Shedding pounds does not fix pregnancy woes among obese women

For women with obesity and unexplained infertility, weight loss can result in improved cardiometabolic health. This benefit, however, does not translate to better pregnancy outcomes.

In the FIT-PLESE study, a 16-week intensive preconception lifestyle intervention that resulted in an average weight loss of 7 percent did not significantly increase the rates of having a healthy live birth or any live birth compared with a standard physical activity-based intervention that was weight neutral (12.2 percent vs 15.2 percent, respectively; rate ratio [RR], 0.81, 95 percent confidence interval [CI], 0.48–1.34; p=0.40). [PLoS Med 2022;19:e1003883]

Likewise, weight loss had no marked effect on pregnancy rates (27.7 percent vs 24.6 percent; RR, 1.12, 95 percent CI, 0.80–1.58; p=0.50), time to pregnancy (163 vs 160 days; p=0.56), or birth weight (3,217.7 vs 3,189.3 g; p=0.95).

Metabolic health, on the other hand, improved after weight loss. The incidence of metabolic syndrome dropped from 52.8 percent at baseline to 32.2 percent at week 16 in the intensive group, and from 53.6 percent to 49.4 percent in the standard group (p=0.003).

“These results were unexpected … [and] support that weight loss per se and improved cardiometabolic health obtained through preconception intervention do not guarantee improved pregnancy outcomes,” according to the study authors.

Too big to become pregnant?

“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are, to our knowledge, routinely counselled to lose weight prior to initiation of infertility treatment,” the authors said.

“We have known for decades that obese women often have difficulty getting pregnant,” said co-author Dr Daniel Haisenleder of the University of Virginia School of Medicine's Center for Research in Reproduction in the US. “For this reason, many physicians advise weight loss prior to conception.”

While epidemiological evidence has established an association between obesity and infertility, along with other unfavourable pregnancy outcomes, there is no Level I evidence to support the recommendation that preconception weight loss in women with obesity and unexplained infertility leads to either a higher chance of a healthy live birth or a shorter time to pregnancy. [Fertil Steril 2008;90:714-726; Obes Res 2002;10:551-554; Obes Rev 2008;9:140-150; J Womens Health 2006;15:720-733]

FIT-PLESE included 379 women with body mass index ≥30 kg/m² and unexplained infertility who had been randomly assigned to the intensive lifestyle intervention group (n=188) or the standard physical activity intervention group (n=190). The intensive intervention involved a weight loss target of 7 percent through increasing physical activity, meal replacements, and medication (orlistat). After the 16-week preconception intervention, both groups received three cycles of ovarian stimulation/intrauterine insemination.

Gastrointestinal side effects occurred with significantly greater frequency in the intensive group. Furthermore, there was a numerically higher rate of first trimester pregnancy loss in the intensive group (33.3 percent vs 23.7 percent in standard; RR, 1.40, 95 percent CI, 0.79–2.50).

However, the small number of pregnancies reduced the statistical power of the study to examine differences in the rate of pregnancy complications between groups, the authors admitted. The findings may also only be specific to women with unexplained infertility as opposed to other disorders such as anovulation due to polycystic ovary syndrome.

“Our live birth rates were also significantly less than we expected, presumably due to both the severity of obesity in our patient population and the comparative ineffectiveness of our frontline infertility therapies,” they pointed out.

Future research

“There are many avenues for future research. Other interventions of varying duration and/or intensity prior to conception may yield more favourable outcomes. A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” the authors said.

They also stressed that the weight-loss intervention should be balanced against the desire of the couple to have a baby as soon as possible and their unwillingness to delay meaningful treatment.

“Infertility within this population [of women with obesity] remains an important health issue and will require further studies to address the problem in the future,” Haisenleder said.