Received April 26, 2026
Accepted May 05, 2026

Background Repeated implantation failure (RIF) poses significant challenges in assisted reproductive technology. This study investigated the effects of hydroxychloroquine, an anti-inflammatory medication, on frozen embryo transfer outcomes in patients with RIF. Methods In this randomized, triple-blind trial, 70 women with a history of RIF were randomly assigned to intervention and control groups. The control group received 4 mg estradiol valerate tablets starting on the third day of the menstrual cycle for four days, followed by 6 mg daily from the seventh day until the endometrial thickness reached at least 8 mm. The intervention group received 200 mg hydroxychloroquine tablets every 12 hours from the third day of the menstrual cycle, in addition to estradiol valerate. Following endometrial preparation, patients received a daily intramuscular injection of 50 mg progesterone and 400 mg of vaginal progesterone suppositories twice daily, then frozen embryo transfer was performed. The primary outcomes were chemical pregnancy and clinical pregnancy rates. Secondary outcomes were multiple pregnancy, abortion, and ongoing pregnancy rates. Results The intervention group exhibited higher rates of chemical pregnancy, clinical pregnancy, and ongoing pregnancy compared to the control group; however, these differences were not statistically significant (P > 0.05). Furthermore, the rate of singleton pregnancies in the intervention group was significantly higher (P = 0.04). Conclusion Although hydroxychloroquine may positively affect pregnancy outcomes, the evidence in this study is not strong enough to draw definitive conclusions. Future studies with larger cohorts are essential to substantiate our findings.