RESUMO
This study aimed to explore the relationship between female age and pregnancy outcomes in patients undergoing their first elective single embryo transfer (eSET) of in vitro fertilization (IVF) cycles. The retrospective cohort study encompassed 7089 IVF/intracytoplasmic sperm injection (ICSI) patients of the Reproductive Medicine Center, Henan Provincial Peoples' Hospital of China, from September 1, 2016, to May 31, 2022. Patients all received the first eSET in their IVF/ICSI cycles. A generalized additive model (GAM) was employed to examine the the dose-response correlation between age and pregnancy outcomes, namely the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR). Logistic regression model was employed to ascertain the correlation between the CPR/OPR and age. The study cohort has an average age of 30.74; 3843 patients got clinical pregnancy rate of 61.40% and ongoing pregnancy rate of 54.21%. The multiple pregnancy rate of is 1.24%. For patients aged 34 and above, the CPR decreased by 10% for every 1-year increase in age (adjusted OR 0.90, 95% CI 0.84-0.96, p < 0.0001). Similarly, the OPR decreased by 16% for every 1-year increase in age (adjusted OR 0.84, 95% CI 0.81-0.88, p < 0.0001). Patients aged 35-37 years had an acceptable OPR of 52.4% after eSET, with a low multiple pregnancy rate (1.1%). Pregnancy outcomes were significantly better in blastocyst cycles compared to cleavage embryo cycles, and this trend was more pronounced in older patients. There was a non-linear relationship between female age and pregnancy outcomes in patients undergoing their first eSET cycles. The clinical pregnancy rate and ongoing pregnancy rate decreased significantly with age, especially in women older than 34 years. For patients under 37 years old, single embryo transfer should be prioritized. For patients over 38 years old with available blastocysts, eSET is also recommended.
Assuntos
Resultado da Gravidez , Taxa de Gravidez , Transferência de Embrião Único , Humanos , Feminino , Gravidez , Adulto , Estudos Retrospectivos , Fertilização in vitro/métodos , Fatores Etários , China , Injeções de Esperma Intracitoplásmicas/métodos , Idade MaternaRESUMO
OBJECTIVE: To utilize vast genetic data to reveal the interplay between 41 systemic inflammatory factors and endometriosis. DESIGN: Bidirectional Mendelian randomization study. MAINS OUTCOME MEASURES: This study obtained believable genetic instrumental variables for systemic inflammatory factors. The effect of systemic inflammatory factors on different endometriosis phenotypes, and the effect of endometriosis on the concentrations of systemic inflammatory factors were investigated. RESULTS: In this mendelian randomization study, we found 20 causal relationships involving 18 systemic inflammatory factors and it was shown that Monocyte chemotactic protein-1, Macrophage inflammatory protein-1a, Granulocyte colony-stimulating factor, Macrophage migration inhibitory factor, Interleukin-4, Interleukin-5, Interleukin-8, Interleukin-9, Interleukin-12p70, Interleukin-16, and Interleukin-17 may be the upstream causes of endometriosis (P<0.05). Additionally, if the definition of exposure in the mendelian randomization was endometriosis, it could suggestively cause an increase in Eotaxin, cutaneous T-cell attracting chemokine, and Interferon gamma-induced protein 10 levels, and a decrease in growth-regulated oncogene-alpha, Interleukin-2 receptor, alpha subunit, platelet-derived growth factor BB, and Interleukin-18 (P<0.05). Reverse causality was not observed between a single systemic inflammatory factor and endometriosis. CONCLUSIONS: Our findings indicate that several systemic inflammatory factors may act as the initiator at the onset of endometriosis. Additionally, several other inflammatory factors are far more probable to involved downstream during disease development.
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BACKGROUND: With the increasing incidence of obesity and the childbearing-age delay among women, a debate over obesity's impacts on pregnancy and neonatal outcomes becomes hot. The potential negative effects of obesity and aging on fertility lead to an idea, whether an obese female pursuing IVF treatment can benefit from an ideal BMI achieved over a long-time weight loss process at the cost of aging? We aimed to assess the association between body mass index (BMI) and clinical or neonatal outcomes in patients undergoing in vitro fertilization (IVF) treatment, for answering whether it is necessary to lose weight first for obese patients, particularly those at advanced age. METHODS: A retrospective cohort study was performed using multicentered data from China. The women were stratified into 5 groups in terms of pre-gravid BMI (kg/m2) with the WHO obesity standard (group 1: BMI < 18.5; group 2: 18.5 ≤ BMI < 23.0; group 3: 23.0 ≤ BMI < 25.0; group 4: 25.0 ≤ BMI < 30.0; group 5: BMI ≥ 30.0). The primary outcome was cumulative live birth rate (CLBR), and other clinical and neonatal outcomes were weighed as secondary outcomes. Multivariate logistic regression analyses were carried to evaluate the association between BMI and the CLBR, or between BMI and some neonatal outcomes. Furthermore, we implemented a machine-learning algorithm to predict the CLBR based on age and BMI. RESULTS: A total of 115,287 women who underwent first IVF cycles with autologous oocytes from January 2013 to December 2017 were included in our study. The difference in the CLBR among the five groups was statistically significant (P < 0.001). The multivariate logistic regression analysis showed that BMI had no significant impact on the CLBR, while women's age associated with the CLBR negatively. Further, the calculation of the CLBR in different age stratifications among the five groups revealed that the CLBR lowered with age increasing, quantitatively, it decreased by approximately 2% for each one-year increment after 35 years old, while little difference observed in the CLBR corresponding to the five groups at the same age stratification. The machine-learning algorithm derived model showed that BMI's effect on the CLBR in each age stratification was negligible, but age's impact on the CLBR was overwhelming. The multivariate logistic regression analysis showed that BMI did not affect preterm birth, low birth weight infant, small for gestational age (SGA) and large for gestational age (LGA), while BMI was an independent risk factor for fetal macrosomia, which was positively associated with BMI. CONCLUSIONS: Maternal pre-gravid BMI had no association with the CLBR and neonatal outcomes, except for fetal macrosomia. While the CLBR was lowered with age increasing. For the IVF-pursuing women with obesity plus advanced age, rather than losing weight first, the sooner the treatment starts, the better. A multicentered prospective study with a large size of samples is needed to confirm this conclusion in the future.
Assuntos
Índice de Massa Corporal , Fertilização in vitro , Obesidade , Humanos , Feminino , Estudos Retrospectivos , Fertilização in vitro/métodos , Gravidez , Adulto , China/epidemiologia , Obesidade/terapia , Obesidade/epidemiologia , Nascido Vivo/epidemiologia , Resultado da Gravidez/epidemiologia , Coeficiente de Natalidade , Recém-Nascido , Taxa de GravidezRESUMO
Cancer stem cells (CSCs), accounting for only a minor cell proportion (< 1%) within tumors, have profound implications in tumor initiation, metastasis, recurrence, and treatment resistance due to their inherent ability of self-renewal, multi-lineage differentiation, and tumor-initiating potential. In recent years, accumulating studies indicate that CSCs and tumor immune microenvironment act reciprocally in driving tumor progression and diminishing the efficacy of cancer therapies. Extracellular vesicles (EVs), pivotal mediators of intercellular communications, build indispensable biological connections between CSCs and immune cells. By transferring bioactive molecules, including proteins, nucleic acids, and lipids, EVs can exert mutual influence on both CSCs and immune cells. This interaction plays a significant role in reshaping the tumor immune microenvironment, creating conditions favorable for the sustenance and propagation of CSCs. Deciphering the intricate interplay between CSCs and immune cells would provide valuable insights into the mechanisms of CSCs being more susceptible to immune escape. This review will highlight the EV-mediated communications between CSCs and each immune cell lineage in the tumor microenvironment and explore potential therapeutic opportunities.
Assuntos
Vesículas Extracelulares , Neoplasias , Células-Tronco Neoplásicas , Microambiente Tumoral , Microambiente Tumoral/imunologia , Humanos , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Animais , Comunicação Celular/imunologia , Evasão Tumoral , ImunomodulaçãoRESUMO
Objective: To investigate the effects of combining gonadotropin-releasing hormone agonist (GnRHa) downregulation with hormone replacement therapy (HRT, GnRHa-HRT) on the clinical outcomes of patients undergoing frozen-thawed embryo transfer (FET). Methods: In this retrospective study, we included patients who had FET between January 2018 and December 2022. They were categorized into HRT and GnRHa-HRT groups based on the endometrial preparation protocol. The study compared the clinical outcomes of patients in two groups. Possible factors affecting clinical outcomes were analyzed using univariate analysis. To analyze the impact of two endometrial preparation methods on clinical outcomes, multifactorial logistic regression was performed. Results: The rates of clinical pregnancy (47.31% vs. 59.60%), embryo implantation (37.58% vs. 49.65%), biochemical pregnancy (52.36% vs. 64.31%), and early abortion (7.07% vs. 10.77%) were statistically different between the two groups (p < 0.05). Analysis using multifactorial logistic regression showed that there was a 1.65-fold increase in clinical pregnancy rates (OR = 1.65, 95% CI: 1.29-2.12, p < 0.001) and a 1.55-fold increase in embryo implantation rates (OR = 1.55, 95% CI: 1.27-1.90, p < 0.001) in the GnRHa-HRT group when compared to the HRT group. For blastocyst transfer, the clinical pregnancy and implantation rates of the GnRHa-HRT group were significantly higher than those of the HRT group (OR = 1.75, 95% CI: 1.30-2.37, p < 0.001; OR = 1.73, 95% CI: 1.35-2.21, p < 0.001). Conclusion: In FET cycles, leuprorelin (as a GnRHa) downregulation combined with HRT may improve the clinical outcome of patients compared to the HRT cycle, especially for the clinical pregnancy and embryo implantation rates of patients with blastocyst transfer.
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Objective: The objective of this study is to investigate the factors that influence the live birth rate (LBR) of the first single euploid frozen-thawed blastocyst transfer (FBT) cycles after preimplantation genetic testing for structural rearrangements (PGT-SR) in couples with balanced chromosomal translocations (BCT). Design: Single center, retrospective and observational study. Methods: A total of 336 PGT-SR and the first single euploid FBT cycles between July 2016 and December 2022 were included in this study. The patients were divided into two groups according to the live birth outcomes. The parameters of the study population, controlled ovarian stimulation cycles, and FBT cycles were analyzed. Multivariable binary logistic regression was performed to find the factors that affected the LBR. Results: The percentage of blastocysts at developmental stage Day 5 compared to Day 6 (51.8% vs. 30.8%; P<0.001) and with morphology ≥BB compared to Assuntos
Criopreservação
, Transferência Embrionária
, Nascido Vivo
, Taxa de Gravidez
, Diagnóstico Pré-Implantação
, Translocação Genética
, Humanos
, Feminino
, Gravidez
, Estudos Retrospectivos
, Adulto
, Transferência Embrionária/métodos
, Masculino
, Diagnóstico Pré-Implantação/métodos
, Coeficiente de Natalidade
, Fertilização in vitro/métodos
, Resultado da Gravidez
, Blastocisto
, Indução da Ovulação/métodos
RESUMO
OBJECTIVE: To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome. METHODS: A patient who had presented at the Henan Provincial People's Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c.853del (p.Ala285Leufs*24) and c.1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c.853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c.1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.
Assuntos
Espermatozoides , Humanos , Masculino , Adulto , Mutação , Sequenciamento do Exoma , Infertilidade Masculina/genética , Proteínas de Transporte/genética , Testes Genéticos , Teratozoospermia/genética , Proteínas dos MicrofilamentosRESUMO
BACKGROUND: PCOS patients with unexpectedly low oocyte yield following conventional ovarian stimulation are referred to as suboptimal responders. However, identifying suboptimal responders presents a significant challenge within reproductive medicine and limited research exists on the occurrence of suboptimal response. This analysis aimed to develop a predictive model of suboptimal response during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments in PCOS patients. METHODS: This retrospective study involved a cohort of 313 PCOS patients undergoing their first IVF/ICSI cycle from 2019 to 2022. Univariate logistic regression analyses, least absolute shrinkage, selection operator regression analysis, and recursive feature elimination were employed to identify relevant characteristics and construct predictive models. Moreover, a nomogram was constructed based on the best model. Receiver operating characteristic curves, decision curve analysis (DCA), and calibration curves were used to evaluate the model. RESULTS: The predictors included in the model were age, Anti-Mullerian hormone, antral follicle count, and basal follicle-stimulating hormone. The area under the receiver operating characteristic curve (AUC) was 0.7702 (95% confidence interval 0.7157-0.8191). The AUC, along with the DCA curve and calibration curve, demonstrated a satisfactory level of congruence and discrimination ability. CONCLUSION: The nomogram effectively predicted the probability of suboptimal response in PCOS patients undergoing gonadotropin-releasing hormone antagonist protocol during IVF/ICSI treatment.
Assuntos
Fertilização in vitro , Hormônio Liberador de Gonadotropina , Indução da Ovulação , Síndrome do Ovário Policístico , Injeções de Esperma Intracitoplásmicas , Adulto , Feminino , Humanos , Gravidez , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Nomogramas , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Estudos Retrospectivos , Curva ROCRESUMO
Objective: To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods: A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings: Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31-0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62-0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion: The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy.
Assuntos
Infertilidade , Reserva Ovariana , Gravidez , Feminino , Humanos , Intenção , Fertilidade , Serviços de SaúdeRESUMO
Among adolescents and young adults, hematological malignancies are the most common malignancies. Although the survival rate of hematological malignancies in young patients has been dramatically improved, due to the continuous improvement and development of tumor diagnosis and treatment options, cytotoxic therapies can significantly reduce a patient's reproductive capacity and cause irreversible infertility. The most two established solutions are embryo cryopreservation and oocyte cryopreservation which can be considered in single female. Sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. A comprehensive consultation with reproductive specialists when once diagnosed is a significantly issue which would help those survivors who want to have children. In this article, we review germ cell toxicity, which happens during the treatment of hematological malignancies, and aims to propose safety, efficacy fertility preservation methods in younger patients with hematological malignancies.
Assuntos
Criopreservação , Preservação da Fertilidade , Neoplasias Hematológicas , Humanos , Preservação da Fertilidade/métodos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicações , Criopreservação/métodos , Feminino , Masculino , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêuticoRESUMO
OBJECTIVE: To investigate the relationship between anti-Müllerian hormone (AMH) level and early pregnancy loss in patients who underwent their first embryo transfer by hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) and analyze the threshold effect. METHODS: A retrospective cohort analysis was performed on pregnant women undergoing HRT-FET at the Reproductive Medical Center of Henan Provincial People's Hospital from January 2016 to December 2021. The patients were divided into four groups based on AMH concentration according to the Poseidon criteria: group A (≤1 µg/L), group B (1-≤2 µg/L), group C (2-≤6 µg/L), and group D (>6 µg/L). Univariate analysis, multivariate logistic regression analysis, smooth curve fitting, and threshold effect analysis were applied to investigate the influence of AMH on the outcome of early pregnancy loss in in vitro fertilization/intracytoplasmic sperm injection and HRT-FET cycles. RESULTS: Of the 6597 pregnant women, early pregnancy loss occurred in 893, giving an early pregnancy loss rate of 13.54%. Univariate regression analysis demonstrated that age, female body mass index, AMH, antral follicle count, endometrial thickness at endometrial transformation day, total retrieved oocyte number, number of pregnancies, duration of infertility, type of infertility, and the number of embryos transferred were all factors influencing the early pregnancy loss rate (P < 0.050). Multivariate logistic regression analysis, after adjusting for confounders, further stratified the analysis of patients of different ages. With group A as the control group, the results showed that when age was younger than 35 years, the pregnancy loss rates in groups B, C, and D were lower than that in group A, with statistical significance (P < 0.050); when age was 35 years or older, there was no statistically significant difference in outcome indicators between the groups (P > 0.050). A threshold effect analysis revealed that the AMH threshold was 2.83 µg/L. When the AMH concentration was less than 2.83 µg/L, the early pregnancy loss rate decreased significantly with increasing AMH concentration; the early pregnancy loss rate decreased by 21% for each unit increase in AMH (odds ratio 0.79; 95% confidence interval 0.71-0.88; P < 0.001); when the AMH concentration was 2.83 µg/L or more, there was no statistical difference in the change in early pregnancy loss rate (odds ratio 1.01; 95% confidence interval 0.99-1.03; P = 0.383). CONCLUSION: For pregnant women after their first embryo transfer, there is a curvilinear relationship between the influences of AMH levels on early pregnancy loss rates in patients younger than 35 years. When the AMH level was less than 2.83 µg/L, the early pregnancy loss rate declined significantly with increasing AMH levels.
Assuntos
Aborto Espontâneo , Hormônio Antimülleriano , Transferência Embrionária , Fertilização in vitro , Terapia de Reposição Hormonal , Injeções de Esperma Intracitoplásmicas , Humanos , Feminino , Hormônio Antimülleriano/sangue , Gravidez , Adulto , Transferência Embrionária/métodos , Estudos Retrospectivos , Aborto Espontâneo/epidemiologia , Fertilização in vitro/métodos , Terapia de Reposição Hormonal/métodos , Criopreservação , China , Modelos LogísticosRESUMO
OBJECTIVE: To investigate the association between pre-pregnancy body mass index (BMI) and the early pregnancy loss rate in patients in first hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) cycles and find the threshold. METHODS: A retrospective cohort study was conducted using a total of 14030 HRT-FET cycles at the Reproductive Center from January 2017 to December 2021. The association of pre-pregnancy BMI on early pregnancy loss rate in patients in HRT-FET cycles was assessed by performing univariate analysis, multivariable logistic regression, curve fitting and threshold effect analysis. RESULTS: There were 2076 cycles of early pregnancy loss, and the pregnancy loss rate was 14.80%. After adjusting for confounding factors, the early pregnancy loss rate of the obese group was significantly higher than that of the normal weight group (P < 0.05). The threshold effect analysis showed that as the pre-pregnancy BMI ranged from 21.2 to 25.8 kg/m2, the early pregnancy loss rate came to the plateau phase at the low level. In addition, when the BMI was ≥ 25.8 kg/m2, the early pregnancy loss rate increased by 3% (aOR = 1.03, P = 0.01) with each 1 kg/m2 increment of BMI. CONCLUSION: The early pregnancy loss rate might achieve a low level when the pre-pregnancy BMI was within the range of 21.2- 25.8 kg/m2. The early pregnancy loss rate would increase when pre-pregnancy BMI is more than 25.8 kg/m2. For patients in HRT-FET cycles, adjusting their pre-pregnancy BMI to the optimal level by following a healthy diet and daily exercise may help to reduce the early pregnancy loss.
Assuntos
Aborto Espontâneo , Índice de Massa Corporal , Transferência Embrionária , Humanos , Feminino , Estudos Retrospectivos , Gravidez , Adulto , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Transferência Embrionária/métodos , Terapia de Reposição Hormonal/métodos , Obesidade/complicações , Infertilidade Feminina/etiologia , CriopreservaçãoRESUMO
Background: Identifying poor ovarian response (POR) among patients with good ovarian reserve poses a significant challenge within reproductive medicine. Currently, there is a lack of published data on the potential risk factors that could predict the occurrence of unexpected POR. The objective of this study was to develop a predictive model to assess the individual probability of unexpected POR during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments. Methods: The development of the nomogram involved a cohort of 10,404 patients with normal ovarian reserve [age, ≤40 years; antral follicle count (AFC), ≥5; and anti-Müllerian hormone (AMH), ≥1.2 ng/ml] from January 2019 to December 2022. Univariate regression analyses and least absolute shrinkage and selection operator regression analysis were employed to ascertain the characteristics associated with POR. Subsequently, the selected variables were utilized to construct the nomogram. Results: The predictors included in our model were body mass index, basal follicle-stimulating hormone, AMH, AFC, homeostasis model assessment of insulin resistance (HOMA-IR), protocol, and initial dose of gonadotropin. The area under the receiver operating characteristic curve (AUC) was 0.753 [95% confidence interval (CI) = 0.7257-0.7735]. The AUC, along with the Hosmer-Lemeshow test (p = 0.167), demonstrated a satisfactory level of congruence and discrimination ability of the developed model. Conclusion: The nomogram can anticipate the probability of unexpected POR in IVF/ICSI treatment, thereby assisting professionals in making appropriate clinical judgments and in helping patients to effectively manage expectations.
Assuntos
Indução da Ovulação , Injeções de Esperma Intracitoplásmicas , Feminino , Humanos , Masculino , Adulto , Injeções de Esperma Intracitoplásmicas/métodos , Indução da Ovulação/métodos , Sêmen , Fertilização in vitro/métodos , OvárioRESUMO
BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder rarely found in Asian populations. Most males with CF are infertile because of obstructive azoospermia (OA) caused by congenital bilateral absence of the vas deferens (CBAVD). Compound heterozygous mutations of cystic fibrosis transmembrane conductance regulator (CFTR) are among the most common pathogenic factors in CBAVD. However, few genealogical analyses have been performed. METHODS: In this study, whole-exome sequencing and cosegregation analysis were performed in a Chinese pedigree involving two siblings with CBAVD. Moreover, in vitro gene expressions were used to analyze the pathogenicity of a novel CFTR mutation. RESULTS: We identified compound heterozygous mutations of CFTR comprising the known disease-causing variant c.1210-11T>G (also known as IVS9-5 T) and c.2144delA;p.q715fs in two siblings with CBAVD. To verify the effects in vitro, we transfected vectors expressing wild-type and mutated CFTR into 293T cells. The results showed that the CFTR protein containing the frameshift mutation (c.2144delA) was 60 kD smaller. With testicular sperm aspiration/intracytoplasmic sperm injection-embryo transfer (TESA/ICSI-ET), both CBAVD patients fathered healthy offspring. CONCLUSION: Our study revealed that compound heterozygous mutations of CFTR are involved in CBAVD, expanding the known CFTR gene mutation spectrum of CBAVD patients and providing more evidence that compound heterozygous mutations can cause familial CBAVD.
Assuntos
Fibrose Cística , Infertilidade Masculina , Doenças Urogenitais Masculinas , Humanos , Masculino , Infertilidade Masculina/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Linhagem , Sêmen , Mutação , Ducto Deferente/anormalidades , Fibrose Cística/genética , Fibrose Cística/patologia , ChinaRESUMO
Folate deficiency contribute to neural tube defects (NTDs) which could be rescued by folate supplementation. However, the underlying mechanisms are still not fully understood. Besides, there is considerable controversy concerning the forms of folate used for supplementation. To address this controversy, we prepared culture medium with different forms of folate, folic acid (FA), and 5-methyltetrahydrofolate (5mTHF), at concentrations of 5 µM, 500 nM, 50 nM, and folate free, respectively. Mouse embryonic fibroblasts (MEFs) were treated with different folates continuously for three passages, and cell proliferation and F-actin were monitored. We determined that compared to 5mTHF, FA showed stronger effects on promoting cell proliferation and F-actin formation. We also found that FOLR1 protein level was positively regulated by folate concentration and the non-canonical Wnt/planar cell polarity (PCP) pathway signaling was significantly enriched among different folate conditions in RNA-sequencing analyses. We demonstrated for the first time that FOLR1 could promote the transcription of Vangl2, one of PCP core genes. The transcription of Vangl2 was down-regulated under folate-deficient condition, which resulted in a decrease in PCP activity and F-actin formation. In summary, we identified a distinct advantage of FA in cell proliferation and F-actin formation over 5mTHF, as well as demonstrating that FOLR1 could promote transcription of Vangl2 and provide a new mechanism by which folate deficiency can contribute to the etiology of NTDs.
Assuntos
Deficiência de Ácido Fólico , Defeitos do Tubo Neural , Animais , Camundongos , Ácido Fólico/metabolismo , Actinas/metabolismo , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Polaridade Celular/genética , Fibroblastos/metabolismo , Via de Sinalização Wnt , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo , Deficiência de Ácido Fólico/metabolismoRESUMO
Backgrounds: The present study was designed to establish and validate a prediction model for high ovarian response (HOR) in the GnRH antagonist protocol. Methods: In this retrospective study, the data of 4160 cycles were analyzed following the in vitro fertilization (IVF) at our reproductive medical center from June 2018 to May 2022. The cycles were divided into a training cohort (n=3121) and a validation cohort (n=1039) using a random sampling method. Univariate and multivariate logistic regression analyses were used to screen out the risk factors for HOR, and the nomogram was established based on the regression coefficient of the relevant variables. The area under the receiver operating characteristic curve (AUC), the calibration curve, and the decision curve analysis were used to evaluate the performance of the prediction model. Results: Multivariate logistic regression analysis revealed that age, body mass index (BMI), follicle-stimulating hormone (FSH), antral follicle count (AFC), and anti-mullerian hormone (AMH) were independent risk factors for HOR (all P< 0.05). The prediction model for HOR was constructed based on these factors. The AUC of the training cohort was 0.884 (95% CI: 0.869-0.899), and the AUC of the validation cohort was 0.884 (95% CI:0.863-0.905). Conclusion: The prediction model can predict the probability of high ovarian response prior to IVF treatment, enabling clinicians to better predict the risk of HOR and guide treatment strategies.
Assuntos
Ovário , Indução da Ovulação , Feminino , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Indução da Ovulação/métodos , Hormônio Liberador de GonadotropinaRESUMO
Background: Endometrial polyps (EPs) are one of the most common intrauterine benign tumors, and are an important cause of uterine bleeding and female infertility. Previous studies have suggested that endometritis may contribute to the onset of EPs. This study aims to reveal the causal effect of endometritis on EPs by a two-sample Mendelian randomization (MR) study. Methods: Utilizing summarized statistics from genome-wide association studies (GWAS) in the European population, we conducted a Mendelian randomization study. In order to select suitable instrumental variables (IVs) that were significantly related to the exposures, a number of quality control approaches were used. For endometritis, 2144 cases and 111,858 controls were included, while for EPs, 2252 cases and 460,758 controls. Utilizing the inverse variance weighted (IVW) as the primary analysis, the data were subjected to a two-sample MR analysis, and the weighted median (WM) technique and MR-Egger regression were carried out additionally. The sensitivity analysis revealed neither heterogeneity nor horizontal pleiotropy. Results: Four independent single nucleotide polymorphisms (SNPs) from endometritis GWAS as IVs were selected. The IVW data did not agree to a causal association between endometritis and EPs (ß=1.11e-04, standard error [SE] =4.88e-04, P = 0.82). Directional pleiotropy did not affect the outcome, according to the MR-Egger regression (intercept = 0.09, P = 0.10); Additionally, it showed no causation association between endometritis and EPs (ß= -3.28e-03, SE = 3.54e-03, P = 0.45). Similar results were obtained using the weighted-median method (ß=8.56e-05, SE=5.97e-04, P = 0.89). No proof of heterogeneity and horizontal pleiotropy between IV estimates was discovered. Conclusion: In conclusion, by large scale genetic data, the results of this MR analysis provided suggestive evidence that the presence of endometritis is not associated with higher EPs risk.
RESUMO
Pressure ulcers (PUs) are a common complication in postoperative patients with traumatic brain injury, and this study used a meta-analysis to assess the effects of comprehensive nursing applied in PUs intervention in postoperative patients with traumatic brain injury. A computerised systematic search of the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (CBM), VIP and Wanfang databases was performed to collect publicly available articles on randomised controlled trials (RCTs) on the effects of comprehensive nursing interventions in postoperative patients with traumatic brain injury published up to August 2023. Two researchers independently completed the search and screening of the literature, extraction of data and quality assessment of the included literature based on the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Twenty-eight articles were finally included, for a cumulative count of 2641 patients, of which 1324 were in the intervention group and 1317 in the control group. The results of the meta-analysis showed that, compared with conventional nursing, comprehensive nursing intervention helped to reduce the incidence of PUs in postoperative patients with traumatic brain injury (5.14% vs. 19.67%, odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.16-0.29, p < 0.00001) and reduced the incidence of postoperative complications (7.87% vs. 25.84%, OR: 0.22, 95% CI: 0.11-0.43, p < 0.0001), while increasing patient satisfaction (96.67% vs. 75.33%, OR: 9.5, 95% CI: 3.63-24.88, p < 0.00001). This study concludes that a comprehensive nursing intervention applied to postoperative patients with traumatic brain injury can significantly reduce the incidence of PUs and postoperative complications as well as improve nursing satisfaction, and it is recommended for clinical promotion. However, due to the limitations of the studies' number and quality, more high-quality, large-sample RCTs are needed to further validate the conclusions of this study.
RESUMO
Recent developments in molecular biological technologies and genetic diagnostic methods, accompanying with updates of relevant terminologies, have enabled the improvements of new strategies of preimplantation genetic testing for monogenic (single gene) disorders (PGT-M) to prevent the transmission of inherited diseases. However, there has been much in the way of published consensus on PGT-M. To properly regulate the application of PGT-M, Chinese experts in reproductive medicine and genetics have jointly developed this consensus statement. The consensus includes indications for patient selection, genetic and reproductive counseling, informed consent, diagnostic strategies, report generation, interpretation of results and patient follow-ups. This consensus statement serves to assist in establishment of evidence-based clinical and laboratory practices for PGT-M.
Assuntos
Diagnóstico Pré-Implantação , Feminino , Humanos , Gravidez , Aneuploidia , Aconselhamento , Testes Genéticos/métodos , Diagnóstico Pré-Implantação/métodos , ChinaRESUMO
Background: Intrauterine adhesions (IUA), arising from diverse etiological factors, pose a significant threat to female fertility, particularly during in vitro fertilization (IVF) treatment. Objective: To assess the effectiveness of hysteroscopic adhesiolysis (HA) combined with periodic balloon dilation in treating IUA and its impact on reproductive outcomes in women undergoing IVF treatment. Methods: A total of 234 patients diagnosed with IUA were included in this study. The IUA women were categorized into three subgroups based on the severity of adhesion. All IUA patients underwent HA separation followed by periodic balloon dilation along with hormone replacement therapy (HRT). Frozen embryo transfer was performed post-treatment, and a comparative analysis of the general characteristics and clinical outcomes among the subgroups was conducted. The control group consisted of patients who underwent their first embryo transfer of HRT cycle without any uterine abnormalities, as assessed by the propensity score matching (PSM). The clinical outcomes of IUA group and control group were compared. Multivariate logistic regression analyses were employed to investigate the risk factors associated with live birth. Results: â The endometrial thickness was significantly increased post-operation compared to pre-operation in all three IUA subgroups (all P <0.001), with the most pronounced change observed in the severe IUA group. After treatment, normal uterine cavity was restored in 218 women (93.16%). â¡ The overall clinical pregnancy rate was 49.57% (116/234) and live birth rate was 29.91% (70/234). The clinical outcomes were similar among the three subgroups after first embryo transfer (all P>0.05). Multivariate logistic regression analyses revealed that age (aOR 0.878, 95% CI 0.817~0.944, P=0.001) and endometrial thickness after treatment (aOR 1.292, 95% CI 1.046~1.597, P=0.018) were the two significant risk factors for live birth rate. ⢠Following the process of matching, a total of 114 patients were successfully enrolled in the control group. The baselines and the clinical outcomes were all comparable between the IUA group and control group (all P>0.05). Conclusion: The combination of HA and periodic balloon dilation is beneficial for improving endometrial receptivity and has a significant clinical impact on patients with IUA undergoing IVF.