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Journal of Lasers in Medical Sciences logoLink to Journal of Lasers in Medical Sciences
. 2023 Sep 25;14:e36. doi: 10.34172/jlms.2023.36

Therapeutic Effects of Low-Level Laser on Male Infertility: A Systematic Review

Amirreza Eghbaldoost 1, Seyed Pooria Salehi Mashhadsari 1, Erfan Ghadirzadeh 2, Alireza Ghoreifi 3, Farzad Allameh 4,*
PMCID: PMC10658110  PMID: 38028870

Abstract

Introduction: The objective of this study was to assess the effectiveness and safety of photobiomodulation (PBM) in the treatment of male infertility.

Methods: We searched Google Scholar, PubMed, and the reference sections of relevant papers published from January 1, 2000 to September 23, 2022. We retrieved all publications related to the impact of PBM on male infertility. After reviewing the titles, abstracts, and full texts, we included fifteen papers in the research. The studies involved 477 semen samples (in vitro studies) and 70 male participants (randomized clinical trials).

Results: All 14 in vitro studies that evaluated effectiveness reported that PBM was successful in increasing the proportion of progressive sperms in semen samples. Various methods were used to evaluate the safety. One study with a sample size of 58 concluded that PBM was not a safe treatment, whereas the other ten studies confirmed its safety. Only one clinical trial evaluated the effect of laser acupuncture on male infertility and found improvements in sperm progressive motility without any serious adverse effects.

Conclusion: All 15 studies evaluating effectiveness reported that the low-level laser was effective for increasing the proportion of progressive sperm in semen samples and that it was safe to use. However, due to the heterogeneity of population characteristics, source characteristics, duration of exposure, sample size, and instruments for measuring safety and efficacy, we cannot conclude that the positive results obtained from the reviewed studies are solely attributable to the low-level laser on the sperm samples.

Keywords: Biostimulation, Laser acupuncture, Low-level light therapy, Male infertility, Photobiomodulation

Introduction

Infertility is defined as the inability to conceive after one year of unprotected regular sexual intercourse, with an incidence of 12% to 18% in the United States, which is often attributed to female infertility.1 However, male factors should also be considered in the management of infertility, as they account for about half of all cases.2,3 Sperm quality is a major male factor in infertility that can be assessed by semen analysis.4 Sperms of infertile men are either low in concentration or number (less than 15 million/mL and a total of 39 million per ejaculate), abnormal in morphology (less than 4% normal morphology), non-viable (less than 58% alive), or reduced in motility (less than 32% progressive motility).4 Motility may not seem to be important for natural pregnancy, but it becomes a critical issue when a high proportion of sperms are immotile in a single ejaculation, especially when performing in vitro assisted reproductive technology procedures such as intrauterine insemination or in vitro fertilization.5,6 Motility can be used as a selection criterion for sperm samples because it increases the chance of pregnancy.6 Typically, hypoxic or stressed cells are immotile or less motile.7 Sperms need intracellular calcium (Ca2 + ) and adenosine triphosphate (ATP), which are provided by mitochondria, to move their flagella.8,9 It is now known that the respiratory chain of immobile cells is inhibited when cytochrome c oxidase binds to mitochondrial produced nitric oxide, thereby decreasing intracellular ATP and Ca2 + levels.10-12 Scientists have explored various treatment options, including injecting chemical compounds into sperm samples.13 However, each has its own limitations and drawbacks. Researchers have recently suggested the use of photons to treat spermatic immobility, but the safety and efficacy of this treatment need further investigations.14,15 Photobiomodulation (PBM), also known as low-level light therapy (LLLT), is a novel treatment that uses light-emitting diodes (LEDs) to apply electromagnetic waves in the visible light and near-infrared (NIR) ranges to the sample’s surface.16 It is safer and more cost-effective than previous alternatives. Numerous in vitro studies evaluating the efficacy and safety of this treatment option at various wavelengths and durations have indicated that this technique can increase sperm motility by stimulating mitochondrial activity and dissociating nitric oxide from its binding sites.17 More ATP is produced and more Ca2 + flows as a result of the resumption of respiratory chains.18 However, the effects of PBM depend heavily on wavelength, number of exposures, and duration of exposure. There is currently no standard intervention guideline for using this method, although research has been conducted to investigate various aspects of efficacy, safety, related exposure and wavelength factors. There are also some studies in the field of clinical use of biostimulation laser therapy for male infertility. Various laser types and body points for radiation have been used. Considering the aforementioned evidence, the aim of the present study was to conduct a systematic literature review to determine the efficacy of PBM in enhancing sperm motility and related factors.

Methods

We conducted this systematic review of the therapeutic effects of low-level laser therapy on male infertility according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and the review protocol. We performed a literature search based on the participants (in vitro semen samples or infertile men), interventions (PBM therapy), comparisons (between case samples and controls or between case samples before and after irradiation), and outcomes (improved sperm quality or conception rate). We excluded meta-analyses, reviews, and case reports. The studies had to be available in English. We searched Google Scholar, PubMed, and the reference sections of related articles published from January 1, 2000 to September 23, 2022. We used the following keywords, their combinations, and related synonyms based on Medical Subject Headings (MeSH) to find the relevant literature: Low-Level Light Therapy, Phototherapy, Photobiomodulation, laser biostimulation, Color therapy, Male Infertility, Subfertility, Sperm, Semen, Testis, Oligoasthenoteratozoospermia, and Spermatozoa. Two reviewers screened the titles and abstracts of all retrieved records on semen samples, assessed them for duplication, and then independently examined the full texts of all potentially relevant studies to select the final studies (E.AR, SM.SP). We assessed the quality of all potentially relevant studies using NHLBI-NIH tools for study quality assessment.19 We used the “Quality Assessment Tool for Controlled Intervention Studies” for controlled trial studies, and for those trials that did not have a control group, we used the “Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group”. We excluded studies with a quality score lower than 5. We resolved discrepancies by consensus. We excluded one study due to lack of stating its population and sample size. We excluded two articles because they were only in Russian. Two researchers (E.AR, SM.SP) independently extracted the following information: study characteristics (authors, publication year, study design, sample size), population characteristics (groups), interventions (source, wavelength, duration), and outcomes (results of safety and efficacy assessments).

Results

We identified 1018 articles through PubMed and Google Scholar, and by hand search. After screening the titles, abstracts, and full texts, we included 15 studies in our study (Figure 1). Table 1 shows the characteristics of the 15 included studies in this systematic review. The sample sizes of the reviewed articles ranged from 3 to 100 male participants. In total, 477 semen samples (in vitro studies) and 70 male subjects (randomized clinical trial) participated in the studies. 14 studies were in vitro controlled trials, and only one study was a double-blind randomized clinical trial. To measure outcomes, 10 studies evaluated both safety and efficacy, four studies only evaluated efficacy, and one study only evaluated safety. Nine studies assessed motility by CASA (Compute-Assisted Sperm Analysis). All 14 studies that assessed efficacy reported that PBM was effective in increasing the rate of progressive (PR) sperms in semen samples, but mostly at moderate time intervals and moderate imposed energy. In four out of seven studies that evaluated motility at different time intervals (including 30 minutes), the highest increase in motility was observed after the 30-minute time point. Table 2 summarizes the efficacy results of the included studies. Safety was assessed by various tests. The most common tests were DFI (DNA Fragmentation Index) used by eight studies, SMI (Sperm Membrane Integrity) used by three studies, and oxidation levels using LPL (Lipid Peroxidation Level), ROS (Reactive Oxygen Species), and SOD (Super Oxide Dismutase) activity, used by four studies. Out of 11 studies that conducted safety tests, only one study with a sample size of 58 concluded that PBM was not a safe method, while the other 10 confirmed its safety. Table 3 summarizes the safety results of the included studies.

Figure 1.

Figure 1

Flowchart of Study Selection

Table 1. Characteristics of the 15 Included Studies in This Systematic Review .

Reference Year Design Population (WHO-Based Type of Samples) Groups Sample Analysis Criteria Sperm Measuring Tool Safety Assessment
Intervention Control Criteria Assessment Tool
Salama and E-Sawy 20 2015 IVCT 27 SS (18 AZ + 9 NZ) 27 washed + 11 non-washed aliquots 27 washed + 11 non-washed aliquots WHO v5 CASA SMI HOS
SHCC ANBS
Espey et al21 2022 IVCT 64 SS (42 AZ + 22 NZ) 3 AES 1 AES WHO v5 CASA DFI LMqPCR
Acrosomal integrity CD46 expression
Salman Yazdi et al22 2014 IVCT 22 SS (22 AZ + 0 NZ) 3 AES 1 AES WHO v4 CASA DFI SCD
SMI HOS
Safian et al23 2020 IVCT 30 SS (0 AZ + 30 NZ) 3 groups of 10 SS ( + 3 AES) 1 AES as control WHO v5 ND Viability ENS
DFI SCD
Allameh et al15 2021 DBRCT 70 men (ND) 35 men (3 SS each) 35 men (3 SS each) ND ND ND ND
Safian et al24 2022 IVCT 24 SS (0 AZ + 24 NZ) 2 AES 1 AES ND ND Quality DFI
LPL
PRM 1 and 2
ADD1
Frangez et al25 2015 IVCT 30 SS (30 AZ + 0 NZ) 4 AES 1 AES WHO v5 CASA ND ND
Safian et al26 2021 IVCT 22 SS (0 AZ + 22 NZ) 1 AES 1 AES WHO v5 CASA Morphology Diff-Quik
Viability ENS
MMP JC-1 dye
ROS DCFDA
LPL (MDA) TBA
Zupin et al27 2020 IVCT 9 SS (ND) 2 AES 1 AES WHO v5 ND Morphology LE-XRF
Elemental distribution
Gabel et al28 2018 IVCT 3 SS (ND) 3 AES 2 AES ND SQA IIB analyzer DFI SCSA
Saeed et al29 2014 IVCT 100 SS (NS) 1 AES 1 AES WHO v4 CASA ND ND
Firestone et al30 2012 IVCT 33 SS (12 AZ + 10 NZ + 11 AO) 1 AES 1 AES WHO v4 CASA DFI Flow cytometry
Shahar et al31 2011 IVCT 30 SS (ND) 1 AES 1 AES ND CASA ROS DFCDA, SOD, Sodium azide
ICC FCI
DFI SCD
Fekrazad et al32 2014 IVCT 25 SS (ND) 2 AES 1 AES WHO v4 CASA ND ND
Highland et a133 2018 IVCT 58 SS (ND) 2 AES of 28 infertile SS 2 AES of 30 fertile SS WHO v4 ND SMI HOS
STI PDNAB
Apoptosis DSM
LPL MDA
SOD SPM
DFI SCD

Abbreviations: ND, no data; IVCT, in vitro controlled trial; DBRCT; double blind randomized controlled trial; SS, semen sample; AZ, asthenozoospermic; NZ, normozoospermic; AO, asthenospermic and oligospermic; AES, aliquots from each sample; CASA, computer-assisted sperm analysis; SMI, sperm membrane integrity; HOS, hypo osmotic swelling test; SHCC, sperm head chromatin condensation; ANBS, aniline blue staining; DFI, DNA Fragmentation Index; LMqPCR, ligand-mediated quantitative polymerase chain reaction; SCD, sperm chromatin dispersion; ENS, eosin nigrosin staining; LPL, lipid peroxidation level; PRM, gene expression levels of protamine; ADD1, adducin 1 alpha; MMP, mitochondrial membrane potential; ROS, reactive oxygen species; DCFDA, 2’7’ dichlorofluorescein diacetate; MDA, malondialdehyde; TBA, thiobarbituric acid; LE-XRF, low energy X-ray fluorescence; SCSA, sperm chromatin structure assay; SOD, super oxide dismutase; ICC, intracellular concentration of free Ca2 +; FCI, fluorescent calcium indicator; STI, sperm toroid integrity; DSM, dual staining method; SPM, spectrophotometry.

Table 2. Efficacy Results of the Included Studies .

Reference Intervention Main Results of efficacy
Salama and El-Sawy20 Red LED (636.6 nm, 1.3 W, at 5 cm) at intervals of 2, 5, and 10 min (0.496, 1.241, 2.482 J/cm2 imposed energy). # A significant increase in PR sperms and a significant decrease in IM sperms at every time point.
# Motility peaked after 5 min, although this peak was not significantly higher than the one happening after 2 min. Then, the PR motility dropped significantly after arriving at the 10-min point.
# Motility in washed samples was significantly higher than that in the non-washed samples.
# A slight non-significant increase in sperm CK activity after 5 min of treatment was detected.
Espey et al21 Pulsed laser probe (655 nm, 50 mW/cm2, 200 sec. impulse duration) at intervals of 0, 30, 60, 90, and 120 min (4, 6, 10 J/cm2 imposed energy). # Doses of 4 and 6 J/cm2 exhibited the strongest effect on motility and velocity.
# The rate of PR raised toward the 32% threshold marker after treatment with 6 J/cm2.
# In the time-independent comparison, the VSL increased in the AZ group after treatment with 4 J/cm2.
# LIN & STR were negatively affected in NZ samples by 10 J/cm2.
# LIN, STR & WOB increased in the AZ group by 6 J/cm2 in the overall group comparison.
Salman Yazdi et al22 GaAlAs laser (830 nm, 100 mW, 0.67 cm2 aperture size) at intervals of 0, 30, 45, and 60 min (0, 4, 6, and 10 J/cm2 imposed energy). # Strongest significant increases in motility were observed in doses of 4 J/cm2 at 60 min, and 6 J/cm2 at 45 min.
# The PR motility significantly increased at each time interval and each dose compared to controls.
# The 10 J/cm2 group showed the least effect on motility.
Safian et al23 Group A: Red laser (630 nm); Group B: NIR laser (810 nm); Group C: Red + NIR laser.
All at 18 cm at intervals of 15, 30, and 60 min. (0.6, 1.2, and 2.4 J/cm2 exposed energy).
# PR sperms in the groups exposed to the three energy densities of the Red + NIR lasers showed a significant increase only after 60 min in all energy densities.
# PR sperms significantly increased in most of the groups exposed to the three energy densities of the NIR laser except the 1.2 J/cm2 after 30 min.
# The best increase in motility resulted from the shortest radiation time (23 s) of the NIR laser at an energy density of 0.6 J/cm2.
# This study confirmed the superiority of the NIR laser at 0.6 J/cm2 compared with the Red and Red + NIR protocols.
Allameh et al15 Light energy was transferred by laser fibers to several specific points performed by technicians of acupuncture using a Laser (810 nm, 300 mW, 18 J/min energy, at 90 degrees) on the skin at intervals of 5 to 10 seconds twice a week for consecutive 5 weeks. In the control group, sham laser acupuncture was performed. Three semen samples were taken from all patients; the first before the intervention, the second immediately after the intervention, and the third three months after the intervention. # Sperm volume and morphology did not differ significantly in both control and intervention groups (all three samples).
# Sperm motility and concentration were significantly higher only in the 3rd sample (3 months after the intervention).
Safian et al24 The control group underwent conventional sperm cryopreservation, group 2 underwent pre-freezing exposure (810 nm, diode laser, and 0.6 J/cm2), and group 3 underwent post-freezing and thawing PBM exposure. # Group 2 exhibited the highest increased motility outcomes compared to groups 1 and 3.
Frangez et al25 Group 1: 850 nm, 2.16 mW/cm2; Group 2: a mix of 625, 660, 850 nm, 3.92 mW/cm2; Group 3: 470 nm, 5.06 mW/cm2; Group 4: a mix of 470, 625, 660 nm, 8.23 mW/cm2. All groups were exposed for 3 min., and their motility was evaluated 30 min. later. # After treatment, the increase in the ratio of PR sperms was statistically significant in all investigated groups.
# The improvement of sperm motility was the largest in group 3 semen samples, although not statistically different from the other treated groups.
# This study indicates that LLLT using LED significantly improves sperm motility regardless of the wavelength.
Safian et al26 Samples received a single dose of NIR exposure from a laser diode (810 nm, 0.6 J/cm2, at 18 cm) before cryopreservation. Samples were analyzed 30, 60, and 90 min. after thawing. # Results showed a significant motility increase in the NIR laser-preconditioning groups compared to the control.
Zupin et al27 Group L1: Class IV diode laser (800 nm, 0.1 W/cm2, 5 J/cm2); Group L2: Class IV diode laser (800 nm, 0.1 W/cm2, 15 J/cm2). Samples were analyzed at 0 and 60 min post-irradiation. # The total motility increases or stays constant in all irradiated samples compared to that of the untreated ones.
# Considering the progressive motility in a couple of cases, it can be seen that the L1 setting induces a decrease while L2 causes an increase, compared to that of the control samples.
Gabel et al28 The 104 LED cluster (56 x 660 nm, 10 mW and 48 x 850 nm, 30 mW, total power 2W at 5 cm with 39.5 mW/cm2) was projected for periods of 25, 50, and 75 seconds to the 1st frozen sample and 50, 100, 200, and 400 seconds to the fresh sample.
The GaAlAs single divergent laser beam (200 mW, 810 nm, at 5 cm with 90 mW/cm2) was projected for periods of 10, 20, and 40 seconds to the 2nd frozen samples and 15, 20, and 30 seconds to the fresh sample.
# 30 min post-irradiation, a maximal effect on motility was achieved.
# The 104 LED cluster caused just over a four-fold increase in motility with 75 s. exposure, whilst the laser produced an optimal effect of just below a four-fold increase at 20 s exposure.
# The best effect on motility 30 min after exposure came from a treatment time of 50 s of LED while the longevity of the effect from higher doses diminished more rapidly.
# The best overall longevity of sperm motility came from the shortest irradiation time (15 s).
# The benefit from higher doses was shorter-lived.
Saeed et al29 Irradiated using a continuous He-Ne laser model (IFHN05) for 30 min. # The results showed that 30-min laser irradiation increases the percentage of PR sperms significantly.
Firestone et al30 Irradiated with a laser system (905 nm, 50 mW/cm2, 1.5 J/cm2) for 30 seconds. Motility was assessed after 30 and 120 min. # Results showed a statistically significant increase in motility in the treated samples 30 min after exposure. This difference was not observed 120 min after exposure.
# Most significantly, those samples that were classified as both AZ + AO exhibited the greatest increase in motility (83.5%) as a result of the treatment.
Shahar et al31 Irradiated for 3 min. with 40 mW/cm2 visible light (400–800 nm) with maximum energy at 600 nm. # Exposure caused a significant increase in PR sperms. However, no effect was seen on total motility.
# This significant effect of light on PR sperms was seen within 10 min of incubation and it continued for at least 3 h.
# A significant increase in VSL and LIN of the samples was observed 30 min after the treatment.
Fekrazad et al32 Red and Infrared lasers with 635 and 830 nm wavelengths were used. # The mean total motility, PR motility, and VLC significantly increased in both Red and Infrared groups. The size of this effect was higher in the Infrared group, but the difference between the Red and Infrared groups was not significant.
Highland et al33 Exposed to a NIR source using a Philips Infrared bulb (750-1100 nm, 230 V, 50 Hz, 150 W) for a short duration of 15 min. In this study, the efficacy of PBM in motility was not assessed and only safety tests were done.

Abbreviations: PR, progressive motile sperms; IM, immotile sperms; CK, creatine kinase; AZ, asthenozoospermic; NZ, normozoospermic; AO, asthenospermic and oligospermic; NIR, near infrared; VSL, straight-line velocity; LIN, linearity of the curvilinear path; STR, straightness of the average path; WOB, wobble parameter for oscillation; PBM, photobiomodulation.

Table 3. Safety Results of the Included Studies .

Reference Results
Salama and El-Sawy20 # CK activity increased insignificantly after 5-minute LED treatment.
# Both SMI and SHCC remained stable after the treatment for 10 min.
Espey et al21 # No significant changes in the DFI were detected after therapy.
# The pattern of CD46 expression confirmed the maintenance of acrosomal integrity after therapy.
Salman Yazdi et al22 # The results of SCD and HOS tests in the 10 J/cm2 group were not significantly different compared to the control group.
Safian et al23 # Both the Red and Red + NIR lasers at 0.6, 1.2 and 2.4 J/cm2 significantly decreased viability and increased DFI. However, this difference was not significant between NIR and control groups.
Allameh et al15 In this study, the safety of PBM in motility was not assessed and only motility tests were done.
Safian et al24 # DFI and LPL were significantly reduced in group 2 compared to group 1.
# Early apoptosis and necrotic cells decreased significantly in group 2 compared to either group.
# The expression levels of PRM1, PRM2, and ADD1 were not significantly different among the study groups.
# PBM therapy prior to cryopreservation has a significant protective role against cryo-damage.
Frangez et al25 In this study, the safety of PBM in motility was not assessed and only motility tests were done.
Safian et al26 # No significant differences were observed in the morphological features.
# PBM treatment before cryopreservation significantly increased the concentration of viable spermatozoa.
# PBM before cryopreservation significantly increased the number of high MMP sperms and decreased the number of low MMP sperms post-thawing.
# The PBM-preconditioning significantly decreased the intracellular ROS level and LPL.
Zupin et al27 # An increase in the Na + content was detected after PBM, suggesting that this change could be vital in the enhancement of sperm movement.
Gabel et al28 # SCSA assay revealed no increase in DFI from the very high doses of both laser and LED therapy.
Saeed et al29 In this study, the safety of PBM in motility was not assessed and only motility tests were done.
Firestone et al30 # DFI was not significantly different.
Shahar et al31 # ROS was produced after 1–3 min of light irradiation, while there was a significant reduction in ROS in the presence of SOD or azide.
# Mitochondrial respiration is the main source of ROS produced by light therapy in sperms.
# HAM in DCF loaded cells was enhanced by light.
# Azide caused complete inhibition of the light effect on HAM.
# Light therapy did not affect DFI.
# Intracellular Ca2 + concentration increased significantly after PBM.
Fekrazad et al32 In this study, the safety of PBM in motility was not assessed and only motility tests were done.
Highland et al33 # The sperm viability significantly decreased in both groups after exposure to NIR which was higher in group 2 compared to group 1.
# A significant decrease in the number of swollen spermatozoa was observed after NIR exposure in both groups as compared to pre-treated samples.
# Percent of apoptotic cells increased more significantly after NIR exposure in both groups as compared to pre-treated groups. This increase was significantly higher in group 2 compared to group 1 post-treatment.
# Toroid disruption increased insignificantly after NIR exposure in group 1, but group 2 showed a highly significant increase.
# The number of sperms with normal chromatin dispersion decreased significantly in groups 1 and 2 after NIR exposure as compared to the pre-treated samples.
# SOD activity diminished significantly after NIR exposure in both groups.
# LPL increased significantly after NIR exposure in groups 1 and 2.

Abbreviations: SMI, sperm membrane integrity; HOS, hypo osmotic swelling test; SHCC, sperm head chromatin condensation; ANBS, aniline blue staining; DFI, DNA Fragmentation Index; LPL, lipid peroxidation level; PRM, gene expression levels of protamine; ADD1, adducin 1 alpha; MMP, mitochondrial membrane potential; ROS, reactive oxygen species; SCSA, sperm chromatin structure assay; SOD, super oxide dismutase.

Discussion

Almost all studies reported that PBM is a safe and effective method for increasing the motility rate of sperm samples. Various types of lasers, including red light, NIR laser, He-Ne laser, and GaAlAs laser, were used in the studies. In one of the studies, laser acupuncture was used to deliver light energy through multiple skin points. The results showed that laser acupuncture was effective in improving sperm motility and concentration in infertile patients with oligospermia and had no significant adverse effects. We can infer from the findings of the studies that PBM efficacy is optimal when applied for a moderate duration and dose of irradiation, and when either of these factors (time or energy dose) is increased, its efficacy decreases or lasts for a shorter time. In four out of seven studies that evaluated motility at different time intervals, the highest increase in motility was observed after the 30-minute time point, but 2 studies reported that the best results could be achieved after 60 minutes or 45 minutes with a higher irradiation dose, and one study reported that the increase in motility was not significant after 30 minutes at 1.2 J/cm2 (Table 2). A possible reason for such discrepancies in the efficacy results of PBM in increasing motility after different time intervals among various studies is the lack of a common standard. Different radiation sources (in terms of wavelength, output power, distance, and other characteristics of the source), various sample sizes and population characteristics (some studies had only NZ (normozoospermic) or AZ (asthenozoospermic) samples or a combination of both), and imposed energies are the potential factors that need standardization. Out of 11 studies that conducted safety tests, only one study concluded that PBM was not a safe method, while the other 10 confirmed its safety. However, it should be noted that since there are some major differences in terms of population characteristics (some studies had only NZ or AZ samples or a combination of both), sample size (from 3 to 100 samples and from 1 to 5 aliquots from each sample), and the type of methods used to conduct safety tests, it is very difficult to draw a strong conclusion on the safety of PBM on semen samples in male subjects (Table 3).

Conclusion

Because of the heterogeneity in the population characteristics, source characteristics, duration of exposure, sample size, and instruments for safety and efficacy measurement, we cannot attribute the positive results obtained from the reviewed studies solely to the effect of PBM on the semen samples.

Author’s Contribution

Conceptualization: Farzad Allameh.

Data curation: Amirreza Eghbaldoost, Seyed Pooria Salehi.

Formal analysis: Amirreza Eghbaldoost, Seyed Pooria Salehi.

Methodology: Amirreza Eghbaldoost.

Project administration: Farzad Allameh.

Resources: Amirreza Eghbaldoost, Seyed Pooria Salehi.

Software: Amirreza Eghbaldoost, Seyed Pooria Salehi.

Supervision: Farzad Allameh.

Validation: Farzad Allameh.

Visualization: Erfan Ghadirzadeh.

Writing–original draft: Erfan Ghadirzadeh.

Writing–review & editing: Amirreza Eghbaldoost.

Competing Interests

The authors declare no competing interests.

Ethical Approval

Not applicable.

Funding

None.

Please cite this article as follows: Eghbaldoost A, Salehi Mashhadsari SP, Ghadirzadeh E, Ghoreifi G, Allameh F. Therapeutic effects of low-level laser on male infertility: a systematic review. J Lasers Med Sci. 2023;14:e36. doi:10.34172/jlms.2023.36.

References

  • 1. Thoma ME, McLain AC, Louis JF, King RB, Trumble AC, Sundaram R, et al. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril 2013;99(5):1324-31.e1. 10.1016/j.fertnstert.2012.11.037. [DOI] [PMC free article] [PubMed]
  • 2.Bhattacharya S, Porter M, Amalraj E, Templeton A, Hamilton M, Lee AJ, et al. The epidemiology of infertility in the North East of Scotland. Hum Reprod. 2009;24(12):3096–107. doi: 10.1093/humrep/dep287. [DOI] [PubMed] [Google Scholar]
  • 3.Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015;13:37. doi: 10.1186/s12958-015-0032-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Winters BR, Walsh TJ. The epidemiology of male infertility. Urol Clin North Am. 2014;41(1):195–204. doi: 10.1016/j.ucl.2013.08.006. [DOI] [PubMed] [Google Scholar]
  • 5.Donnelly ET, Lewis SE, McNally JA, Thompson W. In vitro fertilization and pregnancy rates: the influence of sperm motility and morphology on IVF outcome. Fertil Steril. 1998;70(2):305–14. doi: 10.1016/s0015-0282(98)00146-0. [DOI] [PubMed] [Google Scholar]
  • 6.Miller DC, Hollenbeck BK, Smith GD, Randolph JF, Christman GM, Smith YR, et al. Processed total motile sperm count correlates with pregnancy outcome after intrauterine insemination. Urology. 2002;60(3):497–501. doi: 10.1016/s0090-4295(02)01773-9. [DOI] [PubMed] [Google Scholar]
  • 7.Verratti V, Di Giulio C, D’Angeli A, Tafuri A, Francavilla S, Pelliccione F. Sperm forward motility is negatively affected by short-term exposure to altitude hypoxia. Andrologia. 2016;48(7):800–6. doi: 10.1111/and.12515. [DOI] [PubMed] [Google Scholar]
  • 8.Ruiz-Pesini E, Díez-Sánchez C, López-Pérez MJ, Enríquez JA. The role of the mitochondrion in sperm function: is there a place for oxidative phosphorylation or is this a purely glycolytic process? Curr Top Dev Biol. 2007;77:3–19. doi: 10.1016/s0070-2153(06)77001-6. [DOI] [PubMed] [Google Scholar]
  • 9.Rossato M, Di Virgilio F, Rizzuto R, Galeazzi C, Foresta C. Intracellular calcium store depletion and acrosome reaction in human spermatozoa: role of calcium and plasma membrane potential. Mol Hum Reprod. 2001;7(2):119–28. doi: 10.1093/molehr/7.2.119. [DOI] [PubMed] [Google Scholar]
  • 10.Hamblin MR. Mechanisms and mitochondrial redox signaling in photobiomodulation. Photochem Photobiol. 2018;94(2):199–212. doi: 10.1111/php.12864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Albuquerque-Pontes GM, Vieira RP, Tomazoni SS, Caires CO, Nemeth V, Vanin AA, et al. Effect of pre-irradiation with different doses, wavelengths, and application intervals of low-level laser therapy on cytochrome c oxidase activity in intact skeletal muscle of rats. Lasers Med Sci. 2015;30(1):59–66. doi: 10.1007/s10103-014-1616-2. [DOI] [PubMed] [Google Scholar]
  • 12.Nazari L, Salehpour S, Hosseini S, Allameh F, Jahanmardi F, Azizi E, et al. Effect of antioxidant supplementation containing L-carnitine on semen parameters: a prospective interventional study. JBRA Assist Reprod. 2021;25(1):76–80. doi: 10.5935/1518-0557.20200043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Gruber FS, Johnston ZC, Norcross NR, Georgiou I, Wilson C, Read KD, et al. Compounds enhancing human sperm motility identified using a high-throughput phenotypic screening platform. Hum Reprod. 2022;37(3):466–75. doi: 10.1093/humrep/deac007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Sato H, Landthaler M, Haina D, Schill WB. The effects of laser light on sperm motility and velocity in vitro. Andrologia. 1984;16(1):23–5. doi: 10.1111/j.1439-0272.1984.tb00229.x. [DOI] [PubMed] [Google Scholar]
  • 15.Allameh F, Razzaghi M, Hosseini S, Barati M, Razzaghi Z, Salehi S, et al. The effect of laser acupuncture on semen parameters in infertile men with oligospermia: a randomized clinical trial. J Lasers Med Sci. 2021;12:e84. doi: 10.34172/jlms.2021.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Saltmarche AE. Low level laser therapy for healing acute and chronic wounds - the extendicare experience. Int Wound J. 2008;5(2):351–60. doi: 10.1111/j.1742-481X.2008.00491.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Karu T. Photobiology of low-power laser effects. Health Phys. 1989;56(5):691–704. doi: 10.1097/00004032-198905000-00015. [DOI] [PubMed] [Google Scholar]
  • 18.Lubart R, Friedmann H, Sinyakov M, Cohen N, Breitbart H. Changes in calcium transport in mammalian sperm mitochondria and plasma membranes caused by 780 nm irradiation. Lasers Surg Med. 1997;21(5):493–9. doi: 10.1002/(sici)1096-9101(1997)21:5<493::aid-lsm12>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  • 19. NHLBI N: Study Quality Assessment Tools. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed January 4, 2022.
  • 20.Salama N, El-Sawy M. Light-emitting diode exposure enhances sperm motility in men with and without asthenospermia: preliminary results. Arch Ital Urol Androl. 2015;87(1):14–9. doi: 10.4081/aiua.2015.1.14. [DOI] [PubMed] [Google Scholar]
  • 21.Espey BT, Kielwein K, van der Ven H, Steger K, Allam JP, Paradowska-Dogan A, et al. Effects of pulsed-wave photobiomodulation therapy on human spermatozoa. Lasers Surg Med. 2022;54(4):540–53. doi: 10.1002/lsm.23399. [DOI] [PubMed] [Google Scholar]
  • 22.Salman Yazdi R, Bakhshi S, Jannat Alipoor F, Akhoond MR, Borhani S, Farrahi F, et al. Effect of 830-nm diode laser irradiation on human sperm motility. Lasers Med Sci. 2014;29(1):97–104. doi: 10.1007/s10103-013-1276-7. [DOI] [PubMed] [Google Scholar]
  • 23.Safian F, Ghaffari Novin M, Karimi M, Kazemi M, Zare F, Ghoreishi SK, et al. Photobiomodulation with 810 nm wavelengths improves human sperms’ motility and viability in vitro. Photobiomodul Photomed Laser Surg. 2020;38(4):222–31. doi: 10.1089/photob.2019.4773. [DOI] [PubMed] [Google Scholar]
  • 24.Safian F, Bayat M, Jajarmi V, Abdollahifar MA, Nazarian H, Shams Mofarahe Z, et al. Comparative effect of photobiomodulation on human semen samples pre- and post-cryopreservation. Reprod Sci. 2022;29(5):1463–70. doi: 10.1007/s43032-021-00805-x. [DOI] [PubMed] [Google Scholar]
  • 25.Ban Frangez H, Frangez I, Verdenik I, Jansa V, Virant Klun I. Photobiomodulation with light-emitting diodes improves sperm motility in men with asthenozoospermia. Lasers Med Sci. 2015;30(1):235–40. doi: 10.1007/s10103-014-1653-x. [DOI] [PubMed] [Google Scholar]
  • 26.Safian F, Ghaffari Novin M, Nazarian H, Shams Mofarahe Z, Abdollahifar MA, Jajarmi V, et al. Photobiomodulation preconditioned human semen protects sperm cells against detrimental effects of cryopreservation. Cryobiology. 2021;98:239–44. doi: 10.1016/j.cryobiol.2020.09.005. [DOI] [PubMed] [Google Scholar]
  • 27.Zupin L, Pascolo L, Gianoncelli A, Gariani G, Luppi S, Giolo E, et al. Synchrotron radiation soft X-ray microscopy and low energy X-ray fluorescence to reveal elemental changes in spermatozoa treated with photobiomodulation therapy. Anal Methods. 2020;12(29):3691–6. doi: 10.1039/d0ay00960a. [DOI] [PubMed] [Google Scholar]
  • 28.Gabel CP, Carroll J, Harrison K. Sperm motility is enhanced by low level laser and light emitting diode photobiomodulation with a dose-dependent response and differential effects in fresh and frozen samples. Laser Ther. 2018;27(2):131–6. doi: 10.5978/islsm.18-OR-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Saeed G, Al-Kaisy AZ, Ali M. The effect of the low level laser irradiation on the human sperm motility. Al-Anbar J Vet Sci. 2014;7(2):6–10. [Google Scholar]
  • 30.Firestone RS, Esfandiari N, Moskovtsev SI, Burstein E, Videna GT, Librach C, et al. The effects of low-level laser light exposure on sperm motion characteristics and DNA damage. J Androl. 2012;33(3):469–73. doi: 10.2164/jandrol.111.013458. [DOI] [PubMed] [Google Scholar]
  • 31.Shahar S, Wiser A, Ickowicz D, Lubart R, Shulman A, Breitbart H. Light-mediated activation reveals a key role for protein kinase A and sarcoma protein kinase in the development of sperm hyper-activated motility. Hum Reprod. 2011;26(9):2274–82. doi: 10.1093/humrep/der232. [DOI] [PubMed] [Google Scholar]
  • 32.Fekrazad E, Keyhan H, Fekrazad R, Tajik A. Effect of diode lasers on human sperm motility. Acad Res Int. 2014;5(5):21–5. [Google Scholar]
  • 33.Highland H, Rajput N, Sharma R, George LB. Differential sensitivity of the human sperm cell to near infrared radiation. J Photochem Photobiol B. 2018;183:119–26. doi: 10.1016/j.jphotobiol.2018.04.027. [DOI] [PubMed] [Google Scholar]

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