Antithyroidal Antibodies With or Without Subclinical Hypothyroidism During Pregnancy in Infertile Women

NCT ID: NCT04249271

Last Updated: 2020-01-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 96 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2019-12-31

Brief Summary

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.

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.

Conditions

Thyroid Gland Disease; Pregnancy Complications

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

euthyroid, no antibodies

TSH 0.3 to 2.5 mIU/l and anti-TPO \<100 IU/ml repeated serum sampling

serum sampling

Intervention Type: OTHER

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

serum sampling

Intervention Type: OTHER

repeated serum sampling during pregnancy and thereafter

hypothyroidism, no antibodies

TSH \>4.5 mIU/l and anti-TPO \<100 IU/ml repeated serum sampling

serum sampling

Intervention Type: OTHER

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

serum sampling

Intervention Type: OTHER

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

serum sampling

Intervention Type: OTHER

repeated serum sampling during pregnancy and thereafter

hypothyroidism, with antibodiesal

TSH \>4.5 mIU/l and anti-TPO \>100 IU/ml repeated serum sampling

serum sampling

Intervention Type: OTHER

repeated serum sampling during pregnancy and thereafter

Interventions

serum sampling

repeated serum sampling during pregnancy and thereafter

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Christian De Geyter

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian De Geyter, Prof.

Role: PRINCIPAL_INVESTIGATOR

University of Basel

Locations

Klinik für Gyn. Endokrinologie und Reproduktionsmedizin der Frauenklinik des Universitätsspitals

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

EKNZ 39-009 00960

Identifier Type: -

Identifier Source: org_study_id