Predicting Fertility

In 2006, as Lauren Wise was immersed in researching the fertility of men exposed prenatally to the now-banned drug DES (diethylstilbestrol), she and her husband decided it was time to begin their own family. At 32, the Boston University School of Public Health (SPH) epidemiologist had already published dozens of papers about reproductive risks.

But as the months ticked by fruitlessly, Wise gained personal insight into the same fertility quandary she had explored professionally. “I’m thinking, ‘I’m 32, I should be able to have babies right away,’” she recalls. “But it took longer than I expected. It was frustrating.” Several months later, Wise got pregnant with her first child. And two years after the birth of her daughter, she became pregnant again, soon after beginning to try.

Those varied experiences deepened her determination to identify the myriad factors that influence fertility—a drive that now has her leading the largest internet-based study of fertility in the United States. “I think my own experience helped me to understand the complexities of reproduction—physiologically and emotionally,” Wise says. “It made the concepts very real for me. It fueled my interest and passion.”

Wise, an associate professor of epidemiology and a senior epidemiologist at BU’s Slone Epidemiology Center, is the lead investigator of the PRESTO (Pregnancy Study Online) project, which aims to identify lifestyle factors such as diet, exercise, and medication use that may affect fertility and pregnancy outcomes. The study relies on internet-based methods to recruit and follow 2,500 women, ages 21 to 45; it’s also recruiting male partners, where possible, to examine other factors that may impact the chances of pregnancy.

For Wise, PRESTO is just the latest phase of a search for answers about women’s reproductive health that began 14 years ago, when she started work as a research data analyst at Slone. Her trail, winding from Boston to Denmark, has produced some intriguing findings that challenge old assumptions about fertility and raise new questions about the roles that stress, diet, and environment play.

“We know that fertility rates are declining in the US and the rest of the world, and some of that is related to women delaying childbearing,” Wise says. “But given that, can we identify other factors that might be causing the trend? To me, being able to find answers to questions that have been asked for decades, but also to ask new questions, is extremely gratifying.”

Identifying Obstacles

Infertility is among the most painful problems a couple can face, with emotional repercussions that can last for years—or a lifetime. Fertility rates in the US hit a record low in 2012 for the second consecutive year for women aged 15 to 44, in part because of a decline in the number of teenage pregnancies. In Massachusetts, the Department of Public Health reports that fertility rates are dropping and remain 16 percent below the national average. The causes are often hard to pinpoint and can be difficult to treat.

In 2012, more than 176,000 cycles of assisted reproduction were performed at clinics in the US, with the use of in vitro fertilization and other technologies doubling over the last decade. Wise’s focus on infertility builds on a theme running through her work: identifying obstacles to women’s reproductive health, then figuring out ways around them. As an undergraduate at Bowdoin College in Maine, the Canadian native wrote her honors thesis about contraceptive use, exploring the quandary of women who wanted to both get pregnant and avoid the risk of sexually transmitted diseases.

“I’ve always had an interest in women’s reproductive health, and over time, there’s been a more women-centered perspective on the research agenda,” she says. “It’s been satisfying to be a part of that.” For the last 12 years, Wise has been on the Slone team working on the long-running Black Women’s Health Study, which has examined fertility and other factors among African American women. She first got involved in the study after college, when she landed a one-year job at Slone as a research assistant, processing and editing paper questionnaires.

To date, she has led more than 15 studies on the causes and incidence of uterine fibroids in black women. Diagnosed in about 30 percent of reproductive-age women, uterine fibroids can cause pelvic pain, heavy menstrual bleeding, infertility, and pregnancy complications. They are the primary cause of hysterectomy in the US.

Wise’s research has found that fibroid growth is influenced by factors ranging from genetics, childbearing, diet, and obesity, to dairy and alcohol consumption—and possibly even the use of hair relaxers. She is now leading a study, funded by the National Institutes of Health, looking at whether psychosocial factors, such as child abuse, socioeconomic adversity, and depression, increase fibroid risk.

Her interest in the determinants of uterine fibroids started with her doctoral dissertation, which examined reproductive and hormonal risk factors of the condition. She was drawn to the topic partly because it had received so little attention.

I’ve always had an interest in women’s reproductive health, and over time, there’s been a more women-centered perspective on the research agenda. It’s been satisfying to be a part of that.”                           – Lauren Wise

“It’s a huge problem for African American women, who are two to three times more likely than white women to be diagnosed with fibroids. It affects women in their prime and undermines their quality of life,” Wise says. “Yet it’s been so understudied.”

In 2011, her work on fibroids won her the prestigious Young Investigator’s Award for Distinguished Research in Public Health from the Association of Schools & Programs of Public Health and Pfizer. “A good scientist is curious, inquisitive, skeptical, persistent, and enthusiastic—Lauren is all these things, as well as a good manager of her research team,” says Kenneth Rothman, SPH professor of epidemiology and one of the first US researchers to suggest using online methods to conduct research on fertility. “She is an expert on women’s health, and equally accomplished in the epidemiologic methods needed to address the complicated problems that she is drawn to study.” Besides fibroid research, Wise has tackled other women’s health issues, including risk factors for macrosomia and preterm birth (funded by the Hood Foundation), as well as menopause, endometrial and breast cancers, and infertility.

Finding Fertility Predictors

Wise’s latest project, PRESTO, will build on the findings of an internet-based study of fertility in Denmark that she helped launch with Rothman and Danish colleagues in 2007. The Danish study, headed by Elizabeth Hatch, an SPH professor of epidemiology, has produced a series of high-interest results, covering everything from the impact on fertility of consuming caffeine (it’s OK—soda is not) to age (fertility peaks around 30 for men and women and declines slightly later than suggested in previous studies). Researchers have also found that overexercising may make it harder for healthy-weight women to conceive, while moderate exercising is beneficial, and that shorter menstrual cycle length, obesity, and weight gain are associated with delays in pregnancy

According to Wise, the PRESTO study is breaking new ground in the US by relying on the internet for recruiting and interacting with participants—study methods that may prove more cost-effective than traditional research techniques. “The process of studying people via the internet is really still in its early days,” she says. “We’re testing several ideas here, including whether this kind of research method will work in the United States as well as it does in Denmark. There are cultural differences” related to trust and willingness to participate in scientific studies, she adds.

Wise and her team are searching for fertility factors by casting a wide net that looks beyond age to issues such as lubricant and antidepressant use, socioeconomic factors, and even whether male partners carry their cell phones in their pants’ pockets. Coupled with data from the Danish study, Wise says, findings from PRESTO could identify certain key “fertility predictors”—while also revolutionizing the methods used to study epidemiology. “With women waiting longer to start a family, we really need to identify factors that lead to successful pregnancies in older women—and we just don’t know enough yet,” Wise says. “Our hope is to turn up things that might be modifiable, for men and women.”

As part of PRESTO, participants fill out detailed dietary questionnaires that may provide clues about what kinds of foods help or hurt fertility. Because little is known about dietary factors, it is an area where Wise hopes to make substantial inroads. A subset of women will participate in a smaller study (E-PRESTO) that will seek to determine whether chemical compounds such as plasticizers and bisphenol A (BPA), contained in some consumer products, reduce fertility. The research team also plans to track birth outcomes for participants’ children who are born in Massachusetts through the commonwealth’s birth registry—affording new information on factors that may contribute to adverse outcomes.

Fueled By Hope

With more than 100 published studies, Wise hasn’t lost her curiosity or intensity. When she talks about PRESTO, she brightens as she contemplates possible breakthroughs in understanding how diet, exercise, and menstrual cycles influence fertility.  Although she had two successful pregnancies of her own—she has a 6-year-old daughter and a 4-year-old son—she still draws on the early frustrations and fears of waiting to start a family in her thirties.

“I think I can relate on some important level to what many women experience. Reproduction is not an easy thing,” she says. “That’s why I’m so fascinated by it, because I think there are so many steps along the way where something can go wrong—and I’m always amazed when a healthy baby comes into this world. “If there are things I can do to discover truths about factors that might promote fertility, I want to be able to share that information with other couples. That’s the hope that keeps me going.”