Investigating the Impact of Ziziphus jujuba Hydroalcoholic Extract, Metformin, and Myoinositol on Pregnancy Outcomes in Women with Polycystic Ovary Syndrome (PCOS), A protocol study for randomized control trial

Abstract

Abstract Background: Infertility has a significant global prevalence, affecting approximately 12-15% of couples. The repercussions of infertility extend beyond the physical aspect, encompassing psychological and emotional impacts, hormonal and pharmaceutical side effects, as well as financial burdens, thereby exerting a far-reaching influence on the global population. A substantial proportion of female infertility cases can be attributed to normogonadotropic normoestrogenic Polycystic Ovary Syndrome (PCOS). Given the complexities and cost burdens associated with modern pharmaceutical interventions, the utilization of complementary medicine has emerged as a crucial alternative in addressing PCOS and fertility-related challenges. An attractive contender in this regard is Ziziphus jujuba, distinguished by its abundant flavonoids and antioxidant properties. These attributes hold the potential to influence the pathophysiology of PCOS positively and enhance pregnancy outcomes. Furthermore, its cost-effectiveness, widespread accessibility, and safety profile make it a compelling option for exploration in this contex. Methods: This research will be conducted at the Milad Infertility Center, located in Mashhad, Iran. Following strict adherence to predefined inclusion criteria, a total of 196 individuals diagnosed with Polycystic Ovary Syndrome (PCOS) and infertility will be recruited as study participants. Employing rigorous randomization procedures, the enrolled patients will be assigned to one of four distinct groups: Ziziphus, Myoinositol, Metformin, and Placebo, with each group consisting of 49 individuals. The randomization process will be executed via the Sealedenvelope.com website, employing blocks of 4 or 8 to create a randomized sequence for subject allocation within the study. Over a period of 12 weeks, each participant will receive their respective intervention. Simultaneously, all groups will undergo ovulation induction with the administration of letrozole. Comprehensive data encompassing both biochemical and clinical parameters pertinent to pregnancy outcomes (with emphasis on biochemical and clinical pregnancy as the primary endpoints) will be meticulously collected and analyzed to ascertain the occurrence of pregnancy. Discussion: Polycystic Ovary Syndrome (PCOS) stands as a significant global contributor to female infertility. While the precise pathophysiological mechanisms underlying PCOS remain elusive, prevailing research indicates that pivotal factors such as insulin resistance, obesity, and inflammation play prominent roles. Recent investigations into Ziziphus jujuba suggest its potential to influence these factors positively. As such, we postulate that the integration of Ziziphus jujuba into the treatment regimen for infertile PCOS patients undergoing letrozole-induced ovulation may yield improved pregnancy outcomes. Trial Registration: Register at the Mashhad Medical University of Medical Science: IR.MUMS.MEDICAL.REC.1402.191