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Wang L, Wang JY, Zhang Y, Qian C, Wang XH, Ng EHY, Ai A, Chen ZQ. Comparison of the euploidy rate in preimplantation genetic testing for aneuploidy cycles following progestin-primed versus gonadotropin-releasing hormone antagonist protocol: a randomized controlled study. Reprod Biol Endocrinol 2025; 23:67. [PMID: 40361159 PMCID: PMC12070503 DOI: 10.1186/s12958-025-01404-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 04/25/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Progestins can block endogenous luteinizing hormone secretion from the pituitary gland and have shown similar efficacy in terms of collecting competent oocytes and embryos; however, some inconsistencies have been proposed by the previous papers regarding the quality of oocytes and embryos obtained with the use of progestins. This study aimed to compare the euploidy rate between women treated with progestin-primed ovarian stimulation (PPOS) and the gonadotropin-releasing hormone (GnRH) antagonist protocol. METHODS This is a prospective randomized study of 240 infertile women undergoing PGT-A between August 2021 and July 2023. Infertile women with advanced maternal age (38-45 years), recurrent pregnancy loss (≥ 2 or 3 consecutive miscarriages), and repeated implantation failure (≥ 4 embryos replaced or ≥ 2 blastocysts replaced without success) undergoing PGT-A cycles were included. Women were randomly assigned into the PPOS group (n = 120) or the antagonist group (n = 120) according to a computer-generated randomization list. Dydrogesterone 20 mg per day was given from the start of ovarian stimulation until the trigger day in the PPOS group. In the antagonist group, an antagonist 0.25 mg was given daily from the sixth day of ovarian stimulation until the trigger day. The primary outcome measure was the euploidy rate, defined as the number of euploid blastocysts per injected oocyte. RESULTS No significant differences were observed in the demographic and ovarian stimulation characteristics between the two groups. The euploidy rate was comparable between the PPOS and antagonist group (12.5% vs. 16.0% respectively, P > 0.05). No significant differences were observed between the two groups in positive pregnancy test, clinical pregnancy, miscarriage, ectopic pregnancy, or live birth rates per transfer in the first frozen embryo transfer cycles. CONCLUSION Both PPOS and antagonist protocols had similar euploidy rates in PGT-A cycles. TRIAL REGISTRATION Clinicaltrials. gov identifier: NCT04989348 ( https://www. CLINICALTRIALS gov/ ). Trial registration date: Clinicaltrials. gov: 30 July 2021.
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Affiliation(s)
- Lu Wang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China
| | - Jing Yun Wang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China
| | - Yuan Zhang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China
| | - Chen Qian
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China
| | - Xiao Hui Wang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China
| | - Ernest Hung Yu Ng
- Department of Obstetrics and Gynaecology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, People's Republic of China
| | - Ai Ai
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China.
| | - Zhi Qin Chen
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China.
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Berlincourt J, Gächter S, Vayena E, Ormond KE. Experts' perspectives on human gene editing in Switzerland. J Community Genet 2025; 16:83-90. [PMID: 39699768 PMCID: PMC11950446 DOI: 10.1007/s12687-024-00757-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 11/18/2024] [Indexed: 12/20/2024] Open
Abstract
Despite many specialized studies on the views of the public or stakeholders who face inherited conditions that may be treatable by HGE, limited studies have focused on experts' views towards Human Gene Editing (HGE). Therefore, in this study we conducted exploratory interviews with 14 experts (scientists, clinicians, social scientists, lawyers) in Switzerland to assess their views towards HGE and how they expect the Swiss public to view HGE. We found general acceptance of Somatic Gene Editing (SGE), but opinions towards Germline Gene Editing (GGE) were more divided. Participants emphasized patient autonomy and informed decision-making in pursuing gene editing treatments, and described a need for regulation, as with any other new therapy. Only a few participants (mostly lawyers and ethicists) described the regulations that currently prohibit GGE in Switzerland. Some expressed concern that restrictive regulations would lead to healthcare outsourcing and medical tourism to other nearby countries, as it has in the past with other restricted technologies. The analysis explored the unique Swiss context that is shaped by cultural diversity, conservative attitudes towards new medical technologies, and a democratic system that engages the public in policy and law making. Given that our findings identify areas of difference from that published in other countries, we emphasize the value in conducting similar research across different countries in order to achieve a global sense of attitudes towards HGE, so that regulations can be tailored to the diverse needs of citizens around the world.
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Affiliation(s)
- Jade Berlincourt
- Health Ethics and Policy Lab, Health Sciences and Technologies Department ETH Zurich, Zurich, Switzerland
- Health Sciences and Technologies Department, ETH Zurich, Zurich, Switzerland
| | - Sumanie Gächter
- Health Ethics and Policy Lab, Health Sciences and Technologies Department ETH Zurich, Zurich, Switzerland
| | - Effy Vayena
- Health Ethics and Policy Lab, Health Sciences and Technologies Department ETH Zurich, Zurich, Switzerland
| | - Kelly E Ormond
- Health Ethics and Policy Lab, Health Sciences and Technologies Department ETH Zurich, Zurich, Switzerland.
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del Arco de la Paz A, Giménez-Rodríguez C, Selntigia A, Meseguer M, Galliano D. Advancements and Challenges in Preimplantation Genetic Testing for Aneuploidies: In the Pathway to Non-Invasive Techniques. Genes (Basel) 2024; 15:1613. [PMID: 39766880 PMCID: PMC11675356 DOI: 10.3390/genes15121613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 12/08/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
The evolution of preimplantation genetic testing for aneuploidy (PGT-A) techniques has been crucial in assisted reproductive technologies (ARTs), improving embryo selection and increasing success rates in in vitro fertilization (IVF) treatments. Techniques ranging from fluorescence in situ hybridization (FISH) to next-generation sequencing (NGS) have relied on cellular material extraction through biopsies of blastomeres at the cleavage stage on day three or from trophectoderm (TE) cells of the blastocyst. However, this has raised concerns about its potential impact on embryo development. As a result, there has been growing interest in developing non-invasive techniques for detecting aneuploidies, such as the analysis of blastocoel fluid (BF), spent culture medium (SCM), and artificial intelligence (AI) models. Non-invasive methods represent a promising advancement in PGT-A, offering the ability to detect aneuploidies without compromising embryo viability. This article reviews the evolution and principles of PGT-A, analyzing both traditional techniques and emerging non-invasive approaches, while highlighting the advantages and challenges associated with these methodologies. Furthermore, it explores the transformative potential of these innovations, which could optimize genetic screening and significantly improve clinical outcomes in the field of assisted reproduction.
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Affiliation(s)
- Ana del Arco de la Paz
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- IVIRMA Global Research Alliance, IVIRMA Valencia, 46015 Valencia, Spain
| | - Carla Giménez-Rodríguez
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- IVIRMA Global Research Alliance, IVIRMA Valencia, 46015 Valencia, Spain
| | | | - Marcos Meseguer
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- IVIRMA Global Research Alliance, IVIRMA Valencia, 46015 Valencia, Spain
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Lopes LR, Ho CY, Elliott PM. Genetics of hypertrophic cardiomyopathy: established and emerging implications for clinical practice. Eur Heart J 2024; 45:2727-2734. [PMID: 38984491 PMCID: PMC11313585 DOI: 10.1093/eurheartj/ehae421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 12/05/2023] [Accepted: 06/19/2024] [Indexed: 07/11/2024] Open
Abstract
Pathogenic variation in genes encoding proteins of the cardiac sarcomere is responsible for 30%-40% of cases of hypertrophic cardiomyopathy. The main clinical utility of genetic testing is to provide diagnostic confirmation and facilitation of family screening. It also assists in the detection of aetiologies, which require distinct monitoring and treatment approaches. Other clinical applications, including the use of genetic information to inform risk prediction models, have been limited by the challenge of establishing robust genotype-phenotype correlations with actionable consequences, but new data on the interaction between rare and common genetic variation, as well as the emergence of therapies targeting disease-specific pathogenic mechanisms, herald a new era for genetic testing in routine practice.
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Affiliation(s)
- Luis R Lopes
- Barts Heart Centre, St. Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, UK
- Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, 5 University St, London WC1E 6JF, UK
| | - Carolyn Y Ho
- Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, USA
| | - Perry M Elliott
- Barts Heart Centre, St. Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, UK
- Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, 5 University St, London WC1E 6JF, UK
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Fernandes SLE, de Carvalho FAG. Preimplantation genetic testing: A narrative review. Porto Biomed J 2024; 9:262. [PMID: 38993950 PMCID: PMC11236403 DOI: 10.1097/j.pbj.0000000000000262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 06/18/2024] [Indexed: 07/13/2024] Open
Abstract
Preimplantation genetic testing (PGT) is a diagnostic procedure that has become a powerful complement to assisted reproduction techniques. PGT has numerous indications, and there is a wide range of techniques that can be used, each with advantages and limitations that should be considered before choosing the more adequate one. In this article, it is reviewed the indications for PGT, biopsy and diagnostic technologies, along with their evolution, while also broaching new emerging methods.
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Affiliation(s)
- Sofia L. E. Fernandes
- Genetics—Department of Pathology, Faculty of Medicine, University of Porto, Porto, Portugal
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Tian Y, Li M, Yang J, Chen H, Lu D. Preimplantation genetic testing in the current era, a review. Arch Gynecol Obstet 2024; 309:1787-1799. [PMID: 38376520 DOI: 10.1007/s00404-024-07370-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 01/02/2024] [Indexed: 02/21/2024]
Abstract
BACKGROUND Preimplantation genetic testing (PGT), also referred to as preimplantation genetic diagnosis (PGD), is an advanced reproductive technology used during in vitro fertilization (IVF) cycles to identify genetic abnormalities in embryos prior to their implantation. PGT is used to screen embryos for chromosomal abnormalities, monogenic disorders, and structural rearrangements. DEVELOPMENT OF PGT Over the past few decades, PGT has undergone tremendous development, resulting in three primary forms: PGT-A, PGT-M, and PGT-SR. PGT-A is utilized for screening embryos for aneuploidies, PGT-M is used to detect disorders caused by a single gene, and PGT-SR is used to detect chromosomal abnormalities caused by structural rearrangements in the genome. PURPOSE OF REVIEW In this review, we thoroughly summarized and reviewed PGT and discussed its pros and cons down to the minutest aspects. Additionally, recent studies that highlight the advancements of PGT in the current era, including their future perspectives, were reviewed. CONCLUSIONS This comprehensive review aims to provide new insights into the understanding of techniques used in PGT, thereby contributing to the field of reproductive genetics.
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Affiliation(s)
- Yafei Tian
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China
- MOE Engineering Research Center of Gene Technology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200433, China
| | - Mingan Li
- Center for Reproductive Medicine, The Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian, 223800, Jiangsu Province, China
| | - Jingmin Yang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China
- NHC Key Laboratory of Birth Defects and Reproductive Health, (Chongqing Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute), Chongqing, 400020, China
| | - Hongyan Chen
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China
| | - Daru Lu
- MOE Engineering Research Center of Gene Technology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200433, China.
- NHC Key Laboratory of Birth Defects and Reproductive Health, (Chongqing Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute), Chongqing, 400020, China.
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Liu J, Zeng SC, Wang A, Cheng HY, Zhang QJ, Lu GX. Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome. World J Gastrointest Oncol 2024; 16:1532-1546. [PMID: 38660671 PMCID: PMC11037055 DOI: 10.4251/wjgo.v16.i4.1532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 12/29/2023] [Accepted: 02/03/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Peutz-Jeghers syndrome (PJS) is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11 (STK11/LKB1) gene mutations. Preimplantation genetic testing can protect a patient's offspring from mutated genes; however, some variations in this gene have been interpreted as variants of uncertain significance (VUS), which complicate reproductive decision-making in genetic counseling. AIM To identify the pathogenicity of two missense variants and provide clinical guidance. METHODS Whole exome gene sequencing and Sanger sequencing were performed on the peripheral blood of patients with PJS treated at the Reproductive and Genetic Hospital of Citic-Xiangya. Software was employed to predict the protein structure, conservation, and pathogenicity of the two missense variation sites in patients with PJS. Additionally, plasmids were constructed and transfected into HeLa cells to observe cell growth. The differences in signal pathway expression between the variant group and the wild-type group were compared using western blot and immunohistochemistry. Statistical analysis was performed using one-way analysis of variance. P < 0.05 was considered statistically significant. RESULTS We identified two missense STK11 gene VUS [c.889A>G (p.Arg297Gly) and c.733C>T (p.Leu245Phe)] in 9 unrelated PJS families who were seeking reproductive assistance. The two missense VUS were located in the catalytic domain of serine/threonine kinase, which is a key structure of the liver kinase B1 (LKB1) protein. In vitro experiments showed that the phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) at Thr172 and LKB1 at Ser428 were significantly higher in transfected variation-type cells than in wild-type cells. In addition, the two missense STK11 variants promoted the proliferation of HeLa cells. Subsequent immunohistochemical analysis showed that phosphorylated-AMPK (Thr172) expression was significantly lower in gastric, colonic, and uterine polyps from PJS patients with missense variations than in non-PJS patients. Our findings indicate that these two missense STK11 variants are likely pathogenic and inactivate the STK11 gene, causing it to lose its function of regulating downstream phosphorylated-AMPK (Thr172), which may lead to the development of PJS. The identification of the pathogenic mutations in these two clinically characterized PJS patients has been helpful in guiding them toward the most appropriate mode of pregnancy assistance. CONCLUSION These two missense variants can be interpreted as likely pathogenic variants that mediated the onset of PJS in the two patients. These findings not only offer insights for clinical decision-making, but also serve as a foundation for further research and reanalysis of missense VUS in rare diseases.
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Affiliation(s)
- Jin Liu
- Hunan Guangxiu Hospital, Hunan Normal University, Changsha 410000, Hunan Province, China
- Scientific Research Department, Reproductive and Genetic Hospital of Citic-Xiangya, Changsha 410000, Hunan Province, China
| | - Si-Cong Zeng
- Hunan Guangxiu Hospital, Hunan Normal University, Changsha 410000, Hunan Province, China
- Scientific Research Department, Reproductive and Genetic Hospital of Citic-Xiangya, Changsha 410000, Hunan Province, China
| | - An Wang
- Hunan Guangxiu Hospital, Hunan Normal University, Changsha 410000, Hunan Province, China
| | - Hai-Ying Cheng
- Hunan Guangxiu Hospital, Hunan Normal University, Changsha 410000, Hunan Province, China
| | - Qian-Jun Zhang
- Hunan Guangxiu Hospital, Hunan Normal University, Changsha 410000, Hunan Province, China
| | - Guang-Xiu Lu
- Hunan Guangxiu Hospital, Hunan Normal University, Changsha 410000, Hunan Province, China
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Conrad KP, von Versen-Höynck F, Baker VL. Pathologic maternal and neonatal outcomes associated with programmed embryo transfer. J Assist Reprod Genet 2024; 41:821-842. [PMID: 38536594 PMCID: PMC11052974 DOI: 10.1007/s10815-024-03041-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/21/2024] [Indexed: 04/29/2024] Open
Abstract
PURPOSE In this first of two companion papers, we critically review the evidence recently published in the primary literature, which addresses adverse maternal and neonatal pregnancy outcomes associated with programmed embryo transfer cycles. We next consider whether these pathological pregnancy outcomes might be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation. Finally, in the second companion article, we explore potential etiologies and suggest strategies for prevention. METHODS Comprehensive review of primary literature. RESULTS The preponderance of retrospective and prospective observational studies suggests that increased risk for hypertensive disorders of pregnancy (HDP) and preeclampsia in assisted reproduction involving autologous embryo transfer is associated with programmed cycles. For autologous frozen embryo transfer (FET) and singleton live births, the risk of developing HDP and preeclampsia, respectively, was less for true or modified natural and stimulated cycles relative to programmed cycles: OR 0.63 [95% CI (0.57-0.070)] and 0.44 [95% CI (0.40-0.50)]. Though data are limited, the classification of preeclampsia associated with programmed autologous FET was predominantly late-onset or term disease. Other adverse pregnancy outcomes associated with autologous FET, especially programmed cycles, included increased prevalence of large for gestational age infants and macrosomia, as well as higher birth weights. In one large registry study, FET was associated with fetal overgrowth of a symmetrical nature. Postterm birth and placenta accreta not associated with prior cesarean section, uterine surgery, or concurrent placenta previa were also associated with autologous FET, particularly programmed cycles. The heightened risk of these pathologic pregnancy outcomes in programmed autologous FET does not appear to be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation, although the latter may contribute a modest degree of increased risk for fetal overgrowth and perhaps HDP and preeclampsia in FET irrespective of the endometrial preparation. CONCLUSIONS Programmed autologous FET is associated with an increased risk of several, seemingly diverse, pathologic pregnancy outcomes including HDP, preeclampsia, fetal overgrowth, postterm birth, and placenta accreta. Though the greater risk for preeclampsia specifically associated with programmed autologous FET appears to be well established, further research is needed to substantiate the limited data currently available suggesting that the classification of preeclampsia involved is predominately late-onset or term. If substantiated, then this knowledge could provide insight into placental pathogenesis, which has been proposed to differ between early- and late-onset or term preeclampsia (see companion paper for a discussion of potential mechanisms). If a higher prevalence of preeclampsia with severe features as suggested by some studies is corroborated in future investigations, then the danger to maternal and fetal/neonatal health is considerably greater with severe disease, thus increasing the urgency to find preventative measures. Presupposing significant overlap of these diverse pathologic pregnancy outcomes within subjects who conceive by programmed embryo transfer, there may be common etiologies.
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Affiliation(s)
- Kirk P Conrad
- Departments of Physiology and Aging and of Obstetrics and Gynecology, D.H. Barron Reproductive and Perinatal Biology Research Program, University of Florida College of Medicine, Gainesville, FL, USA.
| | - Frauke von Versen-Höynck
- Department of Obstetrics, Gynecology, and Reproductive Medicine, Division of Gynecologic Endocrinology and Reproductive Medicine, Hannover Medical School, Hannover, Germany
| | - Valerie L Baker
- Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Lutherville, MD, USA
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Bercovich O, Klar G, Shaulov T, Almog B, Kalma Y, Rahav R, Azem F, Malcov M, Cohen Y. A clinical predictive model for live birth in women of advanced age undergoing PGT cycles. Arch Gynecol Obstet 2024; 309:1083-1090. [PMID: 38219242 DOI: 10.1007/s00404-023-07329-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 11/30/2023] [Indexed: 01/16/2024]
Abstract
PURPOSE The trend of delaying childbirth has resulted in a growing number of advanced-aged women who are opting for preimplantation genetic testing (PGT) to screen for monogenic diseases or structural chromosomal rearrangements (PGT-M and PGT-SR). This increase in demand necessitates the development of a clinical predictive model for live birth outcomes in these women. Therefore, the objective of this study is to construct a comprehensive predictive model that assesses the likelihood of achieving a successful live birth in advanced-aged women undergoing PGT-M and PGT-SR treatments. METHODS A retrospective cohort study of 37-45-year-old women undergoing preimplantation genetic testing for monogenic disease or structural chromosomal rearrangement cycles from 2010 to 2021 was conducted at a university hospital reproductive centre. The purpose was to develop a clinical predictive model for live birth in these women. The main outcome studied was the cumulative live birth rate in the first or subsequent cycles. Developing a decision tree enabled a comprehensive study of clinical parameters and expected outcomes. RESULTS The analysis included 158 women undergoing 753 preimplantation genetic testing cycles. The cumulative live birth rate was 37.342% (59/158). Decision tree analysis revealed that women aged ≤ 40.1 or women > 40.1 with one or more top-quality transferable embryos in their first cycle had the best chance for a live baby (56% and 41%, respectively). Those older than 40.1 without top-quality embryos and seven or fewer dominant follicles had no live births. A Kaplan-Meier curve showed that for autosomal dominant diseases, there was a negligible increase in live birth rate after three cycles, compared to six cycles in autosomal recessive inheritance. CONCLUSION In older women, the chance of delivering after repeated cycles is higher in those with at least one top-quality unaffected embryo in their first preimplantation genetic testing cycle. Additional preimplantation genetic testing cycles after three in carriers of an autosomal dominant disorder and six in those with an autosomal recessive disorder should be considered prudently.
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Affiliation(s)
- Or Bercovich
- Helen Schneider Hospital for Women, Rabin Medical Center, Petach-Tikva, Israel.
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel.
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Galia Klar
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Talya Shaulov
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Benny Almog
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Kalma
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Roni Rahav
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Foad Azem
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Mira Malcov
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yoni Cohen
- Racine In Vitro Fertilization Unit, Lis Maternity Hospital, Soraski Medical Centre, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Zhao W, Song Y, Huang C, Xu S, Luo Q, Yao R, Sun N, Liang B, Fei J, Gao F, Huang J, Qu S. Development of preimplantation genetic testing for monogenic reference materials using next-generation sequencing. BMC Med Genomics 2024; 17:33. [PMID: 38262988 PMCID: PMC10807056 DOI: 10.1186/s12920-024-01803-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 01/09/2024] [Indexed: 01/25/2024] Open
Abstract
OBJECTIVE Preimplantation genetic testing for monogenic disorders (PGT-M) has been used for over 20 years to detect many serious genetic conditions. However, there is still a lack of reference materials (RMs) to validate the test performance during the development and quality control of PGT-M. METHOD Sixteen thalassemia cell lines from four thalassemia families were selected to establish the RMs. Each family consisted of parents with heterozygous mutations for α- and/or β-thalassemia and two children, at least one of whom carried a homozygous thalassemia mutation (proband). The RM panel consisted of 12 DNA samples (parents and probands in 4 families) and 4 simulated embryos (cell lines constructed from blood samples from the four nonproband children). Four accredited genetics laboratories that offer verification of thalassemia samples were invited to evaluate the performance of the RM panel. Furthermore, the stability of the RMs was determined by testing after freeze‒thaw cycles and long-term storage. RESULTS PGT-M reference materials containing 12 genome DNA (gDNA) reference materials and 4 simulated embryo reference materials for thalassemia testing were successfully established. Next-generation sequencing was performed on the samples. The genotypes and haplotypes of all 16 PGT-M reference materials were concordant across the four labs, which used various testing workflows. These well-characterized PGT-M reference materials retained their stability even after 3 years of storage. CONCLUSION The establishment of PGT-M reference materials for thalassemia will help with the standardization and accuracy of PGT-M in clinical use.
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Affiliation(s)
- Weihua Zhao
- Department of Obstetrics, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health, Shenzhen, Guangdong, China
| | | | - Chuanfeng Huang
- Division of Physical and Chemical Testing, Division of in Vitro Diagnostic Reagents, National Institutes for food and drug Control (NIFDC), Beijing, China
| | - Shan Xu
- BGI-Shenzhen, Guangdong, Shenzhen, China
| | - Qi Luo
- Department of Obstetrics, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health, Shenzhen, Guangdong, China
| | - Runsi Yao
- Department of Obstetrics, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health, Shenzhen, Guangdong, China
| | - Nan Sun
- Division of Physical and Chemical Testing, Division of in Vitro Diagnostic Reagents, National Institutes for food and drug Control (NIFDC), Beijing, China
| | - Bo Liang
- Laboratory of Metabolic and Developmental Sciences, State Key Laboratory of Microbial Metabolism, Shanghai, China
- Basecare Medical Device Co., Ltd, Jiangsu, China
| | - Jia Fei
- Peking Jabrehoo Med Tech Co., Ltd, Beijing, China
| | | | - Jie Huang
- Division of Physical and Chemical Testing, Division of in Vitro Diagnostic Reagents, National Institutes for food and drug Control (NIFDC), Beijing, China.
| | - Shoufang Qu
- Division of Physical and Chemical Testing, Division of in Vitro Diagnostic Reagents, National Institutes for food and drug Control (NIFDC), Beijing, China.
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Xiao Y, Cheng D, Luo K, Li M, Tan Y, Lin G, Hu L. Evaluation of genetic risk of apparently balanced chromosomal rearrangement carriers by breakpoint characterization. J Assist Reprod Genet 2024; 41:147-159. [PMID: 37993578 PMCID: PMC10789712 DOI: 10.1007/s10815-023-02986-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 10/31/2023] [Indexed: 11/24/2023] Open
Abstract
PURPOSE To report genetic characteristics and associated risk of chromosomal breaks due to chromosomal rearrangements in large samples. METHODS MicroSeq, a technique that combines chromosome microdissection and next-generation sequencing, was used to identify chromosomal breakpoints. Long-range PCR and Sanger sequencing were used to precisely characterize 100 breakpoints in 50 ABCR carriers. RESULTS In addition to the recurrent regions of balanced rearrangement breaks in 8q24.13, 11q11.23, and 22q11.21 that had been documented, we have discovered a 10-Mb region of 12q24.13-q24.3 that could potentially be a sparse region of balanced rearrangement breaks. We found that 898 breakpoints caused gene disruption and a total of 188 breakpoints interrupted genes recorded in OMIM. The percentage of breakpoints that disrupted autosomal dominant genes recorded in OMIM was 25.53% (48/188). Fifty-four of the precisely characterized breakpoints had 1-8-bp microhomologous sequences. CONCLUSION Our findings provide a reference for the evaluation of the pathogenicity of mutations in related genes that cause protein truncation in clinical practice. According to the characteristics of breakpoints, non-homologous end joining and microhomology-mediated break-induced replication may be the main mechanism for ABCRs formation.
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Affiliation(s)
- Yanqin Xiao
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, Hunan, China
| | - Dehua Cheng
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410023, Hunan, China
| | - Keli Luo
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410023, Hunan, China
| | - Mengge Li
- National Engineering and Research Center of Human Stem Cells, Changsha, 410023, Hunan, China
- Hunan Guangxiu Hospital, Changsha, 410023, Hunan, China
| | - Yueqiu Tan
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410023, Hunan, China
| | - Ge Lin
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410023, Hunan, China
- National Engineering and Research Center of Human Stem Cells, Changsha, 410023, Hunan, China
- Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, 410008, Hunan, China
| | - Liang Hu
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, Hunan, China.
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410023, Hunan, China.
- National Engineering and Research Center of Human Stem Cells, Changsha, 410023, Hunan, China.
- Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, 410008, Hunan, China.
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Yadav D, Patil-Takbhate B, Khandagale A, Bhawalkar J, Tripathy S, Khopkar-Kale P. Next-Generation sequencing transforming clinical practice and precision medicine. Clin Chim Acta 2023; 551:117568. [PMID: 37839516 DOI: 10.1016/j.cca.2023.117568] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 09/27/2023] [Accepted: 09/27/2023] [Indexed: 10/17/2023]
Abstract
Next-generation sequencing (NGS) has revolutionized the field of genomics and is rapidly transforming clinical diagnosis and precision medicine. This advanced sequencing technology enables the rapid and cost-effective analysis of large-scale genomic data, allowing comprehensive exploration of the genetic landscape of diseases. In clinical diagnosis, NGS has proven to be a powerful tool for identifying disease-causing variants, enabling accurate and early detection of genetic disorders. Additionally, NGS facilitates the identification of novel disease-associated genes and variants, aiding in the development of targeted therapies and personalized treatment strategies. NGS greatly benefits precision medicine by enhancing our understanding of disease mechanisms and enabling the identification of specific molecular markers for disease subtypes, thus enabling tailored medical interventions based on individual characteristics. Furthermore, NGS contributes to the development of non-invasive diagnostic approaches, such as liquid biopsies, which can monitor disease progression and treatment response. The potential of NGS in clinical diagnosis and precision medicine is vast, yet challenges persist in data analysis, interpretation, and protocol standardization. This review highlights NGS applications in disease diagnosis, prognosis, and personalized treatment strategies, while also addressing challenges and future prospects in fully harnessing genomic potential within clinical practice.
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Affiliation(s)
- Deepali Yadav
- Central Research Facility, Dr. D.Y Patil Medical College, Hospital & Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri Pune 411018, India; Department of Biotechnology, Dr. D. Y. Patil Arts Science and Commerce College, Pimpri Pune 411018, India
| | - Bhagyashri Patil-Takbhate
- Central Research Facility, Dr. D.Y Patil Medical College, Hospital & Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri Pune 411018, India
| | - Anil Khandagale
- Department of Biotechnology, Dr. D. Y. Patil Arts Science and Commerce College, Pimpri Pune 411018, India
| | - Jitendra Bhawalkar
- Department of Community Medicine, Dr. D.Y Patil Medical College, Hospital & Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri Pune 411018, India
| | - Srikanth Tripathy
- Central Research Facility, Dr. D.Y Patil Medical College, Hospital & Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri Pune 411018, India.
| | - Priyanka Khopkar-Kale
- Central Research Facility, Dr. D.Y Patil Medical College, Hospital & Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri Pune 411018, India.
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Qi Q, Gu X, Zhao Y, Chen Z, Zhou J, Chen S, Wang L. The status of surrogacy in China. Biosci Trends 2023; 17:302-309. [PMID: 37081669 DOI: 10.5582/bst.2022.01263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2023]
Abstract
China's birth rates hit a record low in 2021. The high demand for having children has spawned a massive market for surrogacy, which, however, is a dilemma in China involving a series of moral and legal issues under the current circumstances. First, special populations, including infertile patients, families who have lost their sole child, and homosexuals, wanted to have children, giving rise to surrogacy. Then, the development of and innovation in assisted reproductive technology allowed surrogacy to mature. A high return offsets a high risk, and consequently, an underground surrogacy market has emerged, causing various social issues for the Chinese Government, such as civil disputes, gender disproportion, crime, and the spread of disease. At the same time, surrogacy violates moral ethics, traditional Chinese culture, and the rights and interests of vulnerable groups.
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Affiliation(s)
- Qing Qi
- Laboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- The Academy of Integrative Medicine of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Xiaolei Gu
- College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China
| | - Yangyang Zhao
- Clinical Base of Qingpu Traditional Medicine Hospital, the Academy of Integrative Medicine of Fudan University, Shanghai, China
| | - Ziqin Chen
- College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China
| | - Jing Zhou
- Laboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- The Academy of Integrative Medicine of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Song Chen
- College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China
| | - Ling Wang
- Laboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- The Academy of Integrative Medicine of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
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Gao J, Wei N, Zhu X, Li R, Yan L, Qiao J. The correlation between morphological parameters and the incidence of de novo chromosomal abnormalities in 3238 biopsied blastocysts. J Assist Reprod Genet 2023; 40:1089-1098. [PMID: 37058258 PMCID: PMC10239399 DOI: 10.1007/s10815-023-02780-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 03/17/2023] [Indexed: 04/15/2023] Open
Abstract
PURPOSE The aim of this study was to determine the relationship between morphological parameters and the incidence of de novo chromosomal abnormalities. METHODS This was a retrospective cohort study of 652 patients who underwent 921 cycles with 3238 blastocysts biopsied. The embryo grades were evaluated according to Gardner and Schoolcraft's system. The incidence of euploidy, whole chromosomal aneuploidy (W-aneuploidy), segmental chromosomal aneuploidy (S-aneuploidy), and mosaicism in trophectoderm (TE) cell biopsies was analyzed. RESULTS The euploidy decreased significantly with maternal age and was positively correlated biopsy day and morphological parameters. The W-aneuploidy increased significantly with maternal age and was negatively correlated biopsy day and morphological parameters. Parental age, TE biopsy day, and morphological parameters were not associated with S-aneuploidy and mosaicism, except that TE grade C blastocysts had significantly higher mosaicism than TE grade A blastocysts. Subanalysis in different female age groups showed that euploidy and W-aneuploidy had a significant correlation with TE biopsy day among women aged ≤ 30 y and 31-35 y, with expansion degree among women aged ≥ 36 y, with ICM grade among women aged ≥ 31 y, and with TE grade among all female age ranges. CONCLUSION Female age, embryo developmental speed and blastocyst morphological parameters are associated with euploidy and whole chromosomal aneuploidy. The predictive value of these factors varies across female age groups. Parental age, embryo developmental speed, expansion degree, and ICM grade are not associated with the incidence of segmental aneuploidy or mosaicism, but TE grade seemingly has a weak correlation with segmental aneuploidy and mosaicism in embryos.
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Affiliation(s)
- Jiangman Gao
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, (Peking University Third Hospital), Beijing, 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, 100191, China
| | - Nan Wei
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
| | - Xiaohui Zhu
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, (Peking University Third Hospital), Beijing, 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, 100191, China
| | - Rong Li
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, (Peking University Third Hospital), Beijing, 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, 100191, China
| | - Liying Yan
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
- National Clinical Research Center for Obstetrics and Gynecology, (Peking University Third Hospital), Beijing, 100191, China.
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China.
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, 100191, China.
| | - Jie Qiao
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
- National Clinical Research Center for Obstetrics and Gynecology, (Peking University Third Hospital), Beijing, 100191, China.
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China.
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, 100191, China.
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Xu ZX, Jiang LX, Chen YR, Zhang YH, Zhang Z, Yu PF, Dong ZW, Yang HR, Gu GL. Clinical features, diagnosis, and treatment of Peutz-Jeghers syndrome: Experience with 566 Chinese cases. World J Gastroenterol 2023; 29:1483-1493. [DOI: 10.3748/wjg.v29.i10.1483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/10/2023] Open
Abstract
BACKGROUND Peutz-Jeghers syndrome (PJS) is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities, scattered gastrointestinal polyps, and susceptibility to tumors as clinical manifestations. Effective preventive and curative methods are still lacking. Here we summarize our experience with 566 Chinese patients with PJS from a Chinese medical center with regard to the clinical features, diagnosis, and treatment.
AIM To explore the clinical features, diagnosis, and treatment of PJS in a Chinese medical center.
METHODS The diagnosis and treatment information of 566 cases of PJS admitted to the Air Force Medical Center from January 1994 to October 2022 was summarized. A clinical database was established covering age, gender, ethnicity, family history, age at first treatment, time and sequence of appearance of mucocutaneous pigmentation, polyp distribution, quantity, and diameter, frequency of hospitalization, frequency of surgical operations, etc. The clinical data was retrospectively analyzed using SPSS 26.0 software, with P < 0.05 considered statistically significant.
RESULTS Of all the patients included, 55.3% were male and 44.7% were female. Median time to the appearance of mucocutaneous pigmentation was 2 years, and median time from the appearance of mucocutaneous pigmentation to the occurrence of abdominal symptoms was 10 years. The vast majority (92.2%) of patients underwent small bowel endoscopy and treatment, with 2.3% having serious complications. There was a statistically significant difference in the number of enteroscopies between patients with and without canceration (P = 0.004, Z = -2.882); 71.2% of patients underwent surgical operation, 75.6% of patients underwent surgical operation before the age of 35 years, and there was a statistically significant difference in the frequency of surgical operations between patients with and without cancer (P = 0.000, Z = -5.127). At 40 years of age, the cumulative risk of intussusception in PJS was approximately 72.0%, and at 50 years, the cumulative risk of intussusception in PJS was approximately 89.6%. At 50 years of age, the cumulative risk of cancer in PJS was approximately 49.3%, and at 60 years of age, the cumulative risk of cancer in PJS was approximately 71.7%.
CONCLUSION The risk of intussusception and cancer of PJS polyps increases with age. PJS patients ≥ 10 years old should undergo annual enteroscopy. Endoscopic treatment has a good safety profile and can reduce the occurrence of polyps intussusception and cancer. Surgery should be conducted to protect the gastrointestinal system by removing polyps.
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Affiliation(s)
- Zu-Xin Xu
- Fifth Clinical College of Anhui Medical University, Air Force Clinical College of Anhui Medical University, Beijing 100142, China
| | - Li-Xin Jiang
- Air Force Clinical College of China Medical University, Beijing 100142, China
| | - Yu-Rui Chen
- Air Force Clinical College of China Medical University, Beijing 100142, China
| | - Yu-Hui Zhang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Zhi Zhang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Peng-Fei Yu
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Zhi-Wei Dong
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Hai-Rui Yang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Guo-Li Gu
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
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Xu ZX, Jiang LX, Chen YR, Zhang YH, Zhang Z, Yu PF, Dong ZW, Yang HR, Gu GL. Clinical features, diagnosis, and treatment of Peutz-Jeghers syndrome: Experience with 566 Chinese cases. World J Gastroenterol 2023; 29:1627-1637. [PMID: 36970589 PMCID: PMC10037245 DOI: 10.3748/wjg.v29.i10.1627] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/17/2023] [Accepted: 02/16/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND Peutz-Jeghers syndrome (PJS) is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities, scattered gastrointestinal polyps, and susceptibility to tumors as clinical manifestations. Effective preventive and curative methods are still lacking. Here we summarize our experience with 566 Chinese patients with PJS from a Chinese medical center with regard to the clinical features, diagnosis, and treatment. AIM To explore the clinical features, diagnosis, and treatment of PJS in a Chinese medical center. METHODS The diagnosis and treatment information of 566 cases of PJS admitted to the Air Force Medical Center from January 1994 to October 2022 was summarized. A clinical database was established covering age, gender, ethnicity, family history, age at first treatment, time and sequence of appearance of mucocutaneous pigmentation, polyp distribution, quantity, and diameter, frequency of hospitalization, frequency of surgical operations, etc. The clinical data was retrospectively analyzed using SPSS 26.0 software, with P < 0.05 considered statistically significant. RESULTS Of all the patients included, 55.3% were male and 44.7% were female. Median time to the appearance of mucocutaneous pigmentation was 2 years, and median time from the appearance of mucocutaneous pigmentation to the occurrence of abdominal symptoms was 10 years. The vast majority (92.2%) of patients underwent small bowel endoscopy and treatment, with 2.3% having serious complications. There was a statistically significant difference in the number of enteroscopies between patients with and without canceration (P = 0.004, Z = -2.882); 71.2% of patients underwent surgical operation, 75.6% of patients underwent surgical operation before the age of 35 years, and there was a statistically significant difference in the frequency of surgical operations between patients with and without cancer (P = 0.000, Z = -5.127). At 40 years of age, the cumulative risk of intussusception in PJS was approximately 72.0%, and at 50 years, the cumulative risk of intussusception in PJS was approximately 89.6%. At 50 years of age, the cumulative risk of cancer in PJS was approximately 49.3%, and at 60 years of age, the cumulative risk of cancer in PJS was approximately 71.7%. CONCLUSION The risk of intussusception and cancer of PJS polyps increases with age. PJS patients ≥ 10 years old should undergo annual enteroscopy. Endoscopic treatment has a good safety profile and can reduce the occurrence of polyps intussusception and cancer. Surgery should be conducted to protect the gastrointestinal system by removing polyps.
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Affiliation(s)
- Zu-Xin Xu
- Fifth Clinical College of Anhui Medical University, Air Force Clinical College of Anhui Medical University, Beijing 100142, China
| | - Li-Xin Jiang
- Air Force Clinical College of China Medical University, Beijing 100142, China
| | - Yu-Rui Chen
- Air Force Clinical College of China Medical University, Beijing 100142, China
| | - Yu-Hui Zhang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Zhi Zhang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Peng-Fei Yu
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Zhi-Wei Dong
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Hai-Rui Yang
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
| | - Guo-Li Gu
- Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing 100142, China
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Kaye DK. Addressing ethical issues related to prenatal diagnostic procedures. Matern Health Neonatol Perinatol 2023; 9:1. [PMID: 36737803 PMCID: PMC9896777 DOI: 10.1186/s40748-023-00146-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 01/20/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND For women of advanced maternal age or couples with high risk of genetic mutations, the ability to screen for embryos free of certain genetic mutations is reassuring, as it provides opportunity to address age-related decline in fertility through preimplantation genetic testing. This procedure has potential to facilitate better embryo selection, improve implantation rates with single embryo transfer and reduce miscarriage rates, among others, yet confers some risk to the embryo and additional costs of assisted reproductive technology. This raises questions whether, when and which patients should receive routine PGT-A prior to embryo transfer. DISCUSSION Prenatal diagnostic procedures refer to tests done when one or both genetic parents has a known genetic disorder (or has worries about the disorder) and testing is performed on them, their gametes or on the embryos to determine if the latter is likely to carry a genetic disorder. PGT is used to identify genetic defects in gametes or embryos (often created through in vitro fertilization (IVF). The procedures generate immense potential to improve health and wellbeing by preventing conception or birth of babies with undesirable traits, life-limiting conditions and even lethal conditions. However, they generate a lot of information, which often may challenge decision-making ability of healthcare providers and parents, and raise ethical challenges. CONCLUSION Prenatal diagnostic procedures have potential to address uncertainty and risk of having a child affected with a genetic disease. They, however, often raise own uncertainty and controversies, whose origin, manifestation and related ethical issues are presented. There is need to develop individual and couple decision support tools that incorporate patients' values and concerns in the decision-making process in order to promote more informed decisions, during counseling.
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Affiliation(s)
- Dan Kabonge Kaye
- grid.11194.3c0000 0004 0620 0548Department of Obstetrics and Gynecology, Makerere University College of Health Sciences, Kampala, Uganda ,grid.21107.350000 0001 2171 9311Forgarty African Bioethics Postdoctoral Fellow at Johns Hopkins Berman Institute of Bioethics and the School of Public Health, Baltimore, MD USA
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Wang L, Wang J, Zhang Y, Qian C, Wang X, Bai J, Li F, Chen Z, Ai A. Analysis of euploidy rates in preimplantation genetic testing for aneuploidy cycles with progestin-primed versus GnRH agonist/antagonist protocol. Eur J Med Res 2023; 28:28. [PMID: 36642707 PMCID: PMC9841681 DOI: 10.1186/s40001-023-01000-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 01/08/2023] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Progestins can suppress endogenous luteinising hormone (LH) secretion from the pituitary gland and have shown similar efficacy in terms of collecting competent oocytes and embryos; however, some inconsistencies have been proposed regarding the quality of embryos collected with the use of progestins. This study aimed to evaluate euploidy rates and pregnancy outcomes in preimplantation genetic testing for aneuploidy (PGT-A) cycles using the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone (GnRH) agonist/antagonist protocol. METHODS This retrospective cohort study included 608 PGT-A cycles: 146 women in the PPOS group, 160 women in the GnRH agonist group, and 302 women in the GnRH antagonist group. This study was performed at the in vitro fertilisation (IVF) centre of Shanghai First Maternity and Infant Hospital between January 2019 and December 2021. Additionally, 267 corresponding first frozen embryo transfer (FET) cycles were analysed to assess pregnancy outcomes. RESULTS The euploid blastocyst rate per injected metaphase II(MII) oocytes (14.60% vs. 14.09% vs. 13.94%) was comparable among the three groups (p > 0.05). No significant differences were observed among the three groups regarding pregnancy outcomes, including biochemical pregnancy, clinical pregnancy, ongoing pregnancy, implantation, miscarriage, ectopic pregnancy, and live birth rates per transfer in the first FET cycles (p > 0.05). CONCLUSIONS The PPOS protocol had no negative effect on euploid blastocyst formation, and the pregnancy outcomes in FET cycles using the PPOS protocol were similar to those of the GnRH agonist and antagonist protocols. Trial registration This trial was retrospectively registered.
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Affiliation(s)
- Lu Wang
- grid.24516.340000000123704535Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092 People’s Republic of China
| | - Jingyun Wang
- grid.24516.340000000123704535Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092 People’s Republic of China
| | - Yuan Zhang
- grid.24516.340000000123704535Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092 People’s Republic of China
| | - Chen Qian
- grid.24516.340000000123704535Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092 People’s Republic of China
| | - Xiaohui Wang
- grid.24516.340000000123704535Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092 People’s Republic of China
| | - Jie Bai
- grid.24516.340000000123704535Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092 People’s Republic of China
| | - Fang Li
- grid.24516.340000000123704535Department of Obstetrics and Gynecology, East Hospital, School of Medicine, Tongji University, No. 150 Jimo Road, Shanghai, 200120 People’s Republic of China
| | - Zhiqin Chen
- grid.24516.340000000123704535Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092 People’s Republic of China
| | - Ai Ai
- grid.24516.340000000123704535Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092 People’s Republic of China
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Shi B, Ye Y. Case report: A reciprocal translocation-free and pathogenic DUOX2 mutation-free embryo selected by complicated preimplantation genetic testing resulted in a healthy live birth. Front Genet 2023; 14:1066199. [PMID: 36873947 PMCID: PMC9982009 DOI: 10.3389/fgene.2023.1066199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 02/06/2023] [Indexed: 02/19/2023] Open
Abstract
Preimplantation genetic testing (PGT) is an effective approach to improve clinical outcomes and prevent transmission of genetic imbalances by selecting embryos free of disease-causing genes and chromosome abnormalities. In this study, PGT was performed for a challenging case in which a couple simultaneously carried a maternal subchromosomal reciprocal translocation (RecT) revealed by fluorescence in situ hybridization involving the chromosome X (ChrX) and heterozygous mutations in dual oxidase 2 (DUOX2). Carriers of RecT are at increased risk for infertility, recurrent miscarriages, or having affected children due to the unbalanced gametes produced. DUOX2 mutation results in congenital hypothyroidism. Pedigree haplotypes for DUOX2 was constructed after the mutations were verified by Sanger sequencing. Since male carriers of X-autosome translocations may exhibit infertility or other abnormalities, pedigree haplotype for chromosomal translocation was also constructed to identify embryo with RecT. Three blastocysts were obtained by in vitro fertilization and underwent trophectoderm biopsy, whole genomic amplification, and next-generation sequencing (NGS). A blastocyst lacking copy number variants and RecT but carrying the paternal gene mutation in DUOX2, c.2654G>T (p.R885L) was used for embryo transfer, resulting in a healthy female infant whose genetic properties were confirmed by amniocentesis. Cases containing RecT and single gene disorder are rare. And the situation is more complicated when the subchromosomal RecT involving ChrX cannot be identified with routine karyotype analysis. This case report contributes significantly to the literature and the results have shown that the NGS-based PGT strategy may be broadly useful for complex pedigrees.
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Affiliation(s)
- Biwei Shi
- Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yinghui Ye
- Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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20
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Graham ME, Jelin A, Hoon AH, Wilms Floet AM, Levey E, Graham EM. Assisted reproductive technology: Short- and long-term outcomes. Dev Med Child Neurol 2023; 65:38-49. [PMID: 35851656 PMCID: PMC9809323 DOI: 10.1111/dmcn.15332] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 06/06/2022] [Accepted: 06/07/2022] [Indexed: 01/05/2023]
Abstract
Assisted reproductive technology (ART) includes fertility treatment in which either eggs or embryos are handled outside a female's body to promote successful pregnancies and healthy offspring. Current ART procedures encompass in vitro fertilization with or without intracytoplasmic sperm injection. The most common complication of ART is related to the consequences of multiple pregnancy, which can be prevented or minimized by reducing the number of embryos transferred to the uterus, commonly single embryo transfer. ART has been shown to be variably associated with adverse short- and long-term perinatal outcomes, including cerebral palsy, autism, neurodevelopmental imprinting disorders, and cancer. However, there is uncertainty as to whether reported problems are related to the ART procedure itself, to factors related to infertility, to other medical and environmental factors, or a combination thereof. From a pathophysiological perspective, whether ART alters epigenetic mechanisms of gene expression, leading to later developmental, medical, and behavioral disorders, is an area of active investigation. With the meticulously conducted short- and long-term outcome studies completed so far, overall, and after controlling for multiple gestations and preterm delivery, the results suggest that ART is a safe procedure, offering hope to many parent(s) wishing for a healthy child. This paper highlights ART methods and the risk factors and confounders in the interpretation of short- and long-term outcome data, providing the reader with a means to evaluate findings and conclusions of outcome studies. WHAT THIS PAPER ADDS: Assisted reproductive technology (ART) is a relatively safe procedure. Single embryo implantation optimizes outcome. Informed consent, including the risks and benefits of ART, should be required. Ongoing longitudinal studies are necessary to fully understand ART outcomes.
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Affiliation(s)
| | - Angie Jelin
- Department of Genetic MedicineJohns Hopkins University School of MedicineBaltimoreMDUSA
- Department of Gynecology and Obstetrics, Division of Maternal‐Fetal MedicineJohns Hopkins University School of MedicineBaltimoreMDUSA
| | - Alexander H. Hoon
- Department of Pediatrics, Division of Developmental MedicineJohns Hopkins School of MedicineBaltimoreMDUSA
- Phelps Center for Cerebral Palsy and Neurodevelopmental MedicineKennedy Krieger InstituteBaltimoreMDUSA
| | - Anna Maria Wilms Floet
- Department of Pediatrics, Division of Developmental MedicineJohns Hopkins School of MedicineBaltimoreMDUSA
- Center for Autism and Related DisordersKennedy Krieger InstituteBaltimoreMDUSA
- Center for Development and LearningKennedy Krieger InstituteBaltimoreMDUSA
| | - Eric Levey
- Health Services for Children with Special NeedsWashingtonDCUSA
| | - Ernest M. Graham
- Department of Gynecology and Obstetrics, Division of Maternal‐Fetal MedicineJohns Hopkins University School of MedicineBaltimoreMDUSA
- Neuroscience Intensive Care Nursery ProgramJohns Hopkins University School of MedicineBaltimoreMDUSA
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21
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Park JG, Xu CL, Boyd A, Aghajanova L, Mahajan VB, Wood EH. REPRODUCTIVE OPHTHALMOLOGY: The Intersection of Inherited Eye Diseases and Reproductive Technologies. Retina 2022; 42:2025-2030. [PMID: 35963004 PMCID: PMC10593127 DOI: 10.1097/iae.0000000000003591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To propose a working framework for patients with inherited eye diseases presenting to ophthalmologists who are interested in assisted reproductive technology and preimplantation genetic testing. METHODS Retrospective chart review and case series of three families with inherited eye diseases who successfully underwent preimplantation genetic testing, in vitro fertilization, and birth of unaffected children. RESULTS Preimplantation genetic testing was performed for three families with different inherited eye diseases, which included autosomal dominant retinitis pigmentosa, autosomal recessive achromatopsia, and X-linked Goltz syndrome. Preimplantation genetic testing led to the identification of unaffected embryos, which were then selected for in vitro fertilization and resulted in the birth of unaffected children. CONCLUSION A close collaboration between patients, families, ophthalmologists, reproductive genetic counselors, and reproductive endocrinology and infertility specialists is the ideal model for taking care of patients interested in preimplantation genetic testing for preventing the transmission of inherited eye diseases.
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Affiliation(s)
- Jong G Park
- Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California; and
| | - Christine L Xu
- Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California; and
| | - Allison Boyd
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Sunnyvale, California
| | - Lusine Aghajanova
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Sunnyvale, California
| | - Vinit B Mahajan
- Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California; and
| | - Edward H Wood
- Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California; and
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22
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Kanaka V, Proikakis S, Drakakis P, Loutradis D, Tsangaris GT. Implementing a preimplantation proteomic approach to advance assisted reproduction technologies in the framework of predictive, preventive, and personalized medicine. EPMA J 2022; 13:237-260. [PMID: 35719135 PMCID: PMC9203609 DOI: 10.1007/s13167-022-00282-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/05/2022] [Indexed: 10/28/2022]
Abstract
The evolution of the field of assisted reproduction technology (ART) in the last 40 years has significantly contributed to the management of global infertility. Despite the great numbers of live births that have been achieved through ART, there is still potential for increasing the success rates. As a result, there is a need to create optimum conditions in order to increase ART efficacy. The selection of the best sperm, oocyte, and embryo, as well as the achievement of optimal endometrial receptivity, through the contribution of new diagnostic and treatment methods, based on a personalized proteomic approach, may assist in the attainment of this goal. Proteomics represent a powerful new technological development, which seeks for protein biomarkers in human tissues. These biomarkers may aid to predict the outcome, prevent failure, and monitor in a personalized manner in vitro fertilization (IVF) cycles. In this review, we will present data from studies that have been conducted in the search for such biomarkers in order to identify proteins related to good sperm, oocyte, and embryo quality, as well as optimal endometrial receptivity, which may later lead to greater results and the desirable ART outcome.
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Affiliation(s)
- Vasiliki Kanaka
- First Department of Obstetrics and Gynecology, School of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece
- Proteomics Research Unit, Biomedical Research Foundation, Academy of Athens, Athens, Greece
| | - Stavros Proikakis
- Proteomics Research Unit, Biomedical Research Foundation, Academy of Athens, Athens, Greece
| | - Petros Drakakis
- Third Department of Obstetrics and Gynecology, School of Medicine, National and Kapodistrian University of Athens, Attikon Hospital, Athens, Greece
| | - Dimitrios Loutradis
- First Department of Obstetrics and Gynecology, School of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece
| | - George Th. Tsangaris
- Proteomics Research Unit, Biomedical Research Foundation, Academy of Athens, Athens, Greece
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Yanagimachi R. Mysteries and unsolved problems of mammalian fertilization and related topics. Biol Reprod 2022; 106:644-675. [PMID: 35292804 PMCID: PMC9040664 DOI: 10.1093/biolre/ioac037] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 02/10/2022] [Accepted: 02/10/2022] [Indexed: 11/13/2022] Open
Abstract
Mammalian fertilization is a fascinating process that leads to the formation of a new individual. Eggs and sperm are complex cells that must meet at the appropriate time and position within the female reproductive tract for successful fertilization. I have been studying various aspects of mammalian fertilization over 60 years. In this review, I discuss many different aspects of mammalian fertilization, some of my laboratory's contribution to the field, and discuss enigmas and mysteries that remain to be solved.
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Affiliation(s)
- Ryuzo Yanagimachi
- Institute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology, University of Hawaii Medical School, Honolulu, HI 96822, USA
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Shi W, Zhao Z, Xue X, Li Q, Yao Y, Wang D, Wang J, Lu S, Shi J. Ploidy Testing of Blastocoel Fluid for Screening May Be Technically Challenging and More Invasive Than That of Spent Cell Culture Media. Front Physiol 2022; 13:794210. [PMID: 35264976 PMCID: PMC8900197 DOI: 10.3389/fphys.2022.794210] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 01/26/2022] [Indexed: 11/15/2022] Open
Abstract
Background Recent studies have demonstrated that both blastocoel fluid (BF) and spent cell culture media (SCM) have potential as materials for non-invasive or less-invasive pre-implantation genetic analysis. BF may allow more opportunity to obtain cell-free DNA from the inner cell mass (ICM), and it has a lower risk of containing contaminant DNA from cumulus cells, sperm and culture media. There are no data regarding the ICM as a gold standard to evaluate the chromosome constitution of BF or SCM for embryo liquid biopsy. Methods Two hundred eighteen donated human blastocysts were warmed and cultured in blastocyst culture media for 18–24 h. The corresponding SCM was collected, and only clear ICM was biopsied in blastocysts; otherwise, the whole blastocyst (WB) was biopsied. Quantitative PCR was performed to determine the DNA levels in the SCM and BF before and after amplification. ChromInst was used to amplify BF/SCM and blastocyst DNA before sequencing. Chromosomal copy number variation (CNV) was investigated to evaluate the chromosome constitution. Results In total, 212 blastocysts were available for SCM and BF collection. The technical success rates (next-generation sequencing data) were 100 and 69.8% (148/212) for SCM and BF, respectively. Among the 148 blastocysts with both SCM and BF data, 101 were euploid and 47 were aneuploid based on ICM (n = 89) or WB (n = 59) analysis as the gold standard. Among all blastocysts, SCM was comparable to BF [specificity: 80.2 versus 61.4% (P = 0.005, χ2 test); sensitivity: 91.5 versus 87.2% (P = 0.738, χ2 test); negative predictive value (NPV): 95.3 versus 91.2% (P = 0.487, χ2 test); positive predictive value (PPV): 68.3% versus 51.3% (P = 0.042, χ2 test)]. The SCM and BF samples were 83.8% (124/148) and 69.6% (103/148) concordant with the corresponding ICM/WB samples when only two categories, euploid or aneuploid/mosaic, were grouped to calculate the concordance. Conclusions Compared with BF, SCM has superior diagnostic performance, and it is non-invasive for embryos. Clinical Trial Registration [http://www.chictr.org.cn], identifier [ChiCTR-BPD-17014087].
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Affiliation(s)
- Wenhao Shi
- The Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, China
| | - Zhenghao Zhao
- The Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, China
| | - Xia Xue
- The Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, China
| | - Qian Li
- The Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, China
| | - Yaxin Yao
- Department of Clinical Research, Yikon Genomics Company, Ltd., Suzhou, China
| | - Dongyang Wang
- Translational Medicine Center, Northwest Women's and Children's Hospital, Xi'an, China
| | - Jing Wang
- Department of Clinical Research, Yikon Genomics Company, Ltd., Suzhou, China
| | - Sijia Lu
- Department of Clinical Research, Yikon Genomics Company, Ltd., Suzhou, China
| | - Juanzi Shi
- The Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, China
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Tehsin F, Almutawah FH, Almutawah HK, Alwabari ME, AlSultan ZM, Buawadh HS. Preimplantation Genetic Testing: A Perceptual Study From the Eastern Province, Saudi Arabia. Cureus 2021; 13:e20421. [PMID: 35047260 PMCID: PMC8758912 DOI: 10.7759/cureus.20421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2021] [Indexed: 11/14/2022] Open
Abstract
Background: Chromosomal abnormalities affect many children which lead to high rates of morbidity and mortality among them. So, preimplantation genetic testing (PGT) is an evolving technology used to detect a specific genetic disorder in embryos of a couple known to be carriers or affected by a specific mutation. Similarly, it could be used in advanced maternal age which is a high risk of chromosomal abnormalities. Although PGT is a solution for many inherited chromosomal disorders, many ethical dilemmas surround its application. Thus, the aim of this study is to evaluate the community awareness and acceptance of PGT which will eventually lead to a healthier society through disease-free babies in Eastern Province, Kingdom of Saudi Arabia (KSA). Methodology: A qualitative cross-sectional questionnaire-based study was conducted within the population of the Eastern Province of Saudi Arabia. The questionnaire was designed in Arabic and distributed electronically through social media platforms. Results: The study included 837 participants, whose ages ranged from 18 to 65 years with the mean age 33.5 ± 11.9 years. Good awareness and acceptance were detected among 53.7% of the old aged group (50 years or more) compared to 39.5% of the young age group. Also, 44.9% of female participants had good awareness in comparison to 34.2% of males (p=.033). Participants with a higher number of children had significantly higher awareness and acceptance of PGT. Also, 44.3% of participants who knew someone in need of assisted reproductive technology, had good awareness and acceptance levels compared to 36.9% of those who did not (p=.033). Conclusion: The perception of Eastern Province’s Saudi citizens toward PGT is found to be low. Increasing their perception toward such technology is needed as it is known that many chromosomal abnormalities are prevalent among this population, particularly sickle cell disease. Achieving this goal will eventually lead to decrease the burden of prevalent inherited diseases. Since Saudis' opinions are almost influenced by cultural and religious points of view, care should be given to these aspects.
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Excluding embryos with two novel mutations in FREM2 gene by the next-generation sequencing-based single nucleotide polymorphism haplotyping. Aging (Albany NY) 2021; 13:24786-24794. [PMID: 34837691 PMCID: PMC8660615 DOI: 10.18632/aging.203715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 10/27/2021] [Indexed: 11/25/2022]
Abstract
Fraser syndrome is a rare autosomal recessive malformation disorder. It is characterized by cryptophthalmos, syndactyly, urinary tract abnormalities and ambiguous genitalia. This condition is due to homozygous or heterozygous mutations in the FRAS1, FREM1, FREM2, and GRIP1 genes. In the present study, we recruited a Chinese family with Fraser syndrome. Two novel mutations c.7542_7543insG and c.2689C>T in the FREM2 gene were detected in this Fraser syndrome family by PCR-based sequencing. The next-generation sequencing-based single nucleotide polymorphism haplotyping method was applied to exclude these two mutations in 9 blastocysts obtained from the patient. After obtaining consent and informing the risk, the patient received in vitro fertilization and embryo transfer treatment with an embryo carrying a heterozygous mutation. Finally, she delivered a healthy baby without any complications on March 17, 2019. In conclusion, we first reported two novel mutations in the FREM2 gene associated with the risk of Fraser syndrome. Moreover, we described a next-generation sequencing-based single nucleotide polymorphism haplotyping method to select the ‘right’ embryos from patients with Fraser syndrome for in vitro fertilization and embryo transfer treatment.
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27
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Scott JB, Yanes AF, Vivar KL, Yun D, Wagner A, Kruse L, Mancini AJ. Restrictive dermopathy: Three new patients with ZMPSTE24 mutations and a review of the literature. Pediatr Dermatol 2021; 38:1535-1540. [PMID: 34647350 DOI: 10.1111/pde.14822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Restrictive dermopathy (RD) is a rare and lethal laminopathy caused by mutations in LMNA or ZMPSTE24. This series reports 3 patients with RD and reviews the literature of the 113 previously reported cases, including highlights of the unique constellation of clinical findings in RD, as well as histologic, radiographic, and genetic features. Early recognition of these characteristic features is vital to establish a prompt diagnosis and provide adequate family counseling for this terminal condition.
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Affiliation(s)
- Jennifer B Scott
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Arianna F Yanes
- Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Karina L Vivar
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Duri Yun
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Annette Wagner
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Lacey Kruse
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Anthony J Mancini
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.,Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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Sites CK, Bachilova S, Gopal D, Cabral HJ, Coddington CC, Stern JE. Embryo biopsy and maternal and neonatal outcomes following cryopreserved-thawed single embryo transfer. Am J Obstet Gynecol 2021; 225:285.e1-285.e7. [PMID: 33894152 DOI: 10.1016/j.ajog.2021.04.235] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 04/06/2021] [Accepted: 04/17/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Contemporary embryo biopsy in the United States involves the removal of several cells from a blastocyst that would become the placenta for preimplantation genetic testing. Embryos are then cryopreserved while patients await biopsy results, with transfers occurring in a subsequent cycle as a single frozen-thawed embryo transfer, if euploid. OBJECTIVE We sought to determine if removal of these cells for preimplantation genetic testing was associated with adverse obstetrical or neonatal outcomes after frozen-thawed single embryo transfer. STUDY DESIGN We linked assisted reproductive technology surveillance data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System to birth certificates and maternal and neonatal hospitalization discharge diagnoses in Massachusetts from 2014 to 2017, considering only singleton births after frozen-thawed single embryo transfers. We compared outcomes of cycles having embryo biopsy (n=585) to those having no biopsy (n=2191) using chi-square for categorical and binary variables and logistic regression for adjusted odds ratios and 95% confidence intervals, adjusting for mother's age, race, education, parity, body mass index, birth year, insurance, and all infertility diagnoses. RESULTS Considering no biopsy as the reference, there was no difference between groups with respect to preeclampsia (adjusted odds ratio, 0.82; 95% confidence interval, 0.42-1.61; P=.5685); pregnancy-induced hypertension (adjusted odds ratio, 0.85; 95% confidence interval, 0.46-1.59; P=.6146); placental disorders, including placental abruption, placenta previa, placenta accreta, placenta increta, and placenta percreta (adjusted odds ratio, 1.16; 95% confidence interval, 0.60-2.24; P=.6675); preterm birth (adjusted odds ratio, 1.22; 95% confidence interval 0.73-2.03; P=.4418); low birthweight (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.15; P=.7355); cesarean delivery (adjusted odds ratio, 1.04; 95% confidence interval, 0.79-1.38; P=.7762); or gestational diabetes mellitus (adjusted odds ratio, 0.83; 95% confidence interval, 0.50-1.38; P=.4734). In addition, there was no difference between the groups for prolonged hospital stay for mothers (adjusted odds ratio, 1.23; 95% confidence interval, 0.83-1.80; P=.3014) or for infants (95% confidence interval, 1.29; 95% confidence interval, 0.72-2.29; P=.3923). CONCLUSION Embryo biopsy for preimplantation genetic testing does not increase the odds for diagnoses related to placentation (preeclampsia, pregnancy-related hypertension, placental disorders, preterm delivery, or low birthweight), maternal conditions (gestational diabetes mellitus), or maternal or infant length of stay after delivery.
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Moiseeva AV, Kudryavtseva VA, Nikolenko VN, Gevorgyan MM, Unanyan AL, Bakhmet AA, Sinelnikov MY. Genetic determination of the ovarian reserve: a literature review. J Ovarian Res 2021; 14:102. [PMID: 34362406 PMCID: PMC8349022 DOI: 10.1186/s13048-021-00850-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 07/23/2021] [Indexed: 12/30/2022] Open
Abstract
The ovarian reserve is one of the most important indicators of female fertility. It allows for the evaluation of the number of viable oocytes. This parameter is actively used in pregnancy planning and in assisted reproductive technology application, as it determines chances of successful fertilization and healthy pregnancy. Due to increased attention towards diagnostic tests evaluating the ovarian reserve, there has been a growing interest in factors that influence the state of the ovarian reserve. True reasons for pathological changes in the ovarian reserve and volume have not yet been explored in depth, and current diagnostic screening methods often fall short in efficacy. In the following review we analyze existing data relating to the study of the ovarian reserve through genetic testing, determining specific characteristics of the ovarian reserve through genetic profiling. We explore existing studies dedicated to finding specific genetic targets influencing the state of the ovarian reserve.
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Affiliation(s)
| | | | - Vladimir N Nikolenko
- Sechenov University, Mohovaya 11c10, Moscow, Russian Federation.,Moscow State University, Moscow, Russian Federation
| | | | - Ara L Unanyan
- Sechenov University, Mohovaya 11c10, Moscow, Russian Federation
| | | | - Mikhail Y Sinelnikov
- Sechenov University, Mohovaya 11c10, Moscow, Russian Federation. .,Research Institute of Human Morphology, Moscow, Russian Federation.
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30
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Lee I, Alur-Gupta S, Gallop R, Dokras A. Utilization of preimplantation genetic testing for monogenic disorders. Fertil Steril 2021; 114:854-860. [PMID: 33040985 DOI: 10.1016/j.fertnstert.2020.05.045] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 05/06/2020] [Accepted: 05/11/2020] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To determine the rate of utilization, factors influencing the decision-making process, and patient satisfaction with preimplantation genetic diagnosis for monogenic disorders (PGT-M). DESIGN Survey study. SETTING Academic center. PATIENT(S) Genetically at-risk patients seen for PGT-M consultation between January 2010 and 2018. INTERVENTION(S) Electronic survey including demographics, genetic history, consultation experience, decision-making process, and satisfaction with PGT-M process. MAIN OUTCOME MEASURE(S) Rate of utilization of PGT-M, importance of decision-making factors, and satisfaction with PGT-M process. RESULT(S) Among survey respondents (n = 49), the rate of utilization of PGT-M after consultation was 89.8%. Ninety-three percent of participants decided whether to pursue PGT-M within 3 months of consultation. Factors that were considered most important to this decision-making process included information provided at consultation, accuracy of test results after PGT-M, avoidance of suffering of an affected child, and ability to avoid termination of an affected pregnancy. Key barriers to utilization included financial burden and overall complexity of the in vitro fertilization (IVF)/PGT-M process. Of those utilizing PGT-M (n = 44), 72.1% had at least one live birth or were pregnant during the study period. Satisfaction with PGT-M was high, and most couples would use IVF/PGT-M for a future pregnancy (84.1%). Participants with a live birth were more satisfied with the PGT-M process than those who had no live birth. CONCLUSION(S) Most patients seeking consultation for PGT-M were likely to pursue this technology despite financial burden and complexity of the process. Exploring factors that influence patient decision-making regarding PGT-M is important for tailoring the consultation and optimizing the overall experience.
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Affiliation(s)
- Iris Lee
- Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania Hospital, Philadelphia, Pennsylvania
| | - Snigdha Alur-Gupta
- Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania Hospital, Philadelphia, Pennsylvania
| | - Robert Gallop
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Anuja Dokras
- Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania Hospital, Philadelphia, Pennsylvania.
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Xiong S, Liu W, Wang J, Liu J, Gao Y, Wu L, Zhu J, Hao X, Li J, Liu D, Han W, Huang G. Trophectoderm biopsy protocols may impact the rate of mosaic blastocysts in cycles with pre-implantation genetic testing for aneuploidy. J Assist Reprod Genet 2021; 38:1153-1162. [PMID: 33660205 PMCID: PMC7929899 DOI: 10.1007/s10815-021-02137-w] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 02/25/2021] [Indexed: 12/02/2022] Open
Abstract
PURPOSE This study aimed to analyze the impact of different biopsy protocols on the rate of mosaic blastocysts. METHODS This is a retrospective cohort study which included 115 cycles with pre-implantation genetic testing for aneuploidy (PGT-A). Two groups were allocated based on the biopsy protocols: method 1 group, the zona pellucida (ZP) was drilled on day 3 embryos followed by trophectoderm (TE) biopsy; and method 2 group, the ZP was opened on day 5 or 6 blastocysts followed by TE biopsy. All biopsy samples were assessed using next-generation sequencing (NGS) at a single reference laboratory. The euploid, aneuploid, and mosaic blastocyst rates and clinical outcomes were compared. RESULTS The mosaicism rate in the method 1 group was 19.58%, significantly higher than the method 2 group (8.12%; P < 0.05). No statistically significant difference was observed in euploid, aneuploid blastocyst rates, and clinical pregnancy rates between the two groups. Logistic regression analysis indicated that the biopsy protocols were independently associated with the mosaicism rates among all the variables. CONCLUSIONS The present study showed that different biopsy protocols may have an impact on the mosaic blastocyst rate. ZP opening on day 3 combined with TE biopsy might increase the incidence of mosaic blastocysts.
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Affiliation(s)
- Shun Xiong
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China
| | - Weiwei Liu
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China
| | - Jiang Wang
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China
| | - Junxia Liu
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China
| | - Yang Gao
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China
| | - Lihong Wu
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China
| | - Jiahong Zhu
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China
| | - Xiangwei Hao
- Chongqing Clinical Research Center for Reproductive Medicine, Chongqing, People's Republic of China
| | - Jingyu Li
- Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, People's Republic of China
| | - Dongyun Liu
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China
| | - Wei Han
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China.
| | - Guoning Huang
- Chongqing Health Center for Women and Children, Chongqing, People's Republic of China.
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Application of single-sperm sequencing in a male with Marfan syndrome: a case report and a literature review. J Genet 2021. [DOI: 10.1007/s12041-021-01267-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Chen D, Shen X, Xu Y, Ding C, Ye Q, Zhong Y, Xu Y, Zhou C. Successful four-factor preimplantation genetic testing: α- and β-thalassemia, human leukocyte antigen typing, and aneuploidy screening. Syst Biol Reprod Med 2021; 67:151-159. [PMID: 33494632 DOI: 10.1080/19396368.2020.1832158] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Our study established an effective next-generation sequencing (NGS) protocol for four-factor preimplantation genetic testing (PGT) using α- and β-thalassemia, human leukocyte antigen (HLA) typing, and aneuploidy screening. Three couples, in whom both partners were α- and β-double thalassemia carriers, underwent PGT between 2016 and 2018. These individuals sought an opportunity for hematopoietic stem cell transplantation to save their children from β-thalassemia major. A total of 35 biopsied trophectoderm samples underwent multiple displacement amplification (MDA). PGT for α- and β-thalassemia and HLA typing were performed on MDA products using NGS-based single-nucleotide polymorphism (SNP) haplotyping. Although two samples failed MDA, 94.3% (33/35) of samples were successfully amplified, achieving conclusive PGT results. Furthermore, 51.5% (17/33) of the embryos were diagnosed as unaffected non-carriers or carriers. Of the 17 unaffected embryos, nine (52.9%) were tested further and identified as euploid via NGS-based aneuploid screening, in which five had HLA types matching affected children. One family did not achieve any unaffected euploid embryos. The two other families transferred HLA-matched and unaffected euploid embryos, resulting in two healthy 'savior babies.' NGS-PGT results were confirmed in prenatal diagnosis. Therefore, NGS-SNP was effective in performing PGT for multipurpose detection within a single PGT cycle.
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Affiliation(s)
- Dongjia Chen
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Xiaoting Shen
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Yan Xu
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Chenhui Ding
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Qingjian Ye
- Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yiping Zhong
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Yanwen Xu
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Canquan Zhou
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
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Zhou X, Liu X, Shi W, Ye M, Chen S, Xu C. Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer. Front Endocrinol (Lausanne) 2021; 12:762976. [PMID: 34867804 PMCID: PMC8637898 DOI: 10.3389/fendo.2021.762976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 09/27/2021] [Indexed: 11/13/2022] Open
Abstract
An increasing number of studies have related the mitochondrial DNA (mtDNA) content to embryo viability and transfer outcomes. However, previous studies have focused more on the relationship between mtDNA and embryo implantation, few studies have studied the effect of the mtDNA content on live birth. In the study, we investigated whether mtDNA content is a reliable screening biomarker for live birth after single blastocyst transfer. A total of 233 couples with 316 blastocyst stage embryos undergoing in vitro fertilization treatment and pre-implantation genetic testing analysis were included in the study. All embryos were chromosomally normal and had undergone single-embryo transfers. There was no significant difference observed in the blastocyst mtDNA content among the live birth, miscarriage and non-implanted groups (p=0.999), and the mtDNA content in blastocysts from the miscarriage and live birth groups was similar [median (interquartile range), 1.00*108(7.59*107- 1.39*108) vs 1.01*108 (7.37*107- 1.32*108)]. Similarly, no significant association was observed between mtDNA content and embryo implantation potential (p=0.965). After adjusting for multiple confounders in a logistic regression analysis with generalized estimating equations, no associations between mtDNA content and live birth were observed in all blastocysts, Day-5 and Day-6 blastocysts (p=0.567, p=0.673, p=0.165, respectively). The live birth rate was not significantly different between blastocysts with an elevated mtDNA content and blastocysts with a normal mtDNA content (26.7% vs 33.6% p=0.780). Additionally, there was no linear correlation between the mtDNA content and maternal age (p=0.570). In conclusion, the mtDNA content does not seem to be a potential biomarker for embryo transfer outcomes (i.e., implantation and live birth) based on the existing testing tools. Embryos with an elevated mtDNA content also have development potential for successful live birth.
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Affiliation(s)
- Xuanyou Zhou
- International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Xueli Liu
- International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Weihui Shi
- International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Mujin Ye
- International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Songchang Chen
- International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
- *Correspondence: Chenming Xu, ; Songchang Chen,
| | - Chenming Xu
- International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
- *Correspondence: Chenming Xu, ; Songchang Chen,
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Bacus J, Lammers J, Loubersac S, Lefebvre T, Leperlier F, Barriere P, Fréour T, Reignier A. [Pre-implantation genetic testing: Comparison between cleavage stage and blastocyst biopsy]. ACTA ACUST UNITED AC 2020; 49:266-274. [PMID: 33232814 DOI: 10.1016/j.gofs.2020.11.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Preimplantation genetic testing (PGT) refers to the set of techniques for testing whether embryos obtained through in vitro fertilization have genetic defect. There is a lack of global standardization regarding practices between countries or even from one center to another. In ours, biopsies are preferably performed on day 3 embryos, but also at the blastocyst stage on day 5. The blastocyst biopsy often requires systematic freezing of the embryos before obtaining the genetic results, whereas day 3 biopsy allows fresh embryo transfer of the healthy or balanced embryo after getting the genetic results. We wanted to compare the chances of success for couples performing PGT in our center according to the day of the biopsy. METHODS For this, we carried out a retrospective monocentric study including all PGT cycles performed between 2016 and 2019 divided into two groups: day 3 or day 5 biopsy. RESULTS There was no significant difference in terms of live birth rate (P=0.7375) after fresh embryo transfers, as well for pregnancy rates, clinical pregnancy rates, implantation rates and miscarriage rates. On the other hand, we observed higher live birth rates after frozen-thawed embryo transfer when the biopsy was performed on day 5 rather on day 3 (P=0.0001). We also wanted to assess what was the most efficient biopsy strategy in our laboratory. Our rates of useful embryos were similar regardless of the day of the biopsy (34% in D3 and 37.7% in D5, P=0.244). No statistical difference was found in the number of unnecessarily biopsied embryos in the two groups. But still, the percentage of embryos biopsied on D5 and immediately frozen was 42.8% (118 blastocysts), while no embryo biopsied on D3 led to this case. CONCLUSION Therefore, our results are in favor of generalization of the D5 biopsy as the international standard. However, the organizational, financial and logistical implications that this technic would impose make it unsystematic in our center.
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Affiliation(s)
- J Bacus
- Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, 38, boulevard Jean-Monnet, 44093 Nantes cedex 1, France
| | - J Lammers
- Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, 38, boulevard Jean-Monnet, 44093 Nantes cedex 1, France; Inserm, unité mixte de recherche 1064, institut de transplantatino urologie néphrologie, centre de recherche en transplantation et immunologie, Nantes Université, 44000 Nantes, France
| | - S Loubersac
- Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, 38, boulevard Jean-Monnet, 44093 Nantes cedex 1, France; Inserm, unité mixte de recherche 1064, institut de transplantatino urologie néphrologie, centre de recherche en transplantation et immunologie, Nantes Université, 44000 Nantes, France
| | - T Lefebvre
- Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, 38, boulevard Jean-Monnet, 44093 Nantes cedex 1, France
| | - F Leperlier
- Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, 38, boulevard Jean-Monnet, 44093 Nantes cedex 1, France
| | - P Barriere
- Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, 38, boulevard Jean-Monnet, 44093 Nantes cedex 1, France; Inserm, unité mixte de recherche 1064, institut de transplantatino urologie néphrologie, centre de recherche en transplantation et immunologie, Nantes Université, 44000 Nantes, France
| | - T Fréour
- Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, 38, boulevard Jean-Monnet, 44093 Nantes cedex 1, France; Inserm, unité mixte de recherche 1064, institut de transplantatino urologie néphrologie, centre de recherche en transplantation et immunologie, Nantes Université, 44000 Nantes, France
| | - A Reignier
- Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, 38, boulevard Jean-Monnet, 44093 Nantes cedex 1, France; Inserm, unité mixte de recherche 1064, institut de transplantatino urologie néphrologie, centre de recherche en transplantation et immunologie, Nantes Université, 44000 Nantes, France.
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Ahluwalia M, Ho CY. Cardiovascular genetics: the role of genetic testing in diagnosis and management of patients with hypertrophic cardiomyopathy. Heart 2020; 107:183-189. [PMID: 33172912 DOI: 10.1136/heartjnl-2020-316798] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/11/2020] [Accepted: 10/14/2020] [Indexed: 01/17/2023] Open
Abstract
Genetic testing in hypertrophic cardiomyopathy (HCM) is a valuable tool to manage patients and their families. Genetic testing can help inform diagnosis and differentiate HCM from other disorders that also result in increased left ventricular wall thickness, thereby directly impacting treatment. Moreover, genetic testing can definitively identify at-risk relatives and focus family management. Pathogenic variants in sarcomere and sarcomere-related genes have been implicated in causing HCM, and targeted gene panel testing is recommended for patients once a clinical diagnosis has been established. If a pathogenic or likely pathogenic variant is identified in a patient with HCM, predictive genetic testing is recommended for their at-risk relatives to determine who is at risk and to guide longitudinal screening and risk stratification. However, there are important challenges and considerations to implementing genetic testing in clinical practice. Genetic testing results can have psychological and other implications for patients and their families, emphasising the importance of genetic counselling before and after genetic testing. Determining the clinical relevance of genetic testing results is also complex and requires expertise in understanding of human genetic variation and clinical manifestations of the disease. In this review, we discuss the genetics of HCM and how to integrate genetic testing in clinical practice.
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Affiliation(s)
- Monica Ahluwalia
- Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Carolyn Y Ho
- Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Abstract
Approximately 50% of the causes of infertility are of genetic origin. The objective of this study was to analyze the role of genetics in human reproduction by reviewing the main genetic causes of infertility and the use of preimplantation genetic testing in Brazil. This literature review comprised articles in English and Portuguese published on databases PubMed, Scielo, and Bireme from 1990 to 2019. Randomized clinical trials and specialized guidelines were given preference whenever possible. Genetic cause can be traced back to up to 20% of the cases of severe azoospermia or oligozoospermia. Subjects with these conditions are good candidates for genetic screening. In women, genetic causes of infertility (fragile X syndrome, X-trisomy, and Turner's syndrome, some of which diagnosed with karyotyping) culminate with premature ovarian failure. Genetic screening helps advise couples of the risk of experiencing early reproductive capacity loss and of the chances of their offspring carrying genetic disorders. In addition to enhancing the prevention of serious diseases in the offspring of couples at increased risk of genetic diseases, preimplantation genetic screening improves the success rates of assisted reproduction procedures by allowing the selection of euploid embryos for transfer. The interface between genetics and human reproduction has gained significant relevance, but discussions are still needed on which procedures are clinically and ethically acceptable and how they should be regulated.
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Affiliation(s)
| | - Fernanda Polisseni
- Surgery Department, Medical School - Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil
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Brandsema JF, Gross BN, Matesanz SE. Diagnostic Testing for Patients with Spinal Muscular Atrophy. Clin Lab Med 2020; 40:357-367. [PMID: 32718505 DOI: 10.1016/j.cll.2020.05.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Diagnostic genetic testing for spinal muscular atrophy is key in establishing early diagnosis for affected individuals. Prenatal carrier testing of parents with subsequent testing of the fetus for homozygous SMN1 gene deletion in those at risk of this autosomal recessive disorder as well as newborn screening can identify the vast majority of affected individuals before the onset of symptoms. Patients presenting symptomatically must be genetically confirmed as soon as possible because targeted treatments are now available that profoundly impact symptoms and improve quality of life.
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Affiliation(s)
- John F Brandsema
- Division of Neurology, Colket Translational Research Building, 10th Floor, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Brianna N Gross
- Division of Neurology, Colket Translational Research Building, 10th Floor, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA
| | - Susan E Matesanz
- Division of Neurology, Colket Translational Research Building, 10th Floor, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA
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Donovan LN, Kohlmann W, Snow AK, Neklason DW, Schiffman JD, Maese L. Germ Cell Mosaicism: A Rare Cause of Li-Fraumeni Recurrence Among Siblings. JCO Precis Oncol 2020; 4:PO.20.00064. [PMID: 32923893 PMCID: PMC7446446 DOI: 10.1200/po.20.00064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2020] [Indexed: 11/20/2022] Open
Affiliation(s)
| | - Wendy Kohlmann
- University of Utah Huntsman Cancer Institute, Salt Lake City, UT
| | - Angela K. Snow
- University of Utah Huntsman Cancer Institute, Salt Lake City, UT
| | - Deborah W. Neklason
- University of Utah Huntsman Cancer Institute, Salt Lake City, UT
- Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT
| | - Joshua D. Schiffman
- University of Utah Huntsman Cancer Institute, Salt Lake City, UT
- University of Utah Department of Pediatrics, Salt Lake City, UT
| | - Luke Maese
- University of Utah Huntsman Cancer Institute, Salt Lake City, UT
- University of Utah Department of Pediatrics, Salt Lake City, UT
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Zhytnik L, Simm K, Salumets A, Peters M, Märtson A, Maasalu K. Reproductive options for families at risk of Osteogenesis Imperfecta: a review. Orphanet J Rare Dis 2020; 15:128. [PMID: 32460820 PMCID: PMC7251694 DOI: 10.1186/s13023-020-01404-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 05/11/2020] [Indexed: 02/07/2023] Open
Abstract
Background Osteogenesis Imperfecta (OI) is a rare genetic disorder involving bone fragility. OI patients typically suffer from numerous fractures, skeletal deformities, shortness of stature and hearing loss. The disorder is characterised by genetic and clinical heterogeneity. Pathogenic variants in more than 20 different genes can lead to OI, and phenotypes can range from mild to lethal forms. As a genetic disorder which undoubtedly affects quality of life, OI significantly alters the reproductive confidence of families at risk. The current review describes a selection of the latest reproductive approaches which may be suitable for prospective parents faced with a risk of OI. The aim of the review is to alleviate suffering in relation to family planning around OI, by enabling prospective parents to make informed and independent decisions. Main body The current review provides a comprehensive overview of possible reproductive options for people with OI and for unaffected carriers of OI pathogenic genetic variants. The review considers reproductive options across all phases of family planning, including pre-pregnancy, fertilisation, pregnancy, and post-pregnancy. Special attention is given to the more modern techniques of assisted reproduction, such as preconception carrier screening, preimplantation genetic testing for monogenic diseases and non-invasive prenatal testing. The review outlines the methodologies of the different reproductive approaches available to OI families and highlights their advantages and disadvantages. These are presented as a decision tree, which takes into account the autosomal dominant and autosomal recessive nature of the OI variants, and the OI-related risks of people without OI. The complex process of decision-making around OI reproductive options is also discussed from an ethical perspective. Conclusion The rapid development of molecular techniques has led to the availability of a wide variety of reproductive options for prospective parents faced with a risk of OI. However, such options may raise ethical concerns in terms of methodologies, choice management and good clinical practice in reproductive care, which are yet to be fully addressed.
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Affiliation(s)
- Lidiia Zhytnik
- Clinic of Traumatology and Orthopaedics, Tartu University Hospital, Tartu, Estonia.
| | - Kadri Simm
- Institute of Philosophy and Semiotics, Faculty of Arts and Humanities, University of Tartu, Tartu, Estonia.,Centre of Ethics, University of Tartu, Tartu, Estonia
| | - Andres Salumets
- Competence Centre on Health Technologies, Tartu, Estonia.,Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.,Institute of Genomics, University of Tartu, Tartu, Estonia.,COMBIVET ERA Chair, Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Tartu, Estonia
| | - Maire Peters
- Competence Centre on Health Technologies, Tartu, Estonia.,Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
| | - Aare Märtson
- Clinic of Traumatology and Orthopaedics, Tartu University Hospital, Tartu, Estonia.,Department of Traumatology and Orthopaedics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
| | - Katre Maasalu
- Clinic of Traumatology and Orthopaedics, Tartu University Hospital, Tartu, Estonia.,Department of Traumatology and Orthopaedics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
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Balakier H, Kuznyetsova I, Librach CL. The impact of hyaluronan-enriched culture medium and intrauterine infusion of human chorionic gonadotropin on clinical outcomes in blastocyst transfer cycles. Syst Biol Reprod Med 2020; 66:79-88. [PMID: 32129683 DOI: 10.1080/19396368.2020.1727995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Over the last few decades, advances in ovarian hormonal stimulation, embryology laboratory technologies and embryo genetic testing, have significantly enhanced clinical outcomes in human assisted reproduction technologies (ART). However, embryo implantation remains a major bottleneck in achieving better pregnancy and live birth rates. Thus, there is growing interest in establishing new approaches to enhance implantation efficiency after embryo transfer. With advanced molecular techniques, many promising biomarkers associated with embryonic and endometrial changes occurring prior to and during embryo implantation have been identified. However, despite the progress in applying novel procedures into IVF practice, clinical evaluation of those biomarkers has so far reached modest predictive value for enhancing blastocyst developmental potential and endometrial receptivity. Therefore, other simpler strategies have also been introduced to increase the rates of successful clinical pregnancies and live births. One of these approaches is to investigate the impact of using embryo transfer medium containing high concentrations of an adherence compound, such as hyaluronic acid (HA), on IVF outcomes. Additionally, intrauterine infusion of a small volume of human chorionic gonadotropin (hCG) at the time of embryo transfer (ET) has also been proposed as a technique that might be advantageous for increasing the clinical outcomes, considering the fact that hCG plays a critical role in synchronizing endometrial and fetal development. However, the current findings from both interventions remain controversial, demonstrating a mixture of positive and indifferent results of these treatments in ART cycles. Further research will be crucial for a better understanding of the molecular mechanism of cross-talk between the blastocyst and the maternal endometrium during the optimal implantation period when using either hyaluronan-enriched medium or hCG infusion before embryo transfers. Therefore, this review aims to present existing literature related to both treatments, emphasizing their effects on blastocyst implantation.Abbreviations: ART: assisted reproduction technologies; HA: hyaluronic acid; hCG: human chorionic gonadotrophin; IVF: in vitro Fertilization; ET: embryo transfer; pH: hydrogen ions; CO2: Carbone dioxide; O2: Oxygen; PGT: pre-implantation genetic testing; FET: frozen embryo transfer; PCOS: Polycystic ovarian syndrome; DNA: deoxyribonucleic acid; miRNA: micro-ribonucleic acid; EVs: extracellular vesicles; ERA: endometrial receptivity array; CD44 and RHAMM: primary hyaluronan surface receptors; RCT: randomized clinical trials; LBR: life birth rate; CPR: clinical pregnancy rate; IR: implantation rate.
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Affiliation(s)
| | | | - Clifford L Librach
- CReATe Fertility Centre, Toronto, ON, Canada.,Department of Obstetrics and Gynecology, University of Toronto, Toronto, Canada.,Department of Gynecology, Women's College Hospital, Toronto, Ontario, Canada
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Assessment of 6 STR loci for prenatal diagnosis of Duchenne Muscular Dystrophy. Taiwan J Obstet Gynecol 2020; 58:645-649. [PMID: 31542086 DOI: 10.1016/j.tjog.2019.07.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/04/2019] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE Duchenne Muscular Dystrophy is an X-linked recessive disorder characterized by progressive muscular degeneration, patients often develop cardiac failure in the later stage and death occurs before 20 years of age. For a disease with poor postnatal prognosis such as Duchenne Muscular Dystrophy (DMD), providing the carrier mother with the option of prenatal diagnosis in a subsequent pregnancy is accepted practice in many places where termination of pregnancy is allowed. Though methods of direct sequencing such as Sanger's sequencing has been widely used, Next-Generation Sequencing is been increasingly replacing most of its application. For the DMD gene, being the longest gene in the human genome, methods of direct sequencing is often unpractical and time-consuming, instead, STR analysis for linkage analysis would be a cost-effective option and have been used routinely for prenatal diagnosis of DMD. The diagnostic significance of the STRs is based on several criteria, the most important one being the heterozygosity of the locus, power of discrimination (PD) and power of exclusion (PE). MATERIAL AND METHODS In this study, we investigated the feasibility of application and diagnostic value of 6 STR loci (DSTR49, DSTR50, DXS1036, DXS1067, DXS890, DXS9907) in the proximity of the DMD gene, 66 healthy individuals were recruited for STR analysis and 5 cases of prenatal diagnosis for carrier mother were performed. RESULT Allele frequency, heterozygosity, polymorphic information content, the power of discrimination and exclusion and Hardy-Weinberg equilibrium were analyzed and calculated for the 6 STR loci. 5 of these loci (DSTR49, DSTR50, DXS1067, DXS890, DXS9907) were found practical and useful for preimplantation Genetic diagnosis (PGD) and prenatal diagnosis. All 5 cases of prenatal diagnosis using the method had informative STR results and correct diagnosis. CONCLUSION We concluded that our protocol of STR analysis can be applied for prenatal diagnosis and pre-implantation genetic diagnosis of DMD with high confidence and accuracy, especially in clinical settings where diagnostic resources are more limited.
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Murphy NM, Samarasekera TS, Macaskill L, Mullen J, Rombauts LJF. Genome sequencing of human in vitro fertilisation embryos for pathogenic variation screening. Sci Rep 2020; 10:3795. [PMID: 32123222 PMCID: PMC7052235 DOI: 10.1038/s41598-020-60704-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 02/13/2020] [Indexed: 12/22/2022] Open
Abstract
Whole-genome sequencing of preimplantation human embryos to detect and screen for genetic diseases is a technically challenging extension to preconception screening. Combining preconception genetic screening with preimplantation testing of human embryos facilitates the detection of de novo mutations and self-validates transmitted variant detection in both the reproductive couple and the embryo’s samples. Here we describe a trio testing workflow that involves whole-genome sequencing of amplified DNA from biopsied embryo trophectoderm cells and genomic DNA from both parents. Variant prediction software and annotation databases were used to assess variants of unknown significance and previously not described de novo variants in five single-gene preimplantation genetic testing couples and eleven of their embryos. Pathogenic variation, tandem repeat, copy number and structural variations were examined against variant calls for compound heterozygosity and predicted disease status was ascertained. Multiple trio testing showed complete concordance with known variants ascertained by single-nucleotide polymorphism array and uncovered de novo and transmitted pathogenic variants. This pilot study describes a method of whole-genome sequencing and analysis for embryo selection in high-risk couples to prevent early life fatal genetic conditions that adversely affect the quality of life of the individual and families.
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Affiliation(s)
- Nicholas M Murphy
- Genetic Technologies Ltd., Victoria, Australia. .,Monash IVF, Clayton, Victoria, Australia. .,GenEmbryomics Pty. Ltd., Victoria, Australia. .,Drug Delivery Disposition and Dynamics, Faculty of Pharmacy and Pharmaceutical Sciences, Parkville, Melbourne, Victoria, Australia.
| | | | | | | | - Luk J F Rombauts
- Monash IVF, Clayton, Victoria, Australia.,Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia.,Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.,Monash Women's & Newborn Program, Monash Health, Victoria, Australia
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Yeager S, Mehta S, Sodhi M, Shah B. Can preimplantation genetic diagnosis be used for monogenic endocrine diseases? J Pediatr Endocrinol Metab 2019; 32:1305-1310. [PMID: 31490775 DOI: 10.1515/jpem-2019-0184] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 07/22/2019] [Indexed: 11/15/2022]
Abstract
Context Preimplantation genetic diagnosis (PGD) is currently used for over 400 monogenic diseases. Some endocrine conditions that occur due to monogenic defects are either life-threatening or can cause severe morbidities; thus, PGD may be an option to avoid the occurrence of such diseases. Evidence acquisition An initial search in PubMed/Medline search was done to identify monogenic endocrine conditions using appropriate search terms. Eleven articles (1999-2018) reported 15 cases using PGD for monogenic endocrine diseases performed at major reproductive centers. Clinical and outcome data of these cases were reviewed with respect to the number of PGD cycles, successful pregnancy rates, live births and their genetic status. Evidence synthesis Fifteen couples underwent 32 PGD cycles (one to nine per couple), of which 17 resulted in a pregnancy. Seven couples underwent a single PGD cycle. Four couples had successful pregnancies each resulting in live births, one couple had an unsuccessful pregnancy, one needed medical termination of pregnancy and the outcome data were not reported in one. The remaining eight couples underwent multiple PGD cycles (two to nine per couple) and all had successful pregnancies in at least one cycle resulting in 16 live births. Of the total live births, 60% were genetically unaffected and 40% were carriers of the autosomal recessive gene mutation. Conclusions PGD may be a potential tool for preventing the inheritance of severe monogenic endocrine diseases in future generations. Currently, the use of PGD in endocrine disorders is rare but provides a promising option on a case-by-case basis, provided the optimal resources are available.
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Affiliation(s)
| | - Shilpa Mehta
- Division of Pediatric Endocrinology, Department of Pediatrics, New York University School of Medicine, New York, NY, USA
| | - Misha Sodhi
- Division of Pediatric Endocrinology, Department of Pediatrics, New York University School of Medicine, New York, NY, USA
| | - Bina Shah
- Division of Pediatric Endocrinology, Department of Pediatrics, New York University School of Medicine, New York, NY, USA, Phone: +212-562-3793
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Karavani E, Zuk O, Zeevi D, Barzilai N, Stefanis NC, Hatzimanolis A, Smyrnis N, Avramopoulos D, Kruglyak L, Atzmon G, Lam M, Lencz T, Carmi S. Screening Human Embryos for Polygenic Traits Has Limited Utility. Cell 2019; 179:1424-1435.e8. [PMID: 31761530 PMCID: PMC6957074 DOI: 10.1016/j.cell.2019.10.033] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 09/11/2019] [Accepted: 10/25/2019] [Indexed: 12/19/2022]
Abstract
The increasing proportion of variance in human complex traits explained by polygenic scores, along with progress in preimplantation genetic diagnosis, suggests the possibility of screening embryos for traits such as height or cognitive ability. However, the expected outcomes of embryo screening are unclear, which undermines discussion of associated ethical concerns. Here, we use theory, simulations, and real data to evaluate the potential gain of embryo screening, defined as the difference in trait value between the top-scoring embryo and the average embryo. The gain increases very slowly with the number of embryos but more rapidly with the variance explained by the score. Given current technology, the average gain due to screening would be ≈2.5 cm for height and ≈2.5 IQ points for cognitive ability. These mean values are accompanied by wide prediction intervals, and indeed, in large nuclear families, the majority of children top-scoring for height are not the tallest.
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Affiliation(s)
- Ehud Karavani
- Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
| | - Or Zuk
- Department of Statistics, The Hebrew University of Jerusalem, Jerusalem 9190501, Israel
| | - Danny Zeevi
- Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Nir Barzilai
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Genetics, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Nikos C Stefanis
- Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, 115 28 Athens, Greece; University Mental Health Research Institute, 115 27 Athens, Greece; Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, 115 21 Athens, Greece
| | - Alex Hatzimanolis
- Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, 115 28 Athens, Greece; Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, 115 21 Athens, Greece
| | - Nikolaos Smyrnis
- Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, 115 28 Athens, Greece; University Mental Health Research Institute, 115 27 Athens, Greece
| | - Dimitrios Avramopoulos
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Leonid Kruglyak
- Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Gil Atzmon
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Genetics, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Biology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel
| | - Max Lam
- Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Institute of Behavioral Science, Feinstein Institutes of Medical Research, Manhasset, NY 11030, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
| | - Todd Lencz
- Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Institute of Behavioral Science, Feinstein Institutes of Medical Research, Manhasset, NY 11030, USA; Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA.
| | - Shai Carmi
- Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
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Luo H, Chen C, Yang Y, Zhang Y, Yuan Y, Wang W, Wu R, Peng Z, Han Y, Jiang L, Yao R, An X, Zhang W, Le Y, Xiang J, Yi N, Huang H, Li W, Zhang Y, Sun J. Preimplantation genetic testing for a family with usher syndrome through targeted sequencing and haplotype analysis. BMC Med Genomics 2019; 12:157. [PMID: 31699113 PMCID: PMC6836415 DOI: 10.1186/s12920-019-0600-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 10/09/2019] [Indexed: 12/02/2022] Open
Abstract
Background Preimplantation genetic testing for monogenic defects (PGT-M) has been available in clinical practice. This study aimed to validate the applicability of targeted capture sequencing in developing personalized PGT-M assay. Methods One couple at risk of transmitting Usher Syndrome to their offspring was recruited to this study. Customized capture probe targeted at USH2A gene and 350 kb flanking region were designed for PGT-M. Eleven blastocysts were biopsied and amplified by using multiple displacement amplification (MDA) and capture sequencing. A hidden Markov model (HMM) assisted haplotype analysis was performed to deduce embryo’s genotype by using single nucleotide polymorphisms (SNPs) identified in each sample. The embryo without paternal rare variant was implanted and validated by conventional prenatal or postnatal diagnostic means. Results Four embryos were diagnosed as free of father’s rare variant, two were transferred and one achieved a successful pregnancy. The fetal genotype was confirmed by Sanger sequencing of fetal genomic DNA obtained by amniocentesis. The PGT-M and prenatal diagnosis results were further confirmed by the molecular diagnosis of the baby’s genomic DNA sample. The auditory test showed that the hearing was normal. Conclusions Targeted capture sequencing is an effective and convenient strategy to develop customized PGT-M assay.
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Affiliation(s)
- Haining Luo
- Center for Reproductive Medicine, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China
| | - Chao Chen
- Wuhan BGI Clinical Laboratory Co., Ltd, BGI-Wuhan, BGI-Shenzhen, Wuhan, 430074, China.,Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China
| | - Yun Yang
- Wuhan BGI Clinical Laboratory Co., Ltd, BGI-Wuhan, BGI-Shenzhen, Wuhan, 430074, China.,Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Yinfeng Zhang
- Center for Reproductive Medicine, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China
| | - Yuan Yuan
- Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China
| | - Wanyang Wang
- Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China
| | - Renhua Wu
- Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China
| | - Zhiyu Peng
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Ying Han
- School of Medicine, Nankai University, Tianjin, 300070, China
| | - Lu Jiang
- Wuhan BGI Clinical Laboratory Co., Ltd, BGI-Wuhan, BGI-Shenzhen, Wuhan, 430074, China.,Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China
| | - Ruqiang Yao
- Center for Reproductive Medicine, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China
| | - Xiaoying An
- Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China
| | - Weiwei Zhang
- Center for Reproductive Medicine, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China
| | - Yanqun Le
- Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China
| | - Jiale Xiang
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Na Yi
- Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China
| | - Hui Huang
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Wei Li
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Yunshan Zhang
- Center for Reproductive Medicine, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China.
| | - Jun Sun
- Wuhan BGI Clinical Laboratory Co., Ltd, BGI-Wuhan, BGI-Shenzhen, Wuhan, 430074, China. .,Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, 300308, China.
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Analysis of PGT‐M and PGT‐SR outcomes at a Canadian fertility clinic. Prenat Diagn 2019; 39:866-870. [DOI: 10.1002/pd.5496] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 04/24/2019] [Accepted: 05/18/2019] [Indexed: 11/07/2022]
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Somigliana E, Busnelli A, Paffoni A, Vigano P, Riccaboni A, Rubio C, Capalbo A. Cost-effectiveness of preimplantation genetic testing for aneuploidies. Fertil Steril 2019; 111:1169-1176. [DOI: 10.1016/j.fertnstert.2019.01.025] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 01/12/2019] [Accepted: 01/16/2019] [Indexed: 11/17/2022]
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Hou W, Xu Y, Li R, Song J, Wang J, Zeng Y, Pan J, Zhou C, Xu Y. Role of aneuploidy screening in preimplantation genetic testing for monogenic diseases in young women. Fertil Steril 2019; 111:928-935. [PMID: 30922652 DOI: 10.1016/j.fertnstert.2019.01.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 01/10/2019] [Accepted: 01/10/2019] [Indexed: 11/19/2022]
Abstract
OBJECTIVE To investigate whether aneuploidy screening in preimplantation genetic testing (PGT) for monogenic diseases improves the ongoing pregnancy/live birth rate of single frozen/thawed embryo transfer (FET) cycles in young women. DESIGN Retrospective cohort study. SETTING Single university-based fertility center. PATIENT(S) From January 2016 to December 2017, 569 FET cycles were selected for analysis. The aneuploidy screening (AS) group included 131 FET cycles from 105 oocyte retrieval cycles in 98 patients who underwent PGT for monogenic diseases with aneuploidy screening, and the non-AS group included 438 FET cycles from 280 oocyte retrieval cycles in 266 patients who underwent PGT for monogenic diseases without aneuploidy screening. INTERVENTION(S) The patient population was all under the age of 35 years and underwent PGT for monogenic diseases with and without AS. MAIN OUTCOME MEASURE(S) Ongoing pregnancy/live birth rate, live birth rate, implantation rate, and miscarriage rate. RESULT(S) Aneuploidy screening significantly improved the ongoing pregnancy/live birth rate (61.22% vs. 43.98%), implantation rate (64.29% vs. 50.38%), and live birth rate (53.06% vs. 36.09%) of young women carrying monogenic diseases in the first FET cycles. When adjusted for the parity, number of previous miscarriages, and percentage of infertility, the likelihood of implantation was 1.874 times higher (95% confidence interval 1.126-3.119), and an ongoing pregnancy/live birth was 2.139 times more likely (95% confidence interval 1.295-3.534). In addition, the miscarriage rate was significantly decreased (3.17% vs. 11.94%). In the cumulative pregnancy outcomes, the cumulative ongoing pregnancy/live birth rate both per transfer and per patient were significantly higher in the AS group (62.24% vs. 50.38% and 79.59% vs. 68.80%), but no difference existed after adjusting for the parity, number of previous miscarriage, and percentage of infertility. Nevertheless, aneuploidy screening reduced the time interval from the first ET to the achievement a pregnancy. CONCLUSION(S) Aneuploidy screening in PGT significantly improved the ongoing pregnancy/live birth rate of young women carrying monogenic diseases in the first FET cycles.
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Affiliation(s)
- Wenhui Hou
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Yan Xu
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Rong Li
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Junli Song
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Jing Wang
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Yanhong Zeng
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Jiafu Pan
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Canquan Zhou
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Yanwen Xu
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
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Zanetti BF, Braga DPDAF, Azevedo MDC, Setti AS, Figueira RCS, Iaconelli A, Borges E. Preimplantation genetic testing for monogenic diseases: a Brazilian IVF centre experience. JBRA Assist Reprod 2019; 23:99-105. [PMID: 30614237 PMCID: PMC6501745 DOI: 10.5935/1518-0557.20180076] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE To describe the cases of preimplantation genetic testing for monogenic diseases (PGT-M) in fertile couples who had undergone intracytoplasmic sperm injection (ICSI) cycles in a Brazilian in vitro fertilisation (IVF) centre and determine whether these cases were different from those reported from the European Society of Human Reproduction and Embryology (ESHRE). METHODS This retrospective collection included data obtained from ICSI-PGT-M cycles between 2011 and 2016. The disease indication, number of biopsied embryos, biopsy stage, diagnosed and affected embryos, and cycles with embryo to transfer as well as implantation, pregnancy and miscarriage rates were analysed and compared to cycles without genetic diagnosis (PGT) and with ESHRE PGD Consortium collection XIV-XV. RESULTS From 5,070 cycles performed, 72 had indications for PGT-M. The most common time for biopsy was cleavage-stage; 93% of the embryos had a diagnostic result, 59.4% of which were genetically transferable, resulting in 68% of the cycles with transferred embryos, a 22.1% implantation rate, and a 28.6% pregnancy rate. No differences in clinical outcomes of cycles with PGT-M or without PGT were observed. The day of biopsy and diagnostic success as well as implantation, pregnancy and miscarriage rates were similar to ESHRE collection. CONCLUSIONS Although the proportion of cases with PGT-M was low, its efficacy was similar to what was reported in the European collection and represents a viable alternative for families at risk of transmitting a genetic disorder to their offspring. The main difference between our and ESHRE collection were the disease indications, which reflected the admixed, multi-ethnic Brazilian population.
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Affiliation(s)
- Bianca Ferrarini Zanetti
- Fertility - Medical Group, São Paulo, SP - Brazil.,Instituto Sapientiae - Centro de Estudos e Pesquisa em Reprodução Humana Assistida, São Paulo, SP - Brazil
| | | | | | - Amanda Souza Setti
- Fertility - Medical Group, São Paulo, SP - Brazil.,Instituto Sapientiae - Centro de Estudos e Pesquisa em Reprodução Humana Assistida, São Paulo, SP - Brazil
| | | | - Assumpto Iaconelli
- Fertility - Medical Group, São Paulo, SP - Brazil.,Instituto Sapientiae - Centro de Estudos e Pesquisa em Reprodução Humana Assistida, São Paulo, SP - Brazil
| | - Edson Borges
- Fertility - Medical Group, São Paulo, SP - Brazil.,Instituto Sapientiae - Centro de Estudos e Pesquisa em Reprodução Humana Assistida, São Paulo, SP - Brazil
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