The number of previous implantation failures is a critical determinant of intrauterine autologous platelet-rich plasma infusion success in women with recurrent implantation failure.

Purpose: We aimed to identify factors influencing the reproductive outcomes of frozen-thawed embryo transfer (FET) with intrauterine autologous platelet-rich plasma (PRP) infusion in patients with either a thin endometrium or recurrent implantation failure (RIF) despite a normal endometrial appearance. Methods: In this retrospective study of women who underwent PRP-FET, factors influencing PRP-FET outcomes were identified using multivariate logistic regression analysis. Results: We enrolled 111 patients (70 with refractory thin endometrium and 41 with RIF but no thin endometrium). For 99 completed FET cycles, the ß-hCG positivity rate was 46.7%, clinical pregnancy rate (CPR) was 41.0%, and live birth rate (LBR) was 36.2%. PRP treatment was associated with significant improvements over previous cycles, and participants with thin endometria demonstrated thickening. Multivariate logistic regression analysis showed that the number of previous implantation failures in women with RIF was a significant factor affecting the PRP-FET outcomes. The CPR and LBR of women with RIF were lower when there had been ≥3 previous implantation failures occurred. Conclusions: Intrauterine PRP infusion improves the pregnancy outcomes of patients with RIF or a thin endometrium. The number of previous implantation failures is a critical determinant of successful intrauterine PRP infusions in women with RIF.

Age- and endometrial microbiota-related delay in development of endometrial receptivity.

Purpose: We evaluated factors affecting the development of endometrial receptivity according to age and changes in the endometrial microbiota. Methods: We recruited patients with infertility who underwent transcriptomic analyses of endometrial receptivity and the endometrial microbiome prior to frozen embryo transfer. An endometrial biopsy was performed 108 h after initial progesterone administration. Results: In 185 tests from 185 eligible patients, the results of endometrial receptivity analysis were receptive in 111 (60.0%) patients and pre-receptive in 74 (40.0%) patients. Compared with receptive patients, pre-receptive patients had significantly older ages (36.0 ± 0.5 vs. 38.2 ± 0.5, p = 0.0021), a smaller proportion of normal Lactobacillus-dominant microbiota (27.9% vs. 12.2%), and a greater proportion of microbiota with ultralow biomass (22.5% vs. 41.9%) (p = 0.0074). Patient age (adjusted odds ratio: 1.08, 95% confidence interval: 1.01-1.16, p = 0.0351) and a microbiome with ultralow biomass (adjusted odds ratio: 3.82, 95% confidence interval: 1.49-9.82, p = 0.0039) were independent predictive factors for pre-receptive endometrium. Conclusions: Older age was accompanied by a decrease in Lactobacillus-dominant microbiota; aging and endometrial microbiota with ultralow biomass were significantly associated with pre-receptive endometrium. Our findings suggest that the quantity (rather than proportion) of Lactobacillus in the endometrium is important in the development of endometrial receptivity.

Shapes of the uterine cavity are different in women with polycystic ovary syndrome.

Purpose: A cross-sectional study was conducted to evaluate differences in uterine morphology between women with or without polycystic ovary syndrome. Methods: The authors recruited 333 infertile reproductive-age women including 93 with polycystic ovary syndrome diagnosed using the criteria of the Japanese Society of Obstetrics Gynecology-2007. Shapes of uterine cavity were measured by transvaginal three-dimensional ultrasound. Results: The polycystic ovary syndrome group had a significantly deeper indentation (2.2 ± 0.4 mm vs. 0.0 ± 0.2 mm, p < 0.0001) and a significantly more acute indentation angle (162.9 ± 2.2 deg vs. 175.2 ± 1.3 deg, p < 0.0001) than the control group. Conclusion: The depth and the apical angle of fundal indentation of uterine cavity are different in women with polycystic ovary syndrome.

Creation, effects on embryo quality, and clinical outcomes of a new embryo culture medium with 31 optimized components derived from human oviduct fluid: A prospective multicenter randomized trial.

Purpose: Our aim is to make an ideal embryo culture medium close to human oviduct fluid (HOF) components, and to evaluate the quality of this medium with embryo quality and clinical outcomes in assisted reproductive technology (ART) by a prospective randomized controlled trial (RCT). Methods: Study I: HOF was collected laparoscopically from patients (n = 28) with normal pelvic findings. According to HOF analysis results, the new medium "HiGROW OVIT®" (OVIT) was designed. Study II: Embryos (2 pronuclei (2PN) = 9633) were assigned from 1435 patients. The blastulation rate (BR), good BR (gBR), utilized (transferred/cryo-preserved) BR (uBR), pregnancy rate (PR), and miscarriage rate (MR) were compared between the OVIT and control groups by RCT. Results: The novel medium 'OVIT' was produced according to 31 HOF components. The concentrations of essential amino acids (e-AAs) were lower in OVIT than in current media, yet the opposite was true for ne-AA concentrations. gBR and uBR were higher in the OVIT group than in the control group. In the older female group, gBT and uBR were significantly higher in the OVIT group. Conclusions: The novel medium 'OVIT' was produced according to HOF data. The OVIT had significantly better embryo quality and clinical outcomes than the current media.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition.

Gynecology in the office setting is developing worldwide. Clinical guidelines for office gynecology were first published by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011. These guidelines include a total of 72 clinical questions covering four areas (Infectious disease, Malignancies and benign tumors, Endocrinology and infertility, and Healthcare for women). These clinical questions were followed by several answers, backgrounds, explanations and references covering common problems and questions encountered in office gynecology. Each answer with a recommendation level of A, B or C has been prepared based principally on evidence or consensus among Japanese gynecologists.These guidelines would promote a better understanding of the current standard care practices for gynecologic outpatients in Japan.

An investigation of the potential effect of vacuoles in human sperm on DNA damage using a chromosome assay and the TUNEL assay.

BACKGROUND: The aims of this study were to establish whether individual differences exist in the frequency and size of vacuoles found in human sperm and to ascertain whether such vacuoles are involved in causing DNA damage. METHODS: Morphologically normal sperm were obtained from 15 IVF and 2 ICSI patients and 3 fertile donors. (i) Sperm heads were analyzed for the presence of vacuoles under a 1000× differential interference contrast microscope. (ii) In three patients and two donor samples, structural chromosomal damage was evaluated in normal sperm containing large vacuoles and selected at 1000× magnification for injection into mouse oocytes. (iii) In 10 patients and two donor samples, confocal laser microscopy detected DNA damage in sperm-exhibiting large vacuoles and stained with an in situ cell death detection kit. RESULTS: (i) Vacuoles were observed in almost all normal sperm from patient and donor ejaculates and were mainly located at the tip or middle area of the sperm heads. However, average incidence of normal sperm exhibiting large vacuoles was 4.6 and 4.2% in the patient and donor groups, respectively. (ii) Sperm chromosome assays did not reveal any differences in the incidence of structural chromosome aberrations between sperm exhibiting large vacuoles and those without them (9.1 versus 4.1%). (iii) No significant difference in frequency of TUNEL-positive cells was found between normal sperm with large vacuoles and those without them in the samples examined. Among 227 sperm exhibiting large vacuoles, only 7 cells were TUNEL positive. CONCLUSION: The results showed that large vacuoles were not responsible for DNA damage, suggesting that intra-cytoplasmic injection of morphologically selected sperm may not be required for patients who produce high-quality semen.

Correlation between natural cytotoxicity receptors and intracellular cytokine expression of peripheral blood NK cells in women with recurrent pregnancy losses and implantation failures.

PROBLEM: Natural cytotoxicity receptors (NCRs) are unique markers, which regulate NK cell cytotoxicity and cytokine production. We investigated whether women with recurrent pregnancy losses (RPLs) and implantation failures have aberrant correlation between NCRs and intracellular cytokine expression of NK cells. METHOD OF STUDY: Peripheral blood NK cells (CD56(dim) and CD56(bright)) were analyzed for NCRs (NKp46, NKp44 and NKp30) and cytokine expression (TNF-alpha, IFN-gamma, IL-4, IL-10) using flow cytometry in RPL (n = 22), implantation failures (n = 23) or controls (n = 15). RESULTS: In type 1 cytokine studies, CD56(bright)/NKp30(+) cells in controls (r = 0.696, P < 0.05) were positively correlated with CD56(bright)/IFN-gamma(+)/TNF-alpha(+) cells. CD56(bright)/NKp46(+) cells in implantation failures (r = -0.76, P < 0.01) were negatively correlated with CD56(bright)/IFN-gamma(+)/TNF-alpha(-) cells. RPL did not have any correlation. In type 2 cytokine studies, CD56(+)/NKp46(+) cells (r = 0.758, P < 0.01) and CD56(+)/NKp30(+) cells (r = 0.637, P < 0.05) were positively correlated with CD56(bright)/IL-4(+)/IL-10(+) cells in controls. CD56(+)/NKp30(+) cells in implantation failures (r = -0.778, P < 0.05) were negatively correlated with CD56(bright)/IL-10(+)/IL-4(+) cells. There were no correlations in RPL. CONCLUSION: Recurrent pregnancy losses and implantation failures have lack of, or negative correlation between NCRs and intracellular cytokines expression. This observation suggests that excessive pro-inflammatory cytokine expression in NK cells in RPL and implantation failures may be exerted through the NCRs or interruption of signal transduction processes.

Timed sexual intercourse facilitates the recruitment of uterine CD56(bright) natural killer cells in women with infertility.

PROBLEM: The aim of this study was to investigate the influence of sexual intercourse on uterine NK cell subsets. METHOD OF STUDY: Mid-secretory endometrial samples obtained from 56 women were submitted for flow cytometric analysis. Basal body temperature was used to determine the day of ovulation. A total of 27 women had sexual intercourse before ovulation (pre-ovulation group) and eight women had only after ovulation (post-ovulation group) without any contraceptive devices. A total of 21 women did not have sexual intercourse during the experimental cycle (abstinence group). Endometrial NK cells were analyzed for the expression of CD16 and CD56 using 3-color flow cytometry. RESULTS: CD16(-)/CD56(bright) cells were markedly increased in the pre-ovulation group as compared with that of the post-ovulation group (P < 0.01) and the abstinence group (P < 0.01). CD16(+)/CD56(dim) cells were significantly decreased in the pre-ovulation group as compared with that of the post-ovulation group (P < 0.01) and the abstinence group (P < 0.05). CONCLUSION: It is suggested that seminal plasma participates in the recruitment of CD56(bright) NK cells into endometrium.

Erythrocytes counteract the negative effects of female ageing on mouse preimplantation embryo development and blastocyst formation.

BACKGROUND: The low developmental competence of embryos from ageing females remains an enigma; it is presumably attributable to oxidative stress. A number of antioxidant mechanisms exist in the erythrocyte and these have been investigated in other cells and tissues. However, very few studies have reported the effects of erythrocyte supplementation on developmental competence in ageing embryos. METHODS: In Experiment 1, IVF embryos from young (7-10 weeks) mice were cultured in medium supplemented with an oxidizing agent, hypoxanthine/xanthine oxidase, in the presence and absence of erythrocytes. In Experiment 2, the development of embryos derived from young and ageing (40-50 weeks) female mice was assessed in the presence and absence of erythrocytes. RESULTS: In Experiment 1, the presence of hypoxanthine/xanthine oxidase significantly inhibited embryo development (P < 0.0001). Erythrocyte supplementation clearly overcame the detrimental effects in a dose-related manner. In Experiment 2, in the absence of erythrocytes, developmental competence was significantly lower in embryos from ageing females than in those from young females (P < 0.01). However, in ageing females, the supplementation of erythrocytes significantly promoted the development of embryos to the blastocyst stage (51.1% versus 77.3%; P < 0.01). CONCLUSIONS: Supplementation with erythrocytes can counteract the negative effect of maternal ageing on embryo development and blastocyst formation.