High Variability in Human Sperm Membrane Potential over Time Can Limit Its Reliability as a Predictor in ART Outcomes

Sperm membrane potential (<i>E</i>m) hyperpolarization during capacitation is a functional hallmark of fertilizing ability and has been proposed as a predictive biomarker for conventional in vitro fertilization (IVF) success. However, it is unclear whether <i>E</i>m remains s...

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Main Authors: Tomás J. Steeman, Carolina Baro Graf, Analia G. Novero, Mariano G. Buffone, Dario Krapf
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/7/851
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author Tomás J. Steeman
Carolina Baro Graf
Analia G. Novero
Mariano G. Buffone
Dario Krapf
author_facet Tomás J. Steeman
Carolina Baro Graf
Analia G. Novero
Mariano G. Buffone
Dario Krapf
author_sort Tomás J. Steeman
collection DOAJ
description Sperm membrane potential (<i>E</i>m) hyperpolarization during capacitation is a functional hallmark of fertilizing ability and has been proposed as a predictive biomarker for conventional in vitro fertilization (IVF) success. However, it is unclear whether <i>E</i>m remains stable across ejaculates over time and can reliably guide assisted reproductive technology (ART) decisions in advance. Thus, we aimed to evaluate the temporal consistency of human sperm <i>E</i>m within individuals and assess its utility as a prognostic marker when measured days or weeks prior to IVF procedures. <i>E</i>m was assessed in capacitated and non-capacitated sperm from normospermic donors at three time points over 28 days, using a fluorometric assay. Capacitated values were compared to a −48.6 mV threshold previously associated with successful fertilization. Intra-donor <i>E</i>m variability and coefficients of variation (CV) were analyzed statistically. Our results showed that <i>E</i>m values exhibited significant intra-donor variability over time (<i>p</i> = 0.007), with approximately half of the donors crossing the −48.6 mV functional threshold across sessions. Capacitated sperm samples showed significantly greater variability than non-capacitated ones, with several donors exceeding a 30% CV cutoff. No consistent correlation was found between CV and mean <i>E</i>m values. While <i>E</i>m remains a promising functional marker when assessed on the day of IVF, its temporal variability undermines its reliability as a predictive tool for ART decisions made in advance. These findings underscore the importance of timing in functional sperm assessments and call for further studies to identify the physiological factors influencing <i>E</i>m stability.
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spelling doaj-art-9a6f7154b9cd46edbcdac2b03ecc0f4c2025-07-25T13:15:11ZengMDPI AGBiology2079-77372025-07-0114785110.3390/biology14070851High Variability in Human Sperm Membrane Potential over Time Can Limit Its Reliability as a Predictor in ART OutcomesTomás J. Steeman0Carolina Baro Graf1Analia G. Novero2Mariano G. Buffone3Dario Krapf4Instituto de Biología Molecular y Celular de Rosario (IBR CONICET–UNR), Rosario 2000, ArgentinaInstituto de Biología Molecular y Celular de Rosario (IBR CONICET–UNR), Rosario 2000, ArgentinaInstituto de Biología Molecular y Celular de Rosario (IBR CONICET–UNR), Rosario 2000, ArgentinaInstituto de Biología y Medicina Experimental (IBYME–CONICET), Buenos Aires 1428, ArgentinaInstituto de Biología Molecular y Celular de Rosario (IBR CONICET–UNR), Rosario 2000, ArgentinaSperm membrane potential (<i>E</i>m) hyperpolarization during capacitation is a functional hallmark of fertilizing ability and has been proposed as a predictive biomarker for conventional in vitro fertilization (IVF) success. However, it is unclear whether <i>E</i>m remains stable across ejaculates over time and can reliably guide assisted reproductive technology (ART) decisions in advance. Thus, we aimed to evaluate the temporal consistency of human sperm <i>E</i>m within individuals and assess its utility as a prognostic marker when measured days or weeks prior to IVF procedures. <i>E</i>m was assessed in capacitated and non-capacitated sperm from normospermic donors at three time points over 28 days, using a fluorometric assay. Capacitated values were compared to a −48.6 mV threshold previously associated with successful fertilization. Intra-donor <i>E</i>m variability and coefficients of variation (CV) were analyzed statistically. Our results showed that <i>E</i>m values exhibited significant intra-donor variability over time (<i>p</i> = 0.007), with approximately half of the donors crossing the −48.6 mV functional threshold across sessions. Capacitated sperm samples showed significantly greater variability than non-capacitated ones, with several donors exceeding a 30% CV cutoff. No consistent correlation was found between CV and mean <i>E</i>m values. While <i>E</i>m remains a promising functional marker when assessed on the day of IVF, its temporal variability undermines its reliability as a predictive tool for ART decisions made in advance. These findings underscore the importance of timing in functional sperm assessments and call for further studies to identify the physiological factors influencing <i>E</i>m stability.https://www.mdpi.com/2079-7737/14/7/851membrane potentialsperm capacitationhuman fertility
spellingShingle Tomás J. Steeman
Carolina Baro Graf
Analia G. Novero
Mariano G. Buffone
Dario Krapf
High Variability in Human Sperm Membrane Potential over Time Can Limit Its Reliability as a Predictor in ART Outcomes
Biology
membrane potential
sperm capacitation
human fertility
title High Variability in Human Sperm Membrane Potential over Time Can Limit Its Reliability as a Predictor in ART Outcomes
title_full High Variability in Human Sperm Membrane Potential over Time Can Limit Its Reliability as a Predictor in ART Outcomes
title_fullStr High Variability in Human Sperm Membrane Potential over Time Can Limit Its Reliability as a Predictor in ART Outcomes
title_full_unstemmed High Variability in Human Sperm Membrane Potential over Time Can Limit Its Reliability as a Predictor in ART Outcomes
title_short High Variability in Human Sperm Membrane Potential over Time Can Limit Its Reliability as a Predictor in ART Outcomes
title_sort high variability in human sperm membrane potential over time can limit its reliability as a predictor in art outcomes
topic membrane potential
sperm capacitation
human fertility
url https://www.mdpi.com/2079-7737/14/7/851
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