Reproductive Screening Special Interest Group

The Reproductive Screening SIG (formerly the Prenatal Screening SIG) fosters and encourages the provision of clinically useful and scientifically valid prenatal screening.

SIG Topics of Discussion/Interest

  • Serum and ultrasound markers for fetal and maternal conditions
  • cf-DNA based screening
  • Carrier screening for monogenic disorders
  • Quality control and quality assurance
  • Ethical, legal and social aspects
  • Clinical trials
  • New Methods
  • Policies
  • Community Education and Information
  • Health Professional Training
  • Epidemiology

Article submitted to Global Updates, November 2018

Chromosomal mosaicism detected on trophectoderm biopsy during preimplantation genetic testing for aneuploidy (PGT-A): "The elephant in the room"

Francesca Romana Grati1 and Yuval Yaron2

  1. R&D, Cytogenetics and Medical Genetics Unit, TOMA Advanced Biomedical Assays S.p.A., Busto Arsizio, Varese, Italy
  2. Prenatal Genetic Diagnosis Unit, Genetic Institute, Tel Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

In accordance with ISPD policy, Yuval Yaron discloses that he is a member of  the  Clinical Expert Panel for Reproductive and Genomic Health at Illumina, Inc which may be affected by the research reported in the following article. Francesca Romana Grati has no conflict of interest to disclose. 

Chromosomal mosaicism represents one of the main interpretative dilemmas not only in prenatal diagnosis but also in pre-implantation genetic testing for aneuploidy (PGT-A) performed on trophoectoderm. Recent studies have demonstrated that, comprehensive chromosome screening (CCS) of all 24 chromosomes may detect a chromosomal mosaicism in up to 21% of the screened embryos.1 Such results are a troubling source of uncertainty in decision-making regarding embryo transfer.

The Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology have issued a Committee Opinion on the use of PGT-A.2 They note that viable euploid pregnancies have been achieved after the transfer of mosaic embryos, albeit at lower rates. This is in accord with the experience accumulated from prenatal diagnosis using chorionic villus samples (CVS) and amniocentesis, which demonstrate that mosaic aneuploidies are usually confined to trophoblast and placenta without involving fetal tissues.3 Thus, although the transfer of mosaic embryos may be associated with poorer outcome, it is understandable that there is a compelling concern that viable embryos may be unjustifiably discarded because of mosaicism.

To better evaluate the potential of mosaic aneuploid embryos available for transfer, a prioritization scoring system has been devised. Because the trophectoderm cells used for PGT-A are the embryologic precursors of cytotrophoblast cells investigated during cytogenetic analysis of first trimester direct preparation of chorionic villi,4 PGT-A on trophoectoderm might be viewed as a very early direct preparation of CVS. This evidence allowed the utilization the large cytogenetic diagnostic experience on mosaic CVS and confirmatory amniocentesis, as well as on products of conception, to devise an evidence-based algorithm for prioritization of mosaic aneuploid embryo for transfer.5

For each possible chromosomal aneuploidy, risks of four different adverse outcomes were scored including: 1) the likelihood that a mosaic aneuploidy detected in the trophoblast by CVS is also present in the fetus; 2) the risk of uniparental disomy (UPD) in the fetus; 3) the risk of a mosaic aneuploid miscarriage and 4) the likelihood that mosaic or full aneuploidies can lead to viable affected births with a well-characterized phenotype. This score was calculated for all chromosome aneuploidy and for each possible adverse outcome. The composite score was then derived by summing up all risk scores for possible adverse outcome. This allows prioritization of mosaic aneuploid embryo for transfer. In this context, genetic counseling after PGT-A becomes, therefore, a fundamental phase to allow couples and caregivers to evaluate the possibility of a mosaic embryo transfer based on the possible outcomes and clinical manifestations thereof.

The same algorithm could aid for the management of pregnancies obtained after mosaic aneuploid embryo transfer. Based on the composite score, pregnancies from aneuploid mosaic embryos can be stratified into different risk groups with different priority level for confirmatory invasive procedure. Due to the increased risk of finding in CV the same mosaic aneuploidy previously detected during PGT-A on trophectoderm cells, amniocentesis is the best approach for confirmatory invasive procedure in this group of pregnancies. Genomewide cell-free DNA test for all chromosome aneuploidies shows limited clinical utility in these pregnancies as it analyses cell-free DNA circulating fragments derived from the apoptosis of the cytotrophoblast thereby it may be considered a replicate of the PGT-A analysis on trophectoderm cells.

The aforesaid priority scores regarding autosomal trisomies should also apply to the respective mosaic autosomal monosomies. This is because these are most likely the result of a post-zygotic nondisjunction error generating two daughter cells: one trisomic and one monosomic, often in addition to a euploid cell line already present in the conceptus. Therefore, the detection of a monosomic cell line in the biopsied trophoblast would imply the likely presence of the respective trisomic cell line elsewhere in the embryo.

Until prospective clinical follow-up studies on transferred mosaic embryos provide definite answers, this scoring system offers a simple evidence-based tool for decision making and an aid for patient counselling both before embryo transfer as well as during pregnancy .


  1. Munné S, Wells D. Detection of mosaicism at blastocyst stage with the use of high-resolution next-generation sequencing. Fertil Steril. 2017;107(5):1085-109
  2. Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. The use of preimplantation genetic testing for aneuploidy (PGT-A): a committee opinion. Fertil Steril. 2018 Mar;109(3):429-436
  3. Malvestiti F, Agrati C, Grimi B, Pompilii E, Izzi C, Martinoni L, Gaetani E, Liuti MR, Trotta A, Maggi F, Simoni G, Grati FR, 2015. Interpreting mosaicism in chorionic villi: results of a monocentric series of 1001 mosaics in chorionic villi with follow-up amniocentesis. Prenat Diagn.35, 1117-1127
  4. Bianchi DW, Wilkins-Haug LE, Enders AC, Hay ED. Origin of extraembryonic mesoderm in experimental animals: relevance to chorionic mosaicism in humans. Am J Med Genet. 1993 Jun 15;46(5):542-50
  5. Grati FR, Gallazzi G, Branca L, Maggi F, Simoni G, Yaron Y. An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening. Reprod Biomed Online. 2018 Apr;36(4):442-449. doi: 10.1016/j.rbmo.2018.01.005

SIG Leadership

Co-Chair: Lorraine Dugoff, MD

Co-Chair: Liona Poon, MD

Board LiaisonSebastian Illanes, MD, MSc

SIG Roster


11 July 2017 - San Diego, California, USA
11 July 2016 - Berlin, Germany
11 July 2016 - SIGs and Education Committee
13 July 2015 - Washington, DC USA
23 July 2014 - Brisbane, Australia
05 June 2013 - Lisbon, Portugal
06 June 2012 - Miami, Florida, USA
04 June 2008 - Vancouver, Canada