Antithyroidal Antibodies With or Without Subclinical Hypothyroidism During Pregnancy in Infertile Women (Anti-TPO)

Antithyroidale Antikörper Mit Oder Ohne Subklinische Hypothyreose Bei Weiblicher Infertilität in Der Schwangerschaft Und im Wochenbett.

One prospective observational study was carried out in 2009 aiming at identifying the fluctuations of the thyroid hormones in women with normal thyroid gland and in women with anti-TPO antibodies. Serum samples were collected periodically during and after pregnancy in previously infertile women. The samples were stored frozen at -80 °C. Now, the hormone measurements will be carried out.

Study Overview

• Status: Completed
• Conditions: Pregnancy Complications; Thyroid Gland Disease
• Intervention / Treatment: Other: serum sampling

Detailed Description

Exclusion of thyroid disease has long been an integral part of a comprehensive infertility work-up, because thyroid function disorders are also associated with disturbances in the menstrual cycle and can cause complications during pregnancy. Subclinical hypothyroidism is the most frequent disease of the thyroid in women of reproductive age (affecting 5 to 10 %). For a long time, measurement of TSH concentration was the only screening parameter used to exclude thyroid disorders. Not only has the differentiation of normal thyroid function (euthyroidism) from the pathological range been controversial for some years but, recently, the role of an elevated anti-TPO antibody titre has also been identified as a significant and independent risk factor for miscarriages and for complications during late pregnancy, even in otherwise euthyroid women. This discovery implies that solely determining the TSH concentration is insufficient. The mechanism underlying the increased rate of complications during pregnancy is also unclear.

The investigators therefore performed a double study to clarify the relative importance of the various possible parameters of thyroid function in the context of an infertility work-up:

1. Prevalence study: Measurement of TSH and anti-TPO concentrations in 175 women who present with infertility at the Infertility Clinic at the Women's Hospital, University Hospital Basel. In addition, each participant underwent an ultrasound scan of the thyroid. Control group: 175 healthy women of reproductive age and with regular menstrual cycles, but not currently wishing to have children (recruited via posters in the university and Blood Donor Centre). This study has been finished in 2010. The data of the prevalence study were used to carry out the prospective sampling of the serum samples.
2. Prospective measurement of fluctuations in thyroid function during pregnancy and post-partum in a group of euthyroid women and/or those with subclinical hypothyroidism (TSH > 4.5 mIU/l) with/without anti-TPO antibodies. Two different euthyroid groups were defined for the study: Euthyroidism I = TSH 0.3-2.5 mIU/l; Euthyroidism II = TSH 2.5-4.5 mIU/l. Six groups, each with 16 women, divided according to TSH concentration and anti-TPO antibody status, will be required (total 96). All female participants with subclinical hypothyroidism (TSH concentration > 4.5 mIU/l, normal values of peripheral thyroid hormones) receive a T4 supplementation dose. Serum samples will be collected each week from the start of pregnancy up to the 12th week and stored frozen at -80 °C. Thereafter, a serum sample will be collected once a month (up to the 38th week) and stored frozen at -80 °C. Finally, one serum sample post-partum (4 to 6 weeks after delivery) and freeze it. A total of 96 women (16 in each group) were recruited to participate in this study.

After conclusion of the observation period, levels of the following hormones will be measured in the total of 1120 serum samples: TSH, total and free l-thyroxine and fT4 index, total and free triiodothyronine, thyroid autoantibodies (TPO antibodies), hCG, 17β-oestradiol, progesterone, prolactin.

• Study Type: Observational
• Enrollment (Actual): 96

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Klinik für Gyn. Endokrinologie und Reproduktionsmedizin der Frauenklinik des Universitätsspitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Healthy women having become pregnancy after infertility.

Description

Inclusion Criteria:

• previous infertility with known thyroidal function (TSH, anti-TPO)

Exclusion Criteria:

• other endocrine pathology, such as Addison, diabetes mellitus
• manifest thyroidal pathology, such as Graves disease
• contraindication against pregnancy
• after repeated miscarriage (3 or more)
• heavy smokers (20 cig per day or more)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
euthyroid, no antibodies; TSH 0.3 to 2.5 mIU/l and anti-TPO <100 IU/ml repeated serum sampling	Other: serum sampling; repeated serum sampling during pregnancy and thereafter
borderline euthyroid, no antibodies; TSH 2.5 to 4.5 mIU/l and anti-TPO <100 IU/l repeated serum sampling	Other: serum sampling; repeated serum sampling during pregnancy and thereafter
hypothyroidism, no antibodies; TSH >4.5 mIU/l and anti-TPO <100 IU/ml repeated serum sampling	Other: serum sampling; repeated serum sampling during pregnancy and thereafter
euthyroid, with antibodies; TSH 0.3 to 2.5 mIU/l and anti-TPO >100 IU/ml repeated serum sampling	Other: serum sampling; repeated serum sampling during pregnancy and thereafter
borderline euthyroid, with antibodies; TSH 2.5 to 4.5 mIU/l and anti-TPO >100 IU/l repeated serum sampling	Other: serum sampling; repeated serum sampling during pregnancy and thereafter
hypothyroidism, with antibodiesal; TSH >4.5 mIU/l and anti-TPO >100 IU/ml repeated serum sampling	Other: serum sampling; repeated serum sampling during pregnancy and thereafter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deviations from euthyroid function as given by serum levels of TSH (expressed in mIU/l) during pregnancy and after birth.	Impact of antibodies on thyroid function during pregnancy.	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Christian De Geyter, Prof., University of Basel

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: February 17, 2018
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Actual): January 30, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: infertility; pregnancy; antibody; thyroid
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Pregnancy Complications
• Other Study ID Numbers: EKNZ 39-009 00960

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The serum samples are coded and cannot be traced back to individual patients.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No