1. Background
Infertility is defined as the inability to conceive after 12 months of regular, unprotected sexual intercourse (1). Approximately 15% of couples experience infertility, with male factors contributing to 20 - 30% of cases, female factors to 50%, and combined factors to 20 - 30% (2, 3). Male infertility can result from genetic conditions, lifestyle factors, medical comorbidities, or medications (4). Common causes include idiopathic infertility, varicocele, and genital tract infections (5). The World Health Organization (WHO) recommends semen analysis as the initial step to assess male fertility potential, with normal parameters defined as semen volume ≥ 1.5 mL, total sperm count ≥ 39 million per ejaculation, sperm concentration ≥ 15 million/mL, total motility ≥ 40%, and normal morphology ≥ 4% (6, 7).
Treatment for male infertility is categorized as specific (targeting known etiologies) or non-specific (for idiopathic cases), including hormonal and non-hormonal therapies (8). Interest in herbal medicine has prompted research into medicinal plants' effects on male fertility, with sesame (Sesamum indicum L.) showing promise due to its reported benefits on sperm count and motility (9, 10). Known as the "queen of oilseeds," sesame, a member of the Pedaliaceae family, has been cultivated for over 3,000 years in the Middle East and Africa (11, 12). Its antioxidant and anti-inflammatory properties, along with potential effects on blood glucose and cancer cell growth, make it a candidate for therapeutic use (13).
2. Objectives
This study evaluates the effect of sesame on sperm concentration, morphology, and motility in infertile men compared to combination drug therapy.
3. Materials and Methods
3.1. Study Design and Participants
This retrospective cohort study was conducted at the infertility clinics of Fatemieh Hospital and Shahid Beheshti Hospital in Hamadan, Iran, from 2020 to 2022. The study analyzed existing medical records of 80 infertile men with abnormal semen parameters (sperm concentration < 15 million/mL, motility < 40%, or normal morphology < 4%), selected via convenience sampling. Participants were divided into two groups based on treatments prescribed by their attending physician as part of routine clinical care: The combination drug group (n = 40) received oral medications such as FertilAid (one capsule daily, containing L-carnitine, zinc, and antioxidants), while the sesame group (n = 40) consumed 30 g of black sesame seeds daily (approximately 0.5 mg/kg body weight, taken orally once daily with meals). Group assignment was non-randomized, determined by physician discretion based on patient preference, clinical suitability, and treatment availability during the study period. No prospective intervention or randomization was implemented, as the study relied on retrospective data from standard clinical practice.
Exclusion criteria included azoospermia, sesame allergy, unwillingness to participate, significant sesame consumption in the preceding three months, use of oral infertility medications in the preceding three months, or surgical infertility treatment within the past year. Ethical approval was obtained from the Institutional Review Board of Hamadan University of Medical Sciences, which waived the requirement for patient consent due to the retrospective nature of the study and the use of de-identified data.
3.2. Data Collection
A researcher-designed checklist collected data on age, treatment group, and semen parameters (motility, concentration, morphology). Semen samples were collected after 48 - 72 hours of sexual abstinence via masturbation in a laboratory-provided sterile container. Samples were incubated at 37°C and analyzed within one hour using Computer-assisted Sperm Analysis (CASA). Semen parameters were assessed at baseline and after three months of treatment. Follow-up challenges, such as irregular attendance, were mitigated through reminder phone calls. Some participants withdrew due to the study duration, and medication supply issues were resolved by sourcing from alternative pharmacies.
3.3. Data Analysis
Data were analyzed using SPSS version 16. Quantitative variables were expressed as mean ± standard deviation (SD). Paired t-tests compared pre- and post-treatment semen parameters within each group. Independent t-tests compared post-treatment parameters between groups. One-way ANOVA assessed age-related differences within groups. The significance level was set at P < 0.05.
4. Results
Eighty infertile men were included, with 40 in each group. The mean age was 28.87 ± 3.56 years in the sesame group and 29.35 ± 3.37 years in the combination drug group (P = 0.56).
4.1. Within-Group Analysis
Sesame Group: Significant improvements were observed in all semen parameters post-treatment (Table 1). For participants < 30 years (n = 23), motility increased from 41.26 ± 8.82% to 43 ± 8.25% (P < 0.001), concentration from 34.86 ± 13.67 million/mL to 38.13 ± 11.36 million/mL (P < 0.001), and morphology from 23.17 ± 11.18% to 27.69 ± 10.45% (P < 0.001). For those ≥ 30 years (n = 17), motility increased from 39.7 ± 13.85% to 42.05 ± 10.65% (P < 0.001), concentration from 27.11 ± 10.55 million/mL to 28 ± 6.81 million/mL (P < 0.001), and morphology from 22.11 ± 10.36% to 26.58 ± 10.22% (P < 0.001).
Table 1.
Mean Sperm Motility, Morphology, and Concentration Before and After Treatment with Sesame Seeds Based on Age Groups
| Age Groups/Semen Parameters | Number | Mean ± SD | P-Value |
|---|---|---|---|
| < 30 | |||
| Motility | < 0.001 | ||
| Before | 23 | 41.26 ± 8.82 | |
| After | 23 | 43 ± 8.25 | |
| Concentration | < 0.001 | ||
| Before | 23 | 34.86 ± 13.67 | |
| After | 23 | 38.13 ± 11.36 | |
| Morphology | < 0.001 | ||
| Before | 23 | 23.17 ± 11.18 | |
| After | 23 | 27.69 ± 10.45 | |
| ≥ 30 | |||
| Motility | < 0.001 | ||
| Before | 17 | 39.7 ± 13.85 | |
| After | 17 | 42.05 ± 10.65 | |
| Concentration | < 0.001 | ||
| Before | 17 | 27.11 ± 10.55 | |
| After | 17 | 28 ± 6.81 | |
| Morphology | < 0.001 | ||
| Before | 17 | 22.11 ± 10.36 | |
| After | 17 | 26.58 ± 10.22 |
Combination Drug Group: All parameters improved significantly (Table 2). For participants < 30 years (n = 20), motility increased from 37.65 ± 12.05% to 45.05 ± 6.54% (P < 0.001), concentration from 39.2 ± 12.69 million/mL to 45.6 ± 9.28 million/mL (P < 0.001), and morphology from 22.55 ± 11.15% to 26.9 ± 9.22% (P < 0.001). For those ≥30 years (n = 20), motility increased from 37.15 ± 10.78% to 43 ± 6.68% (P < 0.001), concentration from 41.6 ± 14.11 million/mL to 47.55 ± 10.09 million/mL (P < 0.001), and morphology from 23.6 ± 8.65% to 29.1 ± 6.02% (P < 0.001).
Table 2.
Mean Sperm Motility, Morphology, and Concentration Before and After Treatment with Combination Drugs Based on Age Groups
| Age Groups/Semen Parameters | Number | Mean ± SD | P-Value |
|---|---|---|---|
| < 30 | |||
| Motility | < 0.001 | ||
| Before | 20 | 37.65 ± 12.05 | |
| After | 20 | 45.05 ± 6.54 | |
| Concentration | < 0.001 | ||
| Before | 20 | 39.2 ± 12.69 | |
| After | 20 | 45.6 ± 9.28 | |
| Morphology | < 0.001 | ||
| Before | 20 | 22.55 ± 11.15 | |
| After | 20 | 26.9 ± 9.22 | |
| ≥ 30 | |||
| Motility | < 0.001 | ||
| Before | 20 | 37.15 ± 10.78 | |
| After | 20 | 43 ± 6.68 | |
| Concentration | < 0.001 | ||
| Before | 20 | 41.6 ± 14.11 | |
| After | 20 | 47.55 ± 10.09 | |
| Morphology | < 0.001 | ||
| Before | 20 | 23.6 ± 8.65 | |
| After | 20 | 29.1 ± 6.02 |
4.2. Between-Group Analysis
Post-treatment, the combination drug group showed higher sperm concentration (46.57 ± 9.62 million/mL vs. 33.82 ± 10.8 million/mL, P < 0.001) and motility (44.02 ± 6.61% vs. 42.6 ± 9.23%, P = 0.43) compared to the sesame group, though motility differences were not significant. Morphology was similar between groups (28 ± 7.59% vs. 27.22 ± 10.23%, P = 0.58) (Table 3).
Table 3.
Comparison of Mean Sperm Motility, Concentration, and Morphology Before and After Treatment with Sesame Seeds and Combination Drugs
| Semen Parameters/Groups | Mean ± SD | P-Value |
|---|---|---|
| Motility before | ||
| Sesame | 40.6 ± 11.1 | 0.2 |
| Combination drugs | 37.4 ± 11.29 | |
| Motility after | 0.43 | |
| Sesame | 42.6 ± 9.23 | |
| Combination drugs | 44.02 ± 6.61 | |
| Concentration before | 0.003 | |
| Sesame | 31.57 ± 12.89 | |
| Combination drugs | 40.4 ± 13.3 | |
| Concentration after | < 0.001 | |
| Sesame | 33.82 ± 10.8 | |
| Combination drugs | 46.57 ± 9.62 | |
| Morphology before | 0.88 | |
| Sesame | 22.72 ± 10.72 | |
| Combination drugs | 23.07 ± 9.87 | |
| Morphology after | 0.58 | |
| Sesame | 27.22 ± 10.23 | |
| Combination drugs | 28 ± 7.59 |
4.3. Correlation Analysis
Combination drugs showed a stronger positive correlation with improvements in motility (Beta = 0.009, P = 0.04) and concentration (Beta = 0.008, P < 0.001) compared to sesame. Sesame had a notable effect on morphology (Beta = 0.008, P = 0.09), though not statistically significant (Table 4).
Table 4.
Comparison of Effects of Combination Drugs and Sesame on Semen Parameters
| Models | B | Beta | t | P-Value |
|---|---|---|---|---|
| Constant | 0.277 | 0.766 | 0.44 | |
| Motility before | -0.013 | 0.006 | -2.09 | 0.04 |
| Motility after | 0.018 | 0.009 | 2.02 | 0.04 |
| Concentration before | -0.019 | 0.007 | -2.88 | 0.005 |
| Concentration after | 0.041 | 0.008 | 5.399 | 0.000 |
| Morphology before | 0.01 | 0.007 | 1.73 | 0.08 |
| Morphology after | -0.01 | 0.008 | -1.7 | 0.09 |
5. Discussion
Sesame (Sesamum indicum L.) has garnered attention for its potential therapeutic role in male infertility due to its antioxidant and anti-inflammatory properties (14). This retrospective cohort study demonstrates that both sesame and combination drug therapy (e.g., FertilAid) significantly improve sperm parameters in infertile men, with combination drugs showing greater efficacy in enhancing sperm concentration and motility, while sesame notably improves morphology. These findings align with the growing interest in herbal medicine as an adjunct or alternative to conventional treatments for idiopathic male infertility.
The significant improvements in sperm motility, concentration, and morphology observed in the sesame group may be attributed to its bioactive compounds, including lignans (e.g., sesamin and sesamolin), which possess antioxidant properties that mitigate oxidative stress in the testicular microenvironment (14, 15). Oxidative stress is a known contributor to sperm dysfunction, impairing motility and morphology through lipid peroxidation and DNA damage (5, 6). Sesame’s antioxidant effects likely protect spermatozoa from reactive oxygen species (ROS), enhancing their functional parameters. Additionally, sesame may modulate the hypothalamic-pituitary-testicular axis, as suggested by animal studies showing increased testosterone levels and improved epididymal sperm reserves (15, 16). For instance, Abbasi et al. reported enhanced testosterone concentrations and germ cell to Sertoli cell ratios in diabetic rats supplemented with sesame oil, suggesting a hormonal mechanism that may translate to humans (16). Similarly, Mohammadzadeh et al. found that sesame oil, combined with low-dose estradiol, improved testicular function in aged mice, supporting its role in reproductive health (17).
In contrast, the combination drug group, treated with FertilAid, exhibited superior improvements in sperm concentration (46.57 ± 9.62 million/mL vs. 33.82 ± 10.8 million/mL, P < 0.001) and motility (44.02 ± 6.61% vs. 42.6 ± 9.23%, P = 0.43). FertilAid contains a blend of antioxidants (e.g., vitamin C, vitamin E, and coenzyme Q10), L-carnitine, and zinc, which are known to enhance spermatogenesis and sperm function (8). L-carnitine improves sperm motility by supporting mitochondrial energy metabolism, while zinc contributes to DNA synthesis and sperm membrane stability (4, 8). The synergistic action of these compounds likely explains the greater efficacy of combination drugs compared to sesame alone. However, the non-significant difference in post-treatment motility (P = 0.43) suggests that sesame may have comparable effects on motility in certain contexts, potentially due to its antioxidant properties overlapping with those of FertilAid.
Our findings partially align with previous human studies. Khani et al. reported significant improvements in sperm count and motility but not morphology in 25 infertile men treated with sesame for three months (10). In contrast, our study found significant morphology improvements (27.22 ± 10.23% vs. 22.72 ± 10.72%, P < 0.001), possibly due to differences in sesame dosage (30 g/day in our study vs. unspecified in Khani et al.), study population, or analytical methods (CASA vs. manual analysis). Animal studies further corroborate sesame’s benefits. Amini Mahabadi et al. demonstrated improved sperm number, motility, and luteinizing hormone levels in Wistar rats fed sesame seeds (18), while Shittu et al. reported dose-dependent improvements in sperm count, motility, and morphology in rats treated with sesame radiatum phytoestrogens (19). These studies suggest that sesame’s effects may be dose-dependent and species-specific, warranting further investigation in humans.
The clinical implications of these findings are noteworthy. Sesame, as a non-pharmacological intervention, offers a cost-effective and accessible option for men with idiopathic infertility, particularly in regions where combination drugs are expensive or unavailable. Its significant effect on sperm morphology suggests a role in addressing teratozoospermia, a common cause of male infertility (6). However, the superior efficacy of combination drugs in improving sperm count and motility indicates that they may be preferred in cases where rapid improvement is desired, such as in assisted reproductive technologies (ART). The choice between sesame and combination drugs may also depend on patient preferences, tolerance, and cultural acceptability of herbal remedies.
This study has several limitations. The single-center, retrospective design and non-randomized group assignment introduce potential selection bias, as treatment allocation was based on physician discretion and patient preference. The small sample size (n = 80) limits generalizability, and the lack of a placebo group precludes assessment of spontaneous improvements. Additionally, the study did not measure hormonal levels (e.g., testosterone, luteinizing hormone) or oxidative stress markers, which could elucidate sesame’s mechanisms of action. The short follow-up period (three months) may not capture long-term effects on fertility outcomes, such as pregnancy rates. Future research should include randomized controlled trials (RCTs) with larger, multicenter cohorts to confirm these findings. Incorporating hormonal and oxidative stress assays, dose-response studies, and longer follow-up periods could further clarify sesame’s therapeutic potential and optimal administration protocols. Additionally, exploring the combined use of sesame and pharmacological agents may reveal synergistic effects, enhancing treatment outcomes.
In conclusion, both sesame and combination drugs improve sperm parameters in infertile men, with combination drugs being more effective for sperm count and motility, and sesame showing a significant impact on morphology. These findings highlight sesame as a promising adjunct therapy, particularly for morphology-related infertility, while combination drugs remain the preferred choice for comprehensive semen parameter improvement. Further RCTs are needed to establish sesame’s role in clinical practice and to optimize its use in male infertility treatment.
5.1. Limitations
This study is limited by its single-center design and non-randomized group assignment, which may introduce selection bias. The small sample size and retrospective nature further limit generalizability. Future randomized controlled trials with larger, multicenter cohorts are needed to validate these findings.
