Guidelines for Embryo Biopsy
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Background Document on Preimplantation and Prenatal Genetic Testing
DH-BIO/INF (2015) 6 Background document on preimplantation and prenatal genetic testing Clinical Situation Legal situation1 1 Part II of this document presents the legal situation in Council of Europe member states and will be regularly updated (last update 7 May 2015). The updated text is highlighted in green. TABLE OF CONTENTS Introduction ............................................................................................................... 3 Part I. Preimplantation (PGD) and Prenatal (PND) Genetic Diagnosis. Clinical practice, Trends and Technological Developments ................................................... 4 1. Genetic diseases .............................................................................................. 4 1.1 Monogenic diseases ......................................................................................... 4 1.2 Polygenic diseases or multifactorial diseases ................................................... 5 1.3 Chromosomal diseases .................................................................................... 5 2. Preimplantation genetic diagnosis on embryonic cells ...................................... 5 2.1 General description of the procedure ................................................................ 5 2.2 PGD uses ......................................................................................................... 6 2.2.1 Main uses of PGD for medical indications ......................................................... 6 2.2.2 Use of PGD for the benefit of the health -
Educational Objectives Current IVF Practice
2/23/2015 Update from the IVF Lab: Preimplantation Genetic Testing Janet McLaren Bouknight, MD Reproductive Endocrinology and Infertility Department of Obstetrics & Gynecology Educational Objectives • Gain familiarity with the procedures and pregnancy outcomes of current in vitro fertilization practices. • Understand the application of Preimplantation Genetic Diagnosis (PGD) for single‐gene disorders. • Appreciate the role of Preimplantation Genetic Screening (PGS) in maximizing IVF cycle efficiency and encouraging elective single embryo transfer. Current IVF Practice 1 2/23/2015 Current IVF Practice 150,000 cycles 65,000 livebirths Current IVF Practice Current IVF Practice All SART Clinics 2012 <35 35‐37 38‐40 41‐42 >42 Pregnancy Rate 47% 38% 30% 20% 9% Live Birth Rate 41% 31% 22% 12% 4% # embryos transfer 1.9 2.0 2.4 2.9 2.9 % Twins 30% 25% 20% 13% 9% • What are the advanced that have contributed to an increase in success in the IVF Lab? • Improved lab conditions • Extended embryo culture • Improvements in embryo cryopreservation 2 2/23/2015 Current IVF Practice: Improved Lab Conditions Current IVF Practice: Improved Lab Conditions Current IVF Practice: Improved Lab Conditions 3 2/23/2015 Current IVF Practice: Extended Embryo Culture Day 3: Cleavage Stage Day 5: Blastocyst Stage • 8‐cells • 200‐300 cells • 30% implantation rate • 50% implantation rate Increased live birth rates seen in “good prognosis” patients who undergo a Day 5 transfer Current IVF Practice: Extended Embryo Culture Current IVF Practice: Extended Embryo Culture • Supports blastocyst transfer for “good prognosis” patients • Opportunity to consider single embryo transfer • May be associated with a small increased risk of monozygotic twinning 4 2/23/2015 Current IVF Practice: Embryo Cryopreservation Cycles • Improvements in freezing techniques (vitrification) have increased success of cryopreserved embryos. -
Cryopreserved Oocyte Versus Fresh Oocyte Assisted Reproductive Technology Cycles, United States, 2013
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Fertil Steril Manuscript Author . Author manuscript; Manuscript Author available in PMC 2018 January 01. Published in final edited form as: Fertil Steril. 2017 January ; 107(1): 110–118. doi:10.1016/j.fertnstert.2016.10.002. Cryopreserved oocyte versus fresh oocyte assisted reproductive technology cycles, United States, 2013 Sara Crawford, Ph.D.a, Sheree L. Boulet, Dr.P.H., M.P.H.a, Jennifer F. Kawwass, M.D.a,b, Denise J. Jamieson, M.D., M.P.H.a, and Dmitry M. Kissin, M.D., M.P.H.a aDivision of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Emory University, Atlanta, Georgia bDivision of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Emory University, Atlanta, Georgia Abstract Objective—To compare characteristics, explore predictors, and compare assisted reproductive technology (ART) cycle, transfer, and pregnancy outcomes of autologous and donor cryopreserved oocyte cycles with fresh oocyte cycles. Design—Retrospective cohort study from the National ART Surveillance System. Setting—Fertility treatment centers. Patient(s)—Fresh embryo cycles initiated in 2013 utilizing embryos created with fresh and cryopreserved, autologous and donor oocytes. Intervention(s)—Cryopreservation of oocytes versus fresh. Main Outcomes Measure(s)—Cancellation, implantation, pregnancy, miscarriage, and live birth rates per cycle, transfer, and/or pregnancy. -
Preimplantation Genetic Testing for Aneuploidy (PGT-A): the Biology, the Technology and the Clinical Outcomes
Aust N Z J Obstet Gynaecol 2019; 1–8 DOI: 10.1111/ajo.12960 OPINION Preimplantation genetic testing for aneuploidy (PGT-A): The biology, the technology and the clinical outcomes Hayden Anthony Homer1,2,3 1Christopher Chen Oocyte Biology Research Laboratory, UQ Centre Preimplantation genetic testing for aneuploidy (PGT-A) seeks to identify preim- for Clinical Research, The University plantation embryos with a normal chromosome complement (euploid) during in of Queensland, Brisbane, Queensland, Australia vitro fertilisation (IVF). By sifting out embryos with abnormal chromosome num- 2Reproductive Endocrinology and bers (aneuploid), PGT-A should theoretically improve pregnancy success. Infertility Clinic, Royal Brisbane However, earlier versions of PGT-A were ineffective, and in some cases, detri- & Women's Hospital, Brisbane, Queensland, Australia mental, due to biopsy-induced trauma and because the technology at the time 3Queensland Fertility Group, Brisbane, could analyse only a fraction of all chromosomes. More recently, the emergence Queensland, Australia of technologies enabling all chromosomes to be analysed and a switch to less Correspondence: Professor Hayden traumatic blastocyst-stage biopsy have seen widespread uptake of PGT-A. Anthony Homer, Christopher Chen Assessing the full impact of blastocyst biopsy PGT-A requires consideration of Oocyte Biology Research Laboratory, UQ Centre for Clinical Research, The multiple factors, including embryonic mosaicism, sensitivity of the technological University of Queensland, Building platform used, embryo loss during long-term in vitro culture, embryo cryo- 71/918, Royal Brisbane & Women's Hospital Campus, Herston, QLD 4029, preservation and inter-clinic variability in expertise. Significantly, there hasn‘t Australia. yet been an appropriately designed randomised controlled trial (RCT) of blasto- Email: [email protected] cyst biopsy PGT-A analysed by intention-to- treat that accounts for all these pa- Conflicts of Interest: The author report no conflicts of interest. -
Social Freezing: Pressing Pause on Fertility
International Journal of Environmental Research and Public Health Review Social Freezing: Pressing Pause on Fertility Valentin Nicolae Varlas 1,2 , Roxana Georgiana Bors 1,2, Dragos Albu 1,2, Ovidiu Nicolae Penes 3,*, Bogdana Adriana Nasui 4,* , Claudia Mehedintu 5 and Anca Lucia Pop 6 1 Department of Obstetrics and Gynaecology, Filantropia Clinical Hospital, 011171 Bucharest, Romania; [email protected] (V.N.V.); [email protected] (R.G.B.); [email protected] (D.A.) 2 Department of Obstetrics and Gynaecology, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu St., 020021 Bucharest, Romania 3 Department of Intensive Care, University Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu St., 020021 Bucharest, Romania 4 Department of Community Health, “Iuliu Hat, ieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania 5 Department of Obstetrics and Gynaecology, Nicolae Malaxa Clinical Hospital, 020346 Bucharest, Romania; [email protected] 6 Department of Clinical Laboratory, Food Safety, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945 Bucharest, Romania; [email protected] * Correspondence: [email protected] (O.N.P.); [email protected] (B.A.N.) Abstract: Increasing numbers of women are undergoing oocyte or tissue cryopreservation for medical or social reasons to increase their chances of having genetic children. Social egg freezing (SEF) allows women to preserve their fertility in anticipation of age-related fertility decline and ineffective fertility treatments at older ages. The purpose of this study was to summarize recent findings focusing on the challenges of elective egg freezing. -
New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing As a Potential Predictor of Health Status of Babies
Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 306505, 8 pages http://dx.doi.org/10.1155/2014/306505 Review Article New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing as a Potential Predictor of Health Status of Babies Tanya Milachich SAGBAL Dr. Shterev, IVF Unit, Hristo Blagoev 25-31, 1330 Sofia, Bulgaria Correspondence should be addressed to Tanya Milachich; tanya [email protected] Received 24 December 2013; Revised 13 February 2014; Accepted 15 February 2014; Published 24 March 2014 Academic Editor: Irma Virant-Klun Copyright © 2014 Tanya Milachich. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. -
Live Births After Polar Body Biopsy and Frozen-Thawed Cleavage Stage Embryo Transfer: Case Report
JBRA Assisted Reproduction 2016;20(4):253-256 doi: 10.5935/1518-0557.20160049 Case Report Live births after polar body biopsy and frozen-thawed cleavage stage embryo transfer: case report Fernando Guimarães1, Matheus Roque1,2, Marcello Valle1, Alessandra Kostolias1, Rodrigo A de Azevedo1, Ciro D Martinhago3, Marcos Sampaio4, Selmo Geber2,4 1ORIGEN – Center for Reproductive Medicine, Rio de Janeiro/RJ - Brazil 2UFMG – Universidade Federal de Minas Gerais, Belo Horizonte/MG - Brazil 3Chromosome Genomic Medicine, São Paulo/SP - Brazil 4ORIGEN – Center for Reproductive Medicine, Belo Horizonte/MG - Brazil ABSTRACT 2002). To perform the biopsy, it is important to cause a Pre-implantation genetic diagnosis (PGD) or screening disruption of the zona pellucida of the oocyte or embryo (PGS) technology, has emerged and developed in the past occurs, which can be performed mechanically, chemically few years, benefiting couples as it allows the selection and or using laser (Brezina et al., 2012). The key point of PGD/ transfer of healthy embryos during IVF treatments. These PGS is to have access to the genetic material to be evalu- techniques can be performed in oocytes (polar-body biop- ated, without compromising the material analyzed and the sy) or embryos (blastomere or trophectoderm biopsy). In quality of the oocyte/embryo (Xu & Montag, 2012). this case report, we describe the first two live births to be Polar body (PB) biopsy was introduced in 1990 (Ver- published in Brazil after a polar-body (PB) biopsy. In case linsky et al., 1990), and it is associated with a less inva- 1, a 42-year-old was submitted to PB biopsy with PGS due sive technique, presenting advantages, because it main- to advanced maternal age and poor ovarian reserve. -
Preimplantation Genetic Diagnosis
REVIEW Review Preimplantation genetic diagnosis Karen Sermon, André Van Steirteghem, Inge Liebaers Preimplantation genetic diagnosis (PGD) was introduced at the beginning of the 1990s as an alternative to prenatal diagnosis, to prevent termination of pregnancy in couples with a high risk for offspring affected by a sex-linked genetic disease. At that time, embryos obtained in vitro were tested to ascertain their sex, and only female embryos were transferred. Since then, techniques for genetic analysis at the single-cell level, involving assessment of first and second polar bodies from oocytes or blastomeres from cleavage-stage embryos, have evolved. Fluorescence in-situ hybridisation (FISH) has been introduced for the analysis of chromosomes and PCR for the analysis of genes in cases of monogenic diseases. In-vitro culture of embryos has also improved through the use of sequential media. Here, we provide an overview of indications for, and techniques used in, PGD, and discuss results obtained with the technique and outcomes of pregnancies. A brief review of new technologies is also included. Preimplantation genetic diagnosis (PGD) is an early form of described; fluorescence in-situ hybridisation (FISH) has prenatal diagnosis, in which embryos created in vitro are since replaced PCR as a reliable method for the sexing of analysed for well-defined genetic defects; only those free of embryos,7,8 and has been widely used for PGD-AS and for the defects are replaced into the womb.1 The technique is detection of imbalanced forms of chromosomal used mainly in two broad indication groups. The first group aberrations.2,9,10 are individuals at high risk of having a child with a genetic Here, we discuss methods used for diagnosis of genetic disease—eg, carriers of a monogenic disease or of diseases, indications for PGD and PGD-AS, results chromosomal structural aberrations, such as transloca- obtained with the techniques, and subsequent outcomes tions—who have repeatedly opted to terminate their of pregnancies. -
Analysis of Nine Chromosome Probes in First Polar Bodies and Metaphase II Oocytes for the Detection of Aneuploidies
European Journal of Human Genetics (2003) 11, 325–336 & 2003 Nature Publishing Group All rights reserved 1018-4813/03 $25.00 www.nature.com/ejhg ARTICLE Analysis of nine chromosome probes in first polar bodies and metaphase II oocytes for the detection of aneuploidies Aı¨da Pujol*,1, Irene Boiso2, Jordi Benet1, Anna Veiga2, Merce` Durban1, Mercedes Campillo3, Josep Egozcue1 and Joaquima Navarro1 1Departament de Biologia Cel.lular, Fisiologia i Immunologia, Unitat de Biologia, Facultat de Medicina, Universitat Auto`noma de Barcelona, E-08193 Bellaterra, Spain; 2Servei de Medicina de la Reproduccio´, Institut Universitari Dexeus, Pg. Bonanova 89-91, E-08017 Barcelona, Spain; 3Laboratori de Medicina Computacional, Unitat de Bioestadı´stica, Facultat de Medicina, Universitat Auto`noma de Barcelona, Spain We used fluorescent in situ hybridisation (FISH) to detect nine chromosomes (1, 13, 15, 16, 17, 18, 21, 22 and X) in 89 first Polar Bodies (1PBs), from in vitro matured oocytes discarded from IVF cycles. In 54 1PBs, we also analysed the corresponding oocyte in metaphase II (MII) to confirm the results; the other 35 1PBs were analysed alone as when preimplantation genetic diagnosis using 1PB (PGD-1PB) is performed. The frequency of aneuploid oocytes found was 47.5%; if the risk of aneuploidy for 23 chromosomes is estimated, the percentage rises to 57.2%. Missing chromosomes or chromatids found in 1PBs of 1PB/MII doublets were confirmed by MII results in 74.2%, indicating that only 25.8% of them were artefactual. Abnormalities observed in 1PBs were 55.8% whole-chromosome alterations and 44.2% chromatid anomalies. We observed a balanced predivision of chromatids for all chromosomes analysed. -
Triggering Final Oocyte Maturation with Gonadotropin-Releasing
J Assist Reprod Genet (2014) 31:927–932 DOI 10.1007/s10815-014-0248-6 FERTILITY PRESERVATION Triggering final oocyte maturation with gonadotropin-releasing hormone agonist (GnRHa) versus human chorionic gonadotropin (hCG) in breast cancer patients undergoing fertility preservation: an extended experience Jhansi Reddy & Volkan Turan & Giuliano Bedoschi & Fred Moy & Kutluk Oktay Received: 5 February 2014 /Accepted: 5 May 2014 /Published online: 23 May 2014 # Springer Science+Business Media New York 2014 ABSTRACT Conclusions GnRHa trigger improved cycle outcomes as evi- Purpose To analyze the cycle outcomes and the incidence of denced by the number of mature oocytes and cryopreserved ovarian hyperstimulation syndrome (OHSS), when oocyte embryos, while significantly reducing the risk of OHSS in maturation was triggered by gonadotropin-releasing hormone breast cancer patients undergoing fertility preservation. agonist (GnRHa) versus human chorionic gonadotropin (hCG) in breast cancer patients undergoing fertility preservation. Keywords Fertility preservation . Breast cancer . Trigger . Methods One hundred twenty-nine women aged≤45 years, GnRH agonist . hCG diagnosed with stage≤3 breast cancer, with normal ovarian reserve who desired fertility preservation were included in the retrospective cohort study. Ovarian stimulation was achieved utilizing letrozole and gonadotropins. Oocyte maturation was Introduction triggered with GnRHa or hCG. Baseline AMH levels, number of oocytes, maturation and fertilization rates, number of em- Breast cancer is the most common malignancy diagnosed in bryos, and the incidence of OHSS was recorded. women worldwide. Early detection and improvements in Results The serum AMH levels were similar between GnRHa screening have increased the number of premenopausal women and hCG groups (2.7±1.9 vs. -
Oocyte Warming and Insemination Consent Form
Oocyte Warming and Insemination Process, Risk, and Consent While embryos and sperm have been frozen and thawed with good results for many years, eggs have proved much more difficult to manage. Newer egg freezing methods have been more successful, at least in younger women, the main population in which the techniques have been studied. Egg freezing takes place by one of two methods: a slow freeze protocol, or a different “flash freeze” method known as vitrification. USF IVF uses the newer vitrification technology exclusively. There are two sources of frozen eggs. Some women may have chosen to have had their eggs frozen for the purpose of fertility preservation at some time prior to warming. Other women may have obtained frozen eggs donated by an egg donor. This consent reviews the Oocyte warming process from start to finish, including the risks that this treatment might pose to you and your offspring. While best efforts have been made to disclose all known risks, there may be risks of oocyte freezing, subsequent warming, and the IVF process, that are not yet clarified or even suspected at the time of this writing. Oocyte warming and subsequent embryo transfer typically includes the following steps or procedures: Medications to prepare the uterus to receive embryos Oocyte warming Insemination of eggs that have survived warming with sperm, using intracytoplasmic sperm injection (ICSI) Culture of any resulting fertilized eggs (embryos) Placement (transfer) of one or more embryos into the uterus Support of the uterine lining with hormones to permit and sustain pregnancy In certain cases, these additional procedures can be employed: Assisted hatching of embryos to potentially increase the chance of embryo attachment (implantation) Cryopreservation (freezing) of embryos Is pregnancy achieved as successfully with frozen eggs as with fresh eggs? As mentioned, most studies have looked at success rates using either donor eggs or women who produced larger numbers of eggs. -
Polar Body Biopsy – Advantages of the Eppendorf Micromanipulation System
APPLICATION NOTE No. 140 Polar body biopsy – Advantages of the Eppendorf micromanipulation system Markus Montag University Gynecological Hospital Heidelberg, Department of Gynecological Endocrinology and Fertility Disorders, Heidelberg, Germany Abstract A well-established technique which is used in preim- is followed by detection of certain chromosomes using plantation genetic diagnostics (PGD) is polar body (PB) fluorescencein-situ hybridization (FISH) or detection of biopsy. The polar bodies of the oocyte are extruded at all chromosomes by comparative genomic hybridization. the conclusion of the meiotic division; normally the first Using the Eppendorf micromanipulation system with polar body is noted after ovulation; the second polar body manual injectors and the electronic TransferMan® 4m is observed 2–3 h following entry of the sperm into the micromanipulators in combination with the OCTAX Laser oocyte. Removal of the first and second polar bodies takes Shot™ System, fast and sensitive handling of the oocyte place 6–12 hours after the performance of intracytoplasmic and polar bodies can be guaranteed. sperm injection (ICSI). The biopsy of the polar bodies Introduction Over the past few decades the mean age of women conceiving their first child has steadily increased. However, advanced maternal age lowers the chance for pregnancy and increases the risk of miscarriage once a woman is pregnant. One major problem strongly correlated to maternal age is the occurrence of numerical chromosomal abnormalities in human oocytes. In women who are 40 years old and older, up to 70 % of their oocytes can be chromosomally abnormal [1, 2]. In the context of assisted reproduction treatment, it is possible to identify and exclude such oocytes, thereby increasing the success rate.