Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000738921
Ethics application status
Approved
Date submitted
3/06/2020
Date registered
14/07/2020
Date last updated
6/10/2022
Date data sharing statement initially provided
14/07/2020
Date results information initially provided
22/10/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of iodine excess on thyroid function of women undergoing infertility assessment (Hysterosalpingram) using Lipiodol dye and the potential impact on their babies
Scientific title
The effect of acute and chronic iodine excess on thyroid profile and reproductive function of women using lipiodol during hysterosalpingography and the potential impact on thyroid function of their offspring
Secondary ID [1] 301431 0
Nil known
Universal Trial Number (UTN)
U1111-1227-4450
Trial acronym
SELFI trial (Safety and Efficacy of Lipiodol in Fertility Investigations)
Linked study record
nil

Health condition
Health condition(s) or problem(s) studied:
Infertility 317721 0
Subclinical hypothyroidism 317722 0
Hashimotos thyroiditis 317973 0
Condition category
Condition code
Reproductive Health and Childbirth 315794 315794 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 315795 315795 0 0
Complications of newborn
Metabolic and Endocrine 316006 316006 0 0
Thyroid disease
Reproductive Health and Childbirth 316007 316007 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
We recruit women who undergo hysterosalpingogram(HSG) using Lipiodol dye as part of their infertility work up . Lipiodol is an oil soluble dye rich in iodine and had been in use for a century with increased use in last 20 years due to additional therapeutic benefit of increased pregnancy rates.

After screening, eligible participants are recruited for SELFI trial after informed consent.They undergo blood and urine test in the community lab before the HSG and serially for 6 months after the procedure. The investigations are done by the phlebotomist in the local community labs. This involves 8 lab visits over a period of 6 months.The thyroid results are chased by the research team and informed to the fertility doctor and participant. A record is made if thyroid replacement is initiated by the primary fertility doctor. A documentation is made if the participant gets pregnant during the study period. No additional blood or urine tests will be performed on these women beyond the study duration by the research team. However, relevant investigations (eg.thyroid function test) will be passed on to the treating doctor for ongoing care.

If the woman conceives during the study period of 6 months, the newborn's thyroid test is done on seventh day of life. This is by a heel prick test at the community lab or by a home visit by the phlebotomist as per parent's preference. Results are chased by the research team. If any thyroid hormone replacement necessary and started by the paediaric team, a record is kept.

In addition, the radiologist who does the Lipiodol HSG keeps a record of Lipiodol volume used. The Xray films are independently read by reaserch team radiologist to assesss peritoneal spill and they are blinded to the urine iodine levels. These data are used at the analysis to correlate if increased peritoneal retention of Lipiodol correlates with iodine excess and thyroid dysfunction.
Intervention code [1] 317742 0
Early Detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324005 0
Incidene of iodine excess in women undergoing Lipiodol HSG. This will be assessed by urinary iodine/ creatinine ratio
Timepoint [1] 324005 0
at baseline, 7 days after the HSG , 4 weeks, 12 weeks and 24 weeks after the HSG.
Primary outcome [2] 324006 0
Incidence of thyroid function abnormalities in women undergoing Lipiodol HSG. This will be assessed by serum assays of thyroid function
Timepoint [2] 324006 0
at baseline, 7 days after HSG, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks after the HSG.
Primary outcome [3] 324007 0
Incidence of thyroid function abnormalities in offspring conceived within 6 months of Lipiodol HSG. This will be assessed by a serum assay of thyroid function from a heel prick sample
Timepoint [3] 324007 0
on the seventh day of life.
Secondary outcome [1] 383536 0
Peritoneal retention of Lipiodol assessed by radiologist
Timepoint [1] 383536 0
on the pelvic X-ray 45 minutes after HSG

Eligibility
Key inclusion criteria
Any woman of the reproductive age group who is going for a Lipiodol HSG if they have

1. Normal thyroid function demonstrated by normal free T4

2. Subjects with subclinical hypothyroidism (defined as a TSH >97th percentile or 2.5 IU/L and normal Free T4 levels) are included.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject taking medication known to affect thyroid function or iodine metabolism (e.g. Lithium, amiodarone etc.)
2. Active thyroid disease including hyperthyroidism, hypothyroidism, thyroid cancer and benign goitre.
3. A previous radiological dye study within the last 3months for aqueous dyes and6months for fat soluble dyes as this will affect urine iodine interpretation.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample Size Calculation:
The primary outcome is altered TSH levels. However, this will be examined in the context of iodine exposure and in particular the group of women with the highest and most prolonged iodine excess. Although other studies have investigated the association of thyroid function and iodine excess after Lipiodol, the numbers were small, sample heterogeneous and the subjects with higher iodine levels not specifically identified and assessed.

Conservatively assuming 50% of the subjects develop iodine excess (Kaneshige etal, J Clin Endocrinol Metab, 2015. 100(3): p. E469-72) and that 15-20% of adult women of reproductive age will have Hashimoto’s thyroiditis and sub clinical hypothyroidism predisposing to greater thyroid dysfunction, a minimum sample size of 200 subjects will be required. This would identify a group of approximately 100 women with markedly elevated iodine levels (>2SD) of which we can expect approximately 20 to have pre-existing evidence of autoimmune thyroiditis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
28/06/2019
Date of last participant enrolment
Anticipated
30/06/2021
Actual
30/08/2021
Date of last data collection
Anticipated
30/09/2022
Actual
14/02/2022
Sample size
Target
200
Accrual to date
Final
196
Recruitment outside Australia
Country [1] 22651 0
New Zealand
State/province [1] 22651 0
Auckland

Funding & Sponsors
Funding source category [1] 305870 0
Commercial sector/Industry
Name [1] 305870 0
Guerbet
Country [1] 305870 0
France
Primary sponsor type
University
Name
Liggins Institute,University of Auckland
Address
Liggins Institute
The University of Auckland
Private Bag 92019
Victoria Street West
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 306320 0
None
Name [1] 306320 0
none
Address [1] 306320 0
none
Country [1] 306320 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306130 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 306130 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 306130 0
New Zealand
Date submitted for ethics approval [1] 306130 0
14/05/2019
Approval date [1] 306130 0
22/05/2019
Ethics approval number [1] 306130 0
Ethics ref:19/NTB/52

Summary
Brief summary
This is primarily a safety study of an infertility investigation that has been performed since the 1920s. This infertility investigation called hysterosalpingogram (HSG) is a radiology study where radio-opaque dye is injected into the uterus to establish anatomy and the patency of both fallopian tubes. Recently it has been shown that using a fat soluble dye (lipiodol) as the contrast agent in HSG increases the pregnancy rates in unexplained infertility up to 40% in the following 6 months. Though Lipiodol had been in use for a century, the recent confirmation that fertility is substantially increased after these procedures has increased interest in performing these procedures as an intervention for infertility.

However, Lipiodol dye contains very large amounts of iodine and if the dye spills into the abdomen it can be released over several months, potentially causing toxicity for the mother and fetus. This is primarily due to the effect of iodine excess on thyroid function and small studies have suggested that there are changes in thyroid function, both in the women and neonates conceived within a few cycles following a Lipiodol HSG.

This project aims to
1) Investigate the effects of thyroid function in the women and establish protocols to ensure normal thyroid function in those having thyroid function abnormalities.

2) Establish which women are most at risk of these problems.

3)Investigate the effect on thyroid function in the offspring conceived within the six months following the HSG.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102810 0
Prof Paul Hofman
Address 102810 0
Private Bag 92019
Liggins Institute
University of Auckland
Auckland 1142
Country 102810 0
New Zealand
Phone 102810 0
+64 21938897
Fax 102810 0
Email 102810 0
p.hofman@auckland.ac.nz
Contact person for public queries
Name 102811 0
Prof Paul Hofman
Address 102811 0
Private Bag 92019
Liggins Institute
University of Auckland
Auckland 1142
Country 102811 0
New Zealand
Phone 102811 0
+64 21938897
Fax 102811 0
Email 102811 0
p.hofman@auckland.ac.nz
Contact person for scientific queries
Name 102812 0
Prof Paul Hofman
Address 102812 0
Private Bag 92019
Liggins Institute
University of Auckland
Auckland 1142
Country 102812 0
New Zealand
Phone 102812 0
+64 21938897
Fax 102812 0
Email 102812 0
p.hofman@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
8153Study protocol  d.mathews@auckland.ac.nz alternate email-p.hofman@auckland.ac.nz
8154Informed consent form  d.mathews@auckland.ac.nz alternate email-p.hofman@auckland.ac.nz
8155Ethical approval  d.mathews@auckland.ac.nz alternate email-p.hofman@auckland.ac.nz


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes JCEM, accepted, manuscript in production, Sep 19, ... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe impact of prolonged, maternal iodine exposure in early gestation on neonatal thyroid function.2023https://dx.doi.org/10.3389/fendo.2023.1080330
EmbaseThe SELFI Study: Iodine Excess and Thyroid Dysfunction in Women Undergoing Oil-Soluble Contrast Hysterosalpingography.2022https://dx.doi.org/10.1210/clinem/dgac546
N.B. These documents automatically identified may not have been verified by the study sponsor.