Effect of interleukin IL-6 and redox homeostasis in the fluid. Follicular follicle on the outcome of in vitro fertilisation, pre and post dietary supplementation with Coenzyme Q₁₀ .

STUDY CODE: HCB/2023/0998

DEVELOPER: Juan Carlos Álvarez Álvarez. General Manager. Institut Marquès. Barcelona

PRINCIPAL INVESTIGATOR:   Dr. Borja Marqués López-Teijón. Medical Director.

Institut Marquès. Barcelona.

INTRODUCTION

We are writing to inform you about a research study in which you are invited to participate. The study has been approved by the relevant Clinical Research Ethics Committee in accordance with current legislation, and complies with the principles set out in the Biomedical Research Act 14/2007 and the Declaration of Helsinki in its latest update ( Fortaleza, Brazil, October 2013 ).

Our intention is that you receive sufficient and correct information so that you can evaluate whether or not you want to participate in this study. To this end, please read this information sheet carefully and we will clarify any doubts you may have after the explanation. In addition, you can consult with the people you consider appropriate. We inform you that this work is an independent initiative of the study investigators, which is privately funded and for which the participating investigators will not receive any financial compensation.

OBJECTIVE OF THE STUDY

Current evidence suggests that the ovarian follicle is a site of inflammatory reactions. Follicular fluid contains interleukins, some with pro-inflammatory and some with anti-inflammatory functions. Together with hormonal changes, interleukins are involved in processes such as ovarian follicle and egg formation, fertilisation, embryonic development and implantation, among others. On the other hand, cellular metabolism continuously generates free radicals and oxidising molecules, the most reactive cellular elements suitable for oxidation being proteins, lipids and DNA. There is a stable balance between pro-oxidant molecules and antioxidant mechanisms which we call redox homeostasis. Environmental factors or pathophysiological processes can generate excessive amounts of reactive oxygen species (ROS), overwhelming the antioxidant system and disrupting redox homeostasis. This state is often referred to as oxidative stress. Reactive oxygen species (ROS) and antioxidants are components of follicular fluid. In the field of female reproduction, free radicals are recognised as part of intracellular signalling in oocyte maturation, embryo development and pregnancy. We postulate that IL-6 interleukin concentrations and altered redox balance in follicular fluid may have a negative impact on IVF-ICSI outcomes.

To establish the profile of the cytokine IL-6 and redox homeostasis in the follicular fluid of infertile patients undergoing IVF-ICSI by assessing oxidative stress, evaluating its potential effect on oocyte and embryo quality and its impact on the outcome of IVF-ICSI.

DESCRIPTION OF THE STUDY

Your participation in the study does not involve the performance of more procedures (visits, analyses, ultrasound scans, etc.) than those inherent to the IVF-ICSI treatment you are going to undergo, so whether or not you accept to participate in the study, the same tests will be performed.  It is planned to include a number of 100 volunteers over a period of 1 year, with Institut Marqués being the only centre in which this study will be carried out.

The study consists of two phases. In Phase I, the IVF-ICSI cycle will be performed and the previously mentioned biological and reproductive markers will be evaluated. Patients who do not achieve an evolutionary pregnancy may enter Phase II if they wish. In this phase they will receive a dietary supplementation with coenzyme Q₁₀ (CoQ₁₀ ) at a dose of 200 mg every 12 hours for 4 weeks. The IVF-ICSI cycle will be initiated in the first menstrual cycle following the end of supplementation. The same parameters as in Phase I and their impact on IVF-ICSI outcome will be evaluated.  CoQ₁₀    is a dietary supplement  that acts as an effective antioxidant preventing lipid peroxidation and DNA oxidation.

WHAT WILL HAPPEN TO YOU IF YOU DECIDE NOT TO PARTICIPATE IN THIS STUDY?

Your participation in this study is completely voluntary. You may refuse to participate in this study or discontinue your participation at any time. This will not affect your care or your relationship with your doctor in any way. In addition, the investigators may stop your participation in the study (for example, if in their judgment it is in your best interest not to participate or if you are not following the necessary study procedures). If this happens, you will receive appropriate explanations.

 

BIOLOGICAL SAMPLES

• Possibility of unexpected findings

Given the characteristics of the study, it is not expected that the analysis of your samples will yield information with implications for your health, including unexpected findings, which you have the right to know if you wish. In this regard, you may check the appropriate option at the end of this document. In the event that you choose to know the information, if it also has implications for your biological relatives, you are advised that it is advisable for you to pass it on to them personally. In any case, you should be aware that, as required by the regulations, when the information, in the opinion of the doctor in charge, is necessary to avoid serious harm to your health or that of your biological relatives, a close relative or a representative will be informed, after consulting the centre’s Healthcare Ethics Committee.

• Fate of the sample after its use in this research project

After completion of the investigation, the remaining samples shall be destroyed.

BENEFITS AND RISKS OF PARTICIPATING IN THIS STUDY

It is likely that you will not benefit directly from participating in this study. However, we hope that the results of this study will contribute to a better understanding of the impact of the studied interleukins and redox homeostasis on the outcome of IVF-ICSI in infertile women. This knowledge could lead to medical treatment from which she could benefit in the event of having to repeat further IVF-ICSI cycles.

Likewise, you will not be subjected to any risk by your participation. Follicular fluid is obtained during ovarian puncture for oocyte retrieval and is therefore an inherent procedure in IVF treatment, so your participation does not pose any additional risk to you. In general, the administration of CoQ₁₀ does not usually present side effects even with higher than normal doses.

However, you will be informed if during the course of the study any relevant information emerges that could condition your continuation or withdrawal from the study.

CONFIDENTIALITY AND DATA PROTECTION

By signing the document entitled INFORMED CONSENT which accompanies this INFORMATION SHEET, you declare that, in accordance with current legislation on data protection, you expressly consent to the processing of your data for the purpose of participating in the study.

The participating centre and promoter of the study, Institut Marquès, whose corporate name is Institut Marquès Obstetricia I Ginecologia, S.L., will be responsible for the processing of your personal data for the sole purpose of carrying out the study identified.

The legitimate basis for the processing of your data is your express consent as stated in this document. Your data will be retained for the duration of the study and for a maximum of 5 years in order to meet any legal obligations that may have arisen from the relationship. With regard to data processed for scientific research purposes, the Supervisory Authorities of the Autonomous Communities may, at the request of the data controller and in accordance with the procedure re-established by regulation, agree to the full retention of certain data, taking into account the historical, statistical or scientific values in accordance with the legislation applicable to each case.

Access to your personal information will be restricted to the study doctor and his/her collaborators, health authorities, the Research Ethics Committee and the sponsor’s monitors and auditors, who will be subject to the duty of secrecy inherent to their profession, when necessary, to check the data and procedures of the study, but always maintaining the confidentiality of the same in accordance with current legislation (Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on Data Protection (RGPD), on the Protection of Personal Data, Organic Law 3/2018, of 5 December, on the Protection of Personal Data and guarantee of digital rights, and the provisions in this regard contained in Law 41/2002, of 14 November, the basic law regulating Patient Autonomy and rights and obligations regarding clinical information and documentation, as well as any other current and applicable regulations). Therefore, your identity will not be revealed to any person nor will your data be communicated to third parties except in cases of medical emergency or legal requirement.

Finally, you may withdraw the consent given and exercise your rights of access, rectification, suppression, limitation of the processing of your data, opposition and portability, for which you should contact the patient care service of the Marqués Institute in person, or by post addressed to the centre’s «Patient Care Service», with the reference «data protection rights», identifying yourself as a participant in the study and providing a photocopy of your ID card or equivalent document and indicating the right you wish to exercise.

If you have any questions regarding the processing of your data, you can contact our Data Protection Officer at the following email address: lopd@institutomarques.com. We also inform you of the possibility of lodging a complaint with the competent supervisory authority, in accordance with the procedure applicable to the specific case.

 

PUBLICATION OF THE RESULTS

The results of this study will be made public, according to one of the channels accepted by the scientific community, maintaining in all cases the confidentiality and rights of the participants. Under no circumstances will data that allow participants to be identified be published.

FINANCIAL COMPENSATION

This study is an independent initiative of a researcher at the Marqués Institute, which has a private funding source and is conducted on a not-for-profit basis. Neither the researcher, nor the patients, nor the centre will receive financial compensation for their participation in the study. Nor will their participation in the study entail any costs for them.

OTHER RELEVANT INFORMATION DURING THE CONDUCT OF THE STUDY

Any new information concerning the study that may affect your willingness to participate in the study that is discovered during your participation will be communicated to you by your study doctor as soon as possible.

You should also be aware that you may be excluded from the study if the study sponsor or investigators deem it appropriate.

If you need more information about this study, please contact the Principal Investigator of the project, Dr. Borja Marqués López-Teijón or any of his collaborators by phone: (+34)932858216 or email comite.cientifico@institutomarques.com