The Angiotensin-Melatonin Axis in Poor and Hyper Responders for IVF Treatment

NCT05298657 | Unknown DMC

• 2 other identifiers: FCEC-1-21-22-GRD-1-SFREFA073
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Poor Response to Ovulation Induction; PCOS; Endometriosis; Infertility, Female

Outcome Measures

Primary Outcomes (1)

• 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.

  18 months

Study Arms (3)

Poor IVF Treatment Responders

Hyper IVF Treatment Responders

Normal responders/ Control group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

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.

You may qualify if:

• depending on the ART Fertility Clinic patients, we are intending to include:
• Women diagnosed with infertility (when pregnancy is not achieved after 1 year of having regular sexual intercourse without birth control for those under 35 years of age or if pregnancy is not achieved after 6 months of trying to conceive naturally for those older than 35 years of age). Further on, women with proven tubal factor infertility or couples with infertility as a result of a male factor, without the previously mentioned time of not achieving a pregnancy.
• Women undergoing or in the way to undergo IVF and classified as poor responders according to the four groups of the POSEIDON criteria (Conforti et al., 2019), including patients with a previous oral contraceptive intake.
• Women diagnosed with PCOS based on the Rotterdam criteria (Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004.
• Women diagnosed with endometriosis confirmed by Laparoscopy or visible endometrioma without being diagnosed by laparoscopy (If possible to be enrolled in the research).
• Women planned to undergo IVF treatment and categorized as expected normal responders) (Ozkan, 2019).
• Patients under thyroid medication.

You may not qualify if:

• Presence or history of endocrine abnormalities (at the exception of patients who are under thyroid medication).
• Abnormal outcome of blood biochemistry or hematology.
• Obese patients with BMI \> 40.
• Couples for whom the male partner has to undergo surgical sperm retrieval.

Sponsors & Collaborators

• Fatima College of Health Sciences: lead
• ART Fertility Clinics LLC: collaborator

Study Sites (1)

ART Fertility Clinic

Abu Dhabi, Abu Dhabi Emirate, United Arab Emirates

Location

Related Publications (26)

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine samples

MeSH Terms

Conditions

Endometriosis; Infertility, Female

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Study Officials

• Rym Ghimouz, PhD

  Fatima College of Health Sciences

  PRINCIPAL INVESTIGATOR

• Barbara Lawrenz, PhD

  ART Fertility Clinics

  PRINCIPAL INVESTIGATOR

• Luciana Campos, PhD

  Universidade Anhembi Morumbi

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rym Ghimouz, PhD

CONTACT

+971551156892; rym.ghimouz@gmail.com

Barbara Lawrenz, PhD

CONTACT

+971526500757; barbara.lawrenz@artfertilityclinics.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Biology

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: March 28, 2022
• Study Start: September 1, 2022
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

AE (1)