DELAYED ONSET OF MALE INFERTILITY AFTER TREATMENT WITH HIGH DOSE OF CYCLOPHOSPHAMIDE FOR LUPUS NEPHRITIS

PV118 / #653 Poster Topic: AS15 - Lupus Nephritis-Clinical Background/Purpose Systemic Lupus Erythematosus (SLE) is a classical autoimmune disease with manifestations in multiple organs. Urgent immune modulation and immunosuppressive therapy, particularly with cyclophosphamide (CYC), are essential in cases of diffuse vasculitis and involvement of critical organs like the central nervous system or the kidneys. However, due to its significant side effects, particularly on fertility, alternative regimens such as mycophenolate mofetil (MMF) have been used, especially in childbearing population. In the last years, the induction therapy for active lupus nephritis (LN) with intravenous cyclophosphamide (IV CYC) has been changing from high doses (NIH protocol) to lower cumulative doses (EUROLUPUS) with comparable efficacy, but less adverse events such as infections and toxicity. Gonadal function is severely affected following CYC in both sexes. In male SLE patients, the risk of sterility after CYC is higher than in female, due to greater mitotic activity in the testis. The sperm count in SLE males is inversely influenced by disease activity, and worsens with exposure to CYC, and typically declines within a few weeks of therapy. This toxic effect is less in younger age and prepuberty, following lower dose and shorter treatment duration. Male sterility is usually sustained for several years after end of CYC therapy, so it reinforces the need for sperm cryopreservation. Most of the known data regarding CYC toxicity is based on the onco-hematologic literature, while in SLE patients the actual timing of clinically toxic effect on fertility, of IV CYC for LN, is still unclear and needs to be identified. Methods Presenting a case series of 3 males, of Arab origin with SLE who received IV CYC (NIH protocol) for active LE (mainly diffuse and proliferative glomerulonephritis, Type IV) at a young age (ages 20-23). Their fertility records included available sperm tests and their actual reproductive capability was estimated by number of their spouses’ successful pregnancies. These pregnancies occurred naturally without the use of frozen semen samples and their timing after end of IV CYC courses was recorded. Results After semen cryopreservation, age at administration of IV CYC was 20-23 years old,. It was given monthly in 1g doses for 6 consecutive months, and later every 2-3 months for a total of 9-11 g. All cases were followed up in rheumatology clinic for a period of 13-17 years. During the initial 3-4.5 years after CYC therapy, all patients exhibited normal fertility status and their wives conceived and gave birth without complications to a total of 7 babies. Surprisingly, oligospermia and azoospermia emerged subsequently in all patients, with continuous infertility requiring the use of frozen semen specimens for in vitro fertilization in 2 additional pregnancies. Despite difficulty to childbearing after the third year post-chemotherapy, 1 successful pregnancy was recorded with tests showing abnormal semen count, motility and morphology with clear oligospermia. Conclusions SLE-related nephritis requires urgent induction therapy with cyclophosphamide being a cornerstone, despite concerns about gonadal failure and infertility. A presented case series suggests a different pattern of fertility following IV CYC use for Lupus nephritis, with more reassuring results in the first 3-4 years post therapy. The onset of clinical infertility and findings of oligo/azospermia after cyclophosphamide treatment may occur several years later, providing a natural window of opportunity for normal fertilization and family planning. This unique finding in SLE male patients is noteworthy and mandates investigation and confirmation with further observational studies.

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