The SELFI Study

Iodine Excess and Thyroid Dysfunction in Women Undergoing Oil-Soluble Contrast Hysterosalpingography

Divya M. Mathews; Jane M. Peart; Robert G. Sim; Neil P. Johnson; Susannah O'Sullivan; José G. B. Derraik; Paul L. Hofman


J Clin Endocrinol Metab. 2022;107(12):3252-3260. 

In This Article

Abstract and Introduction


Context: Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) improves pregnancy rates. However, OSCM has high iodine content and long half-life, leading to potential iodine excess.

Objective: This work aimed to determine the pattern of iodine excess after OSCM HSG and the effect on thyroid function.

Methods: A prospective cohort study was conducted of 196 consecutive consenting eligible women without overt hypothyroidism or hyperthyroidism. All completed the study with compliance greater than 95%. Participants underwent OSCM HSG (Auckland, 2019–2021) with serial monitoring of thyrotropin (TSH), free thyroxine (FT4), and urine iodine concentration (UIC) for 24 weeks. The main outcome measure was the development of subclinical hypothyroidism (SCH), defined as a nonpregnant TSH greater than 4 mIU/L with normal FT4 (11–22 pmol/L) in those with normal baseline thyroid function.

Results: Iodine excess (UIC ≥ 300 μg/L) was almost universal (98%) with UIC peaking usually by 4 weeks. There was marked iodine excess, with 90% and 17% of participants having UIC greater than or equal to 1000 μg/L and greater than 10 000 μg/L, respectively. Iodine excess was prolonged with 67% having a UIC greater than or equal to 1000 μg/L for at least 3 months. SCH developed in 38%; the majority (96%) were mild (TSH 4–10 mIU/L) and most developed SCH by week 4 (75%). Three participants met the current treatment guidelines (TSH > 10 mIU/L). Thyroxine treatment of mild SCH tended to improve pregnancy success (P = .063). Hyperthyroidism (TSH < 0.3 mIU/L) occurred in 9 participants (5%).

Conclusion: OSCM HSG resulted in marked and prolonged iodine excess. SCH occurred frequently with late-onset hyperthyroidism occasionally. Regular thyroid function tests are required for 6 months following this procedure.


Although oil-soluble contrast medium (OSCM) hysterosalpingography (HSG) was used for the assessment of tubal patency for many decades, it had largely been superseded by the use of water-soluble contrast medium (WSCM) or other methods.[1,2] Recently, OSCM HSG has been shown to improve pregnancy rates in women with unexplained infertility, with reported live birth rates between 23.9% to 39.7%.[3–8] A recent large multicenter trial (H2Oil study) has confirmed the differential improvement in ongoing pregnancy rates with OSCM compared to WSCM (39.7% vs 29.1%).[4] While OSCM HSG is becoming a favored procedure in women with unexplained infertility, there is a need to establish its safety profile. The long history of OSCM use without major complications[9] provides a background for its safety and continued usage. However, concerns remain regarding the effect of iodine excess in women following OSCM exposure. The prototype OSCM used in HSGs, Lipiodol Ultra Fluide (Guerbet) has a high iodine content (480 000 μg/mL) and long half-life (50 days).[10] Ethiodol (Savage Laboratories), an OSCM previously used until 2010 in some countries, has an iodine content similar to Lipiodol.[11] This is in contrast to the lower iodine content (250–350 mg/mL)[8,12,13] and shorter half-life (2–3 days)[10] of WSCM.

Each milliliter of retained contrast following an OSCM HSG would equate to an iodine release of more than 1100 μg/day (upper threshold of iodine intake without notable adverse events)[14] for more than 150 days, based on its iodine content and half-life. Thus, it is important to understand the levels and timing of iodine excess, and their potential effects on thyroid function.

While earlier studies have been published focusing on iodine excess and thyroid function, these were small[15] or retrospective.[16,17] Thus, the aim of this study was to define the safety profile of OSCM HSG more accurately in the context of iodine excess, particularly its effects on thyroid function.