Assisted Reproductive Technology Outcomes Research Articles

Impact of Reductive Stress on Human Infertility: Underlying Mechanisms and Perspectives

Antioxidants have a well-established effect on general health and are essential in preventing oxidative damage to cells by scavenging free radicals. Free radicals are thought to be neutralized by these substances, which include polyphenols, β-carotene, and vitamins C and E, reducing cellular damage. On the other hand, recent data indicates that consuming excessive amounts of antioxidants may have side effects. Apoptosis and cell signaling are two beneficial physiological processes that are affected by excessive supplementation. Other negative effects include paradoxical enhancement of oxidative stress and unbalanced cellular redox potential. Overdosing on particular antioxidants has been associated with increased medication interactions, cancer progression, and fatality risks. Additionally, the complex impacts they may have on fertility might be both useful and adverse, depending on the quantity and duration of usage. This review delves into the dual role of antioxidants and emphasizes the importance of employing antioxidants in moderation. Antioxidant overconsumption may disrupt the oxidative balance necessary for normal sperm and oocyte function, which is one of the potential negative effects of antioxidants on fertility in both males and females that are also investigated. Although modest usage of antioxidants is generally safe and useful, high levels of antioxidants can upset hormonal balance, impair sperm motility, and negatively impact the outcomes of assisted reproductive technologies (ART). The findings emphasize the need to use antioxidant supplements in a balanced way, the importance of further research to optimize their use in fertility treatments, and the importance of supporting reproductive health to avoid adverse effects.

Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial

BackgroundPoor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.MethodsIn this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.ResultsAfter the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.ConclusionAST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.Trial registrationClinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16.Graphical

Methodological approaches in 16S sequencing of female reproductive tract in fertility patients: a review.

The female genital tract microbiome has become a particular area of interest in improving assisted reproductive technology (ART) outcomes with the emergence of next-generation sequencing (NGS) technology. However, NGS assessment of microbiomes currently lacks uniformity and poses significant challenges for accurate and precise bacterial population representation. As multiple NGS platforms and assays have been developed in recent years for microbiome investigation-including the advent of long-read sequencing technologies-this work aimed to identify current trends and practices undertaken in female genital tract microbiome investigations. Areas like sample collection and transport, DNA extraction, 16S amplification vs. metagenomics, NGS library preparation, and bioinformatic analysis demonstrated a detrimental lack of uniformity. The lack of uniformity present is a significant limitation characterised by gap discrepancies in generation and interpretation of results. Minimal consistency was observed in primer design, DNA extraction techniques, sample transport, and bioinformatic analyses. With third-generation sequencing technology highlighted as a promising tool in microbiota-based research via full-length 16S rRNA sequencing, there is a desperate need for future studies to investigate and optimise methodological approaches of the genital tract microbiome to ensure better uniformity of methods and results interpretation to improve clinical impact.

Comparative Analysis of Fluorescence In Situ Hybridization and Next-Generation Sequencing in Sperm Evaluation: Implications for Preimplantation Genetic Testing and Male Infertility

Pre-implantation genetic testing (PGT) is a crucial process for selecting embryos created through assisted reproductive technology (ART). Couples with chromosomal rearrangements, infertility, recurrent miscarriages, advanced maternal age, known single-gene disorders, a family history of genetic conditions, previously affected pregnancies, poor embryo quality, or congenital anomalies may be candidates for PGT. Preimplantation genetic testing for aneuploidies (PGT-A) enables the selection and transfer of euploid embryos, significantly enhancing implantation rates in assisted reproduction. Fluorescence in situ hybridization (FISH) is the preferred method for analyzing biopsied cells to identify these abnormalities. While FISH is a well-established method for identifying sperm aneuploidy, NGS offers a more comprehensive assessment of genetic material, potentially enhancing our understanding of male infertility. Chromosomal abnormalities, arising during meiosis, can lead to aneuploid sperm, which may hinder embryo implantation and increase miscarriage rates. This review provides a comparative analysis of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) in sperm evaluations, focusing on their implications for preimplantation genetic testing. This analysis explores the strengths and limitations of FISH and NGS, aiming to elucidate their roles in improving ART outcomes and reducing the risk of genetic disorders in offspring. Ultimately, the findings will inform best practices in sperm evaluations and preimplantation genetic testing strategies.

Assessment of the effect of using intrauterine platelet-rich-plasma on the success of assisted reproduction: a systematic review and meta-analysis of randomized controlled trials

Intrauterine administration of platelet-rich-plasma (PRP) has shown potential in improving pregnancy outcomes in assisted reproductive technology (ART). However, the efficacy of PRP in enhancing clinical pregnancy and live birth rates remains a topic of debate. This meta-analysis evaluated the effectiveness of intrauterine PRP administration in improving clinical pregnancy and live birth rates. A systematic search of electronic databases was conducted to identify randomized controlled trials (RCTs) comparing intrauterine PRP administration with control in women undergoing ART. The primary outcomes were clinical pregnancy rates and live birth rates. Data were extracted and pooled using a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. Nineteen RCTs involving 1,918 participants were included for clinical pregnancy rates, and six RCTs involving 777 participants were included for live birth rates. The pooled OR for clinical pregnancy rates was 2.49 (95% CI: 1.84, 3.35), indicating a significant improvement in the PRP group. For live birth rates, the pooled OR was 3.28 (95% CI: 1.18, 9.09), also favouring the PRP group. Moderate heterogeneity was observed for clinical pregnancy rates (I²=43%), while substantial heterogeneity was observed for live birth rates (I²=77%). Funnel plots showed no significant publication bias for either outcome. Intrauterine PRP administration significantly improves clinical pregnancy and live birth rates in women undergoing ART. The pooled ORs of 2.49 for clinical pregnancy rates and 3.28 for live birth rates support the potential clinical utility of PRP in enhancing ART outcomes.

Additional Daily Intramuscular Progesterone for Luteal Phase Support does not Improve Live Birth Rates of Programmed Frozen-Thawed Embryo Transfer Cycles

This retrospective cohort study aims to investigate whether additional daily intramuscular progesterone (IMP) for luteal phase support improves live birth rates of programmed frozen-thawed embryo transfer (FET) cycles. The study was conducted at a tertiary level university hospital assisted reproductive technology (ART) center between January 2014 and Jan 2021. Six hundred four infertile patients with single-day 5-6 frozen-thawed blastocyst embryo transfer were enrolled in the study. All patients received either 8% micronized vaginal gel or vaginal progesterone capsules for luteal phase support. Intramuscular progesterone was added to vaginal progesterone depending on the in vitro fertilization (IVF) specialist’s choice. Luteal phase support (LPS) was started 6 days before transfer in frozen-thawed cycles and continued until the end of the first trimester. Cycles were compared depending on vaginal progesterone types (8% gel vs. capsule) and the presence of intramuscular progesterone. The primary outcome was the live birth rate. A total of 604 FET cycles were enrolled. Using 8% micronized progesterone or progesterone capsules did not change the live birth rates (24% vs. 25.9%). As the main result, intramuscular progesterone support with vaginal progesterone compared with only vaginal progesterone did not improve the live birth results (22% vs. 24%). In conclusion, this study demonstrated that routine IMP progesterone given in combination with vaginal progesterone does not improve ART outcomes. This combination may be beneficial in a selective population with a monitored luteal phase. Using any form of vaginal progesterone alone is adequate for LPS.

Association of specific PM2.5 chemical constituents and ozone exposure with pregnancy outcomes in women undergoing assisted reproductive technology treatment in central China

The associations of air pollutants exposure with assisted reproductive technology (ART) pregnancy outcomes are mixed, and the effects of specific components of fine particulate matter (PM2.5) and ozone (O3) are not well understood. We conducted a retrospective longitudinal study to explore the association of PM2.5 constituents and O3 exposure with three ART outcomes among women undergoing ART treatment. The exposure window was segmented into five periods corresponding to the cycle of ovarian stimulation and oocyte retrieval procedure. Generalized linear mixed model (GLMM) was applied to explore the relationships between PM2.5 constituents, O3, Normalized Vegetation Index (NDVI) exposure and three ART outcomes. The combined effect of PM2.5 constituents was evaluated by the quantile g (qg)-computation. We also explored the modifying effect of different covariate. Elevated exposure level of PM2.5 (OR = 0.915, 95% CI: 0.859, 0.974) and its constituents (BC: 0.905, 95% CI: 0.840, 0.975; OM: 0.910, 95% CI: 0.848, 0.976; NO3−: 0.909, 95% CI: 0.850, 0.972, SO42−: 0.905, 95% CI: 0.846, 0.968, and NH4+: 0.902, 95% CI: 0.842, 0.966) exposure throughout the year before oocyte retrieval (period 1) was correlated with a reduced odds ratio (OR) of live birth with statistical significance. Similarly, for each interquartile range (IQR) increase in O3 exposure during periods 2 (85 days prior to oocyte retrieval), 3 (30 days prior to oocyte retrieval), 4 (oocyte retrieval to embryo transfer) and 5 (embryo transfer to hCG test) was significantly related to a decreased OR of live birth. Especially, participants who underwent fresh embryo transfer cycles and received two cleavage-stage embryo transfer, and were younger than 30 years old, showed a higher susceptibility to particulate matter. Findings from this study suggest that PM2.5 constituents and O3 exposure may have adverse effects on the ART outcomes, highlighting the importance of identifying critical exposure periods for various air pollutants and the need for meticulous management of particulate matter.

New therapeutic approaches for improving the outcomes of assisted reproductive technologies

Infertility is a global health problem that affects up to 17.5% of the world’s population. The use of assisted reproductive technologies makes it possible to solve this problem; however, it is not adequately efficient in all observed cases. Implantation failure remains a serious and multifaceted problem faced by clinicians in reproductive technology, despite the significant advances that have been made in this area. This review highlights promising studies on medical and invasive intervention methods and their possible combinations, which potentially improve the clinical treatment of implantation failures. Nevertheless, further study is required to assess the effectiveness and safety of each therapeutic approach, which can introduce new prospects in the treatment of infertility and increase the chances of successful implantation and pregnancy.

An atlas of small non-coding RNAs in human preimplantation development

Understanding the molecular circuitries that govern early embryogenesis is important, yet our knowledge of these in human preimplantation development remains limited. Small non-coding RNAs (sncRNAs) can regulate gene expression and thus impact blastocyst formation, however, the expression of specific biotypes and their dynamics during preimplantation development remains unknown. Here we identify the abundance of and kinetics of piRNA, rRNA, snoRNA, tRNA, and miRNA from embryonic day (E)3-7 and isolate specific miRNAs and snoRNAs of particular importance in blastocyst formation and pluripotency. These sncRNAs correspond to specific genomic hotspots: an enrichment of the chromosome 19 miRNA cluster (C19MC) in the trophectoderm (TE), and the chromosome 14 miRNA cluster (C14MC) and MEG8-related snoRNAs in the inner cell mass (ICM), which may serve as ‘master regulators’ of potency and lineage. Additionally, we observe a developmental transition with 21 isomiRs and in tRNA fragment (tRF) codon usage and identify two novel miRNAs. Our analysis provides a comprehensive measure of sncRNA biotypes and their corresponding dynamics throughout human preimplantation development, providing an extensive resource. Better understanding the sncRNA regulatory programmes in human embryogenesis will inform strategies to improve embryo development and outcomes of assisted reproductive technologies. We anticipate broad usage of our data as a resource for studies aimed at understanding embryogenesis, optimising stem cell-based models, assisted reproductive technology, and stem cell biology.

Effect of body mass index on ovarian reserve and ART outcomes in infertile women: a large retrospective study

BackgroundObesity poses a significant global health challenge, with profound implications for women’s reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients.MethodsWe conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses.ResultsAnti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20–30 and 30–35 years. Among women aged 20–35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia.ConclusionsAn age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility.

Correlation of Seminal Plasma EMMPRIN Levels with Sperm Quality and the Efficacy of Activation Techniques

Background: Infertility is a major global health challenge, impacting 15% to 20% of couples globally. Male infertility, which is typically associated with issues such as low sperm motility, has increased during the last two decades. Male fertility relies heavily on the development of extracellular matrix metalloproteinase inducer (EMMPRIN), a glycosylated transmembrane protein involved in sperm function and embryo implantation. Understanding how sperm preparation techniques affect sperm quality and EMMPRIN expression is crucial for achieving optimal results in assisted reproductive technologies (ART). Objective: To investigate EMMPRIN expression in human sperm and compare the impact of two in vitro sperm preparation procedures, “direct swim-up (DSU) and pellet swim-up (PSU), on various sperm characteristics. To determine the optimum technique for improving sperm quality in ART. Materials and Methods: Masturbation was employed to collect sperm samples from 44 participants (aged 21 to 45). Following liquefaction, samples were evaluated macroscopically and microscopically in accordance with WHO 2021 guidelines. The samples were separated into three aliquots for ELISA assessment of EMMPRIN levels and sperm processing with DSU and PSU techniques. Sperm chromatin immaturity (SCI) was assessed using Aniline Blue staining. Statistical investigations were carried out to determine the correlations between EMMPRIN levels, semen parameters, and the impacts of the two in vitro sperm preparation techniques. Results: Sperm concentration significantly decreased from control (40.25 ± 2.30) to DSU (15.51 ± 1.74) and PSU (9.99 ± 1.16) conditions. However, motility, morphology, and SCI significantly improved, particularly with PSU, which showed a greater reduction in SCI % compared to DSU, indicating its effectiveness in selecting higher-quality sperm. There were no significant associations detected between EMMPRIN levels with semen metrics, although PSU exhibited a slightly higher association with improved sperm parameters. Conclusion: Seminal plasma EMMPRIN levels do not appear to directly influence semen parameters or sperm chromatin maturity. However, the choice of sperm activation technique, particularly PSU, significantly impacts sperm quality. More research is needed to better understand the importance of EMMPRIN in ART outcomes and its potential as a sperm quality indicator.

Impact of BMI on fertility in an otherwise healthy population: a systematic review and meta-analysis.

An increased body mass index (BMI) can lead to subfertility; however, current literature fails to exclude the effect of other confounding medical conditions, raising questions regarding the direct link between increased BMI and fertility outcomes. To conduct a systematic review and meta-analysis to elucidate the effects of increased BMI on fertility outcomes in females with no other comorbidities. A comprehensive search was conducted using EMBASE, MEDLINE and the Cochrane library from January 2000 until July 2023. Two authors independently conducted data extraction and assessed study quality. Odds ratio (OR) (dichotomous data), standardised mean difference (SMD) (continuous data) and 95% CIs were calculated. Nine eligible studies were identified: one natural conception and eight assisted reproductive technology (ART). Aggregated data revealed women with BMI ≥25 were less likely to attain clinical pregnancy (OR 0.76, 95% CIs 0.62 to 0.93, p=0.007), with BMI ≥30 associated with a further decreased likelihood of clinical pregnancy (OR 0.61, 95% CIs 0.39 to 0.98, p=0.04). Women with raised BMI required longer duration of stimulation (SMD=0.08, 95% CIs 0.00 to 0.16, p=0.04) and obtained reduced oocytes (SMD=-0.11, 95% CIs -0.18 to -0.04, p=0.002). These data demonstrate an adverse impact of being overweight/obese on ART outcomes in women with no other diagnosed medical comorbidities and highlight the distinct lack of data concerning the effects of isolated obesity on natural conception. Infertility represents an enormous burden for couples and society; it is essential to identify and tackle modifiable risk factors to improve chances of conception. CRD42022293631.

Reproductive outcomes in fresh transfer cycles and antagonists with premature luteinizing and/or progesterone surge: a single center retrospective cohort study.

The optimal outcome of assisted reproductive technology is a successful live birth after fresh embryo transfer. However, the success pregnancy rate of fresh embryo transfer cycle in antagonist protocol is lower than that observed in other protocols. Despite the use of antagonists (GnRH-ant), the incidence of luteinizing hormone surge and elevated progesterone levels remain at approximately 5%-38%. Progesterone is widely recognized to exert adverse effects on fresh embryo transfer outcomes. This study aimed to investigate the impact of luteinizing hormone surge and progesterone levels on live birth rate following fresh embryo transfer and explore appropriate progesterone thresholds to enhance pregnancy outcomes. This retrospective cohort study included a total of 1,177 antagonist protocol cycles with fresh embryo transfer. The patients were divided into four groups based on the presence of premature LH surge and progesterone level on trigger day>1.5ng/ml. Then, the relationship between the variables and the pregnancy outcome was analyzed and compared in each group. The transient rise of luteinizing hormone did not impact pregnancy outcomes (P=0.345; P=0.3; P=0.787), in contrast to progesterone levels on the day of hCG administration (P=0.047*; P=0.015*; P=0.021*). In cases with luteinizing hormone surge, elevated progesterone levels were correlated with higher antral follicle count (AFC), and as progesterone levels increased, a greater quantity of oocytes and embryos were obtained. However, there was no statistically significant difference in pregnancy outcomes. In cases without luteinizing hormone surge, elevated progesterone levels led to significantly poorer pregnancy outcomes. Furthermore, the curve-fitting and threshold-effect analysis revealed a notable decline in live birth rates when progesterone exceeded or equaled 1.10ng/ml (OR, 0.25; 95% CI, 0.09-0.66; P = 0.005*). The GnRH-ant dosage addition should be carefully selected in flexible antagonist protocols. The presence of elevated progesterone levels may be associated with improved embryo quality when luteinizing hormone surge occurred. In the absence of a luteinizing hormone surge, progesterone levels showed a larger impact on the pregnancy outcome, and fresh embryo transfer should not be performed if the progesterone level on the day of hCG administration is higher than 1.10ng/ml.

Application of Artificial Intelligence in Sperm Quality Analysis and Sperm Screening

Infertility is a global health issue, and more and more people are hoping to have babies by means of assisted reproductive technology. However, there are still many challenges in fertilization and pregnancy outcomes. Sperm quality is a key factor affecting the success rate of assisted reproduction. Therefore, sperm quality screening is crucial for achieving breakthroughs in assisted reproduction technology. At present, with its capabilities in the field of image recognition, artificial intelligence (AI) is providing new ideas and methods for sperm screening. Various attempts have been made with AI-based models to evaluate indicators such as sperm morphology, DNA quality, and motility level, and some results have been achieved. Herein, we reviewed the application of AI in sperm quality analysis and selection, providing support for the future development of AI and the improvement in the fertilization rate and outcomes of assisted reproductive technology.

Use of time-lapse technology on fertilization verification, embryo evaluation, and utilization: A national survey in Japan

BackgroundTime-lapse technology (TLT) has emerged as a significant advancement in the field of assisted reproductive technology (ART), providing continuous observation of embryos. However, limited information exists on the adoption of TLT across ART facilities and the clinical implications of its application in embryo evaluation and fertilization verification. The existing literature has not yet comprehensively examined how TLT data are utilized to optimize ART outcomes, particularly in Japan, where ART practices are highly prevalent. ObjectivesThis study aimed to investigate the adoption rate of TLT and its clinical effects on fertilization verification, embryo evaluation, and utilization of ART in Japan. Study DesignAn online survey was conducted from December 23, 2022, to January 16, 2023, in 616 ART facilities with both email and mailed notices. The survey investigated the utilization of TLT in each facility's evaluation of oocyte morphology, fertilization, embryo culture, and morphology. ResultsOverall, 345 responses were analyzed. Of these, only 42.6% confirmed fertilization at 16 to 18 hours after insemination. Most facilities defined normally fertilized eggs as 2 pronuclei (2PN; 53.3%) or a combination of a second polar body extrusion and 2PN (44.9%). Overall, 54.6% of the facilities had adopted TLT, and 76.9% to 96.9% of these facilities used TLT images for fertilization verification. At these centers, the use of 0PN embryos decreased, whereas the use of 2.1PN embryos increased. The rates of culture medium supplemented with antioxidants and hyaluronan were significantly higher in facilities with TLT than in those without TLT. TLT images were used for embryo evaluation in 94.3% of the facilities, while 31.0% used a combination of TLT images and artificial intelligence-based scoring systems. ConclusionsWhile TLT use is widespread in Japan, its application in evaluating fertilization and embryo development stages varies across facilities. Reaching a consensus on the optimal use of the TLT system will enhance the effectiveness, safety, and efficiency of ARTs.

Prehypertension in male affects both semen quality and pregnancy outcomes in their first single blastocyst frozen-thawed embryo transfer cycles

To investigate whether prehypertension (pre-HTN) in male affects semen quality and assisted reproductive technology (ART) outcomes. Retrospective cohort study. University-affiliated reproductive medicine center. Clinical data were collected from 1,043 couples undergoing their first single blastocyst frozen-thawed embryo transfer cycles. According to the blood pressure (1 mm Hg = 0.133 kPa) in male, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), the subjects were divided into the control group (90 ≤ SBP < 120 mm Hg and 60 ≤ DBP < 80 mm Hg, n = 611) and the pre-HTN group (120 ≤ SBP < 140 mm Hg and/or 80 ≤ DBP < 90 mm Hg, n = 432). The association between pre-HTN and semen quality, and ART outcomes was then evaluated. Primary outcome: live birth rate. semen quality, laboratory embryo outcomes, clinical pregnancy rate, biochemical pregnancy rate, miscarriage rate, and other pregnancy outcomes. Compared with the control group, the pre-HTN group showed lower total sperm motility, total sperm count, sperm progressive motility, progressive sperm count , and higher prevalence of oligozoospermia (17.6% vs. 13.1%), and asthenozoospermia (37.7% vs. 19.8%). Meanwhile, compared with the control group, the pre-HTN group had a lower clinical pregnancy rate (42.8% vs. 57.6%) and a lower live birth rate (32.9% vs. 47.3%). There were no differences in the remaining parameters of semen quality, laboratory embryo outcomes (except for the proportion of intracytoplasmic sperm injection), and pregnancy outcomes between the two groups. Additionally, regression analysis showed that pre-HTN in male was an independent risk factor for clinical pregnancy (adjusted odds ratio, 0.57; 95% confidence interval, 0.44-0.74) and live birth (adjusted odds ratio, 0.58; 95% confidence interval, 0.44-0.75). Prehypertension in male not only results in lower semen quality, but also has negative consequences on the success of ART. It is an independent risk factor for clinical pregnancy and live birth in the first single blastocyst frozen-thawed embryo transfer cycles.

Loss-of-function variant in TDRD6 cause male infertility with severe oligo-astheno-teratozoospermia in human and mice.

Oligo-astheno-teratozoospermia (OAT) is a common cause of male infertility, but the genetic basis of most OAT cases is still unknown. Here, one homozygous loss-of-function (LOF) variant in TDRD6, c.G1825T/p.Gly609X, was identified in an infertile patient with severe OAT by whole-exome sequencing (WES) and Sanger confirmation. Furthermore, Tdrd6-mutant mice (p.Gly615X; equivalent to p.Gly609X in human TDRD6) were generated. Remarkably, the Tdrd6-mutated mice mimicked the severe OAT symptoms of the patient. In addition, the architecture of chromatoid bodies (CBs) were disrupted in round spermatids from Tdrd6-mutant mice, leading to blocked spermatogenesis in the round spermatids. The assembly of PIWIL1, TDRD1, TDRD7 and DDX25 in CBs was disturbed in the Tdrd6-mutant mice. Applying immunoprecipitation-mass spectrometry (IP-MS), we identified some TDRD6-interacting partners, including CB proteins TDRD7, MAEL and PCBP1. Moreover, we described the assisted reproductive technology (ART) outcomes of the infertile patient and his partner. Altogether, our findings provide necessary evidences to support the idea that the homozygous LOF variant in TDRD6 induces male infertility with severe OAT, suggesting that TDRD6 could be a useful genetic diagnostic target for male infertility.

Effects of Embryo Microbial Contamination on ART and Neonatal Outcomes.

This study investigated the incidence and microbial etiology of embryo contamination in assisted reproductive technology (ART), and its influence on embryo development, pregnancy and neonatal outcomes. A retrospective analysis was conducted on embryo contamination at the Reproductive Centre of the Third Affiliated Hospital of Guangzhou Medical University, between 2018 and 2021. In the period from 2018 to 2021, the average incidence of embryo contamination was 0.12%. Bacterial growth was observed in 39 cases, with a preponderance of Escherichia coli (20, 51.28%), Streptococcus agalactiae (7, 17.95%). The fertilization rate of contaminated embryos was 18.18% (Klebsiella pneumoniae) to 94.79% (S. agalactiae), the cleavage rate was 9.09% (Enterobacter cloacae) to 98.90% (S. agalactiae), and the available embryo rate of Day 3 was 0 (Klebsiella pneumoniae, Enterobacter cloacae) to 63.33% (S. agalactiae). Blastocyst formation rate was 3.23% (Proteus mirabilis) to 64.29% (Streptococcus mitis). E. coli contamination occurred mostly on Day 1, and S. agalactiae on Days 3 and 5. After rinsing and rescuing treatment, six healthy male babies were born. E. coli and S. agalactiae were the most common bacterial embryo contaminants. Most microbial contamination can significantly decrease the fertilization rate. Embryo transfer after rinsing and continuing culture had no negative effect on neonatal outcomes, but there was an increased risk of early abortion due to E. coli contamination.

SCM-198 ameliorates the quality of postovulatory and maternally aged oocytes by reducing oxidative stress

Oocyte aging is a key constraint on oocyte quality, leading to fertilization failure and abnormal embryonic development. In addition, it is likely to generate unfavorable assisted reproductive technology (ART) outcomes. SCM-198, a synthetic form of leonurine, was found to rescue the rate of oocyte fragmentation caused by postovulatory aging. Therefore, the aim of this study was to conduct a more in-depth investigation of SCM-198 by exploring its relationship with aged oocytes after ovulation or maternal aging and clarifying whether it affects cell quality. The results indicate that, compared to the postovulatory aged group, the 50 µM SCM-198 group significantly improved sperm-egg binding and increased fertilization of aged oocytes, restoring the spindle apparatus/chromosome structure, cortical granule distribution, and ovastacin and Juno protein distribution. The 50 µM SCM-198 group showed significantly normal mitochondrial distribution, low levels of reactive oxygen species (ROS), and a small quantity of early oocyte apoptosis compared to the postovulatory aged group. Above all, in vivo supplementation with SCM-198 effectively eliminated excess ROS and reduced the spindle/chromosome structural defects in aged mouse oocytes. In summary, these findings indicate that SCM-198 inhibits excessive oxidative stress in oocytes and alters oocyte quality both in vitro and in vivo.Graphical

A Comprehensive Review of the Endometrial Receptivity Array in Embryo Transfer: Advancements, Applications, and Clinical Outcomes.

Embryo transfer is a pivotal procedure in assisted reproductive technologies (ART). Yet, the success of this process hinges on multiple factors, with endometrial receptivity playing a critical role in determining the likelihood of successful implantation. The endometrial receptivity array (ERA) is an advanced diagnostic tool designed to personalize embryo transfer timing by assessing the endometrium's receptivity. This review comprehensively examines the ERA, exploring its biological foundation, technological development, and clinical applications. The ERA's ability to analyze the expression of genes associated with endometrial receptivity offers a tailored approach to identifying the optimal window of implantation (WOI), particularly benefiting patients with recurrent implantation failure (RIF) or repeated unsuccessful in vitro fertilization (IVF) cycles. Clinical outcomes from ERA-guided embryo transfers indicate improvements in implantation rates and overall pregnancy success, although challenges such as result variability and cost-effectiveness persist. This review also discusses the latest advancements in ERA technology, including integrating genomic and transcriptomic analyses, non-invasive techniques, and using artificial intelligence (AI). Controversies regarding the widespread application of ERA and its necessity in all IVF cases are critically examined. By summarizing the current state of ERA in embryo transfer, this review aims to inform clinicians, researchers, and patients about its potential to enhance ART outcomes and to highlight areas for future research and innovation.