The influence of radical trachelectomy on endometrial thickness in in vitro fertilization-embryo transfer.

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).

Switching to brolucizumab from aflibercept in age-related macular degeneration with type 1 macular neovascularization and polypoidal choroidal vasculopathy: an 18-month follow-up study.

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.

Follicle development and its prediction in patients with primary ovarian insufficiency: Possible treatments and markers to maximize the ability to conceive with residual follicles.

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.

Evaluation of chimeric antigen receptor of humanized rabbit-derived T cell receptor-like antibody.

T-cell receptor (TCR)-like Abs that specifically recognize antigenic peptides presented on MHC molecules have been developed for next-generation cancer immunotherapy. Recently, we reported a rapid and efficient method to generate TCR-like Abs using a rabbit system. We humanized previously generated rabbit-derived TCR-like Abs reacting Epstein-Barr virus peptide (BRLF1p, TYPVLEEMF) in the context of HLA-A24 molecules, produced chimeric antigen receptor (CAR)-T cells, and evaluated their antitumor effects using in vitro and in vivo tumor models. Humanization of the rabbit-derived TCR-like Abs using the complementarity-determining region grafting technology maintained their specificity and affinity. We prepared a second-generation CAR using single-chain variable fragment of the humanized TCR-like Abs and then transduced them into human T cells. The CAR-T cells specifically recognized BRLF1p/MHC molecules and lysed the target cells in an antigen-specific manner in vitro. They also demonstrated antitumor activity in a mouse xenograft model. We report the generation of CAR-T cells using humanized rabbit-derived TCR-like Abs. Together with our established and efficient generation procedure for TCR-like Abs using rabbits, our platform for the clinical application of humanized rabbit-derived TCR-like Abs to CAR-T cells will help improve next-generation cancer immunotherapy.

Rapid and efficient generation of T-cell receptor-like antibodies using chip-based single-cell analysis.

Generation of TCR-like monoclonal antibodies using conventional methods is markedly laborious and inefficient. We have proposed improvements of ISAAC (chip-based Ab-secreting cell [ASC] screening method), allows comprehensive analysis of ASCs at the single-cell level to obtain TCR-like antibodies; blocking procedure enables us to avoid the detection of non-TCR-like antibodies.

Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis.

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-1ß), 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-1ß 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-1ß in CSCs, as well as IL-1ß 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-1ß 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-1ß 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.

Long-term changes of choroidal blood flow velocity in Vogt-Koyanagi-Harada disease.

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.

Involvement of Transcription Factor 21 in the Pathogenesis of Fibrosis in Endometriosis.

Repeated tissue injury and repair and fibrosis play a pivotal role in endometriosis. Fibrotic tissue consists of extracellular matrix proteins, regulated by transcriptional factors promoting cell proliferation and survival. Periostin is one of the putative key extracellular matrix proteins. This study aimed to determine whether transcription factor 21 (TCF21) is involved in the development of endometriosis as an upstream regulatory gene of periostin. Formalin-fixed, paraffin-embedded tissue samples [normal endometrium of women without endometriosis; eutopic endometrium of women with endometriosis; ovarian endometriosis (OE); and deep infiltrating endometriosis (DIE)] and respective cells were analyzed. Basal, transiently stimulated, and knocked down periostin and TCF21 concentrations in stromal cells of women with or without endometriosis were examined. Periostin and TCF21 expressions were undetected in normal endometrium of women without endometriosis, weakly positive in eutopic endometrium of women with endometriosis, moderately positive in OE, and strongly positive in DIE. Type 2 helper T-cell cytokines (IL-4, IL-13, and transforming growth factor-ß1) increased the mRNA expression of periostin and TCF21. These cytokines, periostin, and TCF21 colocalized in the stroma of OE and DIE. siRNA against human TCF21 gene suppressed periostin expression. Transfection of TCF21 plasmid vector into stromal cells of women without endometriosis, which originally expressed neither periostin nor TCF21, resulted in TCF21 and periostin expression. TCF21 and periostin are involved in the regulation of fibrosis in endometriosis. TCF21 may be a promising therapeutic target and biomarker in endometriosis.

Impact of perioperative use of GnRH agonist or dienogest on ovarian reserve after cystectomy for endometriomas: a randomized controlled trial.

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_e/ctr_view.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.

Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis.

Folliculogenesis is a complex process, defined by the growth and development of follicles from the primordial population. Granulosa cells (GCs) play a vital role in every stage of follicular growth through proliferation, acquisition of gonadotropic responsiveness, steroidogenesis and production of autocrine/paracrine factors. A recently discovered hypothalamic neuropeptide phoenixin is involved in the regulation of the reproductive system. Phoenixin acts through its receptor, G protein-coupled receptor 173 (GPR173), to activate the cAMP/PKA pathway leading to the phosphorylation of CREB (pCREB). Here, we demonstrated the expression patterns of phoenixin and GPR173 in human ovary and explored its role in folliculogenesis. Phoenixin and GPR173 were both expressed in the human ovarian follicle, with increased expression in GCs as the follicle grows. Phoenixin treatment at 100 nM for 24 h induced the proliferation of human non-luteinized granulosa cell line, HGrC1 and significantly increased the expression levels of CYP19A1, FSHR, LHR and KITL, but decreased NPPC expression levels. These effects were suppressed by GPR173 siRNA. The expression level of CREB1, pCREB and estradiol (E2) production in the culture medium was significantly enhanced by phoenixin treatment in a concentration-dependent manner. Phoenixin also significantly increased the follicular area in a murine ovarian tissue culture model, leading to an increased number of ovulated oocytes with a higher level of maturation. Taken together, our data demonstrate that phoenixin is an intraovarian factor that promotes follicular growth through its receptor GPR173 by accelerating proliferation of GCs, inducing E2 production and increasing the expression of genes related to follicle development.

The association between cone density and visual function in the macula of patients with retinitis pigmentosa.

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.

Molecular mechanism of FSHR expression induced by BMP15 in human granulosa cells.

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.

Animal models of polycystic ovary syndrome: A review of hormone-induced rodent models focused on hypothalamus-pituitary-ovary axis and neuropeptides.

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.

Protective effects of mangafodipir against chemotherapy-induced ovarian damage in mice.

BACKGROUND: Given the seriousness of chemotherapy-induced ovarian injury in female cancer patients, the preservation of fertility, including through the use of cryopreservation technology and pharmaceuticals, requires investigation. Previous studies have shown that damage to the ovaries is related to oxidative stress caused by anticancer drugs. Therefore, superoxide dismutase (SOD) may represent a key factor in the pharmacological protection of the ovaries. The aim of our study was to identify the effects of mangafodipir, a manganese chelate and SOD-mimetic, on suppression of apoptosis in granulosa cells and primordial follicle activation induced by anticancer drugs. METHODS: Cell viability assays using methyltrichlorosilane solutions and immunoblotting for cleaved caspase-3 were performed in in vitro experiments with the simultaneous addition of mangafodipir to human non-luteinized granulosa cell line (HGrC) cultures treated with hydrogen peroxide (H2O2), cisplatin, or paclitaxel. Count and morphological analyses of follicles at each developing stage in the ovaries and immunohistochemistry for cleaved caspase-3, Ki67 and 4-hydroxynonenal, a marker for oxidative stress, were also performed using mangafodipir-injected 6-week-old female ICR mice treated with cisplatin or paclitaxel. Further, mangafodipir was injected into 6-week-old female BALB/c mice inoculated with ES-2 to analyze whether mangafodipir inhibits the anti-tumor effects of cisplatin or paclitaxel treatment. RESULTS: Mangafodipir attenuated apoptosis induced by H2O2 and anticancer drugs in vitro. Mangafodipir also decreased the expression of 4-hydroxynonenal and reduced cisplatin- and paclitaxel-induced apoptosis in granulosa cells in vivo. In addition, mangafodipir inhibited the loss of primordial follicles. Tumor xenograft studies in mice showed that mangafodipir did not affect anticancer drug antitumor effects. CONCLUSIONS: Oxidative stress might be one of the mechanisms of cisplatin- and paclitaxel-induced the loss of primordial follicles. Mangafodipir can reduce cisplatin- and paclitaxel-induced apoptosis in granulosa cells and primordial follicle activation partially via its SOD activity. At the same time, mangafodipir might have other potential mechanisms to inhibit the activation of primordial follicles. Further, mangafodipir attenuated the ovarian damage caused by cisplatin and paclitaxel without affecting their antitumor activities. Mangafodipir, therefore, though its efficacy might be limited, may be a new option for the preservation of fertility during anticancer treatment.

Thyroid Autoantibodies do not Impair the Ovarian Reserve in Euthyroid Infertile Women: A Cross-Sectional Study.

Patients with primary ovarian insufficiency (POI) have a high prevalence of thyroid autoimmune disorders. However, the extent of the contribution of thyroid autoantibodies or elevated thyroid-stimulating hormone (TSH) levels to decreased ovarian reserve is unclear. Therefore, we evaluated the serum levels of anti-Müllerian hormone (AMH) and thyroid autoantibodies [antithyroperoxidase antibody (TPOAb), and antithyroglobulin antibody (TgAb)] in euthyroid infertile women. One hundred and fifty-three women with normal menstrual cycles were recruited for this retrospective study. Serum levels of AMH were compared between patients with positive and negative thyroid autoantibodies. The correlation between serum levels of AMH and each thyroid autoantibody was also evaluated. Participants were observed to be either TPOAb or TgAb positive (n=27), only TPOAb positive (n=8), only TgAb positive (n=7), TPOAb and TgAb positive (double positive; n=12), and TPOAb and TgAb negative (double negative; n=126). No significant differences were found in serum AMH levels between the TPOAb- or TgAb-positive women and the antibody-double negative women. Serum AMH levels did not show a significant correlation with the concentration of TgAb or TPOAb. On the other hand, serum AMH levels negatively correlated with TSH levels in patients who were either positive for TPOAb or TgAb. Thyroid autoantibodies are not likely to influence ovarian reserve in euthyroid women whose TSH levels fall within the normal range although elevated TSH levels may be involved in the decline of serum AMH levels.

Recovery of macular cone photoreceptors in Vogt-Koyanagi-Harada disease.

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.

Clinical application of serum anti-Müllerian hormone as an ovarian reserve marker: A review of recent studies.

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.

Follicle dynamics: visualization and analysis of follicle growth and maturation using murine ovarian tissue culture.

PURPOSE: To visualize and analyze follicle development in ovarian tissue culture using physiological concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in order to establish an ovarian tissue culture system that enables efficient in vitro growth of follicles. METHODS: Ovarian tissues from 4-week-old female ICR mice were sliced and cultured. Images of ovarian tissues in culture were obtained at 24-h or 30-min intervals by using a microscope. The area of each follicle observed in the ovarian tissue slices was tracked and analyzed in association with oocyte maturation. RESULTS: We were able to track the development of each follicle using this culture system. Follicle growth was associated with oocyte maturation. Meiotically matured oocytes (MII) were obtained from 33% of all follicles investigated. Approximately, a quarter of follicles (24%) did not grow and resulted in atresia. CONCLUSION: Follicle dynamics were successfully visualized and analyzed in murine ovarian tissue culture. We were able to obtain mature oocytes from the fully grown follicles in vitro. This culture system would be helpful for efficient in vitro culturing of ovarian tissues.

Results of the Baerveldt® Glaucoma Implant for Neovascular Glaucoma Patients.

Purpose: To evaluate the efficacy and safety of the Baerveldt® glaucoma implant (BGI) for eyes with neovascular glaucoma (NVG). Methods: This was a retrospective study. Thirty-five eyes (31 patients) diagnosed with refractory NVG at Toyama University Hospital were enrolled from January 2012 to December 2015. All patients underwent BGI and were followed up for more than 6 months. Results: The mean age of patients was 62.7±13.9 years old. The mean postoperative follow-up periods was 22.0±12.7 months. The mean preoperative IOP was 35.5±9.6 mmHg and the mean postoperative IOP at 6, 12, 24, 36, 48 month were 12.7±5.9, 12.8±3.7, 12.2±3.3, 13.1±3.3, 15.0±1.4 mmHg respectively. Postoperative visual acuity was not significantly improved. Complications were Hoffmann Elbow erosion in 2 patients who needed additional surgery. The success rate at one year was 82.7%. Postoperative intervention was not required. Conclusion: BGI surgery should be considered a useful treatment to lower the IOP for NVG.

Involvement of mesosalpinx in endometrioma is a possible risk factor for decrease of ovarian reserve after cystectomy: a retrospective cohort study.

BACKGROUND: Serum anti-Müllerian hormone (AMH) concentration has been used to assess ovarian reserve in patients with endometriosis, especially when endometrioma surgery is involved. Previously, we reported that decreased serum AMH levels after cystectomy for endometriomas can recover to preoperative levels in some cases. In this present study, we assessed the sequential changes in serum AMH levels before and after cystectomy in terms of the state of the mesosalpinx prior to surgery. METHODS: The retrospective cohort study recruited 53 patients from a series of prospective studies conducted from 2009 to 2015. All patients underwent laparoscopic cystectomy for endometriomas. If either mesosalpinx was involved in the endometrioma or adnexal adhesion before cystectomy, the case was defined as 'involved mesosalpinx' (n = 14). If both mesosalpinx remained anatomically correct, the case was classified as 'intact mesosalpinx' (n = 39). Blood samples were obtained from the patients 2 weeks before surgery, and at 1 month and 1 year after surgery to assess serum AMH levels. RESULTS: The serum AMH levels (the involved group vs. the intact group) were 1.92 vs. 0.98 (P = 0.552) preoperatively, 0.59 vs. 1.99 (P = 0.049) at 1 month postoperatively, and 0.48 vs. 2.37 ng/mL (P = 0.007) at 1 year postoperatively. The involved mesosalpinx group showed a further decrease in serum AMH levels at 1 year postoperatively, while serum AMH levels in the intact mesosalpinx group tended to recover. CONCLUSION: These results suggest that pre-existing mesosalpinx disturbance, in combination with adhesiolysis, may be involved in the medium- and long-term decrease in ovarian reserve after endometrioma surgery. A disturbance in ovarian blood supply via the mesosalpinx may underlie this. TRIAL REGISTRATION: UMIN-CTR UMIN000019369 . Retrospectively registered October 15, 2015.