Abstract
Purpose
The purpose is a comparison of effectiveness of myo-inositol and metformin in infertile women with polycystic ovary syndrome (PCOS) treated with letrozole.
Methods
This study is a randomized single-blind controlled clinical trial undertaken in 150 infertile PCOS women. For all patients, letrozole is prescribed at a dose of 7.5 mg per day from the third day of menstruation for 5 days. Patients who did not ovulate were included and divided into three pretreatment groups: group I(control group), 200 µg of folic acid (as a placebo); group II, 1500 mg of metformin daily plus 200 µg of folic acid, and group III, inositol 2 g plus 200 µg of folic acid received twice daily for 3 months. In the last cycle, 7.5 mg letrozole was prescribed for the induction of ovulation. Primary outcomes were ovary function and pregnancy.
Results
The ovarian function was not significantly different in those groups, whereas the ovarian function of inositol + folic acid group in normal BMI found significantly higher than other BMI spectra. In addition, the ovarian function is significantly higher in the inositol + folic acid group by increasing the infertility duration. The incidence of pregnancy is lower in letrozole + folic acid + inositol group than the other groups; however, it is not significant.
Conclusion
The addition of inositol and metformin to the treatment of infertile PCOS women with letrozole resistance improves the ovarian function; however, it is not significant. Of note, inositol was more effective than metformin in patients with normal BMI.
IRCT registration number
IRCT2017070234845N1
Similar content being viewed by others
References
Nestler JE et al (1998) Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 338(26):1876–1880
Nardo LG et al (2009) The relationships between AMH, androgens, insulin resistance and basal ovarian follicular status in non-obese subfertile women with and without polycystic ovary syndrome. Hum Reprod 24(11):2917–2923
Melo AS, Ferriani RA, Navarro PA (2015) Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice. Clinics 70(11):765–769
Dehbashi S et al (2006) Time of initiation of clomiphene citrate and pregnancy rate in polycystic ovarian syndrome. Int J Gynaecol Obstet 93(1):44–48
Badawy A, Abdel Aal I, Abulatta M (2009) Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril 92(3):849–52.
Mitwally MF et al (2008) Letrozole step-up protocol: a successful superovulation protocol. Fertil Steril 89(4):S23–S24
Palomba S et al (2009) Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr Rev 30(1):1–50
Bargiota A, Diamanti-Kandarakis E (2012) The effects of old, new and emerging medicines on metabolic aberrations in PCOS. Ther Adv Endocrinol Metab 3(1):27–47
Genazzani AD et al (2012) Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients. Gynecol Endocrinol 28(12):969–973
Genazzani AD et al (2008) Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 24(3):139–144
Gerli S et al (2007) Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci 11(5):347–354
Ciotta L et al (2011) Effects of myo-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci 15(5):509–514
Goud PT et al (1999) Presence and dynamic redistribution of type I inositol 1,4,5-trisphosphate receptors in human oocytes and embryos during in-vitro maturation, fertilization and early cleavage divisions. Mol Hum Reprod 5(5):441–451
Colazingari S et al (2013) The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. Arch Gynecol Obstet 288(6):1405–1411
Thomas RM et al (2011) The adapter protein APPL1 links FSH receptor to inositol 1,4,5-trisphosphate production and is implicated in intracellular Ca(2+) mobilization. Endocrinology 152(4):1691–1701
Ijuin T, Takenawa T (2012) Regulation of insulin signaling and glucose transporter 4 (GLUT4) exocytosis by phosphatidylinositol 3,4,5-trisphosphate (PIP3) phosphatase, skeletal muscle, and kidney enriched inositol polyphosphate phosphatase (SKIP). J Biol Chem 287(10):6991–6999
Kapral M et al (2014) Influence of inositol hexaphosphate on the expression of selected proliferation markers in IL-1beta-stimulated intestinal epithelial cells. Acta Pol Pharm 71(6):987–993
Chiu TT et al (2002) Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod 17(6):1591–1596
Zheng X et al (2017) Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. Medicine 96(49):0000000000008842
Raffone E, Rizzo P, Benedetto V (2010) Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol 26(4):275–280
Hurley EG et al (2017) The addition of metformin during ovulation induction with letrozole does not affect pregnancy outcome in infertile women with polycystic ovary syndrome. Fertil Steril 108(3):e246
Monastra G et al (2018) Alpha-lactalbumin Effect on Myo-inositol Intestinal Absorption: In vivo and In vitro. Curr Drug Deliv 15(9):1305–1311
Funding
This study was funded by a grant from Hormozgan University of Medical Sciences (Grant number: 4675).
Author information
Authors and Affiliations
Contributions
SP: data acquisition, conception and design; writing and confirming the final draft. FB: revise, reading, English diting and confirming the final revised manuscript. SAT: Conception and design; writing and confirming the final draft. MAK: Recording the outcomes; providing resources, reading and confirming the final draft
Corresponding author
Ethics declarations
Conflict of interest
The authors have any conflict of interest to declare regarding the manuscript.
Ethical approval
All procedures in the current study were in accordance with the ethical standards of the Hormozgan University of Medical with the 1964 Helsinki declaration.
Informed consent
All the participants provided their informed written consents before inclusion in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Pourghasem, S., Bazarganipour, F., Taghavi, S.A. et al. The effectiveness of inositol and metformin on infertile polycystic ovary syndrome women with resistant to letrozole. Arch Gynecol Obstet 299, 1193–1199 (2019). https://doi.org/10.1007/s00404-019-05064-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00404-019-05064-5