Trophectoderm Biopsy: Present State of the Art

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2025 Feb 26

PMID 40004463

Authors

Anick De Vos

Neelke De Munck

Affiliations

Soon will be listed here.

Abstract

Trophectoderm (TE) biopsy is at present the most widely used procedure for preimplantation genetic testing (PGT). At the blastocyst stage, more TE cells (five to seven) can be obtained for genetic analysis. While removing TE cells and not touching the inner cell mass (ICM), the procedure is less invasive. Due to a natural selection happening between day 3 and day 5, 6 or 7 of human embryo development, fewer embryos will have to be biopsied and tested. An additional benefit, especially in view of aneuploidy testing (PGT-A), is the lower level of mosaicism present at the blastocyst stage. The biopsy procedure involves two steps: laser-assisted zona pellucida (ZP) opening and the excision of five to eight TE cells from the blastocyst with or without additional laser energy. Different protocols have emerged over time with variations regarding the technique, the exact moment of ZP opening, and the method of cell removal. The 'pulling' method involves laser excision, whereas the 'flicking' method represents a mechanical approach with or without laser assistance. Embryo developmental speed reaching the full/expanded or hatching/hatched blastocyst stage dictates the timing of the procedure, mostly on day 5 post-insemination, and to a lesser extent on day 6 or even on day 7. The inclusion of lesser quality or delayed blastocysts may impact the quality of the TE sample as well as the clinical outcome. Intracytoplasmic sperm injection (ICSI) is still the preferred method of fertilization for PGT-M (monogenic disorders) and PGT-SR (structural rearrangements). However, conventional in vitro fertilization (IVF) seems feasible for PGT-A (aneuploidy testing). In the absence of a (conclusive) genetic result, the re-biopsy of cryopreserved blastocysts is possible, however, with reduced clinical outcomes. So far, neonatal outcome post-TE biopsy has so far been reassuringly documented.

References

Veiga A, Sandalinas M, Benkhalifa M, Boada M, Carrera M, Santalo J . Laser blastocyst biopsy for preimplantation diagnosis in the human. Zygote. 1998; 5(4):351-4. DOI: 10.1017/s0967199400003920. View

Lal A, Roudebush W, Chosed R . Embryo Biopsy Can Offer More Information Than Just Ploidy Status. Front Cell Dev Biol. 2020; 8:78. PMC: 7028688. DOI: 10.3389/fcell.2020.00078. View

Zhang S, Xie P, Lan F, Yao Y, Ma S, Hu L . Conventional IVF is feasible in preimplantation genetic testing for aneuploidy. J Assist Reprod Genet. 2023; 40(10):2333-2342. PMC: 10504148. DOI: 10.1007/s10815-023-02916-7. View

Rosalik K, Carson S, Pilgrim J, Luizzi J, Levy G, Heitmann R . Effects of different frozen embryo transfer regimens on abnormalities of fetal weight: a systematic review and meta-analysis. Hum Reprod Update. 2021; 28(1):1-14. DOI: 10.1093/humupd/dmab037. View

Minasi M, Colasante A, Riccio T, Ruberti A, Casciani V, Scarselli F . Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study. Hum Reprod. 2016; 31(10):2245-54. DOI: 10.1093/humrep/dew183. View

Leigh D, Cram D, Rechitsky S, Handyside A, Wells D, Munne S . PGDIS position statement on the transfer of mosaic embryos 2021. Reprod Biomed Online. 2022; 45(1):19-25. DOI: 10.1016/j.rbmo.2022.03.013. View

Lynch C, Armstrong E, Charitou M, Gordon T, Griffin D . Investigation of the risk of paternal cell contamination in PGT and the necessity of intracytoplasmic sperm injection. Hum Fertil (Camb). 2022; 26(5):958-963. DOI: 10.1080/14647273.2022.2026498. View

Guarneri C, Reschini M, Pinna M, Perego L, Sanzani E, Somigliana E . The impact of a second embryo biopsy for preimplantation genetic testing for monogenic diseases (PGT-M) with inconclusive results on pregnancy potential: results from a matched case-control study. J Assist Reprod Genet. 2024; 41(5):1173-1179. PMC: 11143113. DOI: 10.1007/s10815-024-03078-w. View

He H, Jing S, Lu C, Tan Y, Luo K, Zhang S . Neonatal outcomes of live births after blastocyst biopsy in preimplantation genetic testing cycles: a follow-up of 1,721 children. Fertil Steril. 2019; 112(1):82-88. DOI: 10.1016/j.fertnstert.2019.03.006. View

10.

De Rycke M, Berckmoes V, De Vos A, Van de Voorde S, Verdyck P, Verpoest W . PREIMPLANTATION GENETIC TESTING: Clinical experience of preimplantation genetic testing. Reproduction. 2020; 160(5):A45-A58. DOI: 10.1530/REP-20-0082. View

11.

Yang Z, Liu J, Collins G, Salem S, Liu X, Lyle S . 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(1):24. PMC: 3403960. DOI: 10.1186/1755-8166-5-24. View

12.

Hernandez-Nieto C, Lee J, Slifkin R, Sandler B, Copperman A, Flisser E . What is the reproductive potential of day 7 euploid embryos?. Hum Reprod. 2019; 34(9):1697-1706. DOI: 10.1093/humrep/dez129. View

13.

Lagalla C, Coticchio G, Sciajno R, Tarozzi N, Zaca C, Borini A . Alternative patterns of partial embryo compaction: prevalence, morphokinetic history and possible implications. Reprod Biomed Online. 2020; 40(3):347-354. DOI: 10.1016/j.rbmo.2019.11.011. View

14.

Neal S, Sun L, Jalas C, Morin S, Molinaro T, Scott Jr R . When next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) yields an inconclusive report: diagnostic results and clinical outcomes after re biopsy. J Assist Reprod Genet. 2019; 36(10):2103-2109. PMC: 6823328. DOI: 10.1007/s10815-019-01550-6. View

15.

Neal S, Franasiak J, Forman E, Werner M, Morin S, Tao X . High relative deoxyribonucleic acid content of trophectoderm biopsy adversely affects pregnancy outcomes. Fertil Steril. 2016; 107(3):731-736.e1. DOI: 10.1016/j.fertnstert.2016.11.013. View

16.

Eggenhuizen G, Go A, Sauter Z, Hoffer M, Haak M, Geeven G . The role of confined placental mosaicism in fetal growth restriction: A retrospective cohort study. Prenat Diagn. 2024; 44(3):289-296. DOI: 10.1002/pd.6533. View

17.

Capalbo A, Rienzi L . Mosaicism between trophectoderm and inner cell mass. Fertil Steril. 2017; 107(5):1098-1106. DOI: 10.1016/j.fertnstert.2017.03.023. View

18.

Parriego M, Coll L, Vidal F, Boada M, Devesa M, Coroleu B . Inconclusive results in preimplantation genetic testing: go for a second biopsy?. Gynecol Endocrinol. 2018; 35(1):90-92. DOI: 10.1080/09513590.2018.1497153. View

19.

Harper J, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta S . The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update. 2012; 18(3):234-47. DOI: 10.1093/humupd/dmr052. View

20.

Victor A, Griffin D, Brake A, Tyndall J, Murphy A, Lepkowsky L . Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst. Hum Reprod. 2018; 34(1):181-192. DOI: 10.1093/humrep/dey327. View