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1.
Life Sci ; 255: 117830, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32450172

RESUMO

Advanced glycation end products (AGEs) are heterogeneous products of the non-enzymatic interaction between proteins and reducing sugars. Numerous studies have shown that AGEs are associated with senescence, diabetes, vascular disease, aging and kidney disease. Infertility has been affected approximately 10 to15% of couples of reproductive ages. AGEs accumulation has been shown to play a crucial role in pathogenesis of infertility-related diseases. The present review provides the generation process, mechanism and pathological significance of AGEs and the novel treatment targeting AGEs for infertility.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Infertilidade/fisiopatologia , Animais , Feminino , Humanos , Infertilidade/epidemiologia , Masculino
2.
Arch Biochem Biophys ; 679: 108222, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31816311

RESUMO

Aquaporins (AQPs) are a family of transmembrane channel proteins responsible for the transport of water and small uncharged molecules. Thirteen distinct isoforms of AQPs have been identified in mammals (AQP0-12). Throughout the male reproductive tract, AQPs greatly enhance water transport across all biological barriers, providing a constant and expeditious movement of water and playing an active role in the regulation of water and ion homeostasis. This regulation of fluids is particularly important in the male reproductive tract, where proper fluid composition is directly linked with a healthy and competent spermatozoa production. For instance, in the testis, fluid regulation is essential for spermatogenesis and posterior spermatozoa transport into the epididymal ducts, while maintaining proper ionic conditions for their maturation and storage. Alterations in the expression pattern of AQPs or their dysfunction is linked with male subfertility/infertility. Thus, AQPs are important for male reproductive health. In this review, we will discuss the most recent data on the expression and function of the AQPs isoforms in the human, mouse and rat male reproductive tract. In addition, the regulation of AQPs expression and dysfunction linked with male infertility will be discussed.


Assuntos
Aquaporinas/genética , Aquaporinas/metabolismo , Fertilidade/genética , Regulação da Expressão Gênica , Infertilidade/genética , Infertilidade/metabolismo , Animais , Humanos , Infertilidade/fisiopatologia , Masculino , Reprodução
4.
Fertil Steril ; 112(6): 1015-1021, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843072

RESUMO

OBJECTIVE: To study whether endometrial scratching in the luteal phase before ovarian stimulation increases clinical pregnancy rates in women with one or more previous implantation failures. DESIGN: A nonblinded multicenter randomized clinical trial. SETTING: Fertility clinics. PATIENT(S): Three hundred four eligible patients scheduled for IVF/intracytoplasmic sperm injection were randomized. The intervention group (n = 151) underwent endometrial scratching in the luteal phase before controlled ovarian stimulation, while no intervention was performed in the control group (n = 153). INTERVENTION(S): Endometrial scratching with a Pipelle de Cornier catheter in the luteal phase before ovarian stimulation. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and prenatal and birth data. RESULT(S): There was no overall significant improvement in clinical pregnancy rates between the control and intervention groups (38.5% vs. 44.4%; relative risk = 1.15; confidence interval [0.86-1.55]). However, subgroup analyses revealed that women with three or more previous implantation failures had a significant increase in clinical pregnancy rate (31.1% vs. 53.6%; relative risk = 1.72; confidence interval [1.05-2.83]) after scratching. No difference was seen as regards prenatal and birth data between the two groups. CONCLUSION(S): Endometrial scratching in the luteal phase before ovarian stimulation significantly enhances the clinical pregnancy rate in women with three or more prior implantation failures. This result seems to corroborate previous reports, which found that particularly women with repeated implantation failure seem to gain a positive effect from endometrial scratching. Importantly, there were no significant differences in prenatal data and birth data between the groups. CLINICAL TRIAL REGISTRATION NUMBER: NCT01963819.


Assuntos
Endométrio/cirurgia , Fertilização In Vitro , Infertilidade/terapia , Adolescente , Adulto , Dinamarca , Endométrio/fisiopatologia , Feminino , Fertilidade , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Masculino , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas , Resultado do Tratamento , Adulto Jovem
5.
Fertil Steril ; 112(6): 1080-1093.e1, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843084

RESUMO

OBJECTIVE: To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET). DESIGN: Observational cohort study conducted in two phases: training and validation. SETTING: Private in vitro fertilization centers. PATIENT(S): Euploid blastocysts: 511 and 319 first vitrified-warmed SETs from 868 and 546 patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) in the training and validation phase, respectively. INTERVENTION(S): Data collected from time of polar body extrusion to time of starting blastulation, and trophectoderm and inner-cell-mass static morphology in all embryos cultured in a specific time-lapse incubator with a continuous medium. Logistic regressions conducted to outline the variables showing a statistically significant association with live birth. In the validation phase, these variables were tested in an independent data set. MAIN OUTCOME MEASURE(S): Live births per SET. RESULT(S): The average live birth rate (LBR) in the training set was 40% (N = 207/511). Only time of morulation (tM) and trophectoderm quality were outlined as putative predictors of live birth at two IVF centers. In the validation set, the euploid blastocysts characterized by tM <80 hours and high-quality trophectoderm resulted in a LBR of 55.2% (n = 37/67), while those with tM ≥ 80 hours and a low-quality trophectoderm resulted in a LBR of 25.5% (N = 13/51). CONCLUSION(S): Time of morulation and trophectoderm quality are better predictors of a euploid blastocyst's reproductive competence. Our evidence was reproducible across different centers under specific culture conditions. These data support the crucial role of morulation for embryo development, a stage that involves massive morphologic, cellular, and molecular changes and deserves more investigation.


Assuntos
Blastocisto/patologia , Fertilização In Vitro , Infertilidade/terapia , Mórula/patologia , Transferência de Embrião Único , Imagem com Lapso de Tempo , Adulto , Técnicas de Cultura Embrionária , Implantação do Embrião , Desenvolvimento Embrionário , Feminino , Fertilidade , Fertilização In Vitro/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Cinética , Nascimento Vivo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Taxa de Gravidez , Reprodutibilidade dos Testes , Fatores de Risco , Roma , Transferência de Embrião Único/efeitos adversos , Espanha , Resultado do Tratamento
6.
Fertil Steril ; 112(6): 1094-1102.e2, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843085

RESUMO

OBJECTIVE: To evaluate the effect of elevated maternal prepregnancy body mass index (BMI) on intelligence and growth of singletons after in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI). DESIGN: Cohort study. SETTING: University hospital. PATIENT(S): Singletons born to infertile couples who underwent an autologous IVF/ICSI cycle from 2002 to 2012 and were followed up with at the age of 3-6 years from 2009 to 2017. INTERVENTIONS(S): We compared the health of offspring born to overweight/obese women and normal weight women through assisted reproductive technology (ART). MAIN OUTCOME MEASURE(S): Age- and sex-specific BMI z-scores, verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full intelligence quotient (FIQ). RESULT(S): After adjusting for confounders, obese women were more likely than normal-BMI women to have obese children (20.0% vs. 5.1%), and overweight women had increased risks of having overweight children (13.6% vs. 8.2%) or obese children (10.1% vs. 5.1%) compared with normal-BMI women. Maternal prepregnancy BMI had a weakly negative effect on estimated IQ of children, but after adjusting for parental educational level, the IQ scores of offspring were similar between groups. However, after adjusting for confounders, offspring of obese women showed increased prevalence of intellectual disability (IQ <80) in VIQ (16.9% vs. 8.5%) and FIQ (10.8% vs. 3.9%) compared with normal-BMI women. CONCLUSION(S): Maternal prepregnancy obesity is associated with increased risks for obesity and overweight at early ages in offspring conceived through IVF/ICSI and may also affect the risk of intellectual disability of offspring. Overall, we suggest that weight management is essential for women before entering an IVF/ICSI cycle for ensuring long-term child health.


Assuntos
Índice de Massa Corporal , Comportamento Infantil , Desenvolvimento Infantil , Cognição , Fertilização In Vitro/efeitos adversos , Infertilidade/terapia , Deficiência Intelectual/epidemiologia , Obesidade Materna/epidemiologia , Obesidade Pediátrica/epidemiologia , Adulto , Fatores Etários , Criança , Pré-Escolar , China , Feminino , Fertilidade , Humanos , Infertilidade/diagnóstico , Infertilidade/epidemiologia , Infertilidade/fisiopatologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/fisiopatologia , Inteligência , Nascimento Vivo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade Materna/diagnóstico , Obesidade Materna/fisiopatologia , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/fisiopatologia , Gravidez , Prevalência , Medição de Risco , Fatores de Risco , Fatores Sexuais , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Resultado do Tratamento
7.
Fertil Steril ; 112(6): 1103-1111, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843086

RESUMO

OBJECTIVE: To explore the predictive value of endometrial CD138 expression in the natural cycle preceding frozen embryo transfer in patients with normal endometrial dating and histopathologic features, who previously failed the transfer of two high-quality fresh embryos. DESIGN: Retrospective analysis. SETTING: University-affiliated hospital. PATIENT(S): Women with normal endometrial dating and histopathologic features who previously failed the transfer of two high-quality fresh embryos, and who then underwent an endometrial scratching operation preceding a natural cycle. INTERVENTION(S): Paraffin-embedded endometrial samples cut into sections for immunohistochemistry staining of CD138 (syndecan-1) expression, then clinical information for these patients reviewed and analyzed. MAIN OUTCOME MEASURE(S): Clinical rates of pregnancy and implantation. RESULT(S): A total of 141 women met the inclusion criteria. Of these patients, about 31.2% (44 of 141) were positive for CD138 expression, with CD138 counts ranging from 0 to 33. Receiver operating characteristic (ROC) curves were analyzed to determine whether the number of cells expressing CD138 (CD138+ cells) predicted a successful pregnancy. The areas under the ROC curves based on CD138+ cell density and CD138+ cell count were 0.660 and 0.658, respectively. The clinical pregnancy and embryo implantation rates in patients not expressing CD138 (80.04% and 64.9%, respectively) were statistically significantly higher than rates in CD138+ patients (52.7% and 46.8%, respectively). In addition, the higher the number of cells expressing CD138, the worse the outcome of the pregnancy. Finally, clinical data showed that free pelvic fluid on the day of endometrial sampling (identified using transvaginal ultrasound) might be a risk factor for CD138 expression. CONCLUSION(S): Endometrial CD138+ count might be a valuable marker predicting pregnancy outcomes after frozen embryo transfer in patients with normal endometrial dating and histopathologic features who previously failed the transfer of two high-quality fresh embryos.


Assuntos
Transferência Embrionária , Endometrite/imunologia , Endométrio/imunologia , Infertilidade/terapia , Sindecana-1/análise , Adulto , Biomarcadores/análise , Contagem de Células , Endometrite/diagnóstico , Endometrite/fisiopatologia , Endométrio/patologia , Endométrio/fisiopatologia , Feminino , Fertilidade , Fertilização In Vitro , Humanos , Imuno-Histoquímica , Infertilidade/diagnóstico , Infertilidade/imunologia , Infertilidade/fisiopatologia , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Adulto Jovem
8.
Fertil Steril ; 112(6): 1112-1117, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843087

RESUMO

OBJECTIVE: To determine whether differences exist in angiogenic placental growth factor (PlGF) and antiangiogenic soluble vascular endothelial growth factor receptor 1 (sVEGFR-1; both being early markers of placental ischemic disease) in oocyte-donation (OD) pregnancies, compared with autologous in vitro fertilization (aIVF) and spontaneous pregnancies. DESIGN: Case-control study of residual second-trimester serum samples from women undergoing prenatal screening. SETTING: Academic medical center. PATIENT(S): Fifty-seven OD pregnancies were identified. Each OD pregnancy was matched to two spontaneous pregnancies (n = 114) and one aIVF pregnancy (n = 57). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Second-trimester serum PlGF and sVEGFR-1 levels. RESULT(S): sVEGFR-1, PlGF, and unconjugated E2 levels were similar among the three study groups. The ratio of sVEGFR-1 to PlGF was significantly higher in the OD group. Consistently with previous studies, alpha-fetoprotein (AFP) in the OD group was significantly elevated compared with spontaneous pregnancy. Both aIVF and OD groups had greater levels of inhibin A than the spontaneous pregnancy group, and the OD group had significantly higher levels of inhibin A than the aIVF group. hCG levels were significantly elevated in aIVF compared with spontaneous pregnancy; however, levels were not different between aIVF and OD. CONCLUSION(S): Second-trimester serum sVEGFR-1 and PlGF levels were not significantly altered in OD pregnancies. Our data support previous findings that OD pregnancies have uniquely increased second-trimester AFP, hCG, and inhibin A levels compared with aIVF. However, the biologic basis of these marker elevations in OD may not be related to placental angiogenesis.


Assuntos
Infertilidade/terapia , Doação de Oócitos , Fator de Crescimento Placentário/sangue , Segundo Trimestre da Gravidez/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Biomarcadores/sangue , Gonadotropina Coriônica/sangue , Estradiol/sangue , Feminino , Fertilização In Vitro , Humanos , Infertilidade/sangue , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Inibinas/sangue , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , alfa-Fetoproteínas/análise
9.
Fertil Steril ; 112(6): 1129-1135, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843089

RESUMO

OBJECTIVE: To study the association between mode of conception and offspring infectious morbidity risk. DESIGN: Population-based cohort study. SETTING: Regional university medical center. PATIENT(S): All singleton infants born between the years 1991 and 2014 and discharged alive from the hospital. INTERVENTION(S): Follow-up time in the study was calculated from birth to an event, defined as the first offspring hospitalization with any infectious morbidity. All infectious diagnoses were compared between the study groups, and a multivariable survival model was created to study the association between mode of conception and offspring pediatric hospitalization with infectious morbidity, and adjusting for confounding or clinically significant variables. MAIN OUTCOME MEASURE(S): First offspring pediatric hospitalization with infectious morbidity. RESULT(S): During the study period, 242,187 newborns met the inclusion criteria: 2,603 (1.1%) of which were conceived after undergoing IVF, 1,172 (0.7%) after ovulation induction (OI), and 237,863 (98.3%) were conceived spontaneously. Mothers receiving fertility treatments were older and with higher rates of preterm births and low birthweights. The hospitalizations rates per 1,000 person years of follow-up were 16.34/1,000 person years, 11.61/1,000 person years, and 10.19/1,000 person years, among the IVF, OI, and spontaneously conceived offspring, respectively. The adjusted hazard ratios were 1.26 (95% confidence interval 1.13-1.42) and 1.14 (95% confidence interval 1.00-1.38), for the IVF and OI compared with the spontaneously conceived offspring, respectively. The model adjusted for preterm delivery, birthweight, maternal age, hypertension, diabetes, and cesarean section. CONCLUSION(S): Higher risk for infectious morbidity was found among offspring conceived after fertility treatments compared with spontaneously conceived offspring.


Assuntos
Infecções Bacterianas/epidemiologia , Infertilidade/terapia , Técnicas de Reprodução Assistida/efeitos adversos , Viroses/epidemiologia , Adolescente , Adulto , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Hospitalização , Humanos , Lactente , Recém-Nascido , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Israel/epidemiologia , Masculino , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Viroses/mortalidade , Viroses/terapia , Viroses/virologia , Adulto Jovem
10.
Fertil Steril ; 112(6): 1136-1143.e4, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843090

RESUMO

OBJECTIVE: To study social and demographic differentiation of assisted reproduction technology (ART) use at the population level in the United States. DESIGN: Population-based study. SETTING: Not applicable. PATIENT(S): Women 15-49 years old in the American Community Survey and National Vital Statistics Birth Certificate data from 2010-2017. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Birth rate after ART by major sociodemographic categories and likelihood of having an ART birth. RESULT(S): Net of education, age, period, and marital status, the incidence rates of ART births are lower for black women (0.57 times; 95% CI, 0.52-0.62) and Hispanic women (0.67 times; 95% CI, 0.57-0.62) relative to white women's rates; for Asian women, the incidence rates are 1.21 times that of white women's rates. Further, the incidence rates of ART births are higher for women with more than a 4-year degree (2.08 times; 95% CI, 1.90-2.27) relative to women with a 4-year degree, and are lower for women with less education. Women who are married have an incidence rate of ART that is 5.72 times (95% CI, 5.37-6.09) that of unmarried women. The incidence rates for 2013-2016 are statistically significantly higher than for 2010 by a factor of 1.16 (95% CI, 1.02-1.31), 1.16 (95% CI, 1.03-1.31), 1.27 (95% CI, 1.12-1.43), and 1.51 (95% CI, 1.43-1.82), respectively. The educational differences in ART exist across all age groups from 20 to 49, but are the largest among the 35-39 and 40-44 age groups. CONCLUSION(S): Large differences in the risk of an ART birth and the proportion of births and the total fertility rate due to ART exist across period, age, race, education, and marital status groups in the United States. Current measures of ART births may disguise an unmet need for ART.


Assuntos
Disparidades em Assistência à Saúde/tendências , Infertilidade/terapia , Técnicas de Reprodução Assistida/tendências , Determinantes Sociais da Saúde/tendências , Fatores Socioeconômicos , Adolescente , Adulto , Fatores Etários , Grupos de Populações Continentais , Escolaridade , Feminino , Disparidades em Assistência à Saúde/etnologia , Humanos , Infertilidade/etnologia , Infertilidade/fisiopatologia , Nascimento Vivo , Estado Civil , Pessoa de Meia-Idade , Gravidez , Determinantes Sociais da Saúde/etnologia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
11.
Fertil Steril ; 112(6): 971-972, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843097

RESUMO

Adjuncts, more often known as add-ons, are now part of the landscape of an in vitro fertilization cycle. Since the early days of in vitro fertilization, fertility services have rightly been seeking improved success rates. At present there are a multitude of choices for patients who are usually presented with a menu of add-ons to choose from. This is driven by the desire to give patients the best chances of becoming parents. This Views and Reviews series discusses all aspects of add-ons. It is not exhaustive as even as we are finishing the preparation of the series, there is a new study about the use of cytokines as an add-on. The overall conclusion from this series of articles is that despite considerable efforts to establish benefits with add-ons that there is a paucity of data when we consider the outcome of live birth.


Assuntos
Infertilidade/terapia , Técnicas de Reprodução Assistida , Terapia Combinada , Análise Custo-Benefício , Medicina Baseada em Evidências , Feminino , Fertilidade , Custos de Cuidados de Saúde , Humanos , Infertilidade/diagnóstico , Infertilidade/economia , Infertilidade/fisiopatologia , Nascimento Vivo , Masculino , Gravidez , Taxa de Gravidez , Técnicas de Reprodução Assistida/efeitos adversos , Técnicas de Reprodução Assistida/economia , Resultado do Tratamento
12.
Fertil Steril ; 112(6): 987-993, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843098

RESUMO

The probability of live birth from an in vitro fertilization (IVF) cycle is modest. Many additional treatments (add-ons) are available which promise to improve the success of IVF. This review summarizes the current evidence for common IVF add-ons which are suggested to improve endometrial receptivity. Systematic reviews of randomized controlled trials and individual trials were included. Five add-ons were included: immune therapies, endometrial scratching, endometrial receptivity array, uterine artery vasodilation, and human chorionic gonadotropin instillation. The results suggest there is no robust evidence that these add-ons are effective or safe. Many IVF add-ons are costly, consuming precious resources which may be better spent on evidence-based treatments or further IVF. Large randomized controlled trials and appropriate safety assessment should be mandatory before the introduction of IVF add-ons into routine practice.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Fármacos para a Fertilidade/uso terapêutico , Fertilidade/efeitos dos fármacos , Fertilização In Vitro , Infertilidade/terapia , Endométrio/fisiopatologia , Medicina Baseada em Evidências , Feminino , Fármacos para a Fertilidade/efeitos adversos , Fertilização In Vitro/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Masculino , Gravidez , Taxa de Gravidez , Resultado do Tratamento
13.
Fertil Steril ; 112(6): 994-999, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843099

RESUMO

All the steps in an in vitro fertilization cycle are important but none more so than those that occur in the laboratory. To improve the chance of success, adjuncts, commonly referred to as 'add-ons', are offered. Yet as with other new interventions, add-ons in the laboratory require justification by well-designed studies prior to being offered as routine practice. Add-ons aim to improve the chance of a take-home baby, but, their safety and efficacy is less than clear. In addition, the financial burden from the use of add-ons is often borne by the couple. This review of the most commonly used laboratory add-ons did not find any high-quality evidence to support their use in routine practice.


Assuntos
Fertilização In Vitro , Infertilidade/terapia , Técnicas de Reprodução Assistida , Medicina Baseada em Evidências , Feminino , Fertilidade , Fertilização In Vitro/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Gravidez , Taxa de Gravidez , Técnicas de Reprodução Assistida/efeitos adversos , Resultado do Tratamento
14.
J Assist Reprod Genet ; 36(12): 2425-2433, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31713775

RESUMO

PURPOSE: To assess the effect of assisted hatching (AH) on live birth rate (LBR) in first cycle, fresh in vitro fertilization (IVF) in good and poor prognosis patients. METHODS: Retrospective cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Live birth rate was compared in women who underwent first cycle, autologous, fresh IVF cycles with (n = 48,858) and without (n = 103,413) AH from 2007 to 2015. RESULTS: The propensity-weighted LBR was 39.2% with AH versus 43.9% without AH in all patients. The rate difference (RD) with AH was - 4.7% ([CI - 0.053, - 0.040], P < 0.001) with the calculated number needed to harm being 22. AH affected live birth in both good prognosis and poor prognosis patients. The propensity-weighted monozygotic twinning (MZT) rate was 2.3% in patients treated with AH as compared to 1.2% patients that did not receive AH. The RD with AH on MZT in fresh, first IVF cycles was 1.1% ([0.008, 0.014], P < 0.001). CONCLUSION: AH may affect LBR across all patients and in poor prognosis patients in fresh IVF cycles. Caution should be exercised when applying this technology. More prospective research is needed.


Assuntos
Fertilização In Vitro , Nascimento Vivo , Taxa de Gravidez , Gravidez Múltipla/fisiologia , Adulto , Coeficiente de Natalidade , Transferência Embrionária/métodos , Feminino , Humanos , Infertilidade/genética , Infertilidade/fisiopatologia , Indução da Ovulação/métodos , Gravidez , Prognóstico , Injeções de Esperma Intracitoplásmicas/métodos , Gemelaridade Monozigótica/fisiologia
16.
PLoS Genet ; 15(10): e1008409, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589614

RESUMO

Limited translational genomic research data have been reported on the application of exome sequencing and parallel gene testing for preconception carrier screening (PCS). Here, we present individual-level data from a large PCS program in which exome sequencing was routinely performed on either gamete donors (5,845) or infertile patients (8,280) undergoing in vitro fertilization (IVF) treatment without any known family history of inheritable genetic conditions. Individual-level data on pathogenic variants were used to define conditions for PCS based on criteria for severity, penetrance, inheritance pattern, and age of onset. Fetal risk was defined based on actual carrier frequency data accounting for the specific inheritance pattern (fetal disease risk, FDR). In addition, large-scale application of exome sequencing for PCS allowed a deep investigation of the incidence of medically actionable secondary findings in this population. Exome sequencing achieved remarkable clinical sensitivity for reproductive risk of highly penetrant childhood-onset disorders (1/337 conceptions) through analysis of 114 selected gene-condition pairs. A significant contribution to fetal disease risk was observed for rare (carrier rate < 1:100) and X-linked conditions (16.7% and 41.2% of total FDR, respectively). Subgroup analysis of 776 IVF couples identified 37 at increased reproductive risk (4.8%; 95% CI = 3.4-6.5). Further, two additional couples had increased risk for very rare conditions when both members of a parental pair were treated as a unit and the search was extended to the entire exome. About 2.3% of participants showed at least one pathogenic variant for genes included in the updated American College of Medical Genetics and Genomics v2.0 list of secondary findings. Gamete donors and IVF couples showed similar carrier burden for both carrier screening and secondary findings, indicating no causal relationship to fertility. These translational research data will facilitate development of more effective PCS strategies that maximize clinical sensitivity with minimal counterproductive effects.


Assuntos
Genes Recessivos , Triagem de Portadores Genéticos , Predisposição Genética para Doença , Infertilidade/genética , Adulto , Criança , Pré-Escolar , Doação Dirigida de Tecido , Exoma/genética , Feminino , Testes Genéticos , Genoma Humano/genética , Genômica , Heterozigoto , Humanos , Lactente , Recém-Nascido , Infertilidade/epidemiologia , Infertilidade/fisiopatologia , Masculino , Mutação/genética , Pesquisa Médica Translacional , Sequenciamento Completo do Exoma
18.
Reprod Health ; 16(1): 137, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500644

RESUMO

BACKGROUND: Depression in patients with infertility often goes undiagnosed and untreated. The Patient Health Questionnaire-9 (PHQ-9) and its ultra-brief version (i.e. PHQ-2) are widely used measures of depressive symptoms. These scales have not been validated in patients with infertility. The aim of the present study was to examine the reliability and validity of the PHQ-9 and PHQ-2 in patients with infertility. METHODS: In this cross-sectional study, a total of 539 patients with infertility from a referral infertility clinic in Tehran, Iran completed the PHQ-9, along with other relevant scales: the WHO-five Well-being Index (WHO-5), the Hospital Anxiety and Depression Scale (HADS), and the Generalized Anxiety Disorder-7 (GAD-7). Factor structure and internal consistency of PHQ-9 were examined via confirmatory factor analysis (CFA) and Cronbach's alpha, respectively. Convergent validity was evaluated by relationship with WHO-5, HADS and GAD-7. RESULTS: The mean total PHQ-9 and PHQ-2 scores were 8.47 ± 6.17 and 2.42 ± 1.86, respectively, and using a cut-off value of 10 (for PHQ-9) and 3 (for PHQ-2), the prevalence of depressive symptoms was 38.6 and 43.6%, respectively. The Cronbach's alphas for PHQ-9 and PHQ-2 were, respectively, 0.851 and 0.767, indicating good internal consistency. The CFA results confirmed the one-factor model of the PHQ-9 (χ2/df = 4.29; CFI = 0.98; RMSEA = 0.078 and SRMR = 0.044). Both PHQ-9 and PHQ-2 showed moderate to strong correlation with the measures of WHO-5, HADS-depression, HADS-anxiety, and the GAD-7, confirming convergent validity. In univariate analysis, female sex, long infertility duration, and unsuccessful treatment were significantly associated with depression symptoms. CONCLUSION: Both PHQ-9 and PHQ-2 are brief and easy to use measures of depressive symptoms with good psychometric properties that appear suitable for routine use in patients with infertility.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtorno Depressivo/diagnóstico , Infertilidade/psicologia , Programas de Rastreamento/estatística & dados numéricos , Questionário de Saúde do Paciente/normas , Escalas de Graduação Psiquiátrica/normas , Adulto , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Estudos Transversais , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Feminino , Humanos , Infertilidade/fisiopatologia , Irã (Geográfico)/epidemiologia , Masculino , Reprodutibilidade dos Testes
19.
Reprod Biol Endocrinol ; 17(1): 67, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420039

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder of premenopausal women worldwide and is characterized by reproductive, endocrine, and metabolic abnormalities. The clinical manifestations of PCOS include oligomenorrhea or amenorrhea, hyperandrogenism, ovarian polycystic changes, and infertility. Women with PCOS are at an increased risk of suffering from type 2 diabetes; me\tabolic syndrome; cardiovascular events, such as hypertension, dyslipidemia; gynecological diseases, including infertility, endometrial dysplasia, endometrial cancer, and ovarian malignant tumors; pregnancy complications, such as premature birth, low birthweight, and eclampsia; and emotional and mental disorders in the future. Although numerous studies have focused on PCOS, the underlying pathophysiological mechanisms of this disease remain unclear. Mitochondria play a key role in energy production, and mitochondrial dysfunction at the cellular level can affect systemic metabolic balance. The recent wide acceptance of functional mitochondrial disorders as a correlated factor of numerous diseases has led to the presupposition that abnormal mitochondrial metabolic markers are associated with PCOS. Studies conducted in the past few years have confirmed that increased oxidative stress is associated with the progression and related complications of PCOS and have proven the relationship between other mitochondrial dysfunctions and PCOS. Thus, this review aims to summarize and discuss previous and recent findings concerning the relationship between mitochondrial dysfunction and PCOS.


Assuntos
Mitocôndrias/fisiologia , Ovário/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Pré-Menopausa/fisiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Infertilidade/metabolismo , Infertilidade/fisiopatologia , Mitocôndrias/metabolismo , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/metabolismo , Pré-Menopausa/metabolismo , Fatores de Risco
20.
J Assist Reprod Genet ; 36(10): 1989-1997, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414316

RESUMO

PURPOSE: Pre-pregnancy and post-delivery hospitalizations were compared as markers for health among women who conceived using assisted reproductive technology (ART), non-ART medically assisted reproduction (MAR), no treatment (unassisted subfertile), and who were fertile. METHODS: We analyzed hospital discharge data linked to Massachusetts birth certificates from 2004 to 2013 within 5 years prior to pregnancy and 8-365 days post-delivery. ART deliveries were linked from a national ART database; MAR deliveries had fertility treatment but not ART; unassisted subfertile women had subfertility but no ART or MAR; and fertile women had none of these. Prevalence of diagnoses during hospitalization was quantified. Multivariable logistic regression models with fertile deliveries as reference were adjusted for maternal age, race, education, year, and plurality (post-delivery only) with results reported as adjusted odds ratios (AORs) and 95% confidence intervals (CI). RESULTS: Of 170,605 privately insured, primiparous deliveries, 10,458 were ART, 3005 MAR, 1365 unassisted subfertile, and 155,777 fertile. Pre-pregnancy hospitalization occurred in 6.8% and post-delivery in 2.8% of fertile women. Subfertile groups had more pre-pregnancy hospitalizations (AOR, 95% CI: 1.84, 1.72-1.96 ART; 1.41, 1.24-1.60 MAR; 3.02, 2.62-3.47 unassisted subfertile) with endometriosis, reproductive organ disease, ectopic pregnancy/miscarriage, and disorders of menstruation, ovulation, and genital tract being common. Post-delivery hospitalizations were significantly more frequent in the ART (AOR 1.19, 95% CI 1.05-1.34) and unassisted subfertile (1.59, 1.23-2.07) groups with more digestive tract disorders, thyroid problems, and other grouped chronic disease conditions. CONCLUSIONS: Greater likelihood of hospitalization in the ART, MAR, and unassisted subfertile groups is largely explained by admissions for conditions associated with subfertility.


Assuntos
Fertilidade/genética , Infertilidade/genética , Técnicas de Reprodução Assistida , Adulto , Feminino , Hospitalização , Humanos , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Infertilidade/fisiopatologia , Idade Materna , Gravidez , Resultado da Gravidez , Gravidez Múltipla/fisiologia , Nascimento Prematuro/genética , Nascimento Prematuro/fisiopatologia
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