A common trajectory of gut microbiome development during the first month in healthy neonates with limited inter-individual environmental variations.

The early development of the gut microbiome is governed by multiple factors and has significantly long-term effects on later-in-life health. To minimize inter-individual variations in the environment, we determined developmental trajectories of the gut microbiome in 28 healthy neonates during their stay at a postpartum center. Stool samples were collected at three time points: the first-pass meconium within 24 h of life, and at 7 and 28 days of age. Illumina sequencing of the V3-V4 region of 16S rRNA was used to investigate microbiota profiles. We found that there was a distinct microbiota structure at each time point, with a significant shift during the first week. Proteobacteria was most abundant in the first-pass meconium; Firmicutes and Actinobacteria increased with age and were substituted as the major components. Except for a short-term influence of different delivery modes on the microbiota composition, early microbiome development was not remarkably affected by gravidity, maternal intrapartum antibiotic treatment, premature rupture of membranes, or postnatal phototherapy. Hence, our data showed a similar developmental trajectory of the gut microbiome during the first month in healthy neonates when limited in environmental variations. Environmental factors external to the host were crucial in the early microbiome development.

Associations between the artificial intelligence scoring system and live birth outcomes in preimplantation genetic testing for aneuploidy cycles.

BACKGROUND: Several studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes in cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, the effectiveness of iDAScore in cycles with PGT-A has not been thoroughly investigated. Therefore, this study aims to assess the association between artificial intelligence (AI)-based iDAScore (version 1.0) and pregnancy outcomes in single-embryo transfer (SET) cycles with PGT-A. METHODS: This retrospective study was approved by the Institutional Review Board of Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET cycles (n = 482) following PGT-A at a single reproductive center between January 2017 and June 2021. The blastocyst morphology and morphokinetics of all embryos were evaluated using a time-lapse system. The blastocysts were ranked based on the scores generated by iDAScore, which were defined as AI scores, or by KIDScore D5 (version 3.2) following the manufacturer's protocols. A single blastocyst without aneuploidy was transferred after examining the embryonic ploidy status using a next-generation sequencing-based PGT-A platform. Logistic regression analysis with generalized estimating equations was conducted to assess whether AI scores are associated with the probability of live birth (LB) while considering confounding factors. RESULTS: Logistic regression analysis revealed that AI score was significantly associated with LB probability (adjusted odds ratio [OR] = 2.037, 95% confidence interval [CI]: 1.632-2.542) when pulsatility index (PI) level and types of chromosomal abnormalities were controlled. Blastocysts were divided into quartiles in accordance with their AI score (group 1: 3.0-7.8; group 2: 7.9-8.6; group 3: 8.7-8.9; and group 4: 9.0-9.5). Group 1 had a lower LB rate (34.6% vs. 59.8-72.3%) and a higher rate of pregnancy loss (26% vs. 4.7-8.9%) compared with the other groups (p < 0.05). The receiver operating characteristic curve analysis verified that the iDAScore had a significant but limited ability to predict LB (area under the curve [AUC] = 0.64); this ability was significantly weaker than that of the combination of iDAScore, type of chromosomal abnormalities, and PI level (AUC = 0.67). In the comparison of the LB groups with the non-LB groups, the AI scores were significantly lower in the non-LB groups, both for euploid (median: 8.6 vs. 8.8) and mosaic (median: 8.0 vs. 8.6) SETs. CONCLUSIONS: Although its predictive ability can be further enhanced, the AI score was significantly associated with LB probability in SET cycles. Euploid or mosaic blastocysts with low AI scores (≤ 7.8) were associated with a lower LB rate, indicating the potential of this annotation-free AI system as a decision-support tool for deselecting embryos with poor pregnancy outcomes following PGT-A.

From Infection to Malignancy: Tracing the Impact of Human Papillomavirus on Uterine Endometrial Cancer in a Nationwide Population-Based Cohort Study.

Uterine endometrial cancer (EC) is the most common gynecological malignancy in Taiwan. This study aimed to investigate the association between human papillomavirus (HPV) infection and the development of uterine EC among Taiwanese women. A nationwide population cohort research approach was employed, leveraging longitudinal health insurance databases (LHID 2007 and 2015) from the National Health Insurance Research Database alongside data from the Taiwan Cancer Registry datasets. A comparative analysis examined 472,420 female patients with HPV infection and 944,840 without HPV infection. The results demonstrated that the HPV cohort exhibited a significantly elevated risk of uterine EC, as evidenced by an adjusted hazard ratio (aHR) of 1.588 (95% CI: 1.335-1.888). Furthermore, this elevated risk extended to type 1 EC with an aHR of 1.671 (95% CI: 1.376-2.029), specifically the endometrioid adenocarcinoma subtype with an aHR 1.686 (95% CI: 1.377-2.065). Importantly, these findings were statistically significant (p < 0.001). In conclusion, this research unveils a potential association between HPV infection and an increased risk of uterine EC, particularly the type 1 endometrial cancer subtype, within the Taiwanese female population. These findings have implications for preventive measures and screening programs targeting HPV infection to reduce the risk of this prevalent gynecological malignancy in Taiwan.

Significantly shortened telomere length and altered androgen receptor level in cumulus cells from women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to investigate the correlation between hormone receptor levels and telomere length (TL) in infertile women with and without polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: This prospective cohort study recruited a total of 431 cumulus oocyte complex (COC) from 88 infertile women between July 2012 and June 2014. The participants were divided into three groups: young age (<38 years, n = 42 and 227 COC), advanced age (≥38 years, n = 33 and 107 COC) and PCOS patients (n = 13 and 97 COC). Cumulus cells were collected from individual follicle during oocyte pick-up, and the mRNA levels of hormone receptors and TL were measured using real-time PCR. RESULTS: The cumulus cells of PCOS patients demonstrated lower mRNA levels of LH receptor (75.57 ± 138.10 vs. 171.07 ± 317.68; p < 0.01) and androgen receptor (1.13 ± 1.52 vs. 4.08 ± 9.57; p < 0.01), as well as a shorter TL (2.39 ± 2.58 vs. 3.96 ± 4.72; p < 0.01) compared to those of the young age group. In the young age group, only androgen receptor mRNA level showed a significant association with TL (rho = 0.148, p = 0.026), while FSH receptor mRNA level was the only factor associated with TL (rho = 0.247, p = 0.015) in PCOS patients. For advanced-aged patients, no significant relationship was observed between hormone receptor mRNA levels and TL. Alternative splicing of androgen receptors was identified in some PCOS patients but not in young age controls. CONCLUSION: The findings suggest that the androgen receptor level and function may be altered in the cumulus cells of PCOS patients, leading to a shorter TL in cumulus cells in PCOS patients.

Innovative technology for evaluation of sperm DNA double-strand breaks diagnoses male factor infertility and prevents reproductive failures.

Neutral comet assay has been available for two decades to evaluate sperm double-strand breaks (DSBs). However, its clinical usability is limited due to its complex and time-consuming procedure, as well as the lack of a standardized scoring system. The aim of this study was to: develop a rapid diagnostic method for DSBs, Sperm DNA Fragmentation Releasing Assay (SDFR), and explore the association between DSBs and reproductive outcomes. We pioneered the use of polyacrylamide (PA) for embedding sperm chromatin and optimized the porosity of PA to be between 10 and 13%. The refined PA network allowed the trapping of DSBs, which dispersed halo on an immunological slide; in contrast, intact chromatin failed to develop a halo. A strong correlation was showed between reproducible values obtained from SDFR and neutral comet assay. SDFR were responsive to dose-/time-dependent simulated DSBs, indicating high sensitivity and specificity. Furthermore, we conducted a retrospective study of couples with embryonic aneuploidy screening, and recording DSB profiles of the male partners. Our findings revealed that DSB enabled to predict embryonic aneuploidy whereas basic semen parameters did not. In conclusion, SDFR offers a rapid and user-friendly approach for evaluating DSBs, with potential implications for predictive healthcare in reproductive medicine.

Factors Affecting the Potential Efficacy of Intrauterine Platelet-Rich Plasma Infusion on Thin Endometrium in Women with Recurrent Implantation Failure.

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study aims to identify the risk factors associated with the failure of intrauterine PRP infusion for thin endometrium in women with recurrent implantation failure (RIF). We retrospectively reviewed data from 77 women with RIF, all exhibiting an EMT of <7 mm. These women underwent programmed hormone therapy for frozen embryo transfer (FET) and received two autologous intrauterine PRP infusions. Following intrauterine PRP-lysate (PL) infusions, the mean increase in EMT was 1.9 ± 1.2 mm, with EMT reaching 7 mm in 86% of the cases (66/77; average EMT, 8.3 mm). We identified an exceedingly thin EMT as a risk factor impacting the therapeutic efficacy in increasing EMT (p = 0.04, OR: 3.16; 95% CI: 1.03-9.67). Additionally, the number of previous uterine surgeries emerged as a prognostic factor for pregnancy failure following PL infusion (p = 0.02, OR: 2.02; 95% CI: 1.12-3.64). Our findings suggest that an extremely thin EMT and a history of numerous uterine surgeries can impede successful pregnancy, even when an optimal EMT is achieved following PRP infusion.

SUMO1 and Defective Spermatozoa Correlate with Endogenous Hydrogen Peroxide and Live Birth Outcome in Intrauterine Insemination Cycles for Unexplained Infertility.

This study aimed to investigate the correlation between hydrogen peroxide (H2O2), small ubiquitin-like modifier molecules (SUMO), and pregnancy outcomes in couples with unexplained infertility (UI) undergoing intrauterine insemination (IUI) treatment. We prospectively collected semen samples from 56 couples with UI and divided the spermatozoa into motile and immotile fractions by density gradient centrifugation (DSC). Immunofluorescence staining was used to examine the immunostaining and localization of nuclear pore complex (NPC), SUMO1, and SUMO2/3 in spermatozoa. We detected H2O2 levels by chemiluminescence methods. We found that H2O2 levels correlated with NPC (neck) (r = 0.400) and NPC (tail) (r = 0.473) in motile sperm fractions. In immotile fractions, H2O2 positively correlated with NPC (tail) (r = 0.431) and SUMO1 (neck) (r = 0.282). Furthermore, the positive NPC (tail) group had a significantly lower live birth rate than the negative NPC group (17.9% = 5/28 vs. 42.9% = 12/28). In conclusion, H2O2 positively correlated with SUMO1 (neck) and NPC (tail) in human spermatozoa. The DSC may partially eliminate defective spermatozoa (positive NPC staining); however, if defective spermatozoa remain in the motile fraction, this scenario is associated with a low live birth rate following IUI treatment.

Increased incidence of live births in implanted day 5 versus day 6 blastocysts following single embryo transfers with PGT-A.

Elective single-embryo transfers of euploid or low-level mosaic blastocysts were analyzed in this retrospective study to determine the correlations of live birth (LB) probability with embryonic developmental features of implanted day 5 (D5, n = 245) or day 6 (D6, n = 73) blastocysts using time-lapse (TL) monitoring. According to the logistic regression analyses (adjusted odds ratio [OR] = 0.341, 95% confidence interval [CI] = 0.169-0.685, P < 0.05), the LB probability was negatively associated with the D6 group. The LB rate of the D5 group was higher than the D6 group (88.2% vs. 75.3%; P < 0.05). Compared with the D5 blastocysts, the D6 blastocysts exhibited comparable dysmorphisms except for the multinucleation at the 4-cell stage (10.9% vs. 2.9%, P < 0.05). Moreover, D6 blastocysts had considerably slower developmental kinetics and poorer blastocyst morphologies. Further analysis confirmed that the LB rate was not associated with developmental kinetics or dysmorphisms but rather with blastocyst morphology (inner cell mass [ICM] grade ≤ C vs. ICM grade A, adjusted OR = 0.155, 95% CI = 0.04-0.596, P < 0.05; trophectoderm [TE] grade ≤ C vs. TE grade A, adjusted OR = 0.157, 95% CI = 0.032-0.760, P < 0.05). In conclusion, D6 implanted blastocysts have a considerably lower LB rate than D5 implanted blastocysts. As determined by TL monitoring, the diminished blastocyst morphology can be one of the primary reasons underlying the decreased likelihood of LB.

Chromosomal, gestational, and neonatal outcomes of embryos classified as a mosaic by preimplantation genetic testing for aneuploidy.

OBJECTIVE: To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy. DESIGN: Analysis of data collected between 2017 and 2023. SETTING: Multicenter. PATIENTS: Patients of infertility treatment. INTERVENTION: Comparison of pregnancies resulting from embryos classified as euploid or mosaic using the 20%-80% interval in chromosomal intermediate copy numbers to define a mosaic result. MAIN OUTCOME MEASURES: Rates of spontaneous abortion, birth weight, length of gestation, incidence of birth defects, and chromosomal status during gestation. RESULTS: Implanted euploid embryos had a significantly lower risk of spontaneous abortion compared with mosaic embryos (8.9% [n = 8,672; 95% confidence interval {CI95} 8.3, 9.5] vs. 22.2% [n = 914; CI95 19.6, 25.0]). Embryos with mosaicism affecting whole chromosomes (not segmental) had the highest risk of spontaneous abortion (27.6% [n = 395; CI95 23.2, 32.3]). Infants born from euploid, mosaic, and whole chromosome mosaic embryos had average birth weights and lengths of gestation that were not statistically different (3,118 g and 267 days [n = 488; CI95 3,067, 3,169, and 266, 268], 3052 g and 265 days [n = 488; CI95 2,993, 3,112, and 264,267], 3,159 g and 268 days [n = 194; CI95 3,070, 3,249, and 266,270], respectively). Out of 488 infants from mosaic embryo transfers (ETs), one had overt gross abnormalities as defined by the Centers for Disease Control and Prevention. Most prenatal tests performed on pregnancies from mosaic ETs had normal results, and only three pregnancies produced prenatal test results reflecting the mosaicism detected at the embryonic stage (3 out of 250, 1.2%; CI95 0.25, 3.5). CONCLUSION: Although embryos classified as mosaic experience higher rates of miscarriage than euploid embryos (with a particularly high frequency shortly after implantation), infants born of mosaic ETs are similar to infants of euploid ETs. Prenatal testing indicates that mosaicism resolves during most pregnancies, although this process is not perfectly efficient. In a small percentage of cases, the mosaicism persists through gestation. These findings can serve as risk-benefit considerations for mosaic ETs in the fertility clinic.

Early Gut Microbiota Profile in Healthy Neonates: Microbiome Analysis of the First-Pass Meconium Using Next-Generation Sequencing Technology.

Gut microbiome development during early life has significant long-term effects on health later in life. The first-pass meconium is not sterile, and it is important to know the initial founder of the subsequent gut microbiome. However, there is limited data on the microbiota profile of the first-pass meconium in healthy neonates. To determine the early gut microbiota profile, we analyzed 39 samples of the first-pass meconium from healthy neonates using 16S rRNA sequencing. Our results showed a similar profile of the microbiota composition in the first-pass meconium samples. Pseudomonas was the most abundant genus in most samples. The evenness of the microbial communities in the first-pass meconium was extremely poor, and the average Shannon diversity index was 1.31. An analysis of the relationship between perinatal characteristics and the meconium microbiome revealed that primigravidae babies had a significantly higher Shannon diversity index (p = 0.041), and the Bacteroidales order was a biomarker for the first-pass meconium of these neonates. The Shannon diversity index was not affected by the mode of delivery, maternal intrapartum antibiotic treatment, prolonged rupture of membranes, or birth weight. Our study extends previous research with further characterization of the gut microbiome in very early life.

Live motile sperm sorting device for enhanced sperm-fertilization competency: comparative analysis with density-gradient centrifugation and microfluidic sperm sorting.

PURPOSE: A live motile sperm sorting device (LensHooke® CA0) developed to prevent the deleterious effects of centrifugation was evaluated comparatively with conventional density-gradient centrifugation (DGC) and microfluidic-based device (Zymot) in sperm selection. METHODS: Semen samples from 239 men were collected. CA0 under different incubation intervals (5, 10, 30, and 60 min) and temperatures (20, 25, and 37℃) was conducted. The sperm quality in CA0-, DGC-, and Zymot-processed samples was then comparatively evaluated. Semen parameters included concentration, motility, morphology, motion kinematics, DNA fragmentation index (DFI), and the rate of acrosome-reacted sperm (AR). RESULTS: Total motility and motile sperm concentration increased in a time- and temperature-dependent manner and the total motility peaked for 30 min at 37℃. In paired analysis, CA0 showed significantly higher total motility (94.0%), progressive motility (90.8%), rapid progressive motility (83.6%), normal morphology (10.3%), and lower DFI (2.4%) and AR (4.7%) than the other two methods in normozoospermic samples (all p < 0.05). For non-normozoospermic samples, CA0 had significantly better results than the other two methods (total motility 89.2%, progressive motility 80.4%, rapid progressive motility 74.2%, normal morphology 8.5%, DFI 4.0%, and AR 4.0%; all p < 0.05). CONCLUSION: CA0 yielded spermatozoa with enhanced sperm fertilization potentials; DFI was minimized in samples processed by CA0. CA0 was effective for both normal and abnormal semen samples due to its consistent selection efficiency.

Comparison of clinical outcome between day 5 and day 6 single blastocyst transfers in cycles undergoing preimplantation genetic testing for aneuploidy.

OBJECTIVE: In vitro fertilization (IVF) treatment has gradually adopted the practice of culturing embryos until the blastocyst stage on the D5 or D6 as the standard approach. PGT-A is commonly used in vitro fertilization (IVF). This study aimed to evaluate the clinical outcomes of frozen embryo transfers (FETs) using single blastocyst transfers (SBTs) on the fifth (D5) or sixth (D6) day of development in cycles that underwent preimplantation genetic testing for aneuploidy (PGT-A). MATERIALS AND METHODS: The patients who had at least one euploid or mosaic blastocyst of good quality determined by PGT-A results and received single embryo transfer (SET) cycles were included in the study. In this study, the live birth rate (LBR) and neonatal outcomes were compared after the transfer of single biopsied D5 and D6 blastocysts in frozen embryo transfer (FET) cycles. RESULTS: A total of 527 frozen-thawed blastocyst transfer (FET) cycles (8449 biopsied embryos were analyzed). No significant difference in the implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR) between the transfers of D5 and D6 blastocysts. Birth weight was the only perinatal outcome that showed a significant difference between the D5 and D6 groups. CONCLUSION: The study confirmed that the transfer of a single euploid or mosaic blastocyst, regardless of whether it was on the fifth (D5) or sixth (D6) day of development, can lead to promising clinical results.

The presence of vacuoles in blastocysts is negatively associated with euploidy and live birth rates.

OBJECTIVE: To investigate whether the presence of vacuoles in biopsied blastocysts is associated with the likelihood of aneuploidy and clinical outcomes. DESIGN: Retrospective observational study. SETTING: A single reproductive center. INTERVENTION(S): None. PATIENT(S): This study retrospectively analyzed data obtained through preimplantation genetic testing for aneuploidy performed on 3351 blastocysts from 826 patients at a single reproductive center between August 2018 and July 2020. Ultimately, 167 single euploid blastocyst transfers were performed in these patients. Vacuoles existing in the trophectoderm or inner cell mass were observed using blastocyst biopsy. After the biopsy, all blastocysts were vitrified, and embryo transfer was performed in a subsequent treatment cycle. MAIN OUTCOME MEASURE(S): The associations between vacuoles and euploidy or live birth rates were assessed using logistic regression models and estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULT(S): Of the 3351 blastocysts from 826 patients, 903 (26.9%) were discovered to have vacuoles. The vacuole-positive group had a significantly lower percentage of euploid blastocysts after TE biopsy than the vacuole-negative group (28.8% vs. 35.5%). Embryos with vacuoles were significantly more likely to be poor quality (30.6% vs. 18.2%). Logistic regression analyses revealed that euploid blastocysts were positively associated with the absence of vacuoles, maternal age, and good embryo quality (vacuole-negative group: adjusted OR 1.291; 95% CI: 1.089-1.530; age <38 years: adjusted OR 1.989; 95% CI: 1.692-2.337; good embryo quality: adjusted OR 1.703; 95% CI: 1.405-2.064). The implantation and live birth rates were significantly lower for the transferred single euploid blastocysts with vacuoles than those without (35.5% vs. 56.6%; 29.0% vs. 52.2%, respectively). The live birth rate was positively associated with the absence of vacuoles (adjusted OR 2.792; 95% CI: 1.180-6.608). CONCLUSION(S): The formation of vacuoles in blastocysts is associated with lower rates of euploidy and live birth. Blastocysts without vacuoles should thus be prioritized for embryo transfer in vitro fertilization cycles.

Development and integration of LensHooke® R10 for automatic and standardized diagnosis for sperm DNA fragmentation.

BACKGROUND: The sperm chromatin dispersion assay is commonly used to assess sperm DNA integrity. This approach is time-consuming, demonstrates poor chromatin preservation, and provides an ambiguous and unstandardized evaluation of fragmented chromatin. OBJECTIVES: We aimed to (i) develop an optimized sperm chromatin dispersion assay with reduced operation time, (ii) validate R10 test accuracy by comparing it to a conventional sperm chromatin dispersion assay, and (iii) standardize the sperm DNA fragmentation analysis procedure by integrating artificial intelligence optical microscopic technology. MATERIALS AND METHODS: This cross-section study included 620 semen samples. Aliquots were analyzed by a conventional Halosperm® G2 assay (G2) and LensHooke® R10 assay (R10). The DNA fragmentation index was scored manually, and R10 slides were automatically determined by a LensHooke® X12 PRO semen analysis system (X12). RESULTS: We demonstrated significant improvements in total assay time (40 vs. 72 min, p < 0.001) and in the halo-cytological resolution using R10 compared to G2. Comparing the G2 and R10, DNA fragmentation index results demonstrated good agreement between the two methods (Spearman's rank correlation, rho = 0.8517, p < 0.0001). We introduced the integration of an auto-calculation system to diagnose sperm DNA fragmentation. X12 interpretation showed excellent agreement with manual interpretation (Spearman's rank correlation, rho = 0.9323, p < 0.0001), but had a low coefficient of variation compared to manual interpretation (4% for R10 by X12 vs. 19% for R10 by manual scoring vs. 25% for G2 by manual scoring). DNA fragmentation index was more correlated with total motility (coefficients = -0.3607, p < 0.0001) than sperm morphology and was positively associated with asthenozoospermic semen samples (p = 0.0001). CONCLUSION: The R10 sperm chromatin dispersion assay combined with the X12 semen analysis system is faster, more objective, and provides standardization for sperm DNA fragmentation.

Biphasic oxygen tension promotes the formation of transferable blastocysts in patients without euploid embryos in previous monophasic oxygen cycles.

This study evaluated whether the concentration of biphasic O2 (5-2%) promotes the formation of qualified blastocysts (QBs) and euploid blastocysts and the probability of cycles with transferable blastocysts. The paired experimental design included a total 90 patients (180 cycles) without euploid blastocysts in previous monophasic O2 (5%) cycles were enrolled for an additional cycle of biphasic O2 (5-2%). In the biphasic O2 (5-2%) group, the QB rate (35.8%, 225/628) was significantly higher than that in the monophasic O2 (5%) group (23.5%, 137/582; p < 0.001). In addition, the euploid blastocyst number (0.5 ± 0.8) and the percentage of cycles with transferable blastocysts were significantly higher in the biphasic O2 (5-2%) group (57.8%, 52/90) than those in the monophasic O2 (5%) group (0 and 35.6%, 32/90, respectively; p < 0.01). Multivariable regression analysis also indicated that the QB rate and the probability of cycles with transferable blastocysts correlated with O2 tension (OR 1.535, 95% CI 1.325-1.777, and OR 3.191, 95% CI 1.638-5.679, respectively; p < 0.001). Biphasic O2 culture can be used as an alternative strategy to increase the euploid QBs and the probability of cycles with transferable blastocysts in patients with a poor prognosis.

Association between Leukemia Inhibitory Factor Gene Polymorphism and Clinical Outcomes among Young Women with Poor Ovarian Response to Assisted Reproductive Technology.

BACKGROUND: Does the presence of single-nucleotide polymorphisms (SNPs) in the leukemia inhibitory factor (LIF) gene affect ovarian response in infertile young women? METHODS: This was a case-control study recruiting 1744 infertile women between January 2014 to December 2015. The 1084 eligible patients were stratified into four groups using the POSEIDON criteria. The gonadotropin-releasing hormone receptor (GnRHR), follicle-stimulating hormone receptor (FSHR), anti-Müllerian hormone (AMH), and LIF SNP genotypes were compared among the groups. The distributions of LIF and FSHR among younger and older patients were compared. Clinical outcomes were also compared. RESULTS: The four groups of poor responders had different distributions of SNP in LIF. The prevalence of LIF genotypes among young poor ovarian responders differed from those of normal responders. Genetic model analyses in infertile young women revealed that the TG or GG genotype in the LIF resulted in fewer oocytes retrieved and fewer mature oocytes relative to the TT genotypes. In older women, the FSHR SNP genotype contributed to fewer numbers of mature oocytes. CONCLUSIONS: LIF and FSHR SNP genotypes were associated with a statistically significant reduction in ovarian response to controlled ovarian hyperstimulation in younger and older women with an adequate ovarian reserve, respectively.

Combination treatment with cyclosporin A and arsenic trioxide induce synergistic cell death via non-apoptotic pathway in uterine cervical cancer cells.

Cyclosporin A is an immunosuppressive drug with anti-cancer effect. Arsenic trioxide (As2O3), a well-known cancer-inhibiting drug, induced cytotoxicity via apoptosis and autophagy. The aim of this study is to evaluate the effect of combinational treatment with cyclosporin A and arsenic trioxide on cell viability inhibition in cervical cancer cells. Using MTT assay and combination index, combinational treatment with cyclosporin A and arsenic trioxide induced a synergistic cytotoxic effect in Caski and SiHa cells. Cyclosporin A and arsenic trioxide triggered cell death via non-apoptotic pathway by using annexin V/propidium iodide (PI) assay. Cyclosporin A and arsenic trioxide combined treatment decreased mitochondrial membrane potential and increase reactive oxygen species (ROS) generation. This co-treatment increased LC3B-II expression and autophagosome formation in cervical cancer cells. This study first demonstrated that combinational treatment with cyclosporin A and As2O3 trigger synergistic cytotoxic effect via autophagy in cervical cancer cells.

Risk of Infertility in Males with Obstructive Sleep Apnea: A Nationwide, Population-Based, Nested Case-Control Study.

Obstructive sleep apnea (OSA) yields intermittent hypoxia, hypercapnia, and sleep fragmentation. OSA is associated with chronic medical conditions such as cardiovascular diseases, metabolic syndrome, and neurocognitive dysfunction. However, the risk of infertility in OSA remains unclear due to limited data and lack of long-term population-based studies. The study aims to assess the risk of infertility in obstructive sleep apnea (OSA) by means of a population-based cohort study. The data was utilized from the Taiwan National Health Insurance Research Database (NHIRD) to conduct a population-based cohort study (1997-2013). Compared with the Non-OSA group, the male with OSA and surgery group has the OR (odds ratio) of infertility of 2.70 (95% CI, 1.46-4.98, p = 0.0015), but no significance exists in females with OSA. When the data was stratified according to age and gender, some associations in the specific subgroups were significant. Respectively, males aged 20-35 years old and aged 35-50 years old with a history of OSA and surgery both had a positive association with infertility. (aOR: 3.19; 95% CI, 1.18-8.66, p = 0.0227; aOR: 2.57; 95% CI, 1.18-5.62 p = 0.0176). Male patients with OSA suffer from reduced fertility, but no significant difference was noted in females with OSA. The identification of OSA as a risk factor for male infertility will aid clinicians to optimize long-term medical care. Furthermore, more studies will be encouraged to clarify the effect of OSA on female fertility.

Assessment of Telomere Length and Mitochondrial DNA Copy Number in Granulosa Cells as Predictors of Aneuploidy Rate in Young Patients.

Background: To identify the correlation among female age, cellular aging markers, and aneuploidy rate in in vitro fertilization (IVF) and the preimplantation genetic test for aneuploidy (PGT-A) cycles. Methods: This is a prospective cohort study recruiting 110 infertile women between August 2017 and July 2018. They were divided into young-age (<38 years, n = 60) and advanced-age (≥38 years, n = 50) groups. Peripheral leukocytes were assessed, and the granulosa cells were pooled during oocyte pickup. Mitochondrial DNA (mtDNA) copy number and telomere length (TL) were measured using real-time polymerase chain reaction. PGT-A was performed on the NGS platform. Results: mtDNA copy number and TL were positively correlated in both leukocytes (rho = 0.477, p < 0.001) and granulosa cells (rho = 0.361, p < 0.001), but the two parameters in leukocytes were not correlated with those in granulosa cells. In the young-age group, TL in the granulosa cells was the only factor correlated with the aneuploidy rate (rho = −0.283, p = 0.044), whereas in the advanced-age group, age was the main factor (rho = 0.358, p = 0.018). Conclusions: TL in the granulosa cells was negatively correlated with the aneuploidy rate in the young-age group, supporting the application of PGT-A in younger women.

The effect of multimedia health education on pain and anxiety in women undergoing mammography in Taiwan.

OBJECTIVE: Breast cancer is the most common cancer among women in Taiwan. However, the discomfort of receiving mammograms reduces the willingness to screen. MATERIALS AND METHODS: This study using a quasi-experimental design and recruited 150 participants in a medical center, Taiwan. In the control group, only provided traditional health education sheets, the experimental group has joined the intervention of multimedia health education. State-Trait Anxiety Inventory and Visual Analogue Scale, respectively, were used to compare the differences in anxiety and pain between the two groups before and after receiving mammography. RESULTS: After the intervention, the experimental group's state anxiety score was significantly lower than that of the control group (30.63 ± 8.43 vs. 33.77 ± 10.74, p < .05). However, there was no significant difference in pain scores (4.13 ± 2.37 vs. 4.57 ± 2.31; p = .25). CONCLUSIONS: Younger, prior experience with mammography, and high trait anxiety affect pain and state anxiety of women undergoing mammography. The multimedia health education intervention could reduce anxiety effectively, but it does not significantly relieve the pain undergoing mammography.