Subclinical Hypothyroidism and Normogonadotropic Anovulation

Subclinical Hypothyroidism and Ovarian Reserve Indices in Women With Normogonadotropic Anovulation

Thyroid hormones (TH) can modify the functioning of the hypothalamic-pituitary-ovarian axis, affecting the functions of granulosa cells and the development and apoptosis of preantral follicles. TH receptors are present within the oocytes, and TH and anti-thyroid antibodies (ATA) are present in the follicular fluid. Improper thyroid function can cause ovulation disorders, luteal phase failure, impaired endometrial receptivity and result in implantation failures and recurrent miscarriages. While overt hypothyroidism is treated to improve fertility, the effect of subclinical hypothyroidism (SCH) and the presence of circulating ATAs on fertility and obstetric outcomes is uncertain and data on ovarian reserve rates are conflicting. Among the causes of ovulation disorders (group II according to the WHO classification), polycystic ovary syndrome (PCOS) dominates, found in 3-15% of women of reproductive age, and the remaining group of causes is the so-called Hypothalamic-Pituitary-Ovarian Axis Dysfunction (HPOD). The exact etiology of both entities is unknown.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome; Hypothalamic-Pituitary-Ovarian Axis Dysfunction (Disorder)
• Intervention / Treatment: Other: Comparison of laboratory test results in women in the 4 study arms

Detailed Description

Purpose of the study

Evaluation of ovarian reserve indices in women with normogonadotropic anovulation with SCH and without thyroid disease.

Detailed objectives

i) Assessment of AMH, FSH, LH, estradiol, astral follicle count (AFC)/ovarian volume in the subpopulation of women with PCOS and SCH compared to women with PCOS without thyroid disease ii) Assessment of AMH, FSH, LH, estradiol, AFC/ovarian volume in the subpopulation of women with HPOD (other than PCOS) with SCH compared to women with HPOD without thyroid disease iii) Comparison of AMH, FSH, LH, estradiol, AFC/ovarian volume in women with PCOS and HPOD with and without thyroid disease and evaluation of correlation with US ovarian morphology iv) Calculation of the cut-off point of AMH concentration correlating with a high probability of PCOS diagnosis and TSH correlating with unfavorable parameters of ovarian function/HPO axis.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Poland
  • Krakow, Poland, 31-501
    • Jagiellonian University Medical College, Department of Gynecology and Obstetrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study group will consist of women aged 18-45, diagnosed due to menstrual disorders and/or infertility due to ovulation disorders. Inclusion criteria will include age 18-45 and euthyroidism. The exclusion criteria will be: i) diagnosed and treated thyroid dysfunction, ii) history of thyroidectomy. The study population of women will be characterized in terms of demographic (age, BMI) and obstetric data (pregnancy, childbirth, miscarriage, cycle length, infertility).

Description

Inclusion Criteria:

• age 18-45
• irregular periods
• infertility due to ovulation disorders
• euthyreosis

Exclusion Criteria:

• diagnosed and treated thyroid dysfunction,
• history of thyroidectomy

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; PCOS and SCH	Other: Comparison of laboratory test results in women in the 4 study arms; Comparison of AMH, FSH, LH, estradiol, AFC/ ovarian volume on ultrasound in women in the 4 study arms
2; PCOH without SCH	Other: Comparison of laboratory test results in women in the 4 study arms; Comparison of AMH, FSH, LH, estradiol, AFC/ ovarian volume on ultrasound in women in the 4 study arms
3; HPOD and SCH	Other: Comparison of laboratory test results in women in the 4 study arms; Comparison of AMH, FSH, LH, estradiol, AFC/ ovarian volume on ultrasound in women in the 4 study arms
4; HPOD without SCH	Other: Comparison of laboratory test results in women in the 4 study arms; Comparison of AMH, FSH, LH, estradiol, AFC/ ovarian volume on ultrasound in women in the 4 study arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood serum AMH concentration	Measurement of serum AMH concentration in women in 4 arms of the study	01.07.2022-01.12.2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood serum FSH, LH, estradiol	Measurement of serum FSH, LH, estradiol concentration in women in 4 arms of the study	01.07.2022-01.12.2023
AFC/ovarian volume	Ultrasound measurement of AFC/ovarian volume	01.07.2022-01.12.2023

Collaborators and Investigators

• Sponsor: Jagiellonian University
• Investigators: Study Chair: Robert Jach, Prof., Jagiellonian University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): January 10, 2024

Study Registration Dates

• First Submitted: March 11, 2023
• First Submitted That Met QC Criteria: March 11, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Polycystic ovary syndrome; Anovulation; Ovarian reserve; Hypothalamic-Pituitary-Ovarian axis dysfunction; Any-Mullerian hormone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Thyroid Diseases; Hypothalamic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Polycystic Ovary Syndrome; Hypothyroidism; Pituitary Diseases; Anovulation
• Other Study ID Numbers: 1072.6120.172.2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No