P-703 The role of maternal polymorphic karyotype variants among embryonic ploidy and mosaicism status in patients undergoing IVF treatments
Authors: Linares Á , Ruiz N , Luque L , Ortiz J A , Ayllón B , Bartolomé J , Abellán E , Ten J , Bernabeu R 
Published: June 2023

Study question

Is there a relationship between the chromosomal status of biopsied embryos and the presence of polymorphic variants in the female karyotype in IVF cycles?

Summary answer

The chromosomal status of biopsied embryos is prejudiced because of the presence of specific maternal polymorphic variants (qh-, qh+ and ps+) or combinations of them.

What is known already

Due to the increasing average age of patients who undergo IVF cycles with their own oocytes, more cycles are performed with embryo biopsy for preimplantation genetic test of aneuploidies (PGT-A). Thus, advanced maternal age has been defined as the main factor causing embryonic chromosomal abnormalities.

However, few studies have established direct relationships with other factors. The prevalence of chromosomal polymorphic variants has a higher incidence in the infertile population, which is why there is a need to know the role they play in the genetic inheritance of embryos.

Study design, size, duration

Retrospective evaluation of a cohort of women who underwent autologous IVF cycles and karyotyping. The sample included 162 IVF cycles with embryo biopsy on D5 and/or D6 for PGT-A, performed between July 2017-December 2021: control group (CG) with normal karyotype (86) and study group (SG) with presence of polymorphisms (76).

We studied the connection between maternal karyotype polymorphisms and molecular genetic outcomes in terms of euploid, mosaic, and aneuploid blastocyst rates.

Participants/materials, setting, methods

The analysis of the karyotype of women, prior to the IVF cycle, was performed using the guidelines of the International System for Human Cytogenetic Nomenclature (ISCN).

The trophoectoderm biopsies on D5 and/or D6 blastocysts were analysed by NGS using the Illumina platform (VeriSeq Illumina®, San Diego, CA, USA).

The association between the different polymorphic variants in the female karyotype and chromosomal status of embryos was analysed using R (v. 4.2.0) statistical software.

Main results and the role of chance

We analyzed the results of 483 embryos from 162 IVF-PGT-A cycles. Mean female age was 39.05±2.72 (CG) and 38.97±2.90 (SG). Mean number of mature oocytes (MII) was 7.16±3.94 (CG) and 8.01±5.33 (SG). Mean number of biopsied embryos was 2.97±2.15 (CG) and 2.93±1.88 (SG).

No statistically significant differences were found between the CG and SG groups in terms of the rate of euploid embryos: 26.99% vs 21.50% (p = 0.3), transferable mosaic embryos: 8.90% vs 6.76% (p = 0.5), aneuploid embryos: 61.98% vs 69.96% (p = 0.12) and non-informative embryos: 2.13% vs 1.78% (p = 0.2), respectively.

However, an increase in the rate of chromosomally abnormal embryos was observed when analysing each polymorphism individually. In females carrying the qh+ variant, we found a statistically significant decrease in the euploid embryo rate: 10.97% vs 26.00% found in CG (p = 0.036). Moreover, the variants qh+ and ps+ increased the rate of aneuploid embryos: 84.17% vs 63.48% in CG (p = 0.013) and 73.52% vs 61.30% in CG (p = 0.021), respectively. Furthermore, it is found that the qh- variant increased the rate of transferable mosaic embryos: 20.00% vs 8.90% in CG (p = 0.025).

The results were corrected for confounding variables such as maternal age, oocyte origin and male factor variables, including polymorphic variants in the male karyotype.

Limitations, reasons for caution

Presence of unmeasured variables that may influence the results. Larger prospective studies including homogeneous cohorts are needed in order to corroborate our initial results.

Wider implications of the findings

The results show that polymorphic variants in the female karyotype may have a direct effect on the embryonic ploidy and mosaicism status. Therefore, it would be advisable for patients who undergo IVF-PGT-A cycles to have a karyotype performed and be informed of the implications that it may entail.

Trial registration number

Not applicable