By
Karen Hsu, The Boston Globe
Troy
and Brandy Ciccarelli's story of how they managed to have a baby
is becoming commonplace as the medical community makes strides
in treating infertility. After Troy, 34, was told by doctors that
he had a low sperm count, the couple consented to an increasingly
used fertility technique that injects sperm into the egg.
The
result was twins, a boy and a girl, delivered in August. But as
success stories such as the Ciccarellis' continue to mount, a
new study proves that the mutation that caused his low sperm count
can be passed to the next generation, ensuring that the number
of infertile males will continue to grow. The Ciccarellis knew
of this possibility before the procedure, and indeed, the couple's
son inherited the mutated gene from Troy Ciccarelli. Fertility
experts say they have long warned their patients that their sons
could inherit the infertility.
In
a study published in the July issue of the journal Human Reproduction,
Dr. David Page of the Whitehead Institute for Biomedical Research
in Cambridge, Mass. and Dr. Sherman Silber of the Infertility
Center of St. Louis show that sons inherit the abnormal chromosome
linked to male infertility. The genetic basis for this form of
infertility was established in 1995. Page and colleagues tested
89 infertile men, of whom 12 were missing a fragment of the Y
chromosome known as the AZFc region.
The
loss of the tiny piece appears to account for infertility for
about 13 percent of men who produce little or no sperm, Page said.
Considered experimental in the early 1990s, the technique of injecting
a sperm into an egg, called intracytoplasmic sperm injection,
or ICSI, is now the preferred method for circumventing severe
male infertility. In 1996, 16,011 cycles of ICSI were attempted
in the United States, and 6,098 babies were born from the technique,
according to the American Society for Reproductive Medicine.
In the study published Thursday, the authors examined four sons
of three men who had a deletion in the AZFc region and had undergone
ICSI. In all four cases, the sons had the same Y chromosome deletion.
``We were kind of stumped that my father didn't have it, that
the genetic thing started with me,'' Ciccarelli said. Page said
that for every 2,000 men, one probably carries the missing piece
of the Y chromosome, but researchers do not know how the mutation
happens.
About
40 percent of all couples' infertility is due to problems in the
male. Not all male infertility can be explained by genetics, but
Silber said even subtle genetic mutations might be the answer
for the majority of men. Silber said at least eight other genes
and as many as 30 are involved in sperm production. ``We warn
all our patients there is a risk. Even the ones who don't have
this deletion, we are very careful to tell them that they may
have another mutation that we will discover someday,'' Silber
said.
But
Dr. Richard Reindollar, director of reproductive endocrinology
at Beth Israel Deaconess Medical Center in Boston, said another
possible cause of infertility is chromosomal translocations, which
are chromosomes with fragments switched with fragments from other
chromosomes. ``They could lead to other abnormalities than just
infertility in the offspring,'' said Reindollar, a physician with
Boston IVF, one of the largest fertility clinics in the nation
with more than 2,000 treatment cycles a year, of which 25 percent
are ICSI. Although reproductive technology defies what nature
protected by preventing conception in the first place, most patients
say they are not too worried that their sons, too, will probably
have to make babies via the lab.
Silber,
who was the Ciccarellis' doctor, said couples rarely decide against
the ICSI treatment after they are informed that the mutation can
be passed on. But Dr. Robert Oates, associate professor of urology
at Boston Medical Center, said about 20 percent of his patients
decide not to go through the therapy because they are worried
the infertility problem could be genetic. ``That speaks strongly
to us that we need to inform people as best as we can that infertility
can have a genetic basis,'' Oates said. Oates said other options
include using a sperm donor, or adoption.
Silber
added that another option is the choice to have only daughters,
because they do not carry the Y chromosome. Troy Ciccarelli hopes
that reproductive technologies will become so advanced that it
will be easier to produce a child from the lab 30 years from now.
``I guess some of it was selfishness. After you have been through
the wringer, you want to have a family. We are still so ecstatic,''
Ciccarelli said. ``Obviously, he won't know until we think the
time is right. I don't want him to think he has the green light
to do you know what and not have any worries.''
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