Klinefelter’s Syndrome

As our understanding of Klinefelter’s Syndrome (KS) grows, urologists and male fertility specialists will become more involved with their reproductive care. With an estimated frequency of 1:500-1:1000 of live deliveries, Klinefelter’s is the most common numerical chromosomal abnormality in men. Klinefelter’s Syndrome is identified when the karyotype reflects that there are extra X chromosomes (XXY -XXXXY). These men represent 14% of infertile men who present with azoospermia. The vast majority of the time, you cannot pick a man with KS out of a crowd. KS men may be found in all professions, all socieeconomic groups and all demographics. Most commonly, they are identified through an evaluation for male infertility when a semen sample shows that there are no sperm in the ejaculate. Up to 10% of men with non-obstructive azoospermia may be found to have the Klinefelter’s karyotype. They may have lower testosterone levels and may report some decreased energy, libido and erectile function. These are all signs that their testicles are not doing their job properly: specifically, to make sperm and to make the hormone testosterone.

Genetic studies including a karyotype are routinely performed for men without sperm in their ejaculate. A karyotype is tested by taking a blood sample. Special stains are used to help see each chromosome so that they can be accounted for. KS men will show at least one extra X chromosome when the karytope is done. The predominant non-mosaic XXY karyotype is felt to occur spontaneously. Advanced maternal and paternal age are felt to be associated with an increased risk of KS.

Previously, it was assumed that these men were sterile 100% of the time. In the 21st century, new state-of-the-art microsurgical techniques have offered new hope for these men with a new procedure called a MicroTESE or a Microdissection Testicular Sperm Extraction. Recent data suggest that sperm may be found in approximately 50% of these men. Very rarely, occasional sperm can even be seen in some the ejaculates of some KS men (Schiff et al. J Clin Endocrinol Metab 2005: 90: 62623, Friedler et al. Hum Reprod. 2001: 16: 2616, Tournaye Hum Reprod. 1996: 11: 1644). It is important that you seek out a male fertility specialist near you to help you optimize your reproductive plan. In addition to being able to offer you the specialized MicroTESE procedure, they may be also be able to use medications to help optimize the level of testosterone in your testicles to help optimize sperm production. One such medication is called an aromatase inhibitor (Raman et al. J Urol 2002: 167: 624.)

Click here to learn more about Microdissection of the testicles or MicroTESE.

It is important to note that fertility optimization is only one part of the comprehensive care the KS men need. It is important that KS men seek out an endocrinologist and/or other specialists to help treat hypogonadism (lower than normal testosterone levels) and to monitor for any other associated issues that may include weakening of the bones (osteopenia/osteoporosis), the risk of deep vein thrombosis (clots in your legs) and certain malignancies such as breast cancer and non-Hodgkin’s lymphoma.

You are not alone with Klinefelter’s! Learn more about AAKSIS!

The American Association for Klinefelter Syndrome Information and Support (AAKSIS) is a national volunteer association with the mission of education, support, research, and understanding of 47XXY and its variants, collectively known as Klinefelter Syndrome. Statistics suggest that there are thousands of 47XXY individuals in the United States alone. Many remain undiagnosed. Current and accurate information about 47XXY required by those confronted with a new diagnosis is often unavailable. The mission of AAKSIS is to raise awareness of the condition among medical professionals and the general public. AAKSIS works with its professional advisors to present an annual educational program aimed at providing the latest information and research to its community and anyone interested in learning more about the condition.

To learn more, please contact AAKSIS at their Toll Free Hotline–(888) 466-KSIS or visit their website at www.aaksis.org

To obtain more information about becoming a member of AAKSIS, please download this pdf: Klinefelter_Brochure.pdf

Dr. K, Are there Klinefelter’s community forums on the Web that my partner and I can be a part of? Of course!

The AAKSIS ListServ has been formed to provide support, discussion, and fellowship for the international community of those medically diagnosed WITH 47XXY (Klinefelter Syndrome) and variants, their supporters, family members, spouses, medical, and psychological advisors. To learn more, click here: www.aaksis.org/Visitor/Emailsub.cfm.

In addition to becoming subscribed to the AAKSIS Listserv, the following discussions are also available. Please contact us at [email protected] for subscription information.
XXYWIVES:

This list is for wives and girlfriends of XXY men. Learning and supporting each other is the goal. It is a private list and subscribers must be approved by the list moderator.
XXYNOY:

This list is for parents of XXY sons whose ages are “prenatal to onset of puberty”. Learning and supporting each other is the goal. It is a private list and subscribers must be approved by the list moderator.

XXYNOY2
This list is for parents of XXY sons whose ages are “onset of puberty and up thru adulthood”. Learning and supporting each other is the goal. It is a private list and subscribers must be approved by the list moderator

Dr. K, what’s going on with the latest cutting edge research for men with Klinefelter’s who facing male infertility?

The testicles of men with Klinefelter’s do not function properly and it results in too little testosterone and sperm. New research by Vaucher et al. at Cornell (Data was presented at the American Urological Association meeting in 2009) sheds light as to why the testosterone levels in most of these men will decline over time. Their research suggests that the problem is not that the testicles don’t make enough testosterone, but that the testosterone is being excessively broken down and converted into estrogen. This causes a low sperm count since too much estrogen and too little testosterone actually inhibits sperm production. They found that KS men seem to make over 4 times too much CYP19, a fancy protein that is responsible for converting testosterone to estrogen (an aromatose).

Bottomline: This research group led by Darius Paduch MD is continuing to lead the way on shedding light on “why” Klinefelter’s Syndrome occurs. While our understanding is not advancing in leaps and bounds, we will slowly but surely get there. (112709)

Reproductively, new data from Cornell by Ramasamy et al. (Abstract 2010) confirms the growing body of evidence that finding sperm in azoospermic KS men is very possible. Looking at 69 non-mosaic KS men who underwent 91 attempts of Microdissection of the testicles (MicroTESE), they were pleased to find an overall sperm retrieval rate in 66% of men. For the subset of men who had a low testosterone level, they saw a 72% sperm retrieval rate if their testosterone levels rose by more than 100 ng/dL after medical therapy (use of medications like HCG, clomiphene citrate or aromatase inhibitors). For men with normal baseline testosterone levels, sperm were found in 86%.

Bottomline: It is definitely possible to find sperm in KS men to help them have their own biological children via IVF. Find a male fertility fellowship-trained specialist near you to talk to you more about a Microdissection of the testicles and to see whether medical treatments may benefit you.

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