Comparison of reproductive outcomes in ICSI cycles after sperm selection techniques in advanced paternal age
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20263024Keywords:
Male infertility, Advanced paternal age, Microfluidics, Sperm processing, ICSI, Clinical pregnancyAbstract
Background: Advanced paternal age is associated with declining semen parameters, increased sperm DNA fragmentation (SDF), and oxidative stress, which may negatively affect ART outcomes. Microfluidic sperm sorting has been proposed as a method to reduce SDF and improve sperm quality compared to conventional density gradient centrifugation.
Methods: Single-center retrospective cohort study including 193 ICSI cycles performed between January 2023 and December 2024. Couples were stratified by male age (<40 years vs. ≥40 years) and further subdivided by sperm preparation method (density gradient vs. microfluidics), forming four subgroups (A1: <40/DG, n=56; A2: <40/MF, n=59; B1: ≥40/DG, n=33; B2: ≥40/MF, n=45). Inclusion criteria: ≥10 mature oocytes, ICSI, frozen double blastocyst transfer, and sperm concentration ≥5×106/ml. Exclusion criteria: severe male factor infertility or donor gametes. Primary outcome: live birth rate. Secondary outcomes: clinical pregnancy, miscarriage, fertilization, and blastulation rates.
Results: No significant differences were observed in clinical pregnancy, miscarriage, or live birth rates between preparation methods within either age group (all p>0.05). Fertilization and blastulation rates were comparable across subgroups. A modest reduction in oocyte yield was noted in older males undergoing microfluidic preparation (A2 vs. B2; p=0.034), likely reflecting female- or cycle-specific factors. Demographic/clinical data are detailed in tables in the results section. Multivariate logistic regression showed that female age (OR 1.02, 95% CI 0.96–1.09, p=0.50) and subgroup membership were not significant predictors of clinical pregnancy. Pairwise comparisons with Tukey adjustment confirmed no significant differences between subgroups (e.g., A1 vs. B1: OR 1.91, p=0.515).
conclusion: Male age ≥40 years and sperm preparation method (microfluidics vs. density gradient) were not independent determinants of ART success in this cohort. Clinical decision-making regarding sperm selection should not be guided solely by paternal age or subgroup classification.
References
Sharma R, Agarwal A, Rohra VK, Assidi M, Abu-Elmagd M, Turki RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reprod Biol Endocrinol. 2015;13:35.
Johnson SL, Dunleavy J, Gemmell NJ, Nakagawa S. Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis. Ageing Res Rev. 2015;19:22–33.
Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001;75(2):237–48.
Evenson DP, Wixon R. Clinical aspects of sperm DNA fragmentation detection and male infertility. Ther Adv Urol. 2006;1(1):19–29.
Aitken RJ, De Iuliis GN. On the possible origins of DNA damage in human spermatozoa. Mol Hum Reprod. 2010;16(1):3–13.
Henkel RR. The impact of oxidants on sperm function. Andrologia. 2005;37(6):205–6.
Nosrati R, Graham PJ, Zhang B, Riordon J, Lagunov A, Hannam TG, et al. Microfluidics for sperm analysis and selection. Nat Rev Urol. 2017;14(12):707–30.
Jenkins TG, Aston KI, Pflueger C, Cairns BR, Carrell DT. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genet. 2014;10(7):1004458.
Champroux A, Torres-Carreira J, Gharagozloo P, Drevet JR, Kocer A. Mammalian sperm nuclear organization: resiliencies and vulnerabilities. Basic Clin Androl. 2016;26:17.
Dviri M, Madjunkova S, Koziarz A, Madjunkov M, Mashiach J, Nekolaichuk E, et al. Is there a correlation between paternal age and embryo quality? A systematic review and meta-analysis. Hum Reprod Update. 2021;27(3):486–500.
Wu Y, Kang X, Zheng H, Liu H, Huang Q, Liu J. Effect of paternal age on reproductive outcomes of assisted reproductive techniques. Reprod Biol Endocrinol. 2022;20:30.
Frattarelli JL, Miller KA, Miller BT, Elkind-Hirsch K, Scott RT Jr. Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. Fertil Steril. 2008;90(1):97–103.