AB0588 ADALIMUMAB FOR IMMUNE RELATED INFERTILITY: EFFICACY AND SAFETY FROM PROSPECTIVE FRENCH MULTICENTER REGISTRY

Abstract

BackgroundRecurrent miscarriage (RM) is a frequent condition affecting about 1–3 % of couples and is one of the most frustrating and difficult areas in reproductive medicine since the etiology is often unknown and evidence-based diagnosis and treatment strategies are scarce. Likewise, recurrent implantation failure (RIF) is considered after at least 3 unsuccessful transfers of good quality embryos, and remains unexplained in 45 % of infertile couples.ObjectivesThe primary objective of this study was to describe a real-life prospective cohort of women with unexplained RM and/or RIF under adalimumab, to analyze the impact of the treatment on live birth rates and to evaluate its safety.MethodsThe French infertility multicenter FALCO registry is an ongoing registry from 2017 including patients with unexplained recurrent miscarriages and implantation failures from several university hospitals. Inclusion criteria were [1] at least 3 recurrent miscarriages before 12 weeks of gestation and/or at least 3 implantation failures of at least 2 good quality embryos transfers; [2] absence of any cause for recurrent miscarriages and implantation failures such as uterine, genetic, infectious, hormonal, thrombophilia and autoimmune diseases.The following data was collected:Clinical data including age, number of pregnancies, number of consecutive miscarriages, body mass index, tobacco and alcohol use, tea or coffee consumption during pregnancy, dietary habits, presence of endometriosis, adenomyosis and assessment of the uterine cavity by hysteroscopy or hysterosonography.Laboratory analysis of usual recurrent miscarriages etiological screening: parental karyotypes, ovarian reserve parameters (FSH (IU/L), LH (IU/L), Estradiol (pg/ml), AFC (Antral Follicular Count), AMH rate (ng/ml)), thyroid-stimulating hormone (TSH) levels (mUI/l) and biomarkers of immune origin (antinuclear antibodies, anti TPO/TG).ResultsOverall, between 2017 and December 2022, 2686 pregnancies from 395 patients were included with prospective follow-up. These women had history of recurrent implantation failure for 102 (26%), recurrent miscarriage for 275 (70%) and both for 18 (4%). The median gravidity was 4 [2-6].Regarding the presence of immunity biomarkers, 263 had various autoantibodies (66,6%): 130 patients (33%) with antinuclear antibodies (>1/80e), 18 patients with antiphospholipid antibodies (5%), 44 patients with positive anti thyroid peroxidase antibodies (11%), 24 with positive anti-thyroglobulin antibodies (11%), 4 with anti-transglutaminase antibodies (11%). Most recent AMH count median was 1.73 [0.87, 3.24].Among overall pregnancies, there were 1384 miscarriages (73,6%), 269 live births (14,3%), 89 abortions (4,7%), 24 medical terminations of pregnancies (1,3%), 55 pregnancies over 12 weeks of gestation (2,9%) and 58 extrauterine pregnancies (3,1%)Among 2686 pregnancies, 494 were treated and received immunomodulatory treatment. Among these pregnancies under therapies: steroids in 332 cases (12,4%), hydroxychloroquine in 185 cases (7%), intralipids in 102 cases (3,8%), and adalimumab in 69 cases (2,6%).Patients with pregnancy under adalimumab treatment had a significantly higher rate of cumulative live birth rate than those with untreated ones: OR: 3.52 [1.63 - 7.61]; p < 0.01 after adjustment of age, pregnancy, associated treatment (progesterone, aspirin, vitamin D, prednisone).Adverse events in Adalimumab treated pregnancies were reported in 7 women: herpes and zoster reactivation in 3 cases, cystitis and bronchitis in 4 cases, and no congenital malformation and no maternal deaths.ConclusionIn this large prospective French cohort of women with unexplained immune origin RM and/or RIF, adalimumab has been effective to obtain a live birth pregnancy.Reference[1]Adalimumab for immune related infertility: efficacy and safety from prospective French multicenter registryAcknowledgements:NIL.Disclosure of InterestsNone Declared.