Specialists Trying to Unravel the Mystery of Miscarriage
By EMMA DALY
Published: February 8, 2005
NYT
he first time Patricia McCreary became pregnant, she had a baby.
"I look at that now as this nave bliss time, when I thought
pregnancy meant a baby," said Ms. McCreary, who lives in Seattle.
But five years and four miscarriages later, she said, "When I hear
someone say, 'I'm pregnant,' to me it's like, fear and dread and when
am I going to get my heart smashed."
The agony of infertility for thousands of American women is not that
they cannot conceive, but that they cannot hold on to their babies
beyond the first few weeks of pregnancy - and no one can explain why.
Doctors say that as many as 3 or 4 percent of couples who try to have
children suffer from what doctors call recurrent pregnancy loss, in
which women younger than 40 experience three or more consecutive
miscarriages with the same partner.
A fourth of those couples, doctors say, will probably remain in
the "don't know why" category. Researchers at the Centers for Disease
Control and Prevention estimate that of the 6.23 million pregnancies
recorded in the United States in 1999, 1 million ended in
miscarriage. A 25-year-old has a 15 percent chance of miscarrying. By
42, that figure exceeds 50 percent.
Miscarriages, though common, are rarely discussed. Nor have they been
much studied until recently.
In most women, miscarriages occur because an embryo with genetic
abnormalities is not viable, and that is also true for some losses
among women who miscarry often. In those cases, women can opt for in
vitro fertilization and pre-implantation genetic diagnosis. That
ensures that only embryos deemed genetically normal are implanted in
the uterus.
Other causes of recurrent pregnancy loss include anatomical
abnormalities in the uterus, diseases of the immune system, hormonal
imbalances and problems with blood clotting. Infections and, more
rarely, chromosomal abnormalities in a parent, can also be factors.
Patients and doctors say that treatments can differ wildly from
practice to practice and that there is only a limited consensus on
how to address unexplained recurrent pregnancy loss.
"Doctors forget to order the very basic tests, check the uterus,"
said Dr. William H. Kutteh, a specialist in immunology and
reproductive endocrinology at Fertility Associates of Memphis. Over
half the women Dr. Kutteh sees with recurrent pregnancy loss, he
said, have never been given a cheap, simple test for insulin
resistance, although that problem is associated with higher
miscarriage rates.
Even a treatment as venerable as progesterone, a hormone vital to a
healthy pregnancy, is divisive. Some doctors swear that it helps.
Others argue that it does nothing but postpone an inevitable
miscarriage. New research suggests that very high doses of
progesterone may be effective in some cases, probably a result of the
hormone's immunosuppressive effects.
"How many patients do we save from miscarriage with progesterone
supplements?" Dr. Alan B. Copperman, director of reproductive
endocrinology and infertility at the Mount Sinai Medical Center,
asked. "Not that many. Do we do it routinely? Sure we do. It's a
mostly harmless, inexpensive treatment, which a lot of patients go
on. But it probably doesn't save that many pregnancies."
Dr. Kutteh said that when he was a student 15 years ago "there was no
training on pregnancy loss."
"It's just one of those areas where there wasn't much known," he
added. "And there were not many experts, and there was not a
consensus on what to do."
Now, he said, more than 25 training programs turn out about 50
specialists a year.
Despite exhaustive testing to find a cause, many miscarriages go
unexplained. This was the case for Ms. McCreary and for Isabel
Letsch, 25, of Baltimore, who has charted the reproductive history of
her three miscarriages after failed fertility treatments in a Web
log, Isabel's Journal.
"It's just a big mystery," Ms. Letsch said. "My doctor has given up
hope and told me it's because I'm overweight."
No data support that diagnosis, she said, adding:
"I know I can get pregnant. I've never got as far as to see a
heartbeat. We know it implants. It just doesn't develop any further.
We're just kind of frustrated."
Ms. McCreary said she received conflicting advice from doctors in the
same practice. One advised trying in vitro fertilization with pre-
implantation genetic diagnosis. Another expressed skepticism about
I.V.F. for women who repeatedly miscarry.
"Two people in the same office, and I really respect them both," Ms.
McCreary said. "They have no idea. There's nothing they can point to
except for my age."
Dr. Aydin M. Arici, director of reproductive endocrinology and
infertility at the Yale School of Medicine, said, "Everybody would
agree there's no agreement."
Recurrent miscarriages have many causes, Dr. Arici said.
"For two-thirds of the known causes," he said, "there is a specific
treatment. Then you have about 40 percent where you don't know
exactly what has caused it. So there are some empirically unproven
treatments out there that are highly debatable."
One theory explaining why some women repeatedly miscarry is that the
immune system somehow fails to recognize and protect a pregnancy, and
instead mounts antibodies to attack it.
This idea has led doctors to try two treatments intended to to
restore normal immune function. One is intravenous immunoglobin
therapy, a blood product pooled from thousands of donors and used to
regulate abnormal responses of the immune system. The other is
lymphocyte immune therapy, which uses blood from a woman's partner to
prompt her immune system to recognize a pregnancy.
The immunoglobulin therapy is being studied by Dr. Kutteh and Dr.
Arici. But the lymphocyte treatment, promoted on the Web as a
possible cure, , has been restricted by the Food and Drug
Administration because of fears that it in fact increases
miscarriages.
At least one American doctor is offering the treatment in England,
and some women are traveling to other countries for the therapy. "The
theory is wonderful, but the data never really showed that it
worked," Dr. Kutteh said.
For two years, Dr. Kutteh has run a controlled clinical trial of the
immunoglobulin therapy in a subgroup of women with unexplained
recurrent miscarriages who have given birth at least once.
Dr. Arici has joined the trial, begun by Dr. Mary Stephenson at the
University of Chicago, and early results seem to indicate a possible
benefit to this specific subgroup.
The doctors note that the studies are complicated by the fact that
even without treatment, women whose recurrent miscarriages cannot be
explained have a 60 to 70 percent chance of a successful pregnancy.
"About 40 different treatments over the past century claim to be
successful, and some sound O.K.," Dr. Arici said. "But when you look
at them, all of them claim about a 70 percent success rate. When you
take this unexplained group and give them tender loving care,
contact, reassurance, about 70 percent will carry to term."
Carol Turner, a nurse practitioner in Westport, Conn., had many tests
after two ectopic pregnancies and several miscarriages. No underlying
cause was found.
Yet, all three of her daughters were born without help and after
unsuccessful fertility treatments. The third was conceived after in
vitro fertilization resulted in yet another failed pregnancy.
"We had an exit interview," Ms. Turner said, "and the doctor
said: 'You're not a candidate, I'm never doing that again to you. You
have a zero percent chance. You will never be pregnant again.' And a
month later, I got pregnant on my own with my last baby, who is very
healthy."
Faced with the prospect of doing nothing except waiting and hoping
for the best, many couples seek out expensive experimental
treatments, sometimes found on the Internet.
"When women are going through this, they're desperate to try
anything," said April R. Simonoff, a vice president of the Long
Island chapter of Resolve who had unexplained miscarriages.
Ms. McCreary, who is trying to decide whether to keep trying to have
another child, found some solace when she discovered Chez
Miscarriage, one of several infertility Weblogs that are wickedly
funny, as well as wise, mixing raging profanity and sisterly support
in fairly equal measure.
"I just felt less alone," she said.
Allison Rosen, a therapist who treats people with infertility
problems and is editing a book of essays on the topic, said: "People
don't understand the deep connection to the unborn child, and they
don't understand it's the death of what feels, to the potential
parents, like a real person.
"The grief is so silent. We don't have rituals mourning a
miscarriage. So the pain is isolating."