Controversial embryo screening method improves live birth rates
Preimplantation genetic testing for aneuploidy, or PGT-A, improved in vitro fertilization success rates and guarded against miscarriage, despite guidance suggesting that it is not effective or safe, according to researchers.
Fertility clinics use PGT-A to screen for gross genetic abnormalities in human IVF embryos. While supporters say the treatment is effective and safe, others say randomized clinical trials have not established its safety or efficacy and that patients should not be subjected to it, especially since they have to pay for it.
The Human Fertilisation and Embryology Authority (HFEA) in the United Kingdom agreed that PGT-A’s safety and efficacy have not been established and gave the practice two “red lights” in the past, but recently changed that rating to one red light.
The researchers used freedom of information requests to acquire data from HFEA about PGT-A and non-PGT-A cycle outcomes from 2016 to 2018. The retrospective cohort analysis examined the differences between these groups but without controlling for confounders besides maternal age, which the researchers called the leading known risk factor for chromosome abnormalities. Fresh and frozen transfers were included as well.
“This data will hopefully aid the HFEA in their continual surveillance of the ‘red traffic light’ guidance that currently states there is no evidence that PGT-A is effective or safe,” author Darren Griffin, PhD, professor of genetics at the University of Kent, said in a press release.
The data included total number of cycles, cycles with no embryo transfer, total number of embryos transferred, live birth rate (LBR) per embryo transferred and LBR per treatment cycle. There were 2,464 PGT-A procedures out of a total of 190,010 cycles (1.3%).
The researchers said the LBR per embryo transferred and the LBR per treatment cycle — including cycles with no transfer — was significantly higher for all PGT-A age groups than non-PGT-A age groups, including those aged younger than 35 years (P < .05). Also, LBR for patients aged older than 40 years were three to 11 times greater with PGT-A than without.
Furthermore, the researchers found a reduced number of transfers per live birth, particularly for women aged older than 40 years, implying that patients became pregnant faster when PGT-A was used, the researchers said.
Despite these benefits, the researchers said, they noted that their study was limited in matching complete clinical indication information with its PGT-A and non-PGT-A cohorts.
“The guidance could be revised in the light of this new data for patient benefit. I appreciate the collegial way in which the HFEA have assisted in providing this data and their open-mindedness to the prospect of revisiting their guidance and traffic light system,” Griffin said.
Reference:
Sanders KD, et al. J Assist Reprod Genet. 2021;doi:10.1007/s10815-021-02349-0.
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About 20 years ago, my lab was among the pioneers in PGT-A technology. We now train other labs in performing biopsies on embryos to help determine which ones are the healthiest for transfer.
The primary factor in PGT-A use is the age of the mother. We found the most significant reductions in miscarriage rates in mothers aged older than 40 years. If you’re 41 years old, PGT-A reduces miscarriage rates from close to 30% to lower than 15%. If you’re 43 years old, the risk drops from 43% to around 17%. PGT-A, then, makes IVF more efficient because it increases the chances of getting pregnant and avoiding miscarriage on the first attempt.
I also offer PGT-A to patients with a history of recurrent miscarriage. Miscarriages usually happen because of genetic abnormalities. If you can offer this technology to those patients, you are more likely to end up with a viable pregnancy.
Additionally, I offer this technology to patients with a single gene defect. Patients who already have had affected babies want to ensure their next child doesn’t suffer from this type of disorder. With PGT-A, you can diagnose with 98% accuracy which embryo will go full-term without the affected disease.
We used to biopsy embryos on day 3 when the embryo was only eight cells. That was a risk because we were removing one of the eight cells. But we now biopsy embryos on day 5 when there are 100 cells. We also have perfected the technique, so we remove the placental cells from the outer layer of the embryo. There is minimal effect on embryo development as long as the procedure is performed by an experienced laboratory.
Cost, however, is a major disadvantage. PGT-A adds $5,000 to an already expensive IVF cycle that many people cannot afford. Insurance companies don’t always cover the technology, even though many publications have shown very favorable results for select groups of patients.
Still, it’s important to continue to report data. You need a controlled study. You need a group of 40-year-olds who have used PGT-A, and then a group of 40-year-olds who have not. But not everyone will sign up for that if they know that, for an extra fee, they can be more efficient and have a better success rate.
PGT-A isn’t the standard of care because we don’t have these controlled studies yet. But a lot of academic centers are enrolling high numbers of patients, so these studies will come out. The HFEA is being very cautious because it feels the same way, and this latest report is a retrospective study. It’s not a standard two-group controlled study. We need a randomized clinical trial to establish that PGT-A is unequivocally useful because it’s such a high cost.
When you have a technology like this, it’s good that we’re gathering evidence and weighing whether we should pay that extra $5,000. That’s really the key. Because it’s so expensive, it is not available to many people. As researchers, we need to be careful in what we propose, and we should continue the discussion. We need more data and we need more studies.
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