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

NCT03598374 | Unknown DMC

• 1 other identifier: IROP-1
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Polycystic Ovarian Syndrome; Infertility, Female

Keywords

Inositol; Polycystic ovarian syndrome; Fertility; Clinical pregnancy rate; Miscarriage rate; Live birth rate

Outcome Measures

Primary Outcomes (4)

• 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.

  Within 6 months from the enrollment

• Miscarriage rate

  Number of spontaneous abortion per women diagnosed by positive pregnancy test with subsequent spontaneous interruption of the pregnancy.

  Within 6 months from the enrollment

• Live birth rate

  Number of spontaneous pregnancies per women resulted in a delivered viable fetus.

  Within 18 months from the enrollment

• 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.

  Change in spontaneous ovulation rate, through study completion (an average of 18 months)

Secondary Outcomes (5)

• Glucose metabolism

  Change in glucose metabolism, through study completion (an average of 18 months)

• BMI

  Change in BMI, through study completion (an average of 18 months)

• Lipid metabolism

  Change in Lipid metabolism, through study completion (an average of 18 months)

• Blood pressure

  Change in Blood pressure, through study completion (an average of 18 months)

• Androgens profile

  Change in Androgens profile, through study completion (an average of 18 months)

Study Arms (2)

Inositol + Folic acid

EXPERIMENTAL

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.

Dietary Supplement: Inositol + Folic acid; Behavioral: Regular intercourses

Folic acid

PLACEBO COMPARATOR

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.

Dietary Supplement: Folic acid; Behavioral: Regular intercourses

Interventions

Inositol + Folic acid DIETARY_SUPPLEMENT

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

Inositol + Folic acid

Folic acid DIETARY_SUPPLEMENT

Daily oral supplementation of for 6 months: Folic acid: 400 mcg

Folic acid

Regular intercourses BEHAVIORAL

Couples are required to have regular intercourses with the aim to achieve a spontaneous conception.

Folic acid; Inositol + Folic acid

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Università degli Studi dell'Insubria: lead
• Universita di Verona: collaborator

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Infertility, Female

Interventions

Inositol; Folic Acid

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Infertility

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Antonio Simone Laganà, M.D.

  Università degli Studi dell'Insubria

  PRINCIPAL INVESTIGATOR

• Simone Garzon, M.D.

  Universita di Verona

  PRINCIPAL INVESTIGATOR

• Fabio Ghezzi, M.D.

  Università degli Studi dell'Insubria

  STUDY CHAIR

• Massimo Franchi, M.D.

  Universita di Verona

  STUDY CHAIR

Central Study Contacts

Antonio Simone Laganà, M.D.

CONTACT

‭+39 329 6279579‬; antoniosimone.lagana@asst-settelaghi.it

Simone Garzon, M.D.

CONTACT

‭+39 347 0782287‬; simone.garzon@univr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized multi centre double-blind controlled trial

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: July 26, 2018
• Study Start: January 1, 2022
• Primary Completion: June 30, 2023
• Study Completion: December 31, 2024
• Last Updated: September 30, 2021

Record last verified: 2021-09