Myo-inositol for the Management of Poor Ovarian Responders: A Prospective Randomized Controlled Trial

February 14, 2020 updated by: Antoine Abou Moussa, American University of Beirut Medical Center

The management of poor ovarian responders (POR) remains the most challenging in In-Vitro Fertilization (IVF). The incidence of POR ranges between 9 and 24% (Caprio F, et al, 2015).

POR refers to a reduction in the quantity of primordial follicle pool in reproductive age group (Jirge, P. R., 2016, Sunkara, S. K., et al, 2014), in addition to a higher risk of implantation failure (Kailasam C, et al, 2004).

To overcome this condition, fertility treatments using controlled ovarian stimulation along with IVF is needed to achieve pregnancy. Despite the use of various treatments including high dose gonadotropins, patients with POR have lower rates of pregnancy compared to patients with normal ovarian response (Oudendijk, J. F., et al, 2011). Studies now suggest a variety of regimens like the use of growth hormones, DHEA or androgens to improve the outcomes (Kyrou D, et al, 2009). The main interest of this study is the use of myo-inositol prior to IVF cycles for improvement of reproductive outcomes in poor ovarian responders.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The management of poor ovarian responders (POR) remains the most challenging in In-Vitro Fertilization (IVF). The incidence of POR ranges between 9 and 24% (Caprio F, et al, 2015).

POR refers to a reduction in the quantity of primordial follicle pool in reproductive age group (Jirge, P. R., 2016, Sunkara, S. K., et al, 2014), in addition to a higher risk of implantation failure (Kailasam C, et al, 2004).

To overcome this condition, adjuvant fertility treatments using controlled ovarian stimulation along with IVF is needed to achieve pregnancy. Despite the use of various treatments including high dose gonadotropins, patients with POR have lower rates of pregnancy compared to patients with normal ovarian response (Oudendijk, J. F., et al, 2011). Studies now suggest a variety of regimens like the use of growth hormones, DHEA or androgens to improve the outcomes (Kyrou D, et al, 2009).

Inositol belongs to the vitamin B group, precursor for the synthesis of phosphatidylinositol polyphosphates (PIPs). PIPs belong to the signal transduction system involved in the regulation of different cellular functions such as signal transduction, cell morphogenesis and cytogenesis (Kutateladze TG, 2010). It is involved in cell membrane formation, lipid synthesis and cell growth (Unfer V, et al, 2012). It has been extensively studied in patients with insulin resistance, as inositol has an insulin sensitizing action (Croze ML & Soulage CO, 2013). In addition, researchers have hypothesized different mechanisms of action on different cell types especially at the level of the ovaries. An international consensus has confirmed that myo-inositol pre-treatment is able to improve the oocyte and the embryo quality via enhancing the intracellular Ca2+ oscillation with meiotic progression of germinal vesicle oocytes. Therefore, it acts on improving the oocyte maturation and embryo development (Nestler JE, et al, 1999, Papaleo E, et al, 2009).

Previous studies showed that higher concentrations of myo-inositol in follicular fluid are correlated with a better oocyte quality (Chiu TT, et al, 2002). A study by Jiang demonstrated that inositol supplementation reduces oxidative stress by different agents such as increasing superoxide dismutase and catalase levels (Jiang WD, et al, 2011). In view of its effects on oocyte maturation and quality, the use of myo-inositol in women with POR is promising. However, data is still sparse whether supplementation with myo-inostiol prior to IVF cycles does improve the pregnancy outcomes.

The main interest of this study is the use of myo-inositol prior to IVF cycles for improvement of reproductive outcomes in poor ovarian responders.

Study Type

Interventional

Enrollment (Anticipated)

226

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Antoine Abu Mussa, MD
  • Phone Number: 5445 01350000
  • Email: aa06@aub.edu.lb

Study Locations

  • Lebanon
      • Beirut, Lebanon
        • Recruiting
        • American University of Beirut Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 42 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Age: 18-44 years at the time of interview
  • POR patients defined as: AMH<1.5 ng/nl, AFC of 7 or less, 5 oocytes or less retrieved in a previous cycle

  • Patients undergoing controlled ovarian stimulation for any indication:

    • Male factor
    • Female factor

Exclusion Criteria:

  • Patients with diabetes, thyroid dysfunction
  • Patients with abnormal uterine cavity

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Myo-inositol arm
Patients will be supplemented with 2 grams of Myo-inositol + at least 400 μg of folic acid (received from routinely prescribed multivitamins) every day for 3 months before the IVF cycle.
Drug: Myo-inositol
patients who will be supplemented with 2 grams of Myo-inositol daily for 3 months prior to their in-vitro fertilization cycle
Other Names:
  • Celine
No Intervention: Control arm
Patients will receive at least 400 μg of folic acid from routinely prescribed multivitamins every day for 3 months before the IVF cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retrieved oocytes
Time Frame: 4 months
Number of oocytes retrieved (MII), including total number, number of mature MII, and proportion of dysmorphic oocytes
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cycle cancellation rate
Time Frame: 4 months
number of cycles cancelled before reaching embryo transfer
4 months
Fertilization rate
Time Frame: 4 months
number of zygotes per number of oocytes inseminated
4 months
Implantation rate
Time Frame: 5 months
number of intrauterine gestational sacs observed on transvaginal ultrasound divided by the number of transferred embryos
5 months
Clinical pregnancy rate per started treatment cycle (CPR)
Time Frame: 6 months
the presence of a fetal heart beat on transvaginal ultrasound after 6-7 weeks of gestation
6 months
Ongoing pregnancy per embryo transferred
Time Frame: 7 months
number of viable fetuses beyond 20 weeks' gestation per number of embryos transferred
7 months
Miscarriage rates
Time Frame: 7 months
pregnancy loss prior to 12 weeks' gestation
7 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

American University of Beirut Medical Center

Investigators

  • Principal Investigator: Antoine Abu Mussa, MD, American University of Beirut Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2020

Primary Completion (Anticipated)

February 1, 2022

Study Completion (Anticipated)

February 1, 2023

Study Registration Dates

First Submitted

February 14, 2020

First Submitted That Met QC Criteria

February 14, 2020

First Posted (Actual)

February 18, 2020

Study Record Updates

Last Update Posted (Actual)

February 18, 2020

Last Update Submitted That Met QC Criteria

February 14, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BIO-2018-0357

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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