Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Neoplasms

Syndrome

Diabetes, Gestational

Diabetes Mellitus

Pre-Eclampsia

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Micronutrients

All Drugs and Chemicals

Hematinics

Vitamins

Other Dietary Supplements

Inositol

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

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.

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.

Daily oral supplementation before spontaneous conception until delivery:

Myo-Inositol: 1100 mg D-chiro-inositol: 27.6 mg Folic acid: 400 mcg

Inositol + Folic acid

Daily oral supplementation before spontaneous conception until delivery:

Folic acid: 400 mcg

Folic acid

Antonio Simone Laganà, M.D.

Simone Garzon, M.D.

Fabio Ghezzi, M.D.

Massimo Franchi, M.D.

Antonella Cromi, M.D.

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.

Randomized multi centre double-blind controlled trial

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.

Effects of Oral Inositol Supplementation on Obstetrics Outcomes in PCOS Women

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

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).

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.

Universita di Verona

Università degli Studi dell'Insubria

Principal Investigator

Infertility

Infertility, Female

Abortion, Spontaneous

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.

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

Daily oral supplementation of for 6 months:

Folic acid: 400 mcg

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

Regular intercourses

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.

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

Effects of Oral Inositol Supplementation on Spontaneous Reproductive Outcomes in Infertile Polycystic Ovarian Syndrome Women.

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.

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

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

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.

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)

Lipid profile assessed by evaluation the high density lipoprotein level and triglycerides level.

Serum free testosterone, dehydroepiandrosterone sulfate, and serum SHBG serum concentrations.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effects of Oral Inositol Supplementation on Obstetrics Outcomes in PCOS Women	NCT03585738	Polycystic Ovar...	Inositol + Foli... Folic acid	18 Years - 40 Years	Università degli Studi dell'Insubria
Spontaneous Reproductive Outcomes After Oral Inositol Supplementation in Infertile Polycystic Ovarian Syndrome Women.	NCT03598374	Polycystic Ovar... Infertility, Fe...	Inositol + Foli... Folic acid Regular interco...	18 Years - 40 Years	Università degli Studi dell'Insubria
Effects of Oral Inositol Supplementation on Obstetrics Outcomes in PCOS Women	NCT03585738	Polycystic Ovar...	Inositol + Foli... Folic acid	18 Years - 40 Years	Università degli Studi dell'Insubria

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