INTRODUCTION
Male infertility is defined as the inability of couples who have abstained from contraception and maintained a normal sexual life for at least a year to conceive due solely to male-related factors.[] Infertility affects approximately 15% of couples worldwide, with male factors accounting for about half of these cases.[] Sperm quality is a crucial indicator of male fertility. Recently, however, semen quality among fertile males has deteriorated due to lifestyle habits and occupational pressures, leading to oligozoospermia becoming a prominent cause of male infertility.[] This condition significantly impacts men’s reproductive health and can strain family relationships.
Given the complex mechanisms underlying male infertility, the etiology of oligozoospermia remains unclear in 30%–40% of patients, presenting significant challenges in its management.[,] Moreover, male infertility is not just a reproductive issue; it is also an indicator of potential underlying health conditions, including oncological, cardiovascular, and autoimmune disorders.[] A cohort study highlighted this association, showing that infertile men have a 49% higher risk of developing testicular cancer, non-Hodgkin’s lymphoma, and a broader range of cancers compared to healthy men.[] In addition, male infertility has been included as a parameter in studies designed to assess overall male health, recognizing its potential link to chronic diseases.[] While the direct causality between male infertility and other diseases has yet to be conclusively established, its negative impact on overall wellbeing underscores the importance of prompt diagnosis and timely intervention in addressing male infertility.
The treatment of male infertility includes administering medications, surgery, and the use of assisted reproductive technology (ART), with the treatment regimen tailored to the underlying cause, patient-specific circumstances, and other factors. However, knowledge gaps remain, particularly regarding the role of surgery in the treatment of varicocele (VC) and the choice of surgical methods.[] While surgery can improve sperm quality in VC cases,[] it fails to do so in 20%–37% of cases and is generally not recommended for normal semen or subclinical VC.[,] ART provides a solution for severe oligozoospermia, with the sequential use of ART significantly increasing live birth and pregnancy rates in patients with oligozoospermia and azoospermia.[,] Nonetheless, ART is associated with high costs, variable efficacy, and genetic risks. In light of these challenges, there is growing interest in the application of complementary and alternative medicine (CAM) modalities to male infertility, including acupuncture, natural remedies, and mind–body therapies.[] Studies show that a substantial proportion of infertile couples-approximately 39.8% have incorporated CAM into their pregnancy preparation.[] Thus, there is a need to empirically evaluate the safety and efficacy of CAM approaches in managing male infertility.
Acupuncture originated in China more than 3000 years ago, when ancient practitioners discovered the therapeutic potential of stimulating specific body regions with sharp stones to alleviate pain and treat illnesses, laying the foundations for modern acupuncture practices.[] Based on the theory of meridians and acupoints, acupuncture involves activating designated points to induce favorable physiological and chemical responses throughout the body via meridians. The goal is to clear meridians, harmonize Qi and blood circulation, resolve organ dysfunctions or blockages, and restore physiological balance.
The effectiveness of acupuncture is strongly correlated with patient sensations, such as soreness, numbness, swelling, and a sense of heaviness, which can propagate to distant limbs via meridians. Reports of these sensations are often associated with more favorable treatment outcomes.[,]
As a cornerstone of traditional Chinese medicine (TCM) and a key element of CAM, acupuncture is recognized for its simplicity, rapid therapeutic effects, and excellent safety profile. It has received significant attention, with the World Health Organization endorsing its use in managing respiratory, digestive, urological, endocrine, neurological, reproductive, and various multisystemic disorders.[,] Recently, acupuncture has been increasingly used to treat male infertility, showing promising efficacy.[] In this paper, we critically examine the clinical performance, underlying mechanisms, and challenges of acupuncture in treating male infertility, highlighting its importance in this context.
MALE INFERTILITY: A TRADITIONAL CHINESE MEDICINE PERSPECTIVE
In TCM, the kidneys are considered central to male reproductive health, with “kidney essence” playing a crucial role in reproductive function.[,] TCM attributes male infertility to factors such as kidney deficiency, Qi stagnation, phlegm and dampness, and blood stasis.[]
There are several major advantages associated with employing TCM to treat male infertility. First, due to its holistic approach, TCM can address multiple underlying causes simultaneously. Second, TCM treatments are not only effective but also safe. Furthermore, TCM treatments can improve semen quality and alleviate associated symptoms. Hence, the integrative approach employed in TCM is especially valuable in managing complex cases of male infertility.
MERIDIANS AND ACUPOINTS RELATED TO MALE INFERTILITY
The meridian system is fundamental to acupuncture therapy for two key reasons: (1) it includes specific points, and (2) the meridians connect the body’s surface and internal organs, forming a network that transports Qi and blood throughout the body. This system has a bidirectional regulatory effect. Stimulating points along the meridians can replenish kidney essence and Qi, which aids the treatment of male infertility.[] Scholars such as Ding and Zhao have reviewed the literature on the use of acupuncture for treating male infertility and identified the Ren, Bladder, Spleen, and Stomach meridians as the most frequently used meridians in this context.[] The key acupoints identified include Guanyuan (CV4), Qihai (CV6), Zusanli (ST36), Sanyinjiao (SP6), and Shenshu (BL23) [Table 1].[]
Table 1.
Acupuncture point localization table
| Acupoints | Coding | Localization | Attribution of meridians of TCM |
|---|---|---|---|
| Guanyuan | CV4 | Lower abdomen, on the anterior midline, 3 inches below the navel | Ren meridians |
| Qihai | CV6 | Lower abdomen, on the anterior midline, 1.5 inches below the navel | Ren meridians |
| Zusanli | ST36 | Anterolateral aspect of the calf, 3 inches below the Dubi point, one transverse finger outside the anterior border of the tibia | Stomach meridians |
| Sanyinjiao | SP6 | Medial aspect of the lower leg, 3 inches above the tip of the inner ankle, posterior to the medial aspect of the tibia | Spleen meridians |
| Shenshu | BL23 | In the lumbar region, below the spinous process of the second lumbar vertebra, 1.5 inches aside | Bladder meridians |
According to TCM theory, stimulating acupoints has a therapeutic effect on local and adjacent tissues, as well as on organs and tissues located along the associated meridian pathways. Hence, both local and distant benefits can be gained. The Ren, Bladder, Spleen, and Stomach meridians traverse the male reproductive system [Figure 1], while important acupoints, such as Guanyuan, Qihai, and Shenshu, are located around the reproductive organs in the lumbar and abdominal regions [Figure 2], highlighting their significance in treating male infertility.
Figure 1.
Sketch of the meridian pathways. (A) Ren meridian, connecting major organs such as the genitals, throat, mouth, and eyes; (B) Bladder meridian, linking major organs including the brain, bladder, kidneys, and anus; (C) Spleen meridian, associated with major organs such as the spleen, stomach, and vulva; (D) Stomach meridian, connecting major organs such as the throat, breast, gastrointestinal tract, and genitals.
Figure 2.
Acupuncture point localization sketch.
CLINICAL EFFICACY OF ACUPUNCTURE IN THE TREATMENT OF MALE INFERTILITY
Improvement of sperm quality
The primary and most evident benefit of acupuncture in managing male infertility is enhanced sperm quality, which is a central focus of current research. Meta-analyses have highlighted its effectiveness in improving sperm quality while maintaining a commendable safety record.[] A pioneering clinical study by Riegler demonstrated acupuncture’s positive impact on semen quality in 28 male infertility patients by ruling out a placebo effect and examining its effects from both psychological and physiological perspectives.[] Subsequent studies have confirmed acupuncture’s role in improving semen quality among infertile men.[,]
Despite the challenges associated with treating severe oligozoospermia, which is often treated using ART, acupuncture has shown therapeutic potential in the treatment of this condition, particularly when used in conjunction with ART. A randomized, placebo-controlled trial involving 57 patients with severe oligozoospermia revealed significant improvements in semen quality among those who received acupuncture compared to those who received a placebo after six weeks (P = 0.035).[] In another study,[] researchers investigated the effect of acupuncture on idiopathic male infertility by treating 22 patients who previously had negative intracytoplasmic sperm injection (ICSI) results with twice-weekly acupuncture for eight weeks before retrying ICSI. The results show that acupuncture not only improved the patients’ sperm motility and sperm counts but also significantly increased the fertilization rate from 40.2% to 66.2% (P < 0.01), underscoring its potential as an adjunctive therapy.
With the advent of new technologies, novel therapeutic modalities have emerged that integrate traditional acupuncture with modern technology. Electroacupuncture (EA) combines traditional needles with pulsed electrical stimulation, while transcutaneous electrical acupoint stimulation (TEAS) uses self-adhesive electrodes, eliminating the need for needles.[,] The efficacy of these treatments is closely related to the intensity of the electrical current. A study found that applying TEAS at 2 Hz significantly improved sperm count, viability, and levels of α-glucosidase, zinc, and fructose, which are crucial for sperm maturation and motility, compared to TEAS at 100 Hz.[] In contrast, EA has been shown to primarily enhance the percentage of viable sperm in classes a (rapid progressive motile sperm) and a + b (rapid progressive motile sperm + slow progressive motile sperm).[] In another recent development, laser acupuncture therapy, a non-invasive method in which a laser probe directly contacts the skin, has been introduced. In a study involving 70 oligozoospermic infertile patients, half the patients were treated with laser acupuncture therapy and the other half with sham laser acupuncture therapy, and it was found that laser acupuncture therapy improved sperm viability and concentration.
[] Together, the abovementioned findings highlight the evolving landscape of acupuncture-based therapies for the treatment of male infertility.
Varicose veins of the spermatic cord
VC is characterized by abnormal tortuosity and dilation of the spermatic veins due to obstruction of venous reflux or valvular failure. It has a prevalence of approximately 15% in the general population.[] Although VC is a benign condition, it leads to various pathological changes, including elevated testicular temperature, reflux of metabolites, and testicular hypoxia.[] VC-related infertility accounts for 35%–50% of primary male infertility cases and 69%–81% of secondary infertility cases, making it a leading cause of male infertility.[] The exact mechanism responsible for VC-related sperm damage is not fully understood; however, the induction of oxidative stress (OS) is a primary hypothesis.[]
While surgery is the conventional treatment option for VC-related infertility, acupuncture has emerged as a promising alternative. Stimulating key acupoints, such as Zhongji (CV3), Guanyuan (CV4), Qihai (CV6), bilateral Guilai (ST29), Hegu (LI4), Taichong (LR3), Zusanli (ST36), and Sanyinjiao (SP6), has shown efficacy in treating VC-related infertility.[] Clinical studies indicate that acupuncture improves sperm concentration, viability, and morphology, while also enhancing blood viscosity and reducing VC diameter.[] A comparative study involving 15 varicocele patients who underwent varicocelectomy and 15 varicocele patients who received acupuncture revealed that both groups showed significant improvements in sperm concentration and motility. The increase in sperm concentration was higher in the acupuncture group compared to the varicocelectomy group (P = 0.039). Both groups had a pregnancy rate of 33%. These findings suggest that acupuncture appears to be effective in treating primary infertility due to semen abnormalities in varicocele patients and is comparable to the effects of varicocelectomy.[]
Reproductive system infections
Reproductive system infections in men can negatively impact sperm quality; approximately 15% of male infertility cases have been attributed to genitourinary tract infections.[] Both bacterial and viral infections can directly cause sperm death and reduce sperm count and motility, and they can also indirectly affect sperm production and reproductive organ function by stimulating cytokine production.[] In addition, some of the antibiotics used to treat genitourinary infections, such as fluoroquinolones and aminoglycosides, can adversely affect sperm quality.[,]
Acupuncture presents a safer alternative for treating reproductive system infections, and it may also address the limitations of antibiotics.[] A cohort study found a lower incidence of urinary tract infections among patients who received acupuncture compared to those who did not (95.4 vs. 110.0 per 1000 person-years, Hazard Ratio = 0.76, 95% Confidence Interval = 0.73–0.80).[] Similarly, a meta-analysis of two open-label trials involving 165 participants reported that acupuncture reduced the risk of urinary tract infections (Risk Ratio = 0.48, 95% Confidence Interval = 0.29–0.79).[] Although these studies did not assess semen quality, the reported effectiveness of acupuncture in treating urinary tract infections suggests its potential in managing male infertility related to such infections. Future clinical research should thoroughly investigate the effect of acupuncture on male infertility caused by reproductive system infections to provide stronger evidence for its use.
Effect of acupuncture on achieving pregnancy
Despite the mounting evidence of the positive effect of acupuncture on male infertility, a major clinical concern remains whether acupuncture can ultimately contribute to achieving pregnancy. The results of several studies indicate that acupuncture can improve the pregnancy success rate.[] However, Cheong et al.[] found that while acupuncture had no significant side effects, it did not enhance live birth or pregnancy rates in couples undergoing ART. The results of another meta-analysis also suggest that the evidence linking acupuncture to improved pregnancy outcomes is relatively weak due to considerable methodological variability across studies.[] These findings indicate that while acupuncture may improve semen quality in infertile men, further exploratory studies are needed to determine its efficacy in achieving successful pregnancies.
MECHANISMS OF ACUPUNCTURE TREATMENT FOR MALE INFERTILITY
Endocrine regulation
The hypothalamic–pituitary–testicular (HPT) axis is a fundamental component of the endocrine system, which regulates male reproductive function. The hypothalamus regulates this axis by secreting gonadotropin-releasing hormone (GHRH), which stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This regulatory system maintains homeostasis, ensuring optimal male reproductive function.[] FSH primarily targets Sertoli cells in the testes, supporting the integrity of the blood–testis barrier and facilitating spermatogonial maturation, while LH acts on Leydig cells to regulate testosterone production. The combined action of these hormones is critical for sperm production and maturation.[,] Testosterone, a key androgen, is essential for spermatogenesis; its deficiency, regardless of cause, can lead to male infertility.[] Low testosterone levels are linked to testicular spermatogenic dysfunction, which results in a significantly lower sperm concentration, count, and motility compared to that in healthy individuals.[] Conversely, elevated levels of FSH and LH may indicate abnormal spermatogenesis and testicular dysfunction.[]
Acupuncture has been shown to exert a bidirectional regulatory effect on the HPT axis, helping to restore hormonal balance. Zhang et al.[] conducted a clinical study and reported reductions in elevated FSH and LH levels following acupuncture in patients with sperm abnormalities, alongside improvements in sperm density and viability, suggesting a protective effect on testicular spermatogenesis and potential enhancement of male fertility. Their findings have been supported by basic research, which has shown that EA can normalize FSH and LH levels in rats with semen abnormalities.[] Additionally, acupuncture may increase testosterone levels in men. Zeng et al.[] found that acupuncture at acupoints BL23 and CV4 significantly elevated free and total testosterone levels and alleviated Leydig cell pathology in rats with partial androgen deficiency syndrome. Further research suggests that acupuncture’s effects on androgen secretion might involve increased expression of cytochrome P450 side chain cleavage enzyme (P450scc), steroidogenic factor-1 (SF-1), and 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3).[] In summary, acupuncture positively supports reproductive health by primarily acting through the HPT axis and modulating sex hormone levels.
Antioxidant protection
Elevated levels of reactive oxygen species (ROS) are implicated in 30%–80% of male infertility cases.[] Low ROS levels support sperm functions such as capacitation and the acrosome reaction; however, excessive levels of ROS disrupt the ROS-antioxidant (redox) balance and result in OS.[] Sperm cells, with their unsaturated fatty acid-rich plasma membranes, are particularly susceptible to oxidative damage, which can lead to lipid peroxidation and adenosine triphosphate (ATP) deficiency, ultimately impairing sperm motility or causing cell death.[] The antioxidant system in semen, which includes superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), plays a crucial role in mitigating OS. However, genetic mutations affecting these antioxidant enzymes can disrupt the redox balance, resulting in ROS accumulation, deoxyribonucleic acid (DNA) damage, and mitochondrial dysfunction, with potential consequences for fertilization and implantation outcomes.[]
Acupuncture has been shown to enhance the activity of endogenous antioxidant enzymes and reduce OS biomarkers, thereby mitigating oxidative damage to tissues. Wang et al.[] conducted a clinical study to investigate the effects of acupuncture on OS in patients with oligozoospermia. In this study, 37 patients in the observation group received acupuncture six times per week, while 38 patients in the control group were treated with an antioxidant regimen of vitamins E and C. The results indicated that acupuncture significantly lowered seminal plasma ROS levels and increased SOD expression compared to the control regimen. Additionally, basic research has demonstrated that stimulation of the CV4 and ST36 acupoints enhances the antioxidant capacity of testicular tissues in aging mice, as evidenced by increased nitric oxide synthase (NOS) and CAT content, and reduced malondialdehyde (MDA) levels in the testes of these mice.[]
Furthermore, acupuncture can improve blood circulation, which enhances tissue nourishment and facilitates the removal of metabolic waste, indirectly mitigating the adverse effects of OS. As mentioned earlier, VC is a major cause of male infertility, and while the mechanisms that link VC to infertility are not fully understood, OS may be involved. Studies indicate that in patients with VC, the pressure gradient between the small arteries and veins in the testicular tissue is reversed, leading to persistent hypoxia.[] Additionally, the levels of ROS in the seminal plasma of these patients have been found to significantly positively correlate with VC severity. Thus, improving testicular hemodynamics can effectively alleviate testicular hypoxia and reduce OS, and acupuncture can potentially contribute to this improvement.[] In another study, five minutes of 10 Hz abdominal EA at acupoint ST29 resulted in a significant improvement in the volumetric flow rate (VF), peak systolic velocity (PS), end-diastolic velocity (ED), diameter (D), and area (A) of the testicular arteries compared to pre-stimulation levels.[]
Together, these findings indicate that acupuncture may have a positive influence on male infertility by regulating the redox balance and improving patient health. Future research should further explore the specific mechanisms associated with the effects of acupuncture in various OS models to validate these preliminary findings and optimize treatment strategies.
ANTI-INFLAMMATORY AND IMMUNOMODULATORY EFFECTS OF ACUPUNCTURE
The unique immune-exempt microenvironment of the testis is essential for germ cell development and plays a crucial role in preventing sperm-induced autoimmune reactions.[] This microenvironment is maintained primarily through the secretion of immunosuppressive and negative regulatory factors by macrophages, T lymphocytes, dendritic cells, and mast cells.[] Among these cells, macrophages are particularly important, as they exert immunosuppressive effects by inhibiting inflammatory cell recruitment via the secretion of high levels of anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β).[,] Testicular mesenchymal stromal cells and supportive cells also contribute to maintaining immune tolerance locally through the secretion of anti-inflammatory cytokines and the formation of the blood-testis barrier.[,]
In cases of immune dysfunction caused by pathogenic microbial infections, testicular tissue injury, or autoimmune factors, inflammatory signaling pathways, such as the nuclear factor-kappa B (NF-κB) pathway, become activated. This activation leads to the widespread expression of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6), resulting in systemic or local inflammation that adversely affects spermatogenesis and fertility.[] When pro-inflammatory cytokines stimulate certain receptors on germ cells (e.g., tumor necrosis factor receptor 1 (TNFR1) and interleukin-6 receptor (IL-6R)), passive apoptosis of germ cells and infertility can occur.[] Elevated levels of pro-inflammatory cytokines have been observed in patients with male infertility.[]
Acupuncture can exert anti-inflammatory effects through various mechanisms, including vagus nerve activation, toll-like receptor 4 (TLR4)/NF-κB signaling, macrophage polarization, and the activation of mitogen-activated protein kinase (MAPK) pathways.[] These mechanisms are commonly exploited in the treatment of chronic inflammatory diseases, such as rheumatoid arthritis and allergic rhinitis.[] In the context of male infertility, experimental studies have shown that EA significantly reduces NF-κB p65, cyclooxygenase-2 (COX-2) COX-2, Interleukin-1β(IL-1β), and TNF-α expression in testicular tissues and that reducing the inflammatory response contributes to improved male reproductive aging.[] Furthermore, acupuncture has been shown to effectively treat immune-related infertility. In one study, patients with male immune infertility who received acupuncture demonstrated greater reductions in serum or seminal plasma anti-sperm antibodies (AsAb) than those treated with prednisone.[] This effect may be attributed to acupuncture’s bidirectional regulation of the immune system, although the specific mechanisms involved require further investigation.
OTHER EFFECTS OF ACUPUNCTURE
Acupuncture improves fertility in infertile men through several mechanisms. First, it enhances the function of cation channels (CatSper) in spermatozoa, leading to increased calcium ion influx and improved sperm motility.[] Second, acupuncture affects the expression of calcium and integrin binding protein 1 (CIB1) and cell cycle protein-dependent kinase 1 (CDK1), which play roles in calcium signaling and cell proliferation in sperm cells.[] In patients with oligoasthenozoospermia, these proteins are often dysregulated. EA has been shown to increase CIB1 expression and decrease CDK1 expression, thereby improving sperm quality.[] Finally, a stable microenvironment is crucial for spermatogenesis. EA enhances the expression of waveform protein and α-tubulin in testicular supportive cells, stabilizing the supportive cytoskeleton and providing an optimal environment for spermatogenesis.[]
PROBLEMS AND COUNTERMEASURES IN ACUPUNCTURE TREATMENT OF MALE INFERTILITY
Acupuncture, an ancient and effective intervention, is increasingly being used to treat male infertility. However, several issues remain. First, while TCM advocates selecting acupoints and stimulation techniques that are tailored to the patient’s specific condition, acupuncture protocols need to be standardized and clearly defined. Currently, there is a lack of high-quality industry standards and guidelines for acupoint selection, stimulation parameters, quantitative measures, and treatment duration, which impedes comparability across studies. Second, many studies are limited by small sample sizes and an inadequate design, particularly randomized controlled trials. For instance, sham acupuncture is frequently used as a control treatment; however, its placebo effect may rival that of actual acupuncture.[] Third, while acupuncture’s efficacy is often assessed by improvements in semen quality, less emphasis is placed on achieving pregnancy. Fourth, the mechanisms underlying acupuncture’s effects are not fully understood, which diminishes its perceived efficacy. Therefore, future research in this field should involve a multidisciplinary team of methodologists, clinicians, and basic medical experts who can design rigorous clinical studies, establish unified diagnostic and efficacy standards, and integrate modern medical approaches. This will help (1) clarify the mechanisms of action of acupuncture, (2) determine the impact of acupuncture on pregnancy rates, semen quality, and quality of life, and (3) form a solid foundation for promoting acupuncture as a treatment for male infertility.
CONCLUSION
The current literature suggests that acupuncture may be a viable treatment option for male infertility. However, high-quality randomized controlled double-blind clinical trials and basic research must be conducted to generate robust evidence and clarify the mechanisms underlying acupuncture’s effectiveness in treating male infertility.
Financial support and sponsorship
This study was funded by the National Natural Science Foundation of China (No. 82274517).
Author contributions
Zhang L: Writing—Original draft. Bao B, Wang X, Tong S, Wen H: Investigation, Resources, Liu B: Conceptualization, Writing—Review and Editing. All authors have read and approved the final manuscript.
Ethics approval and consent to participate
Not applicable.
Conflict of interest
All authors declare no conflicts of interest.
Data availability statement
No additional data.
How to cite: Zhang L, Bao BH, Wang XY, et al. Acupuncture in the treatment of male infertility: A review. Integr Med Nephrol Androl. 2024;11:e23-00028. doi: 10.1097/IMNA-D-23-00028
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