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-γ+ /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.

Downregulation of LH receptor mRNA in the rat uterus.

We detected luteinizing hormone receptor (LHR) mRNA in the immature rat uterus by northern blotting and downregulation of this receptor mRNA after pregnant mare serum gonadotropin (PMSG)-human chorionic gonadotropin (hCG) treatment. After administration of hCG, the mRNA levels in the rat uterus declined to an extremely low level from Days 1 to 3 and then rebounded and reached higher than pretreatment values at Day 4. At Day 5 the levels were 3-fold higher than the control levels. The cultured uterus displayed an hCG concentration-dependent increase in cAMP production in the medium. Immunohistochemical experiments showed that these receptor proteins were expressed in the epithelial cells of the endometrium. These results suggest that functional LHRs are present in the immature rat uterus and are downregulated by signals resulting from hCG treatment. These data may support the idea that LH acts on the uterus to inhibit contraction at ovulation. Although the precise role of the LHR in the uterus remains unknown, this study may provide a model with which to investigate the regulation of LHR.

Plasma adrenomedullin levels during multiple pregnancy.

BACKGROUND: To estimate the normal level of adrenomedullin (AM) during multiple pregnancy. METHODS: The study population consisted of 5 women with normal cycles, 130 women with normal pregnancy between 6 and 40 weeks of gestation, 93 women with twin pregnancy and 42 women with triplet pregnancy. RESULTS: Total AM concentration in the first trimester (13.7 +/- 0.58 fmol/ml), second trimester (26.8 +/- 1.13 fmol/ml) and third trimester (37.8 +/- 1.32 fmol/ml) in pregnant women was significantly higher than that in nonpregnant women (8.0 +/- 0.71 fmol/ml). In each trimester, the maternal plasma concentrations of triplet-pregnant women were significantly higher than in twin and singleton-pregnant women. Umbilical venous AM levels (29.9 +/- 2.63 fmol/ml) were higher than umbilical arterial AM (20.2 +/- 2.04 fmol/ml). CONCLUSION: Since alterations in the AM concentration in maternal plasma may mediate compensatory vascular responses in the uterine circulation, it might be useful to know the normal level of AM during multiple pregnancy in order to detect abnormalities during multiple pregnancy.