Obstetric and perinatal outcome of the women with repeated implantation failures or recurrent pregnancy losses who received pre- and post-conception tacrolimus treatment

Problem Previously, we reported the clinical efficacy of tacrolimus in women with repeated implantation failures (RIF) of immune etiologies. Safety of tacrolimus in pregnant women has been reported in women with organ transplantations. However, the safety of tacrolimus for women with RIF undergoing assisted reproductive technology cycles and their babies has not been reported prior. Method of study This study is a prospective observational study of 109 women with RIF or recurrent pregnancy losses (RPL) who showed elevated peripheral blood Th1/Th2 (CD4(+)IFN-gamma(+)/CD4(+)IL-4(+)) cell ratios (>= 10.3). All received tacrolimus before and during pregnancy (1-4 mg/d) and delivered a live-born infant(s). Blood concentrations of tacrolimus were measured. Neuromotor development of the babies was also evaluated. Results Total 113 babies were born from 109 women, including four twin pregnancies. Nine pregnancies including four twins were delivered prematurely (8.3%). Two of 109 women showed obstetric complications, such as hypertensive disorder of pregnancy, and only one baby (0.9%) had a congenital abnormality. There were no differences in babies' birthweight, placental weight, and lymphocyte proportion (%) of the umbilical cord among the women with different tacrolimus dosing. Tacrolimus was detected in the maternal plasma, and its concentration did not significantly fluctuate during pregnancy while on daily administration regimen. Neuromotor development of the babies exposed to tacrolimus in utero was comparable with that of babies from the general population. Conclusion According to our data, tacrolimus treatment for women with RIF and RPL was not associated with obstetrical and perinatal complications. A large size study is needed to confirm this finding.