The ovarian reserve as measured by the anti-Müllerian hormone is not diminished in patients with rheumatoid arthritis compared to the healthy population

Abstract

ObjectiveRheumatoid 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 analyse the relationship between fertility in RA female patients and AMH. The aim of present study is to determine the AMH serum concentrations in a long-standing RA patient group 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. MethodsSerum 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 an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics) 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 gynaecological self-administered questionnaire was given. Serum AMH levels were agecorrelated. 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-values <0.005 were considered significant. ResultsThe 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 AMH 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 AMH levels. However, a negative linear correlation was observed between AMH and IL-10 levels (p=0.033). ConclusionOur study shows that ovarian reserve determined by AMH serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, AMH levels were not affected by disease activity, however, a significant correlation was observed between AMH 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 been recommended in RA pregnant patients.

Potential factors result in diminished ovarian reserve: a comprehensive review

“…A previous study demonstrated that the AMH level was lower in the RA group, but there was no significance of AMH levels in the activity rheumatoid arthritis, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), erosions, C-reactive protein (CRP) level or therapeutic schedule [ 113 ]. Another study reported a similar result, but found a negative correlation between the levels of AMH and IL-10 [ 114 ]. Therefore, we suggest that the decrease in AMH levels in RA patients may not be caused by RF but may be related to a more common inflammatory factor caused by RA, and IL-10 is one of the possibilities (Fig.…”

Premature Ovarian Insufficiency in Systemic Sclerosis

“…A metaanalysis conducted by Zhang et al showed that RA patients tended to have ovarian failure [21]. Conversely, another study showed no difference in ovarian reserve between RA patients and healthy controls [22].…”

A review of autoimmunity and immune profiles in patients with primary ovarian insufficiency

“…Rheumatoid arthritis (RA) is another chronic inflammatory autoimmune disease that often occurs in women of childbearing age. [ 35 ] Although a few studies failed to find impairment in AMH levels in RA women, [ 18 , 36 ] in other studies, AMH levels were reduced [ 19 , 20 ] and showed a more pronounced decline over time in RA women, [ 35 ] suggesting that RA could cause impaired ovarian function.…”

“…[8] According to reports, autoimmune oophoritis is related to various steroidogenic enzymes antigens, such as 17α-hydroxylase (17αOH), cytochrome P450 side chain cleavage enzyme (P450scc), 21-hydroxylase (21OH), and 3β-hydroxysteroid dehydrogenase (3β-HSD). [50,57] Both 17αOH and [9] AITD (mean ± SD) 167 1.16 ± 0.17* 1.28 ± 0.25 Magri et al (2015) [10] AITD (median (range)) 288 1.40 (1.0-1.7)* 2.27 (1.7-2.3) Özalp Akın et al (2018) [11] Hashimoto's thyroiditis (adolescents) (median (range)) 60 1.7 (0.5-5.1) 1.8 (0.29-5.5) Pirgon et al (2016) [12] Hashimoto's thyroiditis (adolescents) (mean ± SD) 60 10.6 ± 10.4* 7.5 ± 7.3 Tuten et al (2014) [13] Hashimoto's thyroiditis (median (range)) 81 4.82 (1.47-7.38)* 2.44 (1.63-3.29) Ma et al (2013) [14] SLE (mean ± SD) 44 1.71 ± 1.29* 3.33 ± 1.76 Malheiro et al (2014) [15] SLE (median (range)) 54 1.23 (0.24-4.63) 1.52 (1.33-1.88) Soto (2009) et al [16] T1DM (mean ± SD) 124 12.1 ± 9.2 (pmol/L) 14.2 ± 10.8 (pmol/L) Kadiroğulları et al (2020) [17] T1DM (mean ± SD) 107 2.10 ± 1.23 (pmol/L)* 3.05 ± 1.89 (pmol/L) Lopez-Corbeto et al (2020) [18] RA (median (range)) 119 1.27 (0.42-2.24) 1.31 (0.46-3.09) Henes et al (2015) [19] RA (median(range)) Unknown 1.8 (0.0-11.3)* 2.4 (0.3-13.2) Brouwer et al (2019) [20] RA (median (range)) Unknown 2.5 (1.54.6) Unclear Aydogan Mathyk et al (2019) [21] Psoriasis (mean ± SD) 72 1.85 ± 1.13* 2.46 ± 1.21 de Souza et al (2015) [22] Dermatomyositis (n (%)) 39 ≤1: 8 (50%)* ≤1: 3 (13%) Yalçın Bahat et al (2021) [23] Ankylosing spondylitis (mean ± SD) 104 1.188 ± 0.891* 2.203 ± 1.110 Karakus et al (2017) [24] Sjögren's syndrome 49 Unclear Unclear Henes et al (2015) [19] Behçet's disease (median (range)) Unknown 1.1 (0-6.1)* 1.9 (0.1-13.2) Henes et al (2015) [19] Spondyloarthritis (median (range)) Unknown 1.5 (0.1-7.4)* 2.3 (0.05-13.2) Thöne et al (2016) [25] Relapsing-remitting multiple sclerosis (mean ± SD) 134 2.47 ± 0.26* 3.34 ± 0.34 AFC (n)…”