A Novel Ovarian Reserve Monitoring Algorithm for Patients at Risk of Ovarian Injury From Gonadotoxic Therapy

Not yet recruiting

• Conditions: Gonadal Disorders; Ovarian Diseases; Fertility Issues

• Registration Number: NCT05048654
• Lead Sponsor: University of Colorado, Denver

Brief Summary

This is an observational cohort study to examine the use of a novel proposed ovarian reserve monitoring algorithm to (1) identify patients who are at risk of DOR and POI from gonadotoxic therapy, (2) minimize time from treatment to utilization of assisted reproductive technologies, and (3) improves prognosis for successful ART based on AFC for patients who pursue fertility or fertility preservation.

Detailed Description

Study Design: This is an observational cohort study to examine the use of a novel proposed ovarian reserve monitoring algorithm to (1) identify patients who are at risk of DOR and POI from gonadotoxic therapy, (2) minimize time from treatment to utilization of assisted reproductive technologies, and (3) improves prognosis for successful ART based on AFC for patients who pursue fertility or fertility preservation.

Group B: Prospectively, survivors will be evaluated by a member of the FPRLE team in the outpatient clinic at 12 months post-therapy completion and every 6 months to 36 months as part of clinical care. AMH and FSH will be drawn at each time point.

Group A: Retrospectively, we will abstract AMH and FSH from survivors seen at CHCO and UCH from October 1st, 2016 to September 31st, 2019 and assess time points.

Approach Aim 1: The Investigator will assess AMH and FSH in both groups and evaluate whether the monitoring algorithm allows for early identification of DOR prior to the occurrence of POI. The investigator will calculate time from end of treatment to diagnosis of DOR and POI to evaluate if the monitoring algorithm detects these conditions earlier than historical controls.

Statistical analysis: The investigator will provide descriptive statistics and time to event analysis by group.

Aim 2: The Investigator will assess time from end of treatment to utilization of ART as defined by ovulation induction with or without insemination, in vitro fertilization, and/or third-party reproduction.

Statistical analysis: The Investigator will provide descriptive statistics and time to event analysis by group (A and B).

Aim 3: The Investigator will assess if early identification of DOR improves prognosis for successful ART for Group B as compared to Group A. The Investigator define success as an AFC greater than or equal to 6 at time of evaluation by REI.

Statistical analysis: The Investigator will provide descriptive statistics for the prevalence of AFC greater than 6 by group (A and B).

Aim 4: The Investigator will characterize barriers to utilization of ART by surveying participants who were referred to REI. The Investigator will assess the following: (1) if participants declined or accepted referral, (2) if they accepted, were they successful, and (3) if they declined, reasons for declining.

Study Timeline

• Study First Submitted: 2021-09-08
• Study First Submitted QC: 2021-09-08
• Study First Posted: 2021-09-17
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-09
• Last Update Posted: 2024-05-10
• Study Start: 2025-12-15
• Primary Completion: 2028-12-31
• Study Completion: 2029-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 26704

Inclusion Criteria

• · Female patients ages 8 - 39 years of age

  • Seen in CHCO or AMC outpatient clinics for any of the following reasons:

    • At risk for fertility problems (Z91.89)
    • Encounter for fertility preservation counseling (Z31.62)
    • Primary ovarian insufficiency
    • Premature ovarian failure/premature menopause
    • Diminished ovarian reserve

  • At least 12 months post-completion of chemotherapy and/or radiation

  • History of a fertility-threatening diagnosis receiving chemotherapy; radiation; or surgery to the reproductive organs for malignancy, including but not limited to:

    • Any type of cancer/malignancy
    • Rheumatoid arthritis
    • Systemic lupus erythematosus
    • Aplastic anemia
    • Fanconi anemia
    • Diamond-Blackfan syndrome
    • Hurler syndrome
    • Other autoimmune conditions

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Exclusion Criteria

• Disorders of sexual development (i.e., gonadal dysgenesis, Turner syndrome/mosaicism, etc.)
• History of bilateral oophorectomy
• Transgender patients not receiving chemotherapy; radiation; or surgery to the reproductive organs for malignancy
• Inability to consent/assent

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Does the novel monitoring algorithm (intervention group) detect early Ovarian disfunction	2 year follow up	We will compare ovarian reserve categories (normal, diminished ovarian reserve, primary ovarian insufficiency), defined using AMH and FSH, in a retrospective group using the standard of care and a prospective group using a new monitoring algorithm.

Secondary Outcome Measures

Name	Time	Method
Time to ART	2 year follow up	Assess if the length of time from end of treatment to utilization of ART is different between the two groups.
Evaluate if there is an improved AFC in the new monitoring algorithm group	2 year follow up	Assess if the proportion of AFC greater than or equal to 6 at time of evaluation by REI is higher in the new monitoring algorithm group compared to the standard of care.
Characterizing barriers to utilization of ART	2 year year follow up	We will examine the following: (1) if participants declined or accepted referral, (2) if they accepted, were they successful, and (3) if they declined, reasons for declining.