Clinical trial NCT03598374: Spontaneous Reproductive Outcomes After Oral Inositol Supplementation in Infertile Polycystic Ovarian Syndrome Women.
Official title: Effects of Oral Inositol Supplementation on Spontaneous Reproductive Outcomes in Infertile Polycystic Ovarian Syndrome Women.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Polycystic Ovarian Syndrome
Infertility, Female
Keywords: Inositol
Polycystic ovarian syndrome
Fertility
Clinical pregnancy rate
Miscarriage rate
Live birth rate
Lead sponsor: Università degli Studi dell'Insubria
Sponsor class: OTHER
Collaborators: name: Universita di Verona
First posted: 2018-07-26
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized multi centre double-blind controlled trial
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Clinical pregnancy rate
timeFrame: Within 6 months from the enrollment
measure: Miscarriage rate
timeFrame: Within 6 months from the enrollment
measure: Live birth rate
timeFrame: Within 18 months from the enrollment
measure: Spontaneous ovulation rate
timeFrame: Change in spontaneous ovulation rate, through study completion (an average of 18 months)
Secondary outcomes:
measure: Glucose metabolism
timeFrame: Change in glucose metabolism, through study completion (an average of 18 months)
measure: BMI
timeFrame: Change in BMI, through study completion (an average of 18 months)
measure: Lipid metabolism
timeFrame: Change in Lipid metabolism, through study completion (an average of 18 months)
measure: Blood pressure
timeFrame: Change in Blood pressure, through study completion (an average of 18 months)
measure: Androgens profile
timeFrame: Change in Androgens profile, through study completion (an average of 18 months)
Other outcomes:
Locations:
Study officials:
affiliation: Università degli Studi dell'Insubria
name: Antonio Simone Laganà, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universita di Verona
name: Simone Garzon, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Università degli Studi dell'Insubria
name: Fabio Ghezzi, M.D.
role: STUDY_CHAIR
affiliation: Universita di Verona
name: Massimo Franchi, M.D.
role: STUDY_CHAIR
References: