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This study aimed to summarize the current knowledge on the benefits of In vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic testing for aneuploidy (PGT-A) and to discuss the role of PGT-A in patients of different ages undergoing assisted reproduction. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Registration number: CRD42022354697. Studies were identified by searching the PubMed, Cochrane Library, Google Scholar, Scopus, Embase, and ClinicalTrials databases. Seven meta-analyses were performed with additional stratification of age and prognosis of the women studied. Clinical pregnancy rate per embryo transfer in patients aged >35 years was higher in the PGT-A group (P=0.0002) than in controls. Live birth rate (LBR) per embryo transfer in women 35 years old or younger (P=0.002) was higher in the PGT-A group. The LBR per patient in women aged >35 years was higher in the PGT-A group (P=0.004). The effects of PGT-A on LBR in patients with poor prognosis showed a statistically significant increase (P=0.003). There was no significant difference in the rate between the two groups. PGT-A is effective and can be recommended for patients aged >35 years undergoing assisted reproduction to improve their reproductive outcomes. Moreover, our study showed the possible benefits of PGT-A in patients with a poor prognosis. Overall, our findings suggest that PGT-A is a valuable tool for improving the reproductive outcomes of assisted reproductive procedures in older women and those with a history of pregnancy complications.

Infertility is a complex disease characterized by extreme genetic heterogeneity, compounded by various environmental factors. While there are exceptions, individual genetic and genomic variations related to infertility are typically rare, often family-specific, and may serve as susceptibility factors rather than direct causes of the disease. Consequently, identifying the cause of infertility and developing prevention and treatment strategies based on these factors remain challenging tasks, even in the modern genomic era. In this review, we first examine the genetic and genomic variations associated with infertility, and subsequently summarize the concepts and methods of preimplantation genetic testing in light of advances in genome analysis technology. [ABSTRACT FROM AUTHOR]

BackgroundWe sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation.MethodsPatients were enrolled from August 2011 to June 2018 at 10 transplant centers in the multi-center Lung Transplant Outcomes Group prospective cohort study. PGD was defined as Grade 3 at 48 or 72 hours, based on the 2016 PGD ISHLT guidelines. Logistic regression and survival models were used to contrast between group effects for event (i.e., PGD and Death) and time-to-event (i.e., death, extubation, discharge) outcomes respectively. Both modeling frameworks accommodate the inclusion of potential confounders.ResultsA total of 1,528 subjects were enrolled with a 25.7% incidence of PGD. Annual PGD incidence (14.3%-38.2%, p = .0002), median LAS (38.0-47.7 p = .009) and the use of ECMO salvage for PGD (5.7%-20.9%, p = .007) increased over the course of the study. PGD was associated with increased 1 year mortality (OR 1.7 [95% C.I. 1.2, 2.3], p = .0001). Bridging strategies were not associated with increased mortality compared to non-bridged patients (p = .66); however, salvage ECMO for PGD was significantly associated with increased mortality (OR 1.9 [1.3, 2.7], p = .0007). Restricted mean survival time comparison at 1-year demonstrated 84.1 days lost in venoarterial salvaged recipients with PGD when compared to those without PGD (ratio 1.3 [1.1, 1.5]) and 27.2 days for venovenous with PGD (ratio 1.1 [1.0, 1.4]).ConclusionsPGD incidence continues to rise in modern transplant practice paralleled by significant increases in recipient severity of illness. Bridging strategies have increased but did not affect PGD incidence or mortality. PGD remains highly associated with mortality and is increasingly treated with salvage ECMO.

Pre-implantation genetic diagnosis (PGD) is not often performed when donor gametes are used, due to its high cost. This is with the presumption that the donors are healthy.

Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores (ESPS). These scores represent individualized predictions of health and other outcomes derived from genomewide association studies in adults to partially predict these outcomes. This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these effects for a variety of clinical and nonclinical traits. Also discussed are potential unintended consequences of ESPS (including selecting for adverse traits, altering population demographics, exacerbating inequalities in society, and devaluing certain traits). Recommendations for the responsible communication about ESPS by practitioners are provided, and a call for a society-wide conversation about this technology is made. (Funded by the National Institute on Aging and others.).

PurposeTo report the rate of fetal anomalies detected on anatomy ultrasound in pregnant patients who underwent IVF with preimplantation genetic testing for aneuploidy (PGT-A) compared to patients who conceived following IVF with unscreened embryos and age-matched patients with natural conceptions.MethodsRetrospective cohort study at a single maternal-fetal medicine practice. Patients with singleton pregnancies who had a mid-trimester anatomy ultrasound between January 2017 and December 2018 were screened for inclusion. A total of 712 patients who conceived after IVF with or without PGT-A were age-matched with natural conception controls. The primary outcome was the rate of fetal and placental anomalies detected on mid-trimester anatomical survey. Secondary outcomes included the rates of abnormal nuchal translucency (NT), second trimester serum analytes, non-invasive prenatal testing (NIPT), and invasive diagnostic testing.Result(s)There were no differences in the rate of fetal anomalies in patients who underwent IVF with PGT-A compared to patients who conceived following IVF with unscreened embryos and age-matched patients with natural conceptions. Rate of abnormal NT, high-risk NIPT, and abnormal invasive diagnostic testing were also similar. Patients who conceived after IVF with or without PGT-A had higher rates of abnormal placental ultrasound findings and abnormal second trimester serum analytes compared to natural conception controls.ConclusionThe use of PGT-A was not associated with a difference in risk of fetal anomaly detection on a mid-trimester anatomical survey. The results of this study highlight the importance of improved patient counseling regarding the limitations of PGT-A, and of providing standard prenatal care for pregnancies conceived through ART, regardless of whether PGT-A was performed.

Background Embryo anomaly is the most common cause of implantation failure and abortion in women of reproductive age. However, there is controversy about the cause of implantation failure or miscarriage that occurs after the transfer of a normal embryo screened by preimplantation genetic testing (PGT) . Objective To analyze the influencing factors affecting implantation failure and miscarriage after PGT assisted reproduction. Methods Three hundred and twenty-nine women who received PGT assisted reproduction in Reproductive Center, the First Affiliated Hospital of Anhui Medical University from December 2018 to February 2021 were enrolled, including 218 with clinical pregnancy〔175 of whom had a live birth (live birth subgroup) , and 43 had an abortion (abortion subgroup) 〕, and 111 with implantation failure. Clinical data, results of accessory examinations, ovulation induction and in vitro embryonic development were compared between women with clinical pregnancy and implantation failure, and between live birth and abortion subgroups. The influencing factors of implantation failure and abortion after PGT assisted reproduction were screened by multivariate logistic regression analysis, and predictive values of the determined factors for implantation failure and abortion were estimated using the receiver operating characteristic (ROC) analysis. Results Multivariate logistic regression analysis showed that, two or more previous abortions〔OR=4.032 0, 95%CI (2.423 0, 6.710 0) 〕 and low level of high-density lipoprotein cholesterol (HDL-C) 〔OR=3.890 0, 95%CI (1.455 0, 10.403 0) 〕were risk factors for implantation failure after PGT assisted reproduction (P

Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is a severe autosomal recessive epileptic encephalopathy characterized by rigidity, intractable multifocal seizures, microcephaly, apnea, and bradycardia immediately after birth. RMFSL is related to a mutation in breast cancer 1-associated ataxia telangiectasia mutated activation-1 protein (BRAT1). We report a case of a female infant born to non-consanguineous Korean parents who developed hypertonia, dysmorphic features, progressive encephalopathy with refractory seizures at birth, and worsening intermittent apnea, leading to intubation and death at 137 days of age. The initial repeated electroencephalographic findings were normal; however, a pattern of focal seizures emerged at 35 days of life. Rapid trio whole-exome sequencing revealed heterozygous mutations c.1313_1314delAG p.(Gln438Argfs*51) and c.1276C>T p. (Gln426*) in BRAT1. After genetic counseling for pregnancy planning, a preimplantation genetic diagnosis for targeted BRAT1 mutations was successfully performed, and a healthy baby was born. To our knowledge, this is the first reported case of a Korean patient with compound heterozygous mutations in BRAT1. An early and accurate genetic diagnosis can help provide timely treatment to patients and indicate the need for reproductive counseling for parents for family planning.

To describe the reproductive and obstetric outcomes of an intracytoplasmic sperm injection cycle with preimplantation genetic testing for aneuploidy in an advanced reproductive-age woman with high-grade mosaic Turner syndrome. Case report of a 39-year-old woman diagnosed with mosaic Turner Syndrome 45,X[90]/46,XX[10] karyotype who underwent in vitro fertilization treatment with blastocyst trophectoderm biopsy for preimplantation genetic testing using next-generation sequencing. Two of the four blastocysts biopsied were euploid. The patient achieved ongoing pregnancy after the first single euploid frozen embryo transfer, followed by the birth of a healthy child. Autologous intracytoplasmic sperm injection cycles can be considered in a select group of advanced reproductive-age women diagnosed with high-grade mosaic Turner syndrome. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is characterized by the homozygous deletion of the survival motor neuron-1 gene. Pre-implantation genetic testing for monogenic diseases through in-vitro fertilization program was developed to provide a reliable genetic diagnostic method for SMA. Case presentation: The couple who was confirmed as carriers of SMA visited the Morula IVF Clinic, Jakarta, Indenesia seeking for an in-vitro fertilization expert opinion in relation to the pre-implantation genetic testing for SMA. Utilizing polymerase chain reaction-restriction fragment length polymorphism, we have successfully screened for unaffected embryos that were characterized by a normal presence of the survival motor neuron-1 exon 7-8 and survival motor neuron-2 exon 7-8. The frozen embryo was subsequently transferred and a healthy unaffected female baby was born with undetected deletion of the survival motor neuron-1 gene. Conclusion: This successful embryo pre-implantation screening case could potentially accommodate the demands of genetically at-risk couples who are apprehensive about conceiving a child who might inherit monogenic disorders such as SMA. [ABSTRACT FROM AUTHOR]

Background: Preimplantation genetic diagnosis (PGD) has been used as an option for couples with the possibility of having a baby with a genetic disorder. The common method for performing this test involves isolating 1 cell from day 3 or a few cells from day 5 embryos and performing genetic studies on the cell-extracted DNA. This method is invasive and can cause abortion after implantation in the uterus. Because of this, 2 noninvasive methods for performing a PGD have been studied: PGD using blastocyst fluid and PGD using embryo culture medium. Objective: The aim of this study is to determine the sensitivity of the polymerase chain reaction (PCR) technique to detect the Y chromosome using cell-free DNA within a culture medium for gender prediction of blastocysts. Materials and Methods: In this study, the gender of 30 embryos on day 5 was determined using embryonic DNA extraction from the culture medium and the PCR technique to evaluate the sex-determining region Y and fragile X mental retardation genes. Then, the accuracy was assessed using ultrasound. Results: The results of the PCR technique showed that 7 embryos were male, but an ultrasound revealed that 13 were male. Conclusion: The given results indicated that, because of the low amount of DNA extracted from the culture medium, the diagnosis of the existence of the Y chromosome by this method is still not accurate enough for detecting the gender of the embryo. [ABSTRACT FROM AUTHOR]

Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the CFTR gene, causing an altered function of the exocrine glands and a subsequent spectrum of hypofunctional and degenerative manifestations. The increasing availability of carrier screening programmes, the enhanced life expectancy of patients due to improved treatment and care strategies and the development of more precise and affordable molecular diagnostic tools have prompted a rise in demand of prenatal diagnosis procedures for at-risk couples, including Preimplantation Genetic Testing (PGT). However, challenges remain: heterogeneity among screening programmes, nuances of variant interpretation and availability of novel treatments demand a considerate and knowledgeable approach to genetic counselling. In this work, we retrospectively evaluated the molecular data of 92 unselected couples who received a diagnosis of CFTR-related status and were referred to the genetics clinic at the University Hospital of Padua for genetic counselling on eligibility for PGT. A total of 50 couples were considered eligible for the procedure based on risk of transmitting biallelic pathogenic variants. We report and discuss our experience with this case series in the context of the Italian medical care system and present an overview of the most relevant issues regarding genetic counselling for PGT in CFTR-related disorders.

Background: GATA1-related cytopenia (GRC) is characterized by thrombocytopaenia and/or anaemia ranging from mild to severe. Haematopoietic stem cell transplantation (HSCT) is a healing therapeutic choice for GRC patients. We identified a novel pathogenic variant (GATA1: c.1019delG) in a boy with GATA1-related cytopenia. Then we performed preimplantation genetic testing (PGT) in this GRC family. After a mosaic embryo transfered, a healthy and HLA-compatible with the proband baby was delivered., Case Presentation: The proband is a 6-year-old boy who was diagnosed to have transfusion-dependent anaemia since 3 year old. Whole-exome sequencing (WES) showed that the proband has a hemizygous variant c.1019delG in GATA1, which is inherited from his mother. His parents decided to undergo PGT to have a health and HLA-compatible offspring. After whole genome amplification (WGA) of biopsied trophectoderm (TE) cells, next generation sequencing (NGS)-based PGT was preformed to analyse embryos on chromosomal aneuploidy, target mutation and HLA typing. There were 3 embryos HLA-matched to the proband. The genotypes of the 3 embryos were heterozygous variant, hemizygous variant, normal respectively. After a heterozygous, mosaic partial trisomy (chr)16, and HLA-matched embryo transfer, a healthy baby was delivered and whose HSCT is compatible with the proband., Conclusions: NGS-based PGT-HLA is a valuable procedure for the treatment of GATA1-related cytopenia caused by GATA1 variants, or other haematological disorders, oncological and immunological diseases. Furthermore, our study reconfirms that mosaic embryos transfer would bring healthy offspring., (© 2024. The Author(s).)

This study aimed to summarize the current knowledge on the benefits of in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic testing for aneuploidy (PGT-A) and to discuss the role of PGT-A in patients of different ages undergoing assisted reproduction. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Registration number: CRD42022354697. Studies were identified by searching the PubMed, Cochrane Library, Google Scholar, Scopus, Embase, and ClinicalTrials databases. Seven meta-analyses were performed with additional stratification of age and prognosis of the women studied. Clinical pregnancy rate per embryo transfer in patients aged >35 years was higher in the PGT-A group (P=0.0002) than in controls. Live birth rate (LBR) per embryo transfer in women 35 years old or younger (P=0.002) was higher in the PGT-A group. The LBR per patient in women aged >35 years was higher in the PGT-A group (P=0.004). The effects of PGT-A on LBR in patients with poor prognosis showed a statistically significant increase (P=0.003). There was no significant difference in the rate between the two groups. PGT-A is effective and can be recommended for patients aged >35 years undergoing assisted reproduction to improve their reproductive outcomes. Moreover, our study showed the possible benefits of PGT-A in patients with a poor prognosis. Overall, our findings suggest that PGT-A is a valuable tool for improving the reproductive outcomes of assisted reproductive procedures in older women and those with a history of pregnancy complications.

Introduction. Most men with non-mosaic Klinefelterʼs syndrome (KS; 47, XXY) have azoospermia, and were until recently considered completely infertile. However, it has been confirmed that some non-mosaic patients had spermatozoa in the ejaculate, although severe oliogasthenoterato-soospermia was present in all of them. Although a high fertilization rate with an intracytoplasmic sperm injection (IC-SI) procedure using sperm from a non-mosaic patient and the cumulative pregnancy rate following in vitro fertilization constitute 53%, the incidence of live births after ICSI using sperm of men with non-mosaic KS is very low: 1 in 8 cases. Case report. At the Clinical Centre of Vojvodina’s Department of Gynecology and Obstetrics, a successful in vitro fertilization treatment was conducted using the sperm of a man with KS non-mosaic syndrome. Preimplantation genetic testing was performed for the embryo selection, and an euploid embryo was transferred in the subsequent natural cycle. Delivery of male newborn was spontaneous, vaginal, with head presentation, after 40 weeks and 3 days. The newborn’s Apgar score was 10/10. His birth weight was 3,950 g, and his length was 55 cm. At 12 months of age, his psychomotor development was assessed as normal on the Brunet-Lézine psychomotor development scale. Conclusion. Due to an increased risk of chromosomal abnormalities (abnormalities of sex or autosomal chromosomes) in embryos from couples with KS males, preimplantation genetic testing is conducted to select a chromosomally normal embryo. This may help achieve pregnancy sooner, decrease the chance of multiple pregnancy and its potential complications, decrease the risk of miscarriage, and reduce the need for invasive prenatal diagnostic procedures and the risks of other complications, as well as the risk of late termination of pregnancy in case of pathological findings of the fetal karyo-type using conventional diagnostic procedures.

Preimplantation genetic diagnosis/screening (PGD/PGS) aims to help couples lower the risks of transmitting genetic defects to their offspring, implantation failure, and/or miscarriage during in vitro fertilization (IVF) cycles. However, it is still being debated with regard to the practicality and diagnostic accuracy of PGD/PGS due to the concern of invasive biopsy and the potential mosaicism of embryos. Recently, several non-invasive and high-throughput assays have been developed to help overcome the challenges encountered in the conventional invasive biopsy and low-throughput analysis in PGD/PGS. In this mini-review, we will summarize the recent progresses of these new methods for PGD/PGS and discuss their potential applications in IVF clinics.

Abstract Background Methylmalonic acidemia (MMA), which is an autosomal recessive metabolic disorder, is caused by mutations in methylmalonyl-CoA mutase (MUT) gene. As a result, the conversion of methylmalonyl-CoA to succinyl-CoA is impaired in this disorder, leading to a wide range of clinical manifestations varying from no signs or symptoms to severe lethargy and metabolic crisis in newborn infants. Since identification of novel mutations in MUT gene can help discover the exact pathogenesis of MMA and also use these disease-causing mutations in prenatal diagnosis, this study was conducted to uncover the possible mutations in an Iranian couple with a deceased offspring clinically diagnosed as having organic acidemia. Moreover, to prevent the occurrence of the mutation in the next pregnancy, we took the advantage of pre-implantation genetic diagnosis (PGD), which resulted in a successful pregnancy. Case presentation The affected individual was a 15-month-old boy who passed away due to aspiration pneumonia. The child presented at the age of 3 months with lethargy, protracted vomiting, hypotonia, and decreased level of consciousness. To find the mutated gene, Next Generation Sequencing (NGS) was performed as carrier testing for the parents and the results revealed a novel (private) heterozygous missense mutation in MUT gene (c.1055A > G, p.Q352R). After performing PGD on three blastomeres, one was identified as being homozygous wild-type that was followed by successful pregnancy. Conclusions Our study identified a novel, deleterious, heterozygous missense mutation in MUT gene in a couple and helps to consider the genetic counselling and prenatal diagnosis more seriously for this family with clinical phenotypes of organic acidemia.

Assisted reproductive technologies (ARTs) are core components of the field of reproductive medicine, encompassing multiple pivotal stages of early development from gamete maturation and fertilization to embryo development. Against the backdrop of a deteriorating trend of global decline in fertility rates, patients with infertility problems increasingly turn to ARTs to realize their dreams of parenthood. However, concomitant with this trend is a growing apprehension regarding the potential adverse effects of ARTs. Herein, we endeavor to discuss several common ARTs procedures utilized in clinical settings and the relevant cutting-edge advancements. The ARTs discussed in the article include in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), biphasic in vitro maturation (biphasic IVM), frozen embryo transfer (FET), preimplantation genetic testing (PGT), non-invasive PGT (niPGT), etc. In addition, we reevaluated their roles within the broader context of assisted reproduction aimed at promoting reproductive health. Additionally, we will delve into the impact of ARTs on the reproductive health of the offspring. By prioritizing the reproductive well-being of both patients and their offspring, the ongoing development and improvement of ARTs to enhance their efficacy and safety will contribute significantly to the advancement of human reproductive health., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Purpose of the Study: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant condition that leads to significant disability and morbidity, characterised by the formation of heterotopic hard tissues within connective tissues. The condition has an incidence of approximately one per two million people worldwide. There is no known single effective treatment available for FOP. We report the world's first case of a healthy infant born following in vitro fertilisation (IVF) and preimplantation genetic testing for monogenic disorder (PGT-M) using Karyomapping for FOP., Case Presentation: A 30-year-old Caucasian female with FOP presented with her partner seeking IVF with PGT-M to achieve a healthy pregnancy with an embryo unaffected by FOP., Methods: The couple underwent IVF and PGT-M using Karyomapping as the testing method. A multi-disciplinary team approach was utilised in planning this case, considering the additional risks of oocyte retrieval, pregnancy and childbirth in women with FOP., Main Findings: The oocyte retrieval was covered with a 5-day course of prednisolone to reduce the risk of a localised inflammatory reaction, which could result in subsequent heterotopic ossification. This was subsequently weaned down with reducing doses every two days. The patient underwent uncomplicated oocyte retrieval, yielding 12 mature oocytes. Following intracytoplasmic sperm injection (ICSI), ten zygotes having two pro-nuclei were cultured, and six underwent trophoectoderm biopsy and vitrification 5-6 days after retrieval. PGT-M via Karyomapping revealed four out of six (66.7%) of blastocysts were not carriers of the maternal high-risk FOP allele. In total, the patient had three separate embryo transfers. Pregnancy was achieved following the third frozen embryo transfer, which went to 37 weeks' gestation, and delivered by Caesarean section. The baby was born in excellent condition and is unaffected by FOP., Conclusion: IVF/ICSI and PGT-M using Karyomapping was successfully implemented to identify embryos carrying the high-risk FOP allele resulting in a healthy livebirth., (© 2024. The Author(s).)

Purpose: To evaluate the use of preimplantation genetic testing (PGT) and live birth rates (LBR) in the USA from 2014 to 2017 and to understand how PGT is being used at a clinic and state level. Methods: This study accessed SART data for 2014 to 2017 to determine LBR and the CDC for years 2016 and 2017 to identify PGT usage. Primary cycles included only the first embryo transfer within 1 year of an oocyte retrieval; subsequent cycles included transfers occurring after the first transfer or beyond 1 year of oocyte retrieval. Results: In the SART data, the number of primary PGT cycles showed a significant monotonic annual increase from 18,805 in 2014 to 54,442 in 2017 (P = 0.042) and subsequent PGT cycles in these years increased from 2946 to 14,361 (P = 0.01). There was a significant difference in primary PGT cycle use by age, where younger women had a greater percentage of PGT treatment cycles than older women. In both PGT and non-PGT cycles, the LBR per oocyte retrieval decreased significantly from 2014 to 2017 (P<0001) and younger women had a significantly higher LBR per oocyte retrieval compared to older women (P < 0.001). The CDC data revealed that in 2016, just 53 (11.4%) clinics used PGT for more than 50% of their cycles, which increased to 99 (21.4%) clinics in 2017 (P< 0.001). Conclusions: A growing number of US clinics are offering PGT to their patients. These findings support re-evaluation of the application for PGT. [ABSTRACT FROM AUTHOR]

ImportanceTo describe the first case of preimplantation genetic diagnosis (PGD) and in vitro fertilization (IVF) performed for the prevention of genetic prion disease in the children of a 27-year-old asymptomatic woman with a family history of Gerstmann-Sträussler-Sheinker syndrome (GSS).ObservationsPGD and fertilization cycles resulted in detection of 6 F198S mutation-free embryos. Of these, 2 were selected for embryo transfer to the patient's uterus, yielding a clinical twin pregnancy and birth of healthy but slightly premature offspring with normal development at age 27 months.Conclusion and relevanceIVF with PGD is a viable option for couples who wish to avoid passing the disease to their offspring. Neurologists should be aware of PGD to be able to better consult at-risk families on their reproductive choices.

Background: Couples who are at risk for having an infant with a serious genetic disorder can benefit from pre-implantation genetic diagnosis (PGD), but many couples still opt for the riskier pre-natal diagnosis (PND). Although couples make this decision together, the male and the female in the couple may have different attitudes toward choosing PGD vs. PND. The objective of this study was to determine if men and women in the same couple with at least one child with a genetic disorder will have significantly different attitudes toward choosing PGD vs. PND. Methodology: In this cross-sectional clinical study, couples with at least one child with a genetic disease attending the King Faisal Specialist Hospital Research Center, Genetic Counseling Clinic (KFSH-RC, GCC), Riyadh, Saudi Arabia were asked to complete an anonymous survey about their attitudes towards PGD vs. PND. The responses were compared between men and women in couples. The study was conducted during May 2017. Results: A total of 38 couples provided complete surveys. In terms of preference for PGD vs. PND, there were no significant differences in aggregate between men and women (p > 0.05). Over half the couples agreed (were concordant) on all statements about PGD vs. PND. An almost equal number of couples with members who disagreed (were discordant) had women preferring PND vs. men preferring PND compared to PGD. Conclusion: This study showed that members of couples sampled were generally in agreement about their preference for PGD vs. PND. Among discordant couples, there was no preference among women for PGD vs. PND. Studies like this are important to help clinicians understand intra-couple dynamics in genetic counseling. [JBCGenetics 2019; 2(1.000): 18-27]

Study Question: To what extent do characteristics of germline genome editing (GGE) determine whether the general public supports permitting the clinical use of GGE?Summary Answer: The risk that GGE would cause congenital abnormalities had the largest effect on support for allowing GGE, followed by effectiveness of GGE, while costs, the type of application (disease or enhancement) and the effect on child well-being had moderate effects.What Is Known Already: Scientific progress on GGE has increased the urgency of resolving whether and when clinical application of GGE may be ethically acceptable. Various expert bodies have suggested that the treatment characteristics will be key in determining whether GGE is acceptable. For example, GGE with substantial risks (e.g. 15% chance of a major congenital abnormality) may be acceptable to prevent a severe disease but not to enhance non-medical characteristics or traits of an otherwise healthy embryo (e.g. eye colour or perhaps in the future more complex traits, such as intelligence). While experts have called for public engagement, it is unclear whether and how much the public acceptability of GGE is affected by the treatment characteristics proposed by experts.Study Design, Size, Duration: The vignette-based survey was disseminated in 2018 among 1857 members of the Dutch general public. An online research panel was used to recruit a sample representing the adult Dutch general public.Participants/materials, Setting, Methods: A literature review identified the key treatment characteristics of GGE: the effect on the well-being of the future child, use for disease or enhancement, risks for the future child, effectiveness (here defined as the chance of a live birth, assuming that if the GGE was not successful, the embryo would not be transferred), cost and availability of alternative treatments/procedures to prevent the genetic disease or provide enhancement (i.e. preimplantation genetic testing (PGT)), respectively. For each treatment characteristic, 2-3 levels were defined to realistically represent GGE and its current alternatives, donor gametes and ICSI with PGT. Twelve vignettes were created by fractional factorial design. A multinominal logit model assessed how much each treatment characteristic affected participants' choices.Main Results and the Role Of Chance: The 1136 respondents (response rate 61%) were representative of the Dutch adult population in several demographics. Respondents were between 18 and 89 years of age. When no alternative treatment/procedure is available, the risk that GGE would cause (other) congenital abnormalities had the largest effect on whether the Dutch public supported allowing GGE (coefficient = -3.07), followed by effectiveness (coefficient = 2.03). Costs (covered by national insurance, coefficient = -1.14), the type of application (disease or enhancement; coefficient = -1.07), and the effect on child well-being (coefficient = 0.97) had similar effects on whether GGE should be allowed. If an alternative treatment/procedure (e.g. PGT) was available, participants were not categorically opposed to GGE, however, they were strongly opposed to using GGE for enhancement (coefficient = -3.37). The general acceptability of GGE was higher than participants' willingness to personally use it (P < 0.001). When participants considered whether they would personally use GGE, the type of application (disease or enhancement) was more important, whereas effectiveness and costs (covered by national insurance) were less important than when they considered whether GGE should be allowed. Participants who were male, younger and had lower incomes were more likely to allow GGE when no alternative treatment/procedure is available.Limitations, Reasons For Caution: Some (e.g. ethnic, religious) minorities were not well represented. To limit complexity, not all characteristics of GGE could be included (e.g. out-of-pocket costs), therefore, the views gathered from the vignettes reflect only the choices presented to the respondents. The non-included characteristics could be connected to and alter the importance of the studied characteristics. This would affect how closely the reported coefficients reflect 'real-life' importance.Wider Implications Of the Findings: This study is the first to quantify the substantial impact of GGE's effectiveness, costs (covered by national insurance), and effect on child well-being on whether the public considered GGE acceptable. In general, the participants were strikingly risk-averse, in that they weighed the risks of GGE more heavily than its benefits. Furthermore, although only a single study in one country, the results suggests that-if sufficiently safe and effective-the public may approve of using GGE (presumably combined with PGT) instead of solely PGT to prevent passing on a disease. The reported public views can serve as input for future consideration of the ethics and governance of GGE.Study Funding/competing Interest(s): Young Academy of the Royal Dutch Academy of Sciences (UPS/RB/745), Alliance Grant of the Amsterdam Reproduction and Development Research Institute (2017-170116) and National Institutes of Health Intramural Research Programme. No competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Leigh syndrome (SL) is a congenital neurometabolic disease included in the group of fatal encephalopathies, with progression and death within 2 years on average. SL is caused by mutations in the DNA that cause changes in the generation of cellular ATP by mitochondria. Mitochondria contain their own DNA (mtDNA) and, unlike nuclear DNA, mtDNA is inherited only from the mother. Women with SL mutations may experience mournful situations when attempting to fulfill the dream of motherhood. Techniques for replacing mutant mtDNA with healthy donor mtDNA provide these women with the possibility of having a genetically related child without SL. The development and clinical application of mtDNA replacement therapies is a reality, and the first baby generated using the technique was born in 2016. However, are these techniques safe? In this article, we review SL and some mtDNA replacement techniques that have been used in humans, which involve zygote pronuclear transfer or oocyte spindle transfer. We conclude that, despite the promising results, it is too early to ensure that mtDNA replacement techniques are clinically applicable to humans. [ABSTRACT FROM AUTHOR]

Mammalian preimplantation embryos often contain chromosomal defects that arose in the first divisions after fertilization and affect a subpopulation of cells - an event known as mosaic aneuploidy. In this issue of the JCI, Chavli et al. report single-cell genomic sequencing data for rigorous evaluation of the incidence and degree of mosaic aneuploidy in healthy human in vitro fertilization (IVF) embryos. Remarkably, mosaic aneuploidy occurred in at least 80% of human blastocyst-stage embryos, with often less than 20% of cells showing defects. These findings confirm that mosaic aneuploidy is prevalent in human embryos, indicating that the process is a widespread event that rarely has clinical consequences. There are major implications for preimplantation genetic testing of aneuploidy (PGT-A), a test commonly used to screen and select IVF embryos for transfer. The application and benefit of this technology is controversial, and the findings provide more cause for caution on its use.

Passionfruit (Passiflora edulis) is a significant fruit crop in the commercial sector, owing to its high nutritional and medicinal value. The advent of high-throughput genomics sequencing technology has led to the publication of a vast amount of passionfruit omics data, encompassing complete genome sequences and transcriptome data under diverse stress conditions. To facilitate the efficient integration, storage, and analysis of these large-scale datasets, and to enable researchers to effectively utilize these omics data, we developed the first passionfruit genome database (PGD). The PGD platform comprises a diverse range of functional modules, including a genome browser, search function, heatmap, gene expression patterns, various tools, sequence alignment, and batch download, thereby providing a user-friendly interface. Additionally, supplementary practical tools have been developed for the PGD, such as gene family analysis tools, gene ontology (GO) terms, a pathway enrichment analysis, and other data analysis and mining tools, which enhance the data's utilization value. By leveraging the database's robust scalability, the intention is to continue to collect and integrate passionfruit omics data in the PGD, providing comprehensive and in-depth support for passionfruit research. The PGD is freely accessible via http://passionfruit.com.cn ., (© 2024. The Author(s).)

Purpose: The primary objective of this investigation is to evaluate how morphological quality affects the pregnancy outcomes in euploid embryos determined by preimplantation genetic testing for aneuploidies (PGT-A). Concurrently, as a secondary objective, we aim to identify which specific aspects of morphological evaluation exert the most significant impact on these outcomes., Methods: A retrospective analysis of 451 single euploid embryo transfer cycles at our clinic was conducted. Embryos were evaluated based on the degree of blastocyst expansion, inner cell mass (ICM), trophectoderm (TE) morphology, and the day of blastocyst vitrification. Outcomes between morphologically low-grade and high-grade embryos were compared. Additionally, the study analyzed which morphological factors most influenced pregnancy outcomes., Results: Pregnancy outcomes were significantly lower in morphologically low-grade blastocysts compared to high-grade ones. Among the morphological evaluations, the ICM assessment was significantly associated with the live birth rate., Conclusion: Our study indicates that the morphological quality of euploid embryos, particularly the evaluation of the ICM, plays a crucial role in IVF-ET success., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Balanced chromosomal translocation is one of chromosomal variations. Carriers of balanced chromosomal translocations have an increased risk of spontaneous miscarriage. To avoid the risk, preimplantation genetic testing (PGT) using comprehensive genomic copy number analysis has been developed. This study aimed to verify whether and how embryos from couples in which one partner is a balanced translocation carrier have a higher ratio of chromosomal abnormalities. A total of 894 biopsied trophectoderms (TEs) were obtained from 130 couples in which one partner was a balanced translocation carrier (Robertsonian translocation, reciprocal translocation, or intrachromosomal inversion) and grouped as PGT-SR. Conversely, 3269 TEs from 697 couples who experienced recurrent implantation failure or recurrent pregnancy loss were included in the PGT-A group. The transferable blastocyst ratio was significantly lower in the PGT-SR group, even when bias related to the sample number and patient age was corrected. Subgroup analysis of the PGT-SR group revealed that the transferable blastocyst ratio was higher in the Robertsonian translocation group. Because the PGT-SR group had a higher proportion of untransferable embryos than the PGT-A group, PGT using comprehensive genomic copy number analysis was more beneficial for balanced translocation carriers than for infertility patients without chromosomal translocations. The frequencies of de novo aneuploidies were further analyzed, and the frequency in the PGT-SR group was lower than that in the PGT-A group. Therefore, we could not confirm the existence of interchromosomal effects in this study., (© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Przeglad Sejmowy is the property of Kancelaria Sejmu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Methylmalonic acidemia (MMA), which is an autosomal recessive metabolic disorder, is caused by mutations in methylmalonyl-CoA mutase (MUT) gene. As a result, the conversion of methylmalonyl-CoA to succinyl-CoA is impaired in this disorder, leading to a wide range of clinical manifestations varying from no signs or symptoms to severe lethargy and metabolic crisis in newborn infants. Since identification of novel mutations in MUT gene can help discover the exact pathogenesis of MMA and also use these disease-causing mutations in prenatal diagnosis, this study was conducted to uncover the possible mutations in an Iranian couple with a deceased offspring clinically diagnosed as having organic acidemia. Moreover, to prevent the occurrence of the mutation in the next pregnancy, we took the advantage of pre-implantation genetic diagnosis (PGD), which resulted in a successful pregnancy. Case presentation: The affected individual was a 15-month-old boy who passed away due to aspiration pneumonia. The child presented at the age of 3 months with lethargy, protracted vomiting, hypotonia, and decreased level of consciousness. To find the mutated gene, Next Generation Sequencing (NGS) was performed as carrier testing for the parents and the results revealed a novel (private) heterozygous missense mutation in MUT gene (c.1055A > G, p.Q352R). After performing PGD on three blastomeres, one was identified as being homozygous wild-type that was followed by successful pregnancy. Conclusions: Our study identified a novel, deleterious, heterozygous missense mutation in MUT gene in a couple and helps to consider the genetic counselling and prenatal diagnosis more seriously for this family with clinical phenotypes of organic acidemia. [ABSTRACT FROM AUTHOR]

Objectives: To report the case of a patient with mosaic Turner syndrome who underwent assisted reproduction treatment with preimplantation genetic testing for aneuploidy and gave birth to a healthy baby girl with normal karyotype; and to conduct a review of the literature on the usefulness of preimplantation genetic diagnosis in women with Turner syndrome. Materials and methods: A case of a 27 year-old woman diagnosed with mosaic Turner syndrome and secondary altered ovarian reserve, seen in a referral center for infertility management in Medellín, Colombia. The patient underwent in vitro fertilization followed by pre-implantation genetic testing to prevent transmission of Turner syndrome to her progeny. A literature search was conducted in the Medline via PubMed, Clinical Key, OVID, Embase, Lilacs, SciELO and Oxford Journals databases using the following terms: "Turner Syndrome," "Mosaic Turner," "Preimplantation Genetic Screening," "Preimplantation Genetic Testing," "Preimplantation Genetic Diagnosis," "Pregnancy," "Successful pregnancy." Inclusion criteria were case series and case reports, cohort studies and review articles published between January 1980 and June 2017 that included women with Turner syndrome achieving pregnancy by means of in vitro fertilization techniques with their own oocytes and who had undergone embryo biopsy for preimplantation genetic diagnosis. The search was limited to articles in Spanish and English. Results: one study met the inclusion criteria. Both in this report and in our case, patients with mosaic Turner syndrome underwent several cycles of intracytoplasmic sperm injection (ICSI) with their own eggs, then performed embryonic biopsy for preimplantation genetic analysis using different techniques. In both cases, euploid embryos were transferred to the uterus with the subsequent birth of healthy girls with normal karyotype. Conclusion: Patients with mosaic Turner syndrome could benefit from preimplantation biopsy and genetic analysis to prevent transmission of the genetic defect to their progeny. [ABSTRACT FROM AUTHOR]

Background: Autosomal recessive polycystic kidney disorder (ARPCKD) is one of the most prevalent hereditary disorders in neonates and children. Its frequency is between 1/6000 to 1/55000 births. In the most severe cases, it can be diagnosed prenatally by the presence of enlarged, echogenic kidneys and oligohydramnios. However, in the milder forms, clinical manifestations are usually detected in neonatal and childhood period. PKHD1 gene located on chromosome 6 is linked with this disorder. About half of detected mutations in this gene are missense ones. The largest protein product of this gene is called the FPC/polyductin complex (FPC). It is a single-membrane spanning protein whose absence leads to abnormal ciliogenesis in the kidneys. Case presentation: Here we present a 5-year-old female patient affected with ARPCKD. She has been born to a non-consanguineous healthy Iranian parents. No similar disorder has been seen in the family. Prenatal history has been normal. In order to find the genetic background, DNA was extracted from patient's peripheral blood lymphocytes. PKHD1 gene exons and exon-intron boundaries were sequenced using next generation sequencing platform. Two novel variants have been detected in compound heterozygote state in the patient (c.6591C>A, c.8222C>A). Bioinformatics tools predicted these variants to be pathogenic. Conclusion: In the present study, we detected two novel variants in PKHD1 gene in a patient with ARPCKD. The relatively mild phenotype of this patient is in accordance with the missense mutations found. Molecular genetic tools can help in accurate risk assessment as well as precise genotype-phenotype correlation establishment in families affected with such disorder to decrease the birth of affected individuals through preimplantation genetic diagnosis or better management of disorder.