search
Back to results

Spontaneous Reproductive Outcomes After Oral Inositol Supplementation in Infertile Polycystic Ovarian Syndrome Women. (IROP-1)

Primary Purpose

Polycystic Ovarian Syndrome, Infertility, Female

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Inositol + Folic acid
Folic acid
Regular intercourses
Sponsored by
Università degli Studi dell'Insubria
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovarian Syndrome focused on measuring Inositol, Polycystic ovarian syndrome, Fertility, Clinical pregnancy rate, Miscarriage rate, Live birth rate

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Women with PCOS diagnosed by Rotterdam criteria in couple that desire to conceive.

Exclusion Criteria:

  • Male infertility factor that require in vitro fertilization technique.
  • Women with infertility factors that require in vitro fertilization technique.
  • Couple with infertility factors that require in vitro fertilization technique.
  • Diabetes mellitus that require insulin or oral drugs treatment.
  • Any other pre-pregnancy or pregnancy-induced/related disease.
  • Any other pharmacological, non-pharmacological or nutraceutical treatment (beside oral folic acid supplementation) more than 3 months before the enrollment (wash-out period) or during the trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Inositol + Folic acid

    Folic acid

    Arm Description

    Couples with PCOS infertile women, diagnosed according to the Rotterdam criteria, who access infertility center with conception desire. These women will receive oral supplementation with Inositol (Myo-inositol and D-chiro-inositol at 40:1 ratio) plus Folic acid for 6 months. Couples are required to have regular intercourse with the aim to achieve a spontaneous conception.

    Couples with PCOS infertile women, diagnosed according to the Rotterdam criteria, who access infertility center with conception desire. These women will receive oral supplementation with Folic acid for 6 months. Couples are required to have regular intercourse with the aim to achieve a spontaneous conception.

    Outcomes

    Primary Outcome Measures

    Clinical pregnancy rate
    Number of spontaneous pregnancies conceived per women diagnosed by transvaginal ultrasound. Diagnosis is based on the identification of intrauterine gestational sac with embryo and/or yolk sac.
    Miscarriage rate
    Number of spontaneous abortion per women diagnosed by positive pregnancy test with subsequent spontaneous interruption of the pregnancy.
    Live birth rate
    Number of spontaneous pregnancies per women resulted in a delivered viable fetus.
    Spontaneous ovulation rate
    Spontaneous ovulation activity evaluated by menstrual cycle regularization. Menstrual cycles evaluated by intervals between menstruations (days), day of menstrual blood flow. Rate evaluate considering the number of women with restored regular menstrual cycles per women with irregular menstrual cycles.

    Secondary Outcome Measures

    Glucose metabolism
    OGTT: values of oral glucose tolerance test. Impaired glucose metabolism is diagnosed if fasting glucose values were abnormal (100-125 mg/dl) or glucose tolerance is impaired (2 h plasma glucose within OGTT range of 140-199 mg/dl), and when glucose values exceed threshold values for gestational diabetes (fasting glu- cose value ≥92mg/dl, 1-hour glucose value ≥180mg/dl or 2- hour glucose value ≥153mg/dl)
    BMI
    Body mass index
    Lipid metabolism
    Lipid profile assessed by evaluation the high density lipoprotein level and triglycerides level.
    Blood pressure
    systolic and diastolic blood pressure
    Androgens profile
    Serum free testosterone, dehydroepiandrosterone sulfate, and serum SHBG serum concentrations.

    Full Information

    First Posted
    June 29, 2018
    Last Updated
    September 28, 2021
    Sponsor
    Università degli Studi dell'Insubria
    Collaborators
    Universita di Verona
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03598374
    Brief Title
    Spontaneous Reproductive Outcomes After Oral Inositol Supplementation in Infertile Polycystic Ovarian Syndrome Women.
    Acronym
    IROP-1
    Official Title
    Effects of Oral Inositol Supplementation on Spontaneous Reproductive Outcomes in Infertile Polycystic Ovarian Syndrome Women.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2022 (Anticipated)
    Primary Completion Date
    June 30, 2023 (Anticipated)
    Study Completion Date
    December 31, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Università degli Studi dell'Insubria
    Collaborators
    Universita di Verona

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Polycystic ovarian syndrome (PCOS) is a heterogeneous, multifaceted and complex disorder characterized by insulin resistance (IR), hyperinsulinemia, and hyperandrogenism leading ovarian disfunction and infertility. Given the central pathogenic role of IR in the endocrine, reproductive, and metabolic disturbances of PCOS, several pharmacological and non-pharmacological approaches have been proposed to counteract the hyper insulinemic IR typical of the syndrome. Two Inositol stereoisomers, Myo-Inositol (MI) and D-chiro-inositol (DCI), captured the attention of researchers for their insulin-sensitizing actions, which configure them as proper candidates for the treatment of PCOS. Very few studies reported on spontaneous clinical pregnancy rates, none were powered for this outcome, and none reported on the clinically relevant outcome of live birth. Therefore, data about clinical pregnancy rate, live birth rate, and miscarriage rate comparing inositols with placebo are limited. Conversely, about infertility and assisted reproduction techniques (ART), improvements have been reported in PCOS women who underwent fertility treatment using inositol in different forms, combinations or doses. This data, considering the different tissue-specific ratios (i.e., 100:1 in the ovary) and the different physiological roles of inositol stereoisomers, suggest that DCI supplementation alone might not be the optimal or appropriate approach for improving IVF outcomes in PCOS patients, and drawn attention to the importance of MI and DCI supplementation in a physiological ratio in order to restore normal ovary functionality. Indeed, the combination of MI and DCI, at a more physiological ratio of 40:1, was able to more quickly restore to normal the hormonal and metabolic parameters in PCOS women than MI treatment alone or DCI treatment alone, improving the endocrine profile and IR of women with PCOS. Nevertheless, regarding infertility the primary outcomes that should be considered are clinical pregnancy rate, miscarriage rate and live birth rate. Although many studies showed improved hormonal and metabolic profile and improved ovulation rate and higher quality and number of oocyte retrieved in ART in PCOS women after inositols administration, data about clinical pregnancy rate, live birth rate, and miscarriage rate are limited with several concerns regarding interpretation of the studies.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Polycystic Ovarian Syndrome, Infertility, Female
    Keywords
    Inositol, Polycystic ovarian syndrome, Fertility, Clinical pregnancy rate, Miscarriage rate, Live birth rate

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    Randomized multi centre double-blind controlled trial
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    The patients, care provides, investigators and outcome assessors are blinded for the treatment: Inositol + Folic acid versus Folic acid alone. The treatment allocation is identified by code number before the study start, and will be revealed only after data analysis.
    Allocation
    Randomized
    Enrollment
    80 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Inositol + Folic acid
    Arm Type
    Experimental
    Arm Description
    Couples with PCOS infertile women, diagnosed according to the Rotterdam criteria, who access infertility center with conception desire. These women will receive oral supplementation with Inositol (Myo-inositol and D-chiro-inositol at 40:1 ratio) plus Folic acid for 6 months. Couples are required to have regular intercourse with the aim to achieve a spontaneous conception.
    Arm Title
    Folic acid
    Arm Type
    Placebo Comparator
    Arm Description
    Couples with PCOS infertile women, diagnosed according to the Rotterdam criteria, who access infertility center with conception desire. These women will receive oral supplementation with Folic acid for 6 months. Couples are required to have regular intercourse with the aim to achieve a spontaneous conception.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Inositol + Folic acid
    Intervention Description
    Daily oral supplementation of for 6 months or until pregnancy conception: Myo-Inositol: 1100 mg D-chiro-inositol: 27.6 mg Folic acid: 400 mcg
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Folic acid
    Intervention Description
    Daily oral supplementation of for 6 months: Folic acid: 400 mcg
    Intervention Type
    Behavioral
    Intervention Name(s)
    Regular intercourses
    Intervention Description
    Couples are required to have regular intercourses with the aim to achieve a spontaneous conception.
    Primary Outcome Measure Information:
    Title
    Clinical pregnancy rate
    Description
    Number of spontaneous pregnancies conceived per women diagnosed by transvaginal ultrasound. Diagnosis is based on the identification of intrauterine gestational sac with embryo and/or yolk sac.
    Time Frame
    Within 6 months from the enrollment
    Title
    Miscarriage rate
    Description
    Number of spontaneous abortion per women diagnosed by positive pregnancy test with subsequent spontaneous interruption of the pregnancy.
    Time Frame
    Within 6 months from the enrollment
    Title
    Live birth rate
    Description
    Number of spontaneous pregnancies per women resulted in a delivered viable fetus.
    Time Frame
    Within 18 months from the enrollment
    Title
    Spontaneous ovulation rate
    Description
    Spontaneous ovulation activity evaluated by menstrual cycle regularization. Menstrual cycles evaluated by intervals between menstruations (days), day of menstrual blood flow. Rate evaluate considering the number of women with restored regular menstrual cycles per women with irregular menstrual cycles.
    Time Frame
    Change in spontaneous ovulation rate, through study completion (an average of 18 months)
    Secondary Outcome Measure Information:
    Title
    Glucose metabolism
    Description
    OGTT: values of oral glucose tolerance test. Impaired glucose metabolism is diagnosed if fasting glucose values were abnormal (100-125 mg/dl) or glucose tolerance is impaired (2 h plasma glucose within OGTT range of 140-199 mg/dl), and when glucose values exceed threshold values for gestational diabetes (fasting glu- cose value ≥92mg/dl, 1-hour glucose value ≥180mg/dl or 2- hour glucose value ≥153mg/dl)
    Time Frame
    Change in glucose metabolism, through study completion (an average of 18 months)
    Title
    BMI
    Description
    Body mass index
    Time Frame
    Change in BMI, through study completion (an average of 18 months)
    Title
    Lipid metabolism
    Description
    Lipid profile assessed by evaluation the high density lipoprotein level and triglycerides level.
    Time Frame
    Change in Lipid metabolism, through study completion (an average of 18 months)
    Title
    Blood pressure
    Description
    systolic and diastolic blood pressure
    Time Frame
    Change in Blood pressure, through study completion (an average of 18 months)
    Title
    Androgens profile
    Description
    Serum free testosterone, dehydroepiandrosterone sulfate, and serum SHBG serum concentrations.
    Time Frame
    Change in Androgens profile, through study completion (an average of 18 months)

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    40 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Women with PCOS diagnosed by Rotterdam criteria in couple that desire to conceive. Exclusion Criteria: Male infertility factor that require in vitro fertilization technique. Women with infertility factors that require in vitro fertilization technique. Couple with infertility factors that require in vitro fertilization technique. Diabetes mellitus that require insulin or oral drugs treatment. Any other pre-pregnancy or pregnancy-induced/related disease. Any other pharmacological, non-pharmacological or nutraceutical treatment (beside oral folic acid supplementation) more than 3 months before the enrollment (wash-out period) or during the trial.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Antonio Simone Laganà, M.D.
    Phone
    ‭+39 329 6279579‬
    Email
    antoniosimone.lagana@asst-settelaghi.it
    First Name & Middle Initial & Last Name or Official Title & Degree
    Simone Garzon, M.D.
    Phone
    ‭+39 347 0782287‬
    Email
    simone.garzon@univr.it
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Antonio Simone Laganà, M.D.
    Organizational Affiliation
    Università degli Studi dell'Insubria
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Simone Garzon, M.D.
    Organizational Affiliation
    Universita di Verona
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Fabio Ghezzi, M.D.
    Organizational Affiliation
    Università degli Studi dell'Insubria
    Official's Role
    Study Chair
    First Name & Middle Initial & Last Name & Degree
    Massimo Franchi, M.D.
    Organizational Affiliation
    Universita di Verona
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Spontaneous Reproductive Outcomes After Oral Inositol Supplementation in Infertile Polycystic Ovarian Syndrome Women.

    We'll reach out to this number within 24 hrs