FRI421 Immunomodulatory Therapy Can Improve Fertility In Women With Autoimmune Premature Ovarian Insufficiency - A Proof Of Concept Study

Abstract

Abstract Disclosure: A.L. Hirschberg: None. S. Björnsdottir: None. I. Gunnarsson: None. F. Sergouniotis: None. E. Vogt: None. M. Øksnes: None. E.S. Husebye: None. S. Bensing: None. O. Kämpe: None. Introduction: Autoimmune disorders are associated with increased risk of premature ovarian insufficiency (POI), leading to early menopause and infertility. The etiology of autoimmune POI remains unknown, but measurable levels of anti-Mullerian hormone indicate that some follicles may be intact. We asked if rituximab, a B cell specific anti-CD20 monoclonal drug could improve the ovarian response to gonadotropin stimulation and restore fertility. Methodology: In this open label pilot study, nine women aged 18-35 years, BMI 19-30 kg/m2 with autoimmune POI (S- FSH > 40 IE/L), of which six had Addison’s disease, were included. The procedure comprised controlled ovarian hyperstimulation according to a standard high dose protocol with daily subcutaneous injections of follitropin alpha, prior to, and 4 months after, two infusions of 1-gram rituximab 2 weeks apart, and a follow-up period of 12 months. If positive response to ovarian stimulation was obtained, GnRH antagonist was given to prevent premature ovulation and choriogonadotropin alpha to induce ovulation. When possible, oocytes were retrieved for cryopreservation and later fertilization. Results: None of the nine patients responded to ovarian stimulation prior to rituximab treatment (mean stimulation days 15.7 ± 1.6 days). After rituximab therapy, five of seven responded with follicular development, and in four women mature eggs were harvested (oocyte yield 3-13 oocytes) for preservation. Four of these five women experienced spontaneous menstrual bleedings and decreased vasomotor symptoms. All responders had autoimmune Addison’s disease, whereas two women with no response had Myasthenia gravis and Hashimoto thyroiditis, respectively. We observed no serious drug reactions or other complications. Conclusions: We have shown for the first time that rituximab can restore menstrual bleedings and enable egg retrieval with the potential to restore fertility in patients with autoimmune POI. This could become an alternative fertility treatment to egg donation, which is the only option today. Presentation: Friday, June 16, 2023