A new study conducted in Spain has made important developments in identifying the best combination of myo-inositol and D-chiro-inositol for women with polycystic ovary syndrome (PCOS) who are undergoing fertility treatments 1 Mendoza N, Diaz-Ropero MP, Aragon M, Maldonado V, Llaneza P, Lorente J, Mendoza-Tesarik R, Maldonado-Lobon J, Olivares M, Fonolla J. Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynaecological Endocrinology. 2019.
What is PCOS?
Polycystic ovary syndrome, or PCOS, is a condition which affects the balance of hormones in women. In particular, women with PCOS have high levels of blood sugar control hormones, which results in a resistance to them.
This can cause problems including weight gain and higher levels of testosterone. Increased testosterone levels also cause symptoms including unwanted hair growth on the face and chest, which is known as hirsutism.
The other major symptoms caused by this imbalance of hormones affect fertility. Many women with PCOS experience irregular periods or have none at all due to the effects on ovulation. Other women may have difficulty getting pregnant, and the symptoms can vary drastically between women. Find out more about PCOS here.
Inositol and PCOS
Inositol is a vitamin-like substance present in beans and fruits. It can occur in different forms, with the two most common types being myo-inositol and D-chiro-inositol.
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Myo-inositol can improve blood sugar control by reducing blood sugar control hormone resistance 2 Unfer V, Facchinetti F, Orru B, Giordani B, Nestler J. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocrine Connections. 2017. 6(8):647-658. It can also improve fertility by restoring ovulation and it can improve pregnancy rates in fertility treatments 3 Zheng X, Lin D, Zhang Y, Lin Y, Song J, Li S, Sun Y. Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. Medicine. 2017. 96(49):e8842. Myo-inositol is also effective at reducing the levels of testosterone in the body 4 Regidor PA, Schindler AE, Lesoine B, Druckman R. Management of PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Hormone Molecular Biology and Clinical Investigation. 2018. 34(2). In this way, myo-inositol can be useful against a range of PCOS symptoms.
D-chiro inositol is also beneficial for women with PCOS. It can increase the action of blood sugar control hormones in PCOS and reduce the level of testosterone 5 Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. The New England Journal of Medicine. 1999. 340:1314-1320. In previous research, scientists have found that it is best to take both myo-inositol and D-chiro-inositol together to improve hormone levels in PCOS 6 Nordio M, Proietti E. 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. European Review for Medical and Pharmacological Sciences. 2012. 16:575-581.
Until now, scientists have generally recommended that women with PCOS take myo-inositol and D-chiro-inositol in the ratio 40:1. This is because this is the proportion in which these compounds are found in the bloodstream 7 Bevilacqua A, Bizzarri M. Physiological role and clinical utility of inositols in polycystic ovary syndrome. Best Practice and Research: Clinical Obstetrics and Gynaecology. 2016. 37:129-139. Previous research has also supported this recommendation, with one study finding that taking myo-inositol and D-chiro-inositol in this ratio improved hormone levels in obese women with PCOS 8 Benelli E, Ghianda SD, Cosmo CD, Tonacchera M. A combined therapy with myo-inositol and D-chiro-inositol improves endocrine parameters and blood sugar control hormone resistance in PCOS young overweight women. International Journal of Endocrinology. 2016.
However this new study by Mendoza and his team suggests that a higher dose of D-chiro-inositol may be more effective than previously thought. This could be because the 40:1 ratio recommended in the past only reflects the levels of myo-inositol and D-chiro-inositol in the bloodstream and not in individual body tissues. In these tissues, the concentrations can vary and the absolute amount may be more important than the ratio.
New study investigates the ratios of myo-inositol and D-chiro-inositol
Mendoza and his team compared two different doses of myo-inositol and D-chiro-inositol in women with PCOS who were undergoing a fertility treatment called intracytoplasmic sperm injection, or ICSI. This is a technique which doctors use as part of IVF treatment. Find out more about fertility treatments here.
Mendoza and his team studied 60 women aged 18-40 years old for a period of 12 weeks. One group of women received 550mg of myo-inositol plus 13.8mg of D-chiro-inositol twice a day. This contains the compounds in the ratio 40 : 1, as previously recommended by scientists. Therefore this group was the “control group”.
The other group of women received a higher dose of D-chiro-inositol therefore this was called the “study group”. These women received 550mg of myo-inositol plus 150mg of D-chiro-inositol twice a day. In this group, the ratio of myo-inositol to D-chiro-inositol was 3.6 : 1.
The two types of inositol were administered in the form of oral soft gelatin capsules. In addition to the two types of inositol, all of the participants in both groups received 400mcg of folic acid per day.
Pregnancy and live birth rates
The team found a significant difference between the pregnancy rates of the two groups. In the study group of women who were taking the higher dose of D-chiro-inositol, the pregnancy rate was higher at 65.5%. In the control group, the pregnancy rate was lower at only 25.9%.
In addition to this, the live birth rate was also higher in the study group than the control group. In the study group the rate was 55.2, compared with only 14.8 in the control group.
Ovarian Hyperstimulation Syndrome
Ovarian Hyperstimulation Syndrome, or OHSS, is a rare condition which can occur in response to fertility medicines which encourage eggs to grow. The body can respond excessively to the medicines resulting in too many eggs developing.
This means that the ovaries can become enlarged and painful, and they release chemicals which make blood vessels leak fluid. The severity of OHSS can vary but in severe cases it can be life-threatening.
In this study, Mendoza and his colleagues found that there was a difference in the risk of developing OHSS between the two groups in the study. The study group of women who were taking a higher dose of D-chiro-inositol had a lower risk of OHSS compared to the control group. The risk in the study group was 3.44% compared to 18.5% in the control group.
Side effects
Previous research has not found any major side effects as a consequence of taking myo-inositol and D-chiro-inositol. The team found that the participants in this study did not suffer from any side effects either, despite the higher dose of D-chiro-inositol.
Quality of study
An important strength of this research is the type of study conducted. Mendoza and his colleagues carried out a randomised controlled trial. This is seen as the gold standard in terms of medical trials as it minimises bias in the results.
However the major limitation of this study is the number of women included. Although the findings in 60 women are significant, this is not a large enough sample size to be representative of women with PCOS in the general population. Therefore more research is needed to verify these results.
Conclusion
This study shows that taking a higher dose of D-chiro-inositol than previously recommended in combination with myo-inositol may improve pregnancy rates and reduce the risk of OHSS in women with PCOS undergoing ICSI. This may be because D-chiro-inositol affects other aspects of reproduction not previously studied such as embryo implantation.
However more research is needed to verify these results and identify whether this higher dose of D-chiro-inositol would be beneficial for women with PCOS who are not undergoing ICSI. For more information and to discuss which treatments would be best for you, it is best to contact your GP or fertility doctor.
Dr. Jones is an experienced consultant in assisted reproduction.
He has worked as a Fertility specialist at Kingston Hospital Assisted Conception and nearly 10 years experience of working in Obstetrics and Gynaecology across hospitals in the UK.
He completed his Masters in Assisted Reproduction Technology and then his PhD, from Imperial College London. Dr. Jones main areas of interest are Single Embryo Transfer, Endometriosis, PCOS and Implantation failure in IVF patients. He is a member of the British Fertility Society and an associate member of the Royal College of Obstetrics and Gynaecology.
Bibliography
- 1Mendoza N, Diaz-Ropero MP, Aragon M, Maldonado V, Llaneza P, Lorente J, Mendoza-Tesarik R, Maldonado-Lobon J, Olivares M, Fonolla J. Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynaecological Endocrinology. 2019
- 2Unfer V, Facchinetti F, Orru B, Giordani B, Nestler J. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocrine Connections. 2017. 6(8):647-658
- 3Zheng X, Lin D, Zhang Y, Lin Y, Song J, Li S, Sun Y. Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. Medicine. 2017. 96(49):e8842
- 4Regidor PA, Schindler AE, Lesoine B, Druckman R. Management of PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Hormone Molecular Biology and Clinical Investigation. 2018. 34(2)
- 5Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. The New England Journal of Medicine. 1999. 340:1314-1320
- 6Nordio M, Proietti E. 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. European Review for Medical and Pharmacological Sciences. 2012. 16:575-581
- 7Bevilacqua A, Bizzarri M. Physiological role and clinical utility of inositols in polycystic ovary syndrome. Best Practice and Research: Clinical Obstetrics and Gynaecology. 2016. 37:129-139
- 8Benelli E, Ghianda SD, Cosmo CD, Tonacchera M. A combined therapy with myo-inositol and D-chiro-inositol improves endocrine parameters and blood sugar control hormone resistance in PCOS young overweight women. International Journal of Endocrinology. 2016
