Impact of Diagnosis and Treatment of Chronic Endometritis on Outcomes Before Starting Assisted Reproductive Technology: A Retrospective Study.

This study aimed to investigate the effect of diagnosis and treatment of chronic endometritis (CE) on the outcome of assisted reproductive technology (ART) with or without repeated implantation failure (RIF). This retrospective analysis included patients who underwent pathological examination for diagnosis of CE at Yamagata University Hospital. The examination was performed for all patients planned for ART with or without RIF. Patients who were examined within 6 months of the first oocyte retrieval or embryo transfer were included. We counted the number of CD138-positive cells within the endometrial stroma in patients' specimens and analyzed the patients' clinical information. Clinical rates of pregnancy and implantation were determined. A total of 80 women met the inclusion criteria: 13 CE-negative patients (17.3%) and 67 CE-positive patients (83.7%). A significant decrease was noted in the CD138-positive cell count between the first biopsy and second biopsy after CE treatment (p < 0.001). In addition, no significant differences were noted in ongoing pregnancy rates between the CE-negative patients and those who underwent CE treatment. The CD138-positive cell counts at first biopsy tended to be lower in each pregnancy group than in the non-pregnancy group. For patients planned to undergo ART, examination for diagnosis of CE with or without RIF could be considered. Pathological CD138-positive cell counts were considered useful for CE diagnosis and treatment decision-making. The study findings suggest the efficacy of antimicrobial agents in CE treatment, contributing to improved pregnancy outcomes.

Septal Rupture During Early Pregnancy and Successful Delivery in Monozygotic Dichorionic Diamniotic Twin After a Single Blastocyst Transfer.

The frequency of twins resulting from a single embryo transfer has been reported to be 1.56%, with the majority being monochorionic. We present a case of septal rupture at 8 weeks of gestation and successful delivery at 36 weeks of gestation of a monozygotic dichorionic diamniotic twin after a single blastocyst transfer. This report could partially clarify the pathogenesis of monozygotic twins and septal disruption. A 37-year-old woman with 9 months of primary infertility was referred to our department. After seven cycles of artificial insemination, she underwent her first in vitro fertilization. Ten cumulous-oocyte complexes were retrieved, of which three were fertilized, and three blastocysts were cryopreserved. The first single blastocyst transfer in a hormone replacement cycle resulted in a dichorionic diamniotic twin pregnancy. Transvaginal ultrasound at 7 weeks and 4 days gestation revealed a size difference in the gestational sacs and a disruption of the inter-amniotic membrane between the two gestational sacs at 8 weeks and 6 days. Both fetuses were seen in the larger gestational sac; however, the umbilical cord of the migrated fetus was from the original gestational sac. Both fetuses developed without discordancy or obvious anomalies. At 36 weeks and 6 days of gestation, the patient underwent cesarean delivery, resulting in the birth of two viable male infants without any congenital anomalies (weighing 2256 g and 2456 g). Two amniotic cavities existed; however, no chorionic villi were present. There have been many reports on septal disruption in monochorionic diamniotic twins; however, only two cases of dichorionic diamniotic twins have been reported. Furthermore, the onsets in both reports were after the second trimester of pregnancy. This report presents the first case of septal disruption in dichorionic diamniotic twins during the first trimester.

Nuclear receptor coactivator-6 is essential for the morphological change of human uterine stromal cell decidualization via regulating actin fiber reorganization.

Nuclear receptor coactivator 6 (Ncoa6), a modulator of several nuclear receptors and transcription factors, is essential for the decidualization of endometrial stromal cells in mice. However, the function of Ncoa6 in the human endometrium remains unclear. We investigated its function in the decidualization of human endometrial stromal cells (HESCs) isolated from resected uteri. Knockdown of Ncoa6 was performed using two independent small interfering RNAs. Decidualization was induced in vitro via medroxyprogesterone and cyclic adenosine monophosphate. We compared decidualized cellular morphology between the Ncoa6 knockdown cells and control cells. Messenger RNA (mRNA) sequencing was performed to determine the Ncoa6 target genes in undecidualized HESCs. We found that the knockdown of Ncoa6 caused the failure of morphological changes in decidualized HESCs compared to that in the control cells. mRNA sequencing revealed that Ncoa6 regulates the expression of genes associated with the regulation of actin fibers. Ncoa6 knockdown cells failed to reorganize actin fibers during the decidualization of HESCs. Ncoa6 was shown to play an essential role in decidualization via the appropriate regulation of actin fiber regulation in HESCs. Herein, our in vitro studies revealed a part of the mechanisms involved in endometrial decidualization. Future research is needed to investigate these mechanisms in women with implantation defects.

Impact of endoplasmic reticulum stress on oocyte aging mechanisms.

Endoplasmic reticulum (ER) stress is associated with several aging-related diseases; however, the mechanism underlying age-related deterioration of oocyte quality is unclear. Here, we used post-ovulatory, in vivo aged mouse oocytes as a model. Super-ovulated oocytes harvested from the oviduct at 14 h and 20 h post-hCG injection were designated as 'fresh' and 'aged', respectively. Embryo development following IVF was compared between fresh, aged and ER stress-induced oocytes. Expression of the ER stress marker GRP78 was examined at each stage. To evaluate the effect of salubrinal, an ER stress suppressor, on embryo development following IVF, expression levels of GRP78 and phospho-eukaryotic initiation factor 2 alpha were compared between aged and salubrinal-treated aged oocytes. Embryo transfer of salubrinal-treated aged oocytes was performed to examine the safety of salubrinal. Similar to aged oocytes, ER stress-induced oocytes showed lower fertilization rates and poor embryo development. Following IVF, expression of GRP78 decreased with embryo development. GRP78 expression was significantly higher in aged oocytes than in fresh oocytes. Salubrinal lowered GRP78 levels and improved embryo development. No adverse effect of salubrinal treatment was found on the birth weight of pups or on organogenesis in mice. The limitation of this study was that protein kinase-like ER kinase was the only ER stress pathway examined; the role of IRE1 and ATF6 pathways was not considered. Nevertheless, salubrinal can significantly improve embryo development in in vivo aged oocytes undergoing ER stress. Hence, regulation of ER stress might represent a promising therapeutic strategy to overcome poor oocyte quality.

Daily Intake of Paraprobiotic Lactobacillus amylovorus CP1563 Improves Pre-Obese Conditions and Affects the Gut Microbial Community in Healthy Pre-Obese Subjects: A Double-Blind, Randomized, Placebo-Controlled Study.

Despite the fact that gut microbiota is closely associated with obesity, few studies have focused on the influences of paraprobiotics as food ingredients on both obesity prevention and the gut microbial community. In this study, we evaluated the effects of fragmented Lactobacillus amylovorus CP1563 (CP1563) as a paraprobiotic for obesity prevention and investigated its effects on the gut microbial community in pre-obese subjects. One hundred sixty-nine healthy subjects with a body mass index from 25.0 to 29.9 kg/m2 ingested beverages with or without the fragmented CP1563 containing 10-hydroxyoctadecanoic acid (10-HOA) for 12 weeks. The changes in abdominal, total, visceral, and subcutaneous fatty areas were significantly lower in the CP1563-10-HOA group than in the placebo group at 12 weeks. Furthermore, 16S rRNA gene sequencing of fecal DNA revealed that the changes in the abundances of the genera Roseburia and Lachnospiraceae;g were significantly greater in the CP1563-10-HOA group than in the placebo group, and the changes in the abundances of the genus Collinsella was significantly smaller in the CP1563-10HOA group than in the placebo group. Our results showed that continuous ingestion of the fragmented CP1563 containing 10-HOA reduced abdominal body fat and affected the gut microbial community in pre-obese healthy subjects. Our findings may contribute to the understanding of the relationship between the anti-obesity effect of paraprobiotics and gut microbiota.

Prognostic factors for patients undergoing vitrified-warmed human embryo transfer cycles: a retrospective cohort study.

We examined the prognostic factors for pregnancy in 210 vitrified-warmed embryo transfer (ET) cycles in 121 patients. The univariate analysis showed that age, gravida, the number of cycles associated with infertility caused by endometriosis, the number of previous assisted reproductive technology (ART) treatment cycles, and the number of ICSI procedures were significantly lower in pregnant cycles compared with non-pregnant cycles. The percentages of ET using at least one intact embryo and of ET using at least one embryo that had developed further after warming were significantly higher in pregnant cycles compared with non-pregnant cycles. Multivariate logistic regression analysis showed that previous ART treatment cycles, ET with at least one intact embryo, and ET using at least one embryo that had developed further were independent prognostic factors for pregnancy in vitrified-warmed ET cycles. We conclude that fewer previous ART treatment cycles, ET using at least one intact embryo, and ET with embryos that have developed further after warming might be favourable prognostic factors for pregnancy in vitrified-warmed ET cycles.

Effect of fragmented Lactobacillus amylovorus CP1563 on lipid metabolism in overweight and mildly obese individuals: a randomized controlled trial.

BACKGROUND: Previously, we showed that fragmented Lactobacillus amylovorus CP1563 (CP1563) functions as a dual agonist of peroxisome proliferator-activated receptor α and γ in vitro and in vivo. OBJECTIVE: Here, we examined the safety and effect of CP1563 ingestion on body fat in obese class I participants in a double-blinded, placebo-controlled, randomized clinical trial (RCT). DESIGN: In the RCT, 200 participants with a body mass index (BMI) of 25-30 kg/m(2) consumed test beverages with or without 200 mg of CP1563 daily for 12 weeks. In total, 197 subjects completed the study without any adverse effects. RESULTS: Body fat percentage, whole body fat, and visceral fat were significantly decreased in the test group compared with the placebo group (p<0.001, p<0.001, and p<0.001, respectively). Triglycerides, total cholesterol, LDL-cholesterol, and diastolic blood pressure showed significant reductions in the test group compared with the placebo group (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). Additionally, significant differences in the changes in blood glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and uric acid were observed between the two groups (p<0.001, p=0.004, p<0.001, and p<0.001, respectively). Improvements in anthropometric measurements and markers were observed in obese class I subjects in the test group. CONCLUSIONS: Daily consumption of beverages containing fragmented CP1563 for 12 weeks by obese class I subjects improved anthropometric measurements and markers related to lipid and glucose metabolism without any adverse effects. These results suggest that the consumption of foods containing fragmented CP1563 reduces body fat and prevents metabolic syndrome.

Regulatory effect of paraprobiotic Lactobacillus gasseri CP2305 on gut environment and function.

BACKGROUND: Lactobacillus gasseri CP2305 (CP2305) is a strain of Lactobacillus isolated from a stool sample from a healthy adult that showed beneficial effects on health as a paraprobiotic. In a previous study, we demonstrated that CP2305-fermented heat-treated milk modified gut functions more than artificially acidified sour milk. Thus, the regulatory activity of the former beverage was attributed to the inactivated CP2305 cells. OBJECTIVE: The aim of this study was to elucidate the contribution of non-viable paraprobiotic CP2305 cells to regulating human gut functions. We thus conducted a randomized, placebo-controlled, double-blinded parallel group trial. DESIGN: The trial included 118 healthy participants with relatively low or high stool frequencies. The test beverage was prepared by adding 1×10(10) washed, heat-treated, and dried CP2305 cells directly to the placebo beverage. The participants ingested a bottle of the assigned beverage daily for 3 weeks and answered daily questionnaires about defecation and quality of life. Fecal samples were collected and the fecal characteristics, microbial metabolite contents of the feces and composition of fecal microbiota were evaluated. RESULTS: The number of evacuations and the scores for fecal odors were significantly improved in the group that consumed the CP2305-containing beverage compared with those of the group that consumed the placebo (p=0.035 and p=0.040, respectively). Regarding the fecal contents of microbial metabolites, the level of fecal p-cresol was significantly decreased in the CP2305 group relative to that of the placebo group (p=0.013). The Bifidobacterium content of the intestinal microbiota was significantly increased in the CP2305 group relative to that of the placebo group (p<0.008), whereas the content of Clostridium cluster IV was significantly decreased (p<0.003). The parasympathetic nerve activity of the autonomic nervous system became dominant and the total power of autonomic activity was elevated in the CP2305 group (p=0.0401 and p=0.011, respectively). CONCLUSIONS: The continuous ingestion of heat-treated CP2305 cells clearly affected intestinal functionality. This is the first report of sterilized Lactobacillus cells having a significant impact on the environment and functions of the intestinal tract. The observed effects might be due, at least in part, to the brain-gut interaction.

Preclinical evaluation of an O(6)-methylguanine-DNA methyltransferase-siRNA/liposome complex administered by convection-enhanced delivery to rat and porcine brains.

The main determinant of glioblastoma (GBM) resistance to temozolomide (TMZ) is thought to be O(6)-methylguanine-DNA methyltransferase (MGMT), which is a DNA-repair enzyme that removes alkyl groups from the O(6)-position of guanine. Previously, we reported that a MGMT-siRNA/cationic liposome complex exerted a clear synergistic antitumor effect in combination with TMZ. Translation to a clinical setting might be desirable for reinforcing the efficacy of TMZ therapy for GBM. In this study, we aim to evaluate the safety of MGMT-siRNA/cationic liposome complexes and determine whether the convection-enhanced delivery of these complexes is suitable for clinical use by undertaking preclinical testing in laboratory animals. No significant adverse events were observed in rats receiving infusions of MGMT-siRNA/cationic liposome complex directly into the brain with or without TMZ administration. A pig which received the complex administered by CED also showed no evidence of neurological dysfunction or histological abnormalities. However, the complex did not appear to achieve effective distribution by CED in either the rat or the porcine brain tissue. Considering these results together, we concluded that insufficient distribution of cationic liposomes was achieved for tumor treatment by CED.

Effect of an excess intake of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro in subjects with normal blood pressure, high-normal blood pressure, or mild hypertension.

A double-blind, placebo-controlled, randomized clinical trial was conducted to evaluate the effects of ingesting an excess of tablets containing casein hydrolysate, incorporating angiotensin I-converting enzyme (ACE) inhibitory peptides such as Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), in subjects with blood pressure ranging from normal to mild hypertension. A total of 48 subjects were given either 5 times more than the effective amount of casein hydrolysate or a placebo in tablet form for 4 weeks. In the active group, systolic blood pressure (SBP) decreased significantly as compared with the placebo group. In stratified analysis, however, this antihypertensive effect was not found in normotensive subjects. In addition, neither an acute or nor an excessive reduction in blood pressure nor clinically important adverse events were observed in this study. These findings suggest that intake of a 5-fold excess of tablets containing casein hydrolysate can lead to a mild improvement in hypertension without side effects.

Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects.

This clinical study was conducted to investigate the safety and effect of D-psicose on postprandial blood glucose levels in adult men and women, including borderline diabetes patients. A randomized double-blind placebo-controlled crossover experiment of single ingestion was conducted on 26 subjects who consumed zero or 5 g of D-psicose in tea with a standard meal. The blood glucose levels at fasting and 30, 60, 90, and 120 min after the meal were compared. The blood glucose level was significantly lower 30 and 60 min after the meal with D-psicose (p<0.01, p<0.05), and a significant decrease was also shown in the area under the curve (p<0.01). The results suggest that D-psicose had an effect to suppress the postprandial blood glucose elevation mainly in borderline diabetes cases. A randomized double-blind placebo-controlled parallel-group experiment of long-term ingestion was conducted on 17 normal subjects who took 5 g of D-psicose or D-glucose with meals three times a day for 12 continuous weeks. Neither any abnormal effects nor clinical problems caused by the continuous ingestion of D-psicose were found.

Effects of astaxanthin on human blood rheology.

Effects of astaxanthin (AX) derived from H. pluvialis on human blood rheology were investigated in 20 adult men with a single-blind method. The experimental group was 57.5 +/- 9.8 years of age and the placebo group was 50.8 +/- 13.1 years of age. A blood rheology test that measures whole blood transit time was conducted using heparinized blood of the volunteers by a MC-FAN apparatus (microchannel array flow analyzer). After administration of AX 6 mg/day for 10 days, the values of the experimental group were decreased from 52.8 +/- 4.9 s to 47.6 +/- 4.2 s (p<0.01) and a comparison of the values between the experimental (47.6 +/- 4.2 s) and the placebo (54.2 +/- 6.7 s) groups showed a significant difference (p<0.05). There were no adverse effects resulting from the administration of AX 6 mg/day for 10 days. Informed consent was obtained from each subject.

Nutrigenomic studies of effects of Chlorella on subjects with high-risk factors for lifestyle-related disease.

In order to clarify the physiological effects of Chlorella intake on subjects with high-risk factors for lifestyle-related diseases, we conducted Chlorella ingestion tests on 17 subjects with high-risk factors for lifestyle-related diseases and 17 healthy subjects over a 16-week period, including a 4-week post-observation period. We conducted blood biochemical tests and analyzed gene expression profile in whole blood cells in the peripheral blood before and after Chlorella intake. We confirmed that in both groups, Chlorella intake resulted in noticeable reductions in body fat percentage, serum total cholesterol, and fasting blood glucose levels. Through gene expression analysis, we found that gene expression profiles varied with Chlorella intake and identified many genes that exhibited behavior such that after the completion of the intake period, expression levels returned to pre-intake expression ones. Among these were genes related to signal transduction molecules, metabolic enzymes, receptors, transporters, and cytokines. A difference in expression level was found between the two groups at the start of the tests, and we were able to identify genes with noticeable variance in expression level resulting from Chlorella intake in the high-risk factor group. These included genes involved in fat metabolism and insulin signaling pathways, which suggests that these pathways could be physiologically affected by Chlorella intake. There were clear variations in the expression profiles of genes directly related to uptake of glucose resulting from Chlorella intake, indicating that the activation of insulin signaling pathways could be the reason for the hypoglycemic effects of Chlorella.