Association Between Diclofenac Sodium Use and Reduced Cycle Cancellation from Premature Ovulation in Women with Diminished Ovarian Reserve Undergoing IVF: A Retrospective Cohort Study

Jing-Yan Song,1,* Ying-Jie Ma,2,* Xian-Ling Cao,2,3 Zhen-Gao Sun1,2 1The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Reproductive Center of Integrated Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Xian-Ling Cao, Reproductive Center of Integrated Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42 Wenhua West Road, Lixia District, Jinan, Shandong, People’s Republic of China, Email caoxianlingling@163.com Zhen-Gao Sun, Reproductive Center of Integrated Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42 Wenhua West Road, Lixia District, Jinan, Shandong, People’s Republic of China, Email sunzhengao77@126.comPurpose: To evaluate whether diclofenac sodium administration reduces premature ovulation and improves in vitro fertilization (IVF) outcomes in patients with diminished ovarian reserve (DOR).Patients and Methods: Retrospective cohort study conducted at a single academic reproductive center from January 2022 to March 2025. We included women with DOR (anti-Müllerian hormone [AMH] < 1.1 ng/mL, antral follicle count [AFC] < 5) undergoing autologous IVF cycles with single dominant follicle development. A total of 1164 cycles from 616 patients were analyzed, comparing 382 cycles with diclofenac sodium 75mg daily from trigger day to oocyte retrieval versus 782 cycles without treatment. The primary endpoint was cycle cancellation due to premature ovulation. Secondary endpoints included oocyte retrieval success, fertilization rates, embryo outcomes, and clinical pregnancy rates. Generalized estimating equation (GEE) models with multivariable adjustment were used to account for correlation between multiple cycles from the same patient. A sensitivity analysis restricted to first cycles per patient (n=616) was performed using logistic regression to validate primary findings.Results: Diclofenac sodium significantly reduced cycle cancellation due to premature ovulation (7.3% vs 19.8%, adjusted odds ratio [OR] 0.39, 95% confidence interval [CI] 0.21– 0.73, P=0.003) and decreased the proportion of cycles with no oocytes retrieved (21.8% vs 27.1%, adjusted OR 0.54, 95% CI 0.34– 0.84, P=0.007). Normal fertilization rates were higher in the diclofenac sodium group (77.5% vs 69.8%, P=0.041), though this lost significance after adjustment (P=0.184). The proportion of cycles without viable embryos was comparable between groups (42.3% vs 41.8%, P=0.727). Among limited fresh embryo transfers (n=124), clinical pregnancy (19.2% vs 11.2%, P=0.847) and live birth rates (15.4% vs 8.2%, P=0.948) were similar. The sensitivity analysis using first cycles per patient (n=616) confirmed these findings, showing a 47% reduction in premature ovulation odds with diclofenac sodium (adjusted OR 0.53, 95% CI 0.29– 0.94, P=0.031).Conclusion: Diclofenac sodium is associated with reduced premature ovulation and improved oocyte retrieval success in DOR patients, though embryonic and pregnancy outcomes remain similar. These observational findings require validation through prospective randomized controlled trials with adequate power to assess cumulative reproductive outcomes.Keywords: diclofenac sodium, premature ovulation, in vitro fertilization, diminished ovarian reserve, oocyte retrieval