GENERAL MEDICAL NEWS
The staff of The Reproductive Times here offers brief referenced notifications on interesting general medical and scientific news with broad relevance to reproductive medicine and biology. Some of these news items may become subjects of more detailed reporting in The Reproductive Times on later occasions. The purpose of these short notifications is to give readers the opportunity to get immediately more detailed information by looking up the reference of the notification.
Excessive weight in infertility as a fertility diagnosis is gaining popularity
Overweight and obesity are suddenly hot issues in the infertility literature. Fertility and Sterility dedicated one of its monthly Views and Reviews series of articles to this issue under the heading, “A weighty issue,” discussing primarily the impact of GLP-1s on in vitro fertilization (IVF) cycle outcomes (1). The introductory article in this series reviewed well the impact of overweight and obesity on reproductive health and female metabolism, describing obesity as a “highly prevalent chronic disease that impacts over 40% of reproductive-age women (2).”
A second interesting paper addressed weight bias in fertility medicine (3). That especially severely obese patients are discriminated against in fertility practice is difficult to deny. At the same time, it, however, is difficult to determine where good medical care ends and discrimination starts. For example, to suggest that morbidly obese women and men lose some weight before starting an IVF cycle, especially now with availability of GLP-1s, allowing for relatively quick weight loss, would appear to represent excellent medical advice in many patients. But it is excellent advice, of course, only if the patient is not too old or has very low functional ovarian reserve.
Such advice, of course, also depends in its appropriateness on how much weight a patient is expected to lose and in what time period. Older studies have suggested that relatively small weight loss will already improve fertility outcomes in IVF; but studies of what represents “best” weight loss at different starting points–which in the past were practically impossible to execute–with the quick weight loss of GLP-1s should now be possible and would appear urgently needed.
We also agree with the authors’ call to avoid body mass index restrictions for IVF treatments. In the end, it should always be the patient who decides what treatment she/he receives–of course, always with patient safety at the forefront.
And finally, a fourth article in the series just offered a somewhat superficial and, in some respects, repetitive review of GLP-1s in association with infertility (4). Still a worthwhile read, but clearly the least interesting article in the series.
The most interesting article on the subject in the same issue of Fertility and Sterility was, however, a systematic review and meta-analysis of preconception weight loss interventions on fertility in women (5). The study confirmed that pregnancy rates were higher in women who had undergone weight loss interventions before conception but also suggested no impact from such interventions on live birth rates and miscarriages.
These are, of course, contradictory findings because considering better pregnancy rates after prior weight loss, one would expect higher live birth rates unless, of course, miscarriage rates were increased (which they weren’t). We attribute these findings to the obvious shortcomings of systematic literature reviews which–frankly speaking–almost always include not only papers of poor quality but papers with greatly differing patient populations. What this study, therefore, reaffirms for us is the urgent need for prospective studies using GLP-1s in obese patients before IVF cycle starts. We urgently need to know how much weight loss is enough to show outcome benefits in subsequent IVF cycles and–if possible–how much weight loss offers the most improvements.
And to complicate this subject even a bit more, in the same issue of Fertility and Sterility investigators from several U.S. institutions also published a research letter trying to determine the effects of improved metabolic syndrome parameters (of course, including obesity) on live birth following intrauterine insemination (IUI) cycles (6). Somewhat surprisingly, women who improved their metabolic syndrome parameters through lifestyle interventions prior to their IUI cycles, did not demonstrate improvements in their fertility or live birth outcomes.
The authors themselves pointed outs several weaknesses in their study, which must be appreciated. This study, however, only further demonstrates the urgent need for properly conducted studies in this rapidly growing patient population which by 2030 is expected to represent half of all patients presenting to infertility clinics.
References
1. Widra EA. Fertil Steril 2024;1222(2);193
2. Schon et al., Fertil Steril 2024;122(2):194—203
3. Boots et al., Fertil Steril 2024;122(2):204—210
4. Goldberg AS, Boots CE. Fertil Steril 2024;122(2):211-218
5. Caldwell et al., Fertil Steril 2024;122(2):326-340
6. Spitzer et al., Fertil Steril 2024’122(2)373-375
What is new regarding glucagon-like peptide-1 (GLP-1
The 2024 Lasker Award went to GLP-1 receptor agonist researchers. One of “The Laskers” – after the Nobel Prize the most prestigious science awards and, often, foreshadowed recipients of a Nobel Prize, this year went to several scientists responsible for the still evolving health revolution induced by the new family of weight-loss drugs, called GLP-1 receptor agonists.
The Lasker-DeBakey Clinical Medical Research Award went this year to three recipients who made essential contributions to the development of these drugs: Joel Habener, MD, is an endocrinologist and Professor of Medicine at Harvard Medical School, who had a research interest in diabetes, specifically the hormone glucagon, hoping that discovery of its gene would allow shutting glucagon down, thereby reducing glucose levels. In the process he in an animal model discovered a protein that resembled glucagon, shortly thereafter by another researcher who had discovered the same protein in a different animal model given the name glucagon-like-peptide-1 (GLP-1).
From left to right: Joel Habener, MD, Svetlana Mojsof, and Lotte Bjerre Knudsen.
Credit Nature magazine.
Habner worked with a biochemist, Svetlana Mojsov, PhD, at the time at Massachusetts General Hospital in Boston and now a professor at Rockefeller University in NYC, and they succeeded in producing the first biologically active form of GLP-1. However, it was not clinically usable because it had too short a lifespan before being metabolized. This is where Lotte Bjerre Knudsen, PhD, a scientist at the by now well-known Danish pharma company Novo Nordisk in Copenhagen came into the picture and solved the problem by attaching the new GLP-1 compound to a fatty acid which extended the time of its function—and the rest is history (1). As detailed in last month’s VOICE, this new family of weight loss drugs not only started a revolution in treating obesity, but it is also becoming increasingly clear that they also exert beneficial effects on many other medical conditions. We suspect that the Nobel Prize cannot be far behind!
Deceptive promotion of GLP-1s: Repeated articles in The Wall Street Journal have called attention to what The Journal considers deceptive promotion of GLPs on platforms such as TikTok, YouTube, and Instagram (2). The newspaper now reports that a newly introduced bill in the Senate targets influencers and telehealth companies for misleading promotions of weight loss and other drug promotions (2). If passed by congress, the bill would allow the FDA to fine individuals and companies up to $500,000 for posting false information online about, for example, Ozempic and Wegovy, still the bestsellers among GLP-1s.
GLP-1s help not only through weight loss – they have other benefits: Evidence that GLP-1s have beneficial effects far beyond just weight loss are accumulating. Here are a few examples. They, for example, reduce alcohol consumption (3), incidence and relapse with cannabis use disorder (4), compulsive behavior (5), and seemingly even the drive to smoke (so-called tobacco use disorder) (6). They beneficially affect heart failure (7,8), and appear to reduce dementia risk in adults (9). And, yes, they also appear to improve sleep apnea (10,11), all-cause mortality, etc.
Especially important for the fertility field is increasingly well documented real-world evidence that GLP-1s–when used preconceptionally and in early pregnancy–do not increase pregnancy complications. Because data on inadvertent early pregnancy use are still sparse, a one-month wash-out period before fertility treatments, however, still appears appropriate.
Finally, two excellent reviews on use of GLP-1s for weight loss deserve attention (12,13), and a recent study confirmed that among GLP-1 receptor agonists on the market the efficiency to result in weight loss varies. As earlier data already suggested a direct comparison now confirmed that in adults with overweight and obesity tirzepatide (Mounjaro®, Zepbound®) resulted in significantly greater weight loss than semaglutide (Ozempic®, Wegovy®). And even more effective drugs are announced and already in trials.
References
1. Lenharo M. Nature, September 19, 2024. https://www.nature.com/articles/d41586-024-03078-x
2. Loftus P, O’Brien SA. The Wal Street Hournal., September 12, 2024. https://www.wsj.com/health/healthcare/senators-target-influencers-telehealth-firms-for-misleading-weight-loss-and-other-drug-promotion-81dbaf40
3. Quddos et al., Scientific Reports 2023;:20998
4. Wang et al., Mol psych 2024;29:2587-2589
5. Arillotta et al., Brain Sci 2024;14(6):617
6. Wang et al., Ann Int Med 2024; 177(8): https://doi.org/10.7326/M23-2718
7. Kosiborod et al., Lancet 2024;404:949-961
8. Hage C. Lancet 2024;404:909-911
9. Shin et al., BMJ 2024386:e079475
10. Blum D. The New York Times, Jue 21, 2024. https://www.nytimes.com/2024/06/21/well/sleep-apnea-weight-loss-drug.html
11. Malhotra et al., Contemp Clin Trials 2024;141:107516
12. Kusminski et al, Cell 2014;187:3829-3876
13. Gudzune KA, Kushner RF. JAMA 2024;332(7):571584
Does maternal fish intake during pregnancy reduce autism risk in offspring?
Not necessarily a new suggestion, but this is what a recent study in the American Journal of Clinical Nutrition recently again reported (1). The study confirmed earlier reports that increased fish consumption during pregnancy appears associated with lower numbers of autism cases and a more modest reduction in autism-related traits. The reason was always assumed to be the omega-3 intake that comes from fish. While this study confirmed the association with fish consumption, it did not support an association with gamma-3 levels. The so-called SRS scores on the Social Responsibility Scale, however, did demonstrate a modest increase with better Omega-3 levels. The authors concluded that fish consumption in pregnancy should be encouraged.
Reference
1. Lyall et al., Am J Clin Nutrition 2024;120(3):5830592