AB0334\u2005THE OVARIAN RESERVE MEASURING THE ANTI-MüLLERIAN HORMONE IS NOT DIMINISHED IN PATIENTS WITH RHEUMATOID ARTHRITISCOMPARED TO THE HEALTHY POPULATION

Abstract

Background Rheumatoid Arthritis (RA) is the most prevalent chronic inflammatory arthritis, affecting 0.5-1% worldwide population and predominates in females. Altered fertility has been reported due to a decrease in ovarian reserve secondary to sustained inflammation. The anti-Müllerian Hormone (AMH) is currently the most reliable biomarker of ovarian reserve. However, few and contradictory studies have been reported to analyze the relationship between fertility in RA women patients and AMH. Objectives The aim of present study is to determine the AMH serum concentrations in a long-standing RA patients and control group. We also sought to determine the correlation between AMH serum levels and disease activity measured by different parameters and the effect of biological DMARDs. Methods Serum AMH levels were measured in 60 women with long-standing RA aged 20-50 y.o. and compared to 59 healthy women. AMH was assessed by ELISA (Gen II Beckman Coulter Inc.) and a large data set of clinical and molecular data was annotated. Demographic parameters, RA disease activity measured by DAS28 score and inflammatory biomarkers such as ESR, CRP, lymphocyte CD4+, CD8+, NK cells, IL-10 and IL-6 were determined. A comprehensive gynecological self-administered questionnaire was given. Serum AMH levels were age-correlated. Differences between groups were calculated using Student’s t-test or Mann-Whitney U test for continuous variables and Fisher’s exact test for categorical variables. Multivariate analysis was conducted by the partial correlation coefficient. Linear regression analysis was performed to study the effect of different variables on proportional AMH change. P value <0.005 were considered significant. Results The median age was similar in AR and control groups (37.4±6.23 vs 37.3±6.27 P=0.937). Mean disease duration was 8.37±5.36 years. The number of previous treatments was <3 in 71.7% of patients and ≥3 in 28.3%. Disease activity measured by DAS28 was 2.89± 1.54. The age-adjusted mean serum concentration of HAM was 1.27 ng/ml [IQR 0.42; 2.24] in RA patients and 1.31 ng/ml [IQR 0.46; 3.09] in controls (P=0.608). Neither disease activity (P=0.862), nor current or previous bDMARDs treatments (P=0.871) were associated with HAM levels. However, a negative linear correlation was observed between HAM and IL-10 levels (P= 0.033). Conclusion Our study shows that ovarian reserve determined by HAM serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, HAM levels were not affected by disease activity however a significant correlation was observed between HAM and IL-10 levels. These results support the role of cytokines profile in the female reproductive system and will focus further investigations in this critical area, mainly once biological DMARDs have be recommended in RA pregnant patients. References [1] Brouwer J, Fleurbaaij R, Hazes JM, Dolhain RJ, Laven JS. Subfertility in rheumatoid arthritis is often unexplained or caused by anovulation. Arthritis Care Res (Hoboken). 2016. [2] Brouwer J, Hazes JM, Laven JS, Dolhain RJ. Fertility in women with rheumatoid arthritis: influence of disease activity and medication. Ann Rheum Dis. 2015;74(10):1836-1841. [3] Brouwer J, Laven JS, Hazes JM, Schipper I, Dolhain RJ. Levels of serum anti-Mullerian hormone, a marker for ovarian reserve, in women with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65(9):1534-1538. [4] Del Junco DJ, Annegers JF, Coulam CB, Luthra HS. The relationship between rheumatoid arthritis and reproductive function. Br J Rheumatol. 1989;28 Suppl 1:33; discussion 42-35. [5] Dewailly D, Andersen CY, Balen A, et al. The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update. 2014;20(3):370-385. Disclosure of Interests None declared