P-541 Prevalence of rare autosomal aneuploidies in pregnancies following assisted reproduction
Authors: Beukeleirs T , Tsuiko O , Vancoillie L , Vermeesch J , Dimitriadou E , Vanhie A 
Published: June 2022

Study question

Is the prevalence of rare autosomal aneuploidies (RAA) at non-invasive prenatal testing (NIPT) higher in ART pregnancies compared to the general population?

Summary answer

At NIPT there is no higher prevalence of rare autosomal aneuploidies in ART pregnancies compared to the general population.

What is known already

Most IVF embryos contain mixtures of euploid and aneuploid cells. Despite the high prevalence of chromosomal mosaicism in embryos, its clinical implications are poorly understood. Chromosomal mosaicism doesn't seem to be preserved at later stages of prenatal and postnatal development, supported by the birth of children with normal karyotype following mosaic embryo transfer. Recently prospective non-selection PGT-A trials showed equivalent live-birth rates and miscarriage rates across euploid, low-grade mosaic and medium-grade mosaic embryos. However, close monitoring of mosaic embryo transfer may also be warranted due to the potential risk of true fetal mosaicism.

Study design, size, duration

Monocentric retrospective study. Power calculation is based on a prevalence of 0.23% of RAA at moment of NIPT in the general population. Sample sizes were calculated for detecting that the prevalence of RAAs in the ART cohort is higher compared to the overall population. For a power of 80% a sample size of 780 patients is necessary, to allow to conclude that the prevalence of RAAs is not higher than 1% in ART pregnancies.

Participants/materials, setting, methods

This trial was conducted at a tertiary care fertility center. We included all patients who had an IVF/ICSI treatment, without PGT-A, resulting in a pregnancy and had their NIPT done at the genetics department of our hospital between 01/07/2017 and the present. The data were compared to the Belgian national NIPT dataset, which included approximately 154K NIPT results from the general population. These are unique data due to the full reimbursement of NIPT.

Main results and the role of chance

Considering the high prevalence of (mosaic) aneuploidy in preimplantation embryos, we aimed to understand whether the use of assisted reproduction might imply a higher relative risk of RAAs in ART cohort. For our primary outcome comparative analysis revealed that the prevalence of RAA was 0.25% (2/804) in the ART group which was not significantly higher compared to 0.23% (350/153.575) in the general Belgian population, p = 0.89 (Chi square test). In addition, de novo segmental aberrations were also detected in two ART pregnancies (0.25%, 2/804), which is also comparable to the general population group (0,07%, 109/153.575, p = 0.06). Upon invasive follow up, none of RAAs or segmental aneuploidies were confirmed in the foetus, indicating confined placental mosaicism. Hence, our study allows to conclude that the prevalence of RAA at 12 weeks of gestation is not higher than 1% in the ART group and does not differ significantly compared to the general population.

Limitations, reasons for caution

With our data we have a sample size that allows us to conclude that the prevalence of RAA is not higher than 1% in the ART-group, which is highly clinically relevant. To conclude that the prevalence is equal to the general population (0.23%), a larger sample size would be needed.

Wider implications of the findings

Our observation that in ART pregnancies after IVF/ICSI without PGT-A the aneuploid embryos or aneuploid cells from mosaic embryos have disappeared already as early as 12 weeks of gestation development, supports the idea that transfer of putative mosaic embryos is not associated with a higher risk of adverse prenatal outcome.

Trial registration number

s66257