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What is the Cause of Polycystic Ovary Syndrome?

 The most common cause of female infertility is polycystic ovary syndrome which may be caused by a hormonal imbalance before birth. It is reported to affect up to one in five women worldwide, three-quarters of whom struggle to fall pregnant. Thankfully, new findings have led to a cure in mice and a drug trial is set to begin in women later this year. 
Polycystic Ovary Syndrome

Polycystic ovary syndrome is characterized by high levels of testosterone, ovarian cysts, irregular menstrual cycles and problems regulating sugar, however, the causes have long been a mystery. According to Robert Norman, at the University of Adelaide in Australia, "it is by far the most common hormonal condition affecting women of reproductive age, but it hasn't received a lot of attention." And while treatments are available for helping affected women get pregnant, their success rates are typically less than 30% across five menstrual cycles. 

Womb changes

Paolo Giacobini at the French National Institute of Health and Medical Research and his colleagues have discovered that the syndrome may actually be triggered before birth by excess exposure in the womb to a hormone called anti-Müllerian hormone. In fact, researchers discovered that pregnant women with polycystic ovary syndrome have 30% higher levels of anti-Müllerian Müllerian hormone than normal. 

Furthermore, since the syndrome is known to run in families, they wondered if this hormonal imbalance in pregnancy might induce the same condition in their daughters. So, in order to test this idea, they injected excess Müllerian hormone into pregnant mice. And as their female offspring grew, they displayed symptoms of polycystic ovary syndrome, including later puberty, infrequent ovulation, delays in falling pregnant and fewer offspring. The excess hormone seemed to trigger this effect by overstimulating a set of brain cells that raise the level of testosterone. 

Polycystic Ovary Syndrome

Finding a cure in mice

In the process of finding a cure, the team was able to reverse this effect in the mice using cetrorelix, an IVF drug routinely used to control women's hormones. After treatment with this drug, the mice stopped showing symptoms of polycystic ovary syndrome. With these positive results, the team is now planning a clinical trial of cetrorelix in women who suffer from this condition. They hope to start before the end of the year. Giacobini says, "it could be an attractive strategy to restore ovulation and eventually increase the pregnancy rate in these women." 

Norman adds, “It’s a radical new way of thinking about polycystic ovary syndrome and opens up a whole range of opportunities for further investigation.” Furthermore, according to Norman, if the syndrome is indeed passed from mothers to daughters via hormones in the womb, it could explain why it's been so hard to pinpoint any genetic cause of the disorder. 

Furthermore, the findings may also explain why women with the syndrome seem to get pregnant more easily in their late 30s and early 40s. Usually, the anti-Müllerian hormone levels are known to decline with age, signaling reduced fertility. But it is believed that in women who start out with high levels, age-related declines may bring them into the normal fertility range. Still, this theory needs to be tested. 

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