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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.

Mitochondrial diseases are distinct types of metabolic and/or neurologic abnormalities that occur as a consequence of dysfunction in oxidative phosphorylation, affecting several systems in the body. There is no effective treatment modality for mitochondrial disorders so far, emphasizing the clinical significance of preventing the inheritance of these disorders. Various reproductive options are available to reduce the probability of inheriting mitochondrial disorders, including in vitro fertilization (IVF) using donated oocytes, preimplantation genetic testing (PGT), and prenatal diagnosis (PND), among which PGT not only makes it possible for families to have genetically-owned children but also PGT has the advantage that couples do not have to decide to terminate the pregnancy if a mutation is detected in the fetus. PGT for mitochondrial diseases originating from nuclear DNA includes analyzing the nuclear genome for the presence or absence of corresponding mutations. However, PGT for mitochondrial disorders arising from mutations in mitochondrial DNA (mtDNA) is more intricate, due to the specific characteristics of mtDNA such as multicopy nature, heteroplasmy phenomenon, and exclusive maternal inheritance. Therefore, the present review aims to discuss the utility and challenges of PGT as a preventive approach to inherited mitochondrial diseases caused by mtDNA mutations. [ABSTRACT FROM AUTHOR]

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 is available to couples at risk of conceiving a pregnancy affected with a known genetic disorder. Assisted reproductive techniques are used in combination with micromolecular diagnostic technologies to recognise at-risk embryos with pathogenic genetic variants at the pre-implantation stage using polar body, blastomere or trophectoderm biopsy. This review will discuss the varying genetic disorders diagnosed by Pre-Implantation Genetic Diagnosis, as well as the ethical, legal and safety implications of the process. Pioneering advances in molecular biology and cytogenomics have been utilised to expand the spectrum of genetic disorders detected. [ABSTRACT FROM AUTHOR]

Mutations in mitochondrial DNA (mtDNA) may lead to a range of mitochondrial diseases that are related to the damage of the mitochondrial respiratory chain. These mitochondrial diseases are characterized by early onset, difficult-to-cure and maternal inheritance. Mutations at site 8 344 in the mitochondrial tRNA lysine gene can result in the reduced translation of the protein encoded by mtDNA and an inadequate energy supply, leading to myoclonic epilepsy associated with ragged red fiber (MERRF) syndrome, with severe myoclonic symptoms, seizures and ataxia. Another characteristic lesion is multiple symmetric lipomatosis (MSL) in the posterior neck and upper back. Among all of pathogenic mtDNA mutations, m.8344A>G mutations were accounted for about 4% . Nuclear gene modification and environmental factors may be involved in the pathogenesis of m.8344A>G mutation. At present, the specific treatment methods for MERRF are lacking. Preimplantation genetic diagnosis and mitochondrial transplantation based on assisted reproductive technology are expected to be new methods for the treatment of this kind of mitochondrial genetic diseases, but the safety and effectiveness still need to be further verified. [ABSTRACT FROM AUTHOR]

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

Objective: To investigate the clinical outcomes of preimplantation genetic testing (PGT) in patients with autosomal dominant polycystic kidney disease (ADPKD) associated with male infertility. Methods: From March 2020 to December 2021, 7 patients with ADPKD associated with male infertility were conducted PGT treatment in the center for reproduction and genetics of the Affiliated Suzhou Hospital of Nanjing Medical University. Data on imaging, sperm quality, sperm ultrastructure, genetic etiology, and preimplantation genetic analysis were retrospectively analyzed. Results: All 7 patients showed different degrees of oligozoospermia, and the PKD1 gene heterozygous mutation. The majority of patients showed dilatation or cystic lesions of the reproductive tract, and the disturbed partially ultrastructure of sperm flagellum. Five clinical pregnancies and successful births were achieved after assisted reproduction in 7 patients. Conclusions: The results of genetic testing can guide the treatment in patients with ADPKD associated with male infertility, and PGT can improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective To analyze the difference in clinical diagnosis results and embryo transfer（ET） outcomes of preimplantation genetic testing（PGT） between the different genders carriers of balanced translocations and Robertsonian translocations. Methods PGT cycles with one of couples as carriers of chromosomal translocation were conducted from October 2018 to August 2022 in the reproductive center of the Nanjing Maternity and Child Health Care Hospital. Single nucleotide polymorphisms（SNP array） or next generation sequencing technology（NGS） was applied to analyze the chromosomes of trophoblast cells. Normal blastocysts rate and cumulative clinical pregnancy rate of different gender carriers of balanced translocations and Robertsonian translocations were compared. Results A total of 129 couples were included, 61 male carriers and 68 female carriers. The normal embryo rate of male carriers was significantly higher than that of female carriers（30.7% vs. 25.1%, P＜0.05）, but no difference in cumulative clinical pregnancy rate. Further analysis was conducted according to different types of translocations. A significant difference was found in normal blastocysts rate between balanced translocations and Robertsonian translocations（24.5% vs. 35.8%, P＜0.01）; There were obvious differences between different genders in the cumulative live birth rate of balanced translocations（81.3% vs. 47.4%, P＜0.01） and live birth weight of Robertsonian translocations（3 325.7±173.5 vs. 3 651.3±270.7, P＜0.01）; However, there was no significant difference in cumulative clinical pregnancy rate between different genders in two types of translocations（P＞0.05）. Conclusion The normal embryo rate of male carriers was significantly higher than that of female carriers; The normal blastocysts rate of balanced translocations was significantly lower than that of Robertsonian translocations; The cumulative live birth rate of male carriers was significantly higher than that of female carriers in balanced translocations; However, the live birth weight of male carriers was significantly lower than that of female carriers in Robertsonian translocations. [ABSTRACT FROM AUTHOR]

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.

Objective: To explore the safety of preimplantation genetic testing (PGT) in frozen -thawed embryos and its effects on the clinical pregnancy outcome. Methods: From August 2016 to December 2021, a total of 95 clinical cases of PGT in frozen-thawed embryos were collected from the Center of Reproductive Medicine, Women′s Hospital of Nanjing Medical University (referred to as the frozen-thawed embryos PGT group, 37 cases had been transplanted up to December 31，2021) and 145 clinical cases of PGT in fresh embryos during the same period (referred to as the fresh-embryos PGT group, 95 cases had been transplanted). The differences in PGT results and the clinical pregnancy outcome of transplanted cases were analyzed between the two groups. Results: ① In 145 cases of the fresh-embryos PGT group, 742 blastocysts were biopsied and 283 euploid embryos were obtained; In 95 cases of the frozen-thawed embryos PGT group, 279 blastocysts were biopsied and 90 euploid embryos were obtained. There was no significant difference in the euploid embryos rates between the two groups (38.14% vs. 32.26%, P=0.082). ② There were no significant differences in the embryo implantation rate (56.84% vs. 54.05%), clinical pregnancy rate (56.84% vs. 54.05%), miscarriage rate (9.26% vs. 15.00%), live birth rate (51.58% vs. 45.95%) and the early birth rate (8.16% vs. 11.76%) between the two groups (all P＞0.05). Conclusions: PGT in the frozenthawed embryos is consistent with PGT in the fresh embryos about diagnostic result and pregnancy outcome. Therefore, PGT in the frozen -thawed embryos can be used as a relatively safe treatment under some special circumstances. [ABSTRACT FROM AUTHOR]

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]

Objective: To analyze the influence of three common schemes of endometrial preparation on the pregnancy outcome and related influencing factors during the frozen-thawed embryo transfer (FET) cycle after preimplantation genetic testing (PGT), so as to provide a reference for the assisted reproduction treatment of PGT patients. Methods: The clinical data and pregnancy outcomes of 195 patients with 219 cycles of FET assisted by PGT from January 2017 to January 2022 at the First Clinical Medical College of Lanzhou University were analyzed retrospectively, including the cycles of PGT for aneuploidies (PGT-A), PGT for monogenetic (PGT-M), and PGT for structural rearrangements (PGT-SR). According to the endometrial preparation schemes, these cycles were divided into three groups: the natural cycle group (NC group, 56), the gonadotropin releasing hormone agonist (GnRHa) combined with hormone replacement therapy (HRT) cycle group (GnRHa+HRT group, 102) and the simple HRT cycle group (61). The general clinical data and pregnancy outcomes of the three groups were compared, and the influencing factors of live birth were analyzed by logistic regression. Results: The NC group, GnRHa+HRT group and HRT group all achieved higher clinical pregnancy rate (64.29%, 80.39%, 73.77%, P＞0.05) and live birth rate (83.33%, 85.37%, 84.44%, P＞0.05). The difference of PGT methods used in the three groups was statistically significant (P=0.002). The ratio of patients receiving PGT-SR in the NC group was higher than that in GnRHa+HRT group (P＜0.05). The ectopic pregnancy rate in the NC group was higher than that in the other two groups (P＜0.05). There were significant differences in the BMI, number of oocytes retrieved, number of transferable embryos and number of high-quality blastocysts between the live birth group and the non live birth group (P＜0.05). In addition to the above four factors, the adverse pregnancy history and total number of blastocysts (P＜0.2) of the two groups were included in the logistic regression analysis. It was found that only the number of high-quality blastocysts had an impact on the pregnancy outcomes, and that the number of high-quality blastocysts ＞2 was a protective factor for the outcome of live birth of PGT patients (OR=0.480, P＜0.05). Conclusions: The clinical pregnancy rate and live birth rate of three FET endometrial preparation protocols are similar, but the ectopic pregnancy rate in the NC group is higher. It should be noted that the BMI, number of oocytes retrieved, number of transferable embryos and number of high-quality blastocysts may jointly affect the outcome of live birth of PGT patients, especially the number of high-quality blastocysts, so as to improve the live birth rate of PGT patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical value of the re -biopsied blastocysts after the first test - unknown preimplantation genetic testing (PGT) cycles, and the effect of the re-biopsied blastocysts on the clinical outcomes of embryo transfer. Methods: The pregnancy outcomes of the 107 re-biopsied blastocysts after the first test -unknown of 75 PGT cycles of 2 199 PGT cycles from September 2015 to May 2021 in the clinical reproductive center of The First Affiliated Hospital with Nanjing Medical University were retrospectively analyzed. Results: In 75 PGT cycles, 107 blastocysts were categorized as unknown diagnosis. Among them, 96 embryos were resuscitated and biopsied, and PGT was successfully carried out in 86 embryos finally. After next -generation sequencing analysis, 46 blastocysts were confirmed as transplantable embryos (39 euploid embryos and 7 chimeric embryos). In 27 warming cycles, 24 blastocysts were survived and entered the transfer cycle. After the second biopsy, the survival rate of embryo resuscitation was 88.89% (24/27), the clinical pregnancy rate 50% (12/24), and the live birth rate 45.8% (11/24). There was one case of early abortion. Conclusions: The blastocysts with unknown diagnosis in the first round of PGT could withstand the second round of biopsy, freezing and resuscitation, and still possessing certain transferable embryos and live birth rate after transplantation. [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]

Objective: To analyze the outcomes of preimplantation genetic testing (PGT) in infertile couples with sex chromosome abnormalities and to explore the risk of embryo sex chromosome abnormalities, so as to evaluate the application value of PGT in the related populations. Methods: The embryo chromosome and embryo transfer outcomes of couples with sex chromosome abnormalities treated with PGT were analyzed retrospectively. The whole genome low depth sequencing was used to analyze the alterations of chromosomal copy number after whole genome amplification of biopsy material from the blastocyst stage. In the freeze-thaw cycles, the clinical pregnancy outcomes of embryo transfer were calculated. Results: A total of 77 detectable blastocysts were obtained in 24 controlled ovulation stimulation cycles from 23 couples with sex chromosome abnormalities, including 6 couples with 47,XYY and mosaicism, 2 couples with 47,XXY and mosaicism, 4 couples with 47,XXX, 8 couples with 45,X mosaicism, 3 couples with X -chromosomal segmental aneuploidy. In 77 detectable blastocysts, 76 (98.70%) were definitively diagnosed, including 40 (52.63%) euploid, 13 (17.10%) mosaic embryos and 23 (30.26%) completely aneuploid embryos. All of abnormal embryos were X-chromosomal segmental aneuploidy in the 3 patients with X-chromosomal segmental aneuploidy; whereas a total of 3(3.95%) sex chromosome mosaic aneuploidies were found in the couples with the other sex chromosome numerical abnormality. Nine (50.00%) healthy live births were obtained during a total of 18 freeze -thaw cycles. Conclusions: The couples with sex chromosome numerical aneuploidy have a low risk of embryonic sex chromosome abnormalities, and PGT is not an essential treatment option; whereas the couples with sex chromosome segmental aneuploidy are at high risk of embryonic sex chromosome abnormalities, and PGT may be considered in combination with ovarian function profile and adequate informed consent from the patients, reducing the risk of sex chromosome abnormalities in offspring. [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]

Purpose: To compare differences in euploidy rates for blastocysts in preimplantation genetic testing for aneuploidy (PGT-A) cycles after gonadotropin-releasing hormone agonist (GnRH-a) long and short protocols, GnRH-antagonist (GnRH-ant) protocol, progestin-primed ovarian stimulation and mild stimulation protocols, and other ovary stimulation protocols., Methods: This was a retrospective cohort study from the Assisted Reproductive Medicine Department of Shanghai First Maternity and Infant Hospital. A total of 1657 PGT-A cycles with intracytoplasmic sperm injection after different controlled ovary hyperstimulation protocols were analyzed, and a total of 3154 embryos were biopsied. Differences in euploidy rate per embryo biopsied, embryo euploidy rate per oocyte retrieved and cycle cancellation rate were compared., Results: For the PGT-A cycles, the euploidy rate per embryo biopsied was lower in the GnRH-ant protocol than in the GnRH-a long protocol (53.26 vs. 58.68%, respectively). Multiple linear regression showed that the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied (β =  -0.079, p = 0.011). The euploidy rate per embryo biopsied was not affected by total gonadotropin dosage, duration of stimulation and number of oocytes retrieved. The embryo euploidy rate per oocyte retrieved was similar in all protocols and was negatively correlated with the total number of oocytes retrieved (β =  -0.003, p = 0.003)., Conclusion: Compared with the GnRH-a long protocol, the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied. The total gonadotropin dosage, duration of stimulation and number of oocytes retrieved did not appear to significantly influence euploidy rates., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To study the association between the blastulation rate, the presence of 1 pronucleus (1PN) zygotes, and the ploidy of the cohort of blastocysts., Methods: A cross-sectional study using the existing databases of 2 university fertility centres in Canada. We included 345 cycles from 235 couples who underwent next-generation sequencing preimplantation genetic testing for the detection of aneuploidy in the study., Results: A total of 1456 blastocysts were biopsied. In multivariate analysis, only female age and the number of 1PN/2PN embryos showed a negative association with euploid ratio. Surprisingly, when the analysis was limited to cycles with no delayed blastulation, the blastulation rate was also negatively associated with the euploid ratio., Conclusions: This study sheds some light on the stages of early embryo development. Further study on the mechanisms governing embryo development and the different cell cycle checkpoints in embryo development is warranted., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Purpose: Investigate patient preferences in embryo selection for transfer regarding quality versus sex in IVF/ICSI cycles with PGT-A and assess associated clinical implications., Methods: Retrospective cohort study at a university fertility practice from January 2012 to December 2021. Included were patients undergoing single frozen euploid transfers with at least one embryo of each sex available. Primary outcomes were preference for embryo selection (quality vs. sex) and sex preference (male vs. female). Trends over 10 years were evaluated and clinical outcomes, including clinical pregnancy rate (CPR), sustained implantation rate (SIR), and live birth rate (LBR), were compared., Results: A total of 5,145 embryo transfer cycles were included; 54.5% chose the best-quality embryo, while 45.5% selected based on sex. Among those choosing based on sex, 56.5% chose male embryos and 43.5% chose female. Preference for quality remained consistent over the decade (p = 0.30), while male embryos were consistently favored (p = 0.64). Best-quality embryos had higher grades (p < 0.001). Clinical outcomes were similar between groups (CPR: 74.4% vs. 71.9%, p = 0.05; SIR: 64.9% vs. 63.4%, p = 0.26; LBR: 58.8% vs. 56.7%, p = 0.13), and between male and female embryo selections., Conclusions: Sex selection remains common, with 45.5% selecting embryos based on sex, predominantly favoring males. This trend persisted over 10 years, with comparable clinical outcomes regardless of selection criteria., (© 2024. The Author(s).)

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).)

Objectives: To study the effect of double trophectoderm biopsy on clinical outcomes following single euploid blastocyst transfer., Study Design: Retrospective cohort study of 2046 single euploid frozen-thawed blastocyst transfers from January 2015 to June 2022 in a single centre. All patients undergoing a frozen-thawed embryo transfer (FTET) cycle with euploid blastocysts, biopsied for any indication, were included. The outcomes were compared for blastocysts which were biopsied and vitrified once (Group 1, n = 1684), biopsied once but vitrified twice (Group 2, n = 312) and biopsied and vitrified twice (Group 3n = 50). We adjusted for confounders and performed subgroup analysis for PGT-A, PGT-M and PGT-SR cycles. The primary outcome was live birth rate. Secondary outcomes included pregnancy, clinical pregnancy, birthweight and sex ratio., Results: After adjusting for confounders (previous failed euploid implantations, embryo quality and day of biopsy), embryos which were biopsied twice had lower OR for clinical pregnancy (0.48, CI 0.26-0.88, p = 0.019) and for live birth (0.50 CI 0.27-0.92, p = 0.025) compared to controls. Embryos which were biopsied once but vitrified twice had no different ORs for all reproductive outcomes compared to controls. No significant difference was observed for neonatal birthweight or sex ratio amongst the three groups. This is a retrospective single centre study with inherent bias and results may not be transferable to all settings., Conclusion: This study is the largest to date assessing the outcomes of FTET cycles following double trophectoderm biopsy. The results are in keeping with the existing literature and can be incorporated into patient counselling. Whilst double biopsy seems to adversely impact LBR, it is only one of the many factors that can affect success rates. The subfertility background and embryo characteristics should not be overlooked. This study provides reassuring evidence since double biopsied embryos still result in live births with no difference in sex ratio or birthweight. However, long term follow up of the off-springs is lacking and should be reported in future studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors work in a private clinic that offers fertility treatment including PGT-A and PGT-M/SR., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

Research Question: What is the clinical outcome of the first attempt at conception between two embryo selection methods, blastocyst morphology and preimplantation genetic testing for aneuploidies (PGT-A), chosen at the initial physician IVF consultation?, Design: In this prospective analysis, a clinical decision regarding embryo selection, blastocyst morphology (group A) or PGT-A (group B) was made during initial physician IVF consultation. Female infertility patients were matched based on maternal age (mean 32.6 ± 3.6 years; range 25-43 years) and a similar time frame of oocyte retrieval. The primary outcome was live birth rate from the initial consultation to the first conception attempt for all female patients and for a subset analysis of patients aged <35 years., Results: The inclusion of PGT-A (group B) for embryo selection during the initial physician IVF consultation resulted in 23 additional women out of the total 100 achieving a healthy live birth following the first conception attempt in this maternally age-matched infertile population (group B = 72.0% versus group A = 49.0%; P = 0.0014). This same benefit was observed for age-matched, younger infertility patients (<35 years), with live birth rates from the initial consultation being significantly higher when the upfront clinical decision included PGT-A for embryo selection (group B = 76.7% versus group A = 53.4%; P = 0.0052). Interestingly, 17 women from group B would have received an aneuploid embryo transfer if selection had been determined by blastocyst morphology alone, as their best-grade embryo was aneuploid., Conclusions: This prospective analysis from the initial physician IVF consultation revealed that euploid embryo selection significantly improved live birth potential with the first conception attempt, even for younger women with infertility., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

This article considers the addition of comprehensive 24-chromosomal microarray (CMA) analysis of products of conception (POC) to a standard evaluation for recurrent pregnancy loss (RPL) to help direct treatment towards expectant management versus IVF with preimplantation genetic testing for aneuploidies (PGT-A). The review included retrospective data from 65,333 miscarriages, a prospective evaluation of 378 couples with RPL who had CMA testing of POC and the standard workup, and data from an additional 1020 couples who were evaluated for RPL but did not undergo CMA testing of POC. Aneuploidy in POC explained the pregnancy loss in 57.7% (218/378) of cases. In contrast, the full RPL evaluation recommended by the American Society for Reproductive Medicine identified a potential cause in only 42.9% (600/1398). Combining the data from the RPL evaluation and the results of genetic testing of POC provides a probable explanation for the loss in over 90% (347/378) of women. Couples with an unexplained loss after the standard evaluation with POC aneuploidy accounted for 41% of cases; PGT-A may be considered after expectant management. Conversely, PGT-A would have a limited role in those with a euploid loss and a possible explanation after the standard workup. Categorizing a pregnancy loss as an explained versus unexplained loss after the standard evaluation combined with the results of CMA testing of POC may help identify patients who would benefit from expectant management versus PGT-A., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mosaicism for unbalanced chromosomal rearrangements segmental mosaicism (SM) is rare, both in patients referred for cytogenetic testing and in prenatal diagnoses. In contrast, in preimplantation embryos SM is a frequent finding and, therefore, is even more challenging. However, there is no consistency among results of published studies on the clinical outcomes of embryos with SM, primarily due to the small number of reported cases. Moreover, there is the problem of predicting the potential for the optimal development of a mosaic embryo to a healthy individual. Therefore, we suggested comparing factors predisposing to favorable and poor prognoses, identified in postnatal and prenatal cohorts of SM carriers, with those obtained from studies on preimplantation embryos. We analyzed 580 published cases of SM including (i) postnatally diagnosed affected carriers, (ii) clinically asymptomatic carriers, (iii) prenatally diagnosed carriers, and (iv) miscarriages. We observed a concordance with preimplantation diagnoses regarding the clinical significance of the extent of mosaicism as well as a predominance of deletions over other types of rearrangements. However, there is no concordance regarding excessive involvement of chromosomes 1, 5, and 9 in unbalanced rearrangements and a preferential involvement of larger chromosomes compared to short ones. Paternal age was not found to be associated with SM in postnatally disease-defined individuals. We have identified maternal age and preferential involvement of chromosome 18 in rearrangements associated with clinical manifestations. Male predominance was found among normal pregnancy outcomes and among disease-defined carriers of rearrangements resulting in a gain of genomic material. Female predominance was found among abnormal pregnancy outcomes, among disease-defined carriers of loss and gain/loss rearrangements, and among transmitting carriers of gonadal SM, both affected and asymptomatic. According to data obtained from "post-embryo" studies, clinical manifestations of chromosomal imbalance are associated with a high proportion of abnormal cells, female gender, the type of rearrangement and involved chromosome(s), and maternal age. We believe these data are instructive in the challenging medical genetic counseling of parents faced with no option other than transfer of an embryo with segmental mosaicism. [ABSTRACT FROM AUTHOR]

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.

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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.

Research Question: Conflicting data exists regarding whether a younger age of donors has a negative influence on the outcomes of oocyte donation cycles. Is there any correlation between a younger age of donors and the rate of embryonic aneuploidy in oocyte donation cycles?, Design: Retrospective study including 515 oocyte donation cycles carried out between February 2017 and November 2022. Comprehensive chromosomal screening was performed on 1831 blastocysts. 1793 had a result which were categorised into groups based on the age of the donor: 18-22 (n = 415), 23-25 (n = 600), 26-30 (n = 488), and 31-35 years (n = 290). The analysis aimed to determine the percentage of biopsy samples that were euploid and the number that were aneuploid, relative to the age group of the oocyte donor. Additionally, linear regression was employed to examine the relationship between age and the proportion of aneuploid embryos, while controlling for relevant variables., Results: Aneuploidy increased predictably with donor age: 18-22 years: 27.5 %; 23-25 years: 31.2 %; 26-30 years: 31.8 %; and 31-35 years: 38.6 %. In the donor group aged 31-35 years, a higher percentage of aneuploid embryos was observed compared to younger donors in univariate analysis (OR: 1.66, 95 % CI: 1.21-2.29, p = 0.002) and multivariate logistic analysis (OR: 2.65, 95 % CI: 1.67-4.23, p < 0.001). The rates of embryonic mosaicism revealed no significant differences., Conclusion: The lowest risk of embryonic aneuploidy was found among donors aged <22 years. Conversely, an elevated prevalence was evident within the donor group aged 31-35 years, in contrast to the younger cohorts. The incidence of mosaic embryos remained consistent across all age groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate whether trophectoderm biopsy increases the risk of adverse maternal and neonatal outcomes in intracytoplasmic sperm injection (ICSI) single frozen-thawed blastocyst transfer cycles., Methods: This respective cohort study enrolled 3373 ICSI single frozen-thawed blastocyst transfer cycles with and without trophectoderm biopsy. Statistical methods including univariate logistic regression analysis, multivariate logistic regression analysis, and stratified analyses were performed to explore the impact of trophectoderm biopsy on adverse maternal and neonatal outcomes., Results: The rates of adverse maternal and neonatal outcomes were comparable between the two groups. Univariate analysis showed that the live birth rate (45.15% vs. 40.75%; P = 0.010) in the biopsied group was statistically higher than that in the unbiopsied group, and the rates of miscarriage (15.40% vs. 20.00%; P = 0.011) and birth defects (0.58% vs. 2.16%; P = 0.007) were statistically lower in the biopsied group. After adjusting for confounding factors, the rates of miscarriage (aOR = 0.74; 95% CI = 0.57-0.96; P = 0.022) and birth defects (aOR = 0.24, 95% CI = 0.08-0.70, P = 0.009) in the biopsied group were significantly lower than those in the unbiopsied group. Stratified analyses showed that the birth defects rate after biopsy was significantly reduced in the subgroups of age < 35 years old, BMI ≥ 24 kg/m 2 , artificial cycle with downregulation, poor-quality blastocysts, and Day 5 poor-quality blastocysts., Conclusion: Preimplantation genetic testing (PGT) with trophectoderm biopsy does not increase the risk of adverse maternal and neonatal outcomes in ICSI single frozen-thawed blastocyst transfer cycles, and PGT can effectively reduce the rates of miscarriage and birth defects., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Preimplantation genetic diagnosis (PGD) has been used not only to avoid genetic diseases and increase conception success rates but also to perform non-medical sex selection, particularly in the surging cross-border reproductive care (CBRC). In the context of commercialised biomedicine, assisted reproductive technologies, such as lifestyle sex selection, have been tailored to meet intended parents' preferences. However, there is a lack of analysis on how individuals' reproductive decisions on PGD-assisted sex selection were shaped within the sociocultural norms and CBRC. This article explores Taiwanese gay fathers' navigations on sex selection while seeking third-party reproduction overseas because of local legal constraints. Drawing on in-depth interviews with 53 gay fathers (to-be), I analysed how 'individual preferences' were dynamically shaped by local sociocultural norms and embedded within transnational settings of routinising PGD in chosen repro-destinations. The findings showed that gay fathers mobilised strategic discourses on non-medical sex selection from both the local and the global to negotiate their decisions in coherence with their LGBTQ+ identity and their role as sons carrying familial responsibility to procreate male heirs. This article proposed a nuanced understanding of gay fathers' reproductive practices of 'gendering the beginning of life' through PGD-assisted sex selection., (© 2023 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for the Sociology of Health & Illness.)

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).)

Objective: To carry out preimplantation genetic testing (PGT) for a Chinese pedigree affected with Rett syndrome (RTT)., Methods: A pedigree affected with RTT who had presented at the First Hospital of Jilin University on June 4, 2021 was selected as the study subject. Variant of the MECP2 gene was analyzed by next generation sequencing (NGS) and Sanger sequencing. Direct sequencing was also used to determine the carrier status for the c.925C>T variant of the MECP2 gene in the blastocysts, and Sanger sequencing was used to validate the results. The MECP2 gene and 168 effective single nucleotide polymorphism (SNP) loci within 2 Mb ranges up- and downstream of the gene were used to construct a haplotype for analyzing the variant site in the embryos, and embryos without the variant were subjected to the analysis for chromosomal aneuploidies., Results: PGT analysis revealed that five out of seven blastocysts did not harbor the pathogenic variant. The results of aneuploidy analysis indicated that two out of five blastocysts without the variant were euploid. Following genetic counselling, the couple had opted to transplant the optimal blastocyst. Following clinical pregnancy, prenatal diagnosis showed that the fetus has a normal chromosomal karyotype, and the c.925C>T variant was not detected in the amniotic fluid sample. A healthy girl was born by Cesarean section at full term., Conclusion: NGS can attain efficient PGT detection and reduce the risk of disease recurrence in families affected with RTT.

Purpose: We explored and compared perspectives of reproductive endocrinology and infertility specialists (REIs) and in vitro fertilization (IVF) patients regarding polygenic embryo screening (PES), a new type of preimplantation screening that estimates the genetic chances of developing polygenic conditions and traits in the future., Methods: Qualitative thematic analysis of semi-structured interviews with US-based REIs and IVF patients., Results: Clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more frequently than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer PES to patients or were willing to do so only under certain circumstances, while many patients expressed interest in PES. Both stakeholder groups envisioned multiple potential benefits or uses of PES and raised multiple potential, interrelated concerns about PES., Conclusion: A gap exists between clinician and patient attitudes toward PES; clinicians generally maintained reservations about such screening and patients indicated interest in it. Clinicians and patients sometimes imagined using PES to prepare for the birth of a predisposed or "affected" individual-a rationale that is often associated with prenatal testing. Many clinicians and patients held different attitudes depending on what is specifically screened, despite the sometimes blurry distinction between conditions and traits. Considerations raised by clinicians and patients may help guide professional societies in developing guidelines to navigate the uncertain terrain of PES., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To investigate whether leukocytospermia (defined as the presence of ≥ 1 × 10 6 white blood cells/mL) affects clinical and embryologic outcomes in in vitro fertilization (IVF) cycles with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A)., Methods: This was a retrospective cohort study including 5425 cycles between January 2012 to December 2021 at a single large university-affiliated fertility clinic. The primary outcome was live birth rate (LBR)., Results: The prevalence of leukocytospermia was 33.9% (n = 1843). Baseline characteristics including female age, BMI, AMH, Day 3 FSH, and male partner's age were similar in cycles with and without leukocytospermia. The LBR after the first euploid embryo transfer was similar in those with and without leukocytospermia (62.3% vs. 63% p = 0.625). Secondary outcomes including clinical pregnancy rate (CPR), sustained implantation rate (SIR), fertilization (2PN) rate, blastulation rate, and aneuploidy rate were also evaluated. The CPR (73.3% vs 74.9%, p = 0.213) and SIR (64.6% vs. 66%, p = 0.305) were similar in both groups. The 2PN rate was also similar in both groups (85.7% vs. 85.8%, p = 0.791), as was the blastulation rate per 2PN (56.7% vs. 57.5%, p = 0.116). The aneuploidy rate was not significantly different between groups (25.7% vs 24.4%, p = 0.053). A generalized estimation equation with logistic regression demonstrated that the presence leukocytospermia did not influence the LBR (adjusted OR 0.878; 95% CI, 0.680-1.138)., Conclusion: Leukocytospermia diagnosed just prior to an IVF cycle with PGT-A does not negatively impact clinical or embryologic outcomes., (© 2024. The Author(s).)

Objective: To investigate the reproductive outcomes of balanced reciprocal translocation carriers and evaluate the association between the number of metaphase-II oocytes retrieved and cumulative live birth rates (LBRs)., Methods: This retrospective analysis included 344 preimplantation genetic testing (PGT) for structural rearrangement cycles of 281 couples with balanced reciprocal translocations between January 2018 and January 2021. All patients included in the analysis had either delivered a baby or had used all their embryos after one stimulation cycle. All women were followed up for at least 2 years., Results: After ovarian stimulation and oocyte fertilization, 44.2% of PGT for structural rearrangements cycles achieved a live birth. Carrier's sex and female age did not affect the cumulative LBR of reciprocal translocation carriers. Cumulative LBRs steadily increased with the number of oocytes, reaching 64% when >20 oocytes were retrieved. The cutoff values for achieving at least one live birth were 9.5 metaphase-II (MII) oocytes and 3.5 biopsied embryos., Conclusion: Couples with reciprocal translocations have lower transferable embryo rates and cumulative LBRs. The MII oocytes retrieved may be a crucial factor for cumulative LBRs. A high ovarian response may further increase cumulative LBRs, but avoidance of ovarian hyperstimulation syndrome or other iatrogenic complications should be considered., (© 2024 International Federation of Gynecology and Obstetrics.)

Purpose: To present the developed preimplantation genetic testing (PGT) for spinocerebellar ataxia type 1 (SCA1) and the outcomes of IVF with PGT., Methods: PGT was performed for two unrelated couples from the Republic of Sakha (Yakutia) with the risk of SCA1 in one spouse. We have developed a system for PGT of a monogenic disease (PGT-M) for SCA1, which includes the analysis of a panel of 11 polymorphic STR markers linked to the ATXN1 gene and a pathogenic variant of the ATXN1 gene using nested PCR and fragment analysis. IVF/ICSI programs were performed according to standard protocols. Multiple displacement amplification (MDA) was used for whole genome amplification (WGA) and array comparative genomic hybridization (aCGH) for aneuploidy testing (PGT-A)., Results: Eight STRs were informative for the first couple and ten for the second. Similarity of the haplotypes carrying pathogenic variants of the ATXN1 gene was noted. In the first case, during IVF/ICSI-PGT, three embryos reached the blastocyst stage and were biopsied. One embryo was diagnosed as normal by maternal STR haplotype and the ATXN1 allele. PGT-A revealed euploidy. The embryo transfer resulted in a singleton pregnancy, and a healthy boy was born. Postnatal diagnosis confirmed normal ATXN1. In the second case, two blastocysts were biopsied. Both were diagnosed as normal by PGT-M, but PGT-A revealed aneuploidy., Conclusion: Birth of a healthy child after PGT for SCA1 was the first case of successful preimplantation prevention of SCA1 for the Yakut couple and the first case of successful PGT for SCA1 in Russia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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).)