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Polycystic Ovary Syndrome (PCOS)

Polycystic Ovary Syndrome (PCOS) and its effect on infertility is discussed by the Center for Human Reproduction’s physician Norbert Gleicher, MD. Listen here for PCOS syndrome treatment options.

PCOS stands for polycystic ovary syndrome or ovarian syndrome. There are many different conditions that can all end up in the final presentation of polycystic ovaries. What those polycystic ovaries represent is really the inability of the follicles to break through– which is the process that is required for ovulation. These women don’t ovulate or at least don’t ovulate regularly. So there are different, what we call, phenotypes – different presentations which all end up in PCOS. Mostly the more obese PCOS patients are at significant risk for insulin resistance and what is called the metabolic syndrome — meaning late in life developing high blood pressure, diabetes and atherosclerotic heart disease. So those patients represent not only a fertility problem but in general a medical problem to their long term health. Yet, others have none of these associated problems and we are obviously talking about very different issues. They are the one big thing. PCOS patients, most of the time, come to our attention because they are infertile, not because they are more fertile. And, it only appears that they produce more eggs because the eggs get arrested in the maturation process, they do not ovulate, and so they line up in the ovary and it looks like ‘wow they have a lot of eggs’. Indeed, if you then start stimulating these patients, whether for egg donation or for an IVF cycle, they are the patients who are at highest risk for overstimulation — or what we call the hyperstimulation syndrome. Because, they have so many immature follicles lined up that once those follicles are stimulated and pushed forward ‘boom’ suddenly we have an explosive response and tons of eggs that mature in parallel and that can be very dangerous. PCOS patients have to be treated very differently from all other fertility patients. If I can summarize it in one word – “carefully”. We do it very tenderly. We start very low and they usually do not respond. Then we go slowly up until we hit the point where they respond and we try to hit that point at the lowest possible level. That is different from other patients where we do not expect and we do not see this kind of explosive response. In PCOS patients we therefore have to be always on the outlook and always cautious about the development of hyperstimulation syndrome. These patients need to be very very carefully managed. We have been very interested in a gene called the FMR1 gene, or as some also call it the ‘Fragile X’ gene, which is a tiny snip-it of genetic material on the X chromosome. We have been perusing quite active research on this gene because we suspected and then confirmed that this gene has major importance for the ovarian aging process. As part of our research, we defined different genotypes – meaning different presentations of this gene – and we have learned that one of these genotypes which we have come to call the heterozygous normal-low genotype is very closely associated with — is characterized by — PCOS genotype at a young age. What that means is that if a woman has this genotype, when she is young she would present like a PCOS patient – a skinny PCOS patient — showing all the classical signs of PCOS. But, she very quickly depletes her egg pool with which she is born and so already by mid-age very often she presents with diminished ovarian reserve. And, that’s when we mostly end up seeing them. Then, as they get older more and more of their ovarian reserve dwindles. So, this is just one more example for the observation that PCOS is not one condition. It is really a whole group of different conditions which all present with polycystic ovaries. The genotype we describe goes even beyond that because these patients don’t keep this PCOS presentation, they only show it while they are relatively young. As they get older they loose this PCOS appearance of their ovaries. So, there is a lot of research going on PCOS and we will have an enormous amount to learn.