FeaturesFeb/Mar 2013 Issue

Why Can’t We Have a Baby? Celiac Disease and Conception

Knowing Where to Look

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When Marisa and Doug Horowitz-Jaffe decided to start a family, they didn’t expect to have trouble. “There weren’t any red flags,” says Marisa, then 30. But after six months of well-timed trying and no signs of pregnancy, the couple went for help.

Doctors discovered Marisa had a blocked fallopian tube and they were optimistic that in-vitro fertilization (IVF) would successfully treat the problem. IVF is a procedure that circumvents blocked tubes by fertilizing a woman’s eggs outside her body (in a lab), transferring the resulting embryo back into her uterus a few days after fertilization.

Days after undergoing IVF treatment, an overjoyed Marisa knew she was pregnant, sensing it before the blood test could confirm it. But her bliss was short-lived. At her first ultrasound, doctors couldn’t find the gestational sac—where the baby develops in the uterus—and it was declared a chemical pregnancy, also known as an early miscarriage.

Marisa and Doug grieved the only way they knew how—they jumped right back on the IVF bandwagon. Over the next five years, the couple traveled from their home in Bronxville, New York, to several of the top fertility clinics around the country. Marisa underwent nine more cycles of IVF and suffered three additional miscarriages. During her eighth IVF cycle, she experienced a particularly devastating miscarriage—a son—at 20 weeks along.

As the couple mourned again, doctors revised their original diagnosis from blocked tubes (also called tubal factor infertility, a fairly straightforward diagnosis) to unexplained infertility, a label that was hard for Marisa to accept.

“It’s an unknown enemy,” she says. “How does one fight it?”

Marisa and Doug decided to press on with IVF at another fertility clinic—their fifth—and they also began researching the possibility of using a gestational carrier to carry their donor egg and donor sperm. (A gestational carrier is a woman who carries a baby not genetically her own.) In addition, they signed up with three adoption agencies. Then a phone call came that changed everything.

Marisa’s sister had just seen an episode of The Dr. Oz Show that featured celiac advocate and The View co-host Elisabeth Hasselbeck. Hasselbeck, now a mother of three, spoke about her struggle with infertility prior to being diagnosed with celiac disease.

“You’ve tried everything,” Marisa’s sister said, encouraging her to get tested. “What’s one more blood test?”

A few weeks later, on New Year’s Eve 2009, Marisa learned she had celiac disease.

Her new doctor, a celiac specialist, told her to go gluten free for six months and then try to conceive naturally. “You may not actually have a fertility problem,” she said to the couple.

“It was too much to process,” recalls Marisa. “I’d been through so much…five years, ten IVFs and untold emotional and financial damage. Even though I knew celiac was a big deal, I thought, how could it be this simple? So I just stop eating gluten and I can get pregnant?”

Knowing Where to Look

Liz Christopher, 37, tried to get pregnant for eight years. After she had no luck with fertility treatments, doctors recommended egg donation as a next step. But as Liz and her husband tucked away money each month to pay for an egg donor, Liz was diagnosed with celiac disease. Less than two years later, she conceived by natural means. Daughter Camille was born in 2011.

“For eight years, there were no missed periods, no miscarriages, nothing,” says Liz. “None of my doctors ever said that celiac disease was the cause.”

In fact, studies haven’t proven celiac can cause infertility. Studies haven’t consistently shown there’s even a link. But that doesn’t mean one isn’t there, says Daniel A. Leffler, MD, MS, director of clinical research at the Celiac Center at Beth Israel Deaconess Medical Center in Boston. “A lot of the early studies on infertility and celiac disease didn’t target those women with unexplained infertility. Instead they lumped all causes of infertility together.”

According to RESOLVE, the National Infertility Association, one in eight couples is affected by infertility, defined as the inability to conceive or carry a pregnancy to term after 12 months of trying. Any one of a number of hormonal or anatomical problems in either the male or female partner (or both) can cause infertility. In a fairly large number of couples—about 20 percent—there’s no identifiable cause (i.e., unexplained infertility).

According to a recent study, many of these women may actually have celiac disease. When researchers at the Celiac Disease Center at Columbia University screened 188 women with infertility for celiac, there was no higher risk of the autoimmune disorder until they narrowed it to just those with unexplained infertility. Of that group, almost 6 percent had celiac disease—a rate nearly six times higher than expected—raising the possibility that “celiac is an important association of unexplained infertility,” the researchers wrote.

Nutritional Deficiencies and More

Liz Christopher didn’t have any of the classic symptoms of celiac—diarrhea, bloating and stomach pain. Instead she suffered from migraines and other neurologic problems. Marisa Horowitz-Jaffe had occasional stomach pains but they never seemed to be correlated to what she ate. To this day she maintains, “I wouldn’t have known I had celiac if I hadn’t tried to get pregnant.”

Marisa’s biopsy, which was performed to confirm her celiac diagnosis, showed that her intestinal villi were flattened. Villi are the fingerlike projections lining the small intestine that allow nutrients to be absorbed. When they’re blunted, nutritional deficiencies are common. (Marisa had abnormalities in her fingernails that, in retrospect, may have hinted at nutritional deficiencies.)

Although it’s not hard to imagine how a calorie- and nutrient-starved woman might have trouble getting pregnant, malnourishment probably isn’t the only mechanism behind celiac-induced infertility, says Leffler. A recent study suggested there’s something about the celiac process itself that could directly affect one’s ability to carry through a pregnancy. The study showed antibodies to tissue transglutaminase—one of the key markers of celiac—can have an effect on the placenta’s development. Tissue transglutaminase (tTG) is an enzyme found throughout the body. It helps repair and remodel tissue, keeping things in good working order.

“In the placenta, there’s tons of tTG activity since there’s not only repair but also very rapid growth to make what is, in essence, a whole new organ in only a matter of months,” says Leffler.

“Early on, the placenta is a little organ,” adds Anthony J. DiMarino, Jr., MD, chief of the Division of Gastroenterology and Hepatology at Thomas Jefferson University Hospital in Philadelphia. “If it’s being attacked by antibodies, you can see how it could directly affect its ability to sustain a pregnancy.”

Indeed, a higher rate of miscarriage, stillbirth and fetal growth problems like intrauterine growth restriction has been well documented in women with undiagnosed celiac disease. Treatment with the gluten-free diet seems to reduce these risks.

“We don’t yet have data to prove that fertility improves on the gluten-free diet,” says Leffler. “But just about every other outcome is better, so it’d be an outlier if it didn’t.”

Leffler recommends waiting until celiac symptoms—when present—are under control and tTG levels have returned to normal before planning to conceive, if possible. This may take six months to a year of strict adherence to the gluten-free diet.

Counting the Costs

By the time Marisa Horowitz-Jaffe was diagnosed with celiac disease, she and Doug had already found egg and sperm donors as well as a surrogate, Courtney, to carry the pregnancy. Marisa called Courtney immediately to ask if she could wait six months: Marisa wanted to go gluten free and then have Courtney try to carry Marisa and Doug’s biological child. After her multiple miscarriages, Marisa didn’t want to even attempt to carry another pregnancy herself.

“I was new to being gluten free and terrified that if I slipped up, I’d end up with another dead baby. I couldn’t handle that kind of pressure,” she says.

Six months later, in May 2010, Marisa and Doug traveled to Dallas, Texas—laws prohibit surrogacy in New York State—and began their eleventh round of IVF.

“The way I responded to the medications, it was like I had a totally different body. Everyone was in awe,” she says.

Two embryos were transferred and their surrogate, Courtney, became pregnant on the first try. Marisa and Doug’s twins were born on December 27, 2010, almost a year to the day of Marisa’s celiac diagnosis. The babies were early but healthy.

Along with the challenges and joys of parenting, Marisa faced reminders of her long ordeal. Infertility had taken a serious toll on her.

“I still have what I consider some form of post-traumatic stress from it,” she says. “Every month when I get my period, I’m hit with feelings of overwhelming sadness and anger.”

In the midst of her fertility struggles, it was deeply painful for Marisa whenever someone close to her announced a pregnancy. She could barely speak to her sister for the better part of a year after her sister became pregnant. Marisa broke off ties with her oldest and dearest friend when she became pregnant with her second baby.

“It was impossible for me to put on a brave face,” Marisa says.

With what seemed like babies being conceived all around her, Marisa retreated to her basement. She became socially isolated and deeply depressed. When she and Doug lost their son at 20 weeks, three years into their infertility journey, Marisa hit rock bottom.

“Nothing mattered to me at that point—not the career I had worked so hard for, my health or my appearance. Even brushing my hair was tough to do some days,” she recalls.

There were times when Marisa was afraid her marriage might also fall apart, yet the couple ultimately grew closer, weathering even the financial stresses of infertility.

“IVF conservatively costs between $12,000 to $15,000 a cycle,” says Corey Whelan, program director at the American Fertility Association, an educational resource on family building. “Although diagnostic tests that point to causes of infertility like hormonal testing are usually covered by insurance, payment for fertility treatments varies by state and insurance plan.”

Marisa and Doug’s insurance covered two rounds of IVF. They were on their own for the rest, which, in addition to IVF, included some “unorthodox” testing, like screening for rare immune disorders and highly specialized sperm analyses.

“We were shooting for anything, praying a test would actually come back positive so we would know what to do finally,” says Marisa. “In the end, it came down to a fairly cheap test that was actually covered by our insurance.”

“A celiac panel is relatively inexpensive, on par with a cholesterol screen,” says Leffler. “From that perspective, you could argue it’s worthwhile to include celiac in a fertility workup. But the flip side is that even in those women who may have celiac disease, you can’t be sure the gluten-free diet will correct the problem. If you have them wait a year to conceive, you could waste precious time. You’ll probably have to run other tests or try IVF anyway.”

Since treating Marisa, Drew Tortoriello, MD, a reproductive endocrinologist and medical director at the Sher Institute for Reproductive Medicine in New York, now tests for celiac disease in women with unexplained infertility. He suspects he’s in the minority.

“I think most doctors consider it unnecessary without overt celiac symptoms,” he says.

Yet without screening guidelines in place—there’s currently no national guideline to test for celiac disease in women with unexplained infertility—it’s hard to blame doctors. Tortoriello thinks guideline-setting organizations like the American Society for Reproductive Medicine may soon take a harder look at the issue.

“We’re only now getting to a point where we have enough studies of high enough quality to make people feel comfortable that there’s a real link and real problem,” he says.

Raising Awareness

Several more studies on celiac disease and infertility are underway. At Thomas Jefferson University Hospital, Anthony J. DiMarino, MD, is overseeing a large study on the reproductive health of women with celiac disease. (The research is ongoing but data was presented at the American College of Gastroenterology’s annual meeting this past fall.) At the Celiac Center at Beth Israel Deaconess Medical Center, researchers are collaborating with the fertility clinic, Boston IVF, on what will be the largest study to date on screening for celiac disease in women with unexplained infertility. The team hopes to have preliminary data in the next year.

“Even if celiac screening doesn’t make it into any guidelines in the near future, we’re working to raise awareness in the fertility world, talking to fertility groups and publishing review articles,” Leffler says.

“So much heartache could be avoided by raising awareness,” says Alice Bast, founder of the National Foundation for Celiac Awareness (NFCA). Before being diagnosed with celiac disease, Bast gave birth to a full-term stillbirth daughter, Emily, and later, she delivered a two-pound preemie. (Her preemie is now a sophomore at the University of Michigan.)

“If someone had run a simple blood test, perhaps I wouldn’t have gone through all the pain and suffering I endured,” Bast says.

She realized she wasn’t the only woman to experience reproductive health problems due to undiagnosed celiac when she ran a celiac support group in the 1990s. The group took a poll of their members and found a startlingly high rate of miscarriage, infertility and preterm babies.

“It burned a hole in my heart,” says Bast, who soon thereafter applied for a National Institutes of Health grant and started the NFCA.

In 2010, the NFCA—which works to raise awareness about all the signs and symptoms of celiac disease—joined forces with the Celiac Center at Beth Israel Deaconess Medical Center and developed a women’s health and celiac disease guide.

“Changing medical practice doesn’t happen overnight,” says Bast. “But by getting the women’s health guide out to the community, we hope women might ask their doctors to be tested for celiac disease today.” (The guide and a celiac symptom checklist are available for free on NFCA’s website, celiaccentral.org.)

Recently, Bast took her awareness campaign to the head physician at the American Congress of Obstetricians and Gynecologists. When she wasn’t able to arrange a meeting, she made an appointment instead—as a patient.

“I was in the exam room without clothes on in order to talk about celiac disease. I told the physician my story and handed her a stack of publications on infertility and reproductive health issues. I asked her, how do we get this on your radar? How can we have celiac disease talked about in reproductive health rotations in medical school?”

“We won’t stop pushing,” says Bast. “I’ve seen the tears of too many women who’ve suffered.”

One woman’s story in particular haunts her:

“I’m 64 years old,” she told Bast. “My entire life I was trying to have kids. Two years ago, I was diagnosed with celiac disease. Maybe a change in diet was all I needed.”

Medical writer Christine Boyd lives in Baltimore, Maryland.