3. Discussion
subfertility, tubal disease, infertility
ADVERSE EVENTS, UNEXPLAINED INFERTILITY, DYSFUNCTION, RECURRENT PREGNANCY LOSS
A large number of couples suffer from unexplained intractable infertility that does not fall into the major categories of ovulatory dysfunction, male factor infertility, and tubal disease. Although immunologic tests are rarely included in the commonly suggested evaluation of subfertility, reproductive failures, including unexplained infertility, recurrent pregnancy loss, and repeated implantation failure, are thought to be highly associated with maternal-to-fetal immunological problems. During pregnancy, various immune cells, extravillous trophoblasts, and decidual stromal cells form a dense network of cellular connections to balance immunity between the mother and fetus. It is equally important for the mothers to be immunologically ready to accept early embryos at the time of implantation. Immunotherapeutic approaches, including corticosteroids, calcineurin inhibitors, intravenous immunoglobulin, and anti-TNF agents, could be targeting the maternal immune system against early embryos or fetuses.The main limitation of this study is the lack of a placebo control group. We designed a 2-dose, single-group controlled trial after careful consideration of the ethical aspects of participants’ welfare. Another limitation is that it is difficult to explain infertility involving maternal-to-fetal immune abnormalities solely on the basis of the Th1/Th2 cell cytokine balance. Finally, the sample size is too small to detect rare adverse events when assessing the safety of tacrolimus treatment in patients with infertility.