Abstract
Disclosure: D. Fraser: None. B. Lam: None. M.M. Kristan: None. Introduction: Existing literature has demonstrated the link between improved fertility and metformin in women who are overweight with a history of PCOS [1]. A recent study reported that treatment of overweight/obese women with PCOS with diabetes using Glucagon-like peptide-1 receptor agonist (GLP-1 RA) monotherapy has led to weight loss and testosterone reduction [2]. A meta-analysis has shown that GLP-1 RAs improve natural pregnancy rate and insulin sensitivity in women with PCOS [3]. This case report will add to the existing literature hypothesizing increased fertility in women with PCOS due to GLP-1 RA improvement of insulin resistance. Clinical Case A mid-20s woman with history of PCOS, obesity, and type 2 diabetes, presented to the clinic for pre-conception weight loss and blood sugar management. Several years ago, she had successfully conceived her first child on metformin, but had begun to experience gastrointestinal side effects limiting her current use. She had been amenorrheic for 2 years and was given a weight loss/BMI goal prior to being eligible for IVF. Although she was interested in weight loss surgery, her diabetes remained uncontrolled with a hemoglobin A1c of 11.0. The patient was started initially on semaglutide in conjunction with her existing metformin and empagliflozin combination tablet, and eventually transitioned to tirzepatide given insurance changes. The patient had a dramatic improvement in both her physical and mental symptoms including a 15lb weight loss, improved blood sugar control with A1C to 5.6, less cravings, and increased energy. While she remained amenorrheic, the patient was found to be unexpectedly pregnant after the dramatic improvement of her symptoms on the GLP-1-GIP agonist. Once pregnant, the GLP-1 RA medication was discontinued, replaced with short and long-acting insulin. The patient delivered her child with a plan to restart the GLP-1 RA medication after she stopped breastfeeding. Clinical Lesson This case is an essential proof of concept where treatment with a GLP-1 agonist in a woman with PCOS, obesity, and diabetes to improve insulin resistance resulted in increased fertility resulting in a successful pregnancy. This evidence will help link treatment with GLP-1 RA to improved fertility in this patient population. References: 1.Papaetis GS, Kyriacou A. GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons. Adv Clin Exp Med. 2022 Nov;31(11):1265-1274.2. Jensterle M, Janez A, Fliers E, DeVries JH, Vrtacnik-Bokal E, Siegelaar SE. The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective. Hum Reprod Update. 2019 Jul 1;25(4):504-517.3.Zhou, L., Qu, H., Yang, L. et al. Effects of GLP1RAs on pregnancy rate and menstrual cyclicity in women with polycystic ovary syndrome: a meta-analysis and systematic review. BMC Endocr Disord 23, 245 (2023). Presentation: Monday, July 14, 2025