Journal of Assisted Reproduction and Genetics最新文献

Purpose: Currently, assisted reproduction clinics employ various sperm selection techniques to identify the best sperm for fertilization. However, these techniques may not assess crucial sperm traits that can substantially impact embryonic quality. To address this, we propose analyzing diverse histone modifications as potential markers of sperm functionality and success in assisted reproduction techniques.

Methods: Cross-sectional pilot study including infertile male patients attending an infertility clinic in CABA, Argentina between April and August 2019 was performed. We used immunofluorescence techniques to evaluate post-translational modifications of histones in sperm and established correlations with in vitro fertilization outcome and embryo quality.

Results: Our findings indicate a negative correlation between H3K4me3 and H3K4me2 marks and fertilization rate and showed a positive correlation of this parameter with H3K9me mark. In addition, there was a positive correlation between H3K27me3 and good embryo quality.

Conclusions: This pilot study proposes a non-invasive strategy to predict embryo quality by analyzing spermatozoa prior to fertilization. The assessment of histone post-translational modifications in sperm samples could provide useful information for the recognition of epigenetic marks that could predict the health of the embryo of an assisted fertilization treatment.

Purpose: Male infertility manifests in the form of a reduction in sperm count, sperm motility, or the loss of fertilizing ability. While the loss of sperm production can have mixed reasons, sperm structural defects, cumulatively known as teratozoospermia, have predominantly genetic bases. The aim of the present review is to undertake a comprehensive analysis of the genetic mutations leading to sperm morphological deformities/teratozoospermia.

Methods: We undertook literature review for genes involved in sperm morphological abnormalities. The genes were classified according to the type of sperm defects they cause and on the basis of the level of evidence determined by the number of human studies and the availability of a mouse knockout.

Results: Mutations in the SUN5, CEP112, BRDT, DNAH6, PMFBP1, TSGA10, and SPATA20 genes result in acephalic sperm; mutations in the DPY19L2, SPATA16, PICK1, CCNB3, CHPT1, PIWIL4, and TDRD9 genes cause globozoospermia; mutations in the AURKC gene cause macrozoospermia; mutations in the WDR12 gene cause tapered sperm head; mutations in the RNF220 and ADCY10 genes result in small sperm head; mutations in the AMZ2 gene lead to vacuolated head formation; mutations in the CC2D1B and KIAA1210 genes lead to pyriform head formation; mutations in the SEPT14, ZPBP1, FBXO43, ZCWPW1, KATNAL2, PNLDC1, and CCIN genes cause amorphous head; mutations in the SEPT12, RBMX, and ACTL7A genes cause deformed acrosome formation; mutations in the DNAH1, DNAH2, DNAH6, DNAH17, FSIP2, CFAP43, AK7, CHAP251, CFAP65, ARMC2 and several other genes result in multiple morphological abnormalities of sperm flagella (MMAF).

Conclusions: Altogether, mutations in 31 genes have been reported to cause head defects and mutations in 62 genes are known to cause sperm tail defects.

Purpose: To investigate factors influencing long-term utilization and disposal patterns of cryopreserved semen straws in oncological patients.

Methods: This retrospective study included all men who cryopreserved semen due to cancer between October 1993 and December 2021. To assess non-used cryopreserved sperm straws, we investigated the following parameters: cryopreserved semen and usage for fertility treatments versus disposal, summarized by total non-used cases. A Kaplan-Meier curve was used to describe last usage and disposal requests over a 15-year analysis. A Log-rank test was applied to compare between age and paternal status categories.

Results: The cohort consisted of 445 patients. Of these, 55 patients utilized thawed semen for fertility treatments, and 65 opted for disposals, leaving 325 patients who neither used nor disposed of their cryopreserved straws. Our findings revealed a distinct pattern based on age, with the youngest age group (< 25 years) exhibiting significantly lower utilization and disposal rates compared to older patient groups. Additionally, men without children exhibited significantly fewer disposal requests compared to fathers. The median cryopreserved straws were 10 (interquartile range, 6 to 17), while the median used straws were only 2 (interquartile range, 2 to 6).

Discussion: Our study brings attention to the additional and needless burden of preservation from both patient and preserved straw perspectives. Implementing a policy based on a cost-effective approach, incorporating time and straw limits, and considering demographic characteristics, could enhance efficiency and necessitate patient consent before preservation.

The field of reproductive medicine has witnessed rapid advancements in artificial intelligence (AI) methods, which have significantly enhanced the efficiency of diagnosing and treating reproductive disorders. The integration of AI algorithms into the in vitro fertilization (IVF) has the potential to represent the next frontier in advancing personalized reproductive medicine and enhancing fertility outcomes for patients. The potential of AI lies in its ability to bring about a new era characterized by standardization, automation, and an improved success rate in IVF. At present, the utilization of AI in clinical practice is still in its early stages and faces numerous ethical, regulatory, and technical challenges that require attention. In this review, we present an overview of the latest advancements in various applications of AI in IVF, including follicular monitoring, oocyte assessment, embryo selection, and pregnancy outcome prediction. The aim is to reveal the current state of AI applications in the field of IVF, their limitations, and prospects for future development. Further studies, which involve the development of comprehensive models encompassing multiple functions and the conduct of large-scale randomized controlled trials, could potentially indicate the future direction of AI advancements in the field of IVF.

Key ideas from a workshop convened by the National Academies of Sciences, Engineering, and Medicine to discuss developments in IVG (National Academies of Sciences, Engineering, and Medicine 2023) chaired by Dr Eli Y. Adashi (former Dean of Medicine and Biological Sciences at Brown University). The authors are solely responsible for the content of this paper, which does not necessarily represent the views of the National Academies of Sciences, Engineering, and Medicine.

Background: Recurrent spontaneous abortion (RSA) is a common complication during pregnancy, which is a burden to patients both physically and mentally. Circular RNAs (circRNAs) play important roles in RSA. However, the roles of circDDX21 in RSA development remain unknown.

Methods: Decidual samples were harvested from healthy pregnant women and RSA patients. In HTR-8/SVneo and Bewo trophoblast cells, proliferation and migration were analyzed by cell counting kit-8 (CCK-8)/5-ethynyl-2'-deoxyuridine (EdU) staining and transwell/wound healing assays, respectively. CD4⁺ T cells from peripheral blood mononuclear cells of patients were incubated with trophoblast-conditioned medium. Regulatory T cells (Treg) proliferation was detected by carboxyfluorescein succinimidyl ester (CFSE) assay. Treg proportion, Treg/T helper 17 cells (Th17) ratio, and cytokines were measured using flow cytometry. The association among genes was validated using dual-luciferase assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP).

Results: CircDDX21 and Forkhead box P3 (FOXP3) decreased, while miR-520a-5p increased in the decidual tissues of RSA patients. CircDDX21 overexpression promoted trophoblast proliferation and migration, and facilitated CD4⁺ T cell differentiation into Treg. CircDDX21 targeted miR-520a-5p to elevate FOXP3. MiR-520a-5p overexpression reversed the promoted trophoblast cell function of circDDX21 overexpression in HTR-8/SVneo cells. FOXP3 overexpression reversed the repressed trophoblast cell function elicited by miR-520a-5p overexpression in HTR-8/SVneo cells. FOXP3 promoted Treg differentiation by transcriptionally upregulating programmed cell death ligand 1 (PD-L1).

Conclusion: CircDDX21 ameliorated trophoblast dysfunction and Treg differentiation in RSA via miR-520a-5p/FOXP3/PD-L1 axis.

Background: Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disorder; however, the understanding of the pathogenesis of PCOS remains unclear. Necroptosis is a newly discovered mechanism of cell death, and it is closely related to reproductive endocrine-related diseases. This study aimed to investigate the hub necroptosis-related genes in PCOS patients and its correlation with immune cell infiltration by bioinformatics methods.

Method: The gene expression chip result matrix and the annotation matrix files of the GSE34526, GSE8157, and GSE5090 datasets were downloaded from the GEO database. We analyzed the expression and correlation of the necroptosis-related genes in all samples, constructed a diagnostic model based on all necroptosis-related genes and genes with significant differences, performed unsupervised clustering of samples and gene enrichment analysis, and evaluated the correlations between the hub gene and immune cell infiltration levels by the R packages GSVA and CIBERSORT. Finally, PPI networks were constructed using the Cytoscape software GeneMANIA plug-in, and the miRNA, transcription factors, RBP, and drugs were predicted.

Conclusion: Necroptosis-related genes have important relationships in the development of PCOS and are potentially associated with immune infiltration in PCOS patients.

Purpose: In cisplatin-induced premature ovarian failure (POF) mice, granulosa cells showed a high level of ferroptosis. Previous research has indicated that the fat mass and obesity-associated protein/activating transcription factor 4 (FTO/ATF4) axis was involved in the regulation of ferroptosis. The purpose of this study was to explore the role of the FTO/ATF4 axis in cisplatin-induced ferroptosis in granulosa cell.

Methods: The extent of ferroptosis was assessed by transmission electron microscopy (TEM) and ROS, GPX, GSH, and MDA assays. Western blotting was used to evaluate the protein expression levels of ferroptosis-related molecules. Ferroptosis activator and inhibitor were also used.

Results: We found that ferroptosis increased in a concentration-dependent manner in cisplatin-induced injured granulosa cells, accompanied by the downregulation of FTO. In addition, gain- and loss-of-function studies showed that FTO affects ferroptosis in injured cells by regulating ATF4 expression. Ferrostatin-1 inhibited the effect of FTO downregulation on injured granulosa cells ferroptosis, and erastin reversed the protective effect of FTO on ferroptosis in injured granulosa cells. Finally, melatonin was used, and we found that melatonin reduced ferroptosis in cisplatin-induced injured granulosa cells by upregulating FTO expression.

Conclusion: Our study demonstrated that cisplatin induced granulosa cell ferroptosis by downregulating the expression of FTO. ATF4 was identified as a downstream target of FTO, and overexpression of ATF4 reversed the effects of decreased FTO on ferroptosis. Additionally, melatonin mitigates the cytotoxic effects of cisplatin by upregulating FTO expression. The melatonin-FTO-ATF4 signaling pathway plays a vital role in the treatment of cisplatin-induced POF.

Purpose: To investigate pregnancy outcomes resulting from transfer of embryos with non-mosaic (NM) segmental aneuploid (SA) results following preimplantation genetic testing for aneuploidy (PGT-A).

Methods: All patients who underwent frozen embryo transfer (FET) of at least one embryo with a NM-SA between March 2021 and April 2024 were retrospectively reviewed. Primary outcomes included live birth rate (LBR) and results of prenatal diagnosis. Embryos with NM-SA results were also compared to those with NM whole chromosome aneuploid (WCA) and mosaic SA results.

Results: Out of 25 NM-SA embryos transferred, the LBR was 24%. Prenatal diagnosis by amniocentesis and/or chorionic villus sampling was performed in 3/6 pregnancies, and results were normal. Embryos with duplications produced more live births compared to those with deletions. NM-SA embryos had a significantly higher ongoing pregnancy (OP)/LBR compared to embryos with NM-WCA results and a significantly lower OP/LBR compared to embryos with mosaic SA results; however, when compared to embryos with high-level SA mosaicism > 40%, the OP/LBR was not significantly different.

Conclusion: Embryos with NM-SAs can result in euploid live births, albeit at reduced rates compared to those with mosaic SAs. These data can be used to aid in patient counseling about PGT-A results and embryo transfer decisions.

Purpose: We aimed to identify the correlation between morphological pronuclear (PN) status and the genetically determined ploidy configuration in preimplantation embryos.

Methods: A retrospective observational study was conducted on 1982 embryos displaying normal fertilization and 380 embryos showing an atypical PN pattern, tested for aneuploidies and ploidy status via preimplantation genetic testing (PGT) between May 2019 and May 2024. Ploidy prediction was performed using a validated targeted-NGS approach and a proprietary bioinformatic pipeline analyzing SNPs B-allele frequency information. Ploidy results were obtained in relation to the morphological PN pattern and further stratified by mode of PN observation, maternal age, and embryo quality parameters.

Results: Abnormal ploidy results in 2PN-derived embryos were 1% (n = 20/1982): 0.8% showed triploidy and 0.2% haploidy. Ploidy results in relation to PN number in atypical fertilization were as follows: 0PN (n = 150/380) associated with 87.3% of diploidy, 8.7% of haploidy, and 4.0% of triploidy; 1PN-derived blastocysts (n = 73/153) were haploid in 47.7% of cases, 6.5% were triploid, and 45.7% diploid; 2.1PN (n = 23/280) and 3PN patterns (n = 54/280) predicted a triploid result in 34.8% and 74.1% of cases, respectively. PN observation with time-lapse increased ploidy status predictivity from 28.3% to 80.4% (p < 0.01) and reduced expected diploid rates to 19.6% (p < 0.01). Diploidy rate was higher for maternal age ≤ 35 years and for morphologically high-grade embryos.

Conclusion: Morphological PN check can be improved by incorporating ploidy analysis within the conventional PGT workflow. Euploid 2PN-derived embryos can be further selected removing haploids and triploids, and some atypical PN pattern can be better classified.