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Asian Journal of Andrology logoLink to Asian Journal of Andrology
. 2026 Jan 13;28(3):246–251. doi: 10.4103/aja202560

Impact of semen quality and maternal age on blastocyst chromosomal abnormalities: a retrospective cohort study based on 1091 PGT-A cycles

Yang Zou 1,2,3,4,5,6,7,*, Xin Xu 8,9,*, Hong-Qiang Xie 1,2,3,4,5,6,7, Ming Gao 1,2,3,4,5,6,7, Xiao-Wei Liu 1,2,3,4,5,6,7, Li-Juan Wang 1,2,3,4,5,6,7, Cheng Li 1,2,3,4,5,6,7, Tao Jing 8,9, Xuan Gao 1,2,3,4,5,6,7, Jun-Hao Yan 1,2,3,4,5,6,7, Zi-Jiang Chen 1,2,3,4,5,6,7,10,11, Yuan Gao 1,2,3,4,5,6,7,✉
PMCID: PMC13258292  PMID: 41527904

Abstract

In this study, we aimed to investigate the influence of paternal oligozoospermia (OZ), asthenozoospermia (AZ), or teratozoospermia (TZ) on blastocyst ploidy and its potential interaction with maternal age. We analyzed 3383 embryos in 1091 preimplantation genetic testing for aneuploidy (PGT-A) cycles via next-generation sequencing (NGS) at the Center for Reproductive Medicine, Shandong University (Jinan, China). Our findings revealed that compared to the normozoospermic (NZ) group, the AZ group exhibited significantly lower euploidy rates (P = 0.022). This effect was more pronounced in cases with advanced maternal age (AMA; ≥38 years), where AZ patients had markedly reduced euploidy rates (P = 0.003), while no significant differences were observed in younger women (<38 years). Multivariate analysis, adjusting for parental age and body mass index (BMI), confirmed that AZ is an independent risk factor for reduced euploidy rates in the AMA subgroup. Notably, OZ and TZ cases showed no significant association with blastocyst ploidy rates. These results suggest that only in cases of advanced maternal age, impaired sperm motility adversely affect blastocyst euploidy rates.

Keywords: blastocyst, euploidy, preimplantation genetic testing for aneuploidy, sperm motility

INTRODUCTION

Chromosomal abnormalities in embryos are a leading cause of early pregnancy loss and implantation failure.1,2,3 Preimplantation genetic testing for aneuploidy (PGT-A) has emerged as a valuable tool to identify and avoid the transfer of these abnormal embryos, thereby improving the chances of successful pregnancy.4

Epidemiological evidence suggests that paternal semen quality may significantly influence embryonic ploidy.5,6,7,8 Studies have reported higher rates of de novo embryonic chromosomal abnormalities in intracytoplasmic sperm injection (ICSI) offspring,9 although the ICSI procedure itself does not increase the proportion of fetal chromosomal abnormalities.10,11 Although previous findings suggested that sperm abnormalities may play a critical role in embryonic chromosomal aneuploidy,12 other studies have found no correlation between impaired semen parameters and aneuploidy rates in preimplantation embryos.7,13,14

It is well established that maternal age is closely related to chromosomal abnormalities in embryos.15,16 Research indicates that pregnancy outcomes may be influenced by paternal gametes in conjunction with maternal age.17,18 Therefore, the combined effects of paternal and maternal factors on embryonic ploidy should be evaluated across different maternal age groups.

Despite these insights, previous studies have often pooled women of different ages and focused primarily on the effects of different sperm qualities on embryo chromosomes.7,14,19,20,21,22 Here, we divided abnormal semen quality into oligozoospermia (OZ), asthenozoospermia (AZ), and teratozoospermia (TZ) groups and evaluated their impact on blastocyst aneuploidy rates across different maternal age groups in a large retrospective cohort study using next-generation sequencing (NGS) in couples undergoing PGT-A cycles.

PARTICIPANTS AND METHODS

Study population

This retrospective cohort study was performed from October 2017 to May 2020 at the Center for Reproductive Medicine, Shandong University (Jinan, China). A total of 3383 embryos (1091 cycles) were analyzed using PGT-A cycles. Patients underwent PGT-A because of (1) advanced maternal age (AMA; defined as maternal age ≥38 years), (2) repeated implantation failures (RIF; three or more failed transfers of good-quality embryos), and (3) recurrent pregnancy loss (RPL; two or more previous miscarriages). Exclusion criteria involved cycles with gamete donation, other types of PGT cycles, such as monogenic disorders and chromosomal abnormalities, and when PGT-A results were unavailable for all biopsy embryos.

Ethics approval

This study was approved by the ethics committees of the Center for Reproductive Medicine, Shandong University (Approval No. 2022-76). All participants signed informed consent, agreeing that their data could be used for research.

Semen analysis

Semen samples were collected by masturbation after 3–5 days of sexual abstinence. After liquefaction, samples were analyzed under World Health Organization (WHO) 2010 guidelines by two operators with good expertise in this field.23 The cohort was divided into four groups based on semen parameters: (1) male partners with normal sperm parameters (normozoospermia [NZ]), (2) sperm concentration of <15 × 106 cells per ml, regardless of sperm motility or morphology (oligozoospermia [OZ]), (3) progressive sperm motility of <32%, regardless of sperm concentration or morphology (asthenozoospermia [AZ]), and (4) normal sperm morphology of <4%, regardless of sperm concentration or motility (teratozoospermia [TZ]).

Clinical and biochemical measurements

Information on age, height, and weight was recorded during the clinical examination. Body mass index (BMI) was calculated as weight/height2 (kg m−2). Blood samples were drawn for baseline hormone level testing (within 2–6 days of a spontaneous menstrual cycle or progestin-induced menstrual bleeding with oligomenorrhea/amenorrhea). Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P4), prolactin (PRL), and total testosterone (tT) were measured with the use of electro-chemiluminescence immunoassay (Roche, Basel, Switzerland). The intra- and inter-assay variation coefficients of variation were <10%.

All the blood samples for anti-Müllerian hormone (AMH) measurements were collected in 5 ml coagulating tubes. Serum was separated within 1 h of venous blood collection and tested immediately. If immediate testing was not feasible, the samples were stored at 2°C–8°C until the next day for testing. AMH levels were determined using chemiluminescent immunoassay (KEYSMILE, Chongqing, China). The functional sensitivity of the assay was 0.01 ng ml−1.

Oocyte and embryo handling procedures

Ovarian-controlled hyperstimulation regimens were performed as previously described, including the long gonadotropin-releasing hormone (GnRH) agonist protocol, short GnRH agonist protocol, GnRH antagonist protocol, and other protocols.24 When two or more follicles measured 18 mm or more, human chorionic gonadotropin (hCG) was given intramuscularly at a dose of 4000 IU to 10 000 IU (2000 IU, chorionic gonadotropin for Injection; Livzon, Zhuhai, China). Oocyte pick-up (OPU) was performed 34–36 h later, under transvaginal ultrasound guide. All the couples underwent PGT-A with intracytoplasmic sperm injection (ICSI).25,26 Oocyte cumulus cells were removed using 80 IU ml−1 hyaluronidase solution (FUJIFILM Irvine Scientific, Orange County, CA, USA) in G-MOPS buffer (Vitrolife, Gothenburg, Sweden). ICSI was carried out immediately after denudation using the strong cytoplasm dislocation.27 Fertilization was assessed 16–18 h after ICSI. Normally fertilized oocytes were considered those with the presence of two pronuclei and a second polar body. Embryos were cultured in MC2004 time-lapse culture dishes (Huchuang, Wuhan, China) with medium G1-plus (Vitrolife) up to day 3 and then in TL301 tissue culture dishes (METIEC; Huchuang) with medium G1-plus (Vitrolife) up to day 5. All cultures were maintained inside EC6S incubators (ASTEC, Kikuchi, Japan) under an atmosphere of 6% CO2, 5% O2, and 89% N2. The blastocyst expansion grade and quality of the inner cell mass and trophectoderm cells were assessed on days 5 and 6 according to the Gardner system,28 as previously described by Yan et al.29 Embryos that did not expand were cultured for an additional 24 h (day 6 of culture) to reach the complete blastocyst stage.

Preimplantation genetic testing for aneuploidy

Trophectoderm biopsy was performed on fully expanded blastocysts with a clearly visible inner cell mass using a laser beam (Saturn Active Laser System; Research Instruments, Falmouth, Cornwall, UK). A laser pulsation was used to create a 10–20 mm hole in the zona pellucida, and a biopsy pipette (SBB-20Z-35; Sunlight Medical, Jacksonville, FL, USA) was used to aspirate 3–5 cells. After the biopsy, all blastocysts were immediately cryopreserved by vitrification with cryoprotectant (Rapid Vit; Vitrolife). Biopsied cells were loaded into 200 µl polymerase chain reaction (PCR) tubes and were amplified following the manufacturer’s instructions for the Sureplex whole genome amplification (WGA) system (Illumina, San Diego, CA, USA). After WGA, the products were fragmented into small fragments (100–200 bp) and then added to unique adapter sequences. The specimens were analyzed using NGS with Illumina MiSeq or Ion Proton instruments (MiSeq; Illumina or Ion Proton, Thermo Fisher Scientific, Waltham, MA, USA). The detailed procedures for analyzing raw data from NGS were carried out following bioinformatics protocols. PGT-A reports provide one of three possible results, including euploidy, aneuploid, and mosaic embryos, as previously described.29

Statistical analyses

All statistical analyses were performed using STATA (version 15; StataCorp, College Station, TX, USA). The Kolmogorov-Smirnov test was performed to check for normality of distribution. Continuous data with a normal distribution were reported as mean±standard deviation (s.d.) and were analyzed by the Student’s t-test. Categorical variables were presented as frequency (percentage) and were compared using the Chi-square test. Logistic regression analyses were used to quantify the effect of paternal semen abnormalities on the probability of live birth, while controlling for confounding factors, such as maternal age, maternal BMI, paternal age, and paternal BMI. A two-tailed P < 0.05 was considered statistically significant.

RESULTS

A total of 3383 blastocyst biopsies generated by 1091 PGT-A cycles were included during our study period. Compared to NZ cases, the maternal age was significantly lower in OZ cases (P = 0.007) and higher in AZ cases (P = 0.002). Maternal LH levels were significantly higher in TZ cases compared with NZ cases (P = 0.037), and the paternal age in the AZ group was significantly higher than that in the NZ group (P < 0.001; Table 1). There were no significant differences in the couple BMI, either totally (Table 1) or per couple age intervals (all P > 0.05; Supplementary Table 1), and women of ≥38 years old were significantly associated with higher male age in AZ and TZ groups (both P < 0.001; Supplementary Table 1). No significant differences were observed regarding the maternal baseline hormone levels of FSH, E2, P4, PRL, T, and AMH (all P > 0.05; Table 1), or in the ovarian stimulation protocols administered regarding the different arms of the study (all P > 0.05; Table 1). There were also no significant differences in the mean number of oocytes retrieved, metaphase II oocytes, two pronuclei (2PN zygotes), high-grade embryos at day 3, blastocyst formation, and blastocysts biopsied (all P > 0.05; Table 1).

Table 1.

Basic characteristics of the study population with different semen abnormalities

Variable NZ (n=466) OZ (n=129) AZ (n=367) TZ (n=424)
Value P Value P Value P
Maternal age (year), mean±s.d. 35.5±5.0 34.2±5.5 0.007* 36.7±5.4 0.002* 35.3±5.2 0.483
Maternal BMI (kg m-2), mean±s.d. 23.72±3.32 23.80±3.35 0.807 24.03±3.01 0.171 24.04±3.19 0.147
Laboratory tests, mean±s.d.
 Basal FSH (IU l−1) 7.02±2.59 6.98±2.23 0.891 7.04±2.43 0.915 7.05±2.36 0.828
 Basal LH (IU l−1) 4.97±2.33 5.38±2.59 0.085 5.23±2.77 0.149 5.34±2.93 0.037*
 Basal E2 (pg ml−1) 41.83±39.17 38.03±17.20 0.284 43.52±49.67 0.584 41.53±40.39 0.913
 Basal P4 (ng ml−1) 0.44±0.98 0.34±0.39 0.237 0.42±1.20 0.762 0.42±0.75 0.677
 Basal PRL (ng ml−1) 18.36±34.50 17.81±8.88 0.858 16.74±9.02 0.382 17.01±8.95 0.436
 Basal tT (ng dl−1) 23.29±15.14 24.52±14.18 0.407 22.93±14.76 0.732 23.60±15.89 0.764
 AMH (ng ml−1) 3.40±3.09 3.94±3.31 0.094 3.44±3.50 0.884 3.37±3.03 0.865
Paternal age (year), mean±s.d. 36.5±5.7 35.6±6.0 0.106 38.2±6.3 <0.001* 36.9±6.7 0.317
Paternal BMI (kg m−2), mean±s.d. 26.64±3.75 26.26±4.04 0.320 26.52±3.80 0.655 26.50±4.04 0.590
Ovarian stimulation protocols, n (%) 0.163 0.885 0.585
 Long GnRH agonist protocol 153 (32.8) 53 (41.1) 130 (35.4) 145 (36.8)
 Short GnRH agonist protocol 117 (25.1) 24 (18.7) 89 (24.3) 98 (24.9)
 GnRH antagonist protocol 156 (33.5) 45 (34.9) 119 (32.4) 120 (30.5)
 Other protocols 40 (8.6) 7 (5.4) 29 (7.9) 31 (7.9)
Number of oocytes retrieved (mean±s.d.) 10.3±6.1 11.1±6.7 0.202 10.6±6.6 0.546 10.9±6.3 0.152
Number of metaphase II oocytes (mean±s.d.) 9.3±5.6 9.6±5.3 0.508 9.1±5.5 0.683 9.4±5.4 0.654
Number of 2PN zygotes (mean±s.d.) 7.1±4.4 7.2±4.0 0.768 7.1±4.5 0.969 7.3±4.5 0.456
2PN zygotes rate (%), mean±s.d. 79.3±21.9 77.2±21.0 0.333 79.8±24.7 0.761 79.4±27.5 0.958
Number of high-grade embryos on day 3 (mean±s.d.) 3.9±2.8 4.3±2.9 0.080 4.2±2.9 0.054 4.1±2.9 0.070
Number of blastocyst embryos (mean±s.d.) 3.5±2.5 3.6±2.3 0.550 3.4±2.5 0.513 3.6±2.7 0.476
Blastocysts/metaphase II oocytes (%), mean±s.d. 39.3±21.7 39.4±19.8 0.961 39.3±22.3 0.991 39.1±21.3 0.910
Number of blastocysts biopsied (mean±s.d.) 3.1±1.8 3.4±2.0 0.109 3.0±1.8 0.642 3.2±1.8 0.535
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*P<0.05, the study group versus NZ group. A two-tailed P<0.05 was considered statistically significant. NZ: normal sperm parameters; OZ: oligozoospermia; AZ: asthenozoospermia; TZ: teratozoospermia; BMI: body mass index; s.d.: standard deviation; FSH: follicle-stimulating hormone; LH: luteinizing hormone; E2: estradiol; P4: progesterone; PRL: prolactin; tT: total testosterone; AMH: anti-Müllerian hormone; GnRH: gonadotropin-releasing hormone; 2PN: two pronuclei

Supplementary Table 1.

Basic characteristics of the study population with different semen abnormalities in women of different age groups

Variable NZ OZ P AZ P TZ P
Maternal age ≤30 years n=92 n=39 n=62 n=95
 Maternal age (year) 28.2±1.8 27.6±2.3 0.127 27.9±2.1 0.320 28.0±2.0 0.401
 Maternal BMI (kg/m2) 23.50±3.56 23.78±3.38 0.674 23.28±2.76 0.676 23.61±3.33 0.429
 Paternal age (year) 29.9±3.2 29.7±3.2 0.789 30.0±3.7 0.853 30.0±3.8 0.416
 Paternal BMI (kg/m2) 26.13±3.50 25.54±4.36 0.415 26.09±4.41 0.948 28.81±4.45 0.166
30 years< maternal age <38 years n=190 n=48 n=110 n=158
 Maternal age (year) 34.2±2.2 34.0±2.1 0.650 34.1±2.0 0.773 34.0±2.00 0.306
 Maternal BMI (kg/m2) 23.59±3.43 24.07±3.30 0.378 23.65±3.13 0.867 23.90±3.15 0.374
 Paternal age (year) 35.6±4.2 35.0±3.2 0.366 35.6±3.5 0.947 35.0±3.6 0.213
 Paternal BMI (kg/m2) 26.66±4.13 26.39±3.98 0.683 26.23±3.80 0.377 26.14±3.85 0.228
Maternal age ≥38 years n=184 n=42 n=195 n=171
 Maternal age (year) 40.5±1.9 40.3±2.2 0.520 40.9±2.2 0.109 40.5±2.1 0.906
 Maternal BMI (kg/m2) 23.97±3.06 23.51±3.42 0.392 24.47±2.96 0.103 24.40±3.13 0.193
 Paternal age (year) 40.7±4.4 41.6±4.4 0.235 42.3±4.5 <0.001* 42.5±5.4 <0.001*
 Paternal BMI (kg/m2) 26.88±3.44 26.79±3.80 0.888 26.82±3.58 0.884 27.21±3.88 0.386
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*P<0.05 versus NZ group. Values are presented as mean±s.d. n presented as the number of cycles included. A two-tailed P<0.05 was considered statistically significant. NZ: normal sperm parameters; OZ: oligozoospermia; AZ: asthenospermia; TZ: teratozoospermia; BMI: body mass index; s.d.: standard deviation

Upon comparing the rates of euploid, aneuploid, and mosaic blastocysts, no significant differences were observed among the NZ, OZ, and TZ groups (all P > 0.05). Additionally, stratified analyses by maternal age groups also revealed no significant differences (all P > 0.05; Table 2). However, when only different maternal ages were compared in the 4 groups regarding the rates of euploid, mosaic, and aneuploid blastocysts, the AZ group evidenced significantly lower total euploid blastocyst rates (P = 0.022), significantly higher total aneuploid blastocyst rates (P = 0.043), and significantly lower euploid blastocyst rates in women aged ≥38 years (P = 0.003; Table 2).

Table 2.

Outcomes of embryologic ploidy from different semen abnormalities stratified by maternal age

Variable NZ (n=1435) OZ (n=435) AZ (n=1113) TZ (n=1337)
Value P Value P Value P
All, n (%)
 Euploid 619 (43.1) 195 (44.8) 0.533 430 (38.6) 0.022* 597 (44.7) 0.421
 Mosaic 221 (15.4) 77 (17.7) 0.251 177 (15.9) 0.729 223 (16.7) 0.359
 Aneuploid 595 (41.5) 163 (37.5) 0.137 506 (45.5) 0.043* 517 (38.7) 0.134
Maternal age ≤30 years
 Number of embryo 346 158 247 387
 Euploid, n (%) 203 (58.7) 82 (51.9) 0.155 151 (61.1) 0.547 228 (58.9) 0.947
 Mosaic, n (%) 61 (17.6) 35 (22.2) 0.230 44 (17.8) 0.954 74 (19.1) 0.603
 Aneuploid, n (%) 82 (23.7) 41 (26.0) 0.585 52 (21.1) 0.447 85 (22.0) 0.576
30 years < maternal age <38 years
 Number of embryo 610 160 381 511
 Euploid, n (%) 291 (47.7) 86 (53.7) 0.173 191 (50.1) 0.457 267 (52.3) 0.130
 Mosaic, n (%) 113 (18.5) 26 (16.3) 0.506 69 (18.1) 0.870 96 (18.8) 0.911
 Aneuploid, n (%) 206 (33.8) 48 (30.0) 0.367 121 (31.8) 0.512 148 (29.0) 0.085
Maternal age ≥38 years
 Number of embryo 479 117 485 439
 Euploid, n (%) 125 (26.1) 27 (23.1) 0.502 88 (18.1) 0.003* 102 (23.2) 0.315
 Mosaic, n (%) 47 (9.8) 16 (13.7) 0.223 64 (13.2) 0.100 53 (12.1) 0.272
 Aneuploid, n (%) 307 (64.1) 74 (63.2) 0.865 333 (68.7) 0.133 284 (64.7) 0.849
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*P<0.05, the study group versus NZ group. A two-tailed P<0.05 was considered statistically significant. NZ: normal sperm parameters; OZ: oligozoospermia; AZ: asthenozoospermia; TZ: teratozoospermia

Women of advanced age are often in the company of men with high paternal age. In order to eliminate the potential impact of paternal age on embryo ploidy, we categorized couples into four groups based on whether both maternal and paternal ages were ≥38 years (Supplementary Table 2). In the group with maternal age <38 years and paternal age <38 years, as well as the group with maternal age < 38 years and paternal age ≥38 years, there was no significant difference between NZ and AZ (both P > 0.05). In the group with maternal age ≥38 years and paternal age <38 years, as well as the group with maternal age ≥38 years and paternal age ≥38 years, the euploid rate was lower in the AZ group compared to the NZ group (P = 0.134 and P = 0.042, respectively).

Supplementary Table 2.

Rate of blastocysts ploidy of couples of NZ and asthenospermia in different parental age

Variable NZ (n=1435) AZ (n=1113) P
Maternal age <38 years and paternal age <38 years
 Number of embryo 797 540
 Euploid, n (%) 426 (53.5) 299 (55.4) 0.489
 Mosaic, n (%) 154 (19.3) 102 (18.9) 0.843
 Aneuploid, n (%) 217 (27.2) 139 (25.7) 0.546
Maternal age <38 years and paternal age ≥38 years
 Number of embryo 159 88
 Euploid, n (%) 68 (42.8) 43 (48.9) 0.356
 Mosaic, n (%) 20 (12.6) 11 (12.5) 0.986
 Aneuploid, n (%) 71 (44.7) 34 (38.6) 0.360
Maternal age ≥38 years and paternal age <38 years
 Number of embryo 107 58
 Euploid, n (%) 40 (37.4) 15 (25.9) 0.134
 Mosaic, n (%) 17 (15.9) 15 (25.9) 0.122
 Aneuploid, n (%) 50 (46.7) 28 (48.3) 0.849
Maternal age ≥38 years and paternal age ≥38 years
 Number of embryo 372 427
 Euploid, n (%) 85 (22.8) 73 (17.1) 0.042*
 Mosaic, n (%) 30 (8.1) 49 (11.5) 0.107
 Aneuploid, n (%) 257 (69.1) 305 (71.4) 0.470
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*P<0.05 versus NZ group. Values are presented as the number of embryo (n) and the rate (%). A two-tailed P<0.05 was considered statistically significant. NZ: normal sperm parameters; AZ: asthenospermia

Logistic regression models were used to quantify the effect of AZ on the probability of embryoploidy, controlled by confounding factors such as maternal age, maternal BMI, paternal age, and paternal BMI (Table 3). The analysis showed that euploidy rates were significantly lower in patients with AZ after adjusting (adjusted odds ratio [aOR]: 0.654, 95% confidence interval [CI]: 0.475–0.901, P = 0.009). The observed reduction in the euploid blastocyst rate in the AZ group combined with advanced female age (≥38 years) was further confirmed (Figure 1). For that, those women were compared to different sperm motility groups: low motility (≤42.0%), intermediate motility (42.0%–62.9%), and high motility (≥62.9%), which confirmed a significantly lower blastocyst euploid rate in cases with decreased sperm motility (Figure 1).

Table 3.

Multivariate logistic regression model for parental confounding factors on the blastocyst ploidies in women of advanced age

Variable OZ AZ TZ
aOR (95% CI) P aOR (95% CI) P aOR (95% CI) P
Euploid 0.771 (0.468–1.269) 0.306 0.654 (0.475–0.901) 0.009* 0.863 (0.630–1.182) 0.359
Mosaic 1.418 (0.757–2.655) 0.275 1.506 (0.998–2.272) 0.051 1.257 (0.816–1.936) 0.299
Aneuploid 1.040 (0.665–1.626) 0.863 1.145 (0.862–1.520) 0.351 1.019 (0.764–1.358) 0.899
Whole chromosome aneuploidy alone 0.806 (0.420–1.546) 0.516 1.277 (0.821–1.986) 0.277 1.073 (0.686–1.679) 0.757
Segmental aneuploidy alone 1.385 (0.579–3.313) 0.465 0.730 (0.382–1.395) 0.340 0.987 (0.528–1.844) 0.967
Segmental + whole chromosomal aneuploidy 1.034 (0.429–2.493) 0.941 0.841 (0.480–1.473) 0.544 0.892 (0.497–1.601) 0.703
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*P<0.05, the study group versus NZ group. Adjustment included maternal age, maternal body mass index, paternal age, and paternal body mass index. A two-tailed P<0.05 was considered statistically significant. NZ: normal sperm parameters; OZ: oligozoospermia; AZ: asthenozoospermia; TZ: teratozoospermia; aOR: adjusted odds ratio; CI: confidence interval

Figure 1.

Figure 1

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The comparison of embryonic ploidy outcomes among different sperm motility groups in women of advanced age. Low motility was defined as total sperm motility ≤42.0%; intermediate motility was defined as total sperm motility >42.0% and <62.9%; high motility was defined as total sperm motility ≥62.9%. *P < 0.05, **P < 0.01.

DISCUSSION

The relationship between abnormal semen quality and chromosomal abnormalities in blastocysts remains unclear. Our study provides novel insights into the combined effects of paternal semen quality and maternal age on blastocyst ploidy. Specifically, we demonstrate that AZ significantly reduces the rate of euploid blastocysts when combined with AMA. This finding underscores the importance of considering both paternal and maternal factors in the context of assisted reproductive technologies (ART).

Our findings indicate that the euploidy rate was lower and the aneuploidy rate was higher in women of AMA compared to younger women from the NZ group. These results align with earlier studies showing a decline in euploidy rate with increasing maternal age in pregnancies conceived through ART.16,30,31 We further confirmed that the association between advanced female age and increased blastocyst aneuploidy rates exists across all groups, including OZ, AZ, and TZ.

We found that neither OZ nor TZ had a significant effect on the blastocyst ploidy. These findings are consistent with previous studies. Mazzilli et al.20 demonstrated that the blastocyst euploidy rates were independent of male factors such as sperm count or morphology. Similarly, Polese et al.21 and Kahraman et al.22 observed no correlation between sperm concentration (below 5 × 106 ml−1) and chromosomal status of blastocysts. Bonus et al.14 reported no significant differences in blastocyst aneuploidy of paternal origin between men with normal and abnormal sperm count or morphology. In contrast, Coates et al.8 reported higher rates of sex chromosome aneuploidy in blastocysts obtained from ICSI cycles involving oligospermic men compared to those from normozoospermic men. A possible explanation for this discrepancy could lie in differences in grouping criteria. In the study of Coates et al.,8 normal semen parameters were defined as sperm concentration >19 × 106 ml−1, gross normal morphology >30%, and motility >30%, while severe oligozoospermia was classified as <6 × 106 ml−1. These definitions differ from the WHO 2010 guidelines23 used in our study.

Our results showed that AZ was associated with a reduction in euploid blastocysts. These data were further analyzed based on different age groups of women (≤30 years vs >30 years, and <38 years vs ≥ 38 years) at the time of OPU. Our findings indicate that low sperm motility in young women (<38 years) was not associated with blastocyst ploidy, which is consistent with the study of Wang et al.32 Surprisingly, we found that when advanced maternal age was involved, AZ was associated with lower euploid rates. Our findings provide evidence against the claim by Bonus et al.14 that sperm motility might not play a role in increasing the likelihood of genetic abnormalities. The difference between these two studies could be attributed to the fact that Bonus et al.14 analyzed the blastocyst aneuploidy originating from paternal contributions, while our study examined the mixed influence of maternal and paternal contributions on blastocyst aneuploidy.

AZ refers to the reduced motility of spermatozoa. The precise mechanisms underlying the combined effects of AZ, AMA, and ploidy in the blastocyst stage remain unclear.33,34,35 Studies have demonstrated that chromosomal abnormalities in zygotes often arise from errors during early mitotic processes.36,37 Following fertilization, chromosomes are driven by sperm centrioles to form a spindle-like structure that aggregates at the inter-nuclear interface.38,39 Sperm centrioles consist of proximal and distal centrioles. Distal centrioles, located at the sperm tail, form the axoneme of the flagellum and play a critical role in sperm motility.40 Proximal centrioles, positioned posterior to the sperm head, primarily contribute to spindle formation in the zygotes, thereby influencing the occurrence of aneuploidy.41,42 We speculate that men with AZ exhibit dysfunctional centrioles, which lead to reduced sperm motility and mitotic errors related to abnormal spindle. Although centrioles are essential for proper chromosome segregation, maternal oocytes possess partial compensatory mechanisms to correct errors, promoting viable embryo development.43,44 However, with advancing maternal age, issues such as misalignment of the spindle assembly checkpoint, aberrant post-translational modifications of histones and microtubules, and mitochondrial dysfunction may impair the compensatory capacity of oocytes.45 We infer that inadequate compensation of oocytes in women of advanced age contributes to higher blastocyst aneuploidy in men with AZ. Overall, future research is needed to investigate how oocytes from women of advanced age undercompensate for embryonic development in men with AZ.

In this study, we demonstrated that the effect of AZ on blastocyst ploidy cannot be dissociated from the combined influence of oocytes derived from AMA. The clinical indications for PGT-A remain contentious, particularly in cases involving male factors. If these findings are corroborated in independent studies and across multiple in vitro fertilization (IVF) centers, the combination of AZ and AMA should be considered a valid indication for PGT-A in the future. This study opens new avenues for investigating the impact of impaired sperm-egg interaction on embryonic meiotic segregation. Furthermore, to strengthen the validity of our hypothesis, we are currently collecting supplementary data. In subsequent investigations, we will address the limitations of this study, especially those stemming from the limited sample size.

This study had some strength. Semen analysis is a routine indicator for evaluating the male fertility. It is valuable to study the effect of semen abnormalities on embryonic ploidy, and we chose the WHO criteria for human semen, which have been widely used. Additionally, we included a large number of PGT-A cycles and embryos, leading to robust results. We acknowledge the limitations of this study. First, it was a retrospective study with the usual bias associated with data collection. The decision to perform PGT-A before embryo transfer was primarily made by the attending physician and may have been influenced by the patient’s fertility history and preferences. We were unable to assess all confounding factors, such as smoking, alcohol consumption, ovarian controlled hyperstimulation regimens, and the trigger of final oocyte maturation regimen. It is important to note that only cases where sperm successfully fertilized an oocyte were included. It appears that a selection process occurs, where only biopsy-eligible blastocysts are analyzed, leaving the condition of developmentally arrested embryos unassessed.

CONCLUSION

Our findings indicate that semen parameters such as sperm concentrations and sperm morphology are not associated with the incidence of aneuploid, mosaic, or euploid embryos in this large cohort of patients undergoing ICSI with PGT-A. In contrast, impaired sperm motility had a negative effect on the ploidy status of blastocysts, particularly in cases influenced by AMA. Our study provides new insights, suggesting that it is the combination of AMA and impaired sperm motility, but not sperm quality alone may represent a new indication for PGT-A. Future research is needed to investigate the combined effect of maternal age and sperm motility on embryo mitosis.

AUTHOR CONTRIBUTIONS

YG, YZ, and XX analyzed the data and drafted the article. YZ, HQX, MG, XWL, and LJW performed preimplantation genetic testing. CL biopsied the embryos. XG, TJ, and JHY provided genetic counseling for the patients. YG and ZJC conceived and designed the study. All authors were involved in interpreting the data and read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.

ACKNOWLEDGMENTS

This study was supported by the National Key R&D Program of China (2022YFC2703200 and 2018YFC1004900), Guangxi Key Research and Development Plan Project (No. AB22035080), and the Natural Science Foundation of Shandong Province (ZR2022MH278).

Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.

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