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.''
