Search

Objective: To compare highly purified human menopausal gonadotropin (HP-hMG) with recombinant follicle-stimulating hormone (rFSH) on ovarian response and pregnancy outcome in downregulated women of advanced reproductive age. Design: A prospective, randomized and controlled study of 127 consecutive normogonadotropic infertile women ≥35 years old undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycles received ovarian stimulation with HP-hMG ( n = 63) or with rFSH ( n = 64) in a long gonadotropin-releasing hormone agonist protocol. Results: More leading (≥18 mm) follicles and oocytes were obtained in rFSH group ( p = 0.008 and p < 0.001, respectively). The proportion of top-quality embryo from oocyte retrieval and live birth rate per started cycle trended towards improvement with HP-hMG (OR 1.3, 95% CI 0.9-1.8; OR 1.9, 95% CI 0.9-3.9; respectively), although they were not significant difference between two groups. At end of stimulation, higher serum progesterone level was found in rFSH group ( p < 0.001). Conclusion: Following downregulated women of advanced reproductive age, superiority of HP-hMG over rFSH in live birth rate could not be concluded from this study, but noninferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality and endocrine response exist between HP-hMG and rFSH, which may be relevant to treatment outcome. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The aim of the present study was to investigate the incidence of intrahepatic cholestasis of pregnancy (ICP) as well as neonatal outcomes between conception via in vitro fertilization (IVF) compared with spontaneous conception (SC) and screen the risk factors of ICP in IVF.This retrospective cohort study included 4467 puerperae who conceived via IVF, and 28 336 puerperae who conceived spontaneously and linked the information from neonates. The general linear model (GLM), multivariate logistic regression analysis, a forest plot, and nomogram were used to assess impact factors and risk prediction.Logistic analysis adjusted for confounders revealed significant differences in the ICP rate of singleton delivery (4.24% vs 3.41%, adjusted OR [aOR] = 1.26; 95% confidence interval [CI] 1.03–1.53, P = 0.025) and in groups with total bile acids (TBA) ≥40 and <100 μmol/L (14.77% vs 10.39%, aOR = 1.31; 95% CI: 1.06–1.63, P = 0.023) between IVF and SC. When we divided newborns into singleton and twins delivery, the GLM revealed a higher rate with Apgar score <7 (13.44% vs 3.87%, aOR = 3.85; 95% CI: 2.07–7.17, P < 0.001) and fetal distress for IVF in comparison with SC (19.32% vs 5.55%, OR = 3.48; 95% CI: 2.39–6.95, P < 0.001) in the singleton group. In multivariate logistic regression analysis, body mass index (BMI) (aOR = 1.29; P = 0.031), number of embryo transfers (ET) (single ET vs double ET, aOR = 2.82; P < 0.001), E2 level on the ET day (aOR = 2.79; P = 0.011), fresh ET which compared with frozen ET (FET) (aOR = 1.45; P = 0.014), embryo stage (cleavage embryo vs blastocyst, aOR = 1.75; P = 0.009) and severe ovarian hyperstimulation syndrome (OHSS) which compared with non‐OHSS (aOR = 3.73; P = 0.006) were independent predictors of ICP. These predictive factors in the logistic regression model were integrated into the nomogram (C‐index = 0.735; 95% CI: 0.702–0.764); for each patient, higher total points indicated a higher risk of ICP.We observed that the ICP rate of singleton delivery was higher in IVF than in SC. In ICP patients, there were higher rates of neonatal Apgar score <7 and fetal distress in IVF than SC and found the predictors of ICP in IVF. [ABSTRACT FROM AUTHOR]

Objective: The objective of this retrospective cohort study is to investigate the impact of monitoring serum estradiol (E2) levels before progesterone administration within hormone replacement therapy (HRT) on pregnancy outcomes in women undergoing frozen-thawed embryo transfer (FET). Methods: Analyzed HRT-FET cycles conducted at a reproductive center from 2017 to 2022. Serum E2 levels were measured prior to progesterone administration. Multivariate stratified and logistic regression analyses were performed on 26,194 patients grouped according to terciles of serum E2 levels before progesterone administration. Results: The clinical pregnancy rate (CPR) and live birth rate (LBR) exhibited a gradual decline with increasing serum E2 levels across the three E2 groups. Even after controlling for potential confounders, including female age, body mass index, infertility diagnosis, cycle category, number of embryos transferred, fertilization method, indication for infertility, and endometrial thickness, both CPR and LBR persistently showed a gradual decrease as serum E2 levels increased within the three E2 groups. The same results were obtained by multivariate logistic regression analysis. Conclusions: This large retrospective study indicates that elevated serum E2 levels before progesterone administration during HRT-FET cycles are associated with reduced CPR and LBR post-embryo transfer. Therefore, it is advisable to monitor serum E2 levels and adjust treatment strategies accordingly to maximize patient outcomes. [ABSTRACT FROM AUTHOR]

This first large-scale report of birth defects in 15,405 offspring conceived by assisted reproductive technologies in China found infants born after IVF alone to have a birth defect frequency comparable to that in the general Chinese population; rates were nonsignificantly higher in infants conceived with use of intracytoplasmic sperm injection compared with those conceived after IVF alone. [Copyright &y& Elsevier]

Background Objectives Materials and methods Results Discussion and conclusion Dysfunction of motile cilia, including respiratory cilia and sperm flagella, typically leads to primary ciliary dyskinesia and male infertility or low fertility in humans. Genetic defects of LRRC6 have been associated with primary ciliary dyskinesia and asthenozoospermia due to abnormal ultrastructure of ciliated axonemes.To identify novel mutations of the LRRC6 gene related to multiple morphological abnormalities of the sperm flagella and male infertility and investigate the underlying molecular mechanisms involved.The LRRC6 mutations were identified by whole exome sequencing and confirmed with Sanger sequencing. Papanicolaou staining, scanning, and transmission electron microscopy were performed to investigate the morphological and ultrastructural characteristics of spermatozoa. Further tandem mass tagging proteomics analyses were performed to explore the effect of mutations and confirmed by immunostaining and western blotting. Intracytoplasmic sperm injection was applied for the assisted reproductive therapy of males harboring biallelic LRRC6 mutations.In this study, we identified a novel homozygous LRRC6 mutation in a consanguineous family, characterized by asthenozoospermia and primary ciliary dyskinesia. Further Semen parameter and morphology analysis demonstrate that the novel LRRC6 mutation leads to a significant reduction in sperm flagella length, a decrease in sperm progressive motility parameters, and abnormalities of sperm ultrastructure. Specifically, the absence of outer dynein arms and inner dynein arms, and incomplete mitochondrial sheath in the flagellar mid‐piece were observed by transmission electron microscopy. In addition, tandem mass tagging proteomics analysis revealed that spermatozoa obtained from patients harboring the LRRC6 mutation exhibited a significant decrease in the expression levels of proteins related to the assembly and function of dynein axonemal arms. Functional analysis revealed that this novel LRRC6 mutation disrupted the function of the leucine‐rich repeat containing 6 protein, which in turn affects the expression of the dynein arm proteins and leucine‐rich repeat containing 6‐interacting proteins CCDC40, SPAG1, and ZMYND10. Finally, we reported a successful pregnancy through assisted reproductive technology with intracytoplasmic sperm injection in the female partner of the proband.This study highlights the identification of a novel homozygous LRRC6 mutation in a consanguineous family and its impact on sperm progressive motility, morphology, and sperm kinetics parameters, which could facilitate the genetic diagnosis of asthenozoospermia and offer valuable perspectives for future genetic counseling endeavors. [ABSTRACT FROM AUTHOR]

Purpose: Zygotes with 2.1 pronuclei (2.1PN) present with two normal-sized pronuclei, and an additional smaller pronucleus, that is approximately smaller than two thirds the size of a normal pronucleus. It remains unclear whether the additional pronucleus causes embryonic chromosome abnormalities. In the majority of cases, in vitro fertilization (IVF) clinics discarded 2.1PN zygotes. Thus, the present study aimed to evaluate the developmental potential and value of 2.1PN zygotes. Methods: 2.1PN-derived embryos from 164 patients who underwent IVF or intracytoplasmic sperm injection (ICSI) treatment between January 2021 and December 2022 were included in the present study. All embryos were monitored using a time-lapse system, and blastocyst formation was used to assess 2.1PN-derived embryo developmental potential. The blastocyst formation was quantified using generalized estimating equations, and chromosome euploidy was analyzed using next-generation sequencing (NGS). In addition, the potential association between age and occurrence of 2.1PN zygotes was determined. Results: The present study demonstrated that numerous 2.1PN zygotes developed into blastocysts. Early cleavage patterns and embryo quality on Day 3 were the independent predictors for the blastocyst formation of 2.1PN-derived embryos. The 2.1PN zygotes displayed a comparable developmental potential compared to 2PN zygotes in advanced age patients (≥ 38). Moreover, there was a tendency that 2.1PN-derived blastocysts showed a similar euploidy rate compared to 2PN-derived blastocysts. Conclusion: Clinicians should consider using 2.1PN-derived euploid embryos for transfer after preimplantation genetic testing in the absence of available 2PN embryo cycles. 2.1PN-derived embryos could be a candidate, particularly beneficial for patients at advanced age. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Could actin-related protein T1 (ACTRT1) deficiency be a potential pathogenic factor of human male infertility? SUMMARY ANSWER A 110-kb microdeletion of the X chromosome, only including the ACTRT1 gene, was identified as responsible for infertility in two Chinese males with sperm showing acrosomal ultrastructural defects and fertilization failure. WHAT IS KNOWN ALREADY The actin-related proteins (e.g. ACTRT1, ACTRT2, ACTL7A, and ACTL9) interact with each other to form a multimeric complex in the subacrosomal region of spermatids, which is crucial for the acrosome-nucleus junction. Actrt1 -knockout (KO) mice are severely subfertile owing to malformed sperm heads with detached acrosomes and partial fertilization failure. There are currently no reports on the association between ACTRT1 deletion and male infertility in humans. STUDY DESIGN, SIZE, DURATION We recruited a cohort of 120 infertile males with sperm head deformations at a large tertiary hospital from August 2019 to August 2023. Genomic DNA extracted from the affected individuals underwent whole exome sequencing (WES), and in silico analyses were performed to identify genetic variants. Morphological analysis, functional assays, and ART were performed in 2022 and 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS The ACTRT1 deficiency was identified by WES and confirmed by whole genome sequencing, PCR, and quantitative PCR. Genomic DNA of all family members was collected to define the hereditary mode. Papanicolaou staining and electronic microscopy were performed to reveal sperm morphological changes. Western blotting and immunostaining were performed to explore the pathological mechanism of ACTRT1 deficiency. ICSI combined with artificial oocyte activation (AOA) was applied for one proband. MAIN RESULTS AND THE ROLE OF CHANCE We identified a whole-gene deletion variant of ACTRT1 in two infertile males, which was inherited from their mothers, respectively. The probands exhibited sperm head deformations owing to acrosomal detachment, which is consistent with our previous observations on Actrt1 -KO mice. Decreased expression and ectopic distribution of ACTL7A and phospholipase C zeta were observed in sperm samples from the probands. ICSI combined with AOA effectively solved the fertilization problem in Actrt1 -KO mice and in one of the two probands. LIMITATIONS, REASONS FOR CAUTION Additional cases are needed to further confirm the genetic contribution of ACTRT1 variants to male infertility. WIDER IMPLICATIONS OF THE FINDINGS Our results reveal a gene–disease relation between the ACTRT1 deletion described here and human male infertility owing to acrosomal detachment and fertilization failure. This report also describes a good reproductive outcome of ART with ICSI-AOA for a proband. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau, 2023MSXM008 and 2023MSXM054). There are no competing interests to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background: Multiple morphological abnormalities of sperm flagella is an idiopathic asthenoteratozoospermia characterized by absent, short, coiled, angulation, and irregular‐caliber flagella. Genetic variants of DNAH1 gene have been identified as a causative factor of multiple morphological abnormalities of sperm flagella and intracytoplasmic sperm injection is an available strategy for infertile males with dynein axonemal heavy chain 1 defects to conceive. Objectives: To identify novel variants and candidate mutant hotspots of DNAH1 gene related to multiple morphological abnormalities of sperm flagella and male infertility in humans. Materials and methods: The DNAH1 variants were identified by whole exome sequencing and confirmed with Sanger sequencing. Papanicolaou staining, scanning and transmission electron microscopy, and immunostaining were performed to investigate the morphological and ultrastructural characteristics of spermatozoa. Intracytoplasmic sperm injection was applied for the assisted reproductive therapy of males harboring biallelic DNAH1 variants. Results: We identified 18 different DNAH1 variants in 11 unrelated families, including nine missense variants (p.A2564T, p.T3657R, p.G1862R, p.L2296P, p.T4041I, p.L611P, p.A913D, p.R1932Q, p.R2356W) and nine loss‐of‐function variants (c.2301‐1G>T, p.Q1518*, p.R1702*, p.D2845Mfs*2, p.P3909Rfs*33, p.Q4040Dfs*33, p.Q4058*, p.E4060Pfs*61, p.V4071Cfs*54). A total of 66.7% (12/18) of the identified variants were novel. Morphological analysis based on Papanicolaou staining and scanning electron microscopy demonstrated the typical multiple morphological abnormalities of sperm flagella characteristics of dynein axonemal heavy chain 1‐deficient spermatozoa. Immunostaining further revealed the absence of inner dynein arms but not outer dynein arms, which induced a general ultrastructural disorganization, such as the loss of central pair and mis‐localization of the microtubule doublets and outer dense fibers. To date, seven affected couples have accepted the intracytoplasmic sperm injection treatment, and three of them have given birth to five healthy babies. Discussion and conclusion: These findings further expand the variant spectrum of DNAH1 gene related to multiple morphological abnormalities of sperm flagella and male infertility in humans, thus providing new information for the molecular diagnosis of asthenoteratozoospermia. The favorable fertility outcomes of intracytoplasmic sperm injection will facilitate the genetic counseling and clinical treatment of infertile males with multiple morphological abnormalities of sperm flagella in the future. [ABSTRACT FROM AUTHOR]

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation (ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-CoA and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos. [ABSTRACT FROM AUTHOR]

Fertility societies worldwide responded to the COVID-19 pandemic by recommending that fertility clinics close, or sharply reduce, the clinical operation, leading to a shift in the management of IVF laboratories in three phases: shutdown preparation; maintenance during shutdown; and restart. Each of these phases carries distinct risks that need identification and mitigation, forcing laboratory managers to rethink and adapt their procedures in response to the pandemic. The sudden and unprecedented nature of the pandemic forced laboratory managers from around the world to base decisions on opinion and experience when evidence-based response options were unavailable. These perspectives on pandemic response were presented during a virtual international symposium on COVID-19, held on 3 April 2020, and organized by the London Laboratory Managers' Group. Laboratory managers from seven different countries at different stages of the pandemic (China, Italy, Spain, France, UK, Brazil and Australia) presented their personal experiences to a select audience of experienced laboratory managers from 19 different countries. The intention of this paper is to collect the learnings and considerations from this group of laboratory managers who collaborated to share personal experiences to contribute to the debate surrounding what constitutes good IVF laboratory practice in extraordinary circumstances, such as the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Omega-3 fatty acid and vitamin E or D co-supplementation may be an important approach to improve metabolic status in gestational diabetes, but the results are conflicting. This systematic review and meta-analysis was conducted to evaluate the effect of omega-3 fatty acid and vitamin co-supplementation on metabolic status in gestational diabetes.Methods: PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) assessing the influence of omega-3 fatty acid and vitamin co-supplementation compared with placebo on metabolic status in gestational diabetes were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies.Results: Four RCTs were included in the meta-analysis. Compared with control interventions for gestational diabetes, omega-3 fatty acid and vitamin E or D co-supplementation was associated with significantly reduced fasting plasma glucose [mean difference (MD) -10.47, 95 % confidence interval (CI) -15.33 to -5.61, p < 0.0001], homeostasis model of assessment-insulin resistance (MD -1.6, 95 % CI=-2.44 to -0.77, p = 0.0002), malondialdehyde (MD -1.00, 95 % CI -1.05 to -0.95, p < 0.00001) and triglycerides (MD 26.22, 95 % CI -38.94 to -13.51, p < 0.0001), as well as increased antioxidant capacity (MD 173.51, 95 % CI 164.72-182.30, p < 0.00001), but showed no obvious effect on nitric oxide (MD 5.95, 95 % CI -7.48 to 19.37, p = 0.39) or total cholesterol (MD 1.63, 95 % CI -13.46 to 16.72, p = 0.83).Conclusions: Omega-3 fatty acid and vitamin co-supplementation may have a favourable effect on metabolic status in gestational diabetes. [ABSTRACT FROM AUTHOR]

Background: The genotype-phenotype relationships between TUBB8 variants and female infertility are difficult to clearly define due to the complex inheritance patterns and the highly heterogeneous phenotypes. This study aims to identify novel TUBB8 variants and relevant phenotypes in more infertile females. Methods: A total of 35 females with primary infertility were recruited from two reproductive centers and investigated for identifying variants in TUBB8. Pedigree analysis, in-silico analysis and molecular remodeling were performed to assess their clinical significance. The effects of the variants on human oocytes and embryos as well as HeLa cells were analyzed by morphological observations, immunostaining and Western blot. Results: We totally identified five novel variants (p.G13R, p.Y50C, p.T136I, p.F265V and p.T366A) and five previously reported variants (p.I4L, p.L42V, p.Q134*, p.V255M and p.V349I) in TUBB8 from 9 unrelated females with primary infertility. These variants were rare and highly conserved among different species, and were inherited in autosomal dominant/recessive patterns, or occurred de novo. In vitro functional assays in HeLa cells revealed that exogenous expression of mutant TUBB8 proteins caused different degrees of microtubule structural disruption. The existence of these pathogenic TUBB8 variants finally induced oocyte maturation arrest or morphological abnormalities, fertilization failure, cleavage failure, embryonic development defects and implantation failure in the affected females. Conclusion: These findings enriched the variant spectrum of TUBB8 gene and could contribute to optimize genetic counselling and clinical management of females with primary infertility. [ABSTRACT FROM AUTHOR]

Purpose: Multiple morphological abnormalities of the sperm flagella (MMAF) are a severe form of sperm defect causing male infertility. Previous studies identified the variants in the CFAP69 gene as a MMAF-associated factor, but few cases have been reported. This study was performed to identify additional variants in CFAP69 and describe the semen characteristics and outcomes of assisted reproductive technology (ART) in CFAP69-affected couples. Methods: Genetic testing with next-generation sequencing (NGS) panel of 22 MMAF-associated genes and Sanger sequencing was performed in a cohort of 35 infertile males with MMAF to identify pathogenic variants. Morphological, ultrastructural, and immunostaining analyses were performed to investigate the characteristics of probands' spermatozoa. ART with intracytoplasmic sperm injection (ICSI) was carried out for the affected couples to get their own progenies. Results: We identified a novel frameshift variant in CFAP69 (c.2061dup, p. Pro688Thrfs*5) from a MMAF-affected infertile male with low sperm motility and malformed morphology of sperm. Furthermore, transmission electron microscopy and immunofluorescence staining revealed that the variant induced the aberrant ultrastructure and reduction of CFAP69 expression in the proband's spermatozoa. Moreover, the partner of the proband birthed a healthy girl through ICSI. Conclusions: This study expanded the variant spectrum of CFAP69 and described the good outcome of ART treatment with ICSI, which is beneficial to the molecular diagnosis, genetic counseling, and treatment of infertile males with MMAF in the future. [ABSTRACT FROM AUTHOR]

Postovulatory aging can trigger deterioration of oocyte quality and subsequent embryonic development, and thus reduce the success rates of assisted reproductive technology (ART). The molecular mechanisms underlying postovulatory aging, and preventative strategies, remain to be explored. The near‐infrared fluorophore IR‐61, a novel heptamethine cyanine dye, has the potential for mitochondrial targeting and cell protection. In this study, we found that IR‐61 accumulated in oocyte mitochondria and reduced the postovulatory aging‐induced decline in mitochondrial function, including mitochondrial distribution, membrane potential, mtDNA number, ATP levels, and mitochondrial ultrastructure. In addition, IR‐61 rescued postovulatory aging‐caused oocyte fragmentation, defects in spindle structure, and embryonic developmental potential. RNA sequencing analysis indicated that the postovulatory aging‐induced oxidative stress pathway might be inhibited by IR‐61. We then confirmed that IR‐61 decreased the levels of reactive oxygen species and MitoSOX, and increased GSH content in aged oocytes. Collectively, the results indicate that IR‐61 may prevent postovulatory aging by rescuing oocyte quality, promoting successful rate in ART procedure. [ABSTRACT FROM AUTHOR]

The aeroelastic effect of gust generator vanes with a high aspect ratio is more significant in large-scale wind tunnels. High-fidelity numerical results based on the computational fluid dynamics (CFD) and computational structural mechanics (CSM) coupling methodology have an extremely high computational cost. To this end, a data-driven method for rapidly estimating unsteady flexible deformations of gust generators vanes is developed. The aeroelastic rigid-elastic reduced-order model is built by the dynamic mode decomposition with control and prediction error minimization (DMDcP) methods. For all cases validated with various pitching amplitudes and frequencies of gust vanes, the maximum cumulative errors of DMDcP reduced-order model solutions are all under 2%. The efficiency of the presented method has the potential to fast estimate unsteady flexible deformations and reduce computational cost in the early stages of gust generator design while maintaining adequate accuracy as the CFD-CSM coupling methodology. [ABSTRACT FROM AUTHOR]

• Novel variants of ZP1, ZP2 and ZP3 are associated with female infertility. • In-vitro functional studies of ZP protein variants indicate pathogenesis. • The ZP3 variant was overcome with ICSI treatment. • Targeted genetic diagnosis of ZP genes may guide fertilization methods. Which genetic variants might explain the causes of empty follicle syndrome (EFS) and abnormal zona pellucida (ZP) and affect the success of treatment with assisted reproductive technologies (ART)? Whole-exome sequencing was performed in probands with EFS and abnormal ZP. Sanger sequencing was used for variant validation. Using HEK-293T cells, the effects of ZP1 and ZP2 variants on protein expression were explored by western blotting, and the effect of the ZP1 variant on protein location was investigated via immunofluorescence. The protein structure was also analysed to investigate the pathogenicity of variants. A homozygous nonsense variant in ZP1 (c.874C>T, p.Gln292*) was detected in a patient with EFS. A novel homozygous frameshift variant in ZP2 (c.836_837delAG, p.Glu279Valfs*6) and a novel heterozygous missense variant in ZP3 (c.1159G>A, p.Val387Met) were identified in two patients with ZP morphological abnormalities, respectively. Western blotting and immunofluorescence analysis showed that the ZP1 variant results in a premature stop codon, leading to the truncated ZP1 protein. The ZP2 variant, which is situated in the N-terminus, triggers the degradation of a premature termination protein. Additionally, the patient with the ZP3 variant achieved clinical pregnancy following intracytoplasmic sperm injection treatment. These findings expand the mutational spectrum of ZP1, ZP2 and ZP3 , and provide new evidence for genetic diagnosis of female infertility. The targeted genetic diagnosis of ZP genes is recommended to choose appropriate fertilization methods and improve success rates of treatment with ART. [ABSTRACT FROM AUTHOR]

Objective: Given that the molecular diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is complicated, we aim to apply blocker displacement amplification (BDA) on the mutational screening of PKD1 and PKD2. Methods: A total of 35 unrelated families with ADPKD were recruited from the Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University (Chongqing, China), from October 2018 to October 2021. Long-range PCR followed by next-generation sequencing were applied for resequencing of PKD1 and PKD2, and the putatively disease-causative variants were verified with BDA. The effects of ADPKD on male and female infertility and the factors influencing the clinical outcomes of preimplantation genetic testing (PGT) for ADPKD were investigated. Results: A total of 26 PKD1 variants and 5 PKD2 variants were identified, of which 13 were newly discovered. The BDA system worked effectively for eliminating the interference of pseudogenes in genetic testing of PKD1 (1–33 exons) with different concentrations of genome DNA. The females with ADPKD have no specific infertility factors, while 68.2% of the affected men were with abnormal sperm concentration and/or motility with an indefinite genotype–phenotype relationship. As for PGT, the fertilization rate of couples with the male partner having ADPKD was relatively lower compared to those with the female partner being affected. The ADPKD patients receiving PGT usually achieved high rates of live births. Conclusion: These findings expanded the variant spectrum of PKD genes and emphasized the application prospect of blocker displacement amplification on PKD1-related genetic diagnosis. [ABSTRACT FROM AUTHOR]

The characteristics of the human pronuclei (PNs), which exist 16–22 h after fertilization, appear to serve as good indicators to evaluate the quality of human oocyte and embryo, and may reflect the status of female and male chromosome composition. Here, a quantitative PN measurement method that is generated by applying expert experience combined with deep learning from large annotated datasets is reported. After mathematic reconstruction of PNs, significant differences are obtained in chromosome‐normal rate and chromosomal small errors such as copy number variants by comparing the size of the reconstructive female PN. After integrating the whole procedure of PN dynamics and adjusting for errors that occur during PN identification, the results are robust. Notably, all positive prediction results are obtained from the female propositus population. Thus, the size of female PNs may mirror the internal quality of the chromosomal integrity of the oocyte. Embryos that develop from zygotes with larger female PNs may have a reduced risk of copy number variations. [ABSTRACT FROM AUTHOR]

Research question: More than 100 variants have been identified in the TUBB8 gene, which account for approximately 30% of infertile women with oocyte maturation defects. But what is the correlation between the highly phenotypic diversity and genetic variability? Are there other variants in TUBB8 related to female infertility? Design: TUBB8 resequencing was performed in 80 female subjects who were experiencing infertility and were seeking treatment with assisted reproductive technologies (ART), or had ever experienced ART failure due to oocyte maturation defects. All variants were evaluated with pedigree analysis, population frequency, in-silico analysis and molecular modelling. The effects of the variants on oocytes/arrested embryos were assessed by morphological observations, immunostaining, embryo biopsies and chromosome euploidy analysis. Results: Nine missense variants and two frameshift variants from an additional 15 families were identified, including four novel variants and seven previously reported recurrent variants. These TUBB8 variants were related to highly variable phenotypes, including abnormalities in oocyte maturation or morphology, fertilization failure, embryonic development abnormalities and implantation failure. Also further clarified were the incomplete penetrance of heterozygous p.E108K, the likely benign significance of heterozygous p.A313V and the clinical effect of a novel variant of p.R380C. Conclusions: This study significantly expands the variant spectrum of the TUBB8 gene and, together with the available findings on TUBB8 variants and female infertility, will potentially facilitate the genetic counselling of infertile women in future. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare the DNA methylation profiles of human embryos cultured in uninterrupted or interrupted incubators. Methods: This study included 9 women, ≤ 30 years old (range: 20–30 years), without a history of genetic diseases or smoking, undergoing ICSI treatment, and each woman donated one oocyte. Embryos were randomly assigned to culture in either time-lapse imaging or standard incubators after ICSI. We compared the DNA methylation profiles of human eight-cell embryos cultured in uninterrupted condition using time-lapse imaging (TLI) incubator (EmbryoScope) to those cultured in interrupted culture model using standard incubators (SI, G185 K-System). Nine single-cell whole-genome bisulfite sequencing (WGBS) datasets were analyzed, including four SI-cultured embryos and five TLI-cultured embryos at the eight-cell stage. Results: A total of 581,140,020 and 732,348,182 clean reads were generated from the TLI and SI groups, respectively. TLI-cultured embryos had similar genome-wide methylation patterns to SI-cultured embryos. There were no significant differences in the methylation and transcription levels of transposable elements and imprinted control regions. Although a total of 198 differentially methylated genes (DMGs) were identified, only five DMGs had significantly different transcription levels between the two groups. Conclusions: This is the first study to compare the DNA methylation profiles of embryos cultured in TLI and SI and will provide a foundation for evaluating the safety of TLI application in assisted reproductive technologies. However, further study with a larger cohort of samples was needed for the data validation. [ABSTRACT FROM AUTHOR]

[Display omitted] • 17 and 3 intrafollicular fluid metabolites related to ovarian hyperstimulation syndrome risk in non-ovarian etiologic infertility and polycystic ovarian syndrome, respectively. • 9 of the ovarian hyperstimulation syndrome-related metabolites overlapped with the differential metabolites of the polycystic ovarian syndrome, 8 of which are unsaturated fatty acids. • Non-ovarian etiologic infertility and polycystic ovarian syndrome display metabolic heterogeneities in the development of ovarian hyperstimulation syndrome. • Ovarian hyperstimulation syndrome has some shared etiological factors with the polycystic ovarian syndrome. Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of ovulation stimulation during assisted reproductive technology. The main objective of this study was to investigate intrafollicular fluid metabolic change profiles of OHSS in non-ovarian etiologic infertility women (CON) and polycystic ovarian syndrome patients (PCOS). 87 infertile women were divided into four subgroups: CON-Norm (CON with normal ovarian response), CON-OHSS (CON with OHSS), PCOS-Norm (PCOS with normal ovarian response), and PCOS-OHSS (PCOS with OHSS). The intrafollicular fluid metabolic profiles were analyzed with gas chromatography-mass spectrometry. The multivariable-adjusted conditional logistic regression was applied to assess the association of metabolites with OHSS risk. We identified 17 and 3 metabolites that related to OHSS risk in CON and PCOS, respectively. 13 OHSS risk-related metabolites in CON were unsaturated fatty acids, 8 of which were also the significantly altered metabolites between all PCOS and CON-Norm. Our study may shed light on the role of intrafollicular fluid metabolic abnormalities in the pathophysiology of OHSS. The findings suggested that there might be some metabolic heterogeneities underlying the development of OHSS in CON and PCOS women and indicated possible shared etiological factors in the development of PCOS and OHSS. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.Single reproductive medical center.All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.Next-generation sequencing platforms for chromosomal analysis.Blastocyst formation and euploid blastocyst rates.In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.Methods: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.Single reproductive medical center.All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.Next-generation sequencing platforms for chromosomal analysis.Blastocyst formation and euploid blastocyst rates.In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.Setting: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.Single reproductive medical center.All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.Next-generation sequencing platforms for chromosomal analysis.Blastocyst formation and euploid blastocyst rates.In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.Subjects: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.Single reproductive medical center.All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.Next-generation sequencing platforms for chromosomal analysis.Blastocyst formation and euploid blastocyst rates.In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.Exposure: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.Single reproductive medical center.All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.Next-generation sequencing platforms for chromosomal analysis.Blastocyst formation and euploid blastocyst rates.In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.Main outcome measures.: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.Single reproductive medical center.All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.Next-generation sequencing platforms for chromosomal analysis.Blastocyst formation and euploid blastocyst rates.In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.Results: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.Single reproductive medical center.All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.Next-generation sequencing platforms for chromosomal analysis.Blastocyst formation and euploid blastocyst rates.In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.Conclusion: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.Single reproductive medical center.All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.Next-generation sequencing platforms for chromosomal analysis.Blastocyst formation and euploid blastocyst rates.In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates. [ABSTRACT FROM AUTHOR]

Is the total duration of spontaneous blastocyst collapse to re-expansion before biopsy related to ploidy and live birth rates after single euploid blastocyst transfer? This was a retrospective cohort study of 600 preimplantation genetic testing cycles for aneuploidy (PGT-A) cycles, involving 2203 biopsied blastocysts, at a large reproductive medicine centre. Features of spontaneous blastocyst collapse from full to expanded stage, before biopsy, were observed using an embryoscope viewer for embryos cultured in a time-lapse incubator. In total, 568 cycles of frozen blastocyst transfers, either single euploid or mosaic, were performed. Correlations between collapse features and PGT-A outcomes were evaluated, as well as live birth rate, following euploid embryo transfer. Blastocysts with lower morphological quality or delayed development had significantly higher rates of collapse, multiple collapses, and a longer duration of collapse to re-expansion. After controlling for confounders, such as oocyte age, morphological quality of blastocyst, and day of biopsy, multivariate logistic regression revealed that the total duration of collapse to re-expansion was an independent predictor of lower euploidy rate; the multivariate OR was 0.85 (95% CI 0.77–0.95; P = 0.00). Furthermore, even with euploid embryo transfer, the probability of a live birth decreased as the total duration of collapse to re-expansion increased; the multivariate OR was 0.79 (95% CI 0.64–0.98; P = 0.033). The total duration of blastocyst collapse to re-expansion could be used as a predictor of lower euploidy and live birth rate. When developing blastocyst algorithms for pregnancy prediction, the duration of spontaneous blastocyst collapse should be included as a significant variable. [ABSTRACT FROM AUTHOR]

In order to study the impact of procedures of IVF/ICSI technology on sex ratio in China, we conducted this multi-center retrospective study including 121,247 babies born to 93,895 women in China. There were 62,700 male babies and 58,477 female babies, making the sex ratio being 51.8% (Male: Female  = 107∶100). In univariate logistic regression analysis, sex ratio was imbalance toward females of 50.3% when ICSI was preformed compared to 47.7% when IVF was used (P<0.01). The sex ratio in IVF/ICSI babies was significantly higher toward males in transfers of blastocyst (54.9%) and thawed embryo (52.4%) when compared with transfers of cleavage stage embryo (51.4%) and fresh embryo (51.5%), respectively. Multiple delivery was not associated with sex ratio. However, in multivariable logistic regression analysis after controlling for related factors, only ICSI (adjusted OR = 0.90, 95%CI: 0.88–0.93; P<0.01) and blastocyst transfer (adjusted OR = 1.14, 95% CI: 1.09–1.20; P<0.01) were associated with sex ratio in IVF/ICSI babies. In conclusion, the live birth sex ratio in IVF/ICSI babies was influenced by the use of ICSI, which may decrease the percentage of male offspring, or the use of blastocyst transfer, which may increase the percentage of male offspring. [ABSTRACT FROM AUTHOR]

It was suggested that the embryo pooling was an alternative for patients with insufficient number of embryos for preimplantation genetic testing (PGT) in a single ovarian stimulation cycle. However, limited study noticed whether it is an efficient strategy to pool cleavage-stage embryos by vitrification. This study included 71 cycles with vitrified-warmed and fresh embryos simultaneously for PGT between May 2016 and May 2021. The embryos from the same patients were split into two groups based on the origin: warming group and fresh group. Embryo development, sequencing results, clinical and neonatal outcomes were compared. The results showed that the rate of high-quality embryos in the warming group was significantly higher than that in the fresh group (64.53% versus 52.61%, P = 0.011); however, the available blastocyst rate in this group was significantly lower than that in the fresh group (47.29% versus 57.83%, P = 0.026). There were 96 and 144 blastocysts that underwent trophectoderm (TE) biopsy in warming and fresh groups, respectively. The high-quality blastocyst rate was significantly lower in the warming group compared to the fresh group (57.29% versus 70.14%, P = 0.041). The rates of genetic transferable blastocyst were comparable between the two groups (P = 0.956). There were no statistical differences in terms of embryo implantation, clinical pregnancy, miscarriage rates, and neonatal outcomes between the two groups. In conclusion, this study demonstrated that the cleavage-stage embryo pooling strategy might be unfavorable for the maintenance of embryonic development potential. If not necessary, it is not recommended to pool cleavage-stage embryos for PGT. [ABSTRACT FROM AUTHOR]

The widespread application of nanoparticles (NPs) in various fields has raised health concerns, especially in reproductive health. Our research has shown zinc oxide nanoparticles (ZnONPs) exhibit the most significant toxicity to pre-implantation embryos in mice compared to other common NPs. In patients undergoing assisted reproduction technology (ART), a significant negative correlation was observed between Zn concentration and clinical outcomes. Therefore, this study explores the impact of ZnONPs exposure on pre-implantation embryonic development and its underlying mechanisms. We revealed that both in vivo and in vitro exposure to ZnONPs impairs pre-implantation embryonic development. Moreover, ZnONPs were found to reduce the pluripotency of mouse embryonic stem cells (mESCs), as evidenced by teratoma and diploid chimera assays. Employing multi-omics approaches, including RNA-Seq, CUT&Tag, and ATAC-seq, the embryotoxicity mechanisms of ZnONPs were elucidated. The findings indicate that ZnONPs elevate H3K9me3 levels, leading to increased heterochromatin and consequent inhibition of gene expression related to development and pluripotency. Notably, Chaetocin, a H3K9me3 inhibitor, sucessfully reversed the embryotoxicity effects induced by ZnONPs. Additionally, the direct interaction between ZnONPs and H3K9me3 was verified through pull-down and immunoprecipitation assays. Collectively, these findings offer new insights into the epigenetic mechanisms of ZnONPs toxicity, enhancing our understanding of their impact on human reproductive health. Schematic diagram of the mechanism of the ZnONPs effects on pre-implantation embryos and mESCs. ZnONPs exposure impairs the development of pre-implantation embryos and pluripotency of mESCs (upper), and a model of ZnONPs-triggered H3K9me3-dependent heterochromatin in the suppression of developmental and pluripotency-related genes (below). [Display omitted] [ABSTRACT FROM AUTHOR]

Pronuclei and blastomeres are key structures in early embryonic development, and by localizing these structures simultaneously, the developmental state of the embryo can be assessed more comprehensively. However, there are several unavoidable problems in localization tasks due to the biological characteristics of embryos, including blastomeres overlap, pronuclei overlap, and similarity between pronuclei and background. In this study, we propose a novel localization network for pronuclei and blastomeres, which can solve these localization problems. Firstly, to address the issues related to the overlap of pronuclei and blastomeres, as well as the pronuclei and background similarity problem, we put the vision transformer with bi-level routing attention module (BiFormer) in the backbone. The BiFormer finds attention regions in the embryo image scene to obtain more edge and texture information of both pronuclei and blastomeres, which allows for a better feature realization of the neck region fusion interaction. Subsequently, to enhance model performance and mitigate redundant computation. The localization network uses partial convolution (PConv) in the backbone. The backbone network allows more efficient extraction of features by simultaneously reducing redundancy in computation with the effect of PConv. In addition, to mitigate the impact of low-quality samples in embryo images on localization, as well as to pay more attention to ordinary quality samples, we use wise intersection over union version 3 (WIoUv3) loss function with a dynamic non-monotonic focusing mechanism in the localization network, thus improving the overall performance of the algorithm. The experimental results show our model mAP@0.5 is 92.4% in localizing pronuclei and blastomeres. In practical terms, the ability to accurately localize pronuclei and blastomeres allows for better assessment of embryo quality and selects the best embryos. [Display omitted] • For the first time, we propose a target localization scheme to locate pronuclei and blastomeres in embryo images. • We use BiFormer to help the network better extract edge, and texture features of pronuclei and blastomeres. • We use partial convolution in YOLOv7-PB to reduce the number of network parameters by reducing redundant computations. • Our proposed YOLOv7-PB network incorporates WIoUv3 as part of the bounding box regression loss. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the link between the GDF9 concentration in day 3 human embryo culture medium and embryo quality and viability. Methods: Two independent, prospective, observational studies were conducted. In study 1, a total of 280 embryos from 70 patients who obtained at least 4 embryos with 6–10 blastomeres (2 transferable and 2 non-transferable embryos) at day 3 were enrolled. In study 2, a total of 119 embryos from 61 patients (29 fully implanted and 32 non-implanted patients) were enrolled. The corresponding GDF9 concentrations in spent culture medium of embryos were quantified by ELISA assay. The expression pattern of GDF9 in human embryos was investigated using Q-PCR and immunofluorescence. Results: GDF9 mRNA and protein were detected from human oocytes to eight-cell embryos and displayed a slow decreasing trend. In study 1, GDF9 concentration in culture medium is lower for transferable embryos compared with non-transferable embryos (331 pg/mL (quartiles: 442, 664 pg/mL) vs. 518 pg/mL (quartiles: 328, 1086 pg/mL), P < 0.001), and increased commensurate with the diminution of the embryo quality (P < 0.001). In study 2, significantly lower GDF9 concentration was detected for implanted embryos than non-implanted embryos (331 pg/mL (quartiles: 156, 665 pg/mL) vs. 518 pg/mL (quartiles: 328, 1086 pg/mL), P < 0.001). The same trend was found between the embryos that led to live birth and those that failed. Conclusion: The GDF9 concentration in culture medium is linked to embryo quality and viability, and exhibited the potential to be a non-invasive biomarker for embryo selection. [ABSTRACT FROM AUTHOR]

The objective of this prospective cohort study was to investigate whether cryopreservation of cleavage or blastocyst stage embryos improves in vitro fertilization outcomes in recurrent implantation failure (RIF) patients. The study comprised 575 patients who were allocated to receive either single frozen/thawed blastocyst-stage transfer (SBT) or frozen/thawed double-cleavage-stage embryo transfer (DET). The clinical pregnancy rate, implantation rate, and ongoing pregnancy rate were higher in the SBT group compared with the DET group (41.15% vs. 27.11%, p < 0.001; 41.15% vs. 19.28%, p < 0.001; 40.03% vs. 25.9%, p < 0.001), but the miscarriage rate did not differ between the two groups. It was concluded that frozen/thawed SBT could be a preferred strategy for RIF patients. [ABSTRACT FROM AUTHOR]

Background: A consensus has been reached on the preferred primary outcome of all infertility treatment trials, which is the cumulative live birth rate (CLBR). Some recent randomized controlled trials (RCTs) and retrospective studies have compared the effectiveness of GnRH-antagonist and GnRH-agonist protocols but showed inconsistent results. Studies commonly used conservative estimates and optimal estimates to described the CLBR of one incomplete assisted reproductive technology (ART) cycle and there are not many previous studies with data of the complete cycle to compare CLBRs in GnRH-antagonist versus GnRH-agonist protocols. Methods: A total of 18,853 patients have completed their first IVF cycle including fresh and subsequent frozen-thawed cycles during 2016–2019, 16,827 patients were treated with GnRH-a long and 2026 patients with GnRH-ant protocol. Multivariable logistic analysis was used to evaluate the difference of GnRH-a and GnRH-ant protocol in relation to CLBR. Utilized Propensity Score Matching(PSM) for sampling by up to 1:1 nearest neighbor matching to adjust the numerical difference and balance the confounders between groups. Results: Before PSM, significant differences were observed in baseline characteristics and the CLBR was 50.91% in the GnRH-a and 33.42% in the GnRH-ant (OR = 2.07; 95%CI: 1.88–2.28; P < 0.001). Stratified analysis showed the CLBR of GnRH-ant was lower than GnRH-a in suboptimal responders(46.89 vs 27.42%, OR = 2.34, 95%CI = 1.99–2.74; P < 0.001) and no differences of CLBR were observed in other patients between protocols. After adjusting for potential confounders, multivariable logistic analysis found the CLBR of GnRH-ant group was lower than that of GnRH-a group (OR = 2.11, 95%CI:1.69–2.63, P < 0.001). After PSM balenced the confounders between groups, the CLBR of GnRH-a group was higher than that of GnRH-ant group in suboptimal responders((38.61 vs 28.22%, OR = 1.60, 95%CI = 1.28–1.99; P < 0.001) and the normal fertilization rate and number of available embryo in GnRH-a were higher than these of GnRH-ant groups in suboptimal responders (77.39 vs 75.22%; 2.86 ± 1.26 vs 2.61 ± 1.22; P < 0.05). No significant difference was observed in other patients between different protocols. Conclusions: It is crucial to optimize the utilization of protocols in different ovarian response patients and reconsider the field of application of GnRH-ant protocols in China. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyze the impact of different biopsy protocols on the rate of mosaic blastocysts. Methods: This is a retrospective cohort study which included 115 cycles with pre-implantation genetic testing for aneuploidy (PGT-A). Two groups were allocated based on the biopsy protocols: method 1 group, the zona pellucida (ZP) was drilled on day 3 embryos followed by trophectoderm (TE) biopsy; and method 2 group, the ZP was opened on day 5 or 6 blastocysts followed by TE biopsy. All biopsy samples were assessed using next-generation sequencing (NGS) at a single reference laboratory. The euploid, aneuploid, and mosaic blastocyst rates and clinical outcomes were compared. Results: The mosaicism rate in the method 1 group was 19.58%, significantly higher than the method 2 group (8.12%; P < 0.05). No statistically significant difference was observed in euploid, aneuploid blastocyst rates, and clinical pregnancy rates between the two groups. Logistic regression analysis indicated that the biopsy protocols were independently associated with the mosaicism rates among all the variables. Conclusions: The present study showed that different biopsy protocols may have an impact on the mosaic blastocyst rate. ZP opening on day 3 combined with TE biopsy might increase the incidence of mosaic blastocysts. [ABSTRACT FROM AUTHOR]

Background: No previous study directly compares the fixed day-5 initiation versus the flexible initiation of GnRH antagonist administration in IVF/ICSI for those patients who are predicted as high ovarian responders without PCOS. To evaluate whether the number of oocytes retrieved is different by using the two GnRH antagonist protocols in Chinese women with predicted high ovarian response except PCOS.Methods: A randomized controlled trial of 201 infertile women with predicted high ovarian response except PCOS undergoing in vitro fertilization. Ovary stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist ganirelix (0.25 mg/d) was started either on day 5 of stimulation (fixed group) or when LH was > 10 IU/L, and/or a follicle with mean diameter > 12 mm was present, and/or serum E2 was > 600 pg/ml. Patient monitoring was initiated on day 3 of stimulation in flexible group.Result(s): No significant difference was observed between the fixed and flexible groups regarding the number of oocytes retrieved (16.72 ± 7.25 vs. 17.47 ± 5.88, P = 0.421), the Gonadotropin treatment duration (9.53 ± 1.07 vs. 9.67 ± 1.03, P = 0.346) and total Gonadotropin dose (1427.75 ± 210.6 vs. 1455.94 ± 243.44, P = 0.381). GnRH antagonist treatment duration in fixed protocol was statistically longer than the flexible protocol (6.57 ± 1.17 vs 6.04 ± 1.03, P = 0.001). There was no premature LH surge in either protocol.Conclusion(s): Fixed GnRH antagonist administration on day 5 of stimulation appear to achieve a comparable oocyte retrieved compared with flexible antagonist administration.Trial Registration: NCT02635607 posted on December 16, 2015 in clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Could the mitochondrial DNA (mtDNA) copy number of cumulus cells be used as a biomarker of the potential of embryo implantation in good prognosis IVF patients? A prospective cohort study on good prognosis IVF patients from a large reproductive medicine centre. A total of 392 embryos from 61 cycles (including 31 implanted and 30 non-implanted cycles) were enrolled in the study. The corresponding cumulus cell mtDNA copy number of embryos was tested by real-time quantitative polymerase chain reaction. The corresponding cumulus cell mtDNA copy numbers were compared between implanted and non-implanted embryos and also compared between high quality and poor quality embryos. Then, a mitochondrial function assay including mitochondrial membrane potentials, concentration of reactive oxygen species (ROS) and ATP content of the corresponding cumulus cells were compared between high quality and poor quality embryos to verify the above experimental findings. For the same population, the mean cumulus cell mtDNA copy numbers for implanted and non-implanted embryos were 255.61 ± 81.02 and 254.50 ± 73.29 (P = 0.47), and those for high quality and poor quality embryos were 266.02 ± 98.56 and 295.71 ± 70.64 (P = 0.99), respectively. There was no significant difference in cumulus cell mtDNA copy number between implanted and non-implanted embryos or between high quality and poor quality embryos. The mitochondrial membrane potential, ROS levels and ATP content of the corresponding cumulus cells did not differ significantly between high quality and poor quality groups. Measurement of cumulus cell mtDNA copy number might not provide any advantage to embryo prioritization in good prognosis IVF patients. Any suggested link between cumulus cell mtDNA copy number and embryo implantation requires further validation. [ABSTRACT FROM AUTHOR]

Background: Along with progress in embryo cryopreservation, especially the vitrification, freeze all strategy has become more acceptable than ever. Some studies have found comparable or higher live birth rate with frozen embryo transfer (FET) than with fresh embryo transfer(ET)in gonadotropin releasing hormone antagonist (GnRH-ant) protocol. However from our literature research, there have been no reports about live birth rate comparison between fresh ET and FET with gonadotropin releasing hormone agonist (GnRH-a) long protocol. The aim of this study is to retrospectively investigate whether patients benefit from freeze all strategy in GnRH-a protocol using real-world data.Methods: This is a retrospective cohort study, in which women undergoing fresh ET or FET with GnRH-a long protocol at Chongqing Reproductive and Genetics Institute from January 2016 to December 2018 were evaluated. The primary outcome was live birth rate. The secondary outcomes were implantation rate, clinical pregnancy rate, pregnancy loss and ectopic pregnancy rate.Results: A total of 7,814 patients met inclusion criteria, implementing 5,216 fresh ET cycles and 2,598 FET cycles, respectively. The demographic characteristics of the patients were significantly different between fresh ET and FET groups, except BMI. After controlling for a broad range of potential confounders including age, infertility duration, BMI, AMH, number of oocytes retrieved and of available embryos, multivariate logistic regression analysis demonstrated that there was no significant difference in clinical pregnancy rate, ectopic pregnancy rate and pregnancy loss rate between two groups (all P > 0.05). However, the implantation rate and live birth rate in fresh ET group were significantly higher than FET group (P < 0.001 and P = 0.012, respectively).Conclusions: Under GnRH-a long protocol, compared to FET, fresh ET was associated with higher implantation rate and live birth rate in infertile patients that underwent in vitro fertilization (IVF). The freeze all strategy should be individualized and made with caution especially with GnRH-a long protocol. [ABSTRACT FROM AUTHOR]

Background: Many studies have demonstrated the benefits of the addition of growth hormone (GH) to the controlled ovarian stimulation protocol in vitro fertilization (IVF) cycles in poor-respond patients, but the effect of GH on patients with poor embryonic development remain unclear. This paper was designed to investigate the efficacy of GH co-treatment during IVF for the patients with poor embryonic development.Method: A randomized controlled trial including 158 patients with poor embryo development was conducted between July 2017 and February 2019. One hundred and seven patients were randomized for GH treatment (GH group) and 51 patients for untreated (control group). The primary end-points were the clinical pregnancy and live birth rates in the two groups. The oocyte competence were assessed through calculating the mitochondrial DNA (mtDNA) copy number in corresponding cumulus granulosa cells (CGCs). Quantitative PCR were used for calculation of mtDNA copy number.Results: Relative to the control group, GH co-treatment resulted in a significantly higher number of retrieved oocytes (10.29 ± 5.92 versus 8.16 ± 4.17, P = 0.023) and cleaved embryos (6.73 ± 4.25 versus 5.29 ± 3.23, P = 0.036). The implantation rate, clinical pregnancy rates per cycle, and live birth rate per cycle were higher in the GH group than in the control group (36.00% versus 17.86%, P = 0.005; 43.93% versus 19.61%, P = 0.005; 41.12% versus 17.65%, P = 0.006). CGCs of the GH group had significantly higher mtDNA copy numbers than CGCs of the control group (252 versus 204, P < 0.001).Conclusions: These data provided further evidence to indicate that GH supplementation may support more live births during IVF, in patients with poor embryonic development. It also appears that oocytes generated under GH co-treatment have a better developmental competence.Trial Registration: ChiCTR1900021992 posted March 19, 2019 (retrospectively registered). [ABSTRACT FROM AUTHOR]

This prospective randomized clinical trial (RCT) was to evaluate the effect of single-dose gonadotrophin-releasing hormone agonist (GnRHa) in artificial cycle frozen-embryo transfer (AC-FET). A total of 868 FET cycles were included and randomized into two groups: Group A (n = 434) received GnRHa 0.1 mg subcutaneous injection on day 3 after embryo transfer (ET); Group B (n = 434) did not receive GnRHa. The demographic characteristics, primary endpoint (implantation rate) and secondary endpoints (chemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate) were compared between two groups and subgroups (aged <35 years and 35-37 years). There were no significant differences in terms of the rates of implantation, clinical pregnancy, ongoing pregnancy, and miscarriage between two groups. While, the subgroups analysis showed the implantation rate was significantly increased in advanced age women (35–37 years) in GnRHa group compared with control group (45.3% vs. 27.8%, p =.03). In conclusion, single dose of GnRHa (0.1 mg triptorelin acetate) supplementation 3 days after ET in AC-FET cycles did not show significant benefit on pregnancy outcomes as a whole. However, in ageing women subgroup, the implantation rate was increasing by adding up GnRHa in peri-implantation periods, and this tendency needs to be further demonstrated by RCT with larger sample size. [ABSTRACT FROM AUTHOR]

In this prospective cohort study, the effects of a time-lapse monitoring system on embryo quality and clinical pregnancy outcomes were assessed. A total of 608 patients undergoing in vitro fertilization between April 2013 and June 2014 at our institution were recruited for this study and group-matched into a time-lapse monitoring (TLM) (N = 304) or a standard incubator (SI) (N = 304). The patients’ characteristics in the TLM and SI groups were not significantly different. The TLM group showed a significantly higher transferable embryo ratio at Day 3 (61.65% vs. 52.87%; p < 0.0010, RR =1.10 [1.02, 1.19]), a higher number of transferable embryos (4.71 ± 2.38 vs. 4.09 ± 2.35; p = 0.0053, SMD =0.26 [0.06, 0.46]) and number of good-quality embryos cryopreserved at Day 3 (2.72 ± 2.35 vs. 2.11 ± 2.33; p = 0.0056, SMD =0.26 [0.06, 0.46]). In addition, the implantation and clinical pregnancy rates were not statistically significant between the TLM and SI groups. However, the TLM group had a higher ongoing pregnancy rate (67.32% vs. 57.22%; p = 0.0410) and live birth rate (65.37% vs. 55%; p = 0.0380) compared with the SI group. The observed beneficial effects could be the result of a more stable environment provided by the TLM system. [ABSTRACT FROM AUTHOR]

Could objective embryo assessment using iDAScore Version 2.0 perform as well as conventional morphological assessment? A retrospective cohort study of fresh day 3 embryo transfer cycles was conducted at a large reproductive medicine centre. In total, 7786 embryos from 4328 cycles with known implantation data were cultured in a time-lapse incubator and included in the study. Fetal heartbeat (FHB) rate was analysed retrospectively using iDAScore Version 2.0 and conventional morphological assessment associated with the transferred embryos. The pregnancy-prediction performance of the two assessment methods was compared using area under the curve (AUC) values for predicting FHB. AUC values were significantly higher for iDAScore compared with morphological assessment for all cycles (0.62 versus 0.60; P = 0.005), single-embryo transfer cycles (0.63 versus 0.60; P = 0.043) and double-embryo transfer cycles (0.61 versus 0.59; P = 0.012). For the age subgroups, AUC values were significantly higher for iDAScore compared with morphological assessment in the <35 years subgroup (0.62 versus 0.60; P = 0.009); however, no significant difference was found in the ≥35 years subgroup. In terms of the number of blastomeres, AUC values were significantly higher for iDAScore compared with morphological assessment for both the <8c subgroup (0.67 versus 0.56; P < 0.001) and the ≥8c subgroup (0.58 versus 0.55; P = 0.012). iDAScore Version 2.0 performed as well as, or better than, conventional morphological assessment in fresh day 3 embryo transfer cycles. iDAScore Version 2.0 may therefore constitute a promising tool for selecting embryos with the highest likelihood of implantation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the incidence of oocytes with severe ovoid zona pellucida (ZP), investigate the development potential of their sibling oocytes and the clinical outcomes from affected cycles. The data were collected from our medical records. Cycles having at least one oocyte with severe ovoid ZP were defined as the ‘severe ovoid group’, cycles having at least one oocyte with mild ovoid ZP were defined as the ‘mild ovoid group’, whereas cycles without oocytes with ovoid ZPs were defined as the ‘control group’ (n = 150 for each group). The results showed that sibling embryos in the ‘severe ovoid group’ were characterized by delayed development and lower available embryo rate. The implantation, clinical pregnancy and live birth rates in this group were also significantly lower than that in the other two groups. There were five cycles in which only one embryo with severe ovoid ZP was transferred and two healthy babies were born. The mild ovoid group showed comparable embryo development and clinical outcomes compared with the control group. This study suggests that cycles containing oocytes with severe ovoid ZPs had delayed embryo development, lower available embryo rate, compromised implantation, clinical pregnancy and live birth rates. [ABSTRACT FROM AUTHOR]

Maternal aging is associated with a decline in oocyte quality, which leads to the decreased fertility. Therefore, developing approaches to reduce aging-induced deterioration of oocyte quality in older women is important. Near-infrared cell protector-61 (IR-61), a novel heptamethine cyanine dye, has the potential for antioxidant effects. In this study, we found that IR-61 can accumulate in the ovaries and improved ovarian function of naturally aged mice; it also increased the oocyte maturation rate and quality by maintaining the integrity of the spindle/chromosomal structure and reducing the aneuploidy rate. In addition, the embryonic developmental competence of aged oocytes was improved. Finally, RNA-sequencing analysis indicated that IR-61 might perform the beneficial effects on aged oocytes by regulating mitochondrial function, this was confirmed by immunofluorescence analysis of mitochondrial distribution and reactive oxygen species. Taken together, our findings demonstrate that IR-61 supplementation in vivo can increase oocyte quality and protect oocytes from aging-induced mitochondrial dysfunction, and thus could improve the fertility of older women and efficiency of assisted reproductive technology. IR-61 can accumulate in the ovaries and improve the quality of aged oocytes by restoring mitochondrial function, enhancing meiotic competence, reducing the aneuploidy rate, and increasing embryonic development potential. These findings provide a theoretical basis for improving the reproductive outcomes of women of advanced maternal age. [Display omitted] • IR-61 accumulates in the ovaries and increases oocyte quantity in aged mice. • IR-61 supplementation enhances maturation competence and reduces the aneuploidy rate of aged oocytes. • IR-61 supplementation improves the developmental potential of aged oocytes. • IR-61 supplementation restores the mitochondrial function of aged oocytes. [ABSTRACT FROM AUTHOR]

ContextGinseng is a widely used herbal medicine in China but its mechanism of action remains unclear. ObjectiveThe objectives of this work were to study the protective effect of ginsenoside Rg1 on subacute murine renal damage induced byd-galactose and its mechanism. Materials and methodsC57BL/6J mice were injected with 120 mg/kg/d (sc)d-galactose for 1 week, followed by a combined treatment of Rg1 20 mg/kg/d (ip) and 120 mg/kg/dd-galactose (sc) for 5 weeks. Mice were injected with the 0.9% saline 0.2 mL/d (sc) and 120 mg/kg/dd-galactose (sc) for 6 weeks in the control group and thed-galactose group, respectively. After 6 weeks, urea, creatinine, uric acid, cystatin (Cys-C), senescence-associated β-galactosidase (SA-β-gal) staining positive kidney cells, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG) were measured. ResultsTreatment with Rg1 ameliorated kidney function and aging state (urea from 17.19 ± 1.09 to 15.77 ± 1.22 mmol·L − 1, creatinine from 29.40 ± 5.72 to 22.60 ± 3.97 μmol·L − 1, uric acid from 86.80 ± 5.97 to 72.80 ± 10.61 μmol·L − 1, Cys-C from 0.23 ± 0.03 to 0.18 ± 0.05 mg·L − 1, ROD of SA-β-gal from 56.32 ± 10.48 to 26.78 ± 7.34, SOD from 150.22 ± 19.07 to 190.56 ± 15.83 U·(mg·prot) −1, MDA from 9.28 ± 1.59 to 3.17 ± 0.82 nmol·(mg·prot) −1, GSH-PX from 15.68 ± 2.11 to 20.32 ± 2.96 U·(mg·prot) −1as well as regulated glomerulus morphology (glomerulus diameter from 775.77 ± 18.41 to 695.04 ± 14.61 μm, renal capsule width from 39.56 ± 3.51 to 31.42 ± 2.70 μm, glomerulus basement membrane from 206.03 ± 16.22 to 157.27 ± 15.70 nm, podocyte slit from 55.21 ± 8.55 to 37.63 ± 6.65 nm). ConclusionsGinsenoside Rg1 can antagonised-galactose subacute renal damage in mice and this may occur due to alleviating oxidative stress injury. [ABSTRACT FROM PUBLISHER]

Objective: The aim of this study was to identify candidates for a morphokinetic embryo selection model for day-3 transfer through the analysis of known implantation data.Study Design: A diagnostic trial study was conducted. Two hundred twelve embryos from 109 patients participating in in-vitro fertilization (IVF) protocols.Results: In this diagnostic trial study, we analyzed cleavage times of transferred embryos with either failed (n=102) or full implantations (n=110). The logistic regression (LR) model of the relationship between the morphokinetic parameters and the implantation rate had a sensitivity of 79.61% and specificity of 47.56%. Results also showed that morphokinetic parameters such as tPNf (the time when pronuclei disappearanced), t2 (t2 for two cells), t4 (t4 for four cells) and t4-t3 were significantly different between embryos in the two groups (p<0.037). Implantation rates of embryos within the time interval of 21.27 h< t2 < 26.725 h were higher than those of embryos outside this period (60.83% vs. 40.21%, p=0.003). Fifty-seven patients with fully implanted embryos included five patients with pregnancy loss and 52 patients with live births. Embryos that met the time interval criteria for t2 and were also within the range of 11hConclusions: Selection and transfer of embryos that reach specific developmental stages within critical time intervals during IVF may improve the outcome of transfers and result in higher implantation rates and live birth rates. [ABSTRACT FROM AUTHOR]

The objective of this prospective diagnostic study was to explore the relationships between the morphological indices of sperm using motile sperm organelle morphology examination (MSOME) and the clinical outcome of in vitro fertilization (IVF). A total of 291 couples were included in this study. The female patients exhibited tubal and pelvic factors, and their partners' gametes were tested prospectively by MSOME. Spearman correlation analysis was used to identify the relationship between MSOME and IVF rates and conventional sperm parameters. The effect of MSOME characteristics on pregnancy outcome was analyzed by multivariate logistic regression. MSOME characteristics showed statistical relationships with sperm concentration (R = 0.130, P = 0.025), progressive motility (R = 0.260, P < 0.001), and strict normal morphology (P = 0.648, R < 0.001). The percentage of sperm with normal morphology and vacuolation in the anterior head of the sperm, as observed by MSOME, was highly correlated with the IVF fertilization rate (R = 0.176, P = 0.002; P = − 0.230, P < 0.001 respectively). The combined incidence of morphologically normal sperm and posterior vacuolation of the sperm head, as assessed by MSOME, was a predictor of clinical pregnancy (CP) after IVF (sensitivity, 92.9%; specificity, 42.47; and area under the ROC curve, 76.59%). The percentage of normal morphology of sperm by MSOME (OR 3.52, 95% CI 2.05–6.05, P < 0.001) and the posterior part vacuolated sperm (OR 0.65, 95% CI 0.52–0.82, P < 0.001) were significant predictors of successful CP. The MSOME index was significantly correlated with fertilization rates and CP after IVF, and testing with MSOME could constitute a valid diagnostic predictor of IVF outcome. [ABSTRACT FROM AUTHOR]

HLX01 is the first rituximab biosimilar produced in China and the first monoclonal antibody biosimilar marketed in China. The purpose of this study was to comprehensively evaluate whether HLX01 is clinically consistent with the original drug based on real-world data to provide evidence for the clinical substitution of biosimilars in China.A single-center retrospective study was conducted to select patients with diffuse large B-cell lymphoma who met the inclusion criteria and were treated with HLX01 or reference rituximab. Baseline characteristics, efficacy and safety results were recorded, and the corresponding statistical analysis was performed for various indicators.Thirty-three patients diagnosed with diffuse large B-cell lymphoma were included and divided into two groups that received HLX01 or reference rituximab. The results showed no significant difference in the overall response rate (86.7% vs. 88.9%; p = 1.000) or complete response rate (46.7% vs. 55.6%; p = 0.889) between the two groups. Kaplan–Meier survival curves also showed no significant difference in time-to-event variables between the two groups (log-rank = 0.244). Safety was also comparable in both groups.HLX01 is a suitable replacement for reference rituximab in the treatment of diffuse large B-cell lymphoma and is relatively inexpensive, thereby reducing the economic burden of patients. Nevertheless, the conclusion of this study still needs to be further validated by large-sample real-world data and explored for HLX01 in other indications, such as follicular lymphoma.Not applicable. [ABSTRACT FROM AUTHOR]

A correction to the article "Efficiency of an Automated Dehydrated Carrier for the Vitrification of Human Embryos Derived from Three Pronuclei Fertilized Zygotes" published in "Reproductive BioMedicine Online 30" is presented.

Failed fertilization after conventional IVF is one of the most frustrating experiences in assisted reproductive technology. 'Late' rescue ICSI may be not an optimal strategy for treating unfertilized oocytes. Short co-incubation of gametes combined with early rescue ICSI has some advantages for complete fertilization failure after IVF. We evaluate the strategy and the optimal time for early rescue ICSI. A total of 180 patients underwent short co-incubation of gametes combined with early rescue ICSI treatment for complete fertilization failure after IVF (study group). A total of 494 ICSI patients with male factor infertility served as a control group. Clinical pregnancy rate, implantation rate, and live birth rate in the two groups were compared. The study group was divided into three different rescue time intervals (＜6 h, 6-8 h, and ＞8 h). Clinical pregnancy rate, implantation rate, and live birth rate were comparable between the study group and the control group. There was a negative correlation between clinical outcomes and rescue time interval. [ABSTRACT FROM AUTHOR]