Male partner’s effects are usually considered negligible during IVF, even though over 40 to 50% of infertility diagnoses are associated with male factor [1, 2]. An increase in paternal age and age-independent degeneration of semen quality can be associated with a decline in viable embryos during IVF [3]. Numerous studies have demonstrated that advanced maternal age is associated with decreased ovarian reserve, oocyte pick-up, fertilization rates, and the production of high-quality embryos [4, 5, 6]. However, concerning paternal age, few studies have examined this association, with some studies demonstrating a significant association between paternal age and the embryo aneuploidy rate [7, 8, 9] as well as deterioration of sperm concentration, motility, and morphology [10, 11, 12, 13, 14]. Therefore, it has been suggested that, under certain circumstances, such as low sperm quality in the presence of advanced paternal age, a couple should consider using donor sperm and PGT-A [15]. This begs the question, when semen quality is considered, does using donor sperm improve IVF outcomes? Furthermore, if the male factor is considered, is this an indication to perform PGT-A? Therefore, this study aimed to compare the embryo aneuploidy rates as well as the implantation and pregnancy rates between paternal sperm and donor sperm, with respect to the sperm source’s age and sperm abnormalities.

We originally identified 457 ova donor cycles. However, using the inclusion and exclusion criteria, 394 IVF cohorts qualified for the study (Fig. 1). As shown in Table 1, 15.7% (95% CI: 12.2–19.8%) were from donor sperm, 19.8% (95% CI: 16.0–23.9%) were from parental sperm with normal seminal parameters (normozoospermic patients), 38.8% (95% CI: 33.8–43.7%) were from parental sperm that suffered from teratozoospermia, whereas 25.6% (95% CI: 21.6–29.9%) were from parental sperm that suffered from severe alterations in one or more seminal parameters (volume, concentration, progressive motility, and morphology). There was a 17-year difference between the average age of partner sperm (42.4 $\pm$ 7.4 years) or donor sperm (25.0 $\pm$ 3.3 years), which is considered small. Even though there was a statistical difference in the ages between the group with paternal sperm with no alterations and the paternal sperm with alterations, this was not clinically different. As expected, the sperm donors were significantly younger. There were no differences between the study groups concerning the ova donors’ ages, and there was no clinical difference between the maternal recipients’ ages. Lastly, the average aneuploidy rates for the study groups (Donor semen normozoospermic: 15.9%, 95% CI: 10.0–21.9%; Patient semen normozoospermic: 22.4%, 95% CI: 16.7–28.2%; Patient semen with teratozoospermia: 17.5%, 95% CI: 13.2–21.7%; and Patient semen with severe abnormalities: 21.3%, 95% CI: 16.4–26.2%) were not significantly different (Fig. 2); moreover, the type of male etiology did not affect the aneuploidy rates (Supplementary Fig. 1). There were no differences between the groups with respect to the type of aneuploidies (monosomies, trisomies, both, and multiple changes) as well as the specific chromosome loss or gain (Supplementary Tables 1,2).

Fig. 1.

The study flow chart in line with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.

Fig. 2.

Aneuploidy rates for embryos developed from donor ova using patient or donor sperm, stratified into normozoospermic donor (left black column), normozoospermic patient (right black column), patients with teratozoospermia (white column), and patients with severe abnormalities (gray column). The column height corresponds to the average aneuploidy rate, whereas the bar length is the standard error. Differences between groups were determined with ANOVA with a post hoc Bonferroni test. Significant differences (p 0.05, two-tailed) are indicated with an asterisk.

For patient sperm, there was a weak correlation between paternal age and the prevalence of semen abnormalities (Pearson’s r ${}_{biserial}$ = 0.165, p = 0.003, data not shown). When the study group was stratified by paternal age into quartiles, there was no significant trend for the donor group (Fig. 3A). For the paternal sperm source, there was also no observable association between the sperm source age and the embryo aneuploidy rate (Fig. 3B). However, when stratified into normozoospermia (Fig. 3C), teratozoospermia (Fig. 3D), and severe sperm abnormalities (Fig. 3E), only the teratozoospermia group presented with an age-dependent association (Spearman rho = 0.165, p = 0.041).

Fig. 3.

Aneuploidy rates for embryos developed from donor ova using patient or donor sperm, stratified by age. Data were separated into quartiles based on the sources’ age of the donor sperm (A) or paternal sperm (B). Afterward, the paternal sperm was categorized, based on etiology, as either normozoospermic (C), teratozoospermic (D), or severe abnormalities (E). The column height corresponds to the average aneuploidy rate, whereas the bar length is the standard error. Associations between the sources’ age and the aneuploidy rate were determined by calculating Spearman’s rho.

When the IVF outcomes were compared, there was no clinical difference between the study groups with respect to the number of ova captured, the number of ova fertilized, the number of blastocysts formed, or the embryo transfer rate (Table 2). Moreover, the sperm source (donor versus paternal) and the etiology present in the sperm sample (normozoospermic versus teratozoospermic versus severe abnormalities) had no difference in the clinical pregnancy rate and embryo implantation.

In the present study, we assessed the age-dependent effects on semen quality between partner and donor samples with respect to embryo implantation. Independent of the semen source, we found no difference in the implantation rate. Moreover, the semen source’s age did not affect the aneuploidy rates if the sperm was diagnosed as normozoospermic. This was a clinical retrospective study, which can only show an association and give credence to future hypotheses for experimental research.

Aneuploid embryos are associated with implantation failure [20, 21], where the ovum is associated with a more significant influence on the aneuploidy rate [22]. Here, using donor ova, the expected aneuploidy rate is between 20 and 30% [23, 24], about 25% of the analyzed embryos presented with aneuploidies. This rate was independent of the sperm source (paternal versus donor) and etiology (Fig. 2). Similar studies by Dubey et al. and Mazzilli et al. confirmed this result as they also observed that sperm morphological alterations do not affect the embryo aneuploidy rate [24, 25, 26]. The proposed explanation suggests that using ICSI still delivers an uncompromised genome and sperm alterations are independent of the sperm chromosome composition. Nevertheless, Coban et al. [27] demonstrated that the severity of the sperm defect, as quantified by Kruger’s criteria, can significantly affect the aneuploidy rate, which is also confirmed by Magli et al. [28]. Here, we observed a prevalence of sperm morphological defects in the analyzed samples (teratozoospermia etiology); however, none of the etiologies correlated with the types of aneuploidies. Still, a sub-analysis was not performed because some of the groups had few samples and significant heterogeneity.

Numerous studies demonstrate the maternal effect age has on aneuploidy rates [4, 29]. Nevertheless, the age of the sperm source has also been shown to have an effect on increasing embryo aneuploidies as well as reducing IVF success [7, 8, 9]. The effect of the semen source’s age is still under debate [30]. Here, we observed no correlation in semen donor samples nor with partner samples. Although the samples were stratified by etiology into normal and abnormal sperm, only the teratozoospermia group positively associated the partner’s age with the aneuploidy rate; moreover, there was a weak correlation between paternal age and the presence of sperm abnormalities. This could be an artifact as the prevalence for specific sperm etiologies is increased with age, and the aneuploidy rate is associated with sperm etiology [27, 31, 32, 33]. Even though our study does not confirm the latter effect, there is a suggested aneuploidy rate difference between certain types of sperm etiologies [27, 28, 34]. Magli et al. [28] demonstrated that the non-obstructive azoospermia and oligoasthenoteratozoospermia groups presented with more chromosomally compromised embryos than the normozoospermia group using fluorescence in-situ hybridization and, as mention above, Coban et al. [27] confirmed this effect. A review by Caseiro et al. [35] nicely explains the association between oligoasthenoteratozoospermia and embryo aneuploidies. Lastly, teratozoospermia was shown to be associated with higher rates for trisomies and monosomies [34]. Still, here, the sample size was not sufficient to demonstrate this effect.

The contribution of spermatozoa to embryos aneuploidies in IVF has been the topic of several debates. Garcia-Ferreyra et al. [9] showed that the aneuploidy rates from ova donation cycles determined a high incidence of aneuploidies when men are older than 50 years. Here, no significant difference was found between the ages of the males (paternal or donors) concerning aneuploidy rates in the analyzed embryos.

Several studies have reported the correlation between the aneuploidy rates in embryos derived from abnormal sperm. Coates et al. [36] determined that the aneuploidy incidence was significantly higher in embryos obtained from sperm with oligozoospermia etiology than those in embryos obtained from sperm with normal male factor, independent of the ova source. However, Mazzilli et al. [26] compared five different male etiologies (normozoospermic patients, patients with moderate male factor, patients with oligoasthenoteratozoospermia/cryptozoospermia, patients with obstructive azoospermia, and patients affected with non-obstructive or secretory azoospermia) for their effects on fertilization, embryonic development, aneuploidies incidence, and gestational results. They found that early embryonic development was impaired in patients with severe male factors with respect to fertilization rates and development potential; however, the euploidy rate and blastocyst implantation potential were independent of the sperm quality. They concluded that the male factor would not be an indication when suggesting Preimplantation Genetic Testing (PGT) for an IVF cycle. In the present study, no significant differences were found regarding embryonic development results (fertilization and blastocyst formation rate) as well as with pregnancy and implantation rates, when compared to patients with normal or altered male factor. Our result is in agreement with Mazzilli et al. [26].

Due to the oocyte’s contribution to the aneuploidy rate, under certain circumstances, such as advanced maternal age, embryos are analyzed by PGT-A. In the present study, we focused on evaluating the impact of the male factor in terms of age and seminal quality in exclusively ova donation cycles. Although no significant correlation was found between age and aneuploidy incidence nor between seminal quality and aneuploidies incidence, we did observe an effect of a male factor on aneuploidy rates. Therefore, it would be beneficial for these patients to consider PGT-A.

This study has a few limitations. First, we did not quantify or qualify the type of embryo aneuploidies. Only euploid embryos were transferred. However, specific aneuploidies could be generated and, through the embryo’s auto-correcting mechanisms, produce a viable euploid fetus [37, 38]. Second, the severity of the sperm deformities was not quantified in samples with teratozoospermia diagnosis or other severe alterations. As mentioned above, the effects of sperm with abnormal etiology are associated with higher aneuploidy rates. Third, only the donor semen samples were frozen until use, whereas patient samples were fresh. The effect of cryopreservation on sperm’s DNA integrity is still unclear and under debate [39]. Fourth, the reasons for oocyte donation were not considered, such as recurrent implantation failure, low reserve, or inability to produce viable embryos, to name a few. Underlining the mechanism associated with each pathology could introduce bias to the results. Fifth, all embryos underwent PGT-A using NGT; therefore, these results are limited to this group. Lastly, this is a clinical retrospective study in which we can show an association but not a causal relationship.

Here, we examine if the sperm source’s age affects the aneuploidy rate determined by NGS-PGT-A, which it does not; however, with the teratozoospermia diagnosis, there was a weak association. Therefore, it would be prudent to perform PGT-A when advanced age and teratozoospermia etiology are concurrent. Lastly, low-quality semen did not affect embryo implantation. Overall, these results promote the use of PGT-A.

BMI, Body-mass index; FSH, Follicle-stimulating hormone; GnRH, Gonadotropin-releasing hormone; hCG, Human chorionic gonadotropin; HSA, Human serum albumin; HTF, human tubal fluid; ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilization; NGS, Next-Generation Sequencing; PCR, Polymerase chain reaction; PGT-A, Preimplantation Genetic Testing for Aneuploidies; WGA, Whole-genome amplification.

JP and ELB conceived and designed the study; JP, HS, and JC performed the experiments, data collection as well as monitored the patients; JP and ELB analyzed the data; JP and ELB wrote the manuscript and critically analyzed it; ELB supervised the study and was responsible for the funding. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

In this retrospective study, no written informed consent was needed besides the general consent for data utilization; nevertheless, the study was conducted following the Declaration of Helsinki. The Ethics Committee of the Institute Ingenes México approved this study (approval number: ISF120516).

We want to express our gratitude to the study participants and the medical staff at Ingenes Institute. We thank Dr. Leonardo M. Porchia for drafting the manuscript and Ing. Lucero Cervantes for her editorial assistance.

The study was funded by Consejo Nacional de Ciencia y Tecnología (Conacyt grant number: 250768) to ELB. The funding source did not have a role in the study design, collection, analysis, and interpretation of data and no part in the report’s writing and submitting the paper for publication.

The authors declare no conflict of interest.