Myo-Inositol + Letrozole for PCOS Infertility

Overseen by Heather Burks, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Oklahoma

Must not be taking: Myo-inositol, Metformin

Disqualifiers: Diabetes, Thyroid dysfunction, others

Trial Summary

What is the purpose of this trial?

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 ovulation induction or until pregnancy is achieved. All participants and members of the research team will be blinded to the treatment arms. Placebo and inositol supplement will be packaged to appear the same, tested, and packaged by a commercial supply company. The inositols will be a 40:1 blend of myo-inositol and D-chiro inositol.

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.

What data supports the effectiveness of the treatment Myo-Inositol + Letrozole for PCOS Infertility?

Research shows that Myo-Inositol can help improve hormonal and metabolic issues in women with PCOS, such as reducing insulin levels and improving menstrual regularity, which may support fertility. ^{1 2 3 4 5}

Is Myo-Inositol safe for use in humans?

Myo-Inositol has been studied in women with polycystic ovary syndrome (PCOS) and is generally considered safe, showing positive effects on metabolism and hormone levels without significant safety concerns reported in the studies. ^{2 4 5 6 7}

How does the Myo-Inositol + Letrozole treatment for PCOS infertility differ from other treatments?

The Myo-Inositol + Letrozole treatment is unique because it combines inositol, which helps improve ovarian function and insulin signaling, with letrozole, a medication that induces ovulation. This combination targets both hormonal and metabolic aspects of PCOS, potentially offering a more comprehensive approach to improving fertility compared to treatments that focus on only one aspect. ^{4 6 7 8 9}

Research Team

Heather Burks, MD

Principal Investigator

OUHSC

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Inositol supplement (Dietary Supplement)
• Placebo supplement (Placebo)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Scott Rollins

University of Oklahoma

Chief Executive Officer since 2016

PhD in Immunology from the University of Oklahoma

Dr. Ondria Gleason

University of Oklahoma

Chief Medical Officer

MD from the University of Oklahoma College of Medicine

Findings from Research

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 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 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]

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]

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 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]

References

1. Netherlands 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. [2022]

3. United States 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. [2013]

4. England 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. [2014]

5. England pubmed.ncbi.nlm.nih.gov

Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. [2020]

6. Poland 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). [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

The effectiveness of inositol and metformin on infertile polycystic ovary syndrome women with resistant to letrozole. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Inositols in PCOS. [2023]

9. Egypt 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. [2020]