Myo-Inositol + Letrozole for PCOS Infertility

Recruiting in Palo Alto (17 mi)

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}

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 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

OUHSC Reproductive Medicine Clinic Oklahoma City, OK

Who Is Running the Clinical Trial?

University of Oklahoma Lead Sponsor

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] Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disease that involves menstrual dysfunction and reproductive difficulty, as well as metabolic problems. The aim of this study was to assess the effectiveness of myo-inositol (MYO) and d-chiro-inositol (DCI) on improving oocyte or embryo quality and pregnancy rates for women with PCOS undergoing intracytoplasmic sperm injection (ICSI). We searched the Web of Knowledge, MEDLINE, EMBASE, Pubmed, Scopus and Cochrane databases for all articles published in any language up to March 2017. The selection criteria were as follows: (population) patients with PCOS; (intervention) treatment with inositol (MYO, DCI, or both, with any dose and any duration) in conjunction with an ovulation-inducing agent versus the ovulation-inducing agent alone; (outcome) oocyte and embryo quality; (study design) randomized controlled trials. Of 76 identified studies, eight RCTs were included for analysis comprising 1019 women with PCOS. MYO supplementation was insufficient to improve oocyte quality (OR 2.2051; 95% CI 0.8260 to 5.8868), embryo quality (OR 1.6231, 95% CI 0.3926 to 6.7097), or pregnancy rate (OR 1.2832, 95% CI 0.8692 to 1.8944). Future studies of appropriate dose, size and duration of DCI are vital to clarify its the role in the management of PCOS.

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

Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. [2022] To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of PCOS patients.

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] In an attempt to evaluate the role of inositol supplementation in insulin-resistant patients with polycystic ovary syndrome (PCOS), undergoing gonadotropin ovulation induction using the low-dose step-down regimen, we conducted a prospective longitudinal study comparing the stimulation characteristics of 15 patients treated with inositol, to a cohort, matched by age and body mass index (BMI), without inositol. Inositol nutritional supplementation produced very good clinical results with a significant reduction in cancellation rate (0 vs. 40%) and the consequent improvement in clinical pregnancy rate (PR) (33.3% vs. 13.3%).

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] Myo-inositol and D-chiro-inositol are capable of improving the ovarian function and metabolism of polycystic ovary syndrome (PCOS) patients. The aim of this work is to compare the effects of myo-inositol and D-chiro-inositol in PCOS. We enrolled 50 patients, with homogeneous bio-physical features, affected by PCOS and menstrual irregularities, and we randomly divided them into two groups: 25 were treated with 4 g of myo-inositol/die plus 400 mcg of folic acid/die orally for six months, 25 with 1 g of D-chiro-inositol/die plus 400 mcg of folic acid/die orally for six months. We analyzed in both groups pre-treatment and post-treatment BMI, systolic and diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), Δ-4-androstenedione, SHBG, prolactin, glucose/immunoreactive insulin (IRI) ratio, homeostatic model assessment (HOMA) index, and the resumption of regular menstrual cycles. Both the isoforms of inositol were effective in improving ovarian function and metabolism in patients with PCOS, although myo-inositol showed the most marked effect on the metabolic profile, whereas D-chiro-inositol reduced hyperandrogenism better.

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

Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. [2020] Myo-inositol (MI) supplementation in women with polycystic ovary syndrome (PCOS) has been evaluated over the last years. Many hormonal and reproductive impairments associated with this disorder seem relieved by the supplement. The objective of the meta-analysis was to assess the effects of MI alone or combined with d-chiro-inositol (DCI) on the endocrine and metabolic abnormalities of women with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE, PubMed and Research Gate (up to November 2016). Only randomized controlled trials (RCTs) investigating the effects of MI alone or combined with DCI were reviewed. Nine RCTs involving 247 cases and 249 controls were included. Significant decreases in fasting insulin (SMD = -1.021 µU/mL, 95% CI: -1.791 to -0.251, P = 0.009) and homeostasis model assessment (HOMA) index (SMD = -0.585, 95% CI: -1.145 to -0.025, P = 0.041) were identified after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve crossed the monitoring boundary, providing firm evidence of the intervention effect. A slight trend toward a reduction of testosterone concentration by MI with respect to controls was found (SMD = -0.49, 95% CI: -1.072 to 0.092, P = 0.099), whereas androstenedione levels remained unaffected. Throughout a subgroup's meta-analysis, a significant increase in serum SHBG was observed only in those studies where MI was administered for at least 24 weeks (SMD = 0.425 nmol/L, 95% CI: 0.050-0.801, P = 0.026). These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.

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] To evaluate the effects of a combined Myo-inositol (MI) and D-chiro-inositol (DCI) therapy on the hormonal and metabolic parameters of women with PCOS. Prospective clinical study. Clinical Study registration number - EUPAS25705 Material and methods: Seventy women diagnosed with PCOS according to the Rotterdam criteria were enrolled in this study. Patients received a combined therapy of one tablet that contained 550 mg of inositol (myo-inositol (MI) and D-chiro-inositol (DCI) in a ratio of 10:1) twice a day for 6 months. At each of 3 visits, the body weight, height and BMI were all recorded; and serum levels of free testosterone (fT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and glucose with insulin during standard OGTT (75 g) were measured. Also at each visit, transvaginal ultrasonography and skin condition assessments were performed.

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

The effectiveness of inositol and metformin on infertile polycystic ovary syndrome women with resistant to letrozole. [2020] The purpose is a comparison of effectiveness of myo-inositol and metformin in infertile women with polycystic ovary syndrome (PCOS) treated with letrozole.

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

Inositols in PCOS. [2023] (1) Background: Myoinositol (MI) and D-chiro-inositol (DCI) are involved in a number of biochemical pathways within oocytes having a role in oocyte maturation, fertilization, implantation, and post-implantation development. Both inositols have a role in insulin signaling and hormonal synthesis in the ovaries. (2) Methods: Literature search (with key words: inositols, myo-inositol, d-chiro-inositol, PCOS) was done in PubMed until Sept. 2020 and 197 articles were identified, of which 47 were of clinical trials (35 randomized controlled trials). (3) Results: Many studies have demonstrated that in patients with polycystic ovarian syndrome (PCOS) MI treatment improved ovarian function and fertility, decreased the severity of hyperandrogenism including acne and hirsutism, positively affected metabolic aspects, and modulated various hormonal parameters deeply involved in the reproductive axis function and ovulation. Thus treating with MI has become a novel method to ameliorate PCOS symptoms, improve spontaneous ovulation, or induce ovulation. The current review is focused on the effects of MI and DCI alone or in combination with other agents on the pathological features of PCOS with focus on insulin resistance and adverse metabolic outcomes. (4) Conclusions: The available clinical data suggest that MI, DCI, and their combination in physiological ratio 40:1 with or without other compound could be beneficial for improving metabolic, hormonal, and reproductive aspects of PCOS.

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] Introduction. We evaluated the effects of a therapy that combines myo-inositol (MI) and D-chiro-inositol (DCI) in young overweight women affected by polycystic ovary syndrome (PCOS), characterized by oligo- or anovulation and hyperandrogenism, correlated to insulin resistance. Methods. We enrolled 46 patients affected by PCOS and, randomly, we assigned them to two groups, A and B, treated, respectively, with the association of MI plus DCI, in a 40 : 1 ratio, or with placebo (folic acid) for six months. Thus, we analyzed pretreatment and posttreatment FSH, LH, 17-beta-Estradiol, Sex Hormone Binding Globulin, androstenedione, free testosterone, dehydroepiandrosterone sulphate, HOMA index, and fasting glucose and insulin. Results. We recorded a statistically significant reduction of LH, free testosterone, fasting insulin, and HOMA index only in the group treated with the combined therapy of MI plus DCI; in the same patients, we observed a statistically significant increase of 17-beta-Estradiol levels. Conclusions. The combined therapy of MI plus DCI is effective in improving endocrine and metabolic parameters in young obese PCOS affected women.