Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction

Gynecological Endocrinology, December 2007; 23(12): 700–703 Myo-inositol in patients with polycystic ovary syndrome: A novelmethod for ovulation induction ENRICO PAPALEO1, VITTORIO UNFER2, JEAN-PATRICE BAILLARGEON3,LUCIA DE SANTIS1, FRANCESCO FUSI1, CLAUDIO BRIGANTE1, GUIDO MARELLI1,ILARIA CINO1, ANNA REDAELLI1, & AUGUSTO FERRARI1 1IVF Unit, Gynaecological-Obstetric Department, IRCCS San Raffaele Hospital, Vita-Salute University, Milan, Italy,2AGUNCO Obstetrics and Gynecology Centre, Rome, Italy, and 3Department of Medicine, University of Sherbrooke,Sherbrooke, Quebec, Canada (Received 11 June 2007; revised 6 September 2007; accepted 10 September 2007) Polycystic ovary syndrome (PCOS) is often characterized by chronic oligo- or anovulation (usually manifested as oligo- or amenorrhea), and hyperandrogenism. In addition, 30–40% of PCOS women have impaired glucose tolerance,and a defect in the insulin signaling pathway (inositol-containing phosphoglycan mediators) seems to be implicated in thepathogenesis of insulin resistance. PCOS patients are subfertile as a consequence of such ovulatory disorders and often needdrugs, such as clomiphene citrate or follicle-stimulating hormone, for ovulation induction, which increases the risk ofmultiple pregnancy and ovarian hyperstimulation syndrome. We hypothesized that the administration of an isoform ofinositol (myo-inositol), belonging to the vitamin B complex, would improve the insulin-receptor activity, restoring normalovulatory function.
Materials and methods.
Twenty-five PCOS women of childbearing age with oligo- or amenorrhea were enrolled in the study.
Ovulatory disorder due to PCOS was apparently the only cause of infertility; no tubal defect or deficiency of male semenparameters was found. Myo-inositol combined with folic acid (Inofolic1) 2 g twice a day was administered continuously.
During an observation period of 6 months, ovulatory activity was monitored with ultrasound scan and hormonal profile, andthe numbers of spontaneous menstrual cycles and eventually pregnancies were assessed.
Twenty-two out of the 25 (88%) patients restored at least one spontaneous menstrual cycle during treatment, of whom 18 (72%) maintained normal ovulatory activity during the follow-up period. A total of 10 singleton pregnancies (40%of patients) were obtained. Nine clinical pregnancies were assessed with fetal heart beat at ultrasound scan. Two pregnanciesevolved in spontaneous abortion.
Myo-inositol is a simple and safe treatment that is capable of restoring spontaneous ovarian activity and consequently fertility in most patients with PCOS. This therapy did not cause multiple pregnancy.
Keywords: Myo-inositol, polycystic ovary syndrome, ovulation induction Gynecol Endocrinol Downloaded from by University Library SZ 100 on 11/30/10 Recently, many investigators have focused on the impaired glucose tolerance that affects 30–40% of Polycystic ovary syndrome (PCOS) is a medical patients with PCOS [3]. Insulin plays a direct role in condition that causes irregular menstrual cycles, the pathogenesis of hyperandrogenemia in PCOS, chronic anovulation most often manifested as oligo- acting synergistically with luteinizing hormone to or amenorrhea, and androgen excess, with the typical enhance the androgen production of theca cells [4].
ovarian ultrasound features [1]. It is the most common cause of ovulatory disorders and female D-chiro-inositol (DCI) is known to have a role in infertility, and affects approximately 6–10% of women activating enzymes that control glucose metabolism in childbearing age [2]. However, its pathogenesis is altered metabolism of DCI or inositol phosphoglycan Correspondence: E. Papaleo, IVF Unit, Gynaecological-Obstetric Department, IRCCS San Raffaele, via Olgettina 60, I-20132 Milan, Italy.
Tel: 39 02 26432202. Fax: 39 02 26434311. E-mail: ISSN 0951-3590 print/ISSN 1473-0766 online ª 2007 Informa UK Ltd.
DOI: 10.1080/09513590701672405 Myo-inositol for ovulation induction in PCOS mediators has been found in PCOS women and may concentrations were statistically compared using the contribute to their insulin resistance [6,7].
Isoforms of inositol belong to the vitamin B Moreover, eventual pregnancies were confirmed complex. Epimerization of the six hydroxyl groups by a positive test for plasma b-human chorionic of inositol results in the formation of up to nine gonadotropin and ascertainment of a fetal heart beat stereoisomers, including myo-inositol (MI) and DCI.
MI is widely distributed in nature whereas DCI, theproduct of epimerization of the C1 hydroxyl group of Elevated concentration of MI in human follicular Baseline clinical and biochemical features of the fluid appears to play a role in follicular maturity PCOS patients are reported in Table I. The outcome and provides a marker of good-quality oocytes [9].
of treatment is shown in Tables I and II.
After a mean of 34.6 + 5.5 days of MI adminis- showed that supplementation of MI in the culture tration, 22 out of the 25 women (88%) had a first medium increased meiotic progression of germinal menstrual cycle. Eighteen of these 22 patients presented monthly menstruations during the follow- up period. All of them maintained spontaneous Thus we hypothesized that the administration of ovulation activity, documented by follicular growth MI, a precursor of DCI, would improve insulin and increased serum progesterone concentrations in activity and restore ovulatory function and fertility in the luteal phase (mean 10.5 + 1.8 ng/ml). Further- more, after treatment with MI, these women showedsignificantly total testosterone (95.6 + 8.5 vs. 45.2 + 6.7 ng/dl; p ¼ 0.003) and free testosterone (1.0 + 0.8 vs.
A total of 25 women, 28 to 38 age years of age, with 0.38 + 0.1 ng/dl; p ¼ 0.005). The length of succes- PCOS defined by oligo- or amenorrhea (six or fewer sive cycles was improved to 31.7 + 3.2 days.
Two out of the 22 women showed only a follicular hyperandrogenism (hirsutism, acne or alopecia) or development on ultrasound without progesterone hyperandogenemia (elevated levels of total or free elevation during weekly blood sampling, while two testosterone) and typical ovarian features on ultra- women did not have any further ovarian activity after sound scan, were enrolled in the study.
All patients attended our IVF Unit for infertility During the observational period of 6 months a that had lasted for more than 14–16 months. Other total of ten biochemical pregnancies occurred. Nine medical conditions causing ovulatory dysfunction, of the ten were singleton pregnancies documented at such as hyperprolactinemia or hypothyroidism, or ultrasound scan, while one of them was a biochem- androgen excess, such as adrenal hyperplasia or ical abortion. One out of the nine pregnancies Cushing’s syndrome, were excluded by hormonaltests. All women underwent assessment of tubalpatency and all male partners were evaluated with Table I. Clinical and biochemical features of the patients.
two different semen sample analyses, without findingany defect. Anovulation was ascertained by weekly Gynecol Endocrinol Downloaded from by University Library SZ 100 on 11/30/10 Thus, at the end of diagnostic procedures, it was determined that the most likely cause of the couple’s subfertility was ovulation dysfunction only.
PCOS women were treated orally with MI 2 g plus folic acid 200 mg (Inofolic1; Loli Pharma, Rome, Italy) as soluble powder, twice daily, continuously, until the end of the study or a positive pregnancy test.
Patients were instructed to register their menstrual bleeding throughout the follow-up period of 6 months. Furthermore, in order to evaluate the restoration of spontaneous ovarian activity, weekly determination of serum progesterone and test- osterone levels, as well as transvaginal ultrasound scan documenting the presence of follicular growth Significant difference compared with baseline: *p ¼ 0.003; menstrual cycle. Pre- and post-treatment hormone Table II. Outcome of treatment with myo-inositol.
luteal phase, in most infertile patients with PCOS.
The present results are in line with other studies evaluating insulin-sensitizing agents in monotherapy No. of patients with menstrual cycle after or in association with clomiphene citrate [7,13,14, No. of patients with restored monthly ovulation 16–18], suggesting the positive effect that MI plays on spontaneous ovarian activity. Furthermore, we found that MI therapy is able to reduce serum No. of pregnancies/no. of treated patients (%) testosterone, both total and free, as already demon- No. of pregnancies/no. patients with restored strated with DCI. All pregnancies obtained in the follow-up period were singleton, and there was no In conclusion, MI is a simple and safe treatment that is able to restore spontaneous fertility in mostpatients with PCOS.
evolved in a spontaneous abortion at 7 weeks ofgestation. No multiple pregnancy was noted.
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