To examine the association between semen parameters, assessed according to World Health Organization (WHO)-2021 criteria, and paternal body mass index (BMI) and age, with embryological and clinical outcomes in ICSI cycles involving preimplantation genetic testing for aneuploidy (PGT-A).
Design
Retrospective study at a private in vitro fertilization (IVF) clinic.
We performed trophectoderm biopsy, and comprehensive chromosome testing to report uniform aneuploidies and vitrified-warmed euploid single-blastocyst-transfers. Regression analyses adjusted for relevant confounders were conducted to outline putative associations of semen analysis and characteristics and paternal BMI and age with all embryological/clinical outcomes.
Results
Maternal age was the only significant confounding variable affecting euploidy blastocyst rate (EBR) (primary embryological outcome). When categorized, motility < 5th-percentile (-2.5%, 95%CI -4.9 to -0.2%, p = 0.03), concentration plus morphology < 5th-percentile (-2.7%,95%CI -4.8 to -0.6%, p = 0.01), concentration plus morphology plus motility < 5th-percentile (-4.0%,95%CI -5.5 to -2.6%, p < 0.01), obstructive-azoospermia [OA] (-5.5%,95%CI -9 to -2%, p = 0.02) and non-obstructive azoospermia (NOA) (-5.8%,95%CI -10.9 to -0.6%, p = 0.03) showed significantly lower results compared to all parameters > 5th-percentile. Furthermore, after adjusting for maternal age and the number of metaphase-II-oocytes inseminated, the only significant confounding variable affecting the chance of obtaining ≥ 1 live birth among completed cycles (primary clinical outcome) was basal and post sperm processing motility. When categorized, concentration plus morphology plus motility < 5th-percentile (multivariable-OR: 0.73, 95%CI 0.58-0.93, p = 0.01) and OA (multivariable-OR: 0.47, 95%CI 0.24-0.92, p = 0.03) showed significantly lower chances compared to all parameters > 5th-percentile. Advanced paternal age (defined as > 44 years) was associated only with lower day 5-blastocyst and Gardner's AA-grade (i.e., top quality) blastocyst rates.
Conclusions
This comprehensive analysis provides IVF professionals with useful figures to counsel infertile couples about their chances of success, taking into account the impact of semen characteristics and paternal BMI and age. These estimates are valuable for personalized decision-making about the most effective reproductive strategies to adopt, especially not underestimating male factor, by improving sperm concentration and motility whenever possible before assisted reproductive technologies.
Mazzilli R et al., 2026·Journal of endocrinological investigation
Male factor could contribute, alone or in combination with female factor, to the inability to conceive in a couple in more than half of cases. The effect of male factor infertility (MFI) on embryological assisted reproductive technology (ART) outcomes remains an ongoing discussion.
to evaluate the impact of MFI on embryo aneuploidy rates, to better understand the role and possible indication for Preimplantation genetic testing for aneuploidies (PGT-A), considering the role of sperm characteristics, paternal age, sperm DNA fragmentation and sperm aneuploidies.
this narrative review included all available articles, published up to January 2026.
Available evidence, often based on heterogeneous and old-fashioned methodologies, suggests that MFI may impair embryonic development, particularly in terms of fertilization rate and blastulation rate, more than embryo euploidy; however, a comprehensive evaluation of MFI should be integrated into clinical practice in the context of couple infertility, to also optimize the efficiency and outcomes of ART. Promising results emerged from sperm DNA fragmentation as a tool to predict embryo euploidy, but further investigations involving larger sample sizes and improved standardization are required.
Grande G et al., 2026·The Journal of clinical endocrinology and metabolism·Free to read
Male factor infertility (MFI) is frequently labelled idiopathic when evaluation relies primarily on semen analysis, potentially overlooking endocrine and pathophysiological mechanisms relevant for targeted management.
To phenotypically define MFI and develop a pathophysiology-based classification aimed at reducing idiopathic infertility following comprehensive evaluation.
Prospective monocentric cohort study conducted at a tertiary referral academic centre.
Eight hundred male partners of infertile couples evaluated between October 2024 and January 2026 after exclusion of isolated female factor infertility.
Prevalence of MFI categories, hormonal patterns across phenotypes, and proportion of idiopathic infertility after comprehensive work-up.
All patients underwent standardized clinical evaluation, hormonal assessment (total testosterone, FSH, LH), testicular ultrasound, and complete semen analysis. Microbiological testing, transrectal ultrasound, and genetic analyses were performed according to guidelines.
Primary spermatogenic failure was the most prevalent category (56.0%), followed by infection/inflammation (22.4%) and hypogonadotropic hypogonadism (8.5%). Idiopathic infertility was identified in only 5.3% of cases. Distinct endocrine profiles were observed, with high-FSH spermatogenic failure representing the dominant phenotype.
Comprehensive phenotyping markedly reduces the proportion of patients classified as having idiopathic infertility and identifies clinically relevant subgroups. This prospective study provides validation of a pathophysiology-based classification and supports a shift toward endocrine-integrated diagnostic strategies in male infertility, with potential implications for targeted management.
Rocca MS et al., 2026·Journal of translational medicine·Free to read
Standard semen analysis has little prognostic value in distinguishing fertile from infertile men. Furthermore, in men with semen parameters within the reference ranges, it cannot distinguish fertile men from infertile men, i.e. partners of couples with idiopathic infertility. Oxidative stress, mitochondrial dysfunction, sperm telomere shortening, and DNA fragmentation have been proposed as contributors to impaired male fertility. However, these biomarkers have not been evaluated as a whole in subjects with normal semen parameters, partners of fertile and infertile couples.
To characterise a multidimensional panel of sperm biomarkers-including sperm telomere length (STL), mitochondrial DNA copy number (mtDNAcn), reactive oxygen species (ROS), lipid peroxidation (LP), sperm chromatin dispersion (SCD), and respiratory control ratio (RCR)-and to identify whether these parameters might discriminate, in men with normal semen parameters, infertile men from fertile controls.
A total of 150 men with semen parameters within the normal ranges were enrolled: 47 male partners of couples with idiopathic infertility and 103 fertile controls. STL and mtDNAcn were quantified by qPCR; ROS were assessed using OxiSperm®II with semiquantitative imaging; LP was measured spectrophotometrically in seminal plasma; SCD was used to determine DNA fragmentation; and mitochondrial function was evaluated by oxygen consumption and RCR. Correlations between biomarkers and semen parameters were analysed using Pearson or Spearman coefficients, and intergroup comparisons were adjusted for age.
Semen parameters did not differ significantly between male partners of fertile and infertile couples. compared to men of fertile couples, men of infertile couples exhibited significantly shorter STL (0.57 ± 0.59 vs 1.21 ± 1.13, p_adj = 0.001) and higher oxidative stress, with both ROS (8300.9 ± 4214.8 vs 6555.3 ± 3394.3, p_adj = 0.027) and LP (88.33 ± 55.50 vs 40.29 ± 46.98, p_adj < 0.001) markedly elevated. mtDNAcn, SCD, and RCR showed no difference between the groups. Across the entire cohort, STL correlated negatively with ROS and LP and positively with RCR. ROS correlated negatively with total sperm count, motility and RCR, and positively with LP. LP displayed the strongest pattern of associations, correlating negatively with concentration, total count, motility, STL and RCR, and positively with age and volume.
Among men with normal semen analysis, partners of couples with idiopathic infertility exhibit a distinct sperm molecular profile characterised by telomere shortening and oxidative imbalance. STL, ROS and LP emerged as age-independent biomarkers associated with infertility status and showed promising discriminatory ability in this cohort, supporting their integration as second-level tests to complement routine semen analysis in cases of normozoospermia.
Ponce MR et al., 2026·Andrology·Free full text on PubMed Central
Transgender individuals assigned male at birth (AMAB) may choose to preserve their fertility prior to starting gender-affirming hormone therapy (GAHT). However, limited data exist regarding the baseline reproductive and hormonal characteristics of this population before and after GAHT.
To characterize semen quality and hormonal profiles in transgender AMAB individuals prior to GAHT and compare findings with cisgender men and with transgender individuals who discontinued GAHT for at least 3 months.
This retrospective study included transgender AMAB individuals from two tertiary andrology centers who underwent sperm cryopreservation before GAHT initiation (treatment-naïve group). Clinical evaluation included anthropometric measures, testicular volume assessment, varicocele detection, and sex hormone measures. Semen parameters were analyzed according to WHO criteria and compared with those of cisgender men and previously treated transgender individuals.
Thirty-two treatment-naïve transgender AMAB individuals were included. Hormonal parameters were generally within reference ranges. Only 46.9% of treatment-naïve individuals met WHO criteria for normozoospermia, compared with 75.5% of cisgender controls. Compared with nine previously treated individuals, estradiol levels were higher and seminal volume lower. A higher frequency of seminal abnormalities was observed, although not statistically significant.
A substantial proportion of treatment-naïve transgender AMAB individuals exhibited impaired semen parameters prior to GAHT initiation. Prior GAHT exposure showed a trend toward poorer semen quality. These findings support early fertility counseling and preservation in transgender individuals prior to GAHT initiation.
Sermondade N et al., 2013·Human reproduction update·Free full text on PubMed Central
BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.
Ecochard R et al., 1999·International journal of andrology
We analysed 12,100 consecutive cycles of artificial insemination by donor spermatozoa in 1901 infertile couples. In our analysis, particular attention was given to finding an appropriate way of taking into account the respective effects of female and male factors on the pregnancy success rate and the level at which these factors act (cycle vs. woman and donation vs. donor). A total of 1213 pregnancies occurred. The pregnancy rate per cycle was lower as the age of the woman increased (p < 0.0001) and varied with the type of infertility: fecundity was higher (p = 0.03) in the case of azoospermia than of severe oligozoospermia. After taking into account these factors, significant unexplained variation in likelihood to conceive remained. A part of this heterogeneity was shown to be due to variation in fecundability between semen donors. In order to explain this heterogeneity between donors, compositional covariates were used, particularly the mean of results of the semen analysis performed for donations from the same donor. For each semen characteristic, the overall mean of the different donations of a donor was an important predictive factor of successful insemination: after taking into account all of the other factors, the odds ratios for an increase of 50 x 10(6)/mL spermatozoa, of a 20% increase in sperm motility and of a 2 point increase in the post-thaw quality index, were, respectively, 1.13, 1.37 and 1.56. After adjustment for these factors, the specific characteristics of each semen donation were no longer significantly predictive of successful insemination. This observation has a biological interpretation: sperm with low parameters but produced by a normally fertile man can have a satisfactory success rate.
Lifshitz K et al., 2026·International urology and nephrology·Free to read
Paternity rates among testicular cancer survivors are reduced. The patient journey, from fertility preservation at diagnosis to attempted paternity or use of assisted reproductive technologies (ART), contains two key gaps in the literature. While baseline semen impairment is well recognized, the relationship between disease stage, tumor pathology, and semen quality remains inconsistent. In addition, prior studies have largely excluded sex-cord stromal tumors, lacked healthy comparators, and rarely performed pathology-specific analyses within the same clinical stage. Reported paternity rates vary widely (6-21%), yet real-world data on ART utilization and live-birth outcomes remain limited. We conducted a retrospective cohort study (2017-2023) at a single tertiary academic referral center within a healthcare system that provided full coverage for sperm cryopreservation for 5 years and ART for up to 2 live births. Primary outcomes included baseline semen parameters by tumor histology and clinical stage, pathology-specific comparisons within each stage, and post-treatment utilization of cryopreserved sperm. Secondary outcomes were ART pregnancy and live-birth rates. The semen parameters were compared with those of healthy sperm donor candidates. The cohort included 126 men (mean age 36.6 ± 10.9 years; 83 seminoma, 35 non-seminoma, 8 sex-cord stromal tumors). Compared with 100 healthy donor candidates, testicular cancer patients demonstrated significantly impaired baseline semen quality across all parameters except volume (all p ≤ 0.01). Post-thaw semen quality was further reduced, with lower motility rates (17.5% vs 44.1%) and total motile counts (1.1 vs 7.8 million), highlighting greater motility and total motile count loss following cryopreservation. Sex-cord stromal tumors exhibited the poorest semen parameters. Semen quality did not differ by stage overall; pathology-specific differences were observed only in stage II disease, favoring non-seminoma tumors (p ≤ 0.05). Overall, 69% (n = 91) elected sperm cryopreservation. Among those, the median number of vials initially frozen was 15 (IQR 10-18), with a mean of 11.6 ± 4.3 vials per patient (range 1-18). During a median follow-up of 5.3 years (IQR: 3.9-6.8), only 8% (n = 7) used their vials for ART, undergoing a median (IQR) of 2.5 (1-4) cycles per couple (15 cycles recorded among 6 of 7 couples; cycle count missing for one couple), resulting in 12 pregnancies and an overall live-birth rate of 67%: 2/2, 100%, 6/10, 60%. Testicular cancer significantly impairs semen quality, with important variation by tumor pathology rather than stage. These findings underscore the need for accurate counseling: fertility preservation often enables future use primarily through IVF and supports banking multiple vials to mitigate freeze-thaw losses.
Liao M et al., 2024·American journal of obstetrics and gynecology
The global trend of delaying childbearing has led to an increasing number of couples seeking in vitro fertilization. The adverse effects of advanced maternal age on pregnancy and perinatal outcomes are well documented, regardless of the conception method. In addition, advanced paternal age may contribute to poor reproductive potential because of high levels of sperm DNA fragmentation. However, it remains challenging to guide older men regarding the effect of paternal age on pregnancy and birth outcomes in the field of assisted reproduction. This study aimed to investigate the association of paternal age with live birth and perinatal outcomes following in vitro fertilization-frozen embryo transfer. A retrospective study was performed at a university-affiliated fertility center, involving women who were younger than 36 years and had undergone frozen embryo transfer from January 2011 to June 2021. Subjects were categorized into 6 groups based on paternal age: <25, 25 to 29, 30 to 34, 35 to 39, 40 to 44, and ≥45 years. A generalized estimating equation logistic regression model was used to account for the clustered nature of data and to adjust for confounders. Paternal age between 25 and 29 years served as the reference group in the logistic regression models. A total of 56,113 cycles who met the inclusion criteria were included in the final analysis. On unadjusted analyses, the reproductive outcome parameters showed a considerable decline with increasing male age. The live birth rate decreased from 47.9% for men aged 25 to 29 years to 40.3% among men aged ≥40 years. Similarly, the clinical pregnancy rate decreased from 54.4% in the reference group to 47.8% in the ≥40 years age group. Conversely, the miscarriage rate increased as male age increased, from 10.2% among men aged 25 to 29 years to 13.5% among men aged ≥45 years. However, the differences in the reproductive outcomes mentioned above were no longer significant in the multivariable models. Compared with the younger controls, advanced paternal age was not associated with a lower chance of live birth (males aged 40-44 years: adjusted odds ratio, 0.94; 95% confidence interval, 0.85-1.04; males aged ≥45 years: adjusted odds ratio, 0.93; 95% confidence interval, 0.79-1.10). In addition, the rates of clinical pregnancy (males aged 40-44 years: adjusted odds ratio, 0.95; 95% confidence interval, 0.85-1.05; males aged ≥45 years: adjusted odds ratio, 0.94; 95% confidence interval, 0.79-1.12) and miscarriage (males aged 40-44 years: adjusted odds ratio, 1.05; 95% confidence interval, 0.85-1.31; males aged ≥45 years: adjusted odds ratio, 1.07; 95% confidence interval, 0.77-1.50) were comparable between the reference and advanced paternal age groups. Furthermore, men in the youngest age group (<25 years) did not have worse pregnancy outcomes than those in the reference group. Regarding perinatal outcomes, there was no difference among the study cohorts in terms of preterm birth, low birthweight, macrosomia, small for gestational age, and large for gestational age, both in the unadjusted and confounder-adjusted models. This study did not demonstrate a significant association between paternal age and live birth and perinatal outcomes after in vitro fertilization-frozen embryo transfer when the female partners were younger than 36 years. With the global trend toward delaying childbirth, our findings provide useful information for counseling patients that increasing paternal age may not adversely affect pregnancy and perinatal outcomes in assisted reproduction.
Male Fertility › Semen Analysis › Reference Standards · Assisted Reproduction › Outcomes and Effectiveness › Outcomes by Diagnosis
Federica Innocenti, Marilena Taggi, Greta Chiara Cermisoni, Sara Ginesi, Lisa Dovere, Laura Albricci, Maurizio Guido, Maria Rosaria Campitiello, Laura Rienzi, Gianluca Gennarelli
F Innocenti, M Taggi, G Cermisoni, S Ginesi, L Dovere, L Albricci, M Guido, M Campitiello, L Rienzi, G Gennarelli
PMID 39609097 39609097 DOI 10.1111/andr.13811 10.1111/andr.13811 Mazzilli et al. 2025, Mazzilli 2025
