Next Generation DNA Sequencing Technique Identifies 'Best' Embryo To Transfer To IVF Patients
Earlier this week came reports of the oldest mother in the U.S. to give birth to a healthy baby through in-vitro fertilization using her own newly harvested eggs. She was 46 at the time of implantation and an exception to the rule of low success rates for IVF at her age. Now, in Italy, a next generation DNA sequencing technique for screening embryos has proven to be an effective and reliable method of selecting the best embryo to transfer to in-vitro fertilization patients. Because the technique is less expensive, faster, and, most importantly, accurate, it has the potential to revolutionize pre-implantation genetic screening (PGS), the researchers believe.
The scientific team behind the new technique was led by Dr. Francesco Fiorentino, from the GENOMA Molecular Genetics Laboratory in Rome, who will present his findings tomorrow at the annual conference of the European Society of Human Genetics.
The next generation DNA sequencing technique (NGS) is a high throughput method, meaning it allows researchers to quickly conduct millions of genetic tests. Fiorentino and his team began their study to compare NGS with an older method known as array-comparative genomic hybridisation (Array-CGH) by enlisting the help of 55 patients. Array-CGH is used extensively worldwide, and it was the first technology to be widely available for analysis of chromosomal abnormalities in the embryo.
Of the total study volunteers, 45 women were undergoing IVF because of advanced age, while 10 reported repeated IVF failures. The average age of the women was 40. The research team obtained 192 blastocysts, or early embryos, from 55 consecutive clinical pre-implantation genetic screening (PGS) cycles. The researchers conducted biopsies and analyzed the genetic make-up of the embryos at both five and six or seven days, depending on the speed of growth, and then measured the consistency of the diagnosis by comparing results from the two sequencing methods.
What did they discover? "We found that results from the NGS and array-CGH diagnostic tests were highly concordant," Fiorentino stated in a press release. For 191 of the 192 embryos analyzed, both methods came to the exact same results. For one embryo, the researchers had a false positive using the NGS technique: The results showed three copies of chromosome 22 (trisomy 22). Both methods, though, had already ruled out this embryo for implantation because they similarly (and accurately) detected several other chromosomal abnormalities.
There were no inaccurate predictions of gender with the NGS method, and no false negative diagnoses for chromosome abnormalities. NGS also showed itself to be as capable as Array-CGH of identifying small, difficult to detect abnormalities.
"NGS allowed us to detect a number of different abnormalities in 4608 chromosomes with a very high degree of accuracy,” Fiorentino said, “and following the transfer of 50 healthy embryos in 46 women, 30 pregnancies continued." All of these pregnancies have now completed at least 20 weeks of gestation. “Our next step will be to participate in a large randomised controlled trial, the results of which will be critical for the acceptance of NGS-based pre-implantation embryo assessment into wider clinical practice," Fiorentino explained.
Whether or not NGS comes into wider use, it is important to remember that it cannot change the odds of an older mother having healthy eggs. A woman’s fertility begins to fall in her early- to mid-thirties. This varies from woman to woman and is mostly due to a decrease in both the number and the quality of eggs in her ovaries.