Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development
Abstract Obese or overweight patients considering IVF are generally counselled to reduce weight closer to target BMI (i.e., < 30 kg/m2) by interventions entailing dietary change with a structured exercise program. There is little disagreement that supervised weight loss can improve reproductive o...
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2025-08-01
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| Series: | Reproductive Biology and Endocrinology |
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| Online Access: | https://doi.org/10.1186/s12958-025-01435-7 |
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| author | E. Scott Sills Conor Harrity Howard I. Chu Jing-Wen Wang Fan Yang Samuel H. Wood |
| author_facet | E. Scott Sills Conor Harrity Howard I. Chu Jing-Wen Wang Fan Yang Samuel H. Wood |
| author_sort | E. Scott Sills |
| collection | DOAJ |
| description | Abstract Obese or overweight patients considering IVF are generally counselled to reduce weight closer to target BMI (i.e., < 30 kg/m2) by interventions entailing dietary change with a structured exercise program. There is little disagreement that supervised weight loss can improve reproductive outcome when successful, although there are refractory cases where weight goals are unmet. Because low-grade chronic inflammation and altered immune function are characteristic of obesity and antagonize implantation, any pre-IVF weight loss facilitated by semaglutide (SG) would be helpful. However, no preclinical data have considered the ovarian implications of SG. Several formulations of SG are now available to assist in chronic weight management, treatment of type-2 diabetes, or both. SG is 31-amino acid lipopeptide with action at the glucagon-like peptide-1 (GLP-1) receptor, which augments insulin secretion while lowering hepatic glucagon output. SG thus enters a multiorgan network where insulin, AMP-activated protein kinase (AMPK), insulin-like growth factor-1 (IGF-1), mammalian target of rapamycin (mTOR), and sirtuin pathways manage ambient nutritional conditions. As GLP-1 directly influences insulin release and curtails satiety, SG adjusts many biochemical cascades where potential interference with oocyte development or embryo/endometrial crosstalk require clarification. Particularly if used outside manufacturer’s guidance (i.e., for aesthetic or personal reasons), SG could bring unwelcome challenges to fertility clinics where obesity and dyslipidemia are merely exchanged for the new problems of starvation and sarcopenia. Here we examine known GLP-1 actions where energy balance, ovarian aging, and oocyte competence converge; off label SG use should be avoided until its signaling effects throughout the reproductive axis are more carefully studied. |
| format | Article |
| id | doaj-art-bc83e2d9f14f486e98d2bfffb3738d6d |
| institution | Kabale University |
| issn | 1477-7827 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Reproductive Biology and Endocrinology |
| spelling | doaj-art-bc83e2d9f14f486e98d2bfffb3738d6d2025-08-20T03:46:17ZengBMCReproductive Biology and Endocrinology1477-78272025-08-012311810.1186/s12958-025-01435-7Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular developmentE. Scott Sills0Conor Harrity1Howard I. Chu2Jing-Wen Wang3Fan Yang4Samuel H. Wood5Pelican Bay Biology Group, Center for Advanced GeneticsDepartment of Obstetrics & Gynaecology, Royal College of Surgeons in IrelandDepartment of Psychobiology, University of California-Los AngelesGen 5 Fertility CenterGen 5 Fertility CenterGen 5 Fertility CenterAbstract Obese or overweight patients considering IVF are generally counselled to reduce weight closer to target BMI (i.e., < 30 kg/m2) by interventions entailing dietary change with a structured exercise program. There is little disagreement that supervised weight loss can improve reproductive outcome when successful, although there are refractory cases where weight goals are unmet. Because low-grade chronic inflammation and altered immune function are characteristic of obesity and antagonize implantation, any pre-IVF weight loss facilitated by semaglutide (SG) would be helpful. However, no preclinical data have considered the ovarian implications of SG. Several formulations of SG are now available to assist in chronic weight management, treatment of type-2 diabetes, or both. SG is 31-amino acid lipopeptide with action at the glucagon-like peptide-1 (GLP-1) receptor, which augments insulin secretion while lowering hepatic glucagon output. SG thus enters a multiorgan network where insulin, AMP-activated protein kinase (AMPK), insulin-like growth factor-1 (IGF-1), mammalian target of rapamycin (mTOR), and sirtuin pathways manage ambient nutritional conditions. As GLP-1 directly influences insulin release and curtails satiety, SG adjusts many biochemical cascades where potential interference with oocyte development or embryo/endometrial crosstalk require clarification. Particularly if used outside manufacturer’s guidance (i.e., for aesthetic or personal reasons), SG could bring unwelcome challenges to fertility clinics where obesity and dyslipidemia are merely exchanged for the new problems of starvation and sarcopenia. Here we examine known GLP-1 actions where energy balance, ovarian aging, and oocyte competence converge; off label SG use should be avoided until its signaling effects throughout the reproductive axis are more carefully studied.https://doi.org/10.1186/s12958-025-01435-7SemaglutideGLP-1InsulinOvaryReproduction |
| spellingShingle | E. Scott Sills Conor Harrity Howard I. Chu Jing-Wen Wang Fan Yang Samuel H. Wood Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development Reproductive Biology and Endocrinology Semaglutide GLP-1 Insulin Ovary Reproduction |
| title | Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development |
| title_full | Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development |
| title_fullStr | Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development |
| title_full_unstemmed | Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development |
| title_short | Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development |
| title_sort | semaglutide and human reproduction caution at the intersection of energy balance ovarian function and follicular development |
| topic | Semaglutide GLP-1 Insulin Ovary Reproduction |
| url | https://doi.org/10.1186/s12958-025-01435-7 |
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