RESUMO
Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy. However, the role of NK cells in fetal growth is unclear. Here, we have identified a CD49a+Eomes+ subset of NK cells that secreted growth-promoting factors (GPFs), including pleiotrophin and osteoglycin, in both humans and mice. The crosstalk between HLA-G and ILT2 served as a stimulus for GPF-secreting function of this NK cell subset. Decreases in this GPF-secreting NK cell subset impaired fetal development, resulting in fetal growth restriction. The transcription factor Nfil3, but not T-bet, affected the function and the number of this decidual NK cell subset. Adoptive transfer of induced CD49a+Eomes+ NK cells reversed impaired fetal growth and rebuilt an appropriate local microenvironment. These findings reveal properties of NK cells in promoting fetal growth. In addition, this research proposes approaches for therapeutic administration of NK cells in order to reverse restricted nourishments within the uterine microenvironment during early pregnancy.
Assuntos
Aborto Habitual/imunologia , Transferência Adotiva , Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Desenvolvimento Fetal/imunologia , Retardo do Crescimento Fetal/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células Matadoras Naturais/transplante , Aborto Habitual/genética , Aborto Habitual/patologia , Adulto , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Microambiente Celular , Citocinas/genética , Citocinas/imunologia , Decídua/imunologia , Decídua/patologia , Feminino , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/imunologia , Retardo do Crescimento Fetal/patologia , Feto , Regulação da Expressão Gênica no Desenvolvimento , Antígenos HLA-G/genética , Antígenos HLA-G/imunologia , Humanos , Integrina alfa1/genética , Integrina alfa1/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/genética , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Transdução de Sinais , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologiaRESUMO
STUDY QUESTION: The objective was to construct a model for predicting the probability of recurrent implantation failure (RIF) after assisted reproductive technology (ART) treatment based on the clinical characteristics and routine laboratory test data of infertile patients. A model was developed to predict RIF. The model showed high calibration in external validation, helped to identify risk factors for RIF, and improved the efficacy of ART therapy. WHAT IS KNOWN ALREADY: Research on the influencing factors of RIF has focused mainly on embryonic factors, endometrial receptivity, and immune factors. However, there are many kinds of examinations regarding these aspects, and comprehensive screening is difficult because of the limited time and economic conditions. Therefore, we should try our best to analyse the results of routine infertility screenings to make general predictions regarding the occurrence of RIF. STUDY DESIGN, SIZE, DURATION: A retrospective study was conducted with 5212 patients at the Reproductive Center of the First Affiliated Hospital of USTC from January 2018 to June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 462 patients in the RIF group and 4750 patients in the control group. The patients' basic characteristics, clinical treatment data, and laboratory test indices were compared. Logistic regression was used to analyse RIF-related risk factors, and the prediction model was evaluated by receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUCs). Further analysis of the influencing factors of live births in the first cycle of subsequent assisted reproduction treatment in RIF patients was performed, including the live birth subgroup (n = 116) and the no live birth subgroup (n = 200). MAIN RESULTS AND THE ROLE OF CHANCE: (1) An increased duration of infertility (1.978; 95% CI, 1.264-3.097), uterine cavity abnormalities (2.267; 95% CI, 1.185-4.336), low AMH levels (0.504; 95% CI, 0.275-0.922), insulin resistance (3.548; 95% CI, 1.931-6.519), antinuclear antibody (ANA)-positive status (3.249; 95% CI, 1.20-8.797) and anti-ß2-glycoprotein I antibody (A-ß2-GPI Ab)-positive status (5.515; 95% CI, 1.481-20.536) were associated with an increased risk of RIF. The area under the curve of the logistic regression model was 0.900 (95% CI, 0.870-0.929) for the training cohort and 0.895 (95% CI, 0.865-0.925) for the testing cohort. (2) Advanced age (1.069; 95% CI, 1.015-1.126) was a risk factor associated with no live births after the first cycle of subsequent assisted reproduction treatment in patients with RIF. Blastocyst transfer (0.365; 95% CI = 0.181-0.736) increased the probability of live birth in subsequent cycles in patients with RIF. The area under the curve of the logistic regression model was 0.673 (95% CI, 0.597-0.748). LIMITATIONS, REASONS FOR CAUTION: This was a single-centre regression study, for which the results need to be evaluated and verified by prospective large-scale randomized controlled studies. The small sample size for the analysis of factors influencing pregnancy outcomes in subsequent assisted reproduction cycles for RIF patients resulted in the inclusion of fewer covariates, and future studies with larger samples and the inclusion of more factors are needed for assessment and validation. WIDER IMPLICATIONS OF THE FINDINGS: Prediction of embryo implantation prior to transfer will facilitate the clinical management of patients and disease prediction and further improve ART treatment outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the General Project of the National Natural Science Foundation of China (Nos. 82,201,792, 82,301,871, 81,971,446, and 82,374,212) and the Natural Science Foundation of Anhui Province (No. 2208085MH206). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR1800018298 ).
Assuntos
Infertilidade , Técnicas de Reprodução Assistida , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Implantação do Embrião , Infertilidade/terapia , Nascido Vivo , Taxa de GravidezRESUMO
BACKGROUND: DNAJBs are highly conserved proteins that are involved in various biological processes. Although several DNAJBs are highly expressed in the testis, the function of DNAJB7 in spermatogenesis and male fertility remains unclear. METHODS: To identify the role of DNAJB7 in the male reproduction process, Dnajb7-deficient mice were generated by the CRISPR/Cas9-mediated genome editing system. Histological and immunofluorescence assays were performed to analyze the phenotype of the Dnajb7 mutants. RESULTS: DNAJB7 is specifically expressed in haploid germ cells. Dnajb7 knockout mice are fertile and do not have any detectable defects in Sertoli cells, spermatogonia, meiotic and postmeiotic cells, indicating that DNAJB7 is not essential for spermatogenesis. CONCLUSIONS: Our findings suggest that DNAJB7 is dispensable for male fertility in mice, which could prevent duplicative work by other groups.
Assuntos
Espermatogênese , Testículo , Camundongos , Masculino , Animais , Testículo/metabolismo , Espermatogênese/genética , Fertilidade/genética , Células de Sertoli/metabolismo , Camundongos KnockoutRESUMO
RESEARCH QUESTION: What are the clinical outcomes and safety implications of early cumulus cell removal after short-term insemination combined with early rescue intracytoplasmic sperm injection (ICSI) in preventing fertilization failure? DESIGN: In this retrospective study, a total of 14,360 cycles were divided into four groups based on insemination method and fertilization ability: conventional IVF group (nâ¯=â¯5519); early cumulus cell removal group (nâ¯=â¯4107); conventional ICSI group (nâ¯=â¯4215); and early rescue ICSI group (where failed or low fertilization was predicted, nâ¯=â¯519). Fertilization outcomes, pregnancy outcomes, neonatal outcomes and birth defects were analysed by comparing the early cumulus cell removal group with the conventional IVF group, and the early rescue ICSI group with the conventional ICSI group. RESULTS: There were no significant differences in the outcomes of fertilization, pregnancy, neonates or birth defects between the conventional IVF group and the early cumulus cell removal group (P > 0.05). When compared with the conventional ICSI group, the early rescue ICSI group had similar rates of two pronuclei (2PN) at fertilization, clinical pregnancy, miscarriage, ectopic pregnancy, live birth, sex, mean gestational age, very low birthweight, macrosomia and birth defects (P > 0.05) but a higher polyploidy rate, lower high-quality embryo rate (both P < 0.001), lower twin pregnancy rate (P < 0.01), lower rate of low birthweight, and a higher rate of normal birthweight (both Pâ¯=â¯0.024). CONCLUSIONS: Early cumulus cell removal combined with early rescue ICSI led to good pregnancy and neonatal outcomes without an increase in birth defects. This approach could therefore be an effective and safe method for patients with fertilization failure in conventional IVF.
Assuntos
Fertilização in vitro , Injeções de Esperma Intracitoplásmicas , Gravidez , Recém-Nascido , Feminino , Humanos , Masculino , Injeções de Esperma Intracitoplásmicas/métodos , Fertilização in vitro/métodos , Estudos Retrospectivos , Células do Cúmulo , Peso ao Nascer , Sêmen , Taxa de Gravidez , FertilizaçãoRESUMO
Currently, the cryopreservation of human spermatozoa must overcome the adverse effects of excessive oxidation. In this study, we aimed to evaluate the effect of supplementation of cryopreservation medium with cyanidin-3-Ο-glucoside (C3G) on sperm quality. Semen samples were obtained from men with normozoospermia according to WHO criteria (n = 39). The sperm parameter values were compared after cryopreservation in medium supplemented with and without C3G.Compared with the control group (without additive), low doses (50 µM and 100 µM) of C3G improved sperm viability and motility and decreased the reactive oxygen species (ROS) of spermatozoa, while high doses (200 µM) of C3G did not obviously enhance sperm quality. The amount of DNA fragmentation index (DFI) and high DNA stainability (HDS) after freezing were higher in the control group than in the C3G supplementation groups. Low-concentration C3G supplementation (50 µM) was negatively correlated with sperm ROS levels (r = -0.2, p = 0.03). Collectively, our findings suggest that C3G could be an efficient semen cryoprotectant that ameliorates oxidative stress in human sperm during cryopreservation.
Assuntos
Preservação do Sêmen , Motilidade dos Espermatozoides , Antocianinas , Criopreservação , Suplementos Nutricionais , Glucosídeos/farmacologia , Humanos , Masculino , Espécies Reativas de Oxigênio , Sêmen , Preservação do Sêmen/efeitos adversos , EspermatozoidesRESUMO
PURPOSE: This study aims to identify the genetic causes of 12 women with primary infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. METHODS: Genomic DNA was isolated from peripheral blood samples. Whole-exome sequencing was performed on the probands, and the identified variants were confirmed by Sanger sequencing. The pathogenicity of the identified variants on the protein was accessed in silico. And we used qRT-PCR to detect the possible effects of the novel mutation on the mRNA level of NLRP5. RESULTS: A novel homozygous frameshift variant (p.V429Efs*30) in NLRP5 and compound heterozygous variants with a novel frameshift variant (p.A297Efs*20) and a recurrent variant (c. 223-14_223-2delCCCTCCTGTTCCA) in PATL2 were identified in two unrelated affected individuals. qRT-PCR showed an obvious decrease of the mutant NLRP5 mRNA. In addition, the truncated proteins of NLRP5 and PATL2 were predicted to be non-functional due to the deletion of the most or the whole region of the critical functional domain(s) respectively. CONCLUSIONS: This study identified novel mutations in NLRP5 and PATL2, further expanding the mutational and phenotypic spectrum of both genes. This is the first report of the NLRP5 mutations that associates with oocyte maturation abnormality in humans.
Assuntos
Autoantígenos/genética , Infertilidade Feminina , Proteínas Mitocondriais/genética , Proteínas Nucleares/genética , Proteínas de Ligação a RNA/genética , Feminino , Humanos , Infertilidade Feminina/metabolismo , Mutação/genética , Oócitos/metabolismo , Oogênese , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Among causes of infertility, teratozoospermia is characterised by a percentage of morphologically abnormal spermatozoa >4%. Macrozoospermia, one form of monomorphic teratozoospermia, is observed in <1% of cases of male infertility and is described as approximately 100% large-headed and/or multitailed spermatozoa. This study reports that an infertile man with large-head spermatozoa presenting compound heterozygosity aurora kinase C (AURKC) mutations (c.382C>T, c.572C>T) by whole-exome sequencing. Consequently, both two novel AURKC mutations had high probability of damage-causing and conserved across species and extremely low allele frequency in the population. Flow cytometry analysis revealed a high ratio of sperm DNA fragmentation. Two intracytoplasmic sperm injection (ICSI) procedures were attempted for the patient, but all were unsuccessful. These results indicate that sequence analysis should be performed for the variants of AURKC in Chinese patients with macrozoospermia.
Assuntos
Infertilidade Masculina , Teratozoospermia , Aurora Quinase C/genética , Humanos , Infertilidade Masculina/genética , Masculino , Mutação , Espermatozoides , Teratozoospermia/genéticaRESUMO
STUDY QUESTION: Do PATL2 mutations account for female infertility with oocyte germinal vesicle (GV) arrest? SUMMARY ANSWER: Four of nine independent families with oocyte GV arrest were identified with biallelic PATL2 mutations, suggesting that these mutations may be responsible for oocyte maturation arrest in primary infertile women. WHAT IS KNOWN ALREADY: Recently, two independent studies have demonstrated that infertility in some women with oocyte maturation arrest at the GV stage was caused by biallelic mutations in PATL2. PATL2 encodes protein PAT1 homolog 2, an RNA-binding protein that may act as a translational repressor. STUDY DESIGN, SIZE, DURATION: In this study, nine unrelated primary infertile females presenting with oocyte GV arrest were recruited during the treatment of early rescue ICSI or ICSI from January 2013 to December 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Genomic DNA was isolated from blood samples obtained from all nine affected individuals and all of their available family members. All the coding regions of PATL2 were sequenced by Sanger sequencing. The pathogenicity of the identified variants and their possible effects on the protein were evaluated in silico. MAIN RESULTS AND THE ROLE OF CHANCE: Five novel point mutations and one recurrent splicing mutation in PATL2 were identified in four of nine (44.4%) unrelated patients. We found a consanguineous family with a homozygous missense mutation in two affected sisters, and their fertile brother. There were no clear phenotypic differences in oocytes between the patient with the homozygous missense mutation, patients with nonsense mutations and undiagnosed patients. LARGE SCALE DATA: n/a. LIMITATIONS, REASONS FOR CAUTION: The function of PATL2 remains largely unknown. Both the exact pathogenic mechanism(s) of mutated PATL2 causing human oocyte maturation arrest and the strategies to overcome this condition should be further investigated in the future. WIDER IMPLICATIONS OF THE FINDINGS: According to our data, mutations in PATL2 account for 44.4% of the individuals with oocyte GV arrest. Our study further confirms that PATL2 is required for human oocyte maturation and female fertility, which indicates a potential prognostic value of testing for PATL2 mutations in primary infertile women with oocyte maturation arrest. STUDY FUNDING/COMPETING INTEREST(S): Natural Science Foundation of Anhui Province (1808085MH241), National Natural Science Foundation of China (81401251 and 81370757) and Central Guided Local Development of Science and Technology Special Fund (2016080802D114) supported this study. None of the authors have any competing interests.
Assuntos
Proteínas de Ligação a DNA/genética , Infertilidade Feminina/genética , Oócitos/patologia , Mutação Puntual/genética , Adulto , Consanguinidade , Proteínas de Ligação a DNA/sangue , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Oócitos/metabolismo , IrmãosRESUMO
Mutations in the tubulin beta 8 class VIII (TUBB8) gene have been proven to cause oocyte maturation arrest. The aim of this study was to describe newly discovered mutations in TUBB8 and to investigate the prevalence of TUBB8 mutations in our cohort. Nine women with oocyte maturation arrest and 100 fertile female controls were recruited. Sanger sequencing of the coding regions of TUBB8 revealed a heterozygous variant c.535G > A (p.V179M) in two unrelated affected individuals and a heterozygous variant c.5G > T (p.R2M) in one affected individual. These TUBB8 variants were inherited from the unaffected fathers and were absent in 100 fertile female control individuals. In total, 33.33% (3/9) of the affected individuals in our cohort obtained a clear genetic diagnosis through sequencing of the TUBB8 gene. These two novel variants extend the spectrum of TUBB8 mutations and this study confirmed that TUBB8 mutations occur in a high proportion of infertile women with oocyte maturation arrest.
Assuntos
Infertilidade Feminina/genética , Oócitos/fisiologia , Oogênese/genética , Tubulina (Proteína)/genética , Adulto , Estudos de Casos e Controles , Pontos de Checagem do Ciclo Celular/genética , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Técnicas de Maturação in Vitro de Oócitos , Masculino , Mutação , Injeções de Esperma Intracitoplásmicas , Falha de TratamentoRESUMO
Natural killer (NK) cells accumulate at the maternal-fetal interface in large numbers, but their exact roles in successful pregnancy remain poorly defined. Here, we provide evidence that T(H)17 cells and local inflammation can occur at the maternal-fetal interface during natural allogenic pregnancies. We found that decidual NK cells promote immune tolerance and successful pregnancy by dampening inflammatory T(H)17 cells via IFN-γ secreted by the CD56(bright)CD27(+) NK subset. This NK-cell-mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent T(H)17 response and extensive local inflammation. This local inflammatory response further affects the regulatory function of NK cells, leading to the eventual loss of maternal-fetal tolerance. Thus, our data identify NK cells as key regulatory cells at the maternal-fetal interface by suppressing T(H)17-mediated local inflammation.
Assuntos
Tolerância Imunológica , Células Matadoras Naturais/imunologia , Troca Materno-Fetal/imunologia , Células Th17/imunologia , Aborto Habitual/etiologia , Aborto Habitual/imunologia , Aborto Habitual/patologia , Adulto , Animais , Antígeno CD56/metabolismo , Citocinas/biossíntese , Decídua/imunologia , Decídua/patologia , Feminino , Feto/imunologia , Humanos , Interferon gama/metabolismo , Isoantígenos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Camundongos Transgênicos , Gravidez , Primeiro Trimestre da Gravidez/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismoRESUMO
The aim of this study was to examine the effects of vitrification with autologous follicular fluid (AFF) supplemented with ethylene glycol (EG) and sucrose on human oocytes with corona radiata. A total of 182 human oocytes with corona radiata from fifteen infertile patients were vitrified using either equilibration solutions (ES) and vitrification solution (VS) consisting of AFF, EG and sucrose (AFF group, n=67) or commercial ES and VS (control group, n=115). All oocytes were thawed in the next cycle, with surviving oocytes being inseminated by conventional IVF. The clinical outcome of vitrified-warmed oocytes by both vitrification methods was analysed retrospectively. In the AFF group, six patients received embryo transfer, with three couples taking four healthy babies home. In the control group, nine patients received embryo transfer, with four couples taking five healthy babies home. There was no significant difference in the survival rate (91.0 vs 92.2%), two pronuclei (2PN) fertilisation rate (73.8 vs 73.6%), cleavage rate (100 vs 100%), top-quality embryo rate (62.2 vs 59.2%), clinical pregnancy rate (50.0 vs 44.4%), implantation rate (33.3 vs 25%) or take-home baby rate (50.0 vs 44.4%) between the AFF group and the control group, respectively. These results show that AFF supplemented with EG and sucrose is an efficient, cost-effective cryoprotectant for human oocyte cryopreservation. A corona radiata on vitrified-warmed oocytes retains the oocytes' fertilisation capability in conventional IVF.
Assuntos
Criopreservação/métodos , Crioprotetores , Etilenoglicol , Fertilização in vitro , Líquido Folicular , Oócitos/fisiologia , Adulto , Implantação do Embrião , Transferência Embrionária , Feminino , Temperatura Alta , Humanos , Recém-Nascido , Infertilidade Feminina/terapia , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Sacarose , Resultado do TratamentoRESUMO
Thin endometrium (TE), which mainly occurs as a result of severe damage to the endometrial basalis, is one of the prominent etiologies of menstrual abnormalities, infertility, and recurrent miscarriage in women. Previous studies have demonstrated that mesenchymal stem cells (MSCs) are considered ideal cells with multipotency for regenerative medicine and exhibit therapeutic effects on TE through their cellular secretions. However, there is limited research on strategies to enhance MSC secretion to improve their therapeutic efficacy. Herein, we isolated menstrual blood-derived mesenchymal stem cells (MenSCs) from menstruation and transformed them into decidualized stromal cells (DSCs), which are specialized cells with enhanced secretory functions. To assess the therapeutic potential of DSCs compared to MenSCs, we conducted a series of experiments in cells and animals. The results demonstrated that DSCs exhibited changes in morphology compared to MenSCs, with a decrease in cell proliferation but a significant improvement in secretion function. Furthermore, DSCs facilitated the restoration of endometrial thickness and increased the number of glands and blood vessel formation. Most importantly, the pregnancy rates in rats were effectively restored, bringing them closer to normal levels. These findings greatly contribute to our understanding of stem cell therapy for TE and strongly suggest that DSCs could hold significant promise as a potential treatment option for TE.
Assuntos
Endométrio , Menstruação , Células-Tronco Mesenquimais , Feminino , Endométrio/citologia , Animais , Humanos , Células-Tronco Mesenquimais/metabolismo , Gravidez , Ratos , Transplante de Células-Tronco Mesenquimais/métodos , Ratos Sprague-Dawley , Fertilidade , Células Cultivadas , Proliferação de Células , Células Estromais/transplante , Células Estromais/metabolismo , AdultoRESUMO
Coronavirus disease 2019 (COVID-19) has been reported to decrease semen quality in reproductive-age men. Semen quality in vaccinated men after SARS-CoV-2 infection remains unclear. We recruited reproductive-age Chinese men scheduled for COVID-19 vaccination from December 2022 to March 2023. Among 1,639 vaccinated participants, an upward trend was found in sperm concentration (p < .001), progressive motility (p < .001), total motility (p < .001), total motile sperm count (TMSC) (p < .001), and normal morphology (p = .01) over time following COVID-19 recovery. Among men with an SARS-CoV-2 infection that lasted less than 30 days, men who received an inactivated vaccine booster had higher sperm progressive (p = .006) and total motility (p = .005) as well as TMSC (p = .008) than those without a booster vaccine, whereas no difference was found in semen parameters among men who received a recombinant protein vaccine. Similarly, an upward trend in semen quality was found among 122 men who provided semen samples before and after COVID-19. Higher risks of asthenozoospermia (odds ratio [OR] = 2.23, p < .001) and teratozoospermia (OR = 2.09, p = .03) were found among men who had an SARS-CoV-2 infection that lasted less than 30 days than among those without COVID-19. Collectively, after receiving SARS-CoV-2 vaccination, adverse but reversible semen parameters were observed in men recovering from COVID-19 over time. Recombinant protein vaccines and inactivated vaccine boosters should be recommended to all reproductive-age men.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Análise do Sêmen , Humanos , Masculino , COVID-19/prevenção & controle , Estudos Retrospectivos , Adulto , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2 , China , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Anti-nuclear antibodies (ANA) are suspected of having relevance to adverse reproductive events. METHODS: This study aims to investigate the potential effect of ANA on IVF/ICSI outcome and the therapeutic role of prednisone plus low-dose aspirin (P + A) adjuvant treatment in ANA + patients. The first IVF/ICSI cycles without P + A of sixty-six ANA + women were enrolled as the ANA + group, and the 233 first IVF/ICSI cycles of matched ANA- women served as the ANA- group. The ANA + group was divided into the Titre < =1:320 subgroup and the Titre > 1:320 subgroup. Twenty-one ANA + women with adverse outcomes in their first cycles (ANA + cycles without P + A) received P + A adjuvant treatment for three months before the second IVF/ICSI cycle (ANA + cycles with P + A). The clinical characteristics and the IVF/ICSI outcomes were compared, respectively, between 1) the ANA + group and the ANA- group, 2) the Titre < =1:320 subgroup and the Titre > 1:320 subgroup, and 3) the ANA + cycles without P + A and the ANA + cycles with P + A. RESULTS: No significant differences were observed between each of the two-group pairs in the clinical characteristics. The ANA + group exhibited significantly lower MII oocytes rate, normal fertilisation, pregnancy and implantation rates, as well as remarkably higher abnormal fertilisation and early miscarriage rates. The Titre < =1:320 subgroup's IVF/ICSI outcomes were as poor as those of the Titre > 1:320 subgroup. After the P + A adjuvant treatment, the number of two pro-nuclei, perfect embryos and available embryos, and the implantation rate increased significantly. CONCLUSIONS: These observations suggest that ANA could exert a detrimental effect on IVF/ICSI outcome that might not be titre-dependent, and P + A adjuvant treatment could be useful for ANA + patients. This hypothesis should be verified in further prospective randomised studies.
Assuntos
Anticorpos Antinucleares/sangue , Aspirina/uso terapêutico , Fertilização in vitro , Prednisona/uso terapêutico , Aborto Espontâneo , Adulto , Aspirina/administração & dosagem , Feminino , Humanos , Gravidez , Resultado da Gravidez , Estudos RetrospectivosRESUMO
Synchronization between embryonic stage and endometrium is vital to achieve a successful pregnancy. The objective of this study was to assess the implantation, clinical pregnancy and live birth rates of cryopreserved embryo transfer cycles using embryos after extended culture for 16h. A prospective randomized controlled pilot study was performed on women who underwent vitrified-warmed embryo transfer. Of the 540 women assessed for eligibility, 479 were randomly allocated to either extended culture for 16-18h (EC group, n=242) or conventional culture for 2h (control group, n=237). Endometrial preparation was the same in both groups. No significant differences were found between the extended culture and control groups respectively in clinical pregnancy rate per embryo transfer (42.48% versus 40.95%), implantation rate (21.79% versus 20.82%) or live birth rate per embryo transfer (37.61% versus 34.05%); however, the spontaneous reduction rate was lower in the extended culture group (10.04% versus 20.80%; P=0.032) In conclusion, extended culture of day-3 cleavage embryos for 16h would not influence the pregnancy outcome of day-3 cryopreserved embryo transfer cycles. Synchronization between embryonic stage and endometrium is vital to achieve a successful pregnancy and most implantation failures are possibly associated with inadequate endometrial receptivity or defects in the embryo-endometrium crosstalk. In this paper, we regulated synchronization via extended post-warming culture using conventional day-3 endometrial preparation in vitrified-warmed embryo transfer cycles and observed the clinical outcomes, including implantation, clinical pregnancy and live birth rates. Extended post-warming culture did not influence the clinical outcomes. This study implies that transfer of embryos at an advanced developmental stage may not affect implantation. This gives clinical doctors more flexibility in the performance of routine cryopreserved embryo transfer cycles.
Assuntos
Técnicas de Cultura Embrionária , Transferência Embrionária/métodos , Adulto , Desenvolvimento Embrionário , Feminino , Humanos , Projetos Piloto , Gravidez , Resultado da GravidezRESUMO
The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0-11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31-3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10-3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.
Assuntos
Astenozoospermia , Análise do Sêmen , Masculino , Humanos , Sêmen , Motilidade dos Espermatozoides , Contagem de Espermatozoides , EspermatozoidesRESUMO
In mammals, the production of mature oocytes necessitates rigorous regulation of the discontinuous meiotic cell-cycle progression at both the transcriptional and post-transcriptional levels. However, the factors underlying this sophisticated but explicit process remain largely unclear. Here we characterize the function of N-acetyltransferase 10 (Nat10), a writer for N4-acetylcytidine (ac4C) on RNA molecules, in mouse oocyte development. We provide genetic evidence that Nat10 is essential for oocyte meiotic prophase I progression, oocyte growth and maturation by sculpting the maternal transcriptome through timely degradation of poly(A) tail mRNAs. This is achieved through the ac4C deposition on the key CCR4-NOT complex transcripts. Importantly, we devise a method for examining the poly(A) tail length (PAT), termed Hairpin Adaptor-poly(A) tail length (HA-PAT), which outperforms conventional methods in terms of cost, sensitivity, and efficiency. In summary, these findings provide genetic evidence that unveils the indispensable role of maternal Nat10 in oocyte development.
Assuntos
Meiose , Oócitos , Animais , Camundongos , Mamíferos/genética , Oócitos/metabolismo , Oogênese/genética , RNA Mensageiro/metabolismoRESUMO
ABSTRACT: Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.
RESUMO
Human oocyte maturation arrest represents one of the severe conditions for female patients with primary infertility. However, the genetic factors underlying this human disease remain largely unknown. The spindle assembly checkpoint (SAC) is an intricate surveillance mechanism that ensures accurate segregation of chromosomes throughout cell cycles. Once the kinetochores of chromosomes are correctly attached to bipolar spindles and the SAC is satisfied, the MAD2L1BP, best known as p31comet, binds mitosis arrest deficient 2 (MAD2) and recruits the AAA+-ATPase TRIP13 to disassemble the mitotic checkpoint complex (MCC), leading to the cell-cycle progression. In this study, by whole-exome sequencing (WES), we identified homozygous and compound heterozygous MAD2L1BP variants in three families with female patients diagnosed with primary infertility owing to oocyte metaphase I (MI) arrest. Functional studies revealed that the protein variants resulting from the C-terminal truncation of MAD2L1BP lost their binding ability to MAD2. cRNA microinjection of full-length or truncated MAD2L1BP uncovered their discordant roles in driving the extrusion of polar body 1 (PB1) in mouse oocytes. Furthermore, the patient's oocytes carrying the mutated MAD2L1BP resumed polar body extrusion (PBE) when rescued by microinjection of full-length MAD2L1BP cRNAs. Together, our studies identified and characterized novel biallelic variants in MAD2L1BP responsible for human oocyte maturation arrest at MI, and thus prompted new therapeutic avenues for curing female primary infertility.