Blood Spot Self-administered Test and Assay

The current study will compare hormone levels of AMH, FSH and inhibin B in blood specimens collected by venipuncture and fingerstick in a sample of pre-menopausal women ages 18-45 years with normal menstrual cycles.

Study Overview

• Status: Completed
• Conditions: Effects of Chemotherapy; Premature Ovarian Failure; Dysfunction; Endocrine

Detailed Description

Recent advances in cancer diagnosis and treatment have led to greater survival rates in patients with malignancies. However, these life-saving treatments, especially alkylating agents, often lead to premature ovarian failure, infertility and related long-term health problems. It is difficult to predict whether, and the extent to which, patients will experience these problems. There are no early clinical signs of decreased fertility potential; even young women who maintain cyclic menses after therapy are at high risk of infertility, early menopause and related health problems. Preliminary studies suggest that several surrogate measures of fertility potential are different in cancer survivors compared with controls. These include follicle stimulating hormone (FSH), estradiol, anti-mullerian hormone (AMH) and inhibin B. Large longitudinal studies are needed to validate these measures with gold standard outcomes such as pregnancy rates, pregnancy outcomes and time to menopause. The main impediment to assessing the value of these markers and generating data that is useful to cancer survivors is the need for frequent and timed blood samples.

Daily or frequent trips to the clinical center are not practical and reduce the compliance of even the most motivated patients. The hypothesis that will be tested by this study is that blood spot assays can be developed that provide robust, personalized data for surrogate markers of reproductive function which can be used to assess reproductive potential in women; furthermore, bloodspots collected at home are an acceptable method for reproductive hormone measurement in women with and without a history of cancer. The current study will compare hormone levels of AMH, FSH and inhibin B in blood specimens collected by venipuncture and fingerstick in a sample of subjects.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19143
      • University of Pennsylvania, Reproductive Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

The target population is 80 pre-menopausal women ages 18-45 years with normal menstrual cycles:

Aim 1: Total 80 subjects:

• 30 cancer survivors
• 30 similar aged healthy controls
• 20 late reproductive aged women

Aim 2: Subset of 60 subjects:

• 30 cancer survivors
• 30 similar aged healthy controls

Description

Inclusion Criteria:

• Adult females
• Age between 18-45 years
• Premenopausal (defined as menses in the past 12 months)
• Postmenarchal
• Presence of an intact uterus and two ovaries
• Ability and willingness to comply with study protocol

Exclusion Criteria:

• Pregnancy within the previous 3 months
• Lactation within the previous 3 months

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cancer Survivor; Pre-menopausal women who are cancer survivors ages 18-45 years with normal menstrual cycles.
Similar aged healthy controls; Pre-menopausal, healthy women ages 18-45 years with normal menstrual cycles
Late Reproductive Age; Pre-menopausal, healthy women of late reproductive age

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AMH pg/mL in dried bloodspot vs serum samples	Serum AMH ELISA assay results will be compared to capillary blood sample AMH collected on filter paper and dried. Recovery of spiked ligands, sensitivity and specificity of the assays will be also assessed.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adequacy of subject's self-collected bloodspot sample vs. sample collected in clinic	A capillary blood sample from a finger-prick is applied to Whatman #903 filter paper, allowed to dry at room temperature for at least 4 hours, and then stored until analysis in the laboratory. Subjects willing to conduct a finger stick at home will collect an additional dried blood spot sample for secondary outcome measures. At home blood spot cards will be compared to those obtained in the office to determine adequacy of collection.	Day 1
Measures of user acceptability through subject report/feedback	Ease of use data reported by subject survey will be summarized to determine the overall acceptability of bloodspot collection and the potential for at- home use	Day 1
AMH pg/mL in cancer survivors vs. healthy control cohorts	AMH in dried blood spots vs. serum collected during the early follicular phase in 30 cancer survivors (15 exposed to low dose cancer therapy, 15 exposed to high dose cancer therapy) and 30 healthy similar aged controls will be compared using tests and multivariable linear regression	Day 1
FSH (mIU/mL) in dried bloodspot vs serum samples	Serum FSH ELISA assay results will be compared to FSH in a dried capillary blood sample applied to filter paper. Recovery of spiked ligands and sensitivity and specificity of the assays will be assessed.	Day 1
Inhibin B (pg/ml) in dried bloodspot vs serum samples	Serum Inhibin B ELISA assay results will be compared to capillary blood sample Inhibin B collected on filter paper and dried. Recovery of spiked ligands and sensitivity and specificity of the assays will be assessed.	Day 1

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Clarisa Gracia, MD, MSCE, University of Pennsylvania

Publications and helpful links

General Publications

• McDade TW, Woodruff TK, Huang YY, Funk WE, Prewitt M, Kondapalli L, Gracia CR. Quantification of anti-Mullerian hormone (AMH) in dried blood spots: validation of a minimally invasive method for assessing ovarian reserve. Hum Reprod. 2012 Aug;27(8):2503-8. doi: 10.1093/humrep/des194. Epub 2012 Jun 6.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: March 17, 2015
• First Submitted That Met QC Criteria: February 11, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: chemotherapy; healthy; premenopausal; alkylating agent; alkylator; postmenarchal; high dose cancer therapy; low dose cancer therapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Primary Ovarian Insufficiency; Menopause, Premature
• Other Study ID Numbers: 812735