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. 2024 Apr 8:15:1289763.
doi: 10.3389/fendo.2024.1289763. eCollection 2024.

Elevated sperm DNA fragmentation is correlated with an increased chromosomal aneuploidy rate of miscarried conceptus in women of advanced age undergoing fresh embryo transfer cycle

Wanting Fu  1   2   3   4 , Qiuying Cui  1   2   3   4 , Zhiqin Bu  1   2   3   4 , Hao Shi  1   2   3   4 , Qingling Yang  1   2   3   4 , Linli Hu  1   2   3   4
Affiliations

Elevated sperm DNA fragmentation is correlated with an increased chromosomal aneuploidy rate of miscarried conceptus in women of advanced age undergoing fresh embryo transfer cycle

Wanting Fu et al. Front Endocrinol (Lausanne). .

Abstract

Background: Male sperm DNA fragmentation (SDF) may be associated with assisted reproductive technology (ART) outcomes, but the impact of SDF on the occurrence of aneuploid-related miscarriage remains controversial.

Methods: Genome-wide single-nucleotide polymorphism-based chromosomal microarray analysis was performed on 495 miscarried chorionic villus samples undergone IVF/ICSI treatment from the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University. SDF was assessed using sperm chromatin structure assay. Patients were divided into four groups according to embryo transfer cycle type and maternal age, and the correlation between SDF and chromosome aberration was analyzed. A receiver operating characteristic (ROC) curve was utilized to find the optimal threshold.

Results: Total chromosomal aneuploidy rate was 54.95%, and trisomy was the most common abnormality (71.32%). The chromosomally abnormal group had higher SDF than the normal group (11.42% [6.82%, 16.54%] vs. 12.95% [9.61%, 20.58%], P = 0.032). After grouping, elevated SDF was significantly correlated with an increasing chromosome aneuploidy rate only in women of advanced age who underwent fresh embryo transfer (adjusted odds ratio:1.14 [1.00-1.29], adjusted-P = 0.045). The receiver operating characteristic curve showed that SDF can predict the occurrence of chromosomal abnormality of miscarried conceptus in this group ((area under the curve = 0.76 [0.60-0.91], P = 0.005), and 8.5% was the optimum threshold. When SDF was ≥ 8.5%, the risk of such patients increased by 5.76 times (adjusted odds ratio: 6.76 [1.20-37.99], adjusted-P = 0.030).

Conclusion: For women of advanced maternal age undergoing fresh embryo transfer, older oocytes fertilized using sperm with high SDF in IVF/ICSI treatment might increase the risk of chromosomal abnormality in miscarried conceptus.

Keywords: assisted reproductive technology; chromosomal abnormality; chromosomal microarray analysis; miscarriage; sperm DNA fragmentation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of study inclusion and exclusion.
Figure 2
Figure 2
Spectrum of abnormal chromosomal karyotype in miscarried conceptus: type and Frequency.
Figure 3
Figure 3
Factors related to chromosomal abnormalities in maternal age ≥35 years undergoing fresh ET. (A) The ROC curve of the subgroup of advanced women aged ≥35 years undergone fresh ET cycle, P < 0.05 was considered statistically significant. (B) The forest plot of the multivariate Logistic regression analysis results of the subgroup of elderly women aged ≥35 years treated with ET. All variables above were adjusted. OR (95%CI) was used in the results and P < 0.05 was considered statistically significant. * Statistically significant. OR, odds ratio; CI, confidence interval; SDF, sperm DNA fragmentation; IVF, in vitro fertilization; ICSI, intracytoplasmic sperm injection; ET, embryo transfer; AMH, anti-mullerian hormone; No., number; AFC, antral follicle.
Figure 4
Figure 4
Comparison of chromosomal abnormalities in different ET strategies and maternal age groups (A) Chromosomal aneuploidy rates at SDF < 8.5% and ≥8.5% in the four subgroups, * Statistically significant. (B) Association between SDF and chromosomal aneuploidy rate of embryos in four subgroups, and maternal age, paternal age, ET days, fertilization method, AMH, number of antral follicle, seminal volume, seminal concentration and progressive sperm motility were adjusted. * Statistically significant, P < 0.05. SDF, sperm DNA fragmentation; ET, embryo transfer.
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References

    1. Gu C, Li K, Li R, Li L, Li X, Dai X, et al. . Chromosomal aneuploidy associated with clinical characteristics of pregnancy loss. Front Genet. (2021) 12:667697. doi: 10.3389/fgene.2021.667697 - DOI - PMC - PubMed
    1. Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J, et al. . Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet. (2021) 397:1658–67. doi: 10.1016/S0140-6736(21)00682-6 - DOI - PubMed
    1. Ozawa N, Ogawa K, Sasaki A, Mitsui M, Wada S, Sago H. Maternal age, history of miscarriage, and embryonic/fetal size are associated with cytogenetic results of spontaneous early miscarriages. J assisted Reprod Genet. (2019) 36:749–57. doi: 10.1007/s10815-019-01415-y - DOI - PMC - PubMed
    1. Li Y, Wang L, Xu J, Niu W, Shi H, Hu L, et al. . Higher chromosomal aberration rate in miscarried conceptus from polycystic ovary syndrome women undergoing assisted reproductive treatment. Fertil Steril. (2019) 111:936–43 e2. doi: 10.1016/j.fertnstert.2019.01.026 - DOI - PubMed
    1. Asgari F, Gavahi A, Karimi M, Vatannejad A, Amjadi F, Aflatoonian R, et al. . Risk of embryo aneuploidy is affected by the increase in sperm DNA damage in recurrent implantation failure patients under ICSI-CGH array cycles. Hum Fertil. (2022) 25:872–80. doi: 10.1080/14647273.2021.1920054 - DOI - PubMed

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