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

Università degli Studi dell'Insubria

Status: Not yet enrolling

Conditions: Polycystic Ovarian Syndrome; Infertility, Female

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03598374

IROP-1

Details and patient eligibility

About

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.

Enrollment: 80 estimated patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Inositol + Folic acid

Experimental group

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.

Treatment:

Behavioral: Regular intercourses

Dietary Supplement: Inositol + Folic acid

Folic acid

Placebo Comparator group

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.

Treatment:

Behavioral: Regular intercourses

Dietary Supplement: Folic acid