Analysis of the Predictive Factors for Chronic Endometritis Recurrence in Infertile Women.

Problem: To identify the predictive factors for the recurrence of chronic endometritis (CE) in infertile women.

Method Of Study: In this case-control study, 1170 infertile women recovered from CE and underwent fertility treatment between December 2018 and August 2021. Among the 146 women (12.

Outcomes of Early Versus Delayed Anemia Treatment in Nondialysis-Dependent CKD.

Introduction: The association of hemoglobin level at treatment initiation with renal and cardiovascular outcomes in patients with anemia in nondialysis-dependent (NDD) chronic kidney disease (CKD) is unclear.

Methods: This retrospective cohort study utilized 2 Japanese databases (Medical Data Vision Co. Ltd.

Therapeutic efficacy of gentle endometrial curettage on antibiotic-resistant chronic endometritis in infertile women.

Purpose: To identify the efficacy of endometrial curettage on antibiotic-resistant chronic endometritis (CE) in infertile women.

Methods: Of 1580 women with CE, 87 with antibiotic-resistant CE after two to five cycles of antibiotic treatment were recruited between 2019 and 2021. The women who underwent endometrial curettage without applying any force and, in the subsequent menstrual cycle, endometrial sampling for CD138 immunostaining without antibiotic use.

Transcriptomic profiling analysis of human endometrial stromal cells treated with autologous platelet-rich plasma.

Purpose: To clarify the mechanisms of intrauterine platelet-rich plasma (PRP) infusion that support embryo implantation in in vitro fertilization treatment.

Methods: Blood and endometrial samples were collected from four infertile women. Human endometrial stromal cells (HESCs) were cultured and passaged equally into four cell culture dishes in each patient.

Comparison of Pregnancy Outcomes Between Fresh Embryo Transfer in a Natural IVF Cycle and IUI Cycle Among Infertile Young Women.

Background: The purpose of the current study was comparing pregnancy outcomes for natural cycle in vitro fertilization (IVF) per fresh embryo transfer (ET) and oocyte pick-up (OPU) in intrauterine insemination (IUI).

Methods: This was a retrospective cohort study of women who underwent either IUI (n=246) or OPU with fresh ET for natural cycle IVF (n=291), conducted between April 2017 and February 2018 at the Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan. Patients in both groups did not receive ovarian stimulation and luteal support; gonadotropin-releasing agonist spray was administered 35 before OPU or IUI.

Therapeutic effects of an oral gonadotropin-releasing hormone receptor antagonist, relugolix, on preventing premature ovulation in mild ovarian stimulation for IVF.

Purpose: Can relugolix, a novel oral gonadotropin-releasing hormone receptor (GnRH) antagonist, function as an alternative ovulation inhibitor to GnRH antagonist injections?

Methods: This single-center, cross-sectional retrospective study compared premature ovulation rates and clinical outcomes in IVF treatment after mild ovarian stimulation with 40 mg of relugolix (relugolix group) or 0.25-mg injections of ganirelix acetate or cetrorelix acetate (injection group) between March 2019 and January 2020. Of 247 infertile women (256 IVF cycles) aged ≤42 years, 223 women (230 cycles) were evaluated.

Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy.

Purpose: Does the OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy, developed for treating repeated implantation failure (RIF), contribute to improving pregnancy outcomes in patients with a history of recurrent pregnancy loss (RPL)?

Methods: Between 2018 and 2019, women with RPL after two or more clinical pregnancy losses underwent RPL testing. We treated chronic endometritis with antibiotics, high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of 168 consecutive women aged ≤43 years, 115 underwent RPL testing.

Effects of Periconceptional Multivitamin Supplementation on Folate and Homocysteine Levels Depending on Genetic Variants of Methyltetrahydrofolate Reductase in Infertile Japanese Women.

Methylenetetrahydrofolate reductase (MTHFR) has various polymorphisms, and the effects of periconceptional folic acid supplementation for decreasing neural tube defects (NTDs) risk differ depending on the genotypes. This study analyzed the effectiveness of multivitamin supplementation on folate insufficiency and hyperhomocysteinemia, depending on MTHFR polymorphisms. Of 205 women, 72 (35.

Increasing number of implantation failures and pregnancy losses associated with elevated Th1/Th2 cell ratio.

Problem: We aimed to assess whether an imbalance of T-helper (Th) 1 and Th2 cells contributes to implantation failure and pregnancy loss.

Method Of Study: In this cross-sectional study, 197 consecutive patients with a history of repeated implantation failure (RIF) after three or more embryo transfer (ET) cycles and/or recurrent pregnancy loss (RPL) after two or more clinical pregnancy losses underwent Th cell testing. After excluding 42 women aged ≥44 and 9 with vitamin D supplementation, we recruited 146 women including 79 with RIF and 81 with RPL.

Impact of chronic endometritis on endometrial receptivity analysis results and pregnancy outcomes.

Background: The aim of this study is to evaluate the relationship between chronic endometritis (CE) and a personalized window of implantation (WOI), identified by results of endometrial receptivity analysis (ERA), and pregnancy outcomes following embryo transfer (ET) based on the ERA outcomes.

Methods: The single-center, cross-sectional study was designed. The study population consisted of 101 infertile women who underwent endometrial sampling between June 2018 and February 2020.

Discovery of novel 2-(3-phenylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3β inhibitors.

We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3β inhibitors from our promising compounds containing a 2-phenylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3β inhibitors. SAR studies focused on the phenyl moiety revealed that a 4-fluoro-2-methoxy group afforded potent inhibitory activity toward GSK-3β.

Discovery of novel 2-(4-aryl-2-methylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3β inhibitors.

We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3β inhibitors from our promising compounds containing a 3-methylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3β inhibitors. SAR studies focused on the nitrogen atom of the piperazine moiety revealed that a phenyl group afforded potent inhibitory activity toward GSK-3β.

Inhibition of mitogen-activated protein kinase kinase, DNA methyltransferase, and transforming growth factor-β promotes differentiation of human induced pluripotent stem cells into enterocytes.

We previously reported that small-molecule compounds were effective in generating pharmacokinetically functional enterocytes from human induced pluripotent stem (iPS) cells. In this study, to determine whether the compounds promote the differentiation of human iPS cells into enterocytes, we investigated the effects of a combination of mitogen-activated protein kinase kinase (MEK), DNA methyltransferase (DNMT), and transforming growth factor (TGF)-β inhibitors on intestinal differentiation. Human iPS cells cultured on feeder cells were differentiated into endodermal cells by activin A.

Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3β inhibitors for Alzheimer's disease.

We herein describe the results of further evolution of GSK-3β inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3β inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models.

Generation of enterocyte-like cells with pharmacokinetic functions from human induced pluripotent stem cells using small-molecule compounds.

The small intestine plays an important role in all aspects of pharmacokinetics, but there is no system for the comprehensive evaluation of small-intestinal pharmacokinetics, including drug metabolism and absorption. In this study, we aimed to construct an intestinal pharmacokinetics evaluation system and to generate pharmacokinetically functional enterocytes from human induced pluripotent stem cells. Using activin A and fibroblast growth factor 2, we differentiated these stem cells into intestinal stem cell-like cells, and the resulting cells were differentiated into enterocytes in a medium containing epidermal growth factor and small-molecule compounds.

2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors.

A series of 2-(2-phenylmorpholin-4-yl)pyrimidin-4(3H)-ones was synthesized and examined for their inhibitory activity against glycogen synthase kinase-3β (GSK-3β). We found 21, 29 and 30 to possess potent in vitro GSK-3β inhibitory activity with good in vitro PK profiles. 21 demonstrated significant decrease of tau phosphorylation after oral administration in mice and excellent PK profiles.

MP-124, a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor, ameliorates ischemic brain damage in a non-human primate model.

Overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) in response to DNA damage is considered to play a crucial role in the development of post-ischemic neuronal injury, such as ischemic stroke. The present study was undertaken to clarify the beneficial effects of MP-124, a novel PARP-1 inhibitor, on neurological deficits and cerebral infarcts following middle cerebral artery occlusion (MCAO) in the monkey. The effects of MP-124 on cerebral infarcts and neurological deficits in monkeys were investigated in permanent MCAO (pMCAO) and transient MCAO (tMCAO) models.

Laparoscopically-assisted transabdominal oocyte retrieval in an infertility patient with ovarian malposition.

Infertility patients with malpositioned ovaries have considerable difficulty conceiving naturally because of extended fallopian tubes and ovarian malposition; such patients turn for help to assisted reproductive technology (ART) treatment. For most of these patients, ovarian malposition prevents transvaginal oocyte retrieval, so the transabdominal approach for oocyte retrieval is required. One of our infertility patients presented with ovarian malposition, and laparoscopy-assisted transabdominal oocyte retrieval was performed.

Optimization of a novel nylon mesh container for human embryo ultrarapid vitrification.

Objective: To evaluate the efficacy of a nylon mesh container in vitrification of human embryos and to determine the optimal osmotic pressure of the initial thawing solution.

Design: Retrospective analysis.

Setting: National Center for Child Health and Development, Tokyo, Japan.

Laparoscopic proximal tubal division can preserve ovarian reserve for infertility patients with hydrosalpinges.

Aim: To investigate whether laparoscopic proximal tubal division for the treatment of hydrosalpinges could preserve ovarian function.

Methods: From June 2002 to October 2006, before assisted reproductive treatment (ART), a total of 17 infertile patients with bilateral hydrosalpinges were studied--11 patients underwent laparoscopic proximal tubal division (PTD group), and six underwent laparoscopic salpingectomy (salpingectomy group). In both groups, the basal follicle-stimulating hormone (FSH) values before and after surgery, the operation time and outcome of ART treatment were retrospectively evaluated.

The ratio of late-follicular to mid-follicular phase LH concentrations efficiently predicts ART outcomes in women undergoing ART treatment with GnRH-agonist long protocol and stimulation with recombinant FSH.

Purpose: To establish an index to predict ART outcomes and to identify infertile patients who need LH supplementation during ovarian stimulation.

Methods: Serum LH concentrations were measured during the mid- and late-follicular phase in 86 normogonadotropic infertile patients who underwent ART treatment using GnRH-agonist long protocol with recombinant-FSH. The relationships between serum LH concentrations at both time points and ART outcomes were retrospectively analyzed, and the relationships between the ratio of late-follicular to mid-follicular LH concentrations and ART outcomes were also evaluated.

[Aging and anti-aging of oocytes].

The functions of organs decrease as the age increases. The fecundity of women also decreases due to mainly the decreasing quality of oocytes. The recent change of life style makes the age of infertility patients elder and infertility treatments more difficult.