Background/Purpose: The low-dose intravenous (IV) cyclophosphamide (CY) Euro-Lupus (EL) regimen (cumulative dose 3g) has been developped to reduce gonadal toxicity. Although no case of premature menopause has been reported, uncertainty persists regarding a marginal effect on the ovarian reserve. To address this issue, we measured serum titers of anti-Mullerian hormone (AMH) in patients suffering from systemic lupus erythematosus (SLE) treated with the EL regimen and compared them to those measured in SLE patients treated with higher doses of IVCY and in those never treated with IVCY.

Methods: Serum anti-Mullerian hormone (AMH) levels were measured by ELISA (Ansh Laboratories, TX, USA) in a cohort of 169 consecutive premenopausal female SLE patients fulfilling the SLICC/ACR criteria. Demographic and clinical data were collected, as well as the cumulative dose of IVCY. Patient’s consent was obtained, as appropriate.

Results: Median serum AMH titers of patients given the 3g EL IVCY regimen (1.15 ng/ml ; n=31) did not differ from those measured in patients never treated with IVCY (1.42 ng/ml ; n=112). By contrast, and as anticipated, serum AMH titers were statistically lower in patients treated with >3g IVCY (median : 0.71 ng/ml; n=26 ; mean ± SD IVCY dose of 8.1 ± 3.7g ; p=0.036 by Mann-Whitney test). These results were confirmed when serum AMH values were adjusted for age (based on titers measured in the cohort of SLE patients who never received IVCY). Patients given >6g IVCY (n=15 ; mean ± SD IVCY dose : 10 ± 3.9g) have much lower median age-adjusted serum AMH values (0.09 ng/ml) compared to patients never given IVCY (p=0.008 by Mann-Whitney test). In 10 patients, paired serum samples were tested before and after EL IVCY. Median AMH values did not differ (1.54 ng/ml before and 1.39 ng/ml after : p=0.49 by Wilcoxon matched-pairs signed rank test).

Conclusion: Based on cross-sectional and longitudinal data, the EL IVCY regimen does not impact the ovarian reserve of SLE patients and can therefore be proposed as induction immunosuppressive therapy in severe patients without risk of compromising fertility.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-low-dose-intravenous-cyclophosphamide-euro-lupus-regimen-does-not-impact-the-ovarian-reserve-of-lupus-patients-as-measured-by-serum-anti-mullerian-hormone-levels/