title: Corticosteroid therapy in assisted reproduction - immune suppression is a faulty premise.
abstract: There is ongoing interest in immune-suppressant corticosteroid drugs such as prednisolone to treat infertility in women with repeated IVF failure and recurrent miscarriage. The rationale draws on the pervasive but flawed view that immune activation is inconsistent with normal pregnancy. This ignores clear evidence that controlled inflammation and activation of the immune response is essential for embryo implantation. Generally, the immune response actively promotes reproductive success - by facilitating endometrial receptivity and tolerance of the foreign embryo, and promoting vascular adaptation to support placental morphogenesis. The peri-conception immune response also establishes developmental trajectories that can impact on fetal growth and gestational age at birth. Here, we describe immune changes accompanying conception that could be impeded by inappropriate corticosteroid administration. While women with specific clinical conditions may benefit from the anti-inflammatory and immune-deviating actions of prednisolone and related drugs, it is incorrect to assume a 'one-size-fits-all' approach. Better diagnostics and more preclinical studies are essential to define patient groups, build evidence for efficacy and fine-tune treatments so as not to inhibit essential actions of immune cells. We argue that unless overt immune pathology is evident, utilization of corticosteroids is not warranted and may be harmful. In most women, perturbing immune adaptation at implantation is expected to adversely influence placental development and impair immune-mediated quality control mechanisms, potentially elevating risk of altered fetal growth and developmental programming, congenital anomalies and preterm birth.
authors: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia sarah.robertson@adelaide.edu.au.
authors: Sarah A
authors: SA
authors: Robertson
authors: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia Second Affiliated Hospital, Medical School, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Min
authors: M
authors: Jin
authors: Second Affiliated Hospital, Medical School, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Danqing
authors: D
authors: Yu
authors: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
authors: Lachlan M
authors: LM
authors: Moldenhauer
authors: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
authors: Michael J
authors: MJ
authors: Davies
authors: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
authors: M Louise
authors: ML
authors: Hull
authors: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia Fertility SA, Level 9, 431 King William Street, Adelaide, SA 5000, Australia.
authors: Robert J
authors: RJ
authors: Norman
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology*; D010064:Embryo Implantation / Q000276:immunology; D004717:Endometrium / Q000276:immunology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D011239:Prednisolone / Q000627:therapeutic use*; D011247:Pregnancy; D027724:Reproductive Techniques, Assisted
chemical_list: D007166:Immunosuppressive Agents; D011239:Prednisolone
keywords: IVF failure; corticosteroid; embryo implantation; endometrium; glucocorticoid; immune cells; immunology; inflammation; pregnancy; recurrent miscarriage