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Alan H Handyside

Alan H Handyside
Vitrolife Sweden AB Gothenburg Sweden

MA PhD (Cantab)

About

310
Publications
23,543
Reads
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Introduction
An internationally-recognised pioneer and expert in human embryology and preimplantation genetics with an extensive research portfolio, track record for innovation in single cell diagnostics (including two patents) and 15 years experience in management in the private IVF sector in the UK.
Additional affiliations
September 2012 - present
University of Kent
Position
  • Honorary Professor of Reproductive Genetics
August 1999 - July 2005
University of Leeds
Position
  • Professor Of Developmental Biology

Publications

Publications (310)
Article
Chromosome testing strategies, such as PGT-A, are designed to improve an IVF embryo transfer outcome by avoiding the unwitting selection of aneuploid embryos as occurs in morphology-based approaches. Newer testing technologies have revealed that some embryos may appear to have intermediate whole chromosome (or parts of a chromosome termed segmental...
Article
Full-text available
Approximately one million in vitro produced (IVP) cattle embryos are transferred worldwide each year as a way to improve the rates of genetic gain. The most advanced programmes also apply genomic selection at the embryonic stage by SNP genotyping and the calculation of genomic estimated breeding values (GEBVs). However, a high proportion of cattle...
Article
Full-text available
Contemporary systems for oocyte retrieval and culture of both cattle and human embryos are suboptimal with respect to pregnancy outcomes following transfer. In humans, chromosome abnormalities are the leading cause of early pregnancy loss in assisted reproduction. Consequently, pre-implantation genetic testing for aneuploidy (PGT-A) is widespread a...
Article
Full-text available
Preimplantation genetic testing for aneuploidy (PGT‐A) by copy number analysis is now widely used to select euploid embryos for transfer. Whole or partial chromosome aneuploidy can arise in meiosis, predominantly female meiosis, or in the postzygotic, mitotic divisions during cleavage and blastocyst formation, resulting in chromosome mosaicism. Mei...
Article
Following early studies showing no adverse effects, cleavage stage biopsy by zona drilling using acid Tyrode's solution, and removal of single blastomeres for preimplantation genetic testing (PGT) and identification of sex in couples at risk of X-linked disease, was performed by Handyside and colleagues in late 1989, and pregnancies reported in 199...
Article
Full-text available
Objective: To evaluate the benefit of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) for embryo selection in frozen-thawed embryo transfer. Design: Randomized controlled trial. Setting: Not applicable. Patient(s): Women aged 25-40 years undergoing IVF with at least two blastocysts that could be...
Article
Despite improvements in culture conditions and laboratory techniques still only about 50% of human embryos reach the blastocyst stage of development in vitro. While many factors influence embryo development, aberrant cleavage divisions have only recently been shown to directly affect the genome in individual cells of human embryos resulting in chro...
Article
Objectives Karyomapping was developed as a means of screening for monogenic and chromosomal disorders simultaneously in human IVF embryos using SNP chips. SNP chips in cattle breeding on the other hand are used for genomic selection i.e. to establish estimated breeding values (e.g. for food conversion efficiencies, milk production etc.). This has l...
Article
Using comprehensive screening techniques, several small and single-center RCTs have shown that Preimplantation genetic testing for aneuploidy (PGT-A) increases pregnancy and live birth rates per transfer compared to morphology alone. These studies were mostly performed by very experienced IVF and PGT laboratories. Next generation sequencing (NGS) b...
Article
Abnormal chromosome number or aneuploidy has been recognised as a major contributor to implantation and pregnancy failure and miscarriage since the earliest years of IVF following the birth of Louise Brown forty years ago. Already in 1986, for example, Angell and colleagues, reported “Evidence was found of nondisjunction, resulting in trisomy, mono...
Article
This study reports the results of a 2-year long IVF programme (‘One by One’) in which all patients (median age 40 years; range 27–45 years) were offered preimplantation genetic testing for aneuploidy (PGT-A) and had all blastocysts vitrified (freeze-only), followed later by single vitrified-warmed blastocyst transfer (vSET) in managed cycles. Betwe...
Article
Full-text available
In cattle breeding, the development of genomic selection strategies based on single nucleotide polymorphism (SNP) interrogation has led to improved rates of genetic gain. Additionally, the application of genomic selection to in-vitro produced (IVP) embryos is expected to bring further benefits thanks to the ability to test a greater number of indiv...
Article
This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.
Article
The first pregnancies and live births following IVF and preimplantation genetic testing (PGT), formerly known as preimplantation genetic diagnosis (PGD), were reported in 1990, almost 30 years ago, in several couples at risk of X-linked inherited conditions, which typically only affect boys inheriting the X chromosome with the affected gene from th...
Article
Aneuploidy is prevalent in human embryos and is the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing with maternal age. Superimposed on these meiotic aneuploidies are frequent errors occurring during early mitotic divisions, contributing to widespread chromosomal mosaicism. Here we reanalyzed a published dataset...
Article
Full-text available
Following in vitro fertilisation (IVF), only about half of normally fertilised human embryos develop beyond cleavage and morula stages to form a blastocyst in vitro. Although many human embryos are aneuploid and genomically imbalanced, often as a result of meiotic errors inherited in the oocyte, these aneuploidies persist at the blastocyst stage an...
Preprint
Full-text available
Aneuploidy is prevalent in human preimplantation embryos and is the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing in frequency with maternal age. Superimposed on these meiotic aneuploidies are a range of errors occurring during early mitotic divisions of the embryo, contributing to widespread chromosomal mosa...
Article
We have developed a protocol for the generation of genome-wide maps (meiomaps) of recombination and chromosome segregation for the three products of human female meiosis: the first and second polar bodies (PB1 and PB2) and the corresponding oocyte. PB1 is biopsied and the oocyte is artificially activated by exposure to calcium ionophore, after whic...
Article
Full-text available
Study hypothesis We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0. Study finding Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS. What is kn...
Article
Objective: To study the effect of artificial oocyte activation (AOA) on chromosome segregation errors in the meiotic divisions. Design: Prospective cohort study with historical control. Setting: Private/academic IVF centers. Patient(s): Fifty-six metaphase II oocytes were donated from 12 patients who had undergone IVF between June 2008 and M...
Article
Blastocyst biopsy is now widely used for both preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). Although this approach yields good results, variable embryo quality and rates of development remain a challenge. Here, a case is reported in which a blastocyst was biopsied for PGS by array comparative genomic hybridiza...
Data
Supplementary Table 3. Recombination frequencies in embryos. Supplementary Table 4. Structural rearrangements to chromosomes in meiosis. Supplementary Table 5. Summary of recombination and chromosome segregation in all trios. Supplementary Table 6. Map distances in embryos. Supplementary Table 7. Crossovers in oocytes. Supplementary Table 8. Recomb...
Data
Supplementary Table 1. Donor information of embryos. Supplementary Table 2. Donor information of oocyte-PB trios.
Article
Full-text available
Crossover recombination reshuffles genes and prevents errors in segregation that lead to extra or missing chromosomes (aneuploidy) in human eggs, a major cause of pregnancy failure and congenital disorders. Here we generate genome-wide maps of crossovers and chromosome segregation patterns by recovering all three products of single female meioses....
Article
Full-text available
IntroductionPreimplantation genetic diagnosis (PGD) of single gene defects by genetic analysis of single or small numbers of cells biopsied from in vitro fertilization (IVF) embryos is clinically well-established. Targeted haplotyping by multiplex fluorescent polymerase chain reaction (PCR) of closely linked or intragenic short tandem repeat (STR)...
Article
Preimplantation genetic diagnosis (PGD) for monogenic disorders has the drawback of time and cost associated with tailoring a specific test for each couple, disorder, or both. The inability of any one single assay to detect the monogenic disorder in question or the chromosomal complement of the embryo also limits its application as separate tests m...
Article
Full-text available
Purpose: Our aim was to compare the accuracy of family- or disease-specific targeted haplotyping and direct mutation-detection strategies with the accuracy of genome-wide mapping of the parental origin of each chromosome, or karyomapping, by single-nucleotide polymorphism genotyping of the parents, a close relative of known disease status, and the...
Article
Chromosome aneuploidy, an abnormal number of chromosomes, in human gametes and embryos is a major cause of IVF failure and miscarriage and can result in affected live births. To avoid these outcomes and improve implantation and live birth rates, preimplantation genetic screening aims to identify euploid embryos before transfer but has been restrict...
Article
Single cell analysis for preimplantation genetic diagnosis (PGD) of single gene defects was first used to identify the sex of embryos in a series of couples at risk of various X-linked conditions, which typically only affect males. The use of PCR at the single cell level was still in its infancy and even doubling the typical number of amplification...
Article
Objective: The timing of embryo development, measured by non-invasive time-lapse imaging, is significantly altered in embryos with single or multiple aneuploidies ascertained by cleavage stage biopsy and single cell analysis by array CGH. The aim in the current study was to identify whether there are significant differences in embryo morphokinetic...
Article
Full-text available
Study question: How accurate is array comparative genomic hybridization (array CGH) analysis of the first polar body (PB1) and second polar body (PB2) in predicting aneuploidies of maternal meiotic origin in the cleavage stage embryos of women of advanced maternal age? Summary answer: Almost all of the aneuploidies detected in cleavage stage emb...
Article
Full-text available
BACKGROUND Genetic testing of preimplantation embryos has been used for preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Microarray technology is being introduced in both these contexts, and whole genome sequencing of blastomeres is also expeted to become possible soon. The amount of extra information such tests...
Article
Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the menopause. Molecular genetic analysis has shown that these are predominantly maternal in origin and trisomies most f...
Article
Introduction: Polar body analysis by array comparative genomic hybridisation (array CGH) has demonstrated a high incidence of errors in female meiosis resulting in aneuploidy in the oocytes and corresponding embryos of women of advanced maternal age undergoing in vitro fertilisation (IVF). These errors are predominantly caused by premature predivis...
Conference Paper
Full-text available
Aim: To analyse the segregation of the translocation chromosomes in the two meiotic divisions in a female carrier (41 yrs) of a reciprocal translocation, 46, ΧΧ, t(16; 17)(q24; p11), by array CGH analysis of the first (PB1) and second polar bodies (PB2) and follow up of the corresponding cleavage stage embryos. Method: PB1 was biopsied from 18 meta...
Article
Full-text available
Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the menopause. Molecular genetic analysis following natural conception and spontaneous miscarriage demonstrates that tri...
Article
Introduction: Polar body analysis by array comparative genomic hybridisation (array CGH) has demonstrated a high incidence of errors in female meiosis resulting in aneuploidy in the oocytes and corresponding embryos of women of advanced maternal age undergoing in vitro fertilisation (IVF). These errors are predominantly caused by premature predivis...
Article
Full-text available
Vitrification of human blastocysts is being used increasingly to cryopreserve supernumerary embryos following IVF. In this study, we investigate the effects of aseptic vitrification on the cytoskeleton and development of human blastocysts, by analysing survival rates and spindle and chromosome configurations by fluorescence and confocal laser scann...
Article
Bisignano et al. (2011) argue that, for preimplantation genetic diagnosis (PGD) of aneuploidy for all 24 chromosomes, microarray-based comparative genomic hybridization (array CGH) is superior to the use of single-nucleotide polymorphism (SNP) genotyping arrays. Published studies indicate that both technologies accurately detect aneuploidy of whole...
Article
Full-text available
Several randomized controlled trials have not shown a benefit from preimplantation genetic screening (PGS) biopsy of cleavage-stage embryos and assessment of up to 10 chromosomes for aneuploidy. Therefore, a proof-of-principle study was planned to determine the reliability of alternative form of PGS, i.e. PGS by polar body (PB) biopsy, with whole g...
Article
Full-text available
The purpose of this study was to assess the technical aspects related to polar body (PB) biopsy, which might have an influence on the results of the microarray comparative genomic hybridization analysis. Furthermore, a comparison was made between two biopsy methods (mechanical and laser). Biopsy of the first and second PB (PB1 and PB2) was performe...
Article
Full-text available
Aneuploidy (the presence of extra or missing chromosomes) arises primarily through chromosome segregation errors in the oocyte at meiosis I but the details of mechanism by which such errors occur in humans are the subject of some debate. It is generally believed that aneuploidy arises primarily as a result of segregation of a whole chromosome to th...
Article
Preimplantation genetic diagnosis (PGD) of inherited conditions following in vitro fertilization (IVF) is now clinically well established worldwide and 7000 children have been born. The range of applications includes single gene defects, chromosome aneuploidy and structural abnormalities, and HLA matching, to identify histocompatible embryos for co...