Chromosomal abnormalities often neglected at the time of embryo selectionConventional methods of embryo selection• Embryoscopy• Physical identification• Morphological characteristics
• Aneuploidy: atypical number of chromosomes results from error in cell division• Translocations: a piece of chromosome go and attached to a wrong chromosome.• Chromosome Deletions : loss of a chromosome segment resulting in an imbalance in the number of genes present• Chromosome inversions: when a single chromosome breaks in two places and the material is reconstituted upside down……leading to embryo death, miscarriage or live birth of an infant with substantial medical problems.
• A healthy baby has 46 chromosomes in each cell of the body• Chromosomal abnormality refers to an atypical number of chromosomes and is generally caused by an error in cell division in either the egg or sperm or in the first few days of embryo development.
Normal cell MeiosisEmbryos with chromosomal abnormalities are less likely to implant and more likely to end in miscarriage
Age in Normal Aneuploidy Otheryears embryos (%) embryos (%) abnormalities (%)25-35 61 8 3136-37 60 10 3038-39 47 18 3540-41 43 26 3142-44 39 30 31 http://www.fertilityindia.com/indications-for-pgd.php
• Decreased embryo transfer• Implantation failure,• Recurrent pregnancy loss, or miscarriage• Birth defects• Mental or physical problems in offspring
Babies born with chromosome abnormalitieshave mental retardation and / or birth defects Ex: Down syndrome
• Age more than 35 years (chances of embryo transfer (<75%)• Couples with a family history of X-linked disorders (25% risk of having an affected embryo)• Carriers of autosomal recessive diseases: means two copies of an abnormal gene (the risk an embryo may be affected is 25%.)• Carriers of autosomal dominant diseases: abnormal gene in one parent (the risk an embryo may be affected is 50%.)
Typical scenario Carrier mother + Normal father 25% chances 25% chances 25% chances 25% chancesof Normal boy of disease boy of Normal girl of carrier girl Disease father + Normal mother 100% chances of 100% chances of Normal boy carrier girl Carrier: Some one has one abnormal gene (No symptoms) is called a carrier
Women with X-linked recessive disorder are rare, since women has two X-chromosomes. Two scenarios: Carrier mother + Disease father 25% chances 25% chances 25% chances 25% chancesof Normal boy of disease boy of carrier girl of disease girl Disease father + Disease mother 100% chances disease boy or girl http://www.fertilityindia.com/indications-for-pgd.php
Egg Sperm Embryo 8 cell stageRemove one cell On day 3rd Test DNA or Test results chromosomes Healthy gen Unhealthy gen conditions conditions Embryo implanted Embryo on day 4 discarded
• Couples with advanced maternal age (>35)• Unexplained infertility• Y-chromosome deletion: found in 5-20% men with low sperm count• Couples who have experienced repeated miscarriages• Couples who have experienced repeated IVF failures• Couples who have previously had a pregnancy with a chromosomal abnormality• Couples at risk of having children with a particular X-linked disorder• couples where one partner carries a balanced chromosomal translocations
• In only few centers it is available in India• Most well known center is Jaslok Hospital, Mumbai• It takes 3 days• It is limited to chromosomes 13, 18, 21 only
• PGD is highly accurate across all chromosomes• It yields quick results which allows for a fresh embryo transfer on day 4 when it is tested on day 3• PGD prevents transmission of genetic disorders onto future generations.
• There are two main types of preimplantation genetic screening – Aneuploidy screening by fluorescent in situ hybridization (FISH) and – Aneuploidy screening by Molecular Array Comparative Genomic Hybridization (CGH-24)
• It screens the most common chromosomes seen in miscarriages and live born abnormality disorders like Down syndrome-chromosomes 13, 16, 18, 21 and 22.• When one parent is carrier of heritable X-linked disease such as Muscular dystrophy, Hemophilia A, or ectodermal Dysplasia.• FISH examines chromosomes X and Y plus chromosomes 13, 18, and 21
• This is single cell technology to test aneuploidy, translocations, inversion and chromosomal abnormality• It is unique and it can make thousands of independent measurements of each chromosome at molecular level• No freezing and ICISI is required• It is automated and high degree of results accuracy• It gives the results with 20 hours than the standard 36-48 hours
• On day 3rd: Biopsy of a blastomere from an embryo at IVF center – The fixation of blastomere on slides for FISH analysis or transfer into PCR tube with lysis buffer for CGH analysis – Test for FISH or CGH at genetic center : results within 12-20 hours• Day 4: Embryo transfer on day 4