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Azoospermia (No Sperm) & Related Syndromes
Zero Sperm Counts & Genetic Links
What has become evident at our Centers over the last several years is
that our ability to diagnose and successfully treat severe male infertility
problems has surpassed our ability to understand the basic causes of these
problems. In the recent past, it was considered that nearly 20% of men with
extremely low or "zero" sperm counts had no known medical reason for their
fertility problems. Most recently, major advances in molecular biology and
genetics have provided the "reasons" for severe infertility (very low or
zero sperm counts) in many men whose fertility problems were previously poorly
understood. We now know that 20-30% of men with such low (under 10 million/ml)
or zero sperm counts have a now identifiable genetic cause for their problem.
While we are now able to assist many, many men previously thought to be
"hopelessly" infertile achieve pregnancy, it remains very important
to not only treat these men, but to provide such couples with genetic information
related to the problem causing the low or zero count. This is important because
many of these genetic characteristics may potentially be passed along to
children conceived with the help of modern male infertility treatments. Genetic
disorders that would previously not have been able to be "passed along" due
to the male's infertility are now being retained in the "gene pool" as a
result of new procedures that overcome most of these previously untreatable
male conditions.
Congenital Absence of the Vas Deferens
Congenital absence of the vas deferens (CAVD) is a syndrome in which
a portion or all of the reproductive ducts (including the epididymis,
vas and seminal vesicles) are missing. This causes an obstruction to the
passage of sperm. These sperm, which are being produced normally in the testicle
become "trapped" in the testicle for lack of a pathway to the ejaculate.
CAVD may be associated with several diseases, including cystic fibrosis (CF)
and malformations of the kidneys (renal malformations). 65% of men with CAVD
will have a detectable genetic mutation in one of the cystic fibrosis genes,
and 15% will have a missing or misplaced kidney. This does not imply that
the man has or will develop cystic fibrosis but it means that he could be
a carrier of the gene. If his spouse is also a carrier, this means that there
is a 25% chance of a child born to them having cystic fibrosis. It is a standard
treatment policy in our Centers that all couples in which the man has CAVD
undergo cystic fibrosis carrier testing of both the man and his spouse/partner.
Once the genetic testing is completed (testing takes about 10 days), an in
vitro fertilization cycle may be planned for the wife, and a "MESA"
(microsurgical epididymal sperm aspiration) procedure planned for the man
to obtain viable sperm. These sperm may then be gently, microsurgically inserted
inside the eggs of the wife (ICSI) that have been obtained from an aspiration
carried out through the vagina. The resulting embryos may then be placed
into the uterus of the female to establish a pregnancy. Success rates remain
very high with this technique, even in men with "zero" sperm counts.
Y Chromosome Microdeletions
The human genome consists of 23 pairs or 46 chromosomes. There are 44
autosomes and two sex chromosomes. The sex chromosomes are called "X" and
"Y". Each genetically normal human has two sex chromosomes. A woman has "X"
and "X" (2X) and a man has one "X" and one "Y". The reproductive gametes
(eggs and sperm) get one or the other of each partner's sex chromosomes.
Because women have 2 "X" chromosomes, each of her eggs will have an "X" sex
chromosome. Because men have one "X" and one "Y" chromosome, half of their
sperm will carry the "X" chromosome and half will carry the "Y" chromosome.
It can therefore be soon that men are responsible for sex determination.
If an "X" egg is fertilized by an "X" sperm, an "XX" female will result.
If an "X" egg is fertilized by a "Y" sperm, an "XY" male will result.
If the "Y" chromosome from the sperm that fertilizes the "X" egg carries
a small mutation or deletion affecting sperm production in part of it's genetic
make-up, a male child resulting from a pregnancy may have the same sperm
production problem. We have found that 10-13% of men with an absent,
or "zero" sperm count will have a mutation or deletion on the "Y" chromosome.
We have also detected "Y" chromosome microdeletions in men with low, but
not zero counts. We offer a very sophisticated blood analysis (test) to determine
if these genetic conditions are present before undertaking therapy that will
lead to pregnancy.
Klinefelter's Syndrome
Klinefelter's Syndrome is a genetic disorder characterized by infertility,
abnormal male breast tissue development (gynecomastia) and small, firm testes.
It is the most common cause of azoospermia (no sperm production). Klinefelter's
Syndrome is caused by an abnormal number of sex chromosomes. Whereas a normal
male genetic make-up includes one "X" chromosome and one "Y" chromosome,
in patients with Klinefelter's Syndrome, an extra "X" chromosome is present,
resulting in three (XXY) sex chromosomes. Thought at one time to be hopelessly
infertile, it has been found that these men can have small amounts of sperm
production occuring within the testicle. Our Center has successfully recovered
sperm in men with this disorder who have gone on to father normal, healthy
children. It is important that all men with very low or absent sperm counts
be tested for Klinefelter's Syndrome before offering IVF and ICSI.
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