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Retained products of conception (RPOC) is a common cause of postpartum bleeding, which may be life-threatening; however, no evidence-based guidelines exist to assist in evaluating the risk of massive hemorrhage in women with RPOC. In this prospective study, we aimed to evaluate the predictive factors for massive hemorrhage in women with RPOC. The primary and secondary endpoints were to validate the usefulness of power Doppler color scoring (PDCS) in evaluating hypervascularity and to identify other predictive factors (such as maximum RPOC diameter and serum βhCG and Hb level at first visit), respectively. Among the 51 women with RPOC included in this study, 16 (31.5%) experienced massive hemorrhage during follow-up. None of the women with PDCS 1 or 2 (18) experienced massive hemorrhage, whereas 16 (48.5%) women with PDCS 3 or 4 (33) did. Multiple logistic regression analysis showed that the odds ratio [95% confidence interval] (P value) for PDCS, assisted reproductive technology (ART), and low serum hemoglobin (Hb) levels were 22.39 [2.25 − 3087.92] (P = 0.004), 5.72 [1.28 − 33.29] (P = 0.022), and 4.24 [0.97 − 22.99] (P = 0.056), respectively. Further, the decision tree method identified PDCS, ART, and low serum Hb levels as potential predictive factors for massive hemorrhage. This study identified PDCS as useful predictor of massive hemorrhage in women with RPOC. With additional inclusion of factors such as ART and low serum Hb levels, the risk of massive hemorrhage may be effectively evaluated, leading to better management of women of reproductive age. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in choroidal blood flow in patients with Vogt-Koyanagi-Harada (VKH) disease after initiation of corticosteroid treatment. Methods: Fourteen patients (10 men and 4 women) with acute VKH disease followed for 2 years were retrospectively reviewed; only right eyes were included in the analysis. Mean blur rate (MBR) in the macula was measured by laser speckle flowgraphy (LSFG) and central choroidal thickness (CCT) was measured by optical coherence tomography (OCT), both prior to treatment and over 2 years after initiation of corticosteroid treatment. Results: Of 14 patients included in this study, 13 received initial treatment consisting of intravenous corticosteroid pulse therapy and one patient was treated using bilateral sub-Tenon injections of triamcinolone acetonide. Mean percentage change in MBR was significantly increased after initiation of treatment compared to pretreatment values (P < 0.001). Mean CCTs were significantly decreased after initiation of treatment, compared to pretreatment thicknesses (P < 0.001). There was no significant change in either MBR change or CCT at 1 month after initiation of treatment through 2 years of follow-up. The mean MBR percentage change was significantly higher in eyes with sunset glow fundus (SGF) compared to eyes without SGF at 1 year. Conclusion: With initiation of corticosteroid treatment in VKH disease patients, choroidal blood flow improved and was maintained for 2 years. However, the presence of SGF should be taken into consideration when interpreting MBR results in VKH disease patients. [ABSTRACT FROM AUTHOR]

Purpose: Follicle-stimulating hormone receptor (FSHR) expression in granulosa cells is critical in enabling follicles to achieve accelerated growth. Although FSHR expression has been reported to be epigenetically regulated, the mechanism is unclear. Cooperation between oocytes and granulosa cells is also essential for normal follicular growth. Among oocyte-derived factors, bone morphogenetic protein 15 (BMP15) promotes follicular growth and is suggested to have epigenetic effects. We examined the role of BMP15 in the acquirement of FSHR in human granulosa cells. Methods: Immortalized non-luteinized human granulosa (HGrC1) cells were stimulated with trichostatin A (TSA) or BMP15 to analyze FSHR expression, histone modifications, and USF1/2 binding at the FSHR promoter region. Histone acetyl transferase (HAT) activity and phosphorylation of Smad 1/5/8 and p38 MAPK were examined with or without BMP15, SB203580, and LDN193189. CYP19A1 expression and estradiol production were also studied. Results: TSA and BMP15 induced FSHR mRNA expression in a dose-dependent manner and histone modifications were observed with increased binding of USF1/2. BMP15 increased FSHR protein expression, which was suppressed by LDN193189. BMP15 increased phosphorylation of Smad 1/5/8 and significantly increased HAT activity, which was inhibited by LDN193189, but not by SB203580. BMP15 increased phosphorylation of p38 MAPK and USF1. LDN193189 suppressed BMP15-induced phosphorylation of both p38 MAPK and USF1, whereas SB203580 suppressed the phosphorylation of USF1. BMP15 increased CYP19A1 mRNA expression and estradiol production. Conclusion: BMP15 induced FSHR expression in human granulosa cells through Smad and non-Smad pathways. This mechanism of FSHR induction by BMP15 may be utilized for controlling follicular growth. [ABSTRACT FROM AUTHOR]

Purpose: To observe long-term changes of the retinal pigment epithelium (RPE) in the eyes of patients with Vogt-Koyanagi-Harada (VKH) disease using an adaptive optics (AO) fundus camera, and their correlation with the findings of spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (AF) imaging. Patients and methods: Three eyes of two patients with new-onset acute VKH disease were retrospectively studied. After the serous retinal detachment was resolved by high-dose corticosteroid treatment, the patients were examined with SD-OCT, blue-wavelength AF, near-infrared (NIR) AF, and an AO fundus camera. AO images of the macula were obtained using the rtx1TM, AO fundus camera. The area around the foveal center of the hyper-reflective lesion in AO imaging was measured manually. The time at which the serous retinal detachment resolved was set as the baseline, and AO and other images were obtained every 3 to 6 months from the baseline. Results: In all three eyes, lesions with elevation or thickening of the RPE layer were observed with OCT imaging in the macula after the serous retinal detachment resolved. These lesions showed hyper-autofluorescence in NIR-AF image and hyper-reflective lesions with clear boundaries in AO image. The area of the hyper-reflective lesions of AO images in each eye showed an approximately 40% decrease at 6 months from baseline. However, the hyper-reflective lesion remained to some extent after 18 months in case 1 and 36 months in case 2. Conclusions: By using OCT, fundus autofluorescence and AO images, it was possible to observe temporal changes of RPE layer in VKH eyes noninvasively. High-resolution AO images also allow us to observe for improvements in the elevation or thickening of the RPE layer quantitatively. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to study changes in macular cone photoreceptors in Vogt-Koyanagi-Harada (VKH) disease patients after high-dose corticosteroid treatment using an adaptive optics (AO) fundus camera.Methods: We retrospectively analyzed 16 eyes of eight patients with new-onset acute VKH disease that were studied retrospectively. After serous retinal detachment (SRD) had resolved, AO images were obtained using the rtx1™ AO fundus camera over a 12-month course. Cone counting was performed in the nasal, temporal, superior and inferior areas of the macula 0.75 mm from the foveal center. A control group of 30 eyes of 30 healthy subjects was established for comparison.Results: In the eyes with VKH disease, the mean cone densities 0.75 mm from the foveal center were 11,847 at baseline (resolution of SRD), and 15,218, 16,684 and 17,686 cones/mm2, at 3, 6, and 12 months later, respectively. The mean cone densities at 3, 6, and 12 months were significantly increased compared to those of baseline (p = 0.007, p < 0.001, and p < 0.001, respectively); however, they were significantly lower than that of the healthy control eyes (p < 0.001). The mean cone densities at areas with a previous presence of cystoid spaces were significantly lower than those without cystoid spaces at the baseline, and at 3, 6, and 12 months (p < 0.001, p = 0.007, p < 0.001, and p = 0.008, respectively).Conclusions: Cone densities were gradually increased after the resolution of SRD in the eyes of VKH disease patients. The presence of cystoid spaces might be a marker of severe damage to cone photoreceptors. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to observe photoreceptors and outer retinal layer thickness by using an adaptive optics (AO) fundus camera and spectral domain optical coherence tomography (SD-OCT) in patients with central serous chorioretinopathy (CSC). Methods: Twelve eyes of 12 patients with resolved CSC were studied. After subretinal fluid (SRF) had resolved, AO images of the macula were obtained by using the rtx1 AO fundus camera (Imagine Eyes, France). Cones in the nasal and temporal areas of the macula, 0.5 mm from the foveal center, were counted. Outer retinal layer thickness was measured as the distance between the outer border of external limiting membrane (ELM) and the inner border of retinal pigment epithelium (RPE) at 0.5 mm from the foveal center. The first measurement was performed after resolution of the subretinal fluid and was defined as the baseline. Then, the second measurement was performed in the same location after 12 months. Results: In the eyes with resolved CSC, the mean logMAR values of visual acuity at baseline and 12 months were 0.16 and 0.01, respectively ( p = 0.0023). The mean cone densities at baseline and 12 months were 12,213 and 17,146 cones/mm, respectively. The mean cone densities at 12 months were significantly increased compared to baseline ( p = 0.0014). The mean outer retinal layer thickness at baseline (53.5 μm) was significantly thinner than that at 12 months (60.7 μm) ( p = 0.0013). The mean cone densities were significantly correlated with outer retinal layer thickness and logMAR visual acuity. Conclusions: Adaptive optics imaging revealed a gradual increase in the number of macular cone densities during 12 months in patients with resolved CSC, which was correlated with outer retinal layer thickness and visual acuity in a short term. [ABSTRACT FROM AUTHOR]

Ovarian reserve reflects the quality and quantity of available oocytes. This reserve has become indispensable for the better understanding of reproductive potential. Measurement of the serum anti-Müllerian hormone (AMH) level allows quantitative evaluation of ovarian reserve. It has been applied to a wide range of clinical conditions, and it is well established that the measurement of serum AMH levels is more useful than qualitative evaluation based on the menstrual cycle. AMH levels are monitored during infertility treatments; in patients undergoing medically assisted reproductive technology; and in the diagnosis of ovarian failure, polycystic ovarian syndrome, and granulosa cell tumor. It is also useful in the evaluation of iatrogenic ovarian damage. Population-based studies have indicated a potential role for serum AMH in the planning of reproductive health management. While AMH is currently the best measure of ovarian reserve, its predictive value for future live births remains controversial. Furthermore, there is a serious practical issue in the interpretation of test results, as currently available assay kits use different assay ranges and coefficients of variation due to the absence of an international reference standard. The pros and cons of the serum AMH level as a definitive measure of ovarian reserve merits further review in order to guide future research. [ABSTRACT FROM AUTHOR]

We assessed the associations between preoperative and postoperative serum anti-Müllerian hormone (AMH) levels and parameters of endometriosis and endometriomas surgery with the success of infertility treatments after cystectomy. Seventeen out of 54 patients got pregnant during the infertility treatments. In these patients, the median interval from surgery to conception was 16.3 months. The serum AMH levels 1-year postoperatively were significantly higher in the pregnant group compared to the non-pregnant group (3.44 ± 1.78 versus 2.17 ± 2.24 ng/ml, p = 0.049). The median interval from surgery to recurrence was 34.4 months, and no significant differences were found in the serum AMH levels at any time point between the recurrence and non-recurrence groups. Serum AMH levels 1 year after laparoscopic cystectomy for endometriomas may predict the success of postoperative infertility treatments, but not a recurrence of endometriomas. [ABSTRACT FROM AUTHOR]

Since serum anti-Müllerian hormone (AMH) levels enable quantitative evaluation of ovarian damage, we conducted a computer-based search, using key words, of all articles published in English through the PubMed database from inception until September 2013 to summarize available studies evaluating ovarian reserve after ovarian toxic interventions to discuss the usefulness of serum AMH levels. We found that most of the studies demonstrated a decline in serum AMH levels when compared to control or pretreatment levels, with levels dependent on the type of treatment modality. Measurement of serum AMH levels enables quantitative evaluation of ovarian damage caused by ovarian toxic interventions, such as chemotherapy and radiotherapy, instead of qualitative evaluation using menstrual condition or basal follicle-stimulating hormone levels. Serum AMH levels are becoming indispensable to assess the ovarian reserve of patients who desire preservation of ovarian function for fertility and endogenous sex steroid hormones. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 9 (GDF9), an oocyte-secreted factor, whose receptors exist in granulosa cells, is involved in follicle progression. Therefore, GDF9 is considered to potentially mediate signals necessary for follicular growth. However, the effect of GDF9 on human granulosa cells is not fully understood. Human immortalized nonluteinized granulosa cell line (HGrC1) which we have previously reported was stimulated with GDF9 and/or follicle-stimulating hormone (FSH). Granulosa cells obtained from in vitro fertilization (IVF) patients were also evaluated with quantitative reverse transcription polymerase chain reaction (RT-PCR). Real-time RT-PCR showed that GDF9 increased messenger RNA (mRNA) levels of enzymes required for cholesterol biosynthesis, such as 3-hydroxy-3-methylglutanyl-CoA synthase 1 (HMGCS1), farnesyl-diphosphate farnesyltransferase 1, squalene epoxidase, lanosterol synthase, and cytochrome P450, family 51, subfamily A, polypeptide 1 (CYP51A1). A greater increase in mRNA levels of HMGCS1 and CYP51A1 was observed by combined treatment with GDF9 and FSH. Clinical samples showed a significant increase in CYP51A1 mRNA in the group of granulosa cells connected with unfertilized oocytes. Our results suggest that GDF9, possibly with FSH, may play significant roles in the regulation of cholesterol biosynthesis and the expression of CYP51A1 which might be a predictor for unfertilization. [ABSTRACT FROM PUBLISHER]

Background: The purpose of this study was to examine cone photoreceptors in the macula of patients with retinitis pigmentosa using an adaptive optics fundus camera and to investigate any correlations between cone photoreceptor density and findings on optical coherence tomography and fundus autofluorescence. Methods: We examined two patients with typical retinitis pigmentosa who underwent ophthalmological examination, including measurement of visual acuity, and gathering of electroretinographic, optical coherence tomographic, fundus autofluorescent, and adaptive optics fundus images. The cone photoreceptors in the adaptive optics images of the two patients with retinitis pigmentosa and five healthy subjects were analyzed. Results: An abnormal parafoveal ring of high-density fundus autofluorescence was observed in the macula in both patients. The border of the ring corresponded to the border of the external limiting membrane and the inner segment and outer segment line in the optical coherence tomographic images. Cone photoreceptors at the abnormal parafoveal ring were blurred and decreased in the adaptive optics images. The blurred area corresponded to the abnormal parafoveal ring in the fundus autofluorescence images. Cone densities were low at the blurred areas and at the nasal and temporal retina along a line from the fovea compared with those of healthy controls. The results for cone spacing and Voronoi domains in the macula corresponded with those for the cone densities. Conclusion: Cone densities were heavily decreased in the macula, especially at the parafoveal ring on high-density fundus autofluorescence in both patients with retinitis pigmentosa. Adaptive optics images enabled us to observe in vivo changes in the cone photoreceptors of patients with retinitis pigmentosa, which corresponded to changes in the optical coherence tomographic and fundus autofluorescence images. [ABSTRACT FROM AUTHOR]

Abstract: Salicylideneaniline (SA) or benzylideneaniline (BA) derivatives with [CpCo(dithiolene)] backbone, which are formulated as [CpCo(S2C2(H)(R))] (R=5-chlorosalicylideneaniline (2a), salicylideneaniline (2b), benzylideneaniline (2c) and 3,5-di-t-butylsalicylideneaniline (2d)), were prepared from the aniline precursor [CpCo(S2C2(H)(C6H4-NH2))] (1) and the corresponding aldehydes. 1 and 2a–2d were identified with spectral data and electrochemical redox potentials. 1 and 2a–2c were structurally determined by X-ray diffraction studies. 1 and 2a showed dithiolene-H⋯X hydrogen bondings (X=N (1), O (2a)), because the dithiolene proton is usually acidic (ca. 9ppm by 1H NMR). In 2a–2c, the dihedral angles between two benzene rings (θ 1) in the SA (or BA) moieties were depending on the substituents on these benzene rings. 2a has small θ 1 angle (7.321°) and the result indicates a short intramolecular OH···N hydrogen bonding distance (1.743Å). In the crystal of 2b (or 2c), there are two (or four) crystallographically independent molecules, and their θ 1 angles are different by the flexible SA (or BA) unit. The crystal 2b contains a non-planar molecule (θ 1 =37.043°) and a relatively planar molecule (θ 1 =22.822°) as well. [Copyright &y& Elsevier]

Abstract: We have recently demonstrated that reactive oxygen species (ROS) play an important role in RAW264.7 cell apoptosis induced by cationic liposomes composed of stearylamine (SA-liposomes). In this study, we investigated whether protein kinase Cδ PKCδ) is involved in apoptosis induced by cationic liposomes. Tyrosine phosphorylation, nuclear localization, and cleavage of PKCδ were observed following the treatment of cells with SA-liposomes, suggesting that SA-liposomes activate PKCδ. Rottlerin, a specific inhibitor of PKCδ, inhibited ROS generation and also suppressed apoptosis. Cell surface proteoglycans may contribute to PKCδ activation by SA-liposomes. These findings suggest that PKCδ is strongly associated with apoptosis induced by SA-liposomes. [Copyright &y& Elsevier]

Abstract: A new ionization method that uses metal-complex-based ionization probes containing the 2,6-bis(oxazolinyl)pyridine (pybox) ligand is presented. This method was proven to effectively ionize large complex molecules, including biomolecules. The preparation of the charged probes and their application to the ionization of biomolecules using cold-spray ionization mass spectrometry are shown. [Copyright &y& Elsevier]

Abstract Background: Hemolytic uremic syndrome (HUS) associated with Shiga toxin (Stx)-producing Escherichia coli O157:H7 infection is one of the diseases causing acute renal failure in young children. Although HUS is still a serious disease in children, no reliable predictive markers for HUS nor markers of disease severity are available so far. Recently, we experienced a sporadic case of typical HUS caused by Stx-producing E. coli O157:H7 and detected, at the prodromal stage, a high level of serum fibrin/fibrinogen degradation product-E (FDP-E) fraction. Methods: To assess the usefulness of FDP-E for the treatment of HUS in clinical practice, we retrospectively examined serum levels of FDP-E in 22 patients with bloody diarrhea with or without HUS. Results: There were significantly increased levels of serum FDP-E in patients with HUS, but not in those without HUS. Furthermore, serum levels of FDP-E may correlate with disease severity in patients with HUS. Conclusions: These results suggest that serum levels of FDP-E may be a useful marker of HUS in clinical practice. [ABSTRACT FROM AUTHOR]

Pathogenic variants of BRCA1/2 constitute hereditary breast and ovarian cancer (HBOC) syndrome, and BRCA1/2 mutant is a risk for various cancers. Whereas the clinical guideline for HBOC patients has been organized for the therapy and prevention of cancer, there is no recommendation on the female reproductive discipline. Indeed, the role of BRCA1/2 pathogenic variants in ovarian reserve has not been established due to the deficiency of appropriate animal models. Here, we used a rat model of Brca2(p.T1942fs/+) mutant of Sprague-Dawley strain with CRISPR-Cas9 editing to evaluate ovarian reserve in females. Fertility and ovarian follicles were evaluated and anti-Müllerian hormone (AMH) was measured at 8–32 weeks of age with a comparison between the wild-type and the mutant rats (MUT). MUT revealed a significantly smaller number of deliveries with fewer total pups. Furthermore, MUT showed a significant decrease in primordial follicles at 20 weeks and a low AMH level at 28 weeks. RNA-sequencing of the ovary at 10 weeks detected acceleration of the DNA damage repair pathway, which was accompanied by oxidative stress-induced DNA double-strand breaks, a decrease in PTEN, and an increase in mTOR in follicular granulosa cells. In conclusion, Brca2(p.T1942fs/+) dissipates primordial follicles via early activation of granulosa cells through oxidative stress, leading to earlier termination of fertility. [ABSTRACT FROM AUTHOR]

Aim: Both morbidity and mortality rates of cervical cancer are increasing, especially in reproductive‐aged women. Radical trachelectomy (RT) is an effective fertility‐preserving surgery for early‐stage cervical cancer. This study aimed to determine the influence of RT on endometrial thickness during in vitro fertilization‐embryo transfer (IVF‐ET). Methods: Forty‐four patients had undergone RT, and 23 women undergoing IVF‐ET treatment (105 ET cycles) were included. Endometrial thickness during hormone replacement therapy (HRT) was retrospectively evaluated and compared between patients with and without RT. Results: Eleven patients (50 ET cycles) in the RT group and 12 (52 ET cycles) in the control group were investigated. Compared with the control group, higher ET cancellation rates were observed in patients in the RT group (1 of 52 cycles [control group] vs. 8 of 50 cycles [RT group], p < 0.01). Endometrial thinning was not affected by patient age at first IVF‐ET treatment, history of artificial abortion, preservation of uterine arteries during RT, or postoperative chemotherapy (p = 0.27, 1, 1, and 1, respectively). Conclusions: Our data revealed that RT influenced endometrial thickness in IVF‐ET. This was not affected by the background of the patients or perioperative management in this study. We could not reveal the underlying mechanism, but it is postulated that the transient postoperative uterine blood flow status and postoperative infections may have some effect on the endometrium. To resolve these issues, accumulation of evidences are required. We recommend informing patients about the impact of RT on IVF‐ET before starting assisted reproductive technology (ART). [ABSTRACT FROM AUTHOR]

Endometriosis has several distinguishing features in the ectopic endometrium, including chronic inflammation and fibrosis. According to the retrograde menstruation theory, endometriotic cells are derived from eutopic endometrial cells, and adhesion of endometrial cells to the extracellular matrix can be the initial step in the development of endometriosis. Therefore, we hypothesized that cell adhesion, which mediates a sequence of events in the development of endometriosis triggering inflammatory responses and tissue fibrosis could be a possible therapeutic target for endometriosis. We found co-upregulation of focal adhesion kinase (FAK) and monocyte chemoattractant protein-1 (MCP-1) in the endometriotic tissues compared with that in the normal endometrium. MCP-1 secretion was significantly higher in the endometriotic stromal cells than in the eutopic endometrial stromal cells. Furthermore, co-culture of U937 cells and endometriotic stromal cells upregulated secretion of transforming growth factor-β1 (TGF-β1). A FAK inhibitor significantly inhibited the secretion of MCP-1 in the endometriotic stromal cells and TGF-β1 in the co-culture with macrophages. FAK inhibitor treatment in the murine endometriosis model demonstrated a decrease in the formation of endometriotic lesions as well as the expression of MCP-1 and TGF-β1. Our results suggest that the FAK-mediated sequential development of endometriosis, including inflammatory response and tissue fibrosis, can be a new therapeutic target in endometriosis. [ABSTRACT FROM AUTHOR]

Purpose: We observed cone photoreceptors by using adaptive optics (AO) fundus camera and optical coherence tomography (OCT) in patients with retinitis pigmentosa (RP) and examined the correlations between cone photoreceptors and visual function over 2 years. Methods: Six patients with RP were studied. All patients underwent measurement using best-corrected decimal visual acuity, OCT, a Humphrey Field Analyzer with the 10-2 test grid pattern, and AO. AO images of the foveal center were obtained using an rtx1™ AO fundus camera, and cone counting was performed at 0.5 mm from the foveal center. Results: AO detected a decrease of cone density over 2 years in RP patients. However, visual acuity, foveal sensitivity, and photoreceptor thickness were not changed over the 2 years. Conclusions: AO images showed a decrease in the number of foveal cone densities over 2 years in patients with RP. AO may shorten the period required to predict the RP progression rate. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS), a common endocrine disorder, is associated with impaired oocyte development, leading to infertility. However, the pathogenesis of PCOS has not been completely elucidated. This study aimed to determine the differentially expressed genes (DEGs) and epigenetic changes in the oocytes from a PCOS mouse model to identify the etiological factors. RNA-sequencing analysis revealed that 90 DEGs were upregulated and 27 DEGs were downregulated in mice with PCOS compared with control mice. DNA methylation analysis revealed 30 hypomethylated and 10 hypermethylated regions in the PCOS group. However, the DNA methylation status did not correlate with differential gene expression. The pathway enrichment analysis revealed that five DEGs (Rps21, Rpl36, Rpl36a, Rpl37a, and Rpl22l1) were enriched in ribosome-related pathways in the oocytes of mice with PCOS, and the immunohistochemical analysis revealed significantly upregulated expression levels of Rps21 and Rpl36. These results suggest that differential gene expression in the oocytes of mice in PCOS is related to impaired folliculogenesis. These findings improve our understanding of PCOS pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effect of switching to brolucizumab from aflibercept on eyes with type 1 macular neovascularization (MNV) and polypoidal choroidal vasculopathy (PCV) at 18 months. Methods: This study was a retrospective, observational case series that included 19 eyes of 19 patients with type 1MNV and 23 eyes of 22 patients with PCV. We compared the injection intervals, visual acuity, total lesion size, and the number of polypoidal lesions between baseline and 18 months. The correlations between the data including treatment interval, total lesion size, and the number of polyps were also assessed. Results: Treatment intervals were significantly extended; from 7.4 ± 1.4 weeks to 11.6 ± 2.6 weeks for type 1 MNV, p < 0.001; from 6.9 ± 1.3 to 11.7 ± 3.1 weeks for PCV, p < 0.001. In type 1 MNV eyes, strong correlation was found between total lesion size and brolucizumab injection intervals (r = − 0.81; p = 0.0002) and moderate correlation was found between treatment frequency with aflibercept and that with brolucizumab (r = 0.76; p = 0.040). In PCV eyes, we found strong correlation between the number of polyps and brolucizumab treatment frequency (r = − 0.81; p = 0.0016) and moderate correlation between total lesion size and brolucizumab treatment interval (r = − 0.48; p = 0.034). Intraocular inflammation occurred in 2 of 19 eyes (10.3%) with type 1 MNV and 5 of 23 eyes (21.7%) with PCV. Conclusion: The properties to extend brolucizumab injection intervals might be the smaller lesion size and lower aflibercept frequency for type 1 MNV and the smaller number of polyps and the smaller size of lesion for PCV. [ABSTRACT FROM AUTHOR]

Background: Primary ovarian insufficiency (POI) is characterized by the development of hypergonadotropic hypogonadism before 40 years of age and leads to intractable infertility. Although in vitro fertilization and embryo transfer with donated eggs enables pregnancy, not a few patients desire pregnancy using their oocytes. However, follicular development is rare and unpredictable in patients with POI. Thus, there is a need for treatments that promote the development of residual follicles and methods to accurately predict infrequent ovulation. Methods: This review discusses the effects of various treatments for obtaining eggs from POI patients. Furthermore, this study focused a potential marker for predicting follicular growth in patients with POI. Main Findings: Different treatments such as hormone‐replacement therapy, dehydroepiandrosterone supplementation, platelet‐rich plasma injection, and in vitro activation have shown varying degrees of effectiveness in retrieving oocytes from patients with POI. To predict follicle development in the cycle, elevated serum estradiol and reduced follicle‐stimulating hormone (FSH) levels are important. However, these markers are not always reliable under continuous estradiol‐replacement therapy. As a novel marker for predicting follicle growth, serum anti‐Müllerian hormone (AMH) levels, measured using the picoAMH enzyme‐linked immunosorbent assay, were found to predict follicle growth in patients and the cycle. Conclusion: This review highlights the challenges and available interventions for achieving pregnancy using a patient's oocytes in cases of POI. We believe that a combination of currently available treatments and prediction methods is the best strategy to enable patients with POI to conceive using their own eggs. Although AMH levels may predict follicle growth, further research is necessary to improve the chances of successful follicular development and conception in patients with POI. [ABSTRACT FROM AUTHOR]

Our previous study found that 17β-estradiol (E2) suppresses primordial follicle activation and growth in cultured mouse ovaries. In this study, we administered tamoxifen, an estrogen receptor antagonist, into the abdominal cavity of mice to clarify the relationship between primordial follicle activation and the physiological concentration of E2 in mouse ovaries. The results showed that tamoxifen promoted primordial follicle activation. Administration of tamoxifen promoted degradation of the extracellular matrix surrounding primordial follicles in the ovaries. Furthermore, tamoxifen decreased the expression of stefin A, an inhibitor of cathepsins that digest some proteins and extracellular matrix, in the ovaries. Mechanical stress produced by the extracellular matrix reportedly suppresses the activation of primordial follicles. The collective results show that tamoxifen can promote primordial follicle activation through the degradation of the extracellular matrix surrounding primordial follicles. Our results indicate that E2 suppresses primordial follicle activation in vivo and that tamoxifen may be useful as a therapeutic agent against infertility. [ABSTRACT FROM AUTHOR]

Serum concentration of anti-Müllerian hormone (AMH) is a useful marker for ovarian reserve. Measurement of AMH in clinical practice has gained widespread use to predict parameters such as the ovarian response, menopause, and recovery after chemotherapy. However, undetectable AMH levels assayed by conventional enzyme-linked immunosorbent assay (ELISA) kits fail to predict depletion of follicles because of low sensitivity of the kits. We investigated whether a recently developed ultrasensitive ELISA kit, picoAMH, would be more effective at detecting very low AMH levels in association with menstrual status. We analyzed 68 women with undetectable serum AMH levels using an ELISA kit, AMH Gen II. The AMH concentration of the same samples was detected in 36 samples using picoAMH; 32 samples were within the standard range, and 4 samples were out of the standard range but still detectable. Thirty-two women whose AMH levels were undetectable using the picoAMH all showed amenorrhea. We also found a significant correlation between the classes of serum AMH levels (undetectable, detectable under the limit of quantification, and measurable within the assay range) and menstrual status. Five of the 6 amenorrheic women with detectable AMH eventually achieved follicle growth. The present study demonstrated that very low AMH levels detectable using picoAMH correspond well to current and future ovulation status. This suggests that serum AMH levels can be useful for the assessment of ovarian reserve and follow-up of women with a declined ovarian reserve. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of women of reproductive age. Ovarian endometriosis (OE) is the most common lesion in endometriosis and may cause infertility, in addition to dysmenorrhea. Hormonal treatments, which are the conventional treatment methods for endometriosis, suppress ovulation and hence are not compatible with fertility. The inflammasome is a complex that includes Nod-like receptor (NLR) family proteins, which sense pathogen-associated molecular patterns and homeostasis-altering molecular processes. It has been reported that the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inflammasome, which contributes to the activation of interleukin-1 beta (IL-1β), might be related to the progression of endometriosis. Therefore, the aim of the present study was to evaluate non-hormonal therapies for OE, such as inhibitors of the NLRP3 inflammasome. Methods: The expression of NLRP3 was measured in the eutopic endometrium (EM) of patients with and without endometriosis and OE samples, as well as stromal cells derived from the endometrium of patients with and without endometriosis and OE samples (endometrial stromal cells with endometriosis [ESCs] and cyst-derived stromal cells [CSCs]). The effects of an NLRP3 inhibitor (MCC950) on ESCs and CSCs survival and IL-1β production were evaluated. We then administered MCC950 to a murine model of OE to evaluate its effects on OE lesions and ovarian function. Results: NLRP3 gene and protein expression levels were higher in OE and CSCs than in EM and ESCs, respectively. MCC950 treatment significantly reduced the survival of CSCs, but not that of ESCs. Moreover, MCC950 treatment reduced the co-localization of NLRP3 and IL-1β in CSCs, as well as IL-1β concentrations in CSCs supernatants. In the murine model, MCC950 treatment reduced OE lesion size compared to phosphate-buffered saline treatment (89 ± 15 vs. 49 ± 9.3 mm3 per ovary; P < 0.05). In the MCC950-treated group, IL-1β and Ki67 levels in the OE-associated epithelia were reduced along with the oxidative stress markers of granulosa cells. Conclusions: These results indicated that NLRP3/IL-1β is involved in the pathogenesis of endometriosis and that NLRP3 inhibitors may be useful for suppressing OE and improving the function of ovaries with endometriosis. [ABSTRACT FROM AUTHOR]

Background: Ovarian endometrioma is a common gynecological disease that is often treated with surgery or hormonal treatment. Ovarian cystectomy, a surgical procedure for ovarian endometrioma, can result in impaired ovarian reserve. Methods: We conducted a randomized controlled trial to evaluate the efficacy of hormonal treatment [gonadotropin-releasing hormone agonist (GnRHa) or dienogest (DNG)] for preserving ovarian reserve after cystectomy for ovarian endometrioma. The primary endpoint was the level of serum Anti-Müllerian hormone (AMH) as a marker of ovarian reserve. Results: Before and after laparoscopic surgery, 22 patients in the GnRHa group and 27 patients in the DNG group were administered hormonal treatment for a total of 4 months. After 1-year follow-up, >60% of the patients in the DNG group retained over 70% of their pretreatment AMH levels, whereas no patient in the GnRHa group retained their AMH levels after cystectomy (P < 0.01). Interleukin-6 (IL-6) is a key cytokine involved in inflammation. Compared with the GnRHa group, patients in the DNG group had lower IL-6 levels at the end of treatment. Conclusions: Our data revealed that DNG is more effective than GnRHa in preserving ovarian reserve after cystectomy of ovarian endometrioma. This is achieved through the reduction of the inflammatory response during the perioperative period and other endometriosis-related inflammatory reactions. Trial registration: The registration number of this trial is UMIN-CTR, UMIN000018569, registered 6 August 2015, https://upload.umin.ac.jp/cgi-open-bin/ctr%5fe/ctr%5fview.cgi?recptno=R000021492, and Japan Registry of Clinical Trials, jRCTs041180140, registered 29 March 2019, https://jrct.niph.go.jp/en-latest-detail/jRCTs041180140. This randomized controlled trial was conducted in accordance with the CONSORT guidelines. [ABSTRACT FROM AUTHOR]

Purpose: We examined the predictive factors for final visual acuity (VA) with macular edema of branch retinal vein occlusion (BRVO) treated by intravitreal injection of bevacizumab (IVB) and examined the differences between patients without recurrent macular edema due to BRVO after a single IVB and patients treated with multiple IVB because of recurrent macular edema. Methods: In this retrospective study, 37 eyes of 37 patients with BRVO were treated with IVB and followed up for more than 24 weeks. Eighteen eyes showed no recurrence of macular edema after a single IVB (single IVB group). The remaining 19 eyes showed recurrent macular edema and underwent multiple IVB (multiple IVB group). VA and morphologic parameters of optical coherence tomography were examined. Results: Mean VA, central retinal thickness, and mean retinal thickness in a circular region of 1-mm diameter at the fovea improved significantly with IVB treatment in both groups. Final VA was correlated with baseline VA and integrity grade of the photoreceptor inner and outer segment (IS/OS) line beneath the fovea. Conclusion: Baseline VA and IS/OS line grade at 4 weeks may be predictive factors for final VA. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic disease of unknown etiology that is characterized by chronic non-caseating granulomatous inflammation with tissue destruction. It is an uncommon disease in children, and renal sarcoidosis in particular is very rare in adults and children. A 17-year-old boy with renal sarcoidosis was referred to our hospital with an initial diagnosis of pyelonephritis. Prior treatment with various antibiotics had not been effective, but tentative oral daily prednisolone (PSL) had partially ameliorated his symptoms, although the symptoms recurred during steroid tapering. We detected non-caseating granulomatous interstitial nephritis and numerous sclerotic glomeruli in a second biopsy specimen, compatible with the diagnosis of renal sarcoidosis. The patient was treated with pulsed methyl-prednisolone and oral daily doses of PSL and mizoribine (MZR). During the treatment with MZR, the PSL was successfully tapered, and the patient has since presented no signs of recurrence. Our treatment of this patient shows that treatment with MZR can allow steroid sparing and prevent recurrence in a patient with sarcoidosis. [ABSTRACT FROM AUTHOR]

We encountered the case of a 4-year-old boy with thrombotic microangiopathy (TMA) of unknown etiology. Verotoxin-induced hemolytic uremic syndrome (HUS), Streptococcus-pneumoniae-related HUS, factor H deficiency, drug-induced thrombotic thrombocytopenic purpura (TTP), and ADAMTS13 (von Willebrand factor-cleaving protease; a disintegrin-like and metalloprotease with thrombospondin type 1 repeats)-related TTP were excluded. His condition was refractory to anticoagulants and plasma exchange, and his clinical course was catastrophic, with central nervous system symptoms and progressive renal failure. However, factual treatment of intravenous gamma globulin (IVIG) ended the hemolysis and resulted in a rise in platelet count. He fully recovered except for end-stage renal failure, but he underwent a successful renal transplant after peritoneal dialysis. He has not suffered a relapse of TMA or an allograft rejection for 4 years. IVIG might be an option for some patients with TMA of unknown etiology refractory to conventional treatment. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate early effects of hydroxychloroquine (HCQ) on the retina using adaptive optics (AO). Methods. This was a prospective observational single-center study of 29 eyes of 29 patients who had been treated with HCQ for the first time and followed with AO for a minimum of two years. Cone counting was performed in 4 quadrants, nasal, temporal, superior, and inferior, at 0.75 mm from the foveal center. The changes of cone density on AO, visual acuity, and foveal thickness within two years of use were analyzed. The changes of mean cone density of patients whose cumulative dose was over 200 g in 2 years were also assessed. We evaluated the correlation between cone density and cumulative dose of HCQ. Results. There was no significant decrease in cone density in the first 2 years of HCQ use. VA and foveal thickness did not show obvious change, either. Among 9 patients whose cumulative dose was over 200 g in 2 years, the mean cone density showed no significant change at 6, 12, 18, and 24 months compared with baseline (P = 0.381 , P = 0.380 , P = 0.281 , and P = 0.534 , respectively). There was no correlation between cone density and cumulative dose of HCQ at two years (Spearman's correlation coefficient, r = −0.0553, P = 0.780 ; n = 29). Conclusion. AO showed no change in cone density in the first two years of HCQ use. [ABSTRACT FROM AUTHOR]

Pediatricians are often faced with both bad temper and decreased daily activity in children with persistent nephrotic syndrome. These problems, which might affect both mental and physical development, have been explained as a consequence of general fatigue due to systemic edema and/or long-term hospitalization. However, other factors, such as cerebral hypoperfusion, may be involved. We experienced a case of a boy with steroid-resistant nephrotic syndrome who showed diffuse cerebral hypoperfusion on single photon emission computed tomography. Diffuse cerebral hypoperfusion dramatically resolved as the nephrotic syndrome remitted. His bad temper, decreased daily activity, and delay of speech and motor development also improved. In our patient, cerebral hypoperfusion might have been associated with his mental problems, physical problems, and delayed development of speech. [Copyright &y& Elsevier]

The purpose of this study was to develop a quick, quantitative, prediction method for the determination of the bitterness of solutions containing one or more of five amino acids (l-isoleucine, l-leucine, l-valine, l-phenylalanine, and l-tryptophan), using an artificial taste sensor. The bitterness of various solutions containing different concentrations (1, 3, 10, 30, and 100 mM) of five amino acids, singly and in combination, was estimated using a multichannel taste sensor and compared with the results of human gustatory sensation tests with nine volunteers. The relative response electric potential patterns were similar for all five amino acids. Large sensor outputs were observed in channels 1–4 (which are negatively charged) while there were no responses in channels 5–8 (positively charged). The sensor output for channel 1, which was the largest output value, was used for prediction of bitterness. The change of membrane potential caused by adsorption (CPA), which corresponds to aftertaste, could not be used as an explanatory variable since the adsorption of the amino acids to the sensor membrane was weak and CPA values were small. The bitterness intensity scores for single, binary, and multi-component amino acid solutions, could be easily predicted on the basis of the sensor output value of channel 1 using regression analysis. Principal component analysis of the sensor output data suggested that the sourness, astringency and/or smell of the solutions also played a role in the perception of bitterness. [Copyright &y& Elsevier]

Patients with primary ovarian insufficiency (POI) occasionally present with follicle growth; however, accurately predicting cycles accompanied by follicle growth is challenging. Early-stage follicles produce serum anti-Müllerian hormone (AMH), a useful marker of ovarian reserve. Therefore, serum AMH levels indicate growth of small follicles (which are difficult to detect ultrasonographically) and may predict follicle growth in patients with POI. Using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit, we observed very low serum AMH levels in patients with POI. We further evaluated follicle growth in each patient during each cycle to determine the usefulness of measuring serum AMH levels as a predictor of follicle growth in patients with POI who receive hormone replacement therapy (HRT). We investigated 19 patients with POI in whom we analyzed 91 cycles; 14 cycles showed positive and 77 cycles showed negative results on serum AMH testing. The rate of cycles showing follicle growth in AMH-positive cycles was higher than that in AMH-negative cycles (64.3% vs. 6.5%, p = 0.0001). The median serum AMH level (7.7 pg/mL [25th and 75th percentiles 4.6 pg/mL and 22.3 pg/mL, respectively]) in AMH-positive cycles was lower than the lower limit of detection of conventional AMH ELISA kits. The positive predictive value of positive serum AMH levels for follicle growth was higher than that of follicle-stimulating hormone (< 10 mIU/mL). These results indicate that a very low level of serum AMH detected using picoAMH assays is a useful predictor of follicle growth in patients with POI receiving HRT. [ABSTRACT FROM AUTHOR]

Several features exist that distinguish endometriotic cells from eutopic endometrial cells. Progesterone resistance is one of the main distinguishing features, although how progesterone resistance affects the phenotype of endometriotic cells is not fully elucidated. Heart and neural crest derivatives expressed 2 (HAND2) is a transcriptional factor that plays an important role in maintaining endometrial function in a progesterone-dependent manner. Therefore, we explored whether progesterone-dependent HAND2 is implicated in the progression of endometriosis. HAND2 was less expressed by endometriotic tissues compared to endometrial tissues. Suppression of HAND2 expression induced fibroblast growth factor 1 (FGF1), FGF2, and FGF9 in endometriotic stromal cells and consequently enhanced migration and invasion capacity. AZD4547, a FGF receptor inhibitor, diminished the migration and invasion of endometriotic cells in vitro. In the murine model of endometriosis, AZD4547 showed suppressive effects on the development of endometriotic lesions at a relatively low concentration. In conclusion, we demonstrated that FGF1, FGF2, and FGF9 are downstream effectors of HAND2 in endometriotic cells. Since HAND2-dependent FGFs play roles in enhancing invasive capacity of endometriotic cells, our results suggest that FGF receptor inhibitors, such as AZD4547, can be promising therapeutic targets for endometriosis. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age and a major cause of infertility; however, the pathophysiology of this syndrome is not fully understood. This can be addressed using appropriate animal models of PCOS. In this review, we describe rodent models of hormone‐induced PCOS that focus on the perturbation of the hypothalamic‐pituitary‐ovary (HPO) axis and abnormalities in neuropeptide levels. Methods: Comparison of rodent models of hormone‐induced PCOS. Main findings: The main method used to generate rodent models of PCOS was subcutaneous injection or implantation of androgens, estrogens, antiprogestin, or aromatase inhibitor. Androgens were administered to animals pre‐ or postnatally. Alterations in the levels of kisspeptin and related molecules have been reported in these models. Conclusion: The most appropriate model for the research objective and hypothesis should be established. Dysregulation of the HPO axis followed by elevated serum luteinizing hormone levels, hyperandrogenism, and metabolic disturbance contribute to the complex etiology of PCOS. These phenotypes of the human disease are recapitulated in hormone‐induced PCOS models. Thus, evidence from animal models can help to clarify the pathophysiology of PCOS. [ABSTRACT FROM AUTHOR]

Abstract: It has been more than 15 years since the measurement of serum anti‐Müllerian hormone (AMH) first allowed the quantitative assessment of ovarian reserve. Meanwhile, the clinical implication of serum AMH has been expanding. The measurement of serum AMH has been applied in various clinical fields, including assisted reproduction, menopause, reproductive disorders and assessment of ovarian damage/toxicity. Well‐known findings about the usefulness of serum AMH revealed by numerous studies executed in the early era include decline with aging, a good correlation with oocyte yield in assisted reproduction, upregulation in polycystic ovarian syndrome and a decrease on ovarian surgery and toxic treatment. More intensive research, including a meta‐analysis, cutting‐edge clinical trial and advances in AMH assays, has yielded newer findings and firmer clinical interpretations in serum AMH in the past few years. Variations in the AMH decline trajectory in the general population do not support the accurate prediction of menopause. The ability to predict pregnancy in infertility treatment and natural conception is poor, while a nomogram integrating serum AMH as a stimulation protocol is useful for avoiding poor and/or hyper‐responses. On the other hand, improvements in measuring very low concentrations of serum AMH may be capable of distinguishing women with poor ovarian function. Age‐independent standardization of AMH values may be helpful for comparing ovarian reserves among women at different ages. [ABSTRACT FROM AUTHOR]

Problem Plasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear. Method of study PAI-1 expression in PCOS ovaries was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-β and TNF-α in peritoneal fluid mononuclear cells (PFMCs) were measured with quantitative PCR. Results Little PAI-1 expression is observed in healthy GCs, whereas GCs of PCOS and atretic follicle exhibit distinct expression in vivo. In vitro study using HGrC1 shows that TGF-β and TNF-α increase PAI-1 mRNA and its activity, and both together exhibit a synergistic effect. The expression of PAI-1 mRNA is suppressed by simvastatin. Moreover, insulin-sensitizing drugs (metformin, pioglitazone, and rosiglitazone) suppress LPS-induced TGF-β and TNF-α mRNA expression in PFMC. Conclusion Statin and insulin-sensitizing drugs may provide a potential therapy for PCOS via down-regulation of PAI-1 expression in GCs and down-regulation of TGF-β and TNF-α expression in PFMC, respectively. [ABSTRACT FROM AUTHOR]

Purpose: To assess the correlation between endothelial dysfunction and frequency of antivascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD). Methods: We examined 64 consecutive patients with nAMD who were evaluated for endothelial function by use of peripheral arterial tonometry (EndoPAT 2000; Itamar Medical, Caesarea, Israel) at Toyama University Hospital from January 2015. We tallied the number of anti-VEGF treatments between January 2014 and December 2015 and determined the correlation between the number of anti-VEGF injections and endothelial function expressed as the reactive hyperemia index (RHI). Multiple regression analysis was also performed to identify the independent predictors of a larger number of injections. Results: The mean number of anti-VEGF injections was 8.2 ± 3.3. The mean lnRHI was 0.47 ± 0.17. The lnRHI correlated with the number of anti-VEGF injections (r = −0.56; P = 0.030). The multiple regression analysis revealed that endothelial function, neovascular subtypes, and treatment regimens were associated with the number of injections. Conclusions: Endothelial dysfunction may affect the efficacy of anti-VEGF therapy. Neovascular subtypes may also predict a larger number of injections. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of infliximab (IFX) on refractory uveoretinitis between Behçet disease (BD) patients with short duration (≤18 months, n = 6) versus long duration (>18 months, n = 7) of their ocular disease.Methods: Records of 13 BD patients treated with IFX for 24 months were retrospectively reviewed.Results: Frequency of ocular attacks decreased with IFX treatment in both groups, with no significant difference. Retinal and disc vascular leakage scores also decreased in both groups, however was significantly lower in the short-duration group. Percentage of eyes with a best-corrected visual acuity (BCVA) of 1.0 or better at year 2 was 100% in the short-duration and 21% in the long-duration group.Conclusions: Induction of early remission using IFX appeared to be more effective in reducing background vascular leakage and in maintaining good visual acuity in BD patients. [ABSTRACT FROM AUTHOR]

Pentraxin 3 (PTX3) is an inflammatory mediator that is released by a wide range of tissues and cells. Elevated PTX3 levels may represent a useful diagnostic and/or prognostic marker for a number of diseases. The purpose of this study was to investigate serum PTX3 levels in benign gynecological conditions including mature cystic teratomas (MCTs), endometriomas, and uterine leiomyomas. Serum PTX3 levels of the MCT group were found to be significantly higher compared to those of the other groups, including healthy controls (p = 0.001), although carbohydrate antigen 19-9 (CA19-9) did not exhibit a significant difference. Serum PTX3 levels of the MCT, but not the endometrioma group, were also found to have significantly decreased post-operatively (mean ± standard deviation, 4.98 ± 2.10 to 3.61 ± 1.53 ng/mL). Immunohistochemical analyses demonstrated positive staining for PTX3 protein in the sebaceous glands, epidermal tissues, and hair roots of MCT specimens. PTX3 is expressed by MCTs and is associated with increased serum concentrations compared to healthy controls and patients with either endometriomas or uterine leiomyomas. We conclude that serum PTX3 levels could be used as a potential diagnostic marker for MCTs, especially helpful in differentiating them from endometriomas with elevated expression of CA19-9. [ABSTRACT FROM AUTHOR]

Kisspeptin, a hypothalamic neuropeptide, is expressed in the arcuate nucleus (ARC) that is considered as the center of the gonadotropin-releasing hormone (GnRH)-pulse generator. We hypothesized that kisspeptin expressed in the ARC is implicated in the disturbance of the hypothalamus−pituitary−ovary axis observed in polycystic ovary syndrome (PCOS). To test this hypothesis, we evaluated the hormonal profiles, luteinizing hormone (LH) pulse, and ARC kisspeptin immunoreactivity in a PCOS rat model using the anti-progestin RU486. We found an alteration of the LH pulse, including a trend towards an increased mean LH concentration and area under the curve, and a significant upregulation of the mean LH pulse amplitude. Additionally, a higher number of kisspeptin-positive cells was observed in the ARC of RU486-treated rats than in the ARC of intact rats. These results suggest the possible involvement of hypothalamic kisspeptin in the hypothalamus−pituitary−ovary axis and therefore, in PCOS pathophysiology. [ABSTRACT FROM AUTHOR]

Objectives. We evaluated histological changes occurring in renal biopsy specimens, between the time before initial induction therapy and after 12 months' maintenance therapy, as well as changes in laboratory parameters, SLE disease activity (SLEDAI), and dosage of corticosteroid (CS) in childhood-onset systemic lupus erythematosus (SLE) patients treated with mycophenolate mofetil (MMF). Methods. A retrospective analysis was performed on nine patients diagnosed with childhood-onset SLE and lupus nephritis. They were treated with pulsed mPSL and intravenous cyclophosphamide as induction therapy and MMF (500-1500 mg/day) plus CS as maintenance therapy. Renal biopsy was performed before the initial induction therapy and after 12 months' maintenance therapy. Results. Pathological findings at second biopsy were improved in eight of nine patients (89%). The findings of SLEDAI, urinalysis, and blood tests also showed improvement. CS doses could be tapered satisfactorily. Adverse events were observed in two patients. No patients treated with MMF experienced any disease flares during maintenance therapy. Conclusions. MMF as maintenance therapy might be useful in that not only the histological findings of lupus nephritis were improved, but also CS doses could be beneficially tapered. Nonetheless, this is a retrospective report of only nine cases and further prospective multicenter studies are necessary. [ABSTRACT FROM AUTHOR]

Anti-Müllerian hormone (AMH) is a relatively novel method for examining the ovarian reserve that reflects female reproductive function. In the era in which the number of women delaying attempts to conceive has increased, a good predictor for long-term fecundability has been explored. We performed the retrospective cohort study to investigate whether initial serum AMH levels are useful for predicting long-term fertility during infertility treatments. We recruited 149 women in the retrospective cohort, and 52 women were gravid during the follow-up period. According to the multiple logistic analyses, only age was found to have a significant correlation with pregnancy success in all women. In women ≥38 years, significantly higher serum AMH levels were detected in the pregnant group (median = 2.83 ng/mL, range = 1.11-6.29 ng/mL) than the non-pregnant group (median = 1.22 ng/mL, range = 0-9.46 ng/mL; p = 0.015). None of the women with serum AMH levels <0.7 ng/mL were pregnant during treatment. AMH may be used to identify poor pregnancy prospects in women who are above 38 years. [ABSTRACT FROM AUTHOR]

Purpose: Assisted hatching (AH) is an artificial disruption of the zona pellucida with the aim of facilitating embryo implantation. We used time-lapse observations of mouse embryos to examine the effect of AH in mouse blastocysts. Methods: AH techniques were performed with acid Tyrode's solution. We compared the rates of blastocyst formation and blastocyst attachment to Ishikawa cells between the control ( n = 28) and the AH group ( n = 24). To analyze the effects of AH, 8-cell mice embryos were cultured under time-lapse observations (every 15 min). The time required for hatching, the hatching rates, the frequency of contraction, and the contraction rates in the blastocysts were analyzed. Results: There were no significant differences between the two groups in hatching rate or attachment rate. The times required for hatching were 286 ± 22 min in the AH group and 990 ± 437 min in the control group ( P = 0.018). The contraction frequencies in blastocysts were 3.5 ± 0.7 times in the AH group and 7.5 ± 2.5 times in the control group ( P = 0.020). Conclusions: From the time-lapse observations we found that the time required for hatching and the frequency of contraction in blastocysts were both reduced by AH, although blastocyst formation and attachment were not affected. [ABSTRACT FROM AUTHOR]

A reduced response to progesterone in the eutopic endometrium with endometriosis and in endometriotic tissues is considered to be the underlying factor for endometriosis. CD10 is known to be expressed by endometrial and endometriotic stromal cells and may be induced by progestins, although the function of CD10 is not fully revealed in endometrial or endometriotic tissues. In the current study, the expression of CD10 was significantly increased by treatment of the cells with progesterone, 17β-estradiol, and dibutyryl cyclic adenosine monophosphate (cAMP) in the endometrial stromal cells. On the other hand, the expression of CD10 following treatment with progesterone, 17β-estradiol, and dibutyryl cAMP was not significantly increased in endometriotic stromal cells. The adhesion assay for endometrial and endometriotic stromal cells to hyaluronan using 5- or 6-(N-succinimidyloxycarbonyl)-fluorescein 3', 6'-diacetate–labeled cells demonstrated that the CD44-dependent adhesion of stromal cells was inhibited by CD10. As far as the induction of CD10 is concerned, the effect of progesterone was different between endometrial stromal cells and endometriotic stromal cells. CD10 might be involved in the development of endometriosis due to its influence on CD44-dependent cell adhesion. [ABSTRACT FROM PUBLISHER]

Purpose: Human follicular fluid constitutes the microenvironment of follicles and includes various biological active proteins that can affect follicle growth and oocyte fertilization. Conducting proteomic evaluations of human follicular fluid may be helpful for identifying potential biomarkers possibly possessing a predictive value for oocyte quality and the success of in vitro fertilization. Method: We performed proteomic profiling of human follicular fluids containing oocytes that were fertilized and resulted in pregnancy and follicular fluids containing oocytes that were not fertilized in the same patients undergoing intracytoplasmic sperm injection using the LTQ Orbitrap coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) analyses. Results: We identified a total of 503 proteins in human follicular fluids containing fertilized and non-fertilized oocytes obtained from 12 patients. We also found that 53 proteins exhibited significantly different spectral counts between the two groups, including heparan sulfate proteoglycan perlecan, which showed significant upregulation in the follicular fluids containing fertilized oocytes in comparison with that observed in the follicular fluids containing non-fertilized oocytes. Conclusion: Our results suggest a possibility that proteins identified by LC/MS/MS in follicular fluid might not only be involved in folliculogenesis, but also function as biomarkers possessing predictive potential for oocyte maturation and the success of IVF when their expression levels are significantly different between fertilized and non-fertilized oocytes, although no distinctive biomarkers were identified in the current study. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protective effect of sphingosine-1-phosphate (S1P) against H2O2-induced apoptosis in human granulosa cell cultures with freshly harvested granulosa cells. Design: Experimental study. Setting: Academic medical center for reproductive medicine. Patient(s): Cultures of primary granulosa cells isolated from women undergoing in vitro fertilization (IVF). Intervention(s): None. Main Outcome Measure(s): Cell apoptosis and Western blot analysis of signaling pathway proteins. Result(s): We found that S1P (1 and 10 mM) statistically significantly decreased granulosa cell apoptosis after H2O2 treatment. The decreased cell apoptosis induced by S1P was abolished after treatment with VPC23019, an inhibitor of S1P1 and S1P3 receptors, W146, an inhibitor of S1P1 receptors, and CAY10444, an inhibitor of S1P3 receptors. A Western blot analysis revealed that the level of phospho-Akt increased and peaked at 10 minutes after 10 mM S1P exposure. Conclusion(s): Treatment with S1P can inhibit the apoptosis of granulosa cells in response to oxidative stress induced by H2O2. The protective effect of S1P is mediated by activating the PI3K/Akt pathway, and the antiapoptotic effect of S1P is mainly mediated through the S1P1 and S1P3 receptor. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The loss of primordial follicles from gonadal damage caused by chemotherapy results in decreased ovarian reserve. To assess the impact of chemotherapy for patients with gestational trophoblastic neoplasia (GTN) on the ovarian reserve, we evaluated the post-chemotherapy serum anti-Müllerian hormone (AMH) levels. Study design: In 22 patients with GTN receiving chemotherapy, serum AMH levels were measured after the administration of chemotherapy and compared with serum AMH levels measured in patients with hydatidiform mole who did not receive chemotherapy, as a control. We also analyzed differences in the serum AMH levels following the administration of different anti-cancer agents. Results: The serum AMH levels measured in the GTN group after chemotherapy was administered (median 1.18, range 0.32–3.94ng/mL) significantly decreased in comparison to those measured in the control group (median 4.22, range 0.77–6.53ng/mL, P =0.002). Serum AMH levels were significantly lower in the patients who had received a regimen including etoposide than in the patients who had not received treatment with etoposide (0.71 vs. 1.30ng/mL, P =0.027). Conclusion: Our results suggest that chemotherapy administered to treat GTN does indeed affect the ovarian reserve, especially in patients who receive a medication regimen that includes etoposide. Measuring their serum AMH levels might therefore be helpful for counseling GTN patients regarding their ovarian reserve. [Copyright &y& Elsevier]