Atsuo Itakura

Impact of frozen-thawed single-blastocyst transfer on maternal and neonatal outcome: an analysis of 277,042 single-embryo transfer cycles from 2008 to 2010 in Japan

OBJECTIVEnTo evaluate the relationship between frozen-thawed single blastocyst transfer (BT) and maternal and neonatal outcomes of pregnancy.nnnDESIGNnRetrospective analysis.nnnSETTINGnJapanese nationwide registry of assisted reproductive technology (ART) with mandatory reporting for all ART clinics in Japan.nnnPATIENT(S)nRegistered from 2008 through 2010 undergoing single embryo transfer cycles (n = 277,042).nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nRates of preterm birth (PTB; <37 weeks gestation), low birth weight (LBW; <2,500 g), small for gestational age (SGA), large for gestational age (LGA), placenta previa, placenta abruption, placenta accreta, and pregnancy-induced hypertension (PIH) after fresh/frozen-thawed and cleaved-embryo/blastocyst transfers were performed.nnnRESULT(S)nFrozen-thawed embryo transfer (FET) was associated with a significantly reduced occurrence of PTB, LBW, and SGA but increased rate of LGA. FET was also associated with a higher incidence of placenta accreta (odds ratio 3.16) and PIH (odds ratio 1.58). BT was associated with a significantly decreased rate of SGA and increased rate of LGA. There was no significant association between BT and maternal complications.nnnCONCLUSION(S)nFrozen-thawed BT is associated with improved general perinatal outcomes of pregnancy but significantly increased maternal risks of placenta accreta and PIH. This finding requires further investigation to assure maternal safety of patients undergoing ART treatment.

Placenta previa increta/percreta in Japan: A retrospective study of ultrasound findings, management and clinical course

Aim:u2002 Placenta accreta is an abnormally firm attachment of placental villi to the uterine wall, which may cause postpartum hemorrhage resulting in maternal morbidity and mortality. The purpose of the present study was to clarify the incidence, clinical background and prognosis of placenta previa increta/percreta treated with different modalities in Japan.

Human chorionic gonadotropin confers resistance to oxidative stress–induced apoptosis in decidualizing human endometrial stromal cells

OBJECTIVEnTo investigate the effect of hCG on the expression of genes involved in oxidative stress resistance observed in decidualizing human endometrial stromal cells (HESCs).nnnDESIGNnIn vitro experiment.nnnSETTINGnSaitama Medical University hospital.nnnPATIENT(S)nPremenopausal women undergoing hysterectomy for myoma uteri.nnnINTERVENTION(S)nHESCs from hysterectomy specimens were isolated and incubated with 8-bromo-cyclic adenosine monophosphate and medroxyprogesterone acetate in the presence or absence of recombinant hCG (rhCG) at various concentrations. Hydrogen peroxide was used as the source of reactive oxygen species (ROS).nnnMAIN OUTCOME MEASURE(S)nApoptotic cells, FOXO1, superoxide dismutase 2 (SOD2), Bax, and Bcl-2 protein expression.nnnRESULT(S)nIn a dose-dependent manner, rhCG conferred additional protection to decidualizing HESCs against oxidative stress-induced apoptosis. In parallel, rhCG augmented the expression of the forkhead transcription factor FOXO1 and its downstream target, the ROS scavenger SOD2. rhCG also inhibited the expression of the proapoptotic Bax protein and up-regulated antiapoptotic Bcl-2 levels in decidualizing HESCs exposed to ROS.nnnCONCLUSION(S)nThe data suggest that hCG might improve the uterine environment upon implantation by suppressing apoptotic responses in the maternal decidua under oxidative stress.

Limitations of internal iliac artery ligation for the reduction of intraoperative hemorrhage during cesarean hysterectomy in cases of placenta previa accreta

Aim:u2002 Our purpose was to evaluate the effect of internal iliac ligation as a bleeding control during cesarean hysterectomy for placenta accreta.

Androgens modulate the morphological characteristics of human endometrial stromal cells decidualized in vitro

The activated androgen receptor (AR) in decidualizing human endometrial stromal cells (HESCs) regulates genes involved in cytoskeletal organization, cell motility, and cell cycle progression. Androgens also enhance the secretion of prolactin, a widely used marker of decidualized HESCs. The purpose of the present study was to investigate the direct effects of androgens on the ultrastructural changes associated with decidual transformation of HESCs. Primary HESC cultures were established and propagated, and confluent cultures were decidualized for 6 days with 8-bromoadenosine 3,5-cyclic monophosphate (8-br-cAMP) and progesterone (P4) in the presence or absence of dihydrotestosterone (DHT). Phase-contrast image analysis demonstrated that DHT increases the shape index of decidualizing cells, which was reversed upon cotreatment with the AR antagonist flutamide. Electron microscopy demonstrated that DHT enhances many of the ultrastructural changes induced by 8-br-cAMP and P4 in HESCs. Decidualizing cells are characterized by an abundant cytoplasm, multiple cell surface projections and, unlike undifferentiated HESCs, form 2 or more cell layers. The DHT further stimulated cytoplasmic expansion, lipid droplet formation, the production of an abundant extracellular matrix, and gap junction formation in decidualized HESCs. The present study demonstrates that androgen signaling has an impact on the morphological and ultrastructural changes associated with the decidual process. Our findings show that androgens promote the development and expansion of cytoplasmic organelles and gap junctions in decidualizing HESCs. These results suggest that androgens in early pregnancy play an important role in promoting the cellular transformation associated with decidualization.

Fibrinogen concentrate substitution therapy for obstetric hemorrhage complicated by coagulopathy

The aim of this study was to assess the efficacy and safety of fibrinogen concentrate therapy for women with obstetric hemorrhage complicated by dilutional or consumptive coagulopathy by retrospectively reviewing the medical records of relevant patients from a single tertiary center.

Androgen signaling in decidualizing human endometrial stromal cells enhances resistance to oxidative stress

OBJECTIVEnTo investigate the effect of androgens on the expression of genes involved in oxidative stress resistance in decidualized human endometrial stromal cells (HESCs).nnnDESIGNnInxa0vitro experiment.nnnSETTINGnUniversity hospital.nnnPATIENT(S)nPremenopausal women undergoing hysterectomy for uterine fibroids.nnnINTERVENTION(S)nHuman endometrial stromal cells isolated from hysterectomy specimens were decidualized with 8-bromo-cyclic adenosine monophosphate (8-br-cAMP) and P in the presence or absence of dihydrotestosterone (DHT) at various concentrations. Hydrogen peroxide was used as a source of reactive oxygen species.nnnMAIN OUTCOME MEASURE(S)nProlactin secretion, apoptosis, FOXO1, and the free radical scavengers superoxide dismutase 2 (SOD2) and SOD1 protein expression.nnnRESULT(S)nProlactin production was induced in HESCs in response to 8-br-cAMP and P. Dihydrotestosterone further enhanced the secretion of PRL in cells treated with 8-br-cAMP plus P. The effect of DHT was blocked by the antiandrogen flutamide. Dihydrotestosterone enhanced resistance to oxidative stress-induced apoptosis on decidualized HESCs. Moreover, DHT enhanced FOXO1 expression in parallel with increased SOD2 protein but not with SOD1.nnnCONCLUSION(S)nAndrogens might play a critical role in the decidualization process at the time of embryo implantation and trophoblast invasion by promoting resistance to oxidative stress.

Activator Protein-2 Impairs the Invasion of a Human Extravillous Trophoblast Cell Line

The reduced migration/invasion of extravillous trophoblasts (EVTs) is a key feature of the genesis of preeclampsia. We and others previously reported that transcriptional factors activator protein-2 (AP-2) alpha and AP-2gamma act as suppressors of tumor invasion. The present study examined the expressions of AP-2alpha and AP-2gamma in preeclamptic placenta vs. control placenta and investigated their effect on the function of EVTs. The expressions of AP-2alpha and AP-2gamma were elevated in the preeclamptic placentas in comparison with the gestational age-matched control placentas. Their expressions also increased in EVTs of the preeclamptic placentas. Thereafter, we transfected AP-2alpha or AP-2gamma into human EVT cell line, HTR-8/SVneo. The overexpression of AP-2alpha or AP-2gamma decreased the migratory and invasive abilities in HTR-8/SVneo cells. This was followed by the reduction of protease activated receptor-1 and matrix metalloproteinases and a significant induction of plasminogen activator inhibitor-1 and the tissue inhibitor of metalloproteinase-1. AP-2alpha and AP-2gamma were weakly expressed in the cultured EVTs and HTR-8/SVneo cells, whereas they were induced by TNF-alpha, which increases in preeclamptic placenta and impairs trophoblast invasion. In the presence of TNF-alpha, the invasion of the HTR-8/SVneo cells was partially restored by a blocking of AP-2 induction using small interfering RNA of AP-2. The present data suggest that AP-2 may suppress trophoblast migration and invasion, thus leading to a shallow placentation in preeclampsia.

Takotsubo cardiomyopathy after cesarean: A case report and published work review of pregnancy‐related cases

Takotsubo cardiomyopathy (TCM) primarily affects postmenopausal women and is an important differential diagnosis of acute coronary syndrome. We describe a rare case of post‐partum TCM, and present a published work review of the cases of pregnancy‐associated TCM. A 24‐year‐old Japanese woman pregnant with twins suffered from premature membrane rupture at 31 gestational weeks. Following emergency cesarean delivery, she complained of sudden dyspnea. Transthoracic echocardiography revealed an inverted Takotsubo pattern (ejection fraction, 46%). On post‐delivery day 8, wall motion abnormalities subsided, and she was discharged on post‐delivery day 16. We reviewed 18 relevant cases of peripartum TCM from the published work. Among them, 16 cases were post‐partum and two cases occurred during pregnancy. Most women (81%) underwent cesarean delivery, and the first symptoms of TCM appeared during surgery in 38% of the cases. The dominant symptoms were chest pain (44%) and dyspnea (28%). Most cases (94%) exhibited electrocardiogram abnormalities, including ST changes and T‐wave inversion. Serum levels of cardiac enzymes were abnormally high in 92% of the cases. Repeated echocardiography documented normalized left ventricular systolic function within 6 months in all cases. This case and review emphasize that TCM may be concealed in post‐partum women by symptoms undistinguishable from acute coronary syndrome, peripartum cardiomyopathy or pulmonary thromboembolism, and that echocardiography may be a useful tool to distinguish them.

Increased ovarian follicle atresia in obese Zucker rats is associated with enhanced expression of the forkhead transcription factor FOXO1

It is well established that hyperinsulinemia, resulting from insulin resistance, plays a role in the pathophysiology of polycystic ovary syndrome (PCOS). The aim of this study was to investigate if ovarian follicular development and atresia are impaired in obese hyperinsulinemic (fa/fa) Zucker rats. To gain insight into the molecular mechanism of follicular atresia, we also examined the expression and localization of forkhead transcription factor FOXO1, a major regulator of cell fate decisions such as differentiation, cell-cycle arrest, and cell death. Serum insulin but not gonadotropin levels were significantly higher in obese (fa/fa) rats when compared to lean controls. Total ovarian follicle number and the percentage of atretic follicles were also significantly increased in obese (fa/fa) rats. Follicle atresia was associated with nuclear accumulation of FOXO1 transcription factor in TUNEL-positive granulosa cells. These results suggest a role for FOXO1 in granulosa cell apoptosis and increased ovarian follicle atresia associated with hyperinsulinemia.