Pre-Implantation Genetic Testing (PGT/PGD) — Procedure Guide, Recovery & Risks | MyMedicPlus

Preimplantation genetic testing (PGT), formerly called preimplantation genetic diagnosis (PGD), analyses embryos created through in vitro fertilisation (IVF) for chromosomal or genetic abnormalities before transfer to the uterus. By selecting genetically normal embryos for transfer, PGT reduces the risk of implantation failure, miscarriage, and the birth of children with serious genetic conditions. Three categories exist: PGT-A (aneuploidy screening, testing all 24 chromosomes), PGT-M (monogenic or single-gene disorder testing, e.g., cystic fibrosis, BRCA1/2), and PGT-SR (structural rearrangements such as translocations). Embryo biopsy is performed at the blastocyst stage (Day 5–6) using laser-assisted trophectoderm biopsy, which removes 3–10 cells from the outer cell mass without damaging the inner cell mass (future foetus). Embryos are cryopreserved while awaiting genetic results, then selected normal embryos are transferred in a frozen embryo transfer cycle. Pre-implantation genetic testing (PGT) — previously called pre-implantation genetic diagnosis (PGD) — is a technique performed alongside in vitro fertilisation (IVF) to screen embryos for genetic abnormalities before transfer to the uterus, preventing the implantation of affected embryos and reducing the risk of pregnancy termination following prenatal diagnosis. PGT encompasses three main applications: PGT-M (for monogenic disorders — cystic fibrosis, BRCA mutations, Huntington disease, beta-thalassaemia), PGT-SR (for structural rearrangements — balanced translocations, inversions), and PGT-A (for aneuploidies — abnormal chromosome number, the most common cause of IVF failure and miscarriage in women over 35). The technique involves embryo biopsy at day 5–6 blastocyst stage, followed by trophectoderm biopsy, genetic analysis (next-generation sequencing, karyomapping, array comparative genomic hybridisation), and cryopreservation of euploid embryos pending results before frozen embryo transfer.

PGT-A is offered to women of advanced maternal age (generally over 37 years) undergoing IVF, couples with recurrent implantation failure (3 or more failed IVF cycles), recurrent pregnancy loss (2 or more miscarriages), or severe male factor infertility with high sperm chromosomal abnormality rates. PGT-M is indicated for carriers of autosomal dominant conditions (Huntington's disease, BRCA1/2 mutations), autosomal recessive carriers (cystic fibrosis, spinal muscular atrophy, thalassaemia) whose partner is also a carrier, and X-linked conditions (Duchenne muscular dystrophy, haemophilia). PGT-SR is required when one partner carries a balanced chromosomal rearrangement (reciprocal or Robertsonian translocation) causing repeated miscarriage or chromosomally unbalanced offspring. Couples must undergo comprehensive genetic counselling before undertaking PGT to fully understand its limitations, technical failure rate, and the ethical considerations around embryo selection.

PGT is integrated into a standard IVF cycle. Ovarian stimulation using gonadotrophin injections over 10–14 days grows multiple follicles, monitored by transvaginal ultrasound and serum oestradiol. Egg retrieval is performed under transvaginal ultrasound guidance with IV sedation; retrieved oocytes are fertilised by intracytoplasmic sperm injection (ICSI) to maximise fertilisation rates and avoid maternal cell contamination in the biopsy. Fertilised embryos are cultured to the blastocyst stage over 5–6 days. Trophectoderm biopsy uses a laser to create a small opening in the zona pellucida; fine glass capillaries aspirate 5–10 trophectoderm cells. Biopsied embryos are vitrified (flash-frozen) while cells are sent for genetic analysis. PGT-A uses next-generation sequencing (NGS) of all 24 chromosomes on the biopsy sample. PGT-M requires a customised probe designed from parental and family DNA, taking 3–6 months to develop before the IVF cycle. Results are available in 1–2 weeks. Genetically normal (euploid or unaffected) embryos are selected for frozen embryo transfer in a subsequent hormonally prepared cycle. Ovarian stimulation, egg retrieval, and ICSI fertilisation follow standard IVF protocols. On day 5–6, blastocysts are biopsied using laser-assisted zona pellucida drilling and aspiration of 4–6 trophectoderm cells using a biopsy pipette. Embryos are vitrified immediately after biopsy pending genetic results (2–5 working days). Next-generation sequencing (NGS) provides comprehensive chromosomal analysis with high sensitivity (over 95%) for detecting aneuploidies. For PGT-M, karyomapping (SNP array haplotyping) or customised PCR protocols are designed using family linkage analysis. Only euploid (chromosomally normal) and unaffected (for PGT-M) embryos are selected for frozen embryo transfer in a subsequent natural or medicated cycle.

PGT-A significantly improves IVF implantation rates per embryo transfer in women of advanced maternal age (35–40 years): clinical pregnancy rates per transfer rise from approximately 35–40% with untested embryos to 55–65% with PGT-A-tested euploid embryos, by eliminating aneuploid embryos that would otherwise fail to implant or miscarry. Miscarriage rates after euploid embryo transfer are reduced from 20–30% (untested) to under 10%. PGT-M has successfully prevented the birth of affected children with over 200 serious inherited conditions, with a misdiagnosis rate of approximately 1–2% across specialist centres. For carriers of balanced translocations, PGT-SR reduces miscarriage from 50–75% (untested) to under 10% per transfer. Overall live birth rates per PGT cycle depend heavily on the number of euploid embryos available, patient age, and uterine factors.

The biopsy procedure itself carries a small risk of embryo damage (approximately 1–2% of biopsied embryos fail to survive cryopreservation or warming), though modern trophectoderm biopsy techniques are significantly safer than cleavage-stage biopsy used historically. Technical failure of genetic analysis occurs in 2–5% of biopsies, preventing a result for that embryo. False-positive or false-negative results (misdiagnosis) occur in approximately 1–2% of PGT-M cycles; confirmatory prenatal testing (amniocentesis or CVS) is recommended after successful pregnancy. Mosaicism — embryos with a mixture of euploid and aneuploid cells — creates diagnostic uncertainty; international guidelines now allow transfer of low-level mosaic embryos when no euploid embryos are available. Ovarian hyperstimulation syndrome (OHSS) is a risk of IVF stimulation in all cycles. Psychological stress from multiple cycles and difficult embryo selection decisions requires specialist counselling support.

After egg retrieval under sedation, patients are monitored for 1–2 hours before discharge. Mild pelvic discomfort, bloating, and light vaginal spotting are common for 1–3 days. Normal activities resume within 24–48 hours; vigorous exercise is avoided for 5–7 days. OHSS symptoms — abdominal bloating, nausea, reduced urine output — are monitored closely and managed with fluid management, analgesics, and in severe cases paracentesis. All embryos are vitrified (frozen) while awaiting genetic results, eliminating the risk of OHSS in a fresh transfer. Frozen embryo transfer takes place 1–3 months later in a hormonally prepared cycle using oestrogen and progesterone support. The luteal support (progesterone pessaries or injections) continues until 10–12 weeks of pregnancy. A pregnancy test is performed 14 days after embryo transfer, with ultrasound confirmation of foetal heartbeat at 6–7 weeks.