title: Ovarian function and reproductive outcomes of female patients with systemic lupus erythematosus and the strategies to preserve their fertility.
abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that mainly affects women of reproductive age. Emerging data from recent molecular studies show us that estrogen hormone plays a central role in the development of this disease. By acting via its cognate receptors ERα and ERβ expressed on immune cells, estrogen can modulate immune function in both the innate and adaptive immune responses. Interestingly, estrogen may also evoke autoimmune responses after binding to B lymphocytes leading to the generation of high-affinity autoantibodies and proinflammatory cytokines (so-called estrogen-induced autoimmunity). Unfortunately, reproductive function of young female patients with this disease is commonly compromised by different pathophysiologic processes. First, ovarian reserve is diminished even in the presence of mild disease suggesting a direct impact of the disease itself on ovarian function possibly due to ovarian involvement in the form of autoimmune oophoritis. Second, SLE patients with severe manifestations of the disease are treated with alkylating chemotherapy agent cyclophosphamide. Cyclophosphamide and other drugs of alkylating category have the highest gonadotoxicity. Therefore, SLE patients exposed to cyclophosphamide have a much higher risk of developing infertility and premature ovarian failure than do the counterparts who are treated with other less toxic treatments. Third, the functions of the hypothalamic pituitary ovarian axis are perturbed by chronic inflammatory state. And finally adverse pregnancy outcomes are more commonly observed in SLE patients such as fetal loss, preterm birth, intrauterine fetal growth restriction, preeclampsia-eclampsia, and fetal congenital heart block. We aimed in this review article to provide the readers an update on how estrogen hormone closely interacts with and induces lupus-prone changes in the immune system. We also discuss ovarian function and other reproductive outcomes in SLE patients and the current strategies to preserve their fertility in the light of the most recent evidence-based findings of the clinical trials and molecular studies.
authors.affiliation: Associate Professor, Department of Obstetrics and Gynecology, Division Reproductive Endocrinology and Infertility, School of Medicine, Koc University, Istanbul, Turkey.|Associate Professor of Obstetrics and Gynecology, Comprehensive Cancer Care and Fertility Preservation Programs, Women's Health Center, Assisted Reproduction Unit, and the Laboratories for Translational Research in Human Reproduction.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Oktem
authors.affiliation: Assistant Professor of Obstetrics and Gynecology, Istanbul Aydin University, School of Medicine, Istanbul, Turkey.
authors.forename: Yılmaz
authors.initials: Y
authors.lastname: Guzel
authors.affiliation: Attending Physician in Obstetrics and Gynecology, Department of Psychiatry, Comprehensive Cancer Care Program, American Hospital, Istanbul, Turkey.
authors.forename: Senai
authors.initials: S
authors.lastname: Aksoy
authors.affiliation: Psychologist, Department of Psychiatry, Comprehensive Cancer Care Program, American Hospital, Istanbul, Turkey.
authors.forename: Elvin
authors.initials: E
authors.lastname: Aydin
authors.affiliation: Professor, Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Division Reproductive Endocrinology and Infertility, School of Medicine, Koc University, Istanbul, Turkey.|Head, Women's Health Center, Assisted Reproduction Unit, Department of Psychiatry, Comprehensive Cancer Care Program, American Hospital, Istanbul, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Urman
mesh_terms: D003520:Cyclophosphamide / Q000009:adverse effects*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000503:physiopathology*; D010053:Ovary / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications; D011256:Pregnancy Outcome; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced* / Q000628:therapy
chemical_list: D004967:Estrogens; D003520:Cyclophosphamide