Myo-Inositol + Letrozole for PCOS Infertility

Overseen By Kyra Woods, BA

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

Must not be taking: Myo-inositol, Metformin

Disqualifiers: Diabetes, Thyroid dysfunction, others

Compensation: Varies

Number of Visits: 2

Duration: Up to 5 cycles

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for women with PCOS (polycystic ovary syndrome) who want to become pregnant. Researchers compare the effectiveness of letrozole with or without an inositol supplement in inducing ovulation, which is crucial for pregnancy. Participants will receive either the inositol supplement or a placebo, but neither they nor the researchers will know which one they are receiving. Women diagnosed with PCOS-related ovulation issues who wish to conceive may be suitable for this trial. As an unphased trial, this study offers participants the chance to contribute to important research that could enhance fertility treatments for women with PCOS.

Will I have to stop taking my current medications?

The trial requires that you stop using metformin at least 6 weeks before joining. If you have been using myo-inositol, you must stop at least 3 months before enrolling. Other medications are not specified, so check with the trial team for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that inositol supplements are generally safe for treating polycystic ovary syndrome (PCOS). Studies have found that people tolerate inositol well, even during pregnancy, with no major reports of harm or serious side effects. Compared to other common treatments, inositol is considered safe. Overall, participants in past studies did not experience significant negative effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for PCOS-related infertility involve hormonal therapies like clomiphene citrate or metformin. Unlike these standard options, the treatment being studied combines myo-inositol and d-chiro-inositol, which are natural compounds thought to improve insulin sensitivity and ovarian function. Researchers are excited about this combination because it offers a non-hormonal alternative that could potentially enhance fertility with fewer side effects. This approach targets the metabolic aspect of PCOS, which is different from traditional hormone-based treatments.

What evidence suggests that this trial's treatments could be effective for PCOS infertility?

Research has shown that myo-inositol can improve the health of women with polycystic ovary syndrome (PCOS). It lowers high levels of male hormones, which can cause issues like excess hair growth and acne. Myo-inositol may also aid fertility by reducing the need for some fertility drugs. Studies suggest that inositol, especially D-chiro-inositol, supports ovulation, which is crucial for pregnancy. In this trial, participants in the Inositol Arm will receive myo-inositol plus D-chiro-inositol supplements. These findings indicate that inositol supplements could effectively treat infertility in women with PCOS. ^{6 7 8 9 10}

Who Is on the Research Team?

Heather Burks, MD

Principal Investigator

OUHSC

Are You a Good Fit for This Trial?

This trial is for women aged 18-36 who want to get pregnant but are dealing with infertility due to polycystic ovary syndrome (PCOS). They should have irregular or no ovulation, at least one open fallopian tube, a normal uterus, and a partner with sufficient sperm count. Women can't join if they've taken myo-inositol recently, used metformin within the last 6 weeks, have diabetes or other causes of infertility.

Inclusion Criteria

My uterine cavity is normal.

I want to become pregnant.

My male partner has a sperm count of at least 14 million/mL.

Exclusion Criteria

My ovulation issues are not due to PCOS but another untreated condition.

I have diabetes.

I have not taken myo-inositol in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pretreatment

Participants undergo pretreatment with inositol or placebo for a variable amount of time before starting letrozole

2-6 weeks

1 visit (in-person)

Treatment

Participants receive letrozole and either inositol or placebo for up to 5 cycles of ovulation induction

Up to 5 cycles

Multiple visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inositol supplement
• Placebo supplement

Trial Overview The study tests whether adding an inositol supplement to letrozole treatment improves fertility in PCOS patients compared to letrozole alone. Participants will receive either a placebo or an inositol blend without knowing which one until the end of up to five treatment cycles or until pregnancy occurs.

How Is the Trial Designed?

Group I: Inositol Arm Active Control 1 Intervention

This group will receive myo-inositol (2,000mg) plus d-chiro-inositol (50mg) supplement powder twice daily.

Group II: Control Arm Placebo Group 1 Intervention

This group will receive placebo powder twice daily.

Inositol supplement is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Myo-Inositol for:

• Polycystic ovary syndrome (PCOS)
• Infertility

Approved in United States as Myo-Inositol for:

• Polycystic ovary syndrome (PCOS)
• Infertility

Approved in Canada as Myo-Inositol for:

• Polycystic ovary syndrome (PCOS)
• Infertility

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Published Research Related to This Trial

In a study involving 70 women with PCOS, a combined therapy of Myo-inositol and D-chiro-inositol significantly improved hormonal and metabolic parameters, including reduced levels of free testosterone, luteinizing hormone, and insulin after 6 months.

The treatment also led to significant weight loss and improved skin conditions within just 3 months, indicating its potential as an effective therapy for managing PCOS symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS). Januszewski, M., Issat, T., Jakimiuk, AA., et al.[2020]

Myoinositol (MI) treatment has been shown to improve ovarian function and fertility in patients with polycystic ovarian syndrome (PCOS), as well as reduce symptoms like acne and hirsutism, based on a review of 47 clinical trials.

The combination of MI and D-chiro-inositol (DCI) in a 40:1 ratio may enhance metabolic, hormonal, and reproductive outcomes in PCOS, indicating a promising therapeutic approach for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inositols in PCOS. Kamenov, Z., Gateva, A.[2023]

In a review of eight randomized controlled trials involving 1019 women with PCOS, myo-inositol (MYO) supplementation did not significantly improve oocyte quality, embryo quality, or pregnancy rates when compared to ovulation-inducing agents alone.

The study highlights the need for further research on d-chiro-inositol (DCI) to determine its effectiveness in managing PCOS, as current findings do not support the efficacy of MYO in enhancing reproductive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inositol supplementation in women with polycystic ovary syndrome undergoing intracytoplasmic sperm injection: a systematic review and meta-analysis of randomized controlled trials. Mendoza, N., Pérez, L., Simoncini, T., et al.[2018]

In a controlled study of 20 overweight PCOS patients, 12 weeks of myo-inositol treatment significantly reduced levels of hormones such as LH, PRL, and testosterone, while also improving insulin sensitivity.

Myo-inositol therapy restored menstrual cyclicity in all patients who had irregular periods, demonstrating its potential effectiveness in managing reproductive health in PCOS, unlike the control group that received only folic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Genazzani, AD., Lanzoni, C., Ricchieri, F., et al.[2022]

Inositol supplementation in insulin-resistant patients with polycystic ovary syndrome (PCOS) significantly reduced the cancellation rate of ovulation induction treatments from 40% to 0%.

The use of inositol also improved the clinical pregnancy rate, with a success rate of 33.3% in the inositol group compared to 13.3% in the control group, highlighting its potential efficacy in enhancing fertility outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of inositol supplementation in patients with polycystic ovary syndrome, with insulin resistance, undergoing the low-dose gonadotropin ovulation induction regimen. Morgante, G., Orvieto, R., Di Sabatino, A., et al.[2013]

In a study of 150 infertile women with PCOS, both myo-inositol and metformin were found to improve ovarian function when added to letrozole treatment, although the differences were not statistically significant.

Myo-inositol showed greater effectiveness in enhancing ovarian function specifically in women with a normal BMI compared to metformin, suggesting it may be a better option for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of inositol and metformin on infertile polycystic ovary syndrome women with resistant to letrozole. Pourghasem, S., Bazarganipour, F., Taghavi, SA., et al.[2020]

In a study of 50 women with polycystic ovary syndrome (PCOS), both myo-inositol and D-chiro-inositol were effective in improving ovarian function and metabolic health over six months.

Myo-inositol had a more significant positive impact on metabolic profiles, while D-chiro-inositol was more effective in reducing symptoms of hyperandrogenism, indicating that both forms of inositol can be beneficial but may serve different therapeutic roles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Pizzo, A., Laganà, AS., Barbaro, L.[2014]

Myo-inositol (MI) supplementation significantly reduces fasting insulin levels and improves metabolic profiles in women with polycystic ovary syndrome (PCOS), based on a meta-analysis of 9 randomized controlled trials involving 496 participants.

MI supplementation for at least 24 weeks leads to a significant increase in serum sex hormone-binding globulin (SHBG), which may help alleviate hyperandrogenism, although testosterone levels showed only a slight reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Unfer, V., Facchinetti, F., Orrù, B., et al.[2020]

In a study of 46 young overweight women with polycystic ovary syndrome (PCOS), a combined therapy of myo-inositol (MI) and D-chiro-inositol (DCI) for six months significantly reduced levels of LH, free testosterone, fasting insulin, and HOMA index, indicating improved metabolic health.

The same therapy also led to a significant increase in 17-beta-Estradiol levels, suggesting that MI and DCI can positively influence both endocrine and metabolic parameters in women with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women. Benelli, E., Del Ghianda, S., Di Cosmo, C., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5655679/

Myo-inositol effects in women with PCOS: a meta-analysis of ... These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1472648325004766

Myo-inositol in reproductive management of women with ... In the context of in vitro fertilization, Myo may reduce gonadotropin requirements and improve some intermediate/secondary outcomes, though data ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10981332/

Treatment With a Patented 3.6:1 Myo-Inositol to D-chiro ... Another randomized study including 283 women with PCOS demonstrated the benefits of the 3.6:1 MYO to DCI ratio in improving the hormonal, ...

4. academic.oup.com academic.oup.com/jcem/article/109/6/1630/7504796

Inositol for Polycystic Ovary Syndrome: A Systematic Review ... Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation, but inositol ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04407754?lat=35.4796467&lng=-97.5006758&locStr=The+University+Of+Oklahoma+Health+Sciences+Center,+North+Lindsay+Avenue,+Oklahoma+City,+OK&distance=39&cond=PCOS-+Polycystic+Ovary+Syndrome&rank=1

NCT04407754 | Myo-Inositol for Infertility in PCOS This will be a prospective, double-blind randomized clinical trial of letrozole and placebo versus letrozole and inositols for up to 5 treatment cycles of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5040057/

The inositols and polycystic ovary syndrome - PMC SAFETY/TOLERABILITY. Inositol is generally regarded as safe and can be used in pregnancy.[25] Its excretion in breast milk, and safety in lactation, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36703143/

Inositol is an effective and safe treatment in polycystic ... Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; ...

8. europeanreview.org europeanreview.org/wp/wp-content/uploads/1015.pdf

Inositol safety: clinical evidences Myo-inositol administration positively affects hy- perinsulinemia and hormonal parameters in over- weight patients with polycystic ovary syndrome. Gynecol ...

9. sogc.org sogc.org/common/Uploaded%20files/Position%20Statements/PCOS%20Position%20Statement_FINAL_02142025.pdf

Inositol for the Management of Polycystic Ovary Syndrome ... inositol for the management of PCOS symptoms and there is mixed data about effectiveness. Nevertheless, the risk of harm with the use of inositol for PCOS.

10. tandfonline.com tandfonline.com/doi/full/10.1080/09513590.2023.2301554

Update on the combination of myo-inositol/d-chiro ... The effect of inositols in the treatment of PCOS is well established, as is their excellent safety profile. There is also good quality ...