Comparative Effect of Nigella Sativa+ Black Pepper and Letrozole + Tamoxifen on Female Infertility in Women with Polycystic Ovarian Syndrome: A Randomized Clinical Trial Original paper

What was studied?

This randomized, double-blind clinical trial investigated the comparative efficacy of a herbal regimen, Nigella sativa (black seed) combined with black pepper, versus standard pharmacological ovulation induction (letrozole plus tamoxifen) in treating infertility among women with polycystic ovarian syndrome (PCOS). Over three menstrual cycles, participants received either the herbal combination or the pharmaceutical agents during days 3–7 of their cycle. The primary outcomes measured were endometrial thickness, dominant follicle size, and follicle count, as assessed by transvaginal ultrasound. The secondary outcomes included pregnancy rates and incidence of ovarian hyperstimulation syndrome (OHSS). The study aimed to determine whether the herbal regimen could offer a comparable or superior alternative to standard pharmacological treatments, with potential implications for safety, cost, and patient acceptability.

Who was studied?

The study enrolled 90 infertile women with PCOS, aged 18 to 42 years, who were referred to an infertility clinic associated with Jahrom University of Medical Sciences, Iran. Participants were diagnosed with PCOS according to the Rotterdam criteria, requiring two out of three features: oligo/amenorrhea, clinical or biochemical hyperandrogenism, and polycystic ovaries on ultrasound. Exclusion criteria included underlying medical conditions (e.g., endocrine disorders, liver/renal disease), abnormal laboratory results, and prior or ongoing use of fertility medications or relevant surgeries. Rigorous randomization and double-blinding ensured comparability between the intervention (Nigella sativa + black pepper) and control (letrozole + tamoxifen) groups, which were closely matched for age, BMI, and baseline hormonal profiles.

Most important findings

The intervention group (Nigella sativa + black pepper) demonstrated a significantly higher pregnancy rate compared to the letrozole + tamoxifen group. By the 12th day of the menstrual cycle, the herbal group also exhibited greater endometrial thickness and dominant follicle size, as well as increased follicle numbers, all with statistically significant differences. Importantly, the incidence of OHSS did not differ significantly between groups, suggesting that the herbal regimen did not increase the risk of this notable adverse effect. While the study did not directly assess microbiome composition, it is notable that both Nigella sativa and black pepper possess well-documented antioxidant and anti-inflammatory properties, which may beneficially influence the metabolic and inflammatory milieu characteristic of PCOS, a condition that has been linked in other research to alterations in the gut and reproductive tract microbiota. The study also noted a significant reduction in serum LH levels in the herbal group, which is relevant given the role of LH/FSH imbalance in PCOS pathogenesis.

Key implications

This study suggests that Nigella sativa combined with black pepper may serve as an effective, low-cost, and low-side-effect alternative to standard pharmaceutical ovulation induction in infertile women with PCOS. The herbal regimen improved pregnancy rates and key reproductive parameters, with a safety profile comparable to conventional agents. The findings support further research into the mechanisms of action, including possible modulation of metabolic and inflammatory pathways relevant to PCOS and potentially mediated by the microbiome. If corroborated by larger and longer-term studies, these results could expand the therapeutic options for PCOS-related infertility, particularly where accessibility, cost, or side-effect profiles limit the use of standard medications.