Ovulation induction in patients with resistant polycystic ovarian syndrome: Comparative study of the efficacy of metformin and inofolic

Document Type : Original Article

Authors

1 Department of Obstetrics and Gynecology, School of medicine, Ahvaz Jundishapur university of Medical sciences, Iran

2 Department of Obstetrics and Gynecology, School of medicine Fertility Infertility and perinatology Research Center Imam Khomeini Hospital, Jundishapur University of Medical Sciences, Ahvaz, Iran.

3 Fertility Infertility and perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

10.32592/JSMJ.22.5.290

Abstract

Background and purpose: Medicines that reduce insulin levels along with increasing insulin sensitivity have created great hope for the treatment of polycystic ovary syndrome. The aim of this study is to compare the effectiveness of metformin and inofolic in inducing ovulation in patients with resistant polycystic ovary syndrome.
Methodology: This randomized clinical trial study was conducted on 40 patients referred to the infertility clinic with PCOS. Patients were randomly divided into two groups: metformin (receive 1 tablet of 500 mg twice a day) and inofolic (receive 1 sachet twice a day, half an hour before breakfast and half an hour before dinner). The treatment continued for 3 months. During the treatment period, both groups underwent ovulation stimulation (received 5 days of oral administration (clomiphene citrate tablet 100 mg daily or letrozole tablet 5 mg daily)) as well as injectable gonadotropin.
Results: The presence of at least one mature follicle in both groups was completely similar, and the number of mature follicles in both groups had a relatively similar pattern (P = 0.26). The pregnancy rate in the group receiving inofolic and metformin was 25% and 15%, respectively.
Conclusion: The findings of the present study showed that the effectiveness of inositol in terms of improving ovarian function and the occurrence of pregnancy in PCOS patients is similar to metformin.

Keywords

Main Subjects


[1] Balen AH. Polycystic ovary syndrome (PCOS). The Obstetrician & Gynaecologist.2017;19(2):119-29. [DOI: 10.1111/tog.12345]
[2] Dewailly D, Lujan ME, Carmina E, Cedars MI, Laven J, Norman RJ, et al. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update. 2014;20(3):334-52. [DOI:10.1093/humupd/dmt061 ] [PMID]
[3] Balen AH, Morley LC, Misso M, Franks S, Legro RS, Wijeyaratne CN, Stener-Victorin E, Fauser BC, Norman RJ, Teede H. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016;22(6):687-708. [DOI:10.1093/humupd/ dmw025 ] [PMID]
[4] Barber TM, Dimitriadis GK, Andreou A, Franks S. Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance. Clin Med (Lond). 2016; 16(3):262. [DOI:10.7861/clinmedicine.16-3-262 ] [PMID]
[5] Unfer V, Nestler JE, Kamenov ZA, Prapas N, Facchinetti F. Effects of inositol (s) in women with PCOS: a systematic review of randomized controlled trials. Int J Endocrinol. 2016;2016: 1849162. [DOI:10.1155/2016/1849162] [PMID]
[6] Lauritsen MP, Bentzen JG, Pinborg A, Loft A, Forman JL, Thuesen LL, Cohen A, Hougaard DM, Nyboe Andersen A. The prevalence of polycystic ovary syndrome in a normal population according to the Rotterdam criteria versus revised criteria including anti-Müllerian hormone. Hum Reprod. 2014;29(4):791-801. [DOI: 10.1093/humrep/det469 ] [PMID]
[7] Franks S. Polycystic ovary syndrome. N Engl J Med. 1995;333(13):853-61. [DOI:10.1056/NEJM199509283331307 ] [PMID]
[8] Kennington AS, Hill CR, Craig J, Bogardus C, Raz I, Ortmeyer HK, et al. Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus. N Engl J Med. 1990;323(6):373-8. [DOI: 10.1056/NEJM199008093230603] [PMID]
[9] Asplin I, Galasko G, Larner J. chiro-inositol deficiency and insulin resistance: a comparison of the chiro-inositol-and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects. Proc Natl Acad Sci USA. 1993;90(13):5924-8. [DOI: 10.1073/pnas.90.13.5924] [PMID] [PMCID]
[10] Cohen P. The twentieth century struggle to decipher insulin signalling. Nat Rev Mol Cell Biol. 2006;7(11):867-73. [DOI: 10.1038/nrm2043] [PMID]
[11] Baillargeon JP, Nestler JE, Ostlund RE, Apridonidze T, Diamanti-Kandarakis E. Greek hyperinsulinemic women, with or without polycystic ovary syndrome, display altered inositols metabolism. Hum Reprod. 2008;23(6):1439-46. [DOI: 10.1093/ humrep/den097] [PMID] [PMCID]
[12] Baillargeon JP, Diamanti-Kandarakis E, Ostlund Jr RE, Apridonidze T, Iuorno MJ, Nestler JE. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care. 2006;29(2):300-5. [DOI: 10.2337/diacare.29.02. 06.dc05-1070] [PMID]
[13] Kane MT, Norris M, Harrison RA. Uptake and incorporation of inositol by preimplantation mouse embryos. J Reprod Fertil.
1992;96(2):617-25. [DOI: 10.1530/jrf.0.0960617] [PMID]
[14] Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod. 2002;17(6):1591-6. [DOI:10.1093/ humrep/17.6.1591 ] [PMID]
[15] Papaleo E, Unfer V, Baillargeon JP, De Santis L, Fusi F, Brigante C, Marelli G, Cino I, Redaelli A, Ferrari A. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol. 2007;23(12):700-3. [DOI: 10.1080/09513590701672405] [PMID]
[16] Zacchè MM, Caputo L, Filippis S, Zacchè G, Dindelli M, Ferrari A. Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome. Gynecol Endocrinol. 2009;25(8):508-13. [DOI: 10.1080/09513590903015544] [PMID]
[17] Gerli S, Papaleo E, Ferrari A, Di Renzo GC. 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. 2007;11(5):347-54. [PMID]
[18] Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17α activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med. 1996;335(9):617-23. [DOI: 10.1056/NEJM199608293350902] [PMID]
[19] Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab. 2000;85(1):139-46. [DOI: 10.1210/jcem.85.1.6293] [PMID]
[20] Velázquez E, Acosta A, Mendoza SG. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol. 1997;90(3):392-5. [DOI: 10.1016/s0029-7844(97) 00296-2] [PMID]
[21] Essah PA, Apridonidze T, Iuorno MJ, Nestler JE. Effects of short-term and long-term metformin treatment on menstrual cyclicity in women with polycystic ovary syndrome. Fertil Steril. 2006;86(1):230-2. [DOI: 10.1016/j.fertnstert.2005. 12.036] [PMID]
[22] Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med. 1998;338(26):1876-80. [DOI: 10.1056/NEJM199806253382603] [PMID]
[23] Kocak M, Caliskan E, Simsir C, Haberal A. Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Fertil Steril. 2002;77(1):101-6. [DOI: 10.1016/s0015-0282(01)02941-7] [PMID]
[24] Vandermolen DT, Ratts VS, Evans WS, Stovall DW, Kauma SW, Nestler JE. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril. 2001;75(2):310-5. [DOI: 10.1016/s0015-0282(00)01675-7][PMID]
[25] Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L. Pregnancy
298
Ghanbar Zadeh R, et al. Resistant Polycystic Ovarian syndrome. JSMJ. 2023; 22(4):???-???
Jundishapur
Journal of Medical Sciences
September & October 2024. Vol 22. No 4
outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod. 2002;17(11):2858-64. [DOI: 10.1093/humrep/17.11.2858] [PMID]
[26] Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003;327(7421):951-3. [DOI: 10.1136/bmj.327.7421.951] [PMID] [PMCID]
[27] Moll E, Korevaar JC, Bossuyt PM, Van der Veen F. Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome?. Hum Reprod. 2008;23(8):1830-4. [DOI: 10.1093/humrep/den182] [PMID] [28] Moll E, Korevaar JC, Bossuyt PM, Van der Veen F. Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome?. Hum Reprod. 2008;23(8):1830-4. [DOI: 10.1093/humrep/den182] [PMID]
[29] Kamenov Z, Kolarov G, Gateva A, Carlomagno G, Genazzani AD. Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol. 2015;31(2):131-5. [DOI: 10.3109/09513590.2014.964640] [PMID]
[30] Pourghasem S, Bazarganipour F, Taghavi SA, Kutenaee MA. The effectiveness of inositol and metformin on infertile polycystic ovary syndrome women with resistant to letrozole. Arch Gynecol Obstet. 2019;299(4):1193-9. [DOI: 10.1007/s00404-019-05064-5] [PMID]
[31] Facchinetti F, Orru B, Grandi G, Unfer V. Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials. Gynecol Endocrinol. 2019;35(3):198-206. [DOI: 10.1080/ 09513590.2018.1540578] [PMID]
6]Commented [M : : Reference 27 and 28 are the same.