that AMH may result in follicles, the fluid-filled sacs that contain developing eggs in the ovaries, maturing too quickly, affecting ovulation. Previously, it was assumed high AMH levels in women with PCOS were purely incidental and did not play a role in causing the symptoms of the syndrome.
'AMH is routinely measured in the clinic to give an indication of how many follicles a woman has growing in her ovaries, and this value is often high in women with PCOS. But no one has ever determined whether a high level of AMH, by itself, can have a negative influence', said Dr Daylon James, assistant professor at Weill Cornell Medicine, who led the study.
Follicles support the growth of developing eggs, known as oocytes. Normally, the oocyte matures as the follicle grows, until a mature egg is released from the follicle during ovulation.
In the 10 percent of women with PCOS, the ovaries contain many small follicles, all of which produce AMH and collectively cause levels to rise. These follicles fail to mature, and when no egg is available for ovulation fertility problems result.
To investigate the role of AMH in PCOS, the research team grafted ovarian tissue from human organ donors with no history of fertility problems or PCOS onto immunocompromised mice. Half of the mice were also transplanted with cells that continuously supplied AMH to the grafted ovarian tissue. The other half were transplanted with control cells, with no AMH.
The researchers found that ovarian tissue exposed to high levels of AMH contained follicles showing signs of a much later stage of development. This suggests that the presence of many small follicles in the ovaries of PCOS patients are the accumulation of follicles undergoing rapid maturation which fail to ovulate.
'AMH is causing the usually coordinated growth process between a follicle and its resident oocyte to fall out of synch', said Dr James. 'It is like baking with the oven too hot. The outside, or the cellular component of the follicle, is overcooked, while the inside, or oocyte, is not done', he said.
Despite the high prevalence of PCOS, the causes behind it are not well known. While some genetic risk factors have been identified (see BioNews 1122), their impact on fertility and diagnosis of the condition remains controversial.
Although treatments exist for the various symptoms of the disease, they often persist until women reach the end of their reproductive lifespan. The findings of this study suggest that AMH might contribute to the accumulation of follicles found in PCOS, as well as the other secondary symptoms commonly observed.