BALTIMORE — Adding a broader genetic test to testing for single-gene disorders among younger patients undergoing in vitro fertilization (IVF) reduced costs — but it also may lower cumulative live birth rates, a cost-effectiveness analysis suggested.
Among patients ages 36 and younger already planning to screen with pre-implantation genetic testing for monogenic disorders (PGT-M), adding on pre-implantation genetic testing for aneuploidy (PGT-A) was modeled to result in a lower cost per initiated cycle ($38,518) compared with PGT-M alone ($40,002), reflecting a cost-effectiveness tradeoff, reported Vania Nwokolo, MD, of the University of Washington in Seattle.
However, patients who opted for both PGT-M and PGT-A also had lower cumulative live birth rates versus those who did PGT-M alone (35.3% vs 52.3%), Nwokolo noted at the American Society for Reproductive Medicine (ASRM) annual meeting.
“What we found is that patients who are 36 and under who just do the PGT-M alone for a disorder or disease, they’re more likely to have an actual live birth; however, the costs are higher,” Nwokolo told MedPage Today.
She explained that those costs are likely higher because PGT-M alone could miss genetic abnormalities in the embryo that weren’t tested for, which may result in a miscarriage. Both treating the miscarriage and doing another embryo transfer would add on costs.
“Whereas if we add a PGT-A on the front end, there’s some cost in the beginning, but you’re less likely to transfer an embryo that has that genetic abnormality,” potentially avoiding miscarriages and additional embryo transfers, Nwokolo said.
“It may not lead to a higher cumulative birth rate, but the costs are cheaper,” she added.
Patients undergoing IVF who want to prevent the transmission of single-gene disorders, such as Huntington’s disease, often opt for PGT-M. Those who want to screen for chromosomal abnormalities more broadly would use PGT-A.
Both genetic tests involve a biopsy, so Nwokolo said that many PGT-M patients ask about adding on PGT-A to potentially decrease their risk of miscarriage.
The likelihood of extra or missing chromosomes increases with maternal age, so Nwokolo noted that women ages 38 and older are usually advised to do PGT-A. However, the benefit for good-prognosis women ages 36 and under remains uncertain.
Rachel Weinerman, MD, an ob/gyn and reproductive endocrinologist at Case Western Reserve University in Cleveland, told MedPage Today that there haven’t been randomized trials showing that PGT-A improves cumulative or per-transfer live birth rates for younger patients, though past research has shown it’s cost-effective in older patients.
Weinerman, who wasn’t involved in the study, said she thinks the difference in cumulative live birth rates may be dependent on how many embryos were transferred.
“When you do PGT-A, you exclude embryos that were segmental aneuploid and sometimes high-level mosaic that you would transfer and may lead to live birth if you didn’t do the testing,” she explained.
For this analysis, Nwokolo and team created a decision tree to compare PGT-M alone and PGT-M plus PGT-A in women ages 36 and under. Embryo yield, including the number of blastocysts and the proportion of euploid and mosaic proportions, were derived from published data in women under age 37.
Primary outcomes were cumulative live birth rate, which is the probability of at least one live birth across all transfers; cost per initiated cycle, including IVF, genetic testing, embryo transfers, pregnancy care, and miscarriage management; and the incremental cost-effectiveness ratio (ICER). The ICER for PGT-M alone was $8,737 per additional live birth.
Embryo outcomes were modeled per transfer. Euploid embryos were prioritized, followed by mosaic embryos, which contain both genetic chromosomal abnormalities and normal cells, if no euploid embryos were available.
Nwokolo said that mosaic embryos were a limitation, because there is debate in the field over whether to transfer low-level mosaics and it’s hard to determine whether genetic abnormalities or normal cells dominate.
In a sensitivity analysis, PGT-M alone remained more expensive but more effective when mosaic transfer was allowed after euploid failure.
