Infertility is defined as the inability to achieve pregnancy after one year of appropriate sexual intercourse without contraception, affecting 10%-15% of couples. The overall infertility rate in Iran has been reported to be 13.2%, with 5.2% being primary infertility and 3.2% being secondary infertility. Globally, the rate of infertility has increased by 50% since 1995. Epidemiological studies in the United States illustrated that the prevalence of infertility decreased from 8.5% in 1982 to 7.4% in 2002, which can be attributed to the use of assisted reproductive technologies. According to the World Health Organization, the global prevalence of infertility is reported to be 12%-15%; nonetheless, the statistics vary due to different definitions of infertility. In Iran, the range of infertility prevalence has been reported to be 2%-20% in different studies.

Infertility can be caused by various factors, with hormones, particularly estrogen, playing a crucial role. Estrogen is one of the two main sex steroid hormones in women, secreted by the ovaries. Most hypothalamus-ovary regulations are affected by the two hormones: estrogen and progesterone. Estrogen has a key role to play in maintaining pregnancy and regulating the growth and differentiation of endometrial cells.

The human endometrium is a unique, elastic, dynamic, and hormone-sensitive tissue that undergoes cyclical changes, including proliferation, differentiation, destruction, and regeneration during the menstrual cycle. It is believed that a thin endometrium can reduce its receptivity. The success of blastocyst implantation, both in natural and in vitro fertilization (IVF) cycles, depends on appropriate endometrial receptivity. Endometrial thickness is used as an indirect index of endometrial receptivity, and studies have pointed to a positive relationship between endometrial thickness, blastocyst implantation, and pregnancy success rates.

Some studies have reported positive fertility outcomes with the use of estrogen to increase endometrial thickness. A wide array of studies have reported the minimum required endometrial thickness to be between 6 and 11 millimeters. Therefore, it seems that adequate endometrial development and appropriate thickness play an important role in the occurrence and success of pregnancy. One of the infertility problems related to the endometrium may be a decrease in estrogen secretion. Given the side effects of chemical drugs used in the treatment of infertility and the greater tendency of women to use herbal medicines, the present study aimed to assess the effect of the herbal combination of fennel and chamomile on endometrial thickness and menstrual cycles.

METHODS

This quasi-experimental study with a parallel group design was conducted on 66 infertile women aged 20-45 years referring to general and specialized treatment centers in Bojnurd during 2021-2022. Sampling was performed purposively with informed written consent. The inclusion criteria were infertility (no pregnancy for one year after unprotected sexual intercourse), an age range of 20-45 years, and a medical diagnosis of menstrual cycle disorders and unsuitable endometrial conditions due to hormonal disturbances, especially estrogen. The participants were randomly assigned to two groups: the first group received the herbal combination of fennel and chamomile, while the second group received a placebo (distilled water and brown color) for 12 weeks. The dose of the herbal combination was based on previous studies: 120 mg of fennel and 1000 mg of chamomile per day. The preparation stages of the drug included plant entry, identification, extraction, formulation, pasteurization, in-process testing, packaging, and final microbiological confirmation.

At the beginning, a demographic questionnaire was completed, and the endometrial thickness was then determined using ultrasound. The study was conducted in a triple-blind manner; that is, only the drug-manufacturing laboratory was aware of the bottle contents, and the subjects, researcher, and statistical analyst remained unaware of it until the end of the statistical analyses. After 12 weeks, the endometrial thickness and menstrual cycles were re-evaluated. The data were analyzed in SPSS software (version 26). In order to compare normally distributed quantitative variables across groups, the Mann-Whitney test and independent t-test were employed, while the Wilcoxon test and paired t-test were utilized for before-and-after intervention. The significance level was set at 0.05 for all tests."

RESULTS

The obtained results pointed out that before the intervention, there was no significant statistical difference between the two groups in terms of the duration, frequency, and amount of menstrual bleeding, as well as endometrial thickness. Nevertheless, after the intervention, there was a statistically significant difference between the two groups in the duration, frequency, and amount of menstrual bleeding, as well as endometrial thickness. After the intervention, menstrual cycle duration (19.97 vs. 47.88), frequency (44.59 vs. 21.72), and amount of bleeding (39.65 vs. 26.97), as well as endometrial thickness (8.970±0.986 vs. 4.750±0.977) and "endometrial thickness (0.986±0.970 vs. 0.977±0.750)" highlighted a statistically significant difference between the intervention and placebo groups (P=0.0001)., Furthermore, in the intervention group, a statistically significant difference was observed in the duration, frequency, and amount of bleeding, as well as endometrial thickness, before and after the intervention; however, no such difference was detected in the placebo group.

As evidenced by the results of this study, the plant extracts of fennel and chamomile were effective in improving menstrual cycle parameters and increasing endometrial thickness in infertile women; therefore, they can be proposed as a suitable and safe therapeutic method in this regard. Given the side effects of available chemical drugs, the use of this herbal combination can be an appropriate alternative for the treatment of infertility related to endometrial factors.

Ethical Considerations

Compliance with ethical guidelines

this study was approved by the Research Ethics Committee of Islamic Azad University, Bojnourd Branch (Ethics code: IR.IAU.BOJNOURD.REC.
1399.029). All participants completed the written consent form. They were assured that the questionnaire was anonymous and that their information would be confidential and analyzed only for research purposes. Moreover, the authors emphasized that participation or non-participation in this study will not harm them and the process of receiving services.

Funding

There was no funding support.

Authors’ Contributions

The authors contributed equally to the conceptualization and writing of the article. All of the authors approved the content of the manuscript and agreed on all aspects of the work.

Conflict of Interest

The authors declared no conflict of interest.

Acknowledgments

The researchers would like to thank the Growth Center of Islamic Azad University, Bojnord branch.