The Male Infertility Battle: Exploiting Nonconventional Therapy
Overview
Global interest in alternative and complementary treatments for male infertility is growing, leading to numerous systematic reviews and meta-analyses. This umbrella review aims to synthesize existing evidence on the effectiveness of these treatments to aid clinical decision-making.
A thorough search was conducted across multiple databases including MEDLINE, CINAHL, PubMed, Scopus, Proquest, Google Scholar, SID, EMBASE, Magiran, Cochrane Library, Iranmedex, ScienceDirect, and SAGE. Two researchers independently extracted data from the identified systematic reviews and meta-analyses and assessed their methodological quality using the AMSTAR 2 tool.
The review included 11 studies, with contributions from Iran (4 studies), Korea (2 studies), and China (5 studies). The findings on the effectiveness of complementary and alternative medicine for male infertility are inconsistent, highlighting the necessity for further investigation. The methodological quality of the evaluated systematic reviews and meta-analyses was generally low or critically low, mainly due to insufficient examination of publication biases and inadequate discussion on the impact of risk of bias.
The current evidence supporting the effectiveness of alternative and complementary medicine in treating male infertility is limited. Additionally, the methodological quality of the reviewed systematic reviews and meta-analyses appears to be low, suggesting that the use of AMSTAR 2 offers a more accurate assessment compared to previous tools.
Introduction
Male infertility is a global health concern with significant impacts on affected couples and childbearing. It is defined as the inability of a man to impregnate a fertile female partner after one year of unprotected intercourse. Male factors account for approximately 50% of infertility cases, highlighting the increasing importance of this issue in medicine. Evidence indicates a rising prevalence of male infertility in certain populations.
The causes of male infertility are complex, involving issues such as abnormalities in spermatogenesis, genital system disorders or obstructions, ejaculatory dysfunction, impaired sperm motility, hormonal imbalances, and compromised immune function. Recent attention has focused on a decline in semen quality, which is critical for male fertility. Over 90% of male infertility cases result from low sperm count or poor sperm quality. Other contributing factors include impaired ejaculation, immune issues, hormonal imbalances, and genetic abnormalities. Environmental conditions and lifestyle factors, such as tobacco and alcohol consumption, sexual practices, and dietary habits, also impact fertility and semen quality, leading to varied infertility patterns across different regions.
Conventional treatments like pharmacotherapy, surgical interventions, in-vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) have helped many men achieve fertility. Pharmacological options include antioxidants, hormones, hexanone theobromine, L-carnitine, and other medications. However, these treatments can have unpredictable side effects, high costs, variable efficacy, and poor outcomes. Consequently, some treatments are ineffective, invasive, costly, or associated with adverse effects and high risks. As a result, couples may seek nonconventional treatment options beyond standard modalities.
Complementary and alternative medicine (CAM) offers another avenue for treating male infertility. CAM encompasses a range of medical practices, products, and systems outside conventional treatments, including diagnostic, therapeutic, and preventive methods. Often, complementary medicine is used alongside standard treatments. There is growing interest globally in modifying lifestyle factors and integrating holistic, complementary, and alternative approaches into male infertility management.
The use of complementary medicine for infertility treatment is documented in various countries, with usage rates in Australia (over 70%), Canada (9%-23%), the United Kingdom (40%), the United States (29%), South Korea (63.5%), Taiwan (96.1%), Lebanon (41%), and Iran (around 50%), indicating a trend towards exploring these treatments. Chinese herbal medicine (CHM) has a long history in China for enhancing male fertility, and many infertile individuals turn to CAM modalities such as acupuncture, herbal medicine, yoga, artificial sleep, homeopathy, meditation, and physical therapy. Studies have shown the efficacy of herbal remedies and homeopathic interventions in improving sperm motility and fertility.
However, concerns persist regarding the lack of empirical evidence supporting the efficacy of complementary treatments for infertility. Research on the impact of these treatments has produced varied outcomes. This study aims to conduct an umbrella review of systematic reviews to examine the role of complementary and alternative medicine in managing male infertility.
Method
This study’s protocol was registered in PROSPERO under registration number CRD42023449357. The primary research objective was to evaluate the current state, effectiveness, and methodological quality of systematic reviews and meta-analyses that focus on complementary and alternative medicine (CAM) for male infertility. Using the PICO framework, the study targeted male participants undergoing various CAM interventions—including acupuncture, herbal treatments, yoga, homeopathy, Ayurveda, traditional medicine, Persian medicine, Chinese traditional medicine, massage therapy, and chiropractic care. The primary outcome measured was the quality of sperm parameters, specifically motility and concentration. The study design included systematic reviews with or without meta-analyses in clinical trials.
Data selection involved two researchers independently reviewing titles and abstracts of identified papers, followed by a full-text assessment against inclusion and exclusion criteria. Disagreements were resolved with input from a third researcher. Data extraction, conducted independently by two researchers, included details such as the first author’s name, publication year, country, number of included RCTs, total population size, participant characteristics, interventions, comparator groups, and outcome measures.
The methodological quality of the studies was assessed using the AMSTAR 2 tool, a validated 16-item instrument for evaluating systematic reviews’ quality. Each item was rated as “yes,” “partial yes,” or “no.” Overall confidence in the study results was determined based on the presence of critical or non-critical issues, leading to confidence levels ranging from high to critically low.
Inclusion Criteria
Inclusion criteria were papers published in English and Persian that employed at least one CAM intervention. The literature search covered papers published from January 2014 to March 2023, utilizing specific keywords across various databases: MEDLINE, CINAHL, PubMed, Scopus, ProQuest, Google Scholar, SID, EMBASE, Magiran, Cochrane Library, Iranmedex, ScienceDirect, and SAGE. Manual searches were also conducted to ensure comprehensive evidence retrieval.
Exclusion Criteria
Exclusion criteria were non-paper publications, conference abstracts, animal studies, and protocols.
Result
Out of an initial pool of 1,570,475 studies, 1,475,236 duplicates were eliminated. The titles and abstracts of the remaining 95,239 studies were screened, resulting in the exclusion of 95,185 studies. Of the 54 studies that underwent full-text review, 43 were excluded for not meeting the study design criteria. Ultimately, 11 studies were included.
Among the 11 included studies, one was conducted in 2014, two in 2018, one in 2019, one in 2020, two in 2021, three in 2022, and one in 2023, indicating an upward trend in recent years. The geographic distribution of these studies was 18% from Korea, 45.5% from China, and 36.5% from Iran.
Seven of the systematic reviews conducted meta-analyses, while four did not. The studies spanned from 2014 to 2023, with four from Iran, two from Korea, and five from China. All reviews were published in English. Four systematic reviews focused on acupuncture’s effects on male infertility, five examined medicinal plants’ impacts on both fertile and infertile men, and two analyzed traditional Chinese medicine’s effects on infertile men.
The AMSTAR 2 appraisal revealed that seven systematic reviews exhibited a critical flaw indicating low methodological quality, while the remaining four displayed multiple critical flaws, categorizing them as critically low quality. None of the reviews achieved a “high” quality rating due to inadequate adherence to AMSTAR 2 critical criteria, particularly items 13 (risk of bias in meta-analyses) and 15 (exploration of publication biases).
Performance on the seven critical AMSTAR 2 items varied: 75% performed well on item 2, 25% on item 4, 83% on item 7, 100% on item 9, 91% on item 11, 58% on item 13, and 50% on item 15. For the nine noncritical items, all reviews performed well on items 5 and 16, 83% on items 8, 12, and 14, 75% on item 1, 91% on items 3 and 6, and 50% on item 10.
Four systematic reviews evaluated acupuncture’s efficacy compared to sham acupuncture, placebo, no treatment, and conventional or Chinese traditional medicine for male infertility. All studies assessed semen parameters, but the effect of acupuncture remains contentious.
Jerng et al. suggested acupuncture might improve sperm motility and concentration in men with oligozoospermia or asthenozoospermia, but the evidence is insufficient. You et al. (2019) found that acupuncture might be more effective than other treatments for oligostenospermia, but called for more robust RCTs. Jia et al. did not find clear evidence of acupuncture’s superiority in improving sperm motility and concentration. Wang et al. highlighted nonpharmacological interventions, particularly warm and electric acupuncture, as potentially effective but emphasized the need for further research.
Five systematic reviews examined herbal drugs’ effects compared to placebo in fertile and infertile men, with mixed results. Maleki et al. reviewed six RCTs on saffron’s effects on semen parameters, finding contradictory results. Roozbeh et al. observed improvements in semen volume and quality but called for further clinical trials. Ahmadian et al. suggested certain plants might treat idiopathic infertility but recommended more precise studies. Shahid et al. highlighted the potential of herbs like Withania somnifera and Hochu-ekki, but stressed the need for future experimental studies. Lee et al. found the effect of Maca on semen parameters inconclusive due to limited RCTs and small sample sizes.
Two systematic reviews assessed Chinese traditional medicine’s effects compared to placebos and vitamins. Zhao et al. found that Wuzi Yanzong Pill could improve sperm parameters in men with oligoasthenozoospermia, but noted study limitations. Wang et al. found that combining Chinese traditional medicine with vitamins improved various sperm parameters and fertility outcomes, suggesting further exploration through larger, long-term clinical studies.
Conclusion
The exploration of complementary medicine’s role in treating infertility is gaining traction among researchers. However, assessing its impact on male infertility remains contentious. This review aimed to evaluate the effects of complementary and alternative medicine (CAM) on semen parameters, particularly sperm motility and concentration, through an analysis of 11 systematic reviews published from January 2014 to March 2023. These reviews included 4–38 randomized controlled trials (RCTs) with 244–3080 participants.
Most studies compared acupuncture with various controls, such as sham acupuncture, placebo, no treatment, conventional pharmacotherapy, or traditional Chinese medicine in men with infertility. Some systematic reviews indicated that acupuncture might influence sperm motility and concentration, but the clinical evidence is currently insufficient or inconclusive, necessitating further research due to study limitations. Conversely, one systematic review found no impact of acupuncture on improving sperm motility and concentration.
The efficacy of herbal interventions, compared against placebo, no treatment, and pharmacotherapy, yielded mixed results. Some reviews suggested potential benefits of specific medicinal plants on sperm quality, but further experimental studies are required to develop more reliable treatments. Other reviews reported inconclusive and conflicting results regarding the effects of herbal interventions on sperm quality.
Evaluations of Chinese traditional medicine’s effects on male infertility through systematic reviews are similarly controversial. While some reviews hinted at its potential efficacy in improving sperm quality, inherent study limitations have prevented definitive conclusions, highlighting the need for more clinical research. It appears that meta-analyses of traditional Chinese medicine have shown more promising results compared to acupuncture and herbal medicine.
The methodological quality of the included systematic reviews was generally low, with significant deficiencies in key areas assessed by AMSTAR2, particularly regarding the discussion of risk of bias and examination of publication biases. These shortcomings underscore the need for caution when interpreting the results, as the methodological quality of the reviews and meta-analyses may have been underestimated.
This umbrella review is subject to several limitations. The overall quality of the included studies, precisely appraised by the latest AMSTAR2, was deemed low. Future systematic reviews should accurately evaluate specific items of AMSTAR2. Additionally, drawing definitive conclusions about the effectiveness of CAM on male infertility is challenging due to the variability in CAM types and intervention timing across the included reviews. The exclusion of non-English studies might have also impacted the analysis, as their inclusion could potentially alter the findings.
In conclusion, the investigation of semen analysis parameters from January 2014 to March 2023 across 11 systematic reviews, comprising 4–38 clinical trials with 244–3080 participants each, emphasized the need for further evidence to determine the impact of CAM on male infertility. The methodological quality of these reviews, as assessed by AMSTAR2, was suboptimal, primarily due to insufficient discussions of risk of bias and publication biases. Thus, more research is required to establish whether CAM positively affects semen analysis parameters.
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