PCR (polymerase chain reaction) is used in pre-implantation genetic diagnosis (PGD) in IVF (in vitro fertilisation) to screen the embryo before implantation, avoiding transfer of an embryo carrying a genetic flaw.

Baby's feet

This has a number of applications:

  • For families at risk of monogenic diseases (diseases caused by a mutation in a single gene) such as cystic fibrosis, Tay-Sachs disease, sickle cell anaemia or Huntington’s disease, or genetic mutations in genes like BRCA-1, which increase the risk of certain cancers.
  • For sex determination in families at risk of X-linked disorders (disorders caused by a genetic mutation carried on the X chromosome) such as haemophilia, fragile X syndrome and neuromuscular dystrophies.
  • For older women or women who have had a number of failed IVF cycles, to look for chromosomal abnormalities.

Getting a sample of genetic material can involve removing the polar body from the egg, which will give information on the mother’s chromosomes, or an embryo biopsy. In an embryo biopsy, a single cell is extracted from the embryo on day three (the 6-10 cell stage; cleavage-stage embryo biopsy) or on day five (more than a hundred cells; blastocyst biopsy).

The challenges of using PCR in IVF

Pre-implantation genetic diagnosis requires tests to be carried out on a single cell, meaning that only minute amounts of DNA are available. Allele drop out (ADO) can also be an issue with PCR, when one allele is not amplified. If the mutation is present on the non-amplified allele, this could allow an affected embryo to be transferred in the IVF process. If it is a dominant genetic disease, this could result in an affected child; if it is a recessive disease, the child could be a carrier.

PCR can improve IVF success rates

One of the issues with IVF is the need to transfer more than one embryo to increase the chance of implantation and a successful pregnancy, raising costs and increasing the risk of multiple births, and the risks associated with them. Before 1991, in the UK, 60% of IVF treatment cycles involved the transfer of three or more embryos. Between 1991 and 2004, the maximum was reduced to three embryos, and in 2004, the policy became a maximum of two for women under 40, and three for women over 40.

PCR-based chromosomal screening may make single embryo transfer realistic (and cost-effective). In a US study, the success rate was 52% for women (42 of 81 cycles) undergoing standard IVF treatment. For the women whose embryos were underwent chromosomal screening using PCR, the success rate increased to 76% (54 of 76 cycles). The rates for delivery also increased.

As Richard T. Scott Jr said to Ob.Gyn. News Digital Network, these increased success rates may override the temptation of implanting more than one embryo, leading to safer and healthier pregnancies carrying one baby. He added: “I think it’s safe to say one screened embryo does as well or better than two unscreened embryos.”

Comparing costs, using the chromosomal screening technique could save an estimated $1.8 million per 100 patients.

Suzanne Elvidge is a freelance science, biopharma, business and health writer with more than 20 years of experience. She is editor of Genome Engineering, a blog that monitors the latest developments in genome engineering and that aims to educate (and sometimes to entertain!) and has written for a range of online and print publications including FierceBiomarkers, FierceDrugDelivery, European Life Science, the Journal of Life Sciences (now the Burrill Report), In Vivo, Life Science Leader, Nature Biotechnology, PR Week and Start-Up. She specialises in writing on pharmaceuticals, biotechnology, healthcare, science, lifestyle and green living, but can write on any topic given enough tea and chocolate biscuits. She lives just beyond the neck end of nowhere in the Peak District with her second-hand bookseller husband and two second-hand cats.