Conquering the Adverse Impact of Obesity on Fertility

BRIEFING: Obesity has become a major societal health problem. That obesity, moreover, adversely affects female as well as male fertility and reduces treatment success in infertility, is now also well established, - yet has so-far not found the deserving recognition in infertility practice. This section of the VOICE, therefore, is dedicated to filling this gap by offering relevant information about nutrition, pharmacological interventions to fight obesity and, where applicable, supplements as integral contributions to a comprehensive treatment approach toward female as well as male infertility. 

Finally bringing anti-obesity drugs into infertility practice 

New anti-obesity drugs like Wegovy,® Ozempic,® and Rybelsus (all semaglutide products) and  Mounjaro® (a tirzepatide product) are among several prescription medicines which appear destined to change medicine by offering virtually guaranteed weight loss at highly significant proportions to everybody who starts injecting these medications.  

Semaglutide acts as an agonist to the so-called glucagon-like peptide (GLP1) receptor and It, thus, pretends to be the GLP-1 hormone which makes us less hungry by sending signals of feeling full to the brain. 

Mounjaro® is a little more complicated because it is made up of two effective substances that induce weight loss, - one again a GLP-1 receptor agonist but, now added to it, a so-called glucose-dependent insulinotropic polypeptide (GIP) and, thus mimics the GLP-1 as well as the GIP hormone in their activities on their respective receptors. Like GLP-1, GIP triggers a feeling of fullness. These drugs, however, likely also affect the brain’s control of food intake and this function has also in general been associated with anti-addictive behavior, a reason why these drugs now are also investigated for their potential effectiveness in drug – and other addictive behaviors. 

Other medications, alleged to be even more effective in inducing weight loss, appear on the way to market. Remarkably, these medications have relatively few and usually easy to overcome side effects and, considering that these drugs have already for several years been in relatively long-term use in diabetic patients, unexpected long-term side effects appear unlikely. 

Even more remarkably, this family of new weight loss medications does not only affect blood sugar levels and causes significant weight loss but, likely because of secondary benefits from significant weight loss, has substantial secondary health benefits, with most not yet even recorded. Mounjaro®, for example, has been shown to reduce systolic blood pressure1 and semaglutide beneficially affects heart health in diabetic patients.2 In mice semaglutide’s cardioprotective effects exceeded, indeed, effects obtained from dietary weight loss, thereby suggesting that beneficial effects may not only come from weight loss.3  

No wonder, producers of this family of anti-obesity drugs  are taking all kind of unusual steps in attempting to boost production of these medications which are all in short supply.4 Moreover Eli Lilly’s – the producer of Mounjaro®- and of other weight loss products that are on the way, market capitalization surpassed Tesla’s market cap, causing The Wall Street Journal to suggest that the company deserves to become one of the “magnificent seven” companies which basically control the stock market. The articles, indeed, suggests that manufacturers of obesity drugs, and not manufacturers of electric vehicles, can be expected to show the kind of revenue growth in coming years that warrants inclusion in this elite group of companies.5  

Because obesity has so many secondary negative effects on health, potential secondary beneficial effects have been also suggested on neurodegenerative diseases like Alzheimer’s and Parkinson’s disease, depression and anxiety, osteoarthritis, fatty liver, inflammation, and others. Avery recent study, moreover, demonstrated weight loss from this family of drugs reduced all cause-mortality among patients with knee and hip osteoarthritis.6,8 Most recent data also suggest beneficial effects on inflammation, 

Even though obesity is by now well established as a contributing factor of infertility in both sexes, the potential effects of these drugs on female as well as male infertility have, however, so-far not been explored. The likely reason is that mouse (and other) data suggested that these medications when used during early pregnancy can cause birth defects and small for age fetuses. This, however, should not be a reason for not using these drugs before pregnancy as part of a strategy to improve pregnancy chances with later fertility treatments. Weight loss has been for decades known to improve the effectiveness of practically all fertility treatments. There were in principle only two major reasons why this knowledge has only so rarely been applied to infertility patients: (i) Weight loss very frequently was unsuccessful; and (ii), - even if successful, weight loss took a very long time to achieve, - time many infertility patients do not have, especially if older. 

What this new family of weight loss drugs now, however, has established without any remaining doubt is that these drugs allow for substantial weight loss in relatively short time. This is important because studies have repeatedly demonstrated that loss of as little as 5% to 7% of body weight (representing only 10-20 pounds) will already significantly improve treatment chances in obese infertile women and men. This goal in many patients can be achieved with as little as 3 months of treatments with these new medications. Time appears to be ripe to start integrating drugs like Vegovia ®and Munjaro® into fertility treatment algorithms for obese infertility patients! The CHR has started to do this, and we will address this issue, therefore, in more detail in the April issue of the VOICE. In the meantime, if you feel that you may benefit in your attempts from losing some weight, come and see us at the CHR. 

References

Lingvay et al., Cardiovasc Diabetol 2023;22:66 

Lincoff et al., N Engl J Med 2023;389:2221-2232

Withaar et al., J Am Coll Cardiol Basic Trans Science 2023;8(10):1298-1314 

Loftus P. The Wall Street Journal. February 6, 2024 

Wainer D. Wall Street Journal, February 7, 2024, page B12 

O’Mary L. WebMD Health News, February 9, 2024. https://www.medscape.com/s/viewarticke/study-suggests-mind-body...0_daily_240209_MSCPEDIT_etide6300414&uac=223637CN&implID=6300414 

Lenharo M. Nature 2024;626:246 

Wei et al., Arthit Rheum 2023; doi: 10.1002/art.42754. Online ahead of print.