An observational study in Poor Response to Ovulation Induction, PCOS and Endometriosis, sponsored by Fatima College of Health Sciences. Status unknown at 1 site in United Arab Emirates. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-07-12.
Sponsored by Fatima College of Health Sciences · Observational
According the World Health Organization (WHO), infertility is a disease of the male or female reproductive system defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. In-vitro-fertilization (IVF) is considered to be a successful tool to overcome infertility. However, the current methods used to assess the ovarian reserve and to develop an optimal individualized controlled ovarian hyperstimulation (COH) protocol have shown some limitations. Growing evidence indicates that altered renal renin-angiotensin system (RAS) and/or melatonin are linked to infertility. Aims and Objectives: The current 2 years duration study aims first to investigate the demographic and clinical profiles of patients undergoing IVF in the UAE. In the second phase of the study, we hypothesis that an altered angiotensin-melatonin axis may be considered as an unfavorable prognosis factor in poor and hyper responders undergoing IVF treatment. This hypothesis will be assessed using an observational, longitudinal, prospective clinical study to determine whether the urinary angiotensinogen and/or melatonin deficiency might be present in poor and hyper responders undergoing IVF treatment. Thus, negatively impacting the clinical pregnancy rate. Methodology: various patient's data will be collected using a questionnaire and the levels of angiotensinogen and melatonin in patient's urine will be measured using ELISA test prior to, during and after the IVF treatment. To determine whether the angiotensinogen-melatonin axis disruption affects the IVF treatment outcome, we will analyze the following parameters: the AMH, Antral Follicular Count (AFC), day 2-4 FSH levels, the stimulation cycle in regards to number of stimulation days and amount of gonadotropins used for stimulation, number of oocytes retrieved and number of mature oocytes, quality and embryo's ploidy, number of available euploid embryos and the clinical pregnancy rate after frozen embryo transfer.
Infertility affects approximately 1 in every 4 couples and the WHO (World Health Organization) has defined infertility as a "disease" (World Health Organization (WHO). International Classification of Diseases, 11th Revision (ICD-11) Geneva: WHO 2018.). Rates of infertility are expected to increase in the future as many couples tend to postpone family planning due to various reasons (Mills et al., 2011). Assisted Reproductive Techniques (ART), with In-vitro-fertilization (IVF) being a part of the treatment options, are a successful tool to overcome infertility (Franasiak \& Scott, 2014). However, more research to thwart the global burden of infertility is required. This is possible if the underlying causes of infertility can be identified, and personalized therapy implemented (Sun et al., 2019).
Poor and hyper responders are a diverse group of IVF patients, with specific needs. Their management can help in increasing the clinical pregnancy rates. Identifying and understanding how the endocrine variants are linked to the success of IVF responsiveness may lead to a better treatment strategy aimed at achieving successful live births.
Growing evidence indicates that altered renal renin-angiotensin system (RAS) and melatonin are linked to infertility, PCOS and endometriosis.
According to the literature, hyperandrogenemia in an experimental rat model of PCOS has been associated with an upregulation of the intrarenal RAS (Torres Fernandez et al. 2019). When compared to the eutopic endometrium in the proliferative phase, patients with endometriotic cysts had a significant increase in the expression of angiotensin type AT1 and AT2 receptors. This suggests that RAS may be involved in the pathophysiology of endometriosis (Nakao et al. 2017; Nakajima et al. 2018). In addition, alterations in the expression of Angiotensin-converting enzyme, ACE-1, ACE-2, and ACE-3 might be one of the most important mechanisms underlying both female and male infertility (Chen, Bi, Su, Chappell, \& Rose, 2016; Pan, Zhan, Le, Zheng, \& Jin, 2013).
On the other hand, the levels of melatonin, a powerful antioxidant and an effective free radical scavenger that protects ovarian follicles during follicular maturation are increasing in preovulatory follicular fluid and seem to have an important role in ovulation (Tamura et al., 2012). Similarly, melatonin requirements appear to increase during pregnancy (Voiculescu, Zygouropoulos, Zahiu, \& Zagrean, 2014). Melatonin levels are found to be lower in patients with PCOS (Mojaverrostami et al. 2019). And several studies suggest a potential link between melatonin and endometriosis (Mosher et al. 2019; Anderson 2019), leading to the use of melatonin as an adjuvant in the treatment of endometriosis (Mosher et al. 2019; Yesildaglar et al. 2016).
Clinical hypothesis:
This observational, longitudinal, prospective clinical study will investigate the IVF population demographic and clinical profile in the UAE. It will also test the hypothesis whether an altered angiotensin-melatonin axis may be considered an unfavorable prognosis factor in poor responders with or without endometriosis and hyper (PCOS) responders undergoing IVF treatment. Thus, negatively impacting the clinical pregnancy rate.
2,506 studies on the registry are indexed under Infertility; 407 are open to participants now.
This study's planned enrollment of 200 is close to the median of 200 across 714 observational studies indexed under Infertility.
Browse Infertility studies →Fatima College of Health Sciences is the lead sponsor of 2 studies on the registry; none are open to participants now.
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From the ART Fertility Clinic, Abu Dhabi, UAE, our collaborator in the project, we are planning to enroll (following the selection criteria detailed below) for a duration of 18 months, IVF female patients aged between 18 and 45 years old and who volunteer to participate in the study. Participants in the study have to sign a participant Information sheet and consent form specific to the urine testing before their enrollment in the study. A questionnaire will be filled out with the different demographics and a summary of the IVF protocol details.
depending on the ART Fertility Clinic patients, we are intending to include:
Exclusion Criteria:
Differences on urine levels of angiotensinogen-melatonin-creatinine ratio between two groups: one with AMH < 1.1 ng/ml against other with AMH > 6.25 ng/ml.
Urinary excretion of angiotensinogen will be analyzed by sandwich-ELISA assay. Urinary melatonin excreted overnight will be determined through the 6-sulfatoxymelatonin molecule. This is a metabolite released in the urine that correlates directly with the melatonin produced, being a noninvasive method of dosing the said molecule. The urinary dosage of 6-sulfatoximelatonin will be performed by the ELISA technique according to the manufacturer's recommendations (IBL International Germany). All molecules will be quantitated using ELISA according to supplier's specifications.
Time frame: 18 months
Plan to share: No
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Fatima College of Health Sciences