An immunosuppressive treatment using tacrolimus improved pregnancy outcome of repeated implantation failure patients with elevated Th1/Th2 ratios.

Background The aim of this study is to evaluate the relationship between chronic endometritis (CE) and a personalized window of implantation (WOI), identified by results of endometrial receptivity analysis (ERA), and pregnancy outcomes following embryo transfer (ET) based on the ERA outcomes. Methods The single‐center, cross‐sectional study was designed. The study population consisted of 101 infertile women who underwent endometrial sampling between June 2018 and February 2020. We recruited 88 patients who underwent ERA testing and immunohistochemistry of the plasma cell marker CD138 to diagnose CE within 3 months of testing. Subjects were divided into three groups as follows: 33 without CE (non‐CE group); 19 with untreated CE at ERA testing (CE group); and 36 successfully treated for CE before ERA testing (cured‐CE group). CE diagnosis was defined as ≥5 CD138‐positive plasma cells per 10 random stromal areas at ×400 magnification. Results In non‐CE, CE, and cured‐CE groups, the numbers of CD138‐positive cells were 0.7 ± 1.0, 28.5 ± 30.4, and 1.3 ± 1.3, respectively (p < .001). The rates of “receptive” endometrium in non‐CE and cured‐CE groups were 57.6% (19 women) and 50.0% (18 women), respectively; however, in the CE group, this rate was significantly lower than the other two groups (p = .009) at only 15.8% (3 women). After CE were treated prior or posterior to the ERA test in cured‐CE or CE groups, the clinical pregnancy rates at the first ET in non‐CE, CE, and cured‐CE groups were 77.8% (21/27 cycles), 22.2% (4/18 cycles), and 51.7% (15/29 cycles), respectively (p < 0.001). Conclusion CE had detrimental effects on the individual WOI, leading to embryo–endometrial asynchrony; therefore, diagnosis and treatment of CE should be done before ERA testing.

Problem What are the pregnancy outcomes after the OPtimization of Thyroid function, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy in patients with repeated implantation failure (RIF)? Method of study Infertile women with a history of RIF after more than three embryo transfer (ET) cycles underwent implantation testing, including a hysteroscopy, endometrial biopsy for CD138 immunostaining and bacterial culture, and serum 25‐hydroxyvitamin D3, interferon‐γ‐producing helper T (Th1) cell, IL‐4‐producing helper T (Th2) cell, thyroid‐stimulating hormone, thyroid peroxidase antibody, and thrombophilia screening between April 2017 and August 2018. We treated chronic endometritis with antibiotics, aberrant high Th1/Th2 cell ratios with vitamin D and/or tacrolimus intake, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low‐dose aspirin. Of the 116 RIF women, 88 women with 133 ET cycles were recruited from a questionnaire‐based survey regarding pregnancy outcomes. Fifty‐nine consecutive RIF patients without the OPTIMUM treatment strategy were also recruited as a control. Results The 116 women with RIF after the OPTIMUM treatment strategy were 38.3 ± 3.8 years old and had an implantation failure history over 5 (3‐19) ET cycles. Implantation testing identified impaired intrauterine circumstances in 75 women (64.7%), an aberrant elevated Th1/Th2 cell ratio in 56 women (48.3%), and thyroid abnormalities in 33 women (28.4%). Cumulative ongoing pregnancy rates including spontaneous pregnancy in the patients aged < 40 and ≥ 40 years were 72.7% and 45.5% within two ET cycles, respectively. The pregnancy outcomes in the OPTIMUM group were significantly higher than those in the control. Conclusions The OPTIMUM treatment strategy improved pregnancy outcomes in patients with RIF.

We confirm our previous report that Th1/Th2 ratio can predict ART outcomes in patients with RIF and immunosuppressant treatment with tacrolimus, and peripheral blood Th1 cell levels were negatively correlated with pregnancy outcome.

Purpose To ascertain whether the use of hyaluronanenriched transfer medium (HETM) improves pregnancy and implantation rates among embryo transfer patients with a history of multiple implantation failures. Methods Patients (n0314) under the age of 40 and with a history of multiple unsuccessful embryo transfers were enrolled. There were three groups of patients: those undergoing fresh embryo transfer (fresh ET [n 0111]), those undergoing vitrified-warmed ET in the natural cycle (WET-N [n0101]) and those undergoing WET in a hormone replacement cycle ). On the day of ET, patients were randomized to HETM (0.5 mg/ml hyaluronan) or control medium containing no hyaluronan. Only patients with good quality embryos on day 3 were included. Results For all three patients groups (fresh ET, WET-N and WET-H) pregnancy rates (37.5 %, 31.4 % and 41.2 %, respectively) were significantly higher when using HETM compared with control medium (10.9 %, 10.0 % and 15.7 %, respectively; p<0.05), and implantation rates when using HETM were also significantly higher compared with control medium (p<0.05). Miscarriage rates were similar in both groups. Conclusion HETM significantly increased pregnancy and implantation rates among embryo transfer patients with a history of multiple unsuccessful implantations-regardless of method used to prepare the endometrium.