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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.Study Funding/competing Interest(s): This study received no funding. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (Academic Medical Center and VU University Medical Center) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and intrepretation of the data. I.R. reports receiving travel fee from Guerbet. C.B.L. reports speakers fee from Ferring in the past and research grants from Ferring, Merck and Guerbet. K.D. reports receiving travel fee and speakers fee from Guerbet. B.W.M. is supported by a 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. V.M. reports receiving travel fee and speakers fee as well as research grants from Guerbet. The other authors do not report conflicts of interest.Trial Registration Number: Netherlands Trial Register NTR 7526 (Neonates born after the H2Oil study), NTR 3270 (original H2Oil study), www.trialregister.nl. [ABSTRACT FROM AUTHOR]

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 Interests: 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., (© The Author(s) 2020. Published byOxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

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.