A WHO 2021-based comprehensive scheme outlining sperm parameters' associations with IVF outcomes in PGT-A cycles

Rossella Mazzilli; Danilo Cimadomo; Federica Innocenti; Marilena Taggi; Greta Chiara Cermisoni; Sara Ginesi; Lisa Dovere; Laura Albricci; Maurizio Guido; Maria Rosaria Campitiello; Susanna Ferrero; Antonio Capalbo; Alberto Vaiarelli; Filippo Maria Ubaldi; Alberto Ferlin; Laura Rienzi; Gianluca Gennarelli

doi:10.1111/andr.13811

A WHO 2021-based comprehensive scheme outlining sperm parameters' associations with IVF outcomes in PGT-A cycles

Mazzilli R, Cimadomo D, Innocenti F, Taggi M, Cermisoni GC, Ginesi S, Dovere L, Albricci L, Guido M, Campitiello MR, Ferrero S, Capalbo A, Vaiarelli A, Ubaldi FM, Ferlin A, Rienzi L, Gennarelli G

Published October 2025 Andrology

DOI 10.1111/andr.13811 PMID 39609097 PMC PMC12476224

RRM Academy Synopsis

Poor semen on all three measures linked to lower live birth odds

Low sperm concentration, motility and shape together went with lower live birth odds per completed cycle in a retrospective study of 3101 couples. Low meant below the WHO 2021 fifth percentile. They had ICSI (one sperm injected into each egg) with embryo chromosome testing (PGT-A). Paternal age and body mass index showed no association with live birth per completed cycle.

Study at a glance, retrospective study of 3101 couples: Poor semen on all three measures went with lower live birth odds. Source: Mazzilli R et al., 2025, PMID 39609097.

Key Findings

At least one live birth per completed cycle: multivariable odds ratio 0.73 (95% CI 0.58 to 0.93) with concentration, motility and morphology all below the fifth percentile, against all parameters above it.
Obstructive azoospermia (a blocked sperm duct), in a group of 56: multivariable odds ratio 0.47 (95% CI 0.24 to 0.92) for at least one live birth per completed cycle.
Euploid blastocyst rate (chromosomally normal embryos per inseminated mature egg) was 4.0% lower (95% CI 2.6% to 5.5% lower) with concentration, motility and morphology all below the fifth percentile.
The same rate was 5.5% lower (95% CI 2% to 9% lower) with obstructive azoospermia and 5.8% lower (95% CI 0.6% to 10.9% lower) with non-obstructive azoospermia.
Paternal age over 44 versus under 38 went with a lower day 5 blastocyst rate (29.4% versus 34.2%, multivariable odds ratio 0.86, 95% CI 0.74 to 0.99, p = 0.04).

Interpretation

This retrospective cohort from one private IVF clinic reports associations. Regression models adjusted for maternal age and the number of eggs inseminated. The authors report that maternal age and egg number had a larger impact than male factors. All couples were Caucasian, used their own eggs and had ICSI with embryo chromosome testing. Azoospermia groups were small (1.4% and 1.0% of the study population), 9% of cycles were incomplete, and sperm DNA fragmentation was not measured. The authors note that future work must determine whether the semen findings themselves or their underlying cause explain the poorer outcomes.

RRM Context

The authors advise improving sperm concentration and motility before IVF whenever feasible. Restorative reproductive medicine evaluates both partners from the start. Its clinicians treat the cause of poor semen results. IVF bypasses the problem without resolving it. The paper lists the woman's infertility as unexplained in 83% of cases. Restorative clinicians treat unexplained infertility as undiagnosed.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

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.

Subjects

3101 couples undergoing 4013 intracytoplasmic sperm injection (ICSI) + PGT-A cycles with own-oocytes (years 2013-2021).

Intervention

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.

Topics

Male Fertility › Semen Analysis › Reference Standards · Assisted Reproduction › Outcomes and Effectiveness › Outcomes by Diagnosis

Rossella Mazzilli, Danilo Cimadomo, Federica Innocenti, Marilena Taggi, Greta Chiara Cermisoni, Sara Ginesi, Lisa Dovere, Laura Albricci, Maurizio Guido, Maria Rosaria Campitiello, Susanna Ferrero, Antonio Capalbo, Alberto Vaiarelli, Filippo Maria Ubaldi, Alberto Ferlin, Laura Rienzi, Gianluca Gennarelli

R Mazzilli, D Cimadomo, F Innocenti, M Taggi, G Cermisoni, S Ginesi, L Dovere, L Albricci, M Guido, M Campitiello, S Ferrero, A Capalbo, A Vaiarelli, F Ubaldi, A Ferlin, L Rienzi, G Gennarelli

PMID 39609097 39609097 DOI 10.1111/andr.13811 10.1111/andr.13811 Mazzilli et al. 2025, Mazzilli 2025

A WHO 2021-based comprehensive scheme outlining sperm parameters' associations with IVF outcomes in PGT-A cycles

Poor semen on all three measures linked to lower live birth odds

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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