Advertisement

Archives of Gynecology and Obstetrics

, Volume 299, Issue 6, pp 1701–1707 | Cite as

The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial

  • Azadeh Akbari Sene
  • Azam Tabatabaie
  • Hossein Nikniaz
  • Ahad Alizadeh
  • Kourosh Sheibani
  • Mona Mortezapour Alisaraie
  • Maryam Tabatabaie
  • Mahnaz Ashrafi
  • Fatemehsadat AmjadiEmail author
Gynecologic Endocrinology and Reproductive Medicine

Abstract

Purpose

The aim of the present study was to evaluate the effect of myo-Inositol administration on oocyte quality, fertilization rate and embryo quality in patients with PCOS during assisted reproductive technology (ART) cycles.

Methods

Fifty infertile PCOS patients were randomly designated in two groups. In the study group, patients received daily doses of 4 g myo-Inositol combined with 400 mg folic acid and in the control group patients received only 400 mg folic acid from 1 month before starting the antagonist cycle until the day of ovum pick up. Oocyte and embryo qualities were assessed according to European Society of Human Reproduction and Embryology (ESHRE) guidelines. The gene expression of PGK1, RGS2 and CDC42 as a factor of oocyte quality in granulosa cells was analyzed using real-time RT-PCR. Levels of total antioxidant capacity (TAC) and reactive oxygen species (ROS) were evaluated by chemiluminescence assay in follicular fluid.

Results

The percentage of metaphase II oocyte, fertilization rate and embryo quality significantly improved in the study group (p < 0.05), but the number of retrieved oocytes and follicle count were not statistically different between groups. Furthermore, the gene expression of PGK1, RGS2 and CDC42 was significantly higher in the study group (p < 0.05) but no differences were found between two groups in terms of TAC and ROS levels.

Conclusions

The present study findings suggest that myo-Inositol alters the gene expression in granulosa cells and improves oocyte and embryo quality among PCOS patients undergoing ART.

Keywords

Polycystic ovary syndrome myo-Inositol Oocyte Fertilization Assisted reproductive technology 

Notes

Acknowledgements

The authors would like to thank Professor Felice Petraglia (University of Florence, Italy) for his input and guidance in revising our manuscript. This study was financed by Iran University of Medical Science (Grant no. 26493).

Author contributions

A.A.S: substantial contributions to the conception or design, interpretation of data and final approval of the version to be published; A.T: acquisition of data and collecting samples; H.N: acquisition of data; A.A: statistical analysis and interpretation of data; K.S: drafting and english editing of the article; M.M.A: acquisition of data; M.T: acquisition of data; M.A: revision the article critically for the important intellectual contents; F.A: substantial contributions to the conception or design, drafting the article and final approval of the version to be published.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest with the subject matter of this manuscript.

References

  1. 1.
    El-Berry S, Razik MA (2010) Nitric oxide donors increases pregnancy rate in clomiphene citrate treated polycystic ovary infertile patients. Middle East Fertil Soc J 15(2):106–109CrossRefGoogle Scholar
  2. 2.
    Amjadi F et al (2018) Distinct changes in the proteome profile of endometrial tissues in polycystic ovary syndrome compared with healthy fertile women. RBM Online 37(2):184–200PubMedGoogle Scholar
  3. 3.
    Chen S, Song J (2008) Oocyte quality and embryo quality of infertile women with polycystic ovarian syndrome. Fertil Steril 90:S132CrossRefGoogle Scholar
  4. 4.
    Teede HJ et al (2018) Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod 33(9):1602–1618CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Salehpour S et al (2012) N-Acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome. J Obstet Gynaecol Res 38(9):1182–1186CrossRefPubMedGoogle Scholar
  6. 6.
    Salehi E et al (2017) Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet 296(6):1219–1227CrossRefPubMedGoogle Scholar
  7. 7.
    Nordio M, Proietti E (2012) The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci 16(5):575–581PubMedGoogle Scholar
  8. 8.
    Phillippy BQ, Graf E (1997) Antioxidant functions of inositol 1,2,3-trisphosphate and inositol 1,2,3,6-tetrakisphosphate. Free Radic Biol Med 22(6):939–946CrossRefPubMedGoogle Scholar
  9. 9.
    Pundir J et al (2018) Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomised trials. BJOG 125(3):299–308CrossRefPubMedGoogle Scholar
  10. 10.
    Croze ML, Soulage CO (2013) Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie 95(10):1811–1827CrossRefPubMedGoogle Scholar
  11. 11.
    Foster SR et al (2017) Effects of combined inositol hexakisphosphate and inositol supplement on antioxidant activity and metabolic enzymes in the liver of streptozotocin-induced type 2 diabetic rats. Chem Biol Interact 275:108–115CrossRefPubMedGoogle Scholar
  12. 12.
    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):509–514PubMedGoogle Scholar
  13. 13.
    Vartanyan EV et al (2017) Improvement in quality of oocytes in polycystic ovarian syndrome in programs of in vitro fertilization. Gynecol Endocrinol 33(sup1):8–11CrossRefPubMedGoogle Scholar
  14. 14.
    Uyar A, Torrealday S, Seli E (2013) Cumulus and granulosa cell markers of oocyte and embryo quality. Fertil Steril 99(4):979–997CrossRefPubMedGoogle Scholar
  15. 15.
    Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81(1):19–25CrossRefGoogle Scholar
  16. 16.
    Gu BX et al (2016) Abnormal expression of TLRs may play a role in lower embryo quality of women with polycystic ovary syndrome. Syst Biol Reprod Med 62(5):353–358CrossRefPubMedGoogle Scholar
  17. 17.
    Benner A (1999) Sample size tables for clinical studies. (2nd edn). In: David Machin, Michael JC, Peter MF, Alain PY, Pinol, Blackwell Science Ltd., Oxford, 1997. No. of pages: x+315. Price: £45. ISBN 0-86542-870-0. Stat Med 18(4):494–495Google Scholar
  18. 18.
    Rago R et al (2015) Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study. J Biol Regul Homeost Agents 29(4):913–923PubMedGoogle Scholar
  19. 19.
    Amjadi F et al (2015) Apolipoprotein A1 as a novel anti-implantation biomarker in polycystic ovary syndrome: a case-control study. J Res Med Sci 20(11):1039CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Pacchiarotti A et al (2016) Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome. Gynecol Endocrinol 32(1):69–73CrossRefPubMedGoogle Scholar
  21. 21.
    Ocal P et al (2012) Recurrent implantation failure is more frequently seen in female patients with poor prognosis. Int J Fertil Steril 6(2):71–78PubMedPubMedCentralGoogle Scholar
  22. 22.
    Papaleo E, et al (2009) Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril 91(5):1750–1754Google Scholar
  23. 23.
    Emekci Ozay O et al (2017) Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: a prospective, controlled, randomized trial. Gynecol Endocrinol 33(7):524–528CrossRefPubMedGoogle Scholar
  24. 24.
    Unfer V et al (2011) Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study. Gynecol Endocrinol 27(11):857–861CrossRefPubMedGoogle Scholar
  25. 25.
    Mendoza N et al (2017) Inositol supplementation in women with polycystic ovary syndrome undergoing intracytoplasmic sperm injection: a systematic review and meta-analysis of randomized controlled trials. Reprod Biomed Online 35(5):529–535CrossRefPubMedGoogle Scholar
  26. 26.
    Ajduk A, Malagocki A, Maleszewski M (2008) Cytoplasmic maturation of mammalian oocytes: development of a mechanism responsible for sperm-induced Ca2+ oscillations. Reprod Biol 8(1):3–22CrossRefPubMedGoogle Scholar
  27. 27.
    Hammes SR (2004) Steroids and oocyte maturation–a new look at an old story. Mol Endocrinol 18(4):769–775CrossRefPubMedGoogle Scholar
  28. 28.
    Wang Q, Moley KH (2010) Maternal diabetes and oocyte quality. Mitochondrion 10(5):403–410CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Nelson VL et al (1999) Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol 13(6):946–957CrossRefPubMedGoogle Scholar
  30. 30.
    Unfer V et al (2017) Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocr Connect 6(8):647–658CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Zeng L, Yang K (2018) Effectiveness of myoinositol for polycystic ovary syndrome: a systematic review and meta-analysis. Endocrine 59(1):30–38CrossRefPubMedGoogle Scholar
  32. 32.
    Bevilacqua A et al (2018) Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model. J Cell Physiol 234(6):9387–9398CrossRefPubMedGoogle Scholar
  33. 33.
    Ducibella T, Schultz RM, Ozil JP (2006) Role of calcium signals in early development. Semin Cell Dev Biol 17(2):324–332CrossRefPubMedGoogle Scholar
  34. 34.
    Condorelli RA et al (2011) Effects of myoinositol on sperm mitochondrial function in-vitro. Eur Rev Med Pharmacol Sci 15(2):129–134PubMedGoogle Scholar
  35. 35.
    Showell MG et al (2018) Inositol for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev 12:CD012378PubMedGoogle Scholar
  36. 36.
    Karuputhula NB et al (2013) Oxidative status in granulosa cells of infertile women undergoing IVF. Syst Biol Reprod Med 59(2):91–98CrossRefPubMedGoogle Scholar
  37. 37.
    Bernhardt ML et al (2015) Regulator of G-protein signaling 2 (RGS2) suppresses premature calcium release in mouse eggs. Development 142(15):2633–2640CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Hamel M et al (2010) Genomic assessment of follicular marker genes as pregnancy predictors for human IVF. Mol Hum Reprod 16(2):87–96CrossRefPubMedGoogle Scholar
  39. 39.
    Gu L et al (2015) Metabolic control of oocyte development: linking maternal nutrition and reproductive outcomes. Cell Mol Life Sci 72(2):251–271CrossRefPubMedGoogle Scholar
  40. 40.
    Mikaeili S et al (2016) Altered FoxO3 expression and apoptosis in granulosa cells of women with polycystic ovary syndrome. Arch Gynecol Obstet 294(1):185–192CrossRefPubMedGoogle Scholar
  41. 41.
    Varras M et al (2012) Expression of antiapoptosis gene survivin in luteinized ovarian granulosa cells of women undergoing IVF or ICSI and embryo transfer: clinical correlations. Reprod Biol Endocrinol 10:74CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Patel SS, Carr BR (2008) Oocyte quality in adult polycystic ovary syndrome. Semin Reprod Med 26(2):196–203CrossRefPubMedGoogle Scholar
  43. 43.
    Tu S, Cerione RA (2001) Cdc42 Is a Substrate for Caspases and Influences Fas-induced Apoptosis. J Biol Chem 276(22):19656–19663CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Azadeh Akbari Sene
    • 1
  • Azam Tabatabaie
    • 1
  • Hossein Nikniaz
    • 2
  • Ahad Alizadeh
    • 3
  • Kourosh Sheibani
    • 4
  • Mona Mortezapour Alisaraie
    • 1
  • Maryam Tabatabaie
    • 1
  • Mahnaz Ashrafi
    • 1
    • 5
  • Fatemehsadat Amjadi
    • 1
    • 2
    Email author
  1. 1.Shahid Akbarabadi Clinical Research Development Unit (ShACRDU)Iran University of Medical SciencesTehranIran
  2. 2.Department of Anatomy, School of Medicine SciencesIran University of Medical SciencesTehranIran
  3. 3.Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran
  4. 4.Basir Eye Health Research CenterTehranIran
  5. 5.Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran

Personalised recommendations