Abstract
Study question
Does the selection of non-apoptotic sperm via magnetic-activated cell sorting (MACS) reduce the aneuploidy rate of embryos from couples undergoing ICSI cycles with PGT-A using the patients’ own oocytes?
Summary answer
It does. The aneuploidy rate in the MACS group was 4.34% lower than the one obtained using semen samples processed according to standard clinical practice.
What is known already
MACS is a successful tool in eliminating proapoptotic sperm from a semen sample. However, the true effect of this technique on reproductive outcomes and the quality of the resulting embryos are a matter of controversy. Some studies report that its use improves the percentage of good quality blastocysts in women older than 30 years old compared to standard ICSI. Randomized clinical trials that compare MACS to a control sample consider parameters of embryo quality such as morphology at day 3 or day 5, symmetry of the blastomeres, blastocysts’ stage of expansion, but they do not consider embryo ploidy.
Study design, size, duration
Retrospective, multicentre, observational cohort study. 14,145 patients and 18,710 cycles were evaluated in the reference group. In the MACS group, 615 patients and 974 cycles were considered. Data were exported from cycles performed in Spanish IVIRMA clinics between January 2008 and February 2020.
Participants/materials, setting, methods
Unselected males in couples undergoing PGT-A cycles, then subdivided into male factor (MF) - total progressive motile sperm count lower than 5 million - and non-male factor (NMF) infertility. Statistical analysis performed using R v.4.0.0. Means were calculated and compared using two-tailed paired t-test, while proportions were compared using Fisher’s exact test and the chi-squared test and the appropriate correction for multiple comparisons. The aneuploidy rates for each group were compared using Fisher’s exact test.
Main results and the role of chance
In the control group 73,228 biopsied embryos, from which 71,439 were informative in the PGT-A. In the MACS group 3,919 biopsied embryos, from which 3,843 were informative. The aneuploidy rate, computed per informative embryo, was 68.87% (68.40%, 69.34%) in the reference group and 64.53% (62.43%, 66.64%) in the MACS group. Both comparisons were statistically significant (p-value ˂0.00001). According to these results, an embryo in the PGT-A programme using non-apoptotic sperm selected through MACS and autologous oocytes had a 5% less chance of being aneuploid than those embryos fertilised with standardly selected sperm (relative risk of 0.95 (0.91–0.98) p = 0.006769). Embryos conceived from NMF patients whose semen had been processed using MACS had a 4.27% lower aneuploidy rate than the reference (65.52% (63.16%, 67.88%) vs 69.79% (69.20%, 70.37%) respectively). This difference was statistically significant. Those embryos conceived using semen from patients with MF using MACS also showed a lower aneuploidy rate than the reference with MF (0.28% (55.48%, 65.08%) vs (64.94% (63.35%, 66.23%) respectively), although this difference was not statistically significant. Thus, the decrease in aneuploidy rate observed when comparing MACS and reference groups undergoing PGT-A cycles using autologous oocytes remained approximately the same in both MF and NMF semen samples.
Limitations, reasons for caution
The retrospective nature of the study subjects the data to biases or inaccuracies in their annotation in the clinics’ informatic platform from which they were exported. However, the statistical analysis aimed at controlling these biases as much as possible.
Wider implications of the findings: The vast amount of data compiled for this study confirms that the selection of non-apoptotic sperm through MACS slightly decreases the aneuploidy rate of embryos compared to semen samples processed according to the clinics’ standards. This would be interesting for patients who are considering undergoing PGT-A cycles in the future.
Trial registration number
Not applicable
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