Preimplantation Genetic Testing
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Direct answer
Testing an embryo before it is transferred requires IVF: oocytes are fertilised in vitro, embryos cultured to the blastocyst, a few cells of the trophectoderm (the future placenta) biopsied on day 5-6, and the genetic payload read by next-generation sequencing or array comparative genomic hybridisation while the embryo is vitrified. Preimplantation genetic testing divides into PGT-A for aneuploidy (embryo selection by chromosome count, mainly in advanced maternal age and recurrent implantation failure), PGT-M for monogenic disease (targeted testing for a known familial mutation — Huntington disease, beta-thalassaemia, haemophilia), and PGT-SR for structural rearrangements (translocations and inversions causing recurrent miscarriage). Its celebrated strength is avoiding transmission of severe Mendelian disease without terminating pregnancies; its contested territory is PGT-A, where mosaicism in the biopsy, apparent embryo self-correction and mixed randomised-trial evidence temper enthusiasm. Any resulting pregnancy still warrants confirmatory prenatal diagnosis, because the biopsied cells are placental lineage and may not represent the fetus.
What you must remember
- Taxonomy to quote: PGT-A (aneuploidy, formerly PGS), PGT-M (monogenic, formerly PGD), PGT-SR (structural rearrangements) — the current international nomenclature examiners now expect.
- Biopsy staging: day-3 cleavage biopsy is historical; trophectoderm biopsy at the blastocyst on day 5-6 with vitrification and frozen transfer is the standard — fewer cells damaged, better DNA yield, inner cell mass untouched.
- PGT-M mechanics: a known familial mutation plus linked marker haplotyping (to avoid allele drop-out); requires family DNA samples and a bespoke test build taking weeks to months.
- PGT-A rationale and reality: aneuploidy rises steeply with maternal age (a major driver of IVF failure and miscarriage); euploid transfer improves selection per transfer, but randomised evidence for higher cumulative live births remains debated.
- Mosaicism: a proportion of biopsies show intermediate copy-number results; mosaic embryos can be transferred in rank order after euploid ones under counselling frameworks, with documented healthy births but elevated miscarriage risk.
- Confirmation rule: PGT of any type is followed by recommendation of CVS or amniocentesis in the pregnancy, because trophectoderm sampling represents placental lineage.
- Indian specifics: PGT-M for beta-thalassaemia is the classic national use-case, given carrier rates of 3-7 per cent in some communities; PCPNDT rules ban sex selection, so PGT for social sex choice is illegal; clinics operate under the ART Regulation Act 2021.
- Limitations to volunteer: PGT cannot detect de novo disease, all mosaicism, polygenic risk or mitochondrial disorders; a euploid transfer still fails sometimes for non-genetic reasons.
A clinical journey worth following
A couple with two children affected by beta-thalassaemia major — both parents carriers of the same mutation — seek a pregnancy free of the disease and, ideally, HLA-matched to their affected elder child. The pathway: IVF stimulation and retrieval, ICSI fertilisation (standard with PGT to avoid sperm DNA contamination), blastocyst culture, trophectoderm biopsy and vitrification. The PGT-M laboratory, using the family's haplotypes, reports which embryos are unaffected carriers versus affected, and adds HLA typing — the "saviour sibling" strategy — so a matched, unaffected embryo is transferred first. Pregnancy is confirmed, and CVS at 11-12 weeks verifies the result; a matched cord blood donation at birth can treat the sibling. Every step is consented and legally channelled: no sex selection, records under the ART Regulation framework, counselling about the possibility of no transferable embryo. Contrast a 41-year-old doing IVF for age-related infertility who adds PGT-A: her rationale is different — selecting the few euploid embryos among many — and her counselling must cover mosaic results and the honest caveat that PGT-A speeds the path per transfer but does not create eggs that never existed.
Where students slip
The recurring confusions: equating PGT with a guarantee — it reduces but does not abolish genetic risk, and confirmatory prenatal diagnosis remains advised. Mixing up lineages: the biopsy is trophectoderm (placenta), so a mosaic result may not describe the inner cell mass — the biological root of both false positives and self-correction reports. Outdated labels — answering "PGD/PGS" when the question wants PGT-M/A/SR invites correction. Finally, forgetting legality in India: sex-selection PGT is barred, and clinics operate under the ART Regulation Act 2021 — points Indian examiners increasingly probe.
Frequently asked questions
What are the three current categories of PGT?
PGT-A for chromosome copy-number selection, PGT-M for known monogenic disease, and PGT-SR for parental structural rearrangements such as translocations.
Why is trophectoderm biopsy preferred over day-3 biopsy?
Blastocyst-stage trophectoderm biopsy yields more cells with better genetic resolution while sparing the inner cell mass, and paired vitrification allows testing before frozen transfer.
What is mosaicism in PGT-A?
An intermediate copy-number result suggesting a mixture of cell lines in the embryo; such embryos may still yield healthy births and are transferable in counselling frameworks after euploid embryos.
Does a normal PGT result eliminate the need for prenatal testing?
No — because the biopsied trophectoderm represents placental lineage, confirmatory CVS or amniocentesis is still recommended in the pregnancy.
Can PGT be used for sex selection in India?
No — sex selection is prohibited under the PCPNDT Act; PGT-M for disease avoidance (for example beta-thalassaemia) is the lawful indication.