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Supplementation of Myo Inositol & D-Chiro Inositol and its Effects on Fertility

Infertility affects about 10 in 100 women ages 15-44 years in the United States. [1] Causes of infertility in women include structural and hormonal issues (causing ovulation problems), diminished ovarian reserve and other factors such as poor diet, stress and overexposure of chemicals or toxins. [2] Polycystic ovary syndrome (PCOS), a complex hormonal condition, is one of the most common causes of infertility mainly due to anovulation that presents in this syndrome. [3]   

The supplementation of inositol isomers, particularly the combination of Myo Inositol (MI) and D-Chiro Inositol (DCI), show a promising treatment alternative to supporting fertility in women, particularly those with PCOS.

Remember to talk with your primary care doctor before starting any supplements, especially if taking other medications.

What are Inositols and Their Role in Reproduction?

Organic compounds found widely in nature, inositols are part of the cell membrane and act as second messengers for different hormones. [4] As part of the inositol family, MI and DCI are molecules that act as insulin mediators. Although each with specific roles, both are synergistically involved in processes that increase insulin sensitivity in tissues [5] and in the metabolism of glucose. [6]

In particular, MI has been found to be involved in human reproduction. Studies have shown that high MI concentration in the follicular fluid was directly correlated with high oocyte quality and maturation. [7, 8, 3] At the ovarian level, MI has been shown to have a key role in signal transduction, cell morphogenesis and cytogenesis – processes involved in oocyte maturation and embryo development. [9]

How Fertility is Affected by PCOS

To better understand how inositols can support fertility, here’s a further explanation about how the PCOS condition specifically affects fertility in women.

Commonly observed in women with PCOS, insulin resistance has been identified as playing a central role in the syndrome’s development. [10] Insulin resistance causes hyperinsulinemia, a condition that ultimately leads to an imbalance of various hormones including luteinizing hormone (LH), androgen, sex hormone binding globulin (SHBG), and gonadotropins – all of which are involved in reproduction. [11] This hormonal imbalance is a factor in the development of menstrual irregularity and anovulatory cycles, [11] decreasing chances of pregnancy.

In addition, insulin resistance alters the balance of MI and DCI, which have specific ratios in various tissues. [4] In women with PCOS, a depletion of MI in the ovary is observed and may be responsible for poor oocyte quality, due to its important role there. [8] Poor quality of oocytes can also create negative effects in the stimulation of important reproductive hormones, such as follicular-stimulating hormone (FSH), and in ovulation and follicular maturation. [11]

How Myo Inositol & D-Chiro Inositol Can Support Fertility (in Women with PCOS)

Looking at the overall picture, restoring the MI + DCI levels through supplementation can alleviate insulin resistance, preventing hyperinsulinemia and its negative cascading effects on fertility in women with PCOS, described above.

Multiple studies have shown that a high percentage of women with PCOS taking MI + DCI established regular menstrual cycles and showed evidence of improved ovulation rates in addition to improved hormonal and metabolic profiles. [12, 13, 14] With improved frequency of menstrual cycles, supplementation also has the potential to reduce risk of endometrial hyperplasia. [13]

MI is shown to mainly exert its effects on numerous ovarian functions, while DCI mainly effects insulin sensitivity. Both target key features of PCOS interdependently, thus a combination therapy has been suggested to be most beneficial [4]

In studies covering assisted reproductive technology (ART), the importance of the quality of oocytes were highlighted to be the main predictors of positive results. [15] In PCOS women undergoing ART treatment, other studies have suggested overall therapeutic benefits on reproductive outcomes after inositol supplementation. [10, 16] 

Combined therapy (MI + DCI) was able to improve oocyte and embryo quality and pregnancy rates in women undergoing in-vivo fertilization embryonic transfer (IVF-ET), compared with isolated or no supplementation, in one study. [17, 18] Further, the primary findings of another study showed that high doses of DCI in combination with MI increased the pregnancy rate percentage in women with PCOS undergoing intracytoplasmic sperm injection (ICSI). [15]

What About Women Who Don’t Have PCOS?

The promising treatment of inositol supplementation in supporting fertility has thus far been focused on women with PCOS. Although there are studies that have examined these effects in non-PCOS women experiencing infertility, [3, 9] there is limited consistent data available at present.

 

Article References:

[1] Office of Population Affairs. (2019, February 21). Female infertility. https://www.hhs.gov/opa/reproductive-health/fact-sheets/female-infertility/index.html

[2] Cleveland Clinic. (2016, May 10). Infertility causes. https://my.clevelandclinic.org/health/diseases/16083-infertility-causes

[3] Lisi, F., Carfagna, P., Oliva, M. M., Rago, R., Lisi, R., Poverini, R., Manna, C., Vaquero, E., Caserta, D., Raparelli, V., Marci, R., & Moscarini, M. (2012). Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study. Reproductive Biology and Endocrinology, 10(52), 1-7. http://www.rbej.com/content/10/1/52

[4] Kalra, B., Kalra, S., & Sharma, J. (2016). The inositols and polycystic ovary syndrome. Indian Journal of Ednocrinology and Metabolism, 20(5), 720-724. DOI: 10.4103/2230-8210.189231

[5] Benelli, E., Del Ghianda, S., Di Cosmo, C., & Tonacchera, M. (2016). A combined therapy with myo-inositol and d-chiro-inositol improves endocrine parameters and insulin resistance in PCOS young overweight women. International Journal of Endocrinology. DOI: http://dx.doi.org/10.1155/2016/3204083

[6] Sortino, M. A., Salomone, S., Carruba, M. O., & Drago, F. (2017). Polycystic ovary syndrome: insights into the therapeutic approach with inositols. Journal Frontiers in Pharmacology, 8(341), 1-13. DOI: 10.3389/fphar.2017.00341

[7] Papaleo, E., Unfer, V., Baillargeon, J.P., & Chiu, T.T. (2009). Contribution of myo-inositol to reproduction. European Journal of Obstetrics & Gynecology and Reproductive Biology, 147(2), 120-123. DOI: https://doi.org/10.1016/j.ejogrb.2009.09.008

[8] Carlomagno, G., Unfer, V., & Roseff, S. (2011). The D-chiro-inositol paradox in the ovary. Fertility and Sterility, 95(8), 2515-2516. DOI: 10.1016/j.fertnstert.2011.05.027

[9] Caprio, F., D’Eufemia, M.D., Trotta, C., Campitiello, M.R., Ianniello, R., Mele, D., & Colacurci, N. (2015). Myo-inositol therapy for poor-responders during IVF: a prospective controlled observational trial. Journal of Ovarian Research, 8. DOI: 10.1186/s13048-015-0167-x

[10] U.S National Library of Medicine. (2018, July 26). Spontaneous reproductive outcomes after oral inositol supplementation in infertile polycystic ovarian syndrome women. https://clinicaltrials.gov/ct2/show/NCT03598374

[11] Lagana, A.S., Rossetti, P., Buscema, M., La Vignera, S., Condorelli, R.A., Gullo, G., Granese, R., & Triolo, O. (2016). Metabolism and ovarian function in PCOS women: A therapeutic approach with inositols. International Journal of Endocrinology, 2016, 1-9. https://doi.org/10.1155/2016/6306410

[12] Reproductive Science Center. (2015, August 14). Myo-inositol for fertility treatment. https://rscbayarea.com/integrative-medicine-blog/myo-inositol-for-fertility-treatment

[13] Pundir, J., Psaroudakis, D., Savnur, P., Bhide, P., Sabatini, L., Teede, H., Coomarasamy, A., & Thangaratinam, S. (2017). Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomized trials. An International Journal of Obstetrics and Gynaecoloy, 299-308. DOI: 10.1111/1471-0528.14754

[14] Benelli, E., Del Ghianda, S., Di Cosmo, C., & Tonacchera, M. (2016). A combined therapy with myo-inositol and d-chiro-inositol improves endocrine parameters and insulin resistance in PCOS young overweight women. International Journal of Endocrinology, 2016. https://doi.org/10.1155/2016/3204083

[15] Gurevich, Rachel. (2019, September 21). Here’s why an FSH test is important for monitoring your fertility. https://www.verywellfamily.com/day-3-fsh-levels-test-1960172

[16] Bhide, P., Pundir, J., Gudi, A., Shah, A., Homburg, R., & Acharya, G. (2019). The effect of myo-inositol/di-chiro-inositol on markers of ovarian reserve in women with PCOS undergoing IVF/ICSI: A systematic review and meta-analysis. Obstetrics & Gynaecology, 98(10). https://doi.org/10.1111/aogs.13625

[17] U.S. National Library of Medicine. (2011, April 20). Role of myo-inositol and d-chiro-inositol on oocyte quality. https://clinicaltrials.gov/ct2/show/NCT01338844

[18] Colazingari, S., Treglia, M., Najjar, R., & Bevilacqua, A. (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. Archives of Gynecology and Obstetrics, 288, 1405-1411. https://doi.org/10.1007/s00404-013-2855-3

 

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