P-090 Is preimplantation genetic testing for aneuploidy (PGT-A) necessary in the treatment strategy for ICSI with testicular sperm?
Authors: Maekawa T , Mizuta S , Morimoto T , Matsubayashi H , Takeuchi T , Ishikawa T 
Published: July 2024

Abstract

Study question
Does the combination of testicular sperm extraction (TESE) and ICSI increase the risk of embryo aneuploidy?

Summary answer
Embryo aneuploidy occurrence is not increased when using testicular sperm and is not affected by the etiology of azoospermia.

What is known already
TESE-ICSI, especially in patients with non-obstructive azoospermia (NOA), has been reported to result in poor outcomes and difficulty in obtaining good blastocysts, which may be due to immature sperm retrieved by TESE. In addition, patients who require TESE have been shown to be at particularly high risk of chromosomally abnormal sperm. These factors may increase the risk of embryo aneuploidy in TESE-ICSI and contribute to poor outcomes. However, few reports have investigated the results of PGT-A following TESE-ICSI. This study was therefore designed to investigate whether using testicular sperm is more likely to result in embryo aneuploidy.

Study design, size, duration
This retrospective study included 81 couples and 197 TESE-ICSI cycles undergoing PGT-A (average maternal age: 38.1±5.4 years) between September 2016 and November 2023. Of the total cycles, 94 cycles were case of obstructive azoospermia (OA) and 53 cycles were cases of NOA. The etiologies of NOA included were unexplained (22 cycles), Klinefelter’s syndrome (KS) (10 cycles), post-chemotherapy (3 cycles), post-orchiopexy (11 cycles), and microdeletion of azoospermia factor (AZF) c on the Y chromosome (7 cycles).

Participants/materials, setting, methods
ICSI outcomes were compared between different etiologies (OA vs. NOA). A total of 356 blastocysts acquired were analyzed using PGT-A with next-generation sequencing (NGS). The PGT-A results were classified according to maternal age (&lt;38, 38-41, &gt;41 years) and paternal age (&lt;40, ≥40 years). In addition, TESE-ICSI cycles were limited to the maternal age of &lt; 38 years to remove the effect of maternal factors, the euploidy rates were compared between different etiologies or morphological grade.

Main results and the role of chance
The rates of fertilization and blastocyst formation for TESE-ICSI were significantly lower in NOA than OA (47.4% vs. 61.6%, P &lt; 0.001 and 37.3% vs. 50.7%, P &lt; 0.01, respectively). The rate of good-quality blastocyst (16.6% vs. 21.2%) was also lower, but not statistically significant. The euploidy rate of all evaluated TESE-ICSI embryos decreased with increasing maternal age (52.9% in &lt; 38, 29.3% in 38-41, 10.0% in &gt; 41 years), but was not affected by the paternal age (40.6% in &lt; 40, 42.5% in ≥ 40 years). For cycles with the maternal age of &lt; 38 years, the euploidy rate was not significantly different between OA and NOA patients (55.3% vs. 49.3%). In addition, the association between embryo euploidy and morphological grade (using Gardner’s classification, ≥BB for good-quality vs. &lt;BB for poor-quality embryos) was evaluated, and the euploidy rate was significantly higher in good-quality embryos compared to poor-quality embryos (60.3% vs. 33.3%, P &lt; 0.01). These results indicate the frequency of embryo aneuploidy in TESE-ICSI is comparable to commonly used ejaculated sperm. Furthermore, it suggests that embryo aneuploidy is dependent on maternal age or morphological grade of embryo, but not on paternal age or the etiology of azoospermia.

Limitations, reasons for caution
Patients with chromosomal abnormalities, i.e. KS, could not be evaluated due to the small number of cases and patients with chromosomal translocation were not included in this study. Therefore, the effects of male factors in NOA on embryo aneuploidy require extended investigation.

Wider implications of the findings
In TESE-ICSI, especially in the case of NOA, it is difficult to obtain good quality embryos due to poor ICSI outcomes. However, if good quality embryos are obtained, the euploidy rate is high and there is no need to perform PGT-A on the sole basis of using testicular sperm.

Trial registration number
not applicable