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Objective: We invented a two-tiered structure device based on stereolithography for residual mandible repositioning in mandibular reconstruction with fibular flap, and examined its usefulness., Patients and Methods: A total of eight patients (six carcinomas and two osteomyelitis) who had undergone mandibular reconstruction with fibular flap were included. Mandibular defects according to Jewer's classification were L for five, LC for two, and H for one patient (range of bone defect size, 7.7-13.3 cm). Based on a stereolithographic mandibular model, a two-tiered structure device was made preoperatively with resin, and was applied during surgery to define the accurate position of residual mandible following segmental mandibulectomy. Postoperative aesthetic and functional outcomes, including dental status, diet, and speech were evaluated., Results: The device was applied without any problems during surgery. Follow-up period ranged from eight to twenty-two months. Good postoperative alignment of the grafts and occlusion were also achieved in all eight patients. Five patients were able to return to eating meals as they had pre-surgery, and two patients required dental rehabilitation with dentures. As for speech, four patients scored ten points, three patients scored eight points, and one patient scored four points in Hirose's scoring system, which means that seven patients was rated as excellent, and one patient was rated as poor. Aesthetic outcomes were excellent in three patients, good in three patients, and fair in two patients., Conclusion: Our device was easy to prepare, successfully maintained the precise position of the residual mandible, and facilitated bone graft cutting and insetting during reconstruction. © 2016 Wiley Periodicals, Inc. Microsurgery 37:509-515, 2017., (© 2016 Wiley Periodicals, Inc.)

Aim: To determine the effectiveness of a formula diet in weight reduction and the recovery of menstruation in obese patients with ovulatory disorders., Methods: After the enrollment of 39 obese women with ovulatory disorders, they replaced one or two of their three normal meals with a microdiet (MD) (240 kcal/meal) for 24 weeks. Physical, endocrinological, and biochemical tests were conducted before and at 12 and 24 weeks of the study. Of the 39 women enrolled, 26 were not taking clomiphene. They were divided into three groups according to their body weight outcomes and then analyzed for menstruation recovery., Results: A weight reduction of ≥5% was observed in 31 (81.5%) of the 39 women. There were significant decreases in the body weight and Body Mass Index during the study. Menstruation returned in 18 (69%) of the 26 patients without clomiphene treatment, with the recovery being significantly more prevalent in the groups (totally 81.0%) that exhibited a 5%-10% weight reduction and ≥10% weight reduction, compared to the group with a <5% weight reduction., Conclusion: The use of a formula diet effectively reduced the patients' body weight and led to the recovery of menstruation in these obese patients with ovulatory disorders.

Aim: The Japan Society of Obstetrics and Gynecology implemented a registry report system for the clinical practice of assisted reproductive technology in 1986. The aggregated results from 1992 to 2014 are reported herein., Methods and Results: The total number of registered treatments was 393 745 cycles, of which 66 550 were pregnancy cycles and 46 008 were cycles with a live birth. Compared to the number of registered treatments in 2008, when the cycle-based registry was newly introduced, there was a 2.07-fold increase in the total number of treatments and a 2.25-fold increase in the number of cycles with a live birth. As the average age of patients who receive assisted reproductive technology has become markedly higher year by year, the most common age of those patients who received assisted reproductive technology in 2014 was 40 years., Conclusion: The total numbers of both assisted reproductive technology treatments and assisted reproductive technology live births are likely to be higher in the future. In addition, the trend toward aging patients seems to be continuing into the future.

Aim: Endometriosis is defined as the presence of endometrial glandular and stromal cells outside of the uterine cavity. A previous study reported that microRNA (miR)-542-3p plays a critical role in eutopic endometrial decidualization. This study aims to clarify the potential role of miR-542-3p and the target gene, IGFBP-1 (insulin-like growth factor-binding protein 1), in the impairment of the decidualizing capacity of human ectopic endometrial stromal cells (HEcESCs)., Methods: In vitro analysis of primary undifferentiated and decidualizing human eutopic endometrial stromal cells (HEuESCs) and HEcESCs was conducted. The primary HEuESCs or HEcESCs were expanded in culture and decidualized with 8-bromo-cyclic adenosine monophosphate (8-bromo-cAMP) and medroxyprogesterone acetate (MPA)., Results: The morphological and biological differentiating capacities of the HEcESCs were markedly impaired. In contrast to the HEuESCs, the HEcESCs that were treated with the decidual stimulus retained the mesenchymal phenotype and capacity for migration. The down-regulation of miR-542-3p in the HEcESCs treatment with 8-bromo-cAMP and MPA was much weaker than that of the HEuESCs. High expression of miR-542-3p led to a significant decrease in the expression of IGFBP1 in the HEcESCs., Conclusion: Impairment of the differentiating capacity by the overexpression of miR-542-3p could influence the capacity for migration and invasion of endometriotic cells in an ectopic environment.

Endometrial decidualization represents an essential step for the successful implantation of the embryo; however, the molecular mechanism behind this differentiation process remains unclear. This study aimed to identify novel microRNAs (miRNAs) involved in the regulation of decidual gene expression in human endometrial stromal cells (HESCs). An in vitro analysis of primary undifferentiated and decidualizing HESCs was conducted. HESCs were isolated from hysterectomy specimens from normally cycling premenopausal women with uterine fibroids, who were not on hormonal treatment at the time of surgery. Primary HESCs were expanded in culture and decidualized with 8-bromo-cyclic adenosine monophosphate and medroxyprogesterone acetate. Microarray analysis identified six miRNAs differentially expressed in response to decidualization of HESCs. All but one miRNA were downregulated upon decidualization, including miR-542-3p. We demonstrated that miR-542-3p overexpression inhibits the induction of major decidual marker genes, including IGFBP1, WNT4 and PRL. In addition, miR-542-3p overexpression inhibited the morphological transformation of HESCs in response to deciduogenic cues. A luciferase reporter assay confirmed that the 3'-untranslated region of IGFBP1 mRNA is targeted by miR-542-3p. The results suggest that miR-542-3p plays an important role in endometrial decidualization by regulating the expression of major decidual marker genes.

Aim: Outside of Japan, recombinant-human chorionic gonadotropin (r-hCG) is widely used for the induction of final follicular maturation and early luteinization in women undergoing ovulation induction; whereas in Japan, urine-derived hCG (u-hCG) is predominantly used. The primary objective of this study was to demonstrate the non-inferiority of r-hCG to u-hCG for ovulation induction, as assessed by the ovulation rate., Methods: This was an open-label, parallel-group, randomized, multicenter, phase III trial in Japanese women with anovulation or oligo-ovulation secondary to hypothalamic-pituitary dysfunction or polycystic ovary syndrome, undergoing ovulation induction with recombinant-human follicle-stimulating hormone. The women were randomized (2:1) to receive either a single 250 μg s.c. dose of r-hCG or a single 5000 IU i.m. dose of u-hCG for ovulation triggering., Results: Eighty-one women were randomized to either r-hCG (n=54) or u-hCG (n=27). Ovulation occurred in 100% of the participants and treatment with r-hCG was observed to be non-inferior to u-hCG for ovulation induction. Overall, the type and severity of adverse events were as expected for women receiving fertility treatment., Conclusion: This study demonstrated that r-hCG was non-inferior to u-hCG for inducing ovulation. Furthermore, r-hCG demonstrated an expected safety profile, with no new safety concerns identified.

Aim: This study evaluated the efficacy and safety of vaginal progesterone gel that was administered daily for luteal phase support as part of in vitro fertilization/embryo transfer (IVF/ET) cycles in Japanese women., Methods: This was a phase III, multicenter, open-label, single-arm trial in Japanese women undergoing IVF/ET, using the Japanese Society of Obstetrics and Gynecology 2009 registry as a historical control. The primary objective was to demonstrate the non-inferiority, with regard to the clinical pregnancy rate per ET, of vaginal progesterone gel that was administered once daily, compared with the historical standard value in IVF/ET cycles in Japan. The biochemical pregnancy (positive serum β-hCG pregnancy test but no clinical pregnancy) rate per ET also was investigated, as were the safety and tolerability of the vaginal progesterone gel., Results: Of the 178 women who were enrolled, 123 underwent IVF/ET. The clinical pregnancy rate per ET was non-inferior in the prospective arm, compared with the historical population. The biochemical pregnancy rate per ET was 7.3%. The safety profile of the vaginal progesterone gel was as expected, with no new safety issue identified., Conclusion: The vaginal progesterone gel was efficacious, with a safety profile as expected, in this study in Japanese women undergoing IVF/ET cycles.

Introduction: To elucidate whether trophoblast expansion and invasion are modulated by androgen signaling in an in vitro co-culture model system with decidualizing endometrial stromal cells (ESCs)., Methods: We employed an in vitro co-culture model of early embryo implantation, consisting of human ESCs (EtsT499 cells) and spheroids generated by extravillous trophoblast (EVT) derived HTR8/Svneo. The ESCs were decidualized with 8-bromo-cAMP (8-br-cAMP) in the presence or absence of dihydrotestosterone (DHT) at various concentrations for 5 days before co-culture with EVT spheroids. Trophoblast expansion was monitored by fluorescent time-lapse imaging microscopy. ESCs motility was visualized by using CellTracker™ Orange CMRA fluorescent probe. Apoptosis of ESCs was detected by CellEvent™ Caspase-3/7 ® green detection reagent. Invasion assays were performed to quantify EVT invasion through a chemotaxis cell membrane., Results: Expansion of EVT spheroids was significantly enhanced by decidualized compared to undifferentiated ESCs. This process was further stimulated if ESCs were first decidualized in the presence of DHT. In contrast to decidualized ESCs, undifferentiated cells actively migrated away from expanding EVT spheroids. Invasiveness of EVT toward decidualized ESCs was significantly attenuated in comparison to undifferentiated ESCs. DHT had no effect on EVT invasion. However, an inhibitor of intercellular gap junction communication significantly enhanced EVT invasion towards decidualized ESCs., Conclusions: These results indicate distinct roles for androgen signaling and gap junction formation in decidual cells in regulating trophoblast expansion and invasion., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Study Question: What were utilization, outcomes and practices in assisted reproductive technology (ART) globally in 2008, 2009 and 2010?, Summary Answer: Global utilization and effectiveness remained relatively constant despite marked variations among countries, while the rate of single and frozen embryo transfers (FETs) increased with a concomitant slight reduction in multiple birth rates., What Is Known Already: ART is widely practised in all regions of the world. Monitoring utilization, an approximation of availability and access, as well as effectiveness and safety is an important component of universal access to reproductive health., Study Design, Size, Duration: This is a retrospective, cross-sectional survey on utilization, effectiveness and safety of ART procedures performed globally from 2008 to 2010., Participants, Setting, Methods: Between 58 and 61 countries submitted data from a total of nearly 2500 ART clinics each year. Aggregate country data were processed and analyzed based on forms and methods developed by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). Results are presented at country, regional and global level., Main Results and the Role of Chance: For the years 2008, 2009 and 2010, >4 461 309 ART cycles were initiated, resulting in an estimated 1 144 858 babies born. The number of aspirations increased by 6.4% between 2008 and 2010, while FET cycles increased by 27.6%. Globally, ART utilization remained relatively constant at 436 cycles/million in 2008 and 474 cycles/million population in 2010, but with a wide country range of 8-4775 cycles/million population. ICSI remained constant at around 66% of non-donor aspiration cycles. The IVF/ICSI combined delivery rate (DR) per fresh aspiration was 19.8% in 2008; 19.7% in 2009 and 20.0% in 2010, with corresponding DRs for FET of 18.8, 19.7 and 20.7%. In fresh non-donor cycles, single embryo transfer increased from 25.7% in 2008 to 30.0% in 2010, while the average number of embryos transferred fell from 2.1 to 1.9, again with wide regional variation. The rates of twin deliveries following fresh non-donor transfers were, in 2008, 2009 and 2010, 21.8, 20.5 and 20.4%, respectively, with a corresponding triplet rate of 1.3, 1.0 and 1.1%. Fresh IVF and ICSI carried a perinatal mortality rate per 1000 births of 22.8 (2008), 19.2 (2009) and 21.0 (2010), compared with 15.1, 12.8 and 14.6/1000 births following FET in the same periods of observation. The proportion of women aged 40 years or older undergoing non-donor ART increased from 20.8 to 23.2% from 2008 to 2010., Limitations, Reason for Caution: The data presented are reliant on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of the world ART activity., Wider Implications of Findings: The ICMART World Reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment continues to increase globally, the wide disparities in access to treatment and embryo transfer practices warrant attention by clinicians and policy makers., Study Funding/competing Interests: The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART acknowledges financial support from the following organizations: American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Reproductive Technology; Government of Canada (Research grant), Ferring Pharmaceuticals (Grant unrelated to World Reports)., Trial Registration: not applicable., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The dielectric properties of complex plasma containing either metal or dielectric spherical inclusions (macroparticles, dust) are investigated. We focus on surface plasmon resonances on the macroparticle surfaces and their effect on electromagnetic wave propagation. It is demonstrated that the presence of surface plasmon oscillations can significantly modify plasma electromagnetic properties by resonances and cutoffs in the effective permittivity. This leads to related branches of electromagnetic waves and to the wave band gaps. The conditions necessary to observe the band-gap structure in laboratory dusty plasma and/or space (cosmic) dusty plasmas are discussed.

Objective: To investigate whether the introduction of single embryo transfer (SET) policy in Japan has improved perinatal outcomes., Design: A retrospective cohort study., Setting: Not applicable., Patient(s): A total of 140,718 live births and 510 stillbirths (after 22 weeks of gestation) conceived by assisted reproductive technology in Japan between 2007 and 2012 were reviewed., Intervention(s): None., Main Outcome Measure(s): Preterm birth (PTB), low birth weight (LBW), very low birth weight (VLBW), small for gestational age (SGA), large for gestational age (LGA), perinatal mortality, and other pregnancy complications., Result(s): The rate of SET increased significantly from 52.2% in 2007 to 82.6% in 2012, while the rate of multiple pregnancy decreased significantly from 10.7% to 4.1% over the same period. The rates of PTB, LBW, and SGA decreased significantly, while that of LGA increased. Perinatal mortality decreased from 0.70% to 0.40% in fresh cycles, while that of frozen cycles did not change. Double ET or more was associated with a significantly increased risk for multiple pregnancy, placenta accreta, preterm premature rupture of membrane, cesarean section (CS), PTB, LBW, SGA, and early neonatal death compared with SET. Compared with before the SET policy was launched, the risks of multiple pregnancy, CS, early PTB before 32 weeks, LBW, VLBW, and SGA were significantly decreased after the policy was launched, with significant interactions of fresh/frozen status., Conclusion(s): The results suggest that the SET policy improved perinatal outcomes in Japan. The impact of SET policy was different in fresh and frozen cycles for several perinatal outcomes., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The present study aimed to measure the levels of coagulation factors in stored whole blood of pregnant women and to determine their usefulness in treating pregnant women who developed coagulopathy. A prospective study to measure coagulation factors in stored donated whole blood from pregnant and non-pregnant women was conducted. Fibrinogen, FV, FVII, FVIII, FXIII, and von Willebrand factor were measured in blood stored at 4°C for 0, 1, 3, and 5 weeks. All coagulation factors except for factor XIII decreased during storage. Fibrinogen and factor VII in the blood collected from pregnant women gradually decreased over time and their levels were significantly higher after 5 weeks of storage than those of non-pregnant women at week 0. Whole blood donated by pregnant women for autologous blood transfusion and stored at 4°C may be expected being effectively for the prevention of coagulopathy and the treatment of circulatory blood volume loss.

To determine the efficacy of computed tomography (CT) attenuation of cystic lesions measured on an image browsing system to distinguish abscess from hematoma in women with acute abdomen. The medical records of female patients of reproductive age with acute abdomen who were treated over a 7-year period in a single center and who had undergone laparotomy or laparoscopic surgery and preoperative pelvic CT scanning were retrospectively analyzed to identify those with hematoma or abscess cyst formation. Nineteen patients with tubo-ovarian abscess (abscess group) and six patients with hematoma (hematoma group) formation in the pelvis were included in the analysis. The preoperative CT images of the tubo-ovarian cyst were retrospectively investigated on the basis of cyst attenuation. CT attenuation of the cyst measured by both two gynecologists could be used to clearly distinguish inflammatory disease with abscess formation from bleeding disease with hematoma. CT attenuation on a picture archiving and communication system can distinguish hematoma from abscess in women with acute abdomen. This may significantly contribute to making differential diagnosis without interpretation by a medical radiologist.

Previous study indicated that bleeding into the peritoneum may accelerate inflammatory response in endometriosis-like grafts in mice. To identify changes in protein levels in the grafts from mice that underwent unilateral ovariectomy (uOVX), which causes bleeding from ovarian arteries and vein, the grafts were generated by injecting a suspension of human endometrial cells in BALB/c nude female mice, and protein profile changes were compared with non-uOVX control mice. The level of α1-antitrypsin (α1-AT) decreased in grafts from nude mice that underwent uOVX. The levels of phosphorylated Akt, mammalian target of rapamycin, S6K, regulatory factors for cell survival, and of phosphorylated nuclear factor κB, an inflammatory mediator, were higher in endometriosis-like grafts from the uOVX group than from the control. The grafts were mostly comprised of stromal cells. The bioactivity of α1-AT was assessed by investigating cytokine expression in protease-activated receptor (PAR) 1/2 agonists-stimulated stromal cells. The PARs promoted the expression of interleukin 8 (IL-8), but treatment with α1-AT blocked IL-8 expression dose dependently. Knocking down α1-AT expression increased the constitutive IL-6, IL-8, and cyclooxygenase 2 expression as well as PAR1 agonist-stimulated IL-6 expression. These findings support the notion that decreased α1-AT protein in the grafts constituted with human endometrial cells in mice may have exacerbated inflammation in endometriosis-like grafts, suggesting the possible involvement of α1-AT in the pathophysiology of endometriosis., (© The Author(s) 2015.)

Aim: To evaluate whether the presence of amniotic components in the maternal uterine vasculature could be a specific pathological indicator for amniotic fluid embolism (AFE)., Methods: Medical records of patients treated between January 2006 and March 2013 were retrospectively examined to identify patients who underwent post-partum hysterectomy or autopsy due to maternal death. Three subjects with AFE with disseminated intravascular coagulation (DIC)-type post-partum hemorrhage (PPH), and 13 non-AFE subjects were included in analysis. Histochemical staining using hematoxylin-eosin (HE) and alcian blue, and immunohistochemical staining for sialyl-Tn were conducted to detect amniotic components in the maternal uterine vasculature., Results: Alcian blue was positive for amniotic components in the uterine vasculature of all subjects with AFE and of several subjects without AFE. Similarly, HE and sialyl-Tn were negative in some AFE subjects and positive in some non-AFE subjects., Conclusions: The presence of maternal intravascular fetal material is not a specific indicator for AFE with DIC-type PPH. Therefore, the presence of fetal components in the uterine vasculature is unlikely to be a definitive indicator for AFE., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

The expression of numerous microRNAs (miRNAs) in the trophoblasts changes under low oxygen conditions. However, little is known regarding the regulation of the trophoblast invasion by miRNAs under low oxygen conditions. The aim of this study was to identify those miRNAs and their target genes associated with the trophoblast invasion under low oxygen conditions. Culturing the extravillous trophoblast (EVT) cell line, HTR-8/SVneo, at 2% oxygen as compared to 20% oxygen suppressed trophoblast invasion that correlated with increased expression of microRNA-135b (miR-135b) and decreased expression of the its predicted target gene CXCL12. Overexpression of miR-135b suppressed CXCL12 mRNA expression and invasion of HTR-8/SVneo cells. Adding a neutralizing antibody against CXCL12 to the culture medium suppressed HTR-8/SVneo cell invasion. Reporter assays showed that the 3'UTR sequence of CXCL12 was directly targeted by miR-135b. Our results suggest that miR-135b and CXCL12 play important roles in modulating the EVT invasion under low oxygen conditions., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To analyze information on assisted reproductive technology (ART) performed worldwide, and trends in outcomes over successive years., Design: Cross-sectional survey on access, efficiency, and safety of ART procedures performed in 55 countries during 2007., Setting: Not applicable., Patient(s): Infertile women and men undergoing ART globally., Intervention(s): Collection and analysis of international ART data., Main Outcome Measure(s): Number of cycles performed, by country and region, including pregnancies, single and multiple birth rates, and perinatal mortality., Result(s): Overall, >1,251,881 procedures with ART were reported, and resulted in 229,442 reported babies born. The availability of ART varied by country, from 12 to 4,140 treatments per million population. Of all aspiration cycles, 65.2% (400,617 of 614,540) were intracytoplasmic sperm injection. The overall delivery rate per fresh aspiration was 20.3%, and for frozen-embryo transfer (FET), 18.4%, with a cumulative delivery rate of 25.8%. With wide regional variations, single-embryo transfer represented 23.4% of fresh transfers, and the proportion of deliveries with twins and triplets from fresh transfers was 22.3% and 1.2%, respectively. The perinatal mortality rate was 19.9 per 1,000 births for fresh in vitro fertilization using intracytoplasmic sperm injection, and 9.6 per 1,000 for FET. The proportion of women aged ≥40 years increased to 19.8% from 15.5% in 2006., Conclusion(s): The international trend toward <3 transferred embryos continued, as did the wider uptake of FET. This was achieved without compromising delivery rates. The application of ART for women aged >40 years was a major component of ART services in some regions and countries., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The pathogenesis of endometriosis remains poorly understood at least in part because early stages of the disease process are difficult to investigate. Previous studies have proposed a three-dimensional fibrin matrix culture model to study human endometriosis. We examined the ultrastructural features of the endometriosis in this model and assessed the effect of a progestin on endometrial outgrowth and apoptosis in this culture system. Endometrial explants were placed in three-dimensional fibrin matrix culture and treated with and without various concentrations of the progestin dienogest. By the second week, endometrial gland-like formation was established in outgrowths both attached to and at a distance from the explants. These cells formed a combination of clumps and tubular monolayers surrounding a central cavity. Electron microscopy demonstrated that these cells are polarized with microvilli on the apical surface, desmosome-like structures, and basement membrane; features consistent with glandular epithelial cells. Outgrowth of endometrial stromal cells and glandular formation was impaired in response to dienogest in a dose-dependent manner. Our study shows that the human endometrial explants cultured in three-dimensional fibrin matrix establish outgrowths that ultrastructurally resemble ectopic endometrial implants. This model may provide insight into the cellular processes leading to endometriosis formation and enables screening of therapeutic compounds.

Purpose: To assess the incidence of monozygotic twinning (MZT) among cases undergoing assisted reproductive technology (ART) treatment., Methods: We performed a retrospective observational study and analyzed the data of patients who were registered in the national ART registry system of Japan from January to December 2010; only the data of patients with single embryo transfer (ET) were included., Results: Of 30,405 pregnancies, 425 resulted in MZT following fresh and frozenthawed ET. The MZT incidence among women undergoing ART was 1.4 %. Multiple logistic regression analysis indicated that cases undergoing fresh and frozen-thawed ET, blastocyst transfer had a significantly increased MZT rate (P < 0.01). Assisted hatching (AH) and frozen-thawed ET and maternal age did not significantly affect the MZT incidence. Of 8510 fresh ET pregnancies, 104 resulted in MZT. Multiple logistic regression analysis indicated that blastocyst transfer significantly increased the MZT rate in cases undergoing fresh ET. Ovarian stimulation, intracytoplasmic sperm injection, AH, and maternal age did not significantly affect the MZT incidence., Conclusions: Blastocyst transfer was associated with an increased MZT incidence. We have to be aware of the potential risk of MZT caused by blastocyst transfer. However, further studies are required to assess the correlation among specific AH types, embryo culture conditions, and MZT incidence.

Study Question: What are the access, effectiveness and safety of assisted reproductive technology (ART) worldwide in 2006?, Summary Answer: ART access, effectiveness and safety vary markedly among countries. Overall, there was an increase in the use of ICSI, single embryo transfer (SET) and frozen embryo transfer (FET). There was a decline in the multiple delivery rate (DR) and preterm birth rate., What Is Known Already: ART is widely practiced worldwide and there is a need for its continuous monitoring to improve the comprehensiveness and quality of ART data and services., Study Design, Size, Duration: This is a retrospective, cross-sectional survey of ART cycles undertaken worldwide in 2006., Participants, Setting, Methods: A total of 2352 clinics in 56 countries provided data. Data were analyzed at a country and regional level. The forms for data collection were developed by the International Committee Monitoring Assisted Reproductive Technologies (ICMART) and sent to each country or regional ART register., Main Results and the Role of Chance: A total of >1,050,300 initiated cycles resulted in an estimated >256,668 babies. The overall pregnancy rates (PRs) and DRs per aspiration for IVF were 30.7 and 22.8%, respectively, and for ICSI 29.7 and 20.0%, respectively. The PRs and DRs for FETs were 26.4 and 17.8%, respectively. Multiple DR per PR were 22.2% for twins and 1.5% for triplets following fresh IVF/ICSI and 16.4% for twins and 0.8% for triplets for FETs. Ovarian hyperstimulation syndrome complicated >4585 cycles (0.6%). Access to ART varied from 11 to 3988 cycles per million population. ICSI comprised 66.0% of all initiated cycles, FET 27.4% and SET 20.7%. Perinatal mortality rate was 25.2 per 1000 births for fresh IVF/ICSI and 17.5 per 1000 for FETs., Limitations, Reasons for Caution: 44.6% of the countries provided incomplete data. Quality of data varies among individual countries and is dependant on the policy of the local regulatory authority for monitoring ART clinics. Continuous efforts are needed to improve comprehensiveness and quality of data collected., Wider Implications of the Findings: Adopting the policy of SET, FET and the cessation of transferring more than two embryos should be widely applied. ICMART will continue helping countries and regions to establish their own ART registries., Study Funding/competing Interest(s): ICMART receives financial support from medical societies: European Society for Human Reproduction and Embryology (ESHRE), American Society for Reproduction Medicine (ASRM), Fertility Society of Australia (FSA), Japan Society for Reproductive Medicine (JSRM), Latin American Network for Reproductive Medicine (REDLARA) and Middle East Fertility Society (MEFS) and Society for Assisted Reproductive Technology (SART). All authors have no conflict of interest in relation to this work. We declare no support or financial relationship with any organizations or any activities that could appear to have influenced the submitted work.

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., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Aim: The aim of this study was to assess the efficacy of assisted hatching (AH) in assisted reproductive technology (ART) treatment., Material and Methods: In this retrospective observational study, the data of patients who were registered in the National ART Registry System of Japan between January and December 2010 were analyzed. The descriptive statistics and validity of AH in fresh embryo transfer (ET) and frozen-thawed ET were assessed by using multiple logistic regression analyses., Results: From a total of 105,450 single ET, 46,029 (43.7%) cycles underwent AH. A total of 9737 (21.3%) and 36,292 (60.9%) cycles underwent AH from 45,818 fresh single ET and 59,632 frozen-thawed single ET, respectively. In the fresh ET patients that underwent AH, the clinical pregnancy and live birth rate were significantly decreased in patients of all ages compared with that of the non-AH group. In the frozen-thawed ET patients, there was no significant difference in pregnancy and live birth rate between the AH group and the non-AH group., Conclusion: AH treatment was more frequently performed in frozen-thawed ET patients than in fresh ET patients, and in the blastocyst stage than in the early cleavage stage. A significantly decreased pregnancy and live birth rate was observed in the fresh ET patients who underwent AH. In the frozen-thawed ET patients who underwent AH, improvement in the clinical pregnancy and live birth rate was not observed. Further studies on the indication and application of AH in ART treatment are required., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Aim: The aim of this study was to calculate and assess the cost of assisted reproductive technology (ART) treatment cycles and live-birth events in Japan in 2010., Material and Methods: We performed a retrospective analysis of 238,185 ART cycles, registered with the national registry of assisted reproductive treatment during 2010. Costs were calculated, using a decision analysis model., Results: The average cost per live birth was ¥1,974,000. This varied from ¥1,155,000 in women aged < 30 years to ¥50,189,000 in women aged ≥ 45, which was 29.6 times higher than that of women aged 35-39 years. This rose sharply in the early 40s and upwards. Public funding per live birth was ¥442,000. This was ¥6,118,000 in women aged ≥ 45, 15.4 times higher than that of the 35-39-year-old age group., Conclusions: The costs and public funding of a live birth after ART treatment rises with age due to the lower success rates in older women. It may provide economic background to improve the current subsidy system for ART and to provide practical knowledge about fertility for the general population., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Purpose: This study aimed to evaluate the efficacy, safety, and trends in assisted reproductive technology (ART) in Japan., Methods: Data pertaining to treatment cycles, pregnancy rate, live birth rate, age distribution, single embryo transfer rate, and multiple pregnancy rate were analyzed for patients registered in the national ART registry system of Japan from 2007 to 2010., Results: The total number of treatment cycles was 161,164, 190,613, 213,800, and 242,161 in 2007, 2008, 2009, and 2010, respectively. The number of ART treatments administered to patients aged ≥40 years was 31.2 %, 32.1 %, 33.4 %, and 35.7 %, respectively, showing an increasing trend from 2007 to 2010. In each of these years, the total pregnancy rate per embryo transfer was 24.4 %, 21.9 %, 22.3 %, and 21.9 % for fresh cycles, respectively, and 32.0 %, 32.1 %, 32.5 %, and 33.7 % for frozen cycles, respectively. The single embryo transfer rate was 49.9 %, 63.6 %, 70.6 %, and 73.0 %, respectively, showing an increasing trend, while the multiple pregnancy rate was 11.5 %, 6.8 %, 5.3 %, and 4.8 %, respectively, showing a decreasing trend., Conclusions: From 2007 to 2010 in Japan, the number of ART treatment cycles, number of elderly patients treated, and the single embryo transfer rate increased, while the multiple pregnancy rate decreased. However, the overall pregnancy rate remained stable during the study period.

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.

The Japan Society of Obstetrics and Gynecology Reproductive Endocrinology Committee summarizes the activities of each subcommittee below from April 2011 to March 2013. 1. Survey for clinical outcomes of infertility treatment for women with adenomyosis and complications of pregnant women with adenomyosis. 2. Survey for multiple pregnancies after controlled ovarian stimulation in non-assisted-reproductive-technology infertility treatment cycles: population-based study in Japan. 3. Study on the effect of endometriosis management on ovarian reserve., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Objective: To analyze information on assisted reproductive technology (ART) performed worldwide and trends in outcomes over successive years., Design: Cross-sectional survey on access, effectiveness, and safety of ART procedures performed in 53 countries during 2005., Setting: A total of 2,973 clinics from national and regional ART registries., Patient(s): Infertile women and men undergoing ART globally., Intervention(s): Collection and analysis of international ART data., Main Outcome Measure(s): Number of cycles performed by country and region, including pregnancies, single and multiple birth rates, and perinatal mortality., Result(s): Overall, 1,052,363 ART procedures resulted in an estimated 237,315 babies born. The availability of ART varied by country from 15 to 3,982 cycles per million of population. Of all initiated fresh cycles, 62.9% were intracytoplasmic sperm injection. The overall delivery rate per fresh aspiration was 19.6% and for frozen embryo transfer 17.4%, with a cumulative delivery rate of 23.9%. With wide regional variations, single embryo transfer represented 17.5% of cycles, and the proportion of deliveries with twins and triplets from fresh transfers was 23.6% and 1.5%, respectively., Conclusion(s): Systematic collection and dissemination of international ART data allows patients, health professionals, and policy makers to examine and compare the impact of reproductive strategies or lack of them as markers of reproductive health., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To systematically quantify the impact of consumer cost on assisted reproduction technology (ART) utilization and numbers of embryos transferred., Design: Ordinary least squared (OLS) regression models were constructed to measure the independent impact of ART affordability-measured as consumer cost relative to average disposable income-on ART utilization and embryo transfer practices., Setting: Not applicable., Patient(s): Women undergoing ART treatment., Intervention(s): None., Main Outcome Measure(s): OLS regression coefficient for ART affordability, which estimates the independent effect of consumer cost relative to income on utilization and number of embryos transferred., Result(s): ART affordability was independently and positively associated with ART utilization with a mean OLS coefficient of 0.032. This indicates that, on average, a decrease in the cost of a cycle of 1 percentage point of disposable income predicts a 3.2% increase in utilization. ART affordability was independently and negatively associated with the number of embryos transferred, indicating that a decrease in the cost of a cycle of 10 percentage points of disposable income predicts a 5.1% increase in single-embryo transfer cycles., Conclusion(s): The relative cost that consumers pay for ART treatment predicts the level of access and number of embryos transferred. Policies that affect ART funding should be informed by these findings to ensure equitable access to treatment and clinically responsible embryo transfer practices., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the relationship between frozen-thawed single blastocyst transfer (BT) and maternal and neonatal outcomes of pregnancy., Design: Retrospective analysis., Setting: Japanese nationwide registry of assisted reproductive technology (ART) with mandatory reporting for all ART clinics in Japan., Patient(s): Registered from 2008 through 2010 undergoing single embryo transfer cycles (n = 277,042)., Intervention(s): None., Main Outcome Measure(s): Rates 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., Result(s): Frozen-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., Conclusion(s): Frozen-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., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The dynamic circulation of dust particles in a cylindrical complex plasma is studied experimentally. A levitated cloud of charged dust particles rotates around an axis in an ion flow induced by the coupling of applied magnetic field with the electric field due to plasma density gradient. The vertical and horizontal cross sections of the cloud reveal the dynamic circulation with helical trajectories of dust particles with meridional ascending motion near the axis. The dust particles in the center bottom in the cloud remain near a stagnation point and act like tea leaves in a teacup as described by Einstein in 1926.

Successful pregnancy requires coordination of embryo development, decidualization of endometrium, and placenta formation. Decidualization denotes the transformation of endometrial stromal cells into specialized secretory cells, a process further characterized with influx of specialized immune cells into stroma, predominantly uterine natural killer cells and macrophages, and vascular remodeling. This differentiation process depends on the convergence of the cyclic adenosine monophosphate and progesterone signaling pathways. The decidual process is indispensable for the formation of a functional feto-maternal interface as it controls tissue homeostasis during endovascular trophoblast invasion and bestows tissue resistance to environmental stress signals, including protection against oxidative cell death. FOXO proteins have emerged as key mediators of cell fate because of their ability to regulate either pro-apoptotic genes or genes involved in differentiation, cell cycle arrest, oxidative defenses, and DNA repair. In the endometrium, FOXO1 is of particular importance as a critical regulator of progesterone-dependent differentiation, menstrual shedding, and protection of the feto-maternal against oxidative damage during pregnancy.

Study Question: Have changes in assisted reproductive technology (ART) practice and outcomes occurred globally between 2003 and 2004?, Summary Answer: Globally, ART practice has changed with an increasing prevalence of the use of ICSI rather than conventional IVF. In 2004, a small but increasing number of countries are incorporating single embryo transfer. There remain unacceptably high rates of three or more embryo transfers in select countries resulting in multiple births and adverse perinatal outcomes., What Is Known Already: World data on the availability, effectiveness and safety of ART have been published since 1989. The number of embryos transferred is a major determinant of the iatrogenic increase in multiple pregnancies and is highly correlated with the likelihood of multiple birth and excess perinatal morbidity and mortality., Study Design, Size, Duration: Cross-sectional survey of countries and regions undertaking surveillance of ART procedures started in 2004 and their corresponding outcomes., Participants/materials, Setting, Methods: Of total, 2184 clinics from 52 reporting countries and regions. Number of ART clinics, types of cycles and procedures, pregnancy, delivery and multiple birth rates and perinatal outcomes., Main Results and the Role of Chance: A total of 954 743 initiated cycles resulted in an estimated 237 809 babies born. This was a 2.3% increase in the number of reported cycles from 2003. The availability of ART varied by country and ranged from 14 to 3844 treatment cycles per million population. Over one-third (37.2%) of ART clinics performed <100 cycles per year with only 19.9% performing ≥ 500 cycles per year. Of all cycles, 60.6% were ICSI. Frozen embryo transfers (FETs) represented 31% of the initiated cycles. The overall delivery rate per fresh aspiration for IVF and ICSI was 20.2% compared with 16.6% per FET. The average number of embryos transferred was 2.35. Single (16.3%) and double embryo transfers accounted for 73.2% of cycles. The overall proportion of deliveries with twins and triplets from IVF and ICSI was 25.1 and 1.8%, respectively, but varied widely by country and region. The proportion of premature deliveries per fresh aspiration for IVF and ICSI was 33.7% compared with 26.3% per FET. The perinatal death rate was 25.8 per 1000 births for fresh aspiration for IVF and ICSI compared with 14.2 per 1000 births per FET., Limitations, Reasons for Caution: Data are incomplete with seven countries not providing data to the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in 2004 that had in 2003. The validity of data reflects current data collection practice. In 2004, 79.3% of the clinics in participating countries reported to their national or regional registries and to ICMART. In addition, the number of ART cycles per million population is a measure which is affected by a country's government policy, regulation, funding and the number of service providers., Wider Implications of the Findings: ART practice, effectiveness and outcomes vary markedly internationally. Notably, the increasing proportion of cycles that are FET, the change in practice to single embryo transfer and the cessation of the transfer of three or more embryos in some countries has resulted in improved perinatal outcomes with minimal impact on pregnancy rates., Study Funding/competing Interest(s): ICMART receives financial support from ASRM, ESHRE, FSA, Japan Society for Reproductive Medicine, REDLARA, MEFS and SART.

Aim: 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., Material and Methods: Eighteen cases of coagulopathy (8 dilutional, 10 consumptive) administered fibrinogen concentrate at our center over the past 5 years for treating hypofibrinogenemia were identified. Hemoglobin levels, platelet counts, fibrinogen levels, prothrombin time, activated partial thromboplastin time, and D-dimer levels were examined before and after fibrinogen substitution. Units of red blood cells, fresh frozen plasma, and pooled platelet concentrates transfused; blood loss volume; patient outcomes; and adverse events were obtained from medical and laboratory records., Results: The overall response to fibrinogen concentrate was considered good in 12 cases, moderate in four, and poor in two. The response rate was good or moderate in 88% (7/8) of dilutional coagulopathy cases and 89% (9/10) of consumptive coagulopathy cases. Fibrinogen levels significantly increased after fibrinogen substitution therapy (approximately 40 mg/L per g fibrinogen concentrate) in both groups. Although prothrombin time and activated partial thromboplastin time improved after substitution, hemoglobin levels, platelet counts, and D-dimer levels remained unchanged. No serious adverse event was causally associated with fibrinogen substitution therapy., Conclusion: Fibrinogen concentrate substitution therapy for obstetric hemorrhage increases fibrinogen levels and appears to be effective in managing dilutional or consumptive coagulopathy., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Objective: To evaluate the implications of assisted reproductive technologies (ART) on neonatal birth weight., Design: A retrospective study using analysis of covariance and multiple logistic regression analysis of the Japanese ART registry., Setting: Japanese institutions providing ART treatment., Patient(s): A total of 25,777 singleton neonates reaching term gestation following ART during the years 2007-2008, with 11,374 achieved through fresh embryo transfers (fresh ET) and 14,403 achieved through frozen-thawed embryo transfers (FET)., Intervention(s): None., Main Outcome Measure(s): Birth weight., Result(s): The mean birth weight after FET was significantly higher compared with fresh ET and all Japanese births (3,100.7 ± 387.2 g, 3,009.8 ± 376.8 g, and 3,059.6 ± 369.6 g, respectively). The risk for low birth weight in FET was significantly lower compared with fresh ET. In fresh ET, ovarian stimulations were associated with about twofold risk of low birth weight compared with natural cycle. Regarding to the duration of embryonic culture, the risks resulting from a shorter culturing time were significantly higher compared with a longer culturing time in fresh ET., Conclusion(s): The best method of embryo transfer for fetal growth was FET after extended culturing until blastocyst stage. However, further investigations should be performed to understand the safety of ART treatment., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries. Here we describe and validate a fluorescence-activated cell sorting-based protocol that can be used with adult mouse ovaries and human ovarian cortical tissue to purify rare mitotically active cells that have a gene expression profile that is consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and can spontaneously generate 35- to 50-μm oocytes, as determined by morphology, gene expression and haploid (1n) status. Injection of the human germline cells, engineered to stably express GFP, into human ovarian cortical biopsies leads to formation of follicles containing GFP-positive oocytes 1-2 weeks after xenotransplantation into immunodeficient female mice. Thus, ovaries of reproductive-age women, similar to adult mice, possess rare mitotically active germ cells that can be propagated in vitro as well as generate oocytes in vitro and in vivo.

A bow shock is observed in a two-dimensional supersonic flow of charged microparticles in a complex plasma. A thin conducting needle is used to make a potential barrier as an obstacle for the particle flow in the complex plasma. The flow is generated and the flow velocity is controlled by changing a tilt angle of the device under the gravitational force. A void, microparticle-free region, is formed around the potential barrier surrounding the obstacle. The flow is bent around the leading edge of the void and forms an arcuate structure when the flow is supersonic. The structure is characterized by the bow shock as confirmed by a polytropic hydrodynamic theory as well as numerical simulation.

Structures of Coulomb clusters formed by dust particles in a plasma are studied by numerical simulation. Our study reveals the presence of various types of self-organized structures of a cluster confined in a prolate spheroidal electrostatic potential. The stable configurations depend on a prolateness parameter for the confining potential as well as on the number of dust particles in a cluster. One-dimensional string, two-dimensional zigzag structure and three-dimensional double helical structure are found as a result of the transition controlled by the prolateness parameter. The formation of stable double helical structures resulted from the transition associated with the instability of angular perturbations on double strings. Analytical perturbation study supports the findings of numerical simulations.

Objective: To investigate the effect of androgens on the expression of genes involved in oxidative stress resistance in decidualized human endometrial stromal cells (HESCs)., Design: In vitro experiment., Setting: University hospital., Patient(s): Premenopausal women undergoing hysterectomy for uterine fibroids., Intervention(s): Human 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., Main Outcome Measure(s): Prolactin secretion, apoptosis, FOXO1, and the free radical scavengers superoxide dismutase 2 (SOD2) and SOD1 protein expression., Result(s): Prolactin 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., Conclusion(s): Androgens might play a critical role in the decidualization process at the time of embryo implantation and trophoblast invasion by promoting resistance to oxidative stress., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Tubal choriocarcinoma is an extremely rare condition and can be of gestational or non-gestational origin. The appropriate management of choriocarcinoma begins with the categorization of the tumor. However, it is difficult to discriminate the two types by routine histological examination. We report the first case of gestational choriocarcinoma of the Fallopian tube to be confirmed by a combination of p57(KIP2) immunostaining and DNA polymorphism analysis at 15 short tandem repeat loci, along with X and Y chromosome markers. The patient had no detectable metastasis or evidence of recurrence 15 months after treatment, which involved surgery without adjuvant chemotherapy. This case demonstrates the usefulness of a combination of p57(KIP2) immunostaining and DNA polymorphism analysis in determining the origin of extrauterine choriocarcinoma (i.e. gestational or non-gestational), which helps to determine the strategy for treatment of the disease., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

Human chorionic gonadotropin (hCG) is one of the earliest signals secreted by the implanting embryo. In addition to its well-known luteotropic function in early pregnancy, hCG also acts directly on decidualizing endometrium. Recently, we demonstrated that recombinant hCG (rhCG) prevented apoptosis in decidualizing human endometrial stromal cells (HESCs) exposed to oxidative stress. Two hCG preparations are widely used clinically: rhCG, produced by recombinant DNA technology, and urinay hCG (uhCG), extracted from urine of post-menopausal women. However, an analysis of the direct effects of rhCG and uhCG on the decidual phenotype of HESCs has not yet been done. In this study, we investigated the effects of uhCG and rhCG on the morphological and functional profiles of decidualizing HESCs. We demonstrate that neither rhCG nor uhCG alter the morphological appearance of the decidual HESC cultures, although rhCG but not uhCG attenuated prolactin expression, a major decidual marker protein. Moreover, rhCG, but not uhCG, protected decidualizing HESCs from oxidative cell death, mediated at least in part by two major mechanisms. First, rhCG, but not uhCG, enhances the expression of manganese superoxide dismutase, a cardinal enzyme in the cellular defense against oxidative damage. Second, rhCG signaling selectively limits activation of the apoptotic machinery in decidualizing HESCs by enhancing Bcl-2 expression whereas uhCG induces the expression of Fas ligand. Our results suggest that rhCG might be a preferable agent to protect the maternal decidua against oxidative damage in pregnancy, especially at the time of implantation and beyond., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Free fetal DNA (ffDNA) in maternal plasma has now become a valuable source for noninvasive prenatal diagnosis. Being able to accurately identify the size of ffDNA in maternal plasma is essential for a noninvasive prenatal diagnosis. Furthermore, it is important to investigate the molecular characteristics related to apoptosis which gives rise to ffDNA. We investigated the fragment size of ffDNA in each sample more precisely, using both Y-STR and SRY primers, in 20 maternal plasma samples from the 17th to 39th weeks of gestation. PCR was conducted with Y-STR and SRY primers which can be used to amplify 100-524 bp fragments. In samples from 10 pregnant women carrying male fetuses, the maximum fragment size detected by Y-STR and SRY primers ranged from 219 to 313 bp. As a result, the mean average maximum fragment size of free fetal DNA detected by Y-STR and SRY primers was 286 +/- 28 bp. The Y-STR alleles detected in each maternal plasma DNA sample were all in agreement with the results of their cord blood samples. We concluded that the fragment size of ffDNA comprises 2 nucleosomal complexes or less, but not exceeding 3.

The Great Eastern Japan Earthquake of 2011 and consequent tsunami affected many IVF clinics in northeastern Japan. Twelve clinics lost at least one embryo, but all the frozen embryos stored in liquid nitrogen tanks were safe. Emergency power supply is the first priority issue in an unpredictable natural disaster., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze information on assisted reproductive technologies (ART) performed globally., Design: Data on access, efficacy, and safety of ART were collected for the year 2003 from 54 countries., Setting: National and regional ART registries globally., Patient(s): Patients undergoing ART globally., Intervention(s): Collection and analysis of international ART registry data., Main Outcome Measure(s): Number of cycles performed in reporting countries and regions globally for different ART procedures with resulting pregnancy, live birth and multiple birth rates., Result(s): A total of 433,427 initiated cycles reported in this registry resulted in 173,424 babies born. This corresponded to a delivery rate per aspiration of 22.4% for in vitro fertilization (IVF), 23.3% for intracytoplasmic sperm injection (ICSI), and a delivery rate per transfer of 17.1% for frozen embryo transfer. Although there is wide variation among countries and regions, the overall proportion of deliveries with twins and triplets from IVF and ICSI was 24.8% and 2.0%, respectively. There were wide variations in access, and compared with the previous report (year 2002), there was a 3.9% increase in the number of reported cycles and a minor increase in the delivery rate per aspiration. There was also a marginal decline in the mean number of embryos transferred and in the rate of multiple births., Conclusion(s): ART access, efficacy, and safety varies greatly globally. Collection and analysis of data over time will benefit ART patients, providers, and policy makers., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of frozen-thawed blastocyst transfer on ectopic pregnancy (EP) rate., Design: Retrospective analysis., Setting: Japanese registry of assisted reproductive medicine., Patient(s): Women who were registered during 2008., Intervention(s): None., Main Outcome Measure(s): Rates of live birth, EP, and spontaneous abortion in single blastocyst and cleavage-stage ET cycles in both fresh and frozen-thawed were determined., Result(s): In the frozen-thawed single blastocyst transfer cycles, 84 EPs of 10,312 clinical pregnancies (0.81%) were reported. There were 25 EPs of 1,361 clinical pregnancies (1.8%) in fresh IVF single blastocyst transfer cycles and 19 of 1,352 (1.4%) in fresh intracytoplasmic sperm injection single blastocyst transfer cycles. The rate of EPs after frozen-thawed single blastocyst transfers varied between 0.56% and 0.97% after stratification by age group., Conclusion(s): Frozen-thawed blastocyst transfers have reduced EP rates significantly compared with fresh blastocyst transfers., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of hCG on the expression of genes involved in oxidative stress resistance observed in decidualizing human endometrial stromal cells (HESCs)., Design: In vitro experiment., Setting: Saitama Medical University hospital., Patient(s): Premenopausal women undergoing hysterectomy for myoma uteri., Intervention(s): HESCs 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)., Main Outcome Measure(s): Apoptotic cells, FOXO1, superoxide dismutase 2 (SOD2), Bax, and Bcl-2 protein expression., Result(s): In 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., Conclusion(s): The data suggest that hCG might improve the uterine environment upon implantation by suppressing apoptotic responses in the maternal decidua under oxidative stress., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Bisphenol A (BPA) is a monomer used in manufacturing a wide range of chemical products, including epoxy resins and polycarbonate. BPA, an important endocrine disrupting chemical that exerts estrogen-like activities, is detectable at nanomolar levels in human serum worldwide. The pregnancy associated doses of 17beta-estradiol (E2) plus tumor-necrosis factor-alpha (TNF-alpha) induce distorted maturation of human dendritic cells (DCs) that result in an increased capacity to induce T helper (Th) 2 responses. The current study demonstrated that the presence of BPA during DC maturation influences the function of human DCs, thereby polarizing the subsequent Th response. In the presence of TNF-alpha, BPA treatment enhanced the expression of CC chemokine ligand 1 (CCL1) in DCs. In addition, DCs exposed to BPA/TNF-alpha produced higher levels of IL-10 relative to those of IL-12p70 on CD40 ligation, and preferentially induced Th2 deviation. BPA exerts the same effect with E2 at the same dose (0.01-0.1 microM) with regard to DC-mediated Th2 polarization. These findings imply that DCs exposed to BPA will provide one of the initial signals driving the development and perpetuation of Th2-dominated immune response in allergic reactions.

Purpose: To study the correlation between stress urinary incontinence (SUI) and the mobility and funneling of the bladder neck (BN) by observation of pre- and postoperative course by perineal ultrasound (PUS)., Methods: We investigated 123 cases that underwent reconstructive surgery for pelvic organ prolapse (POP). We prospectively checked bladder neck mobility (BNM) during the Valsalva maneuver and funneling of the BN at rest by PUS. We defined the width multiplied by the depth of the funnel-like profile of the BN as the funneling index (FI). We checked BNM, FI, and the presence of SUI just before the operation, and we checked the postoperative course of BNM and SUI., Results: When BNM was ≥10 mm before surgery, the odds ratio for accompanying SUI was 2.68 relative to BNM <10 mm (p = 0.031). When FI was ≥150 before surgery, the odds ratio for accompanying SUI was 4.12 relative to FI <150 (p = 0.004). Although postoperative BNM values were significantly improved immediately after surgery, they gradually increased within 2 years. Among the cases with preoperative SUI, the recurrence rate was significantly higher in the patients whose FI was <150 (p = 0.019)., Conclusions: Our results yielded by PUS suggested that larger BNM and FI values were the causative factors of SUI. PUS may be beneficial for selecting a suitable surgical procedure for POP, and it may also be helpful for assessing surgical efficacy.