[Show abstract][Hide abstract] ABSTRACT: To assess the incidence of monozygotic twinning (MZT) among cases undergoing assisted reproductive technology (ART) treatment.
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.
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.
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.
Journal of Assisted Reproduction and Genetics 04/2014; · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to evaluate the efficacy, safety, and trends in assisted reproductive technology (ART) in Japan.
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.
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.
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.
Journal of Assisted Reproduction and Genetics 02/2014; · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a paucity of information on perinatal data regarding gestational diabetes mellitus (GDM) by the new criteria from a real experience because the number of health care associations implementing the new criteria is still limited. The aim of this study is to investigate perinatal features of the new criteria-defined GDM. We reviewed a total of 995 women with singleton pregnancy that underwent GDM screening followed by a diagnostic oral glucose tolerance test (OGTT). All women found to have GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. Of the 995 women, 141 had GDM (14.2%): 104 with one, 27 with two, and 10 with three abnormal OGTT values. Women with two or three abnormal OGTT values needed insulin treatment more frequently than those with one abnormal OGTT value (1-AV) (70.3% vs 23.1%, P < 0.0001). After adjustment for age, pregravid overweight, gestational weeks at diagnosis, a first-degree family history of diabetes was correlated with the implementation of insulin treatment in women with 1-AV (adjusted odds ratio 3.9; 95% Confidence Interval 1.7-9.2; P = 0.001). When compared perinatal outcomes between women with normal glucose tolerance and GDM, fetal growth and the occurrence of pregnancy-induced hypertension were comparable between the two groups. Our data suggest that the IADPSG-defined GDM with 1-AV show less severe glucose intolerance, but might be at risk of insulin requirement when a first-degree family history of diabetes exists.
[Show abstract][Hide abstract] ABSTRACT: We induced differentiation of human amnion-derived mesenchymal stem cells (AMCs) and menstrual blood-derived mesenchymal stem cells (MMCs) into endometrial stroma-like cells, which could be useful for cell therapy to support embryo implantation. Interestingly, the expression patterns of surface markers were similar among AMCs, MMCs, and endometrial stromal cells. In addition, whereas treatment with estrogen and progesterone was not very effective for decidualizing AMCs and MMCs, treatment with 8-Br-cAMP prompted remarkable morphological changes in these cells as well as increased expression of decidualization markers (prolactin and insulin-like growth factor binding protein-1) and attenuated expression of surface markers unique to mesenchymal stem cells. These results demonstrated that bone marrow-derived stem cells, which are considered a potential source of endometrial progenitor cells, as well as AMCs and MMCs show in vitro decidualization potential, which is characteristic of endometrial stromal cells.
[Show abstract][Hide abstract] ABSTRACT: Recently, infertility treatment-related psychological effects are receiving increased attention. However, whether sexual satisfaction is reduced amongst infertile couples remains to be elucidated. In this study, sexual satisfaction of Japanese infertile couples was assessed using a validated questionnaire designed to assess the male and female partner individually, and the couple as a whole for the first time. This study randomly included 170 infertile couples seen at the outpatient clinic and 170 couples that had recently achieved spontaneous pregnancy. All couples were given the Japanese version of the Golombok-Rust Inventory of Sexual Satisfaction (GRISS). In couples aged 35 years or older, the male partners showed significantly worse sexual satisfaction scores than the female partners. Sexual satisfaction also deteriorated with therapeutic interventions, with mental factors affected more than physical factors. Therapeutic interventions such as timed sexual intercourse and assisted reproductive technology were considered emotionally stressful for infertile couples, with sexual satisfaction accordingly lower in this group than in couples achieving spontaneous pregnancy. GRISS successfully evaluated lower sexual satisfaction associated with infertility, and hence is a useful tool for identifying couples whose sexual satisfaction could be enhanced by counselling or other stress-reduction modalities.
[Show abstract][Hide abstract] ABSTRACT: Objective
To clarify the molecular basis of hypogonadotropic hypogonadism (HH).
Genome-wide copy number analysis by array-based comparative genomic hybridization and systematic mutation screening of 29 known causative genes by next-generation sequencing, followed by in silico functional assessment and messenger RNA/DNA analyses of the mutants/variants.
Fifty-eight patients with isolated HH (IHH), combined pituitary hormone deficiency (CPHD), and syndromic HH.
Main Outcome Measure(s)
Frequency and character of molecular abnormalities.
Pathogenic defects were identified in 14 patients with various types of HH, although oligogenicity was not evident in this patient group. As rare abnormalities, we identified a submicroscopic deletion involving FGFR1 and an SOX3 polyalanine deletion in patients with IHH, and a WDR11 splice site mutation in a patient with CPHD. No disease-associated polymorphism was detected in the 58 patients.
The present study provides further evidence that mutations and deletions in the known causative genes play a relatively minor role in the etiology of HH and that submicroscopic rearrangements encompassing FGFR1 can lead to IHH as a sole recognizable clinical feature. Furthermore, the results indicate for the first time that polyalanine deletions in SOX3 and mutations in WDR11 constitute rare genetic causes of IHH and CPHD, respectively.
Fertility and Sterility. 01/2014; 102(4):1130-1136.
[Show abstract][Hide abstract] ABSTRACT: Oocytes may undergo two types of aging. The first is induced by exposure to an aged ovarian microenvironment before being ovulated, known as 'reproductive or maternal aging', and the second by either a prolonged stay in the oviduct before fertilization or in vitro aging prior to insemination, known as 'postovulatory aging'. However, the molecular mechanisms underlying these aging processes remain to be elucidated. As telomere shortening in cultured somatic cells triggers replicative senescence, telomere shortening in oocytes during reproductive and postovulatory aging may predict developmental competence. This study aimed to ascertain the mechanisms underlying altered telomere biology in mouse oocytes during reproductive and postovulatory aging.
We studied Tert expression patterns, telomerase activity, cytosolic reactive oxygen species (ROS) production, and telomere length in fresh oocytes from young versus reproductively-aged female mice retrieved from oviducts at 14 h post-human chorionic gonadotropin (hCG), in vivo or in vitro postovulatory-aged mouse oocytes at 23 h post-hCG. Oocytes were collected from super-ovulated C57BL/6 J mice of 6--8 weeks or 42--48 weeks of age. mRNA and protein expressions of the Tert gene were quantified using real-time quantitative reverse transcriptase polymerase chain reaction (Q-PCR) and immunochemistry. Telomerase activity was measured by a telomeric repeat amplification protocol assay, while telomere length was measured by Q-PCR and quantitative fluorescence in situ hybridization analyses.
The abundance of Tert expression in oocytes significantly decreased during reproductive and postovulatory aging. Immunofluorescent staining clearly demonstrated an altered pattern and intensity of TERT protein expression in oocytes during reproductive aging. Furthermore, relative telomerase activity (RTA) in oocytes from reproductively-aged females was significantly lower than that in oocytes from young females. In contrast, RTA in postovulatory-aged oocytes was similar to that in fresh oocytes. Oocytes from reproductively-aged females and postovulatory-aged oocytes showed higher ROS levels than oocytes from young females. Relative telomere length (RTL) was remarkably shorter in oocytes from reproductively-aged females compared to oocytes from young females. However, postovulatory aging had no significant effect on RTL of oocytes.
Long-term adverse effects of low telomerase activity and increased ROS exposure are likely associated with telomere shortening in oocytes from reproductively-aged female mice.
Reproductive Biology and Endocrinology 11/2013; 11(1):108. · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.
[Show abstract][Hide abstract] ABSTRACT: To investigate the correlation between the ooplasmic volume and the number of mitochondrial DNA (mtDNA) copies in embryos and how they may affect fecundity.
Using real-time PCR, mtDNA quantification was analyzed in unfertilized oocytes and uncleaved embryos. The size of the ovum was also assessed by calculating the ooplasmic volume at the time of granulosa cell removal for IVF or ICSI. Quantification analysis of the mtDNA in blastomeres was performed by real-time PCR at the 7-8 cell stage of the cleaved embryos at 72 h after oocyte retrieval. We calculated the cytoplasmic volume of the blastomeres.
Our studies showed a significantly lower mtDNA copy number in unfertilized oocytes and uncleaved embryos in women who were older than 40 years of age (p < 0.05). The larger ooplasmic volume was also associated with earlier and more rapid cleavage (p < 0.05). The ooplasmic volume was also significantly larger in the group achieving pregnancy. We found a significant positive correlation between blastomere volume and the number of mtDNA copies (r = 0.76, p < 0.01, from Pearson product-moment correlation coefficient).
We have shown that blastomere volume is directly proportional to the number of mtDNA copies. Therefore, larger cytoplasmic volume, with earlier cleavage speed, implies more mtDNA copies. Evaluation of mtDNA quantification and the measurement of ooplasmic and blastomere volume may be useful for selection of high quality embryo and pregnancy outcome.
Journal of Assisted Reproduction and Genetics 07/2013; · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nerve growth factor (NGF) has been recently proposed as one of the key factors responsible not only for promotion of nerve fiber growth but also for the onset and maintenance of pain in a variety of diseases. The aim of this study was to investigate the role of NGF in the pelvic pain associated with endometriosis. Tissue and peritoneal fluid samples were collected from 95 women with laparoscopically and histopathologically confirmed endometriosis and 59 control women without endometriosis. Expression levels of NGF mRNA and protein were examined using real-time RT-PCR and immunohistochemistry, respectively. Concentration of NGF in the peritoneal fluid (PF-NGF) was measured using ELISA. The degree of dyspareunia and dysmenorrhea was evaluated using a verbal rating scale. Real-time RT-PCR analysis revealed that NGF mRNA was significantly more abundant in the ovarian endometriomas and peritoneal endometriosis than in the normal control endometrium. Immunohistochemical analyses demonstrated that NGF was prominently expressed and preferentially localized to the glands of the ovarian endometriomas and peritoneal endometriosis, whereas it was only weakly detectable in the normal endometrium. Although PF-NGF was undetectable in some normal subjects and endometriosis patients, elevated PF-NGF in the peritoneal fluid was more frequently observed in endometriosis patients with severe pain than in those with less severe pain. Our results suggest that NGF produced locally in the peritoneal cavity may be involved in the generation of endometriosis-associated pelvic pain.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Studies on myocardial characteristics examined by speckle-tracking echocardiography are limited. AIMS: To compare myocardial performance between the right and left ventricles during the fetal development using velocity vector imaging (VVI). SUBJECTS AND STUDY DESIGN: Echocardiograms of 95 uncomplicated singleton fetuses (19-36weeks pregnancy) were retrospectively analyzed by VVI to measure global longitudinal peak velocity, strain, and strain rate of both the right ventricle (RV) and left ventricle (LV). The regional values were calculated for three segments (base, mid, and apex) of the ventricular free wall and segment. OUTCOME MEASURES: The VVI-derived measurements were examined for gestational age and compared between ventricles. RESULTS: The global peak systolic and diastolic velocity values of both ventricles significantly increased over gestation examined, whereas the global systolic strain and strain rate were stable (RV: strain -22.6±5.0%, strain rate -2.6±0.7/s; LV: strain -21.5±5.6%, strain rate -2.5±0.7/s). Compared to the LV, the RV showed significantly higher global velocity in systole and diastole (P=0.001 for systole, P<0.001 for diastole). The global systolic velocity of the LV increased close to the RV toward term, whereas the RV was dominant in diastole throughout the examined gestation. Basal strain and strain rate in the RV were significantly greater than that of the LV, although there were no significant differences in the middle and apical values between ventricles. CONCLUSION: Our findings suggest the RV predominance of longitudinal contraction and dilatation, compared to the LV in uncomplicated fetuses.
Early human development 05/2013; · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Recently, the concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged. Chronic uterine inflammation is a known cause of implantation failure and is associated with high matrix metalloproteinase (MMP) activity in uterine cavity flushing. MMP activity of women with RIF has been reported to be higher than that of fertile women. In the present retrospective study we evaluated the efficacy of treatment for high MMP activity in the uterine cavity of patients with RIF. METHODS: Of the 597 patients recruited to the study, 360 patients underwent MMP measurements and 237 patients did not (control group). All patients had failed to become pregnant, despite at least two transfers of good-quality embryos. Gelatinase MMP-2 and MMP-9 activity in uterine flushing fluid was detected by enzymology (MMP test). All samples were classified into two groups (positive or negative) based on the intensity of the bands on the enzyme zymogram, which represents the degree of MMP activity. Patients who tested positive on the initial test were treated for 2 weeks with a quinolone antibiotic and a corticosteroid, and subsequently underwent a second MMP test. Negative results on the second MMP tests after treatment and subsequent rates of pregnancy and miscarriage were used to evaluate the efficacy of treatment. Data were analyzed by the Mann--Whitney U-test and the chi-square test. RESULTS: Of the patients who underwent the MMP test, 15.6% had positive results (high MMP activity). After treatment, 89.3% of patients had negative results on the second MMP test. These patients had a significantly better pregnancy rate (42.0%) than the control group (26.6%), as well as a lower miscarriage rate (28.5% vs 36.5%, respectively). CONCLUSIONS: A 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity.
Reproductive Biology and Endocrinology 05/2013; 11(1):37. · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During feto-placental development, chorion-amnion fusion occurs in early second trimester and persistent separation of the membranes beyond 17 weeks' gestation is considered abnormal (1). Several reports have shown that complete chorion-amnion separation, defined as the amnion being separated from the chorion on at least three sides of the gestational sac, is associated with prenatal invasive procedures including amniocentesis (2-4). We would like to call attention to a case of complete chorion-amnion separation that occurred without any invasive procedures. This article is protected by copyright. All rights reserved.
Acta Obstetricia Et Gynecologica Scandinavica 05/2013; · 1.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: STUDY QUESTION: What are the reproductive and obstetric outcomes in patients undergoing radical abdominal trachelectomy (RAT) for early-stage cervical cancer? SUMMARY ANSWER: When RAT was performed before a pregnancy achieved with fertility treatments, pregnancy rate of 36.2% was obtained and 71.4% of these women gave birth at ≥32 weeks of gestation. WHAT IS KNOWN ALREADY: Reproductive and obstetric outcomes after radical vaginal trachelectomy (RVT) are well documented; however, these outcomes after RAT have not been well studied. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of patients at a single institution who underwent RAT and became pregnant. Reproductive and obstetric outcomes of 114 patients who had undergone RAT from September 2002 to December 2010 were investigated. PARTICIPANTS/MATERIAL, SETTING, METHODS: Women of reproductive age with early-stage cervical cancer who wished to preserve their fertility were documented. MAIN RESULTS AND THE ROLE OF CHANCE: Patients' median age was 33 years (25-40 years). A total of 31 pregnancies were achieved in 25 patients and 6 patients had 2 pregnancies. Eighteen of 25 patients (72.0%) had infertility problems; 17 patients conceived with IVF-embryo transfer and 1 patient with intrauterine insemination. The pregnancy rate among patients who wished to conceive was 36.2% (25/69). Among 31 pregnancies in 25 patients, 4 patients had first trimester miscarriage and 1 patient had second trimester miscarriage. Excluding the five patients who miscarried and the five ongoing pregnancies, all the 21 patients had deliveries by Cesarean section. Four patients had a preterm birth in the second trimester and 17 patients delivered in the third trimester. Of the 17 pregnancies that reached the third trimester, 2 (11.8%) were preterm births between 29 and 32 weeks, 11 (64.7%) were delivered between 32 and 37 weeks and 4 (23.5%) at ≥37 weeks of gestation. LIMITATIONS, REASONS FOR CAUTION: Because of the retrospective data collection, not all pregnancies may have been recorded. WIDER IMPLICATIONS OF THE FINDINGS: Prospective multicenter studies are needed to determine if the results shown in this retrospective cohort can be generalized to all patients with early-stage cervical cancer who wish to undergo the fertility-sparing RAT procedure. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for this study. No conflicts of interest.
[Show abstract][Hide abstract] ABSTRACT: Women with primary ovarian insufficiency (POI)/premature ovarian failure exhibit hypergonadotropic hypogonadism due to follicle dysfunction and depletion before the age of 40 years. Because ovulation is extremely rare and thought to be unpredictable in women with POI and because no ovulation induction regimens have been shown to be efficacious, oocyte donation is the only evidence-based treatment for women with POI with desired fertility. Oocyte donation is, however, extremely limited in several countries including Japan. Here, we report four women with POI who achieved pregnancies resulting from timed intercourse or intrauterine insemination in combination with cyclic estrogen/progesterone therapy and close monitoring of follicle development. These four patients were diagnosed with POI at the mean age of 27.5 ± 8.5 (mean ± SD; range, 19-35), subjected to follicle monitoring at the mean age of 29.8 ± 5.7 (23-35), and conceived at the mean age of 34.5 ± 3.9 (29-38). The interval between the initiation of follicle monitoring and pregnancy was 4.8 ± 2.8 (2-8) years. In one of the patients, her most recent ovulation occurred after a three-year interval. All four patients had uncomplicated pregnancies with term deliveries. In the event that oocyte donation and adoption are not available and/or various treatments with intensive ovulation induction have been unsuccessful, close and continuous monitoring of follicle growth to identify very rare ovulatory events might be considered for patients with POI and desired fertility.
[Show abstract][Hide abstract] ABSTRACT: The human uterus is composed of the endometrial lining and the myometrium. The endometrium, in particular the functionalis layer, regenerates and regresses with each menstrual cycle under hormonal control. A mouse xenograft model has been developed in which the functional changes of the endometrium are reproduced. The myometrium possesses similar plasticity, critical to permit the changes connected with uterine expansion and involution associated with pregnancy. Regeneration and remodeling in the uterus are likely achieved through endometrial and myometrial stem cell systems. Putative stem/progenitor cells in humans and rodents recently have been identified, isolated and characterized. Their roles in endometrial physiology and pathophysiology are presently under study. These stem/progenitor cells ultimately may provide a novel means by which to produce tissues and organs in vitro and in vivo.
[Show abstract][Hide abstract] ABSTRACT: The canonical Wnt/β-catenin signaling pathway plays a crucial role in the maintenance of the balance between proliferation and differentiation throughout embryogenesis and tissue homeostasis. β-Catenin, encoded by the Ctnnb1 gene, mediates an intracellular signaling cascade activated by Wnt. It also plays an important role in the maintenance of various types of stem cells including adult stem cells and cancer stem cells. However, it is unclear if β-catenin is required for the derivation of mouse embryo-derived stem cells. Here, we established β-catenin-deficient (β-cat(Δ/Δ)) mouse embryo-derived stem cells and showed that β-catenin is not essential for acquiring self-renewal potential in the derivation of mouse embryonic stem cells (ESCs). However, teratomas formed from embryo-derived β-cat(Δ/Δ) ESCs were immature germ cell tumors without multilineage differentiated cell types. Re-expression of functional β-catenin eliminated their neoplastic, transformed phenotype and restored pluripotency, thereby rescuing the mutant ESCs. Our findings demonstrate that β-catenin has pleiotropic effects in ESCs; it is required for the differentiation of ESCs and prevents them from acquiring tumorigenic character. These results highlight β-catenin as the gatekeeper in differentiation and tumorigenesis in ESCs.
PLoS ONE 01/2013; 8(5):e63265. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The human uterus mainly consists of two layers: an inner endometrium and an outer layer, the myometrium, made of smooth muscle. The uterus is characterized by its unique capacity for regeneration. This capacity permits cyclical regeneration and remodeling of the tissue over the course of a woman's reproductive life. During each menstrual cycle, the endometrium regenerates, and the uterus enlarges to make room for fetal growth. This cyclic physiologic pattern suggests that myometrial stem/progenitor cells are present in the tissue and play a role in myometrial functions. Our group (and others) recently characterized and isolated putative stem/progenitor cells in the myometrium. These findings are permitting a better understanding of myometrial physiology and pathology. We review current studies of myometrial stem/progenitor cells and suggestions that, in combination with hypoxia, these cells may contribute to uterine remodeling during pregnancy and the formation of myomas.
Seminars in Reproductive Medicine 01/2013; 31(1):77-81. · 3.21 Impact Factor