The DOI matches its Crossref record; 36 of the 37 references it cites were found in a registry or an index.
Hyperinsulinemia Alters Myoinositol to d-chiroinositol Ratio in the Follicular Fluid of Patients With PCOS
Abstract
Myoinositol (MI) and d-chiroinositol (DCI) are 2 stereoisomers and insulin sensitizers. Their physiological ratio differs from tissue to tissue, and they are regulated by an insulin-dependent epimerase whose activity is drastically reduced in conditions of insulin resistance. Based on literature data and on the fact that MI phospholipids are follicle-stimulating hormone (FSH) second messengers, we speculated that patients with polycystic ovary syndrome (PCOS) having hyperinsulinemia, present an enhanced MI to DCI epimerization in the ovary, leading to MI deficiency that impairs FSH signaling, resulting in reduced oocyte quality. In the present study, 20 patients with PCOS and 20 healthy women were enrolled for measurement of MI and DCI levels in their follicular fluid. Follicular fluid samples were taken using a vaginal probe and both MI and DCI were quantified analytically. Results showed that the ratio of MI-DCI dropped from 100:1 in healthy participants to 0.2:1 in patients with PCOS who additionally displayed significantly higher levels of insulin resistance, hyperinsulinemia, and luteinizing hormone. This study is the first one to analyze the misbalance in the MI-DCI ratio in the ovary of patients with PCOS, supporting the concept that maintaining the physiological levels of the 2 stereoisomers is crucial, in restoring the ovarian functionality.
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“In women without PCOS, the ovarian MI:DCI ratio is 100:1, but in women with PCOS, the ratio is 0.2:1 (13).”
From Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines (2024) · cites this paper as [13]
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1 retracted
Papaleo, E., Unfer, V., Baillargeon, J.-P., Fusi, F., Occhi, F., & De Santis, L. (2009) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.01.088 · Cited by 197 · cited 2×
“MI-DCI ratio in the ovary, which might impair FSH signaling and worsen oocyte quality, as it has been shown by previously reported data.(24,35) Therefore, these new findings support the concept that a crucial factor for women with PCOS ovarian function is to maintain the physiological ovarian MI-DCI ratio.”
BackgroundResultRetracted(2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.10.004 · Cited by 9,050
The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group (2004) · Human Reproduction · doi:10.1093/humrep/deh098 · Cited by 6,138
Men at risk: occupation and male infertility.
Claman, P. (2004) · Fertility and Sterility · doi:10.1016/s0015-0282(03)01188-9 · Cited by 2,219
Nestler, J. E., Jakubowicz, D. J., Falcon de Vargas, A., Brik, C., Quintero, N., & Medina, F. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.6.4886 · Cited by 617
Ovulatory and Metabolic Effects of d-Chiro-Inositol in the Polycystic Ovary Syndrome
Nestler, J. E., Jakubowicz, D. J., Reamer, P., Gunn, R. D., & Allan, G. (1999) · New England Journal of Medicine · doi:10.1056/nejm199904293401703 · Cited by 518
Baillargeon, J.-P., Jakubowicz, D. J., Iuorno, M. J., Jakubowicz, S., & Nestler, J. E. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2004.02.127 · Cited by 300
D-Chiro-Inositol – Its Functional Role in Insulin Action and its Deficit in Insulin Resistance
Larner, J. (2002) · International Journal of Experimental Diabetes Research · doi:10.1080/15604280212528 · Cited by 279
Should all women with PCOS be treated for insulin resistance?
Marshall, J. C., & Dunaif, A. E. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.11.036 · Cited by 224
Rice, S., Christoforidis, N., Gadd, C., Nikolaou, D. S., Seyani, L., Donaldson, A., Margara, R. A., Hardy, K., & Franks, S. (2004) · Human Reproduction · doi:10.1093/humrep/deh609 · Cited by 224
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Items 101–104 of 104
Inositol and herbal substances as elements of complementary therapy in patients with PCOS
Aab, A., Zarańska, J., Kędra, K., MICHALIK, I., Bielak, M., & Zarański, B. (2023) · Journal of Education Health and Sport · doi:10.12775/jehs.2023.16.01.012
Effect of Myo-Inositol in Treating Polycystic Ovary Syndrome (PCOS): A Review
Alam, S. (2024) · Journal of Obstetrics and Gynecological Surgery · doi:10.52916/jogs244039
Spritzer, P. M., dos Santos, G. R., Vega, M. L. M., Chedraui, P. A., Pilnik, S., Lascano, A. C., Belardo, A., Elizalde-Cremonte, A., Ramírez, A. V., Balán, A. R., et al. (2025) · Gynecological Endocrinology · doi:10.1080/09513590.2025.2456578 · Cited by 2
A Comprehensive Review of Management of Patients with Infertility having Polycystic Ovarian Syndrome
Sharma, S., Pahwa, S., Kumar, R., Singh, N., Singh, J., & Bhandari, V. (2026) · AMEI's Current Trends in Diagnosis & Treatment · doi:10.5005/jp-journals-10055-0187
Metadata
- Authors
- Unfer, V., Carlomagno, G., Papaleo, E., Vailati, S., Candiani, M., & Baillargeon, J.-P.
- Affiliations
- Agunco (IT)
- IRCCS Ospedale San Raffaele (IT)
- Université de Sherbrooke (CA)
- Corresponding author
- Carlomagno, Gianfranco
- Venue
- Reproductive Sciences
- Published
- 2014-07
- Volume
- 21
- Issue
- 7
- Pages
- 854-858
- ISSN
- 1933-7191 (ISSN-L)
- 1933-7205
- OpenAlex
- W2106706873
- Cited by
- 105
- References
- 37
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 8 · 2023: 16 · 2022: 10 · 2021: 11 · 2020: 11 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 11 · 2015: 4 · 2014: 2
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reproductive Sciences (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- polycystic ovary syndrome, hyperinsulinemia, myo-inositol, follicular fluid, insulin resistance, epimerase, oocyte quality, luteinizing hormone
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