Committee Opinion No. 406: Prenatal Testing After IVF With Preimplantation Genetic Testing for Aneuploidy

Published:August 21, 2020DOI:



      To review the approach to prenatal genetic screening and diagnosis for chromosomal abnormalities in pregnancies conceived through in vitro fertilization and following preimplantation genetic testing for aneuploidy.

      Intended Users

      General practitioners, family physicians, obstetricians, midwives, nurses, maternal–fetal medicine specialists, fertility specialists, genetic counsellors, geneticists, and other health care providers involved in prenatal screening.

      Target Population

      All individuals or couples who conceivd through in vitro fertilization and underwent preimplantation genetic testing for aneuploidy.


      Literature published in or before September 2018 was retrieved through searches of Medline, PubMed, and the Cochrane Library.


      • 1
        Preimplantation genetic testing for aneuploidy is a screening test for aneuploidy; its precise sensitivity and specificity are not known because of limited available data.
      • 2
        Blastocyst mosaicism can contribute to errors (false positive and false negative results) in preimplantation genetic testing for aneuploidy and the results may or may not reflect the chromosomal complement of the inner cell mass.
      • 3
        Traditional prenatal genetic screening algorithms for trisomies 21 and 18 are not appropriate for pregnancies conceived after preimplantation genetic testing for aneuploidy and euploid embryo transfer.
      • 4
        Given the performance of preimplantation genetic testing for aneuploidy as a screening test, multiple marker screening (including enhanced first-trimester screening) for trisomies 21 and 18 is not recommended for pregnancies conceived after preimplantation genetic testing for aneuploidy and euploid embryo transfer.
      • 5
        Non-invasive prenatal testing using maternal plasma circulating cell-free DNA for common aneuploidies can be considered for pregnancies conceived after preimplantation genetic testing for aneuploidy and euploid embryo transfer in combination with thorough genetic counselling of the patient.
      • 6
        Universal screening for adverse pregnancy outcomes using maternal serum markers for aneuploidy is currently not recommended outside of an investigational protocol and with informed consent. This recommendation applies to pregnancies conceived by in vitro fertilization with or without preimplantation genetic testing for aneuploidy.
      • 7
        All women who conceive after euploid embryo transfer with preimplantation genetic testing for aneuploidy should be offered an ultrasound scan between 110 and 140 weeks gestation.
      • 8
        Any abnormal findings at the time of the ultrasound scan at 110 to 140 gestation should prompt a referral for consideration of invasive diagnostic testing, irrespective of history of preimplantation genetic testing for aneuploidy and euploid embryo transfer.
      • 9
        Invasive diagnostic testing is not recommended for pregnancies conceived after preimplantation genetic testing for aneuploidy and transfer of a euploid embryo unless abnormal findings are detected on ultrasound or non-invasive prenatal testing indicates a high risk of aneuploidy.
      • 10
        Genetic counselling is strongly recommended for all women considering the transfer of a mosaic embryo.
      • 11
        All women who become pregnant after preimplantation genetic testing for aneuploidy and mosaic embryo transfer should be offered an ultrasound scan between 110 and 140 weeks gestation.
      • 12
        Multiple marker screening is not recommended for pregnancies conceived after preimplantation genetic testing for aneuploidy and mosaic embryo transfer.
      • 13
        Non-invasive prenatal testing is not recommended for pregnancies conceived after preimplantation genetic testing for aneuploidy and mosaic embryo transfer.
      • 14
        In pregnancies conceived after mosaic embryo transfer, invasive diagnostic testing is highly recommended, with amniocentesis strongly preferred over chorionic villus sampling.
      • 15
        Consultation with the genetic laboratory should take place prior to any invasive diagnostic procedure to ensure appropriate testing is initiated based on the results of preimplantation genetic testing for aneuploidy.



      IVF (in vitro fertilization), NGS (next-generation sequencing), NIPT (non-invasive prenatal testing), PGT-A (preimplantation genetic testing for aneuploidy), PGT-M (preimplantation genetic testing for monogenic diseases), PGT-SR (preimplantation genetic testing for structural rearrangements), SNP (single nucleotide polymorphism)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Obstetrics and Gynaecology Canada
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Gardner D
        • Schoolcraft W
        In vitro culture of human blastocysts.
        in: Jansen R Mortimer D Towards reproductive certainty: fertility and genetics beyond 1999: the plenary proceedings of the 11th World Congress on in vitro fertilization & human reproductive genetics. Pearl River. Parthenon, NY1999: 378-388
        • Zegers-Hochschild F
        • Adamson GD
        • Dyer S
        • et al.
        The International Glossary on Infertility and Fertility Care, 2017.
        Hum Reprod. 2017; 32: 1786-1801
        • Kung A
        • Munné S
        • Bankowski B
        • et al.
        Validation of next-generation sequencing for comprehensive chromosome screening of embryos.
        Reprod Biomed Online. 2015; 31: 760-769
        • Dahdouh E
        • Balayla J
        • Audibert F
        • et al.
        Technical update 323: preimplantation genetic diagnosis and screening.
        J Obstet Gynaecol Can. 2015; 37: 451-463
        • Forman E
        • Hong K
        • Ferry K
        • et al.
        In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial.
        Fertil Steril. 2013; 100: 100-107
        • Forman EJ
        • Hong KH
        • Franasiak JM
        • et al.
        Obstetrical and neonatal outcomes from the BEST trial: single embryo transfer with aneuploidy screening improves outcomes after in vitro fertilization without compromising delivery rates.
        Am J Obstet Gynecol. 2014; 210 (e1–6): 157
        • Yang Z
        • Salem SA
        • Liu X
        • et al.
        Selection of euploid blastocysts for cryopreservation with array comparative genomic hybridization (aCGH) results in increased implantation rates in subsequent frozen and thawed embryo transfer cycles.
        Mol Cytogenet. 2013; 6: 32
        • Yang Z
        • Liu J
        • Collins GS
        • et al.
        Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study.
        Mol Cytogenet. 2012; 5: 24
        • Scott RJ
        • Upham K
        • Forman E
        • et al.
        Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial.
        Fertil Steril. 2013; 100: 697-703
        • Munné S
        • Kaplan B
        • Frattarelli JL
        • et al.
        Global multicenter randomized controlled trial comparing single embryo transfer with embryo selected by preimplantation genetic screening using next-generation sequencing versus morphologic assessment.
        Fertil Steril. 2017; 108: e19
        • Maxwell SM
        • Grifo JA.
        Should every embryo undergo preimplantation genetic testing for aneuploidy? A review of the modern approach to in vitro fertilization.
        Best Pract Res Clin Obstet Gynaecol. 2018; 53: 38-47
        • Rosenwaks Z
        • Handyside AH
        • Fiorentino F
        • et al.
        The pros and cons of preimplantation genetic testing for aneuploidy: clinical and laboratory perspectives.
        Fertil Steril. 2018; 110: 353-361
        • Fragouli E
        • Munne S
        • Wells D
        The cytogenetic constitution of human blastocysts: insights from comprehensive chromosome screening strategies.
        Hum Reprod Update. 2019; 25: 15-33
        • Scott RJ
        • Ferry K
        • Su J
        • et al.
        Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study.
        Fertil Steril. 2012; 97: 870-875
        • Victor AR
        • Griffin DK
        • Brake AJ
        • et al.
        Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst.
        Hum Reprod. 2019; 34: 181-192
        • Fragouli E
        • Lenzi M
        • Ross R
        • et al.
        Comprehensive molecular cytogenetic analysis of the human blastocyst stage.
        Hum Reprod. 2008; 23: 2596-2608
        • Johnson DS
        • Cinnioglu C
        • Ross R
        • et al.
        Comprehensive analysis of karyotypic mosaicism between trophectoderm and inner cell mass.
        Mol Hum Reprod. 2010; 16: 944-949
        • Liu J
        • Wang W
        • Sun X
        • et al.
        DNA microarray reveals that high proportions of human blastocysts from women of advanced maternal age are aneuploid and mosaic.
        Biol Reprod. 2012; 87: 148
        • Orvieto R.
        Preimplantation genetic screening- the required RCT that has not yet been carried out.
        Reprod Biol Endocrinol. 2016; 14: 35
        • Huang J
        • Yan L
        • Lu S
        • et al.
        Re-analysis of aneuploidy blastocysts with an inner cell mass and different regional trophectoderm cells.
        J Assist Reprod Genet. 2017; 34: 487-493
        • Tiegs A
        • Hodes-Wertz B
        • McCulloh D
        • et al.
        Discrepant diagnosis rate of array comparative genomic hybridization in thawed euploid blastocysts.
        J Assist Reprod Genet. 2016; 33: 893-897
        • Werner MD
        • Leondires MP
        • Schoolcraft WB
        • et al.
        Clinically recognizable error rate after the transfer of comprehensive chromosomal screened euploid embryos is low.
        Fertil Steril. 2014; 102: 1613-1618
        • Munné S
        • Weier HUG
        • Grifo J
        • et al.
        Chromosome mosaicism in human embryos.
        Biol Reprod. 1994; 51: 373-379
        • Greco E
        • Minasi MG
        • Fiorentino F
        Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts.
        N Engl J Med. 2015; 373: 2089-2090
        • Munné S
        • Blazek J
        • Large M
        • et al.
        Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing.
        Fertil Steril. 2017; 108 (e8): 62-71
        • Spinella F
        • Fiorentino F
        • Biricik A
        • et al.
        Extent of chromosomal mosaicism influences the clinical outcome of in vitro fertilization treatments.
        Fertil Steril. 2018; 109: 77-83
        • Chitayat D
        • Langlois S
        • Wilson RD
        • et al.
        Prenatal screening for fetal aneuploidy in singleton pregnancies.
        J Obstet Gynaecol Can. 2011; 33: 736-750
        • Benn P
        • Borrell A
        • Chiu RWK
        • et al.
        Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis.
        Prenat Diagn. 2015; 35: 725-734
        • Committee on Practice Bulletins—Obstetrics, Committee on Genetics, Society for Maternal-Fetal Medicine
        Practice bulletin no. 163: screening for fetal aneuploidy.
        Obstet Gynecol. 2016; 127: e123-e137
        • Willems PJ
        • Dierickx H
        • Vandenakker E
        • et al.
        The first 3,000 non-invasive prenatal tests (NIPT) with the Harmony test in Belgium and the Netherlands.
        Facts Views Vis Obgyn. 2014; 6: 7-12
        • Gagnon A
        • Wilson RD
        • SOGC Genetics Committee
        Obstetrical complications associated with abnormal maternal serum markers analytes.
        J Obstet Gynaecol Can. 2008; 30: 918-932
        • Huang T
        • Hoffman B
        • Meschino W
        • et al.
        Prediction of adverse pregnancy outcomes by combinations of first and second trimester biochemistry markers used in the routine prenatal screening of Down syndrome.
        Prenat Diagn. 2010; 30: 471-477
        • Metcalfe A
        • Langlois S
        • MacFarlane J
        • et al.
        Prediction of obstetrical risk using maternal serum markers and clinical risk factors: serum markers and obstetrical history for obstetrical risk prediction.
        Prenat Diagn. 2014; 34: 172-179
        • Audibert F
        • De Bie I
        • Johnson J-A
        • et al.
        No. 348-joint SOGC-CCMG guideline: update on prenatal screening for fetal aneuploidy, fetal anomalies, and adverse pregnancy outcomes.
        J Obstet Gynaecol Can. 2017; 39: 805-817
        • Munné S
        • Grifo J
        • Wells D
        Mosaicism: “survival of the fittest” versus “no embryo left behind.”.
        Fertil Steril. 2016; 105: 1146-1149
      1. PGDIS Position Statement on Mosaic Embryos. Available Accessed January 3, 2020.

        • Fragouli E
        • Alfarawati S
        • Spath K
        • et al.
        Analysis of implantation and ongoing pregnancy rates following the transfer of mosaic diploid–aneuploid blastocysts.
        Hum Genet. 2017; 136: 805-819
        • Besser AG
        • Mounts EL.
        Counselling considerations for chromosomal mosaicism detected by preimplantation genetic screening.
        Reprod Biomed Online. 2017; 34: 369-374
        • Harton GL
        • Cinnioglu C
        • Fiorentino F
        Current experience concerning mosaic embryos diagnosed during preimplantation genetic screening.
        Fertil Steril. 2017; 107: 1113-1119
        • Sachdev NM
        • Maxwell SM
        • Besser AG
        • et al.
        Diagnosis and clinical management of embryonic mosaicism.
        Fertil Steril. 2017; 107: 6-11
        • Besser AG
        • McCulloh DH
        • Grifo JA
        What are patients doing with their mosaic embryos? Decision making after genetic counseling.
        Fertil Steril. 2019; 111 (e1): 132-137
        • Grati FR
        • Gallazzi G
        • Branca L
        • et al.
        An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening.
        Reprod Biomed Online. 2018; 36: 442-449