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Article

Anti-Müllerian Hormone Serum Levels as Biomarker of Ovarian Reserve in Adult Women with Juvenile Idiopathic Arthritis Treated with csDMARDs and/or bDMARDs: A Pilot Study

by
Clara Di Mario
1,†,
Maria Rita Gigante
2,†,
Angelina Barini
3,
Luca Petricca
2,
Antonella Barini
3,
Antonio Bianchi
4,5,
Stefano Alivernini
1,2,6,
Barbara Tolusso
1 and
Elisa Gremese
1,6,*
1
Immunology Research Core Facility, Gemelli Science and Technology Park, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
2
Division of Rheumathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
3
Chemistry, Biochemistry and Molecular Biology Clinic, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
4
Endocrinology and Diabetes Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
5
Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
6
Clinical Immunology Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
BioChem 2024, 4(4), 313-322; https://doi.org/10.3390/biochem4040016
Submission received: 15 August 2024 / Revised: 21 September 2024 / Accepted: 14 October 2024 / Published: 18 October 2024
(This article belongs to the Special Issue Feature Papers in BioChem)
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Versions Notes

Abstract

:
Background/Objectives: Juvenile idiopathic arthritis (JIA) is a chronic childhood disease that often persists into the reproductive years. JIA may impact long-term fertility due to the prolonged exposure to immunosuppressive therapies. Methods: A total of 35 adult JIA female patients of childbearing age and 20 age-matched healthy controls were studied to test their anti-Müllerian hormone (AMH) serum levels as a biomarker of ovarian reserve. Demographic characteristics, disease duration, previous and current treatments, disease activity (DAS44), and a health assessment questionnaire (HAQ) were recorded. Results: JIA patients had a mean age of 22.3 ± 2.9 years, a disease duration of 12.3 ± 6.1 years, and a DAS44 of 1.24 ± 0.61. No differences were found in AMH serum levels between JIA and controls (5.78 ± 2.37 ng/mL vs. 6.60 ± 2.68 ng/mL, respectively; p = 0.17). Among the patients, 22 (62.9%) were receiving a stable dose of methotrexate (MTX) and 19 (54.3%) a dose of TNFα inhibitors. No difference in AMH serum levels was observed between JIA patients who were or were not exposed to MTX (p = 0.29) or to TNFα inhibitors (p = 0.50). Conclusions: Ovarian reserve as assessed by AMH serum levels appears to be comparable between those with JIA and age-matched controls and does not appear to be influenced by disease characteristics or prior/concomitant exposure to immunosuppressive drugs.

1. Introduction

Juvenile Idiopathic Arthritis (JIA) refers to all forms of chronic arthritis of unknown origin lasting for at least 6 weeks in children and adolescents [1,2], being the most common arthropathy of childhood. It affects hundreds of thousands of children worldwide, representing a leading cause of short- and long-term disability [2,3,4]. Disease onset is usually before 16 years of age, and the disease often persists into reproductive age [2]. Therefore, in this category of patients, fertility preservation should be considered among the priority outcomes, as several studies have shown that patients with JIA or childhood-onset Systemic Lupus Erythematosus (SLE) had an increased risk of decreased reproductive potential as a consequence of their chronic inflammatory condition or drug exposure. However, an estimate of the actual risk of infertility in such patients is still unknown [5]. Fertility has been found to be unaffected in women with JIA [5], but it may be potentially compromised by physical, hormonal, or immunological mechanisms, as well as pharmacological treatments such as prolonged exposure to immunosuppressive therapy in young female patients [6,7]. Conversely, several studies have investigated fertility in female rheumatoid arthritis (RA) patients, particularly in a case-control study with age-matched controls, reporting no relationship between RA and nulliparity, infertility, oral contraceptive use, and adverse pregnancy outcomes [8].
Multiple autoimmune mechanisms are involved in the decrease of the ovarian follicle pool, resulting in premature ovarian failure (POF) (i.e., failure of ovarian function before the age of 40) [9,10]; in fact, the presence of antiovarian antibodies has been reported in premature ovarian aging [11,12]. As previously observed in SLE patients, ovarian function can be impaired by the presence of antibodies directed against the corpus luteum (anti-CoL) [13] and can be decreased by autoimmune oophoritis, leading to a reduction in hormones involved in the ovarian reserve [14]. In JIA, anti-CoL antibodies have rarely been detected, but a decrease in hormones related to ovarian function and reserve has been observed [15].
The quantity and quality of the ovarian follicle pool represent the ovarian reserve; they decay with age, resulting in a decrease in the woman’s reproductive functions [16]. There is considerable individual variability in the age of menopause and subfertility [17], so chronological age is not a good predictor of ovarian reserve. To date, there is no proven marker directly related to ovarian follicle number, although serum levels of follicle-stimulating hormone (FSH), inhibin B, estradiol, and anti-Müllerian hormone (AMH) and the assessment of the ovarian antral follicle count (AFC) by transvaginal ultrasound evaluation have emerged as interesting biomarkers for the prediction of ovarian reserve [18].
These tests have some restrictions, which include lack of sensitivity and, in some cases, their dependence on the phase of menstrual cycle [19,20,21]. In a recent set of recommendations, the Practice Committee of the American Society for Reproductive Medicine stated that combined ovarian reserve test models do not consistently improve predictive ability more than a single ovarian reserve test, suggesting measurement of AMH as a reliable screening test for poor ovarian reserve [19]. In this context, several studies have shown a good predictive value in the evaluation of the ovarian follicle pool by serum levels of AFC and AMH, better than FSH [20,21]. AMH is a growth and differentiation factor of the transforming growth factor β family, produced in the granulosa cells of preantral and small antral follicles [22]. In women, AMH serum levels are undetectable at birth, reaching a maximum level after puberty and then progressively decreasing during reproductive life, until AMH becomes undetectable in menopause [23]. Moreover, it has been observed that the phase of the menstrual cycle does not influence AMH serum levels [24,25]. All these aspects make AMH a good predictive biomarker that reflects well the ovarian reserve over time.
To date, multiple pieces of evidence from the cancer field have demonstrated that AMH serum levels decrease during and after chemotherapy treatment in women, indicating AMH as an early and sensitive biomarker of ovarian reserve damage [26,27].
In recent years, several studies have been published on AMH as a biomarker of ovarian reserve in autoimmune rheumatic diseases [28,29,30,31,32,33,34,35,36,37,38,39] and it has been reported that chronic inflammatory joint diseases, such as RA and spondyloarthritis (SpA), negatively impact the ovarian reserve [34,37]. In JIA adult patients, a significant decrease in AMH levels appears to be unaffected by immunosuppressive therapies like methotrexate (MTX) or biological agents [15].
The aims of this study were (i) to evaluate AMH serum levels in a cohort of JIA adult women of childbearing age compared with age-matched healthy subjects, and (ii) to assess the influence of previous exposure to conventional disease-modifying anti-rheumatic drugs (cDMARDs) and/or biological DMARDs (bDMARDs), as well as of disease parameters on the ovarian reserve in adult women of childbearing age with JIA.

2. Materials and Methods

2.1. Subjects

Thirty-five consecutive female adult patients with a diagnosis of JIA according to ILAR criteria [40] were enrolled in the study at the Fondazione Policlinico Universitario A. Gemelli-IRCCS in Rome. Each enrolled patient had to meet the following inclusion criteria: age between 18 and 30 years, regular menses with no diagnosis of ovarian failure, no current or previous exposure to cytotoxic therapy or radiation for cancer, no previous diagnosis of polycystic ovarian syndrome (PCOS) [41], and no use of oral contraceptives or current pregnancy. At study entry, each enrolled JIA patient underwent peripheral blood sampling for serum AMH determination (see below). Complete ovarian function was assessed during the early follicular phase of the menstrual cycle (between the first and fifth day of menses) with estradiol and follicle-stimulating hormone (FSH). Moreover, clinical and demographic characteristics, disease duration, prior and current therapies, 44-joint disease activity score (DAS), and a health assessment questionnaire (HAQ) were collected at the time of sampling. All participants were asked to answer questions about their lifestyle and their gynecological and obstetric history, including age at menarche, menstrual cycle duration, gynecological disorders, number of full-term pregnancies, and number of miscarriages. Twenty age-matched healthy controls were included as a comparison group. The subjects who participated in this study were all Caucasian women. The study protocol was approved by the Ethics Committee of the Università Cattolica del Sacro Cuore (Ethics Committee protocol number: 0047470/17—31 October 2017) and all subjects provided signed informed consent.

2.2. Determination of Ovarian Reserve: Anti-Müllerian Hormone (AMH) Assay

At study entry, each enrolled subject underwent peripheral blood sampling. The blood was collected in a serum separator tube (BD Vacutainer™ SST™ II Advance) containing spray-coated silica and a polymer gel for serum separation. After peripheral blood drawing, each sample was centrifuged at 300 g within 15 min of collection and stored at −80 °C until assayed [36]. Serum AMH levels were determined with a 2-stage enzyme-linked immunosorbent assay using a commercially bought kit (AMH Gen II ELISA, Beckman Coulter, Inc., Brea, CA, USA) according to the manufacturer’s revised protocol [42,43]. Each AMH assessment was run in duplicate for each sample [37,38]. The intra-assay CV (coefficient of variation) was 3.7% (at 3.8 ng/mL) and 3.4% (at 16.4 ng/mL). The interassay CV was 4.4% (at 3.8 ng/mL) and 3.4% (at 16.4 ng/mL). The assay range was 0.4–21 ng/mL and the sensitivity was 0.08 ng/mL [36]. All experiments were performed in accordance with relevant guidelines and regulations.

2.3. Statistical Analysis

Data were analyzed using SPSS Statistics 22.0 (IBM, Armonk, NY, USA) and Prism software 8.0 (Graph-Pad, San Diego, CA, USA). Categorical and quantitative variables were registered as frequencies, percentage, mean ± standard deviation (SD) as appropriate. The nonparametric Mann–Whitney U test was used to compare the continuous variables. The nonparametric χ2 test was used to assess the differential distribution of the categorical variables. The Spearman’s rank correlation was used to analyze the relationship between AMH serum levels and inflammatory and clinical parameters. p-values < 0.05 were considered statistically significant.
Regarding sample size calculation, this prospective interventional cohort study aimed to evaluate the potential differences in serum AMH levels between young adult women with JIA compared to age-matched healthy controls as its primary endpoint. To date, knowledge about ovarian reserve in women with JIA is scarce, and only one study by Ferreira et al. [15] addressed this topic on a small sample of JIA patients, albeit without significant variation between patients and age-matched controls. The Practice Committee of the American Society for Reproductive Medicine (ASRM) and the Endocrine Society in 2020 [19,44,45,46] suggested measuring AMH as a reliable screening for poor ovarian reserve, providing 1.5–3.0 ng/mL as normal values up to 25 years, with mean values around 2.0 ± 0.4 ng/mL. Thus, assuming a 20% reduction in AMH serum levels in JIA patients, with a power of 80% (type II beta error = 20%) and type I alpha error of 5%, a 95% two-sided confidence interval and a case-to-control ratio of 2:1, a group sample size of 27 and 14 would achieve 81.2% power to detect the hypothesized difference. Hypothesizing a potential dropout of 30% due to laboratory testing issues, we planned to enroll 35 women with JIA (cases) and 20 age-matched controls, respectively. The sample size calculation was performed using PASS2022 statistical software 22.0.3 with a two-sided Mann–Whitney U test [47].

3. Results

3.1. Demographic and Clinical Characteristic of the Cohort of Adult Female JIA Patients of Childbearing Age

A total of 35 consecutive JIA patients and 20 age-matched controls were included in the analysis. Table 1 summarizes the study population characteristics. The mean age of patients at baseline was 22.3 ± 2.9 years, comparable to the control group (23.1 ± 1.9 years, p = 0.07). The mean age at disease onset was 9.5 ± 5.0 years and the mean disease duration at the time of peripheral blood drawing was 12.3 ± 6.1 years (Figure 1). Considering the disease phenotype, systemic onset was observed in four (11.4%) patients, oligoarticular onset in nine (25.7%), polyarticular onset in 20 (57.1%), enthesis-related arthritis in one (2.8%) and psoriatic arthritis in one patient (2.8%), respectively. At enrolment, the mean DAS was 1.24 ± 0.61 and the HAQ was 0.30 ± 0.67 (Table 1).
Considering the previous and concomitant pharmacological treatments in the JIA cohort, 11 (31.4%) patients were taking low-dose prednisone (less than 7.5 mg/daily), 22 (62.9%) had previous exposure to methotrexate (MTX) for a mean period of 2.4 ± 3.4 years, and 19 (54.3%) were treated with anti-TNFα drugs for 2.1 ± 2.7 years during their disease course. Eight JIA (22.9%) patients were exposed to combination therapy (MTX + anti-TNFα) and ten (29.4%) to one or more other csDMARD (i.e., azathioprine, leflunomide, sulphasalazine or cyclosporine, respectively) (Table 1). Regarding ovarian function, no difference was found between JIA patients and healthy controls in FSH and Estradiol serum levels. As for their reproductive background, there were no differences between JIA adult patients compared to controls in mean age at menarche [12.1 ± 1.7 years for patients and 12.9 ± 1.6 years for the control group (p = 0.21)]; none of the patients and controls had had full-term pregnancy or miscarriage.

3.2. Association between AMH Serum Levels with Clinical Characteristic and Pharmacological Treatments in Adult Female JIA Patients Cohort

Evaluation of AMH serum levels revealed that JIA patients did not differ from the control group (5.78 ± 2.37 ng/mL vs. 6.60 ± 2.68 ng/mL, respectively; p = 0.17) (Figure 2A). At disease onset, 12 (35.3%) JIA patients had already experienced menarche, with AMH serum levels similar between patients who experienced menarche before or after disease onset (5.28 ± 2.02 ng/mL and 6.17 ± 2.51 ng/mL; p = 0.50). Moreover, there was no correlation between baseline AMH serum levels and age (R = 0.09; p = 0.61), as well as age at disease onset (R = −0.37; p = 0.83) and disease duration (R = 0.03; p = 0.88) in the JIA cohort. Based on pharmacological treatments, JIA patients receiving MTX (cumulative MTX dose >5 g) showed similar AMH serum levels compared to JIA patients not receiving MTX (4.99 ± 2.30 vs. 6.24 ± 2.34 ng/mL in MTX users and MTX nonusers, respectively, p = 0.29) (Figure 2B). Similarly, JIA patients on anti-TNFα therapy did not show different AMH serum levels from those not using anti-TNFα therapy (6.14 ± 2.68 vs. 5.34 ± 1.93 ng/mL in anti-TNFα-exposed and anti-TNFα-unexposed, respectively, p = 0.50) (Figure 2C).
Looking at treatment exposure, no correlation was found between AMH serum levels and duration of MTX therapy (R = 0.24; p = 0.16) or anti-TNFα therapy (R = 0.33; p = 0.06).
Finally, no difference was found in AMH serum levels among JIA patients treated with MTX alone (n = 8; 6.08 ± 1.30 ng/mL, p = 0.59), anti-TNFα alone (n = 5; 5.60 ± 2.51 ng/mL; p = 0.37), and MTX + anti-TNFα combination (n = 8; 6.74 ± 2.60 ng/mL; p = 0.91) compared to controls (Figure 2D). Despite the limited number of patients, the results are in line with data already published in the literature. Furthermore, no correlations were found between AMH serum levels and duration of exposure to MTX alone (p = 0.10) or anti-TNFα alone (p = 0.08), respectively.

4. Discussion

In this pilot study, we evaluated the serum levels of AMH, a biomarker of ovarian reserve, in a cohort of adult women with JIA, during reproductive age, compared with age-matched healthy controls, to determine whether concomitant chronic inflammatory disease and/or exposure to conventional and/or biological DMARDs could have a detrimental effect on their ovarian reserve. We found that AMH serum levels in the JIA adult cohort did not differ from the aged-matched controls, regardless of prior or concomitant medications.
The AMH serum level has emerged as a good surrogate for estimating ovarian reserve, although recent data on decreased ovarian reserve as assessed by AMH in patients with rheumatic diseases have yielded some conflicting results [29,30,31,32,33]. In particular, in a study conducted on patients with early RA, Brouwer et al. [34] found a comparable concentration in AMH serum levels between the study cohort of RA patients and healthy controls at the time of diagnosis and at a six-month follow-up, as reported in long-standing RA patients [48], while Henes et al. found a significant reduction in ovarian reserve as measured by AMH level in RA patients compared with controls, as well as in spondyloarthritis and Behçet’s disease patients [49].
To date, there are few data on the assessment of fertility in patients with JIA, in their postpubertal age, with AMH used as a biomarker of ovarian reserve [50]. Ferreira et al. documented a significantly lower ovarian reserve in JIA patients, not associated with the hypothalamic–pituitary–gonadal axis, compared to controls, deducing that the disease itself could have a negative influence on the patients’ ovarian reserve [15]. In our study, we found no association between AMH serum levels and age in both JIA patients and healthy controls, and, in contrast to Ferreira et al., no significant difference in AMH serum levels was found between JIA patients and age-matched controls, suggesting a limited effect of this concomitant rheumatic disease on patients’ ovarian reserve. This result could be explained by the narrow range of age distribution of the patients in our study and by the strict selection criteria that excluded patients undergoing cytotoxic drugs, which is relevant as it can influence the ovarian reserve parameters. Furthermore, focusing on the therapeutic profile, we found no significant differences in AMH serum levels among JIA patients exposed to MTX or bDMARDs alone or to MTX + anti-TNFα combination therapies compared to age-matched controls. These results are in agreement with a recent study in which no effect of biological drugs used to treat JIA was observed on AMH, FSH, LH, and estradiol levels even though the cohort of JIA patients was prepubertal and pubertal [50], thus suggesting the hypothesis that exposure to MTX or/and bDMARDs does not affect the ovarian reserve at each different woman’s reproductive phase.
There are few data on the effects of csDMARDs and bDMARDs therapy on ovarian reserve. Scrivo et al. did not observe a change in AMH, FSH, and LH serum levels in SpA after 8 months of treatment with anti-TNFα, assuming that these drugs do not affect fertility [51]. It was observed that Balb/c mice exposed to MTX (5 g/m2) could undergo destruction of primordial follicles [52], and Araujo and colleagues [53] observed that in adult patients with SLE diagnosed in childhood, a high cumulative dose of MTX could have a detrimental consequence on ovarian reserve, while no effect of MTX on ovarian reserve has been documented in JIA patients. However, as shown by Tomioka et al., in a cohort of 23 JIA patients, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may induce luteinized unruptured follicle (LUF) syndrome without compromising ovarian reserve [54].
The present study should be interpreted in the light of some considerations. The term JIA refers to a clinically heterogeneous group of arthritides with different clinical and patho-physiological manifestations, and the small sample size did not allow us to stratify AMH values according to the different clinical phenotypes of JIA. Another consideration is the stringent selection criteria of our cohort of JIA patients aged 18–30 years without a diagnosis of ovarian failure and the exclusion of cytotoxic therapies. In addition, this is a cross-sectional study with no data on AMH serum levels available prior to exposure to drugs administered during the JIA course.
In conclusion, in young adult women with JIA, the disease itself and the exposure to immunosuppressive therapies do not seem to compromise ovarian reserve as assessed by the AMH serum levels, and this may be relevant information also in light of the transition of JIA patients from pediatric age to adulthood [55]. Future prospective studies in larger cohorts of JIA patients are needed to determine whether long-term use of immunosuppressive therapy could influence ovarian reserve and to evaluate possible changes in AMH serum levels before and after exposure to conventional and biologic therapies, also in light of new treatments and strategies in disease management. Furthermore, observation of patients in a long-term follow-up, including data on pregnancies, is necessary to evaluate the impact on their future fertility.

Author Contributions

Conceptualization, C.D.M., M.R.G. and E.G.; Methodology, C.D.M., A.B. (Angelina Barini), A.B. (Antonella Barini) and B.T.; Formal analysis, C.D.M., M.R.G., L.P., S.A., B.T. and E.G.; Data curation, M.R.G., L.P. and S.A.; Writing—original draft, C.D.M., M.R.G., A.B. (Antonio Bianchi) and S.A.; Writing—review & editing, E.G.; Visualization, A.B. (Antonio Bianchi); Supervision, E.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Fondazione Policlinico Universitario A. Gemelli (protocol code 0047470/17; date of approval: 31 October 2017).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Data is contained within the article.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Scheme showing disease course and menarche timeline of individual adult JIA patients belonging to the enrolled study cohort.
Figure 1. Scheme showing disease course and menarche timeline of individual adult JIA patients belonging to the enrolled study cohort.
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Figure 2. (A–D). Anti-Müllerian hormone serum levels in adult women JIA patients and healthy controls. (A) AMH serum levels in adult women JIA patients and age-matched controls enrolled in the study. (B,C) AMH serum levels in adult women JIA patients stratified based on MTX (B) and anti-TNFα exposure (C) compared to those that did not receive these drugs and to controls. (D) AMH serum levels in JIA patients treated with MTX, anti-TNFα and MTX/anti-TNFα combination, compared to controls. AMH: Anti-Müllerian hormone; TNF: tumor necrosis factor; JIA: juvenile idiopathic arthritis; MTX: methotrexate.
Figure 2. (A–D). Anti-Müllerian hormone serum levels in adult women JIA patients and healthy controls. (A) AMH serum levels in adult women JIA patients and age-matched controls enrolled in the study. (B,C) AMH serum levels in adult women JIA patients stratified based on MTX (B) and anti-TNFα exposure (C) compared to those that did not receive these drugs and to controls. (D) AMH serum levels in JIA patients treated with MTX, anti-TNFα and MTX/anti-TNFα combination, compared to controls. AMH: Anti-Müllerian hormone; TNF: tumor necrosis factor; JIA: juvenile idiopathic arthritis; MTX: methotrexate.
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Table 1. Demographic and clinical characteristics of the adult female JIA cohort.
Table 1. Demographic and clinical characteristics of the adult female JIA cohort.
Demographic and Clinical CharacteristicsJIA
(n = 35)		Controls
(n = 20)		p
Age, years22.3 ± 2.923.1 ± 1.90.07
Age at disease onset, years9.5 ± 5.0--
Disease duration, years12.3 ± 6.1--
BMI (kg/m2)22.7 ± 5.222.1 ± 4.30.91
Smoking habit, n (%)10 (28.6)3 (13.6)0.2
HAQ0.30 ± 0.67--
DAS441.24 ± 0.61--
ESR, mm/1 h17.4 ± 13.8--
CRP, mg/L3.9 ± 7.2--
Systemic onset, n (%)4 (11.4)--
Oligoarticular onset, n (%)9 (25.7)--
Polyarticular onset, n (%)20 (57.1)--
Enthesitis-related arthritis, n (%)1 (2.8)--
Psoriatic arthritis, n (%)1 (2.8)--
Treatment (previous or current)
MTX, n (%)22 (62.9)--
MTX treatment duration, years2.4 ± 3.4--
Anti-TNFα, n (%)19 (54.3)--
Anti-TNFα treatment duration, years2.09 ± 2.71--
MTX + anti-TNFα, n (%)8 (22.9)--
Other csDMARDs, n (%)10/34 (29.4)--
Prednisone (less than 7.5 mg/day)11 (31.4%)--
Gynecological and obstetric data
Age at menarche, years12.1 ± 1.712.9 ± 1.60.31
Subjects with full-term pregnancy, n (%)0 (0)0 (0)-
Subjects with miscarriage, n (%)0 (0)0 (0)-
FSH, mUI/mL4.3 ± 2.44.9 ± 3.70.84
Estradiol pg/mL97.9 ± 49.6111.5 ± 46.80.44
AMH, ng/mL5.8 ± 2.46.6 ± 2.80.17
Values are shown as mean ± SD, unless otherwise indicated. BMI: body mass index; DAS: disease activity score; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; MTX: methotrexate; csDMARDs: conventional synthetic disease-modifying antirheumatic drugs; FSH: follicle-stimulating hormone AMH: anti-Müllerian hormone.
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MDPI and ACS Style

Di Mario, C.; Gigante, M.R.; Barini, A.; Petricca, L.; Barini, A.; Bianchi, A.; Alivernini, S.; Tolusso, B.; Gremese, E. Anti-Müllerian Hormone Serum Levels as Biomarker of Ovarian Reserve in Adult Women with Juvenile Idiopathic Arthritis Treated with csDMARDs and/or bDMARDs: A Pilot Study. BioChem 2024, 4, 313-322. https://doi.org/10.3390/biochem4040016

AMA Style

Di Mario C, Gigante MR, Barini A, Petricca L, Barini A, Bianchi A, Alivernini S, Tolusso B, Gremese E. Anti-Müllerian Hormone Serum Levels as Biomarker of Ovarian Reserve in Adult Women with Juvenile Idiopathic Arthritis Treated with csDMARDs and/or bDMARDs: A Pilot Study. BioChem. 2024; 4(4):313-322. https://doi.org/10.3390/biochem4040016

Chicago/Turabian Style

Di Mario, Clara, Maria Rita Gigante, Angelina Barini, Luca Petricca, Antonella Barini, Antonio Bianchi, Stefano Alivernini, Barbara Tolusso, and Elisa Gremese. 2024. "Anti-Müllerian Hormone Serum Levels as Biomarker of Ovarian Reserve in Adult Women with Juvenile Idiopathic Arthritis Treated with csDMARDs and/or bDMARDs: A Pilot Study" BioChem 4, no. 4: 313-322. https://doi.org/10.3390/biochem4040016

APA Style

Di Mario, C., Gigante, M. R., Barini, A., Petricca, L., Barini, A., Bianchi, A., Alivernini, S., Tolusso, B., & Gremese, E. (2024). Anti-Müllerian Hormone Serum Levels as Biomarker of Ovarian Reserve in Adult Women with Juvenile Idiopathic Arthritis Treated with csDMARDs and/or bDMARDs: A Pilot Study. BioChem, 4(4), 313-322. https://doi.org/10.3390/biochem4040016

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