BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple gen...BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at once.Here,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-M)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)couple.CASE SUMMARY A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling.They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)genotype.Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both parents.The couple requested in vitro fertilization(IVF)and PGT-M for PA.From IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality embryos.Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid.Endpoint polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo.Both embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn screening.CONCLUSION We show that using PGT-M with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.展开更多
Preimplantation genetic testing(PGT),which was developed as an alternative to prenatal genetic testing,allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus...Preimplantation genetic testing(PGT),which was developed as an alternative to prenatal genetic testing,allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus.Originally used for early onset monogenic conditions,PGT is now used to prevent various types of inherited cancer conditions based on the development of PGT technology,assisted reproductive techniques(ARTs),and in vitro fertilization(IVF).This review provides insights into the potential benefits and challenges associated with the application of PGT for hereditary cancer and provides an overview of the existing literature on this test,with a particular focus on the current challenges related to laws,ethics,counseling,and technology.Additionally,this review predicts the future potential applications of this method.Although PGT may be utilized to predict and prevent hereditary cancer,each case should be comprehensively evaluated.The motives of couples must be assessed to prevent the misuse of this technique for eugenic purposes,and non-pathogenic phenotypes must be carefully evaluated.Pathological cases that require this technology should also be carefully considered based on legal and ethical reasoning.PGT may be the preferred treatment for hereditary cancer cases;however,such cases require careful case-by-case evaluations.Therefore,this study concludes that multidisciplinary counseling and support for patients and their families are essential to ensure that PGT is a viable option that meets all legal and ethical concerns.展开更多
The International Society of Reproductive Genetics(ISRG)assembled a workgroup made up of clinicians,clinical laboratory directors,and scientists for the purpose of creating the guidelines for preimplantation genetic t...The International Society of Reproductive Genetics(ISRG)assembled a workgroup made up of clinicians,clinical laboratory directors,and scientists for the purpose of creating the guidelines for preimplantation genetic testing(PGT).The most up-to-date information and clinical insights for the optimal PGT practice were incorporated in these guidelines.Recommendations are provided for embryologists,medical geneticists,clinical laboratorians,and other healthcare providers to improve the wellbeing of patients seeking assisted reproductive treatment and their offspring.展开更多
Objective:The objective of this study is to study whether preimplantation genetic testing for aneuploidy(PGT-A)improves the clinical outcomes of infertile patients with repeated implantation failure(RIF)undergoing fro...Objective:The objective of this study is to study whether preimplantation genetic testing for aneuploidy(PGT-A)improves the clinical outcomes of infertile patients with repeated implantation failure(RIF)undergoing frozen-thawed embryo transfer.Methods:This is a retrospective analysis of clinical pregnancy,live birth,miscarriage rates,and obstetric and perinatal outcomes of women with RIF with or without PGT-A.Statistical analyses of categorical data were performed using propensity score matching(PSM),χ^(2)test,and Student’s t test.Results:We enrolled 466 patients with RIF,of which,209 were in the RIF-PGT-A group.The rate of euploid blastocysts was significantly associated with age and day 5 or 6 blastocysts.There were significant differences between the RIF-PGT-A group and the RIF-non-PGT-A group across several parameters.After PSM,positive serum human chorionic gonadotropin(56.9%and 33.9%,P<0.01),clinical pregnancy(49.5%and 31.2%,P<0.01),live birth(43.1%and 25.7%,P<0.01),and fetal heart rates(50.0%and 29.8%,P<0.01)per transfer were significantly higher in the RIF-PGT-A group.Conclusion:Elective single-embryo transfer PGT-A can minimize the risk of obstetric and perinatal outcomes,especially fetal body weight,in women with RIF.Additionally,PGT-A can significantly improve pregnancy and live birth rates.展开更多
Objective:To evaluate whether preimplantation genetic testing for aneuploidy(PGT-A)with comprehensive chromosome screening increases live birth rate(LBR)in normal karyotype couples with recurrent pregnancy loss(RPL).M...Objective:To evaluate whether preimplantation genetic testing for aneuploidy(PGT-A)with comprehensive chromosome screening increases live birth rate(LBR)in normal karyotype couples with recurrent pregnancy loss(RPL).Methods:A retrospective cohort follow-up study of 506 couples with RPL was conducted between April 2014 and March 2017.Couples were allocated to two groups according to their decision to choose PGT-A or not.The primary outcome was LBR per start/transfer cycle;secondary outcomes were ongoing pregnancy rate and miscarriage rate.Statistical analyses were conducted using univariate and multivariate logistic regression models adjusted for maternal age.Results:LBR per start(26.6%vs.15.4%,relative risk[RR]:2.66,95%confidence interval[CI][1.69-4.20],P<0.0001;adjusted RR[aRR]:2.40,95%CI[1.49-3.86],P=0.0004)and per transfer(44.9%vs.25.1%,RR:3.00,95%CI[1.96-4.60],P<0.0001;aRR:2.64,95%CI[1.68-4.14],P<0.0001)was significantly higher in the PGT-A group than in the non-PGT-A group.The miscarriage rate was significantly lower in the PGT-A group compared to the non-PGT-A group(15.7%vs.34.6%,RR:0.27,95%CI[0.13-0.57],P=0.00005;aRR:0.26,95%CI[0.12-0.57],P=0.0007).Conclusions:LBR per start cycle following PGT-A is significantly higher,and risk of miscarriage is significantly lower among infertile couples with RPL,irrespective of maternal age.PGT-A should be recommended to infertile couples with RPL.展开更多
Preimplantation genetic testing(PGT)is an early form of prenatal genetic diagnosis,which can identify the abnormal embryos cultured in vitro,allow only transfer of genetically normal embryos,and improve the pregnancy ...Preimplantation genetic testing(PGT)is an early form of prenatal genetic diagnosis,which can identify the abnormal embryos cultured in vitro,allow only transfer of genetically normal embryos,and improve the pregnancy rate.In recent years,the rapid development of microarrays and next-generation sequencing(NGS)technologies has remarkably accelerated the clinical application of PGT.In particular,a variety of detection methods have emerged and achieved significant progress in PGT for structural rearrangements(PGT-SR).The detection-related abilities of these methods range from the detection of limited chromosome aneuploidy to comprehensive chromosome screening of the whole genome to differentiation of embryos with normal or balanced translocation/inversion karyotypes.In this study,we reviewed PGT-SR-related detection techniques to provide a better reference for clinical application and research.We have also discussed the potential development of novel techniques in the future.展开更多
Background: Reciprocal translocation(RCP) causes male infertility and female recurrent pregnancy loss. Male and female carriers have different responses to meiotic disturbances. Gender difference in outcomes of the RC...Background: Reciprocal translocation(RCP) causes male infertility and female recurrent pregnancy loss. Male and female carriers have different responses to meiotic disturbances. Gender difference in outcomes of the RCP couples undergoing preimplantation genetic testing(PGT) is unknown.Methods: We conducted a retrospective analysis of 238 RCP couples(124 female and 114 male carriers) divided by gender of carrier from March 2014 to March 2017. Blastocysts were divided by day 5 and day 6. Females were divided into older(≥38 years) and younger(<38 years). Logistic regression was fitted for the relationship between gender of carriers and euploidy. Euploidy rate of each group, pregnancy rate, and live birth rate between different genders were analyzed.Results: The sperm live rate, forward motile sperm rate, and normal morphology rate of serum in male RCP group were significantly decreased. The euploidy rate was 30.30% in female group and 34.90% in male group(P = 0.131); 34.50% in day 5 group and 27.50% in day 6 group(P = 0.039); 33.40% in age <38 years group and 22.40% in age ≥38 years group(P = 0.063). Day 5(odds ratio [OR] = 1.388, 95% confidence interval [CI ] = 1.012–1.904; P = 0.042) and younger age(OR = 1.753, 95% CI = 0.97–3.17; P = 0.063) were associated with euploidy. The clinical pregnancy rate(37.90% vs. 41.20%), ongoing pregnancy rate(33.10% vs. 37.70%), and live birth rate(25.80% vs. 31.60%) per initiated were not significantly different in two gender groups.Conclusions: Although gender influence is not significant, couples with male carrier showed better clinical outcomes. The embryo growing rate and female age are important predictions estimating euploidy in RCP couples.展开更多
Objective:To evaluate the effect of preimplantation genetic testing for aneuploidy(PGT-A)in infertile patients with recurrent pregnancy loss(RPL).Methods:A prospective randomized clinical trial was performed in a univ...Objective:To evaluate the effect of preimplantation genetic testing for aneuploidy(PGT-A)in infertile patients with recurrent pregnancy loss(RPL).Methods:A prospective randomized clinical trial was performed in a university-affiliated fertility center in Shanghai,China.Patients in the PGT-A group underwent blastocyst biopsy followed by single-nucleotide polymorphism microarray-based PGT-A and single euploid blastocyst transfer,whereas patients in the control group underwent routine in vitro fertilization/ICSI procedures and frozen embryo transfer of 1-2 embryos selected according to morphological standards.Results:Two hundred and seven infertile patients with RPL were included in this study and randomly assigned to either the control or the PGT-A group.Baseline variables and cycle characteristics were comparable between the two groups.The results showed that PGT-A significantly improved the ongoing pregnancy rate(55.34%vs.29.81%)as well as the live birth rate(48.54%vs.27.88%)and significantly reduced the miscarriage rate(0.00%vs.14.42%)on a per-patient analysis.A significant increase in cumulative ongoing pregnancy rates over time was observed in the PGT-A group.Subgroup analysis showed that the significant benefit diminished for patients who attempted≥2 PGT-A cycles.Conclusions:PGT-A significantly improved the ongoing pregnancy and live birth rate,while reduced miscarriage rate in infertile RPL patients.However,the significance diminished in patients attempting≥2 cycles;thus,further studies are warranted to explore the most cost-effective number of attempts in these patients to avoid overuse.展开更多
Rationale:If one of the partners is having balanced autosomal translocation,it is usually observed that the offspring inherit either normal chromosomes,balanced translocation identical to one of the parent or unbalanc...Rationale:If one of the partners is having balanced autosomal translocation,it is usually observed that the offspring inherit either normal chromosomes,balanced translocation identical to one of the parent or unbalanced chromosomal rearrangements of the same parental chromosome having translocation.Concern:A unique case presented with history of 8 miscarriages for genetic counseling.The last abortus material evaluation showed monosomy of chromosome X(Turner syndrome)in all the analyzed cells.There was a history of infertility and also repeated second trimester abortions on the paternal side.On the maternal side,there was a history of intellectual disability.Diagnose:History of repeated abnormal pregnancy outcomes.Wife’s karyotype is normal;however,husband shows translocation between chromosome 4 and 22.Intervention:Peripheral blood sample around 3 mL was collected for karyotype.Embryo biopsy was done and DNA was extracted and processed for whole exome sequencing.Outcomes:Wife’s karyotype is normal and husband has translocation between chromosome 4 and 22.Surprisingly,the entire pregnancy outcome including embryo screening has different,complete or partial aneuploidies of chromosomes other than chromosome 4 and 22.Main lesson:Though the translocation in one of the parent is balanced,we have to think beyond traditional ways for evaluating a couple with repeated pregnancy loss as we cannot predict the errors at cell division.Option of in vitro fertilization and preimplantation genetic diagnosis in couples having balanced translocations should be discussed so that early intervention can prevent the agony of pregnancy loss.展开更多
Background:The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate.Some algorithms have been used to assess the ploidy status ...Background:The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate.Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome,who subjected to preimplantation genetic testing for aneuploidy(PGT-A)treatment.However,it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods:From February 2020 to May 2021,we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos,the clinical information of couples,and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment.Initially,we developed a novel deep learning model called the Attentive Multi-Focus Selection Network(AMSNet)to analyze time-lapse videos in real time and predict blastocyst formation.Building upon AMSNet,we integrated additional clinically predictive variables and created a second deep learning model,the Attentive Multi-Focus Video and Clinical Information Fusion Network(AMCFNet),to assess the euploidy status of embryos.The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements.The receiver operating characteristic curve(ROC)was used to evaluate the superiority of the model.Results:A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task,and 1422 qualified blastocysts received PGT-A(n=589)or PGT for chromosomal structural rearrangement(PGT-SR,n=833)were enrolled for the euploidy assessment task in this study.The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy.The real-time accuracy for AMSNet to predict blastocyst formation reached above 70%on the day 2 of embryo culture,and then increased to 80%on the day 4 of embryo culture.Combing with 4 clinical features of couples,the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement.Conclusion:Integrating seven focal raw time-lapse images of embryos and parental clinical information,AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.展开更多
Preimplantation genetic testing (PGT) is a widely adopted screening method that can be performed to identify and select embryos with normal ploidy;however, PGT relies on embryo biopsy, that is, polar body, embryo cell...Preimplantation genetic testing (PGT) is a widely adopted screening method that can be performed to identify and select embryos with normal ploidy;however, PGT relies on embryo biopsy, that is, polar body, embryo cells, or trophectoderm biopsy, to obtain embryonic DNA, increase its technical limitations. Studies have indicated that biopsy may have an influence on the quality and development of embryos, and increase the chance of abnormal epigenetic modifications. Therefore, non-invasive PGT (niPGT) detection of cell-free DNA (cfDNA) has gradually become a hot research topic in the field of assisted reproduction. Studies showed cfDNA could be detected in blastocyst fluid and spent culture medium (SCM) in vitro cultured embryos. The cfDNA collection requires less skill and makes lower risk to embryos. Some studies have been conducted to evaluate the feasibility of SCM-based niPGT approaches. When comparing the ploidy consistency of cfDNA in SCM, its consistency to the conventional PGT for aneuploidies results fluctuated widely, it is critical to recognize the factors influencing accuracy. These contradictory results may be related to factors such as the difference in SCM sampling methods and sampling time, and the definition of consistency. In this review, we aimed to comprehensively summarize how researchers use embryonic cfDNA to conduct niPGT detection. It also systematically reviews the factors affecting the accuracy of the test and its underlying issues, as well as prospective applications. We hope to provide a basis for future niPGT research and a useful reference for the standardized operation of niPGT that can be widely applied in clinical practice.展开更多
This retrospective study demonstrates the clinical outcomes of patients with nonmosaic Klinefelter's syndrome(KS)who underwent preimplantation genetic testing(PGT)with frozen-thawed testicular spermatozoa.Microdis...This retrospective study demonstrates the clinical outcomes of patients with nonmosaic Klinefelter's syndrome(KS)who underwent preimplantation genetic testing(PGT)with frozen-thawed testicular spermatozoa.Microdissection testicular sperm extraction(micro-TESE)was performed for sperm retrieval.Next-generation sequencing(NGS)was conducted for embryo analysis.A total of 18 couples aged≤35 years were included,and 22 oocyte retrieval cycles were completed.Euploidy was detected in 29 of 45(64.4%)embryos.Additionally,the numbers of aneuploid and mosaic embryos detected were 8(17.8%)and 8(17.8%),respectively,regardless of a lack of sex chromosome abnormalities.Finally,13 couples with euploid embryos completed 14 frozen embryo transfer(FET)cycles.Ten couples had clinical pregnancies,and 6 of them had already delivered 5 healthy babies and 1 monozygotic twin.There were also 4 ongoing pregnancies and 2 biochemical pregnancies,but no early pregnancy loss was reported.Based on our results,we speculate that for KS patients,when sperm can be obtained by micro-TESE,the cryopreservation strategy makes the ovarian stimulation procedure more favorable for female partners.The paternal genetic risk of sex chromosome abnormalities in their offspring is extremely low in men with KS.In addition to PGT,the intracytoplasmic sperm injection(ICSI)procedure is comparably effective but more economical for young nonmosaic KS couples.ICSI should be offered as an option for such couples,but monitoring by prenatal genetic diagnosis is recommended.展开更多
Objective:To explore the roles of advanced paternal age(APA)and abnormal paternal weight on embryo quality and pregnancy outcomes for unexplained recurrent pregnancy loss(uRPL)couples who underwent preimplantation gen...Objective:To explore the roles of advanced paternal age(APA)and abnormal paternal weight on embryo quality and pregnancy outcomes for unexplained recurrent pregnancy loss(uRPL)couples who underwent preimplantation genetic testing for aneuploidies(PGT-A).Methods:This study included 779 uRPL couples who underwent their first PGT-A cycles between 2014 and 2018.Male patients’aging and nutritional status were quantified by paternal age and body mass index(BMI).Routine semen parameters and sperm DNA fragmentation index(DFI)were used to reflect the seminal quality.Blastocyst formation rate and aneuploidy rate were used to reflect the embryo quality.Cycle cancellation rate,implantation rate,pregnancy loss rate,and live birth rate were measured to evaluate the treatment efficiency from IVF.To remove the interference of maternal age,only the women younger than 38 years old were included.After univariate screening,interaction tests were performed in a generalized linear model(GLM)to further examine the effects of paternal age and BMI on each outcome indicator.Results:In the total population(779 cycles),there were no statistical differences in aneuploidy rate,cycle cancellation rate,implantation rate,pregnancy loss rate,and live birth rate,whether stratified by paternal age or paternal BMI.Similar results occurred in the younger men(<40 y.o.,633 cycles).Conversely,among the men with advanced age(≥40 y.o.,146 cycles),there were statistical differences between the three BMI groups in four semen parameters(total sperm number,total motility,progressive motility,and total motile sperm count),implantation rate,and live birth rate.After interaction testing,the results of GLM suggested that the interaction effect between APA and paternal obesity was associated with the low implantation rate of uRPL couples.Conclusions:For the uRPL couples seeking for PGT-A treatment,if the male patients have both advanced age and obesity,their spouses are at higher risks for embryo implantation failure.展开更多
文摘BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at once.Here,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-M)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)couple.CASE SUMMARY A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling.They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)genotype.Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both parents.The couple requested in vitro fertilization(IVF)and PGT-M for PA.From IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality embryos.Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid.Endpoint polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo.Both embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn screening.CONCLUSION We show that using PGT-M with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.
文摘Preimplantation genetic testing(PGT),which was developed as an alternative to prenatal genetic testing,allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus.Originally used for early onset monogenic conditions,PGT is now used to prevent various types of inherited cancer conditions based on the development of PGT technology,assisted reproductive techniques(ARTs),and in vitro fertilization(IVF).This review provides insights into the potential benefits and challenges associated with the application of PGT for hereditary cancer and provides an overview of the existing literature on this test,with a particular focus on the current challenges related to laws,ethics,counseling,and technology.Additionally,this review predicts the future potential applications of this method.Although PGT may be utilized to predict and prevent hereditary cancer,each case should be comprehensively evaluated.The motives of couples must be assessed to prevent the misuse of this technique for eugenic purposes,and non-pathogenic phenotypes must be carefully evaluated.Pathological cases that require this technology should also be carefully considered based on legal and ethical reasoning.PGT may be the preferred treatment for hereditary cancer cases;however,such cases require careful case-by-case evaluations.Therefore,this study concludes that multidisciplinary counseling and support for patients and their families are essential to ensure that PGT is a viable option that meets all legal and ethical concerns.
基金National Key Research and Development Program of China(2021YFC2700701,2021YFC2701002,2020YFA0804000,2018YFC1004901)National Natural Science Foundation of China(82171677,81901495,82088102,81971344,82171686,82071661)+6 种基金Clinical Research Project of Shanghai Municipal Health Commission(202140110)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-064)International Science and Technology Collaborative Fund of Shanghai(18410711800)Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)Shanghai Municipal Commission of Science and Technology Program(21Y21901002,22S31901500)Clinical Research Plan of SHDC(SHDC2020CR1008A)Shanghai Frontiers Science Research Base of Reproduction and Development,and Shanghai"Science and Technology Innovation Action Plan"Hong Kong,Macao,and Taiwan Science and Technology Cooperation Project(19410760100)
文摘The International Society of Reproductive Genetics(ISRG)assembled a workgroup made up of clinicians,clinical laboratory directors,and scientists for the purpose of creating the guidelines for preimplantation genetic testing(PGT).The most up-to-date information and clinical insights for the optimal PGT practice were incorporated in these guidelines.Recommendations are provided for embryologists,medical geneticists,clinical laboratorians,and other healthcare providers to improve the wellbeing of patients seeking assisted reproductive treatment and their offspring.
基金National Natural Science Foundation of China(No.81901558)
文摘Objective:The objective of this study is to study whether preimplantation genetic testing for aneuploidy(PGT-A)improves the clinical outcomes of infertile patients with repeated implantation failure(RIF)undergoing frozen-thawed embryo transfer.Methods:This is a retrospective analysis of clinical pregnancy,live birth,miscarriage rates,and obstetric and perinatal outcomes of women with RIF with or without PGT-A.Statistical analyses of categorical data were performed using propensity score matching(PSM),χ^(2)test,and Student’s t test.Results:We enrolled 466 patients with RIF,of which,209 were in the RIF-PGT-A group.The rate of euploid blastocysts was significantly associated with age and day 5 or 6 blastocysts.There were significant differences between the RIF-PGT-A group and the RIF-non-PGT-A group across several parameters.After PSM,positive serum human chorionic gonadotropin(56.9%and 33.9%,P<0.01),clinical pregnancy(49.5%and 31.2%,P<0.01),live birth(43.1%and 25.7%,P<0.01),and fetal heart rates(50.0%and 29.8%,P<0.01)per transfer were significantly higher in the RIF-PGT-A group.Conclusion:Elective single-embryo transfer PGT-A can minimize the risk of obstetric and perinatal outcomes,especially fetal body weight,in women with RIF.Additionally,PGT-A can significantly improve pregnancy and live birth rates.
基金This study was supported by Shanghai Municipal Commission of Health and Family Planning Project(No.201640365)Shanghai Shen Kang Hospital Development Center Municipal Hospital New Frontier Technology Joint Project(SHDC12017105).
文摘Objective:To evaluate whether preimplantation genetic testing for aneuploidy(PGT-A)with comprehensive chromosome screening increases live birth rate(LBR)in normal karyotype couples with recurrent pregnancy loss(RPL).Methods:A retrospective cohort follow-up study of 506 couples with RPL was conducted between April 2014 and March 2017.Couples were allocated to two groups according to their decision to choose PGT-A or not.The primary outcome was LBR per start/transfer cycle;secondary outcomes were ongoing pregnancy rate and miscarriage rate.Statistical analyses were conducted using univariate and multivariate logistic regression models adjusted for maternal age.Results:LBR per start(26.6%vs.15.4%,relative risk[RR]:2.66,95%confidence interval[CI][1.69-4.20],P<0.0001;adjusted RR[aRR]:2.40,95%CI[1.49-3.86],P=0.0004)and per transfer(44.9%vs.25.1%,RR:3.00,95%CI[1.96-4.60],P<0.0001;aRR:2.64,95%CI[1.68-4.14],P<0.0001)was significantly higher in the PGT-A group than in the non-PGT-A group.The miscarriage rate was significantly lower in the PGT-A group compared to the non-PGT-A group(15.7%vs.34.6%,RR:0.27,95%CI[0.13-0.57],P=0.00005;aRR:0.26,95%CI[0.12-0.57],P=0.0007).Conclusions:LBR per start cycle following PGT-A is significantly higher,and risk of miscarriage is significantly lower among infertile couples with RPL,irrespective of maternal age.PGT-A should be recommended to infertile couples with RPL.
基金supported by the Science and Technology Innovation Action Plan Program of Shanghai(18411953800)Shanghai Municipal Health Commission(20194Y0002).
文摘Preimplantation genetic testing(PGT)is an early form of prenatal genetic diagnosis,which can identify the abnormal embryos cultured in vitro,allow only transfer of genetically normal embryos,and improve the pregnancy rate.In recent years,the rapid development of microarrays and next-generation sequencing(NGS)technologies has remarkably accelerated the clinical application of PGT.In particular,a variety of detection methods have emerged and achieved significant progress in PGT for structural rearrangements(PGT-SR).The detection-related abilities of these methods range from the detection of limited chromosome aneuploidy to comprehensive chromosome screening of the whole genome to differentiation of embryos with normal or balanced translocation/inversion karyotypes.In this study,we reviewed PGT-SR-related detection techniques to provide a better reference for clinical application and research.We have also discussed the potential development of novel techniques in the future.
基金sponsored by the Shanghai Municipal Commission of Health and Family Planning Project(No.201640365).
文摘Background: Reciprocal translocation(RCP) causes male infertility and female recurrent pregnancy loss. Male and female carriers have different responses to meiotic disturbances. Gender difference in outcomes of the RCP couples undergoing preimplantation genetic testing(PGT) is unknown.Methods: We conducted a retrospective analysis of 238 RCP couples(124 female and 114 male carriers) divided by gender of carrier from March 2014 to March 2017. Blastocysts were divided by day 5 and day 6. Females were divided into older(≥38 years) and younger(<38 years). Logistic regression was fitted for the relationship between gender of carriers and euploidy. Euploidy rate of each group, pregnancy rate, and live birth rate between different genders were analyzed.Results: The sperm live rate, forward motile sperm rate, and normal morphology rate of serum in male RCP group were significantly decreased. The euploidy rate was 30.30% in female group and 34.90% in male group(P = 0.131); 34.50% in day 5 group and 27.50% in day 6 group(P = 0.039); 33.40% in age <38 years group and 22.40% in age ≥38 years group(P = 0.063). Day 5(odds ratio [OR] = 1.388, 95% confidence interval [CI ] = 1.012–1.904; P = 0.042) and younger age(OR = 1.753, 95% CI = 0.97–3.17; P = 0.063) were associated with euploidy. The clinical pregnancy rate(37.90% vs. 41.20%), ongoing pregnancy rate(33.10% vs. 37.70%), and live birth rate(25.80% vs. 31.60%) per initiated were not significantly different in two gender groups.Conclusions: Although gender influence is not significant, couples with male carrier showed better clinical outcomes. The embryo growing rate and female age are important predictions estimating euploidy in RCP couples.
基金Shanghai Shenkang Hospital Development Center Program(SHDC12017105).
文摘Objective:To evaluate the effect of preimplantation genetic testing for aneuploidy(PGT-A)in infertile patients with recurrent pregnancy loss(RPL).Methods:A prospective randomized clinical trial was performed in a university-affiliated fertility center in Shanghai,China.Patients in the PGT-A group underwent blastocyst biopsy followed by single-nucleotide polymorphism microarray-based PGT-A and single euploid blastocyst transfer,whereas patients in the control group underwent routine in vitro fertilization/ICSI procedures and frozen embryo transfer of 1-2 embryos selected according to morphological standards.Results:Two hundred and seven infertile patients with RPL were included in this study and randomly assigned to either the control or the PGT-A group.Baseline variables and cycle characteristics were comparable between the two groups.The results showed that PGT-A significantly improved the ongoing pregnancy rate(55.34%vs.29.81%)as well as the live birth rate(48.54%vs.27.88%)and significantly reduced the miscarriage rate(0.00%vs.14.42%)on a per-patient analysis.A significant increase in cumulative ongoing pregnancy rates over time was observed in the PGT-A group.Subgroup analysis showed that the significant benefit diminished for patients who attempted≥2 PGT-A cycles.Conclusions:PGT-A significantly improved the ongoing pregnancy and live birth rate,while reduced miscarriage rate in infertile RPL patients.However,the significance diminished in patients attempting≥2 cycles;thus,further studies are warranted to explore the most cost-effective number of attempts in these patients to avoid overuse.
基金support from ICMR-National Institute for Research in Reproductive Health(ICMR-NIRRH).
文摘Rationale:If one of the partners is having balanced autosomal translocation,it is usually observed that the offspring inherit either normal chromosomes,balanced translocation identical to one of the parent or unbalanced chromosomal rearrangements of the same parental chromosome having translocation.Concern:A unique case presented with history of 8 miscarriages for genetic counseling.The last abortus material evaluation showed monosomy of chromosome X(Turner syndrome)in all the analyzed cells.There was a history of infertility and also repeated second trimester abortions on the paternal side.On the maternal side,there was a history of intellectual disability.Diagnose:History of repeated abnormal pregnancy outcomes.Wife’s karyotype is normal;however,husband shows translocation between chromosome 4 and 22.Intervention:Peripheral blood sample around 3 mL was collected for karyotype.Embryo biopsy was done and DNA was extracted and processed for whole exome sequencing.Outcomes:Wife’s karyotype is normal and husband has translocation between chromosome 4 and 22.Surprisingly,the entire pregnancy outcome including embryo screening has different,complete or partial aneuploidies of chromosomes other than chromosome 4 and 22.Main lesson:Though the translocation in one of the parent is balanced,we have to think beyond traditional ways for evaluating a couple with repeated pregnancy loss as we cannot predict the errors at cell division.Option of in vitro fertilization and preimplantation genetic diagnosis in couples having balanced translocations should be discussed so that early intervention can prevent the agony of pregnancy loss.
基金supported by grants from the National Natural Science Found of China(No.81270750)Natural Science Found of Guangdong China(No.2019A1515011845)+1 种基金Stem Cell Research Founding from Chinese Medical Association(No.19020010780)Sun Yat-sen University 5010 Clinical Research Project(No.2023003).
文摘Background:The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate.Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome,who subjected to preimplantation genetic testing for aneuploidy(PGT-A)treatment.However,it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods:From February 2020 to May 2021,we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos,the clinical information of couples,and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment.Initially,we developed a novel deep learning model called the Attentive Multi-Focus Selection Network(AMSNet)to analyze time-lapse videos in real time and predict blastocyst formation.Building upon AMSNet,we integrated additional clinically predictive variables and created a second deep learning model,the Attentive Multi-Focus Video and Clinical Information Fusion Network(AMCFNet),to assess the euploidy status of embryos.The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements.The receiver operating characteristic curve(ROC)was used to evaluate the superiority of the model.Results:A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task,and 1422 qualified blastocysts received PGT-A(n=589)or PGT for chromosomal structural rearrangement(PGT-SR,n=833)were enrolled for the euploidy assessment task in this study.The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy.The real-time accuracy for AMSNet to predict blastocyst formation reached above 70%on the day 2 of embryo culture,and then increased to 80%on the day 4 of embryo culture.Combing with 4 clinical features of couples,the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement.Conclusion:Integrating seven focal raw time-lapse images of embryos and parental clinical information,AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.
基金This work was supported by the Science and Technology Major Projects of Birth Defect Collaborative Prevention in Hunan Province(No.1019SK1010).
文摘Preimplantation genetic testing (PGT) is a widely adopted screening method that can be performed to identify and select embryos with normal ploidy;however, PGT relies on embryo biopsy, that is, polar body, embryo cells, or trophectoderm biopsy, to obtain embryonic DNA, increase its technical limitations. Studies have indicated that biopsy may have an influence on the quality and development of embryos, and increase the chance of abnormal epigenetic modifications. Therefore, non-invasive PGT (niPGT) detection of cell-free DNA (cfDNA) has gradually become a hot research topic in the field of assisted reproduction. Studies showed cfDNA could be detected in blastocyst fluid and spent culture medium (SCM) in vitro cultured embryos. The cfDNA collection requires less skill and makes lower risk to embryos. Some studies have been conducted to evaluate the feasibility of SCM-based niPGT approaches. When comparing the ploidy consistency of cfDNA in SCM, its consistency to the conventional PGT for aneuploidies results fluctuated widely, it is critical to recognize the factors influencing accuracy. These contradictory results may be related to factors such as the difference in SCM sampling methods and sampling time, and the definition of consistency. In this review, we aimed to comprehensively summarize how researchers use embryonic cfDNA to conduct niPGT detection. It also systematically reviews the factors affecting the accuracy of the test and its underlying issues, as well as prospective applications. We hope to provide a basis for future niPGT research and a useful reference for the standardized operation of niPGT that can be widely applied in clinical practice.
文摘This retrospective study demonstrates the clinical outcomes of patients with nonmosaic Klinefelter's syndrome(KS)who underwent preimplantation genetic testing(PGT)with frozen-thawed testicular spermatozoa.Microdissection testicular sperm extraction(micro-TESE)was performed for sperm retrieval.Next-generation sequencing(NGS)was conducted for embryo analysis.A total of 18 couples aged≤35 years were included,and 22 oocyte retrieval cycles were completed.Euploidy was detected in 29 of 45(64.4%)embryos.Additionally,the numbers of aneuploid and mosaic embryos detected were 8(17.8%)and 8(17.8%),respectively,regardless of a lack of sex chromosome abnormalities.Finally,13 couples with euploid embryos completed 14 frozen embryo transfer(FET)cycles.Ten couples had clinical pregnancies,and 6 of them had already delivered 5 healthy babies and 1 monozygotic twin.There were also 4 ongoing pregnancies and 2 biochemical pregnancies,but no early pregnancy loss was reported.Based on our results,we speculate that for KS patients,when sperm can be obtained by micro-TESE,the cryopreservation strategy makes the ovarian stimulation procedure more favorable for female partners.The paternal genetic risk of sex chromosome abnormalities in their offspring is extremely low in men with KS.In addition to PGT,the intracytoplasmic sperm injection(ICSI)procedure is comparably effective but more economical for young nonmosaic KS couples.ICSI should be offered as an option for such couples,but monitoring by prenatal genetic diagnosis is recommended.
基金the National Key Research and Development Program of China(2018YFC1002804).
文摘Objective:To explore the roles of advanced paternal age(APA)and abnormal paternal weight on embryo quality and pregnancy outcomes for unexplained recurrent pregnancy loss(uRPL)couples who underwent preimplantation genetic testing for aneuploidies(PGT-A).Methods:This study included 779 uRPL couples who underwent their first PGT-A cycles between 2014 and 2018.Male patients’aging and nutritional status were quantified by paternal age and body mass index(BMI).Routine semen parameters and sperm DNA fragmentation index(DFI)were used to reflect the seminal quality.Blastocyst formation rate and aneuploidy rate were used to reflect the embryo quality.Cycle cancellation rate,implantation rate,pregnancy loss rate,and live birth rate were measured to evaluate the treatment efficiency from IVF.To remove the interference of maternal age,only the women younger than 38 years old were included.After univariate screening,interaction tests were performed in a generalized linear model(GLM)to further examine the effects of paternal age and BMI on each outcome indicator.Results:In the total population(779 cycles),there were no statistical differences in aneuploidy rate,cycle cancellation rate,implantation rate,pregnancy loss rate,and live birth rate,whether stratified by paternal age or paternal BMI.Similar results occurred in the younger men(<40 y.o.,633 cycles).Conversely,among the men with advanced age(≥40 y.o.,146 cycles),there were statistical differences between the three BMI groups in four semen parameters(total sperm number,total motility,progressive motility,and total motile sperm count),implantation rate,and live birth rate.After interaction testing,the results of GLM suggested that the interaction effect between APA and paternal obesity was associated with the low implantation rate of uRPL couples.Conclusions:For the uRPL couples seeking for PGT-A treatment,if the male patients have both advanced age and obesity,their spouses are at higher risks for embryo implantation failure.