Want a baby? Relax . . .

Scientists have just confirmed what obstetricians knew anecdotally for years — that women under stress can have a difficult time getting pregnant. What’s new: Biochemical markers quantified the degree of stress — and potentially the type — affecting fertility.

Researchers at the Eunice Kennedy Shriver National Institute of Child Health & Human Development, in Rockville, Md., teamed up with colleagues at Ohio State University and the University of Oxford to analyze data from 374 women in and around Oxford, England. All had been actively attempting to become pregnant.

Each woman completed a questionnaire on lifestyle issues. And for half a year — or until a woman became pregnant or gave up — the recruits also kept a daily diary of their sexual activity and clues to their reproductive cycle.

All but 100 of the women also provided dozens of urine samples each month that allowed the researchers to track hormone concentrations and pinpoint the recruits’ precise ovulatory window — that is, when these women should have been able to conceive. Finally, saliva samples on day six of each woman’s menstrual cycle offered precise data on cortisol and alpha-amylase, two independent chemical markers of perceived psychological or social stress.

Over the course of the study, 64 percent of the women who provided urine and saliva samples became pregnant. But “Stress significantly reduced the probability of conception each day during [a woman’s] fertile window,” Germaine M. Buck Louis of NICHD and her coworkers now report online, ahead of print, in Fertility and Sterility.

They linked high alpha-amylase values in saliva — but not high cortisol —with diminished fertility. This link held even after accounting for other factors known to reduce a woman’s chance of becoming pregnant, including obesity, increasing age and heavy alcohol use.
 
“To our knowledge, this is the first study to empirically demonstrate that stress is significantly associated with reduced female fecundity” as measured by stress markers, Louis’ group reports. And this correlation wasn’t affected by which day a woman had engaged in intercourse — or how often — during her “fertile window” of opportunity.

Alpha-amylase is a major salivary protein regulated by something known as the sympathetic medullar system. “When stimulated,” Louis says, “it releases adrenaline and alpha-amylase — sort of the body’s fight-or-flight response [agents]. And the thinking is that this tends to be a reflection of acute stressors.” Cortisol, by contrast, is more a marker of chronic stress, she points out.

Among the women studied, those whose alpha-amylase fell within the top 25 percent were about 12 percent less likely to become pregnant — all other things being equal — than were women whose alpha-amylase had been within the bottom 25 percent.

But this association was statistically significant only within the recruits’ first menstrual cycle analyzed. So I asked Louis what happened in those subsequent cycles.

Actually, she notes, “We did see the same basic patterns in all of the cycles to which a woman contributed [saliva and urine], but we didn’t have enough statistical power for those later ones because we had fewer and fewer women. Part of it has to do with the fact that the women were enrolled for only 6 months,” she suspects — “and the majority were pregnant by then.”

Louis’ group has another chance to probe the issue in a newer and bigger American trial that just wrapped up. Known as the LIFE study — for Longitudinal Investigation of Fertility and the Environment — it followed 501 couples living in Michigan or Texas for a year. Unlike the Oxford study, which only collected biomarkers of stress until conception or the end of the trial, whichever came first, the LIFE study collected such data through the end of 12 months or delivery of any baby, whichever came last.

The numbers haven’t been crunched yet to confirm whether stress markers again correlate with fertility. But there are a few additional questions that Louis’ group hopes their LIFE data will answer. Such as: Does stress build as a couple fails to become pregnant — further diminishing likelihood of conception or successful births? And does stress prior to conception — or throughout pregnancy — alter normal sex ratios?

Ordinarily, slightly more newborns are male than female. Following cataclysmic events, however, from the Sept. 11 terrorism attacks to volcanic eruptions, sex ratios often swing toward a slight preponderance of female babies. LIFE would offer the first prospective look at this, with actual biochemical data to gauge the magnitude and duration of any chronic or acute stress.

Until such data become available, would-be moms should take some comfort from learning that most women who want to get pregnant do so. Stress just appears to shift the odds somewhat against them.