Background: The H2Oil study demonstrated that in women with unexplained infertility, tubal flushing during hysterosalpingography (HSG) with oil-based contrast resulted in an increased ongoing pregnancy rate of 10% compared to using water-based contrast. It remains unclear if the fertility-enhancing effect of oil-based contrast extends to women with other factors contributing to infertility. Methods: The H2Oil2 study was an open-label, randomised controlled trial, conducted in 11 centres across The Netherlands, China and The United Kingdom (trial registration: CTIS 2024-512571-12-00). Infertile women with an indication to undergo HSG were eligible if they were aged ≥39 years and/or had an ovulation disorder, and/or were at high risk for tubal pathology. After informed consent, women were randomly allocated to HSG with oil-based contrast or with water-based contrast. The primary outcome measure was pregnancy within 6 months after randomisation, leading to live birth. Our analysis followed the intention-to-treat principle. Findings: Between August 2019 and June 2024, 932 women were randomly allocated to HSG with oil-based contrast (n=469) or HSG with water-based contrast (n=463). In the oil-group, 108 women had a live birth, compared to 98 women in the water-group (23·5% vs. 21·5%; adjusted HR 1·18, 95% CI 0·89 to 1·57 p=0·26). Thyroid dysfunction occurred in 75 out of 299 women in the oil-group and in 7 out of 292 women in the water-group (25·1% vs. 2·4%, RR 10·64, % CI 4·96-22·8, p<0·001). Interpretation: In women aged ≥39 years and/or with ovulation disorders, and/or at high risk for tubal pathology, tubal flushing with oil-based contrast does not increase live birth rates compared to tubal flushing with water-based contrast.

Does oil-based contrast hysterosalpingography lead to higher pregnancy rates compared to water-based contrast hysterosalpingography in infertile women with age or ovarian or tubal contributory factors? In infertile women with age or ovarian or tubal contributory factors, hysterosalpingography with oil-based or water-based contrast did not result in different ongoing pregnancy rates. The H2Oil study demonstrated that in women with unexplained infertility, tubal flushing during hysterosalpingography (HSG) with oil-based contrast (OBCM) resulted in more ongoing pregnancies than HSG with water-based contrast (WBCM) (39.7% vs 29.1%; rate ratio 1.37; 95% confidence interval [CI], 1.16 to 1.61) (Dreyer at al., 2017). This fertility enhancing effect has been confirmed in a regular meta-analysis, a network meta-analysis and a recent Cochrane review. However, to date, evidence regarding the potential fertility enhancing effect of HSG with OBCM in women aged over 39 years, or with ovulation disorders or at high risk for tubal pathology is lacking. The H2Oil2 study is an international, multicentre, randomised controlled trial, which took place in the Netherlands, China and the UK between July 2019 and December 2024. In total, 11 hospitals participated in this study. We studied infertile women, aged above 39 years and/or with ovulation disorders and/or at high risk for tubal pathology undergoing HSG during fertility work-up. Participants were randomly allocated to HSG with OBCM or WBCM. The follow-up period was six months and primary endpoint was conception leading to live birth. Since all data on live births is not yet available, this abstract reports on ongoing pregnancy rates. Outcomes were analysed according to the intention-to-treat principle. Between August 2019 and June 2024, we randomised 932 patients (of which 490 in the Netherlands, 353 in China and 72 in the UK), of whom 459 were allocated to OBCM and 456 to WBCM. Median age was 33.4 (interquartile range [IQR]:30.0-37.8) years, median duration of infertility was 21.0 (IQR:16.0, 30.0) months and 46.8% (n = 427) of the women had primary infertility. Baseline characteristics were comparable between the groups. HSG showed bilateral tubal pathology in 48 (10.5%) of the women randomised for OBCM versus 53 (11.6%) of the women randomised for WBCM. Ongoing pregnancy rates in the first six months following randomisation were 24.2% in the intervention (OBCM) versus 21.5% in the control group (WBCM) (RR:1.13, 95% CI: 0.89-1.43). Similar non-significant findings were observed when comparing HSG with OBCM to WBCM. across the three subgroups: women of advanced age (≥39 years) (10.6% vs. 9.8%; RR: 1.08, 95% CI: 0.54–2.15), women with oligo- or anovulation (32.7% vs. 29.7%; RR: 1.10, 95% CI: 0.78-1.55), and women at high risk for tubal pathology (23.5% vs. 21.0%; RR: 1.12, 95% CI: 0.81–1.55). Presented results are based on ongoing pregnancy, as some participants are still pregnant. Complete follow-up on live birth rates will be available at the ESHRE 2025 meeting. This RCT shows that for women of advanced age, with ovulation disorders, or at high risk for tubal pathology, tubal flushing with OBCM does not increase pregnancy rates compared to tubal flushing with WBCM. HSG with OBCM as a therapeutic procedure should only be offered to women with unexplained subfertility. Yes

Abstract Study question Is tubal flushing with ethiodized oil during transvaginal hydrolaparoscopy (THL) feasible and what is the live birth rate within 6 months after THL? Summary answer Additional flushing with ethiodized oil during THL is feasible and safe with a live birth rate of 32.0% compared to 23.4% using solely water-based-contrast (p = 0.25). What is known already The use of ethiodized oil during hysterosalpingography (HSG), an alternative method to test tubal patency, has shown to have a positive effect on the live birth rate, compared to the use of water-based contrast (methylene blue). The benefit of THL over HSG as a tubal testing method is the possibility to also explore tubo-ovarian structures and the pouch of Douglas. Currently, only water-based media are used for tubal flushing during THL. Study design, size, duration A single-center cohort study at Máxima MC, the Netherlands, including 50 subfertile women who underwent THL and in whom there was at least unilateral tubal patency for methylene blue. Outcomes of interest included feasibility, safety and 6- months live birth rate. Our data were compared with a historical cohort of 111 subfertile women who underwent THL using solely water-based contrast (van Kessel MA. et al., 2021). Univariate – and multivariate logistic regression analysis were performed. Participants/materials, setting, methods Women with an iodine allergy and/or manifest thyroid dysfunction were excluded. Participants received additional tubal flushing with ethiodized oil (Lipiodol® Ultra Fluid). Main outcomes were appearance of oil and cell/mucus debris at the tubal fimbriae, pain scores (Visual Analogue Scale, VAS) and acceptability scores (0-10, completely unacceptable-acceptable). Secondary outcomes included; amount of ethiodized oil used, thyroid function four weeks afterwards, adverse events and live birth rate within 6 months after THL. Main results and the role of chance In 48 of the 50 THL procedures there was bilateral patency to methylene blue, ethiodized oil appeared from the tubal fimbriae bilateral in 77% (37/48), unilateral in 17% (8/48), while it did not appear in 6% (3/48). In two procedures there was unilateral patency to methylene blue. Ethiodized oil appeared unilateral in one and did not appear during the other THL. The amount of ethiodized oil used was 5 mL [3.4–6.3). The median reported pain scores on the VAS were 2.9 [IQR 1.0–5.0] after flushing with methylene blue and 3.0 [IQR 1.0–5.0] after ethiodized oil. The acceptability of the procedure was rated as 10 out of 10 [IQR 8–10]. Four weeks after the procedure 14% (6/42) had developed subclinical hypothyroidism, one woman had overt hypothyroidism (FT4 slightly decreased to 11.0 pmol/L, TSH 5.60 mU/L) and one woman had isolated hypothyroxinemia (FT4 11.0 pmol/L, TSH 3.40 mU/L). One adverse event, persistent bleeding at the trocar insertion site was reported, for which a diagnostic laparoscopy was performed. The live birth rate within 6 months after a THL was 32% (16/50), compared to 23% (26/111) in our historical cohort using solely water-based contrast (OR = 1.54, 95% CI 0.74–3.22, P = 0.25). Limitations, reasons for caution As this is a pilot study without a power analysis, the study is presumably underpowered to show an effect on the live birth rate. Also, the control group was historical. Wider implications of the findings By proving feasibility of using ethiodized oil during THL we encourage further research on its effect on pregnancy rates. Furthermore, the direct observation of tubal flushing with ethiodized oil during THL enables further investigation of the contrast characteristics, which are presumably responsible for its positive effect on live birth rate. Trial registration number NL8696

In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90

Objective: Oocyte retrieval is a painful, but essential element of IVF/ICSI. Evidence for the best method of analgesia is lacking. In the Netherlands, the three most common analgesia protocols entail administration of oral analgesics, intravenous opioids, and intramuscular opioids. The aim of this study was to compare these methods. Methods: A retrospective cohort study was conducted at three clinics. Clinic one provided oral analgesics (1000 mg paracetamol and 500 mg naproxen). The main component of analgesia at clinic two was opioids intravenously (50-100 mu g fentanyl), and at clinic three, this was opioids intramuscularly (0.01 mg/kg alfentanil). Intraprocedural pain was registered on an 11-point scale. Univariate analyses were performed to identify factors significantly associated with pain scores. A mixed linear model was used to uncover mean pain scores per clinic. Results: In total, 2,127 oocyte retrievals were included. Pain scores were lower in older women; scores decreased 0.06 points per year (95%-confidence interval (CI): 0.04-0.08). Per extra follicle, scores were 0.05 points higher (95%-CI: 0.03-0.06). Endometriosis resulted in 0.45-point higher scores (95%-CI: 0.01-0.88). Primary subfertility resulted in a 0.36-point increase in scores (95%-CI: 0.15-0.56). Nulliparous women had a 0.41-point higher score than multiparous women (95%-CI: 0.19-0.63). These effects were mostly similar in all clinics. Mean pain scores were 5.6 at clinic number 1 (95%-CI: 5.3-5.8), 5.1 at clinic number 2 (95%-CI: 4.9-5.3), and 3.9 at clinic number 3 (95%-CI: 3.8-4.1). Conclusion: The lowest pain scores were achieved in the clinic that used intramuscular administration of alfentanil, followed by intravenous fentanyl and, finally, non-sedative oral analgesics. Significant correlations between patient characteristics and pain scores were identified. (c) 2022 Elsevier Masson SAS. All rights reserved.

Background: Oil-based contrast has been shown to have a fertility-enhancing effect during hysterosalpingography (HSG) but is not yet used during transvaginal hydro laparoscopy (THL). Objective: To asses if additional tubal flushing with oil-based contrast during THL is feasible. Materials and methods: Case report with video assessment. A healthy 29-year-old woman with primary unexplained subfertility, underwent a THL under local anaesthesia. First, chromopertubation was performed by methylene blue. Afterwards, tubal flushing with 3mL oil-based contrast (Lipiodol® UltraFluid, Guerbet) was performed. Main outcome measures: In this case report we evaluated the feasibility of additional tubal flushing with oil- based contrast during THL, in terms of; the visibility of the oil-based contrast at the tubal fimbriae, the pain and acceptability scores. Results: Both fallopian tubes were patent to methylene-blue as well as to oil-based contrast. Interestingly, the oil-based contrast came out of the fallopian tube in the form of free droplets with strong internal bonding. Furthermore, some residue of the droplets was visible on the surface of the peritoneal wall in the form of oily micro-droplets. Conclusions: We present the first sub-fertile woman, in which additional tubal flushing with oil-based contrast during THL was performed. It is likely, that the residue of oily micro-droplets is also present inside the fallopian tube, where it may enhance the cilia movement by introducing lubrication. These lubricating characteristics of the oil-based contrast may be important for its fertility-enhancing effect. More research is necessary to confirm this hypothesis and the feasibility of tubal flushing with oil-based contrast during THL in more women.

Hysterosalpingographies (HSGs) have formed an essential part of the fertility workup for more than a century. More recently, tubal flushing, especially with oil-based contrast, has been shown to significantly improve the natural conception rates. Critically, the mechanism of this fertility-enhancing effect during tubal flushing is still unclear. This article postulates hypotheses, based on published and own research, on the potential mechanisms and root cause of tubal flushing fertility enhancement. Possible explanations for the increased fertility rates, especially with oil-based contrast, are divided into the biochemical and interfacial effects derived from the contrast properties. The biochemical effects may include the immunological response of the endometrium or peritoneum, the impact on the endometrial opioid receptors or the iodine content. The interfacial effects may include improvement of interfacial factors due to the lubricant effect or dislodgement of mucus debris within the Fallopian tubes. Impact StatementWhat is already known on this subject? Tubal flushing during hysterosalpingographies (HSGs) increases natural conception rates, and using oil-based over water-based contrast increases that effect even further. However, the underlying mechanism of the observed fertility-enhancing effect is still poorly understood.What do the results of this study add? This article postulates different hypotheses on the potential mechanisms and root cause of the fertility enhancement from tubal flushing.What are the implications of these findings for clinical practice and/or further research? We suggest additional research on the different hypotheses, intending to determine which subfertile women will benefit most from tubal flushing using oil-based contrast and at which stage of their subfertility. Furthermore, we suggest research on administering tubal flushing with oil-based contrast, besides in HSG.

To clarify the mechanism by which Cd initiates rat testicular cancer, the ability of Cd or H2O2 to induce DNA single strand breakage was evaluated in testicular Leydig cells using a simple and rapid DNA precipitation method. Effects of Cd, Fe, Zn and Ca on the oxidant-induced DNA damage and effects of reduced glutathione (GSH) on the genotoxicity caused by the peroxide and/or Fe were also assessed. H2O2 induced strong DNA single strand breakage. Cd alone did not exhibit such a genotoxicity nor did it enhance the peroxide-induced DNA damage. Ca and Fe(II) potentiated the oxidant-induced DNA single strand breakage, while Zn partially protected cells from the oxidative damage of DNA caused by the peroxide. GSH attenuated single strand breaks of DNA brought about by H2O2 and/or Fe. These results suggest that the initiation of carcinogenesis in the rat testis by Cd is triggered by active oxygen species such as H2O2, which is generated by the metal exposure, rather than by a direct genotoxicity of Cd. The oxidant-mediated initiation is clearly a complicated event accomplished by multiple factors.

Recent meta-analyses have shown that a hysterosalpingography (HSG) with oil-based contrast increases pregnancy rates in subfertile women. However, the frequency of complications during or after an HSG with oil-based contrast in subfertile women and/or their offspring is still unclear. This systematic review and meta-analysis, without restrictions on language, publication date or study design, was performed to fill this knowledge gap. The results show that the most frequently reported complication was intravasation of contrast, which occurred in 2.7% with the use of oil-based contrast (31 cohort studies and randomized controlled trials [RCT], 95% CI 1.7-3.8, absolute event rate 664/19,339), compared with 2.0% with the use of water-based contrast (8 cohort studies and RCT, 95% CI 1.2-3.0, absolute event rate 18/1006). In the cohort studies and RCT there were 18 women with an oil embolism (18/19,339 HSG), all without serious lasting consequences. Four cases with serious consequences of an oil embolism were described (retinal oil embolism [n = 1] and cerebral complaints [n = 3]); these reports did not describe the use of adequate fluoroscopy guidance during HSG. In conclusion, the most frequently reported complication after an HSG with oil-based contrast is intravasation occurring in 2.7%. In total four cases with serious consequences of oil embolisms in subfertile women were published.

Sir, The recently published article reporting results of a survey on complications after hysterosalpingography (HSG) with oil-soluble contrast media (OSCM) versus water-soluble contrast media (WSCM) found an intravasation rate of 4.8% with OSCM and 1.3% with WSCM (Roest et al., 2020). This result is consistent with meta-analysis (Wang et al., 2019) and our local experience of an intravasation rate of 4.2% in 769 OSCM (Lipiodol) HSG patients (Peart et al., 2019). However, intravasation is more readily detected when using OSCM and the apparently lower rate of intravasation of WSCM is likely attributable to a lower rate of detection. While the factors predisposing to intravasation remain unclear, there is generally considered to be an increased risk of intravasation in patients with a history of recent uterine interventions, in the early follicular and late luteal phase, with tubal obstruction or with the use of high injection pressures. Other possible predisposing factors, including menometrorrhagia, secondary infertility, endometriosis and Mullerian anomalies are also cited (Dusak et al., 2013). These factors would not be expected to differ between patients undergoing an HSG with OSCM or WSCM, and the intravasation rate is expected to be independent of the contrast agent used. The most commonly used OSCM is Lipiodol, which has an iodine concentration of 480 mg/ml compared with 300–350 mg/ml for commonly used WSCM, representing a 35–60% greater iodine concentration in OSCM. This results in greater opacity of OSCM compared with WSCM, with enhanced visibility of small amounts of contrast (Lindequist et al., 1991). In addition, the viscosity of Lipiodol is at least 2.5 times that of WSCM (Lindequist et al., 1991) and transit of any Lipiodol in small vessels is likely to be slower than that of WSCM. Thus, intravasation of WSCM is less readily detected than intravasation of OSCM, due to the physical and chemical properties of OSCM. It is undisputed that the rates of detected intravasation of OSCM are greater than detected intravasation of WSCM. However, it is important to distinguish between rates of detected intravasation and rates of actual intravasation, with the latter being more difficult to detect. It is not clear whether the true intravasation rates for OSCM and WSCM differ significantly and the reported rates of intravasation do not support the quoted conclusion that the risk of intravasation is higher with the use of OSCM compared with WSCM. The risk of oil embolism as a result of intravasation of OSCM is a reasonable concern, and a belief that intravasation is more common with the use of OSCM may discourage the uptake of OSCM HSG for tubal flushing and assessment of tubal patency, despite the associated fertility enhancement (Dreyer et al., 2017; Wang et al., 2019). Importantly, there have been no sequelae of intravasation of OSCM reported in the recent literature, likely due to the ready detection of early myometrial intravasation on fluoroscopy and prompt termination of the procedure (Roest et al., 2020). Rather than being a cause for concern, the higher rate of detection of intravasation of OSCM is reassuring and reflects early detection of intravasation, with a reduced likelihood of oil embolism or other complication of intravasation.

Abstract STUDY QUESTION What is the incidence of complications after hysterosalpingography (HSG) using oil-based contrast versus water-based contrast? SUMMARY ANSWER Among 5165 women undergoing HSG, the most frequently reported complication after HSG with oil- and water-based contrast was intravasation of contrast medium (4.8% versus 1.3%, respectively), which was without further consequences, and pulmonary embolization or death did not occur. WHAT IS KNOWN ALREADY An HSG with oil-based contrast increases pregnancy rates in women with unexplained infertility. However, there have been some concerns regarding complications, including the risks of intravasation of the contrast medium, oil embolism and infection. Here, we present the incidence of complications after HSG with different types of contrast media used in the Netherlands in the year 2017. STUDY DESIGN, SIZE, DURATION In January 2018, an electronic survey was sent to all 73 clinics in the Netherlands that perform HSG. The survey consisted of 12 questions addressing the number of HSGs performed in 2017, the amount and type of contrast medium used, the occurrence of post-procedural complications and what their clinical consequences were. Non-responding clinics were sent multiple reminders. PARTICIPANTS/MATERIALS, SETTING, METHODS We calculated the incidence of the complications and reported on their clinical consequences. Furthermore, we examined the average amount of contrast used as well as the administration of prophylactic antibiotics. MAIN RESULTS AND THE ROLE OF CHANCE The response rate was 96% (67/70) (during the study, one site closed and was not included while two clinics no longer performed HSGs). In the 67 clinics, 3289 HSGs with oil-based contrast and 1876 HSGs with water-based contrast were performed in 2017. The median amount of contrast used was 8.0 ml (interquartile range (IQR) 7.0–10.0) for oil-based contrast and 10.0 ml for water-based contrast (IQR 10.0–10.0). Antibiotic prophylaxis was administered in 61% (41/67) of the clinics. Intravasation occurred in 4.8% of the HSGs performed with oil-based contrast and in 1.3% of the HSGs with water-based contrast (relative risk (RR), 3.6; CI, 2.4–5.4). Pulmonary embolism or death was not reported. Pelvic inflammatory disease (PID) occurred in 0.3% of the HSGs performed with oil-based contrast versus 0.4% with water-based contrast. PID occurred in 0.3% of the HSGs in clinics using antibiotic prophylaxis and 0.2% in clinics not using antibiotic prophylaxis. Allergic reactions were reported in one HSG performed with oil-based contrast (0.03%) compared with two HSGs performed with water-based contrast (0.1%). Anaphylactic reactions did not occur. The overall complication rate was 5.1% in the clinics that used oil-based contrast versus 1.8% in the clinics that used water-based contrast (RR, 2.8; CI, 1.9–4.0; P-value, <0.0001). LIMITATIONS, REASONS FOR CAUTION Half of the clinics did not routinely register complications, and the incidence of the complications in their clinic was based on the recall of the clinician. Estimated complication rates in the clinics with and without systematic registration did not significantly differ. The survey asked about the frequency of intravasation but no classification system is being used in daily practice, which may create differences in reporting. There was no standard screening of post-HSG thyroid function for the mother and the foetus. WIDER IMPLICATIONS OF THE FINDINGS In this nationwide cohort study, the complication rates after HSG were low. Intravasation occurred more frequently with the use of oil-based contrast compared with water-based contrast but did not lead to any problems or symptoms in any of the women. We therefore conclude that safety concerns should not be a reason to deny the use of oil-based contrast in women with unexplained infertility. The data also support that fluoroscopy appears to be an essential safety measure during HSG. STUDY FUNDING/COMPETING INTEREST(S) This work was partly funded by Guerbet, France. I.R. reports receiving travel fee for presenting at the Congress of the American Society for Reproductive Medicine 2019 from Guerbet. V.M. reports receiving travel and speaker’s fee as well as research grants from Guerbet. K.D. reports receiving travel and speaker’s fee from Guerbet. B.W.M. is supported by an National Health and Medical Research Council (NHMRC) Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER N19.056.

OBJECTIVE:Which analgesia methods are used during oocyte retrieval in the Netherlands? STUDYDESIGN:In April 2017, an online survey containing questions on the analgesia protocol used for IVF/ICSI oocyte retrieval was sent to all clinics in the Netherlands that perform oocyte retrievals. RESULTS:The response rate was 97%. We uncovered the large variety of medication protocols used for pain relief during oocyte retrieval in the Netherlands. Based on the main component of the given analgesia, we distinguished the three most frequently used analgesia protocols: intravenously (i.v.) administered opioids, intramuscularly (i.m) administered opioids, and non-sedative oral analgesics. Aside from analgesia, 61% provided anxiolysis with a benzodiazepine. Nearly half of the clinics registered pain scores. The vital functions were monitored at all clinics administering opioids i.v., but at none of the clinics administering opioids i.m. CONCLUSIONS:A wide variety of analgesia protocols are used. The three most frequently used are i.v. administered opioids, i.m. administered opioids, and non-sedative oral analgesics. The variety of analgesia protocols is not desirable in the context of good clinical practice, and considering the risks of combining opioids and benzodiazepines. Monitoring of vital functions was only performed after administration of i.v. medication. A comparison of the pain scores could be a first step in finding the optimal method of analgesia, thereby forming the basis of guidelines for analgesia during oocyte retrieval.

STUDY QUESTION: Does exposure to preconceptional hysterosalpingography (HSG) with iodinated oil-based contrast affect neonatal thyroid function as compared to iodinated water-based contrast? SUMMARY ANSWER: Preconceptional HSG with iodinated contrast did not influence the neonatal thyroid function. WHAT IS KNOWN ALREADY: HSG is a commonly applied tubal patency test during fertility work-up in which either oil- or water-based contrast is used. Oil-based contrast contains more iodine compared to water-based contrast. A previous study in an East Asian population found an increased risk of congenital hypothyroidism (CH) in neonates whose mothers were exposed to high amounts of oil-based contrast during HSG. STUDY DESIGN, SIZE, DURATION: This is a retrospective data analysis of the H2Oil study, a randomized controlled trial (RCT) comparing HSG with the use of oil- versus water-based contrast during fertility work-up. After an HSG with oil-based contrast, 214 women had an ongoing pregnancy within 6 months leading to a live birth compared to 155 women after HSG with water-based contrast. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 369 women who had a live born infant, 208 consented to be approached for future research and 138 provided informed consent to collect data on the thyroid function tests of their offspring (n = 140). Thyroid function tests of these children were retrieved from the Dutch neonatal screening program, which includes the assessment of total thyroxine (T4) in all newborns, followed by thyroid-stimulating hormone only in those with a T4 level of <= -0.8 SD score. Furthermore, amount of contrast medium used and time between HSG and conception were compared between the two study groups. MAIN RESULTS AND THE ROLE OF CHANCE: Data were collected from 140 neonates conceived after HSG with oil-based (n = 76) or water-based (n = 64) contrast. The median T4 concentration was 87.0 nmol/l [76.0-96.0] in the oil group and 90.0 nmol/l [78.0-106.0] in the water group (P = 0.13). None of the neonates had a positive screening result for CH. The median amount of contrast medium used was 9.0 ml [interquartile range (IQR), 6.0-11.8] in the oil-group and 10.0 ml [IQR, 7.5-14.0] in the water group (P = 0.43). No influence of the amount of contrast on the effect of contrast group on T4 concentrations was found (P-value for interaction, 0.37). LIMITATIONS, REASONS FOR CAUTION: A relatively small sample size and possible attrition at follow-up are limitations of this study. Although our results suggest that the use of iodinated contrast media for HSG is safe for the offspring, the impact of a decrease in maternal thyroid function on offspring neurodevelopment could not be excluded, as data on maternal thyroid function after HSG and during conception were lacking. WIDER IMPLICATIONS OF THE FINDINGS: As HSG with oil-based contrast does not affect thyroid function of the offspring, there is no reason to withhold this contrast to infertile women undergoing HSG. Future studies should investigate whether HSG with iodinated contrast influences the periconceptional maternal thyroid function and, consequently, offspring neurodevelopment.