Effects of Oral Inositol Supplementation on Obstetrics Outcomes in PCOS Women (IPOSI-1)

Effects of Oral Inositol Supplementation on Obstetrics Outcomes in Polycystic Ovary Syndrome Women After Spontaneous Conception

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.

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 Assisted Reproductive Technology (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.

Furthermore, independently by the effect on PCOS related infertility, few data are available about the role of inositol on obstetrics outcomes of pregnancies conceived after treatment with inositol and/or orally supplemented during pregnancy. Considering that the combination of MI and DCI alleviate many of the metabolic dysregulations typical of PCOS thanks to insulin-sensitizing actions, it is plausible consider a beneficial effects on pregnancy complications such as gestational diabetes and preeclampsia.

Study Overview

• Status: Not yet recruiting
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Dietary supplement: Inositol + Folic acid; Dietary supplement: Folic acid

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnancy spontaneously conceived in women with PCOS diagnosed by Rotterdam criteria that starts oral supplementation before conception.

Exclusion Criteria:

• Any kwon pre-pregnancy 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, or until the development or pregnancy-induced/related diseases requiring pharmacological treatments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inositol + Folic acid; 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 before spontaneous conception until delivery.	Dietary supplement: Inositol + Folic acid; Daily oral supplementation before spontaneous conception until delivery: Myo-Inositol: 1100 mg D-chiro-inositol: 27.6 mg Folic acid: 400 mcg
Placebo Comparator: Folic acid; 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 before spontaneous conception until delivery.	Dietary supplement: Folic acid; Daily oral supplementation before spontaneous conception until delivery: Folic acid: 400 mcg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational diabetes prevalence	Gestational diabetes prevalence: number of women that develop gestational diabetes diagnosed based on oral glucose tolerance test (OGTT) cut-off (92 - 180 - 153 mg/dl).	During pregnancy at 16-18 week or 24-28 weeks as recommended
Preeclampsia prevalence	Preeclampsia prevalence: number of women that develop preeclampsia diagnosed based on blood pressure higher than 140/90 mmHg after 20 week of gestation plus 24h proteinuria higher that 300mg.	During pregnancy after the 20 week of gestation
Birth weight	gr	At delivery.
Weight gain in pregnancy	Kg	Change in weight before pregnancy and at the 38 week of gestation

Collaborators and Investigators

• Sponsor: Università degli Studi dell'Insubria
• Collaborators: Universita di Verona
• Investigators: Principal Investigator: Simone Garzon, M.D., Univerisity of Verona; Study Chair: Massimo Franchi, M.D., Univerisity of Verona; Principal Investigator: Antonella Cromi, M.D., Università degli Studi dell'Insubria

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: June 29, 2018
• First Submitted That Met QC Criteria: June 29, 2018
• First Posted (Actual): July 13, 2018

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Pregnancy; Preeclampsia; Gestational diabetes; Polycystic ovarian syndrome; Inositol; Obstetrics outcomes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Physiological Effects of Drugs; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex; Inositol
• Other Study ID Numbers: IPOSI-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No