‘Patients need honest data’: Why weight loss is not an easy answer for infertility

Key takeaways:

• Women with obesity can successfully become pregnant, often without fertility treatments.
• Clinicians should avoid perpetuating stigma when discussing weight loss with patients struggling to conceive.

DENVER — Obesity prevalence is increasing among reproductive-age people and unhealthy weight is associated with infertility in both sexes, yet the impact of weight reduction on fertility outcomes is complex, according to a speaker.

As new weight-loss medications like GLP-1 receptor agonists help patients lose greater amounts of weight, the topic of obesity is coming up more frequently during infertility counseling sessions, according to Richard S. Legro, MD, FACOG, chair of the department of obstetrics and gynecology at Penn State College of Medicine and Penn State Health in Hershey, Pennsylvania. But for women who are struggling to become pregnant, weight loss comes with its own list of risks and benefits that must be carefully considered, Legro told Healio.

“We cannot tell our patients, ‘If you lose weight, everything will be perfect,’” Legro told Healio. “There are sequalae to weight loss that might not be beneficial.”

Healio spoke with Legro about the impact of excess weight on pregnancy outcomes, concerns that come with weight-loss medications and bariatric surgery, and how to lead a thoughtful conversation with patients about their options. Legro participated in a discussion on using weight-inclusive approaches to address obesity in male and female infertility at the ASRM Scientific Congress & Expo.

Healio: How common is obesity in patients today who seek fertility care? How does excess weight impact fertility?

Legro: Approximately 40% of patients seeking infertility treatment have obesity, depending on where one lives in the U.S. Obesity is associated with every adverse fertility outcome, including delayed time to pregnancy, increased pregnancy loss, increased pregnancy complications leading to preterm delivery, increased gestational diabetes and preeclampsia, increased operative deliveries and C-sections, large for gestational age infants. The list is exhaustive.

A big issue, however, is that the effects of obesity are exaggerated in the public’s mind and in the clinician’s mind. While there is an effect, the effect size is not as large as many people imagine. That is a problem when one tries to conduct studies based on a huge effect size with some weight loss, when the effect size is modest and your ability to improve [outcomes] will also be modest. The problem to date with studies, including studies we have done, is they are probably underpowered given the small effect sizes in weight increments on these outcomes. We also need to take a larger view than live birth as the only study outcomes. Outcomes should include a healthy live birth, a healthy mother and infant. If we have a more holistic approach, then we will see the benefits of preconception weight loss and weight management.

Healio: You note that the impact of weight reduction on fertility outcomes is complex. Can you explain?

Legro: The whole field is in its infancy. As I said earlier, there have not been many well-powered studies. Everyone is excited about GLP-1 receptor agonists; however, there have been no prospective studies done with women seeking pregnancy; the drug companies are not going to fund it because of the liabilities with pregnancy loss and complications. Bariatric studies for the most part are not prospective; they are typically large cases series.

For the studies that are controlled, one of the things you have to look at are risks and benefits of surgery vs. no surgery. Part of the risk with weight loss is, especially with restrictive bariatric procedures, there is often malabsorption of key nutrients. How can we supplement for that during pregnancy? Does that also happen when we alter weight through lifestyle management? Are we somehow nutritionally depleting the women anticipating pregnancy? We have to look carefully at miscarriage and other outcomes, and that will take a combination of registries and randomized trials.

We cannot tell our patients, “If you lose weight, everything will be perfect.” There are sequalae to weight loss that might not be beneficial.

Healio: What role might newer anti-obesity medications, such as GLP-1 receptor agonists, play in fertility care? Where do they fit alongside lifestyle and other options such as bariatric surgery?

Legro: I prescribe GLP-1 receptor agonists a lot. They are effective. But how should GLP-1 receptor agonists be used in terms of fertility? The package insert says to stop 2 months prior to attempting pregnancy, but there is no justification for that in the literature. Given the weight rebound after going off of these drugs, one could argue that perhaps patients should continue to use them until they conceive. Unless we do the study, we will never know.

One big question is, what do we do once we stop using the GLP-1 receptor agonist? What should that patient do? We talk a lot about exercise. I do not think we have a good substitute for GLP-1s during pregnancy yet. We have to figure out what to do to prevent the rebound weight gain. It is relevant to preconception weight rebound and pregnancy weight rebound, where weight gain is inevitable and expected. How do you achieve appropriate gestational weight gain for people off the GLP-1 receptor agonists who are not doing caloric restriction during pregnancy?

Healio: How can clinicians address weight management with patients seeking infertility treatment in ways that do not perpetuate stigma?

Legro: First, do not reinvent the wheel. Every patient is aware of the effects of overweight and obesity, from my experience. Ask patients what their impression is and document what steps they have taken. Most have tried to lose weight. Do not assume they have not tried anything; that is most likely not the case. Have an honest discussion about how difficult it is to lose weight, how long it takes and how expensive it is. Many of these patients do not have access to drugs or bariatric surgery or may not want either of those options. Work with patients. You want to counsel but not scare them.

Do not overestimate the effects of obesity on reproductive outcomes. Patients need honest data. Screen women for the obesity-associated comorbidities like impaired glucose tolerance, diabetes and hypertension and treat those appropriately. We are learning that more aggressive treatment of what we considered borderline or even “normal” levels of glucose and blood pressure in the past are giving us improved obstetric outcomes during pregnancy. We should probably be treating these issues preconception.

Finally, walk into the labor and delivery unit here, and you are going to see 40% to 50% of those patients have obesity. Most of those patients did not go through infertility treatments. I am not so sure I buy the idea that obesity is the cause of unexplained infertility. There are other factors. Do not put that burden on the patient by suggesting, “The reason you are not getting pregnant is because you are obese and if you lose weight, you will get pregnant.” There is not any evidence that either one of those points is fact. I address obesity the same way I address hypertension and glucose intolerance. These are conditions we want to optimize prior to conception, but we may not be able to. And unlike dysglycemia and hypertension, which we can optimize in fairly quick fashion, weight loss takes time. Do you ask a 40-year-old women to take a year off [attempting pregnancy] to lose weight? You have to factor a woman’s age and ovarian reserve into any treatment plan.

For more information:

Richard S. Legro, MD, FACOG, can be reached at rlegro@pennstatehealth.psu.edu.