Lipiodol flushing under ultrasound guidance at time of hystero-salpingo contrast sonography (HyCoSy): A retrospective observational study.

BACKGROUND: Up to 30% of female infertility can be attributed to tubal abnormalities. Assessment of fallopian tube patency forms a component of the basic assessment of infertility. Tubal patency can be checked through hysterosalpingogram (HSG) under radiologic guidance with oil- or water-based contrast medium (OBCM or WBCM), or hystero-salpingo contrast sonography (HyCoSy) under ultrasound guidance with WBCM. Tubal flushing with OBCM has been shown to improve fertility rates. OBJECTIVES: To study the feasibility and tolerability of performing Lipiodol (ethiodised oil) flush concurrently with HyCoSy. To examine the in vivo sonographic visibility of Lipiodol vs normal saline. MATERIALS AND METHODS: Retrospective observational study of patients with subfertility referred for Lipiodol flushing under ultrasound guidance between August 2017-September 2020 at six private ultrasound practices in Sydney, Australia. RESULTS: There were 412 patients who were referred for Lipiodol flushing. Of these, 86 patients did not have concurrent Lipiodol flush at HyCoSy performed due to strict exclusion criteria. Of the 326 patients who proceeded with Lipiodol flushing at HyCoSy, all cases were successful, with no cases of extravasation. There were no major complications. In vivo sonographic visualisation of Lipiodol was similar to that of the commonly used agitated 0.9% saline (n = 20; mean visibility score 4.3 ± 0.9 vs 4.0 ± 1.2). CONCLUSION: Our study has shown that Lipiodol flushing at time of HyCoSy as a single procedure is feasible and tolerable to patients. Flushing with Lipioidol during HyCoSy is likely as sonographically visible as 0.9% saline.

A prospective self-controlled study on shortening the time before taking delayed radiographs with iodized oil hysterosalpingography.

OBJECTIVES: To verify the feasibility of walking to shorten the time before obtaining delayed radiographs after iodized oil hysterosalpingography (HSG). MATERIAL AND METHODS: One hundred women with infertility were selected for HSG from June 2018 to December 2018 at the Women's Hospital of Nanjing Medical University; the subjects were randomly divided into walking and control groups. The walking group was required to walk more than 12,000 steps within 6 hours after HSG, while the control group was prohibited from performing high-intensity exercise. The degree of pelvic adhesion was diagnosed with delayed radiographs acquired at 6 and 24 hours, and the diagnostic consistency of the radiographs at the two time points was evaluated. RESULTS: No significant difference was observed in the baseline data between groups (p > 0.05). The delayed radiograph results in the walking group showed good agreement (p = 0.255 > 0.05, Kappa value 0.781 > 0.75), while those in the control group showed general agreement (p = 0.002 < 0.05, Kappa value 0.493 > 0.40 < 0.75). CONCLUSIONS: The time for acquiring delayed radiographs can be shortened by instructing patients to walk after HSG. This method improves the diagnostic efficiency of Iodized oil, saves time and costs, and may contribute to the popularization of HSG for female infertility screening, while offering good clinical application prospects.

Lipiodol flush under ultrasound guidance in Australia.

BACKGROUND: Lipiodol tubal flushing is offered to select subfertile women primarily to confirm tubal patency and to increase pregnancy rates. AIMS: To investigate the safety of hystero-salpingo contrast sonography (HyCoSy) using Lipiodol flush (through frequency of adverse events and mean recalled pain score) and secondarily to quantify pregnancy rates. MATERIALS AND METHODS: Retrospective observational Phase 1 study of subfertile women in three centres across Australia between June 2017 and June 2019. Cases were identified from medical records, and women telephoned to assess adverse outcomes, procedure tolerability and confirm pregnancy outcomes within six months from procedure. RESULTS: A total of 325 cases were identified; 14 were excluded due to incomplete or abandoned procedure, 32 were lost to follow-up, leaving 279 for analysis. Fourteen women (5% overall) experienced mild vasovagal reactions, with one case of infection and no reports of anaphylaxis or allergy. There were 141 conceptions reported (51%) within six months after Lipiodol flush, and an ongoing pregnancy in 43% (119) of women. For women with ongoing pregnancies, 55% (78/119) conceived spontaneously, and 45% (63/119) via artificial reproductive technology. Mean recalled pain score was 5.7 (SD 3.2; range 0-10) at a single site. CONCLUSIONS: This Phase 1 study has indicated that Lipiodol flush using HyCoSy may be a safe and efficacious alternative to hysterosalpingography in the workup for infertility. The low adverse effect profile observed in this study coupled with a substantial ongoing pregnancy rate indicates that further investigation of Lipiodol under HyCoSy is warranted.

Lipiodol hysterosalpingogram: A modified HSG technique to minimize risks associated with lipiodol use.

Assessment of tubal patency and therapeutic tubal flushing using Lipiodol, an oil-soluble contrast media (OSCM), has been shown to enhance fertility, resulting in increased interest in the use of Lipiodol. A modified hysterosalpingogram (HSG) technique, including a supplementary ultrasound with the contrast in situ, is recommended when using Lipiodol, taking into account both safety issues and technical challenges specific to Lipiodol.

Ethiodized poppyseed oil versus ioversol for image quality and adverse events in hysterosalpingography: a prospective cohort study.

BACKGROUND: This study aimed to investigate the image quality and adverse events (AEs) of ethiodized poppyseed oil (EPO) compared with ioversol as contrast agents in hysterosalpingography (HSG). METHODS: Two hundred twenty-eight patients underwent HSG were consecutively recruited in this prospective cohort study, and were accordingly divided into EPO group (N = 165) and ioversol group (N = 63). The quality of image was assessed according to the European Guidelines on quality criteria for diagnostic radiographic images. AEs during, within 2 h and at 1-month post-HSG were recorded. RESULTS: EPO displayed elevated image quality compared with ioversol including the total image quality score (P < 0.001), the cervical canal display score (P < 0.001), shape and outline of uterus score (P < 0.01), cervical mucosa or folds score (P < 0.001), oviduct isthmus score (P < 0.001), ampulla and fimbriae of oviduct score (P < 0.001) and celiac diffuse image score (P < 0.001). Multivariate linear regression displayed that EPO (P < 0.001) was an independent predictive factor for increased total image quality score. AEs were similar between EPO group and ioversol group during and within 2 h post-HSG (all P > 0.05). However, at 1-month post-HSG, the number of patients had unchanged and faded menstrual blood color decreased but the proportion of patients with deepened menstrual color increased in EPO group compared with ioversol group (P = 0.007). In addition, the number of patients had iodine residue in uterine cavity was elevated in EPO group compared with ioversol group (P < 0.001). CONCLUSION: EPO is more efficient in image quality and equally tolerant compared to ioversol as contrast agents in HSG.

Oil-based or water-based contrast for hysterosalpingography in infertile women: a cost-effectiveness analysis of a randomized controlled trial.

OBJECTIVE: To determine the cost effectiveness of the use of oil-based versus water-based contrast in infertile women undergoing hysterosalpingography (HSG). DESIGN: Economic evaluation alongside a multicenter randomized trial. SETTING: Hospitals. PATIENT(S): Infertile women with an ovulatory cycle, 18-39 years of age, low risk of tubal pathology. INTERVENTION(S): Use of oil-based versus water-based contrast during HSG. MAIN OUTCOME MEASURE(S): Costs per additional ongoing pregnancy and per live birth within 6 months of randomization, incremental cost-effective ratios (ICERs). RESULT(S): A total of 1,119 women were randomized to HSG (oil-based contrast, n = 557; water-based contrast, n = 562). After HSG, most women had no additional treatment; a minority had IUI or IVF. In the oil group, 39.7% women had an ongoing pregnancy within 6 months of randomization versus 29.1% women in the water group. There was a 10.7% increase in the live birth rate in the oil group. For ongoing pregnancy, the mean costs per couple were US$2,014 in the oil group and US$1,144 in the water group, with a corresponding ICER of US$8,198 per additional ongoing pregnancy. For live birth, the mean costs per couple were US$11,532 in the oil group and US$8,310 in the water group, with a corresponding ICER of US$30,112 per additional live birth. CONCLUSION(S): Hysterosalpingography with oil-based contrast results in higher 6-month ongoing pregnancy and live birth rate. If society is willing to pay US$8,198 for an additional ongoing pregnancy, HSG with oil-based contrast is a cost-effective strategy compared with HSG with water-based contrast for infertile, ovulatory women at low risk for tubal pathology. CLINICAL TRIAL REGISTRATION NUMBER: Dutch Trial Register, NTR 6577 (www.trialregister.nl).

Thyroid Dysfunction in Neonates Born to Mothers Who Have Undergone Hysterosalpingography Involving an Oil-Soluble Iodinated Contrast Medium.

BACKGROUND/AIMS: Patients developing neonatal thyroid dysfunction following maternal hysterosalpingography (HSG) involving the use of oil-soluble iodinated contrast medium (ethiodized oil) have been reported. The present study aimed to investigate the frequency and risk factors for neonatal thyroid dysfunction following HSG. METHODS: We studied 212 infants born to mothers who had become pregnant after undergoing HSG involving the use of ethiodized oil. RESULTS: Five of the 212 infants tested positive during congenital hypothyroidism screening; this frequency (2.4%) was higher than the recall rate among first congenital hypothyroidism screening results (0.7%) in Tokyo, Japan. Two of the 5 screening-positive infants showed hypothyroidism, and 3 showed hyperthyrotropinemia. The urinary iodine concentrations in 4 out of the 5 screening-positive infants were 1,150, 940, 1,570, and 319 µg/l. The subjects were divided into thyroid dysfunction (n = 5) and normal thyroid function (n = 207) groups. The median dosage of ethiodized oil in the thyroid dysfunction group was significantly higher than in the normal thyroid function group (20 vs. 8 ml, p = 0.033). CONCLUSION: When infertile women undergo HSG, the dosage of oil-soluble iodinated contrast medium should be as low as possible to minimize the risk of fetal or neonatal thyroid dysfunction.

Changes in serum iodine concentration, urinary iodine excretion and thyroid function after hysterosalpingography using an oil-soluble iodinated contrast medium (lipiodol).

OBJECTIVE: Reports of hypothyroidism after hysterosalpingography (HSG) using lipiodol are emerging. The present study was designed to investigate the changes in serum iodine concentration (SIC), urinary iodine concentration/creatinine excretion (UI/Cr), and thyroid function before and after HSG using lipiodol. METHODS: The prospective observation study included 22 infertile euthyroid women with no previous history of thyroid disease. All underwent HSG between April 2007 and August 2008 at our institution. We examined SIC, UI/Cr, and thyroid function before HSG, and at 4, 8, 12, and 24 weeks, and 9-12 months after HSG. RESULTS: The median value of SIC and UI/Cr peaked at 4 weeks after HSG and remained at significantly high levels at 8, 12, and 24 weeks post-HSG compared with pre-HSG. In sync with the increase of iodine, the mean level of TSH significantly increased at 4, 8, 12, and 24 weeks post-HSG compared with pre-HSG. After 24 weeks, differences in SIC, UI/Cr, and TSH levels before and after HSG became nonsignificant. The mean value of free triiodothyronine and free thyroxine showed no significant difference at any of the time points compared with pre-HSG. Three cases (13.6%) showed transient high TSH (>5 µIU/L) with normal thyroid hormones at 4 or 8 weeks after HSG. CONCLUSION: Thyroid monitoring should be conducted in the first 4-8 weeks after HSG using lipiodol and attention to thyroid dysfunction should be paid for up to 6 months after the procedure due to the possibility of excess iodine.

Lidocaine-prilocaine cream as analgesia for hysterosalpingography: a randomized, double blinded, controlled study.

OBJECTIVE: The efficacy of lidocaine-prilocaine cream (EMLA(®)) analgesia in the practice of hysterosalpingography is controversial. This study provides new drill results and a new method of application in terms of mode, time and place. The aim of the paper is to investigate the efficacy of 5% lidocaine 25 mg-prilocaine 25 mg/g cream applied to the uterine cervix for reducing pain during hysterosalpingography. STUDY DESIGN: A randomized, double blinded, controlled study set in the general gynaecology clinic of a university teaching hospital between September 2012 and June 2013. One hundred successive patients programmed to undergo hysterosalpingography were randomized to either 3 ml of EMLA (50) cream or 3 ml of placebo (50), placed endocervically and exocervically, 10 min before hysterosalpingography. Patients' intensity of pain was assessed in four steps: at baseline (speculum application), after application of Pozzi tenaculum and cannula on the uterine cervix, during cervical traction and after contrast medium injection, using a 10-cm Visual Analogue Scale (VAS) immediately after the procedure. The most painful step was also identified. VAS was administered again at one-month follow-up visit. TRIAL REGISTRATION: NCT01303614. RESULTS: The contrast medium injection was the most painful step of hysterosalpingography in both groups (EMLA 3.96, placebo 4.54, 95%CI: -0.481 to 1.641). No differences were found between the two groups (P=0.281) during this step. When comparing the VAS scale after the application of Pozzi tenaculum and cannula (EMLA 1.06, placebo 3.34, 95%CI: 1.495-3.065) and after cervical traction (EMLA 2.54, placebo 3.46, 95%CI: 0.034-1.806), significantly less pain was experienced by the EMLA group than the placebo group: P=0.000 and P=0.042, respectively. CONCLUSION: Endocervical and exocervical topical application of EMLA 10 min before performing hysterosalpingography significantly reduced pain during cervical manipulation with tenaculum and cannula and during cervical traction, but did not reduce pain during injection of contrast that was the most painful step.

Oil-soluble contrast during hysterosalpingography in women with proven tubal patency.

To determine if there are therapeutic advantages to oil-soluble contrast medium compared with water-soluble medium during hysterosalpingography.A randomized, controlled trial including 56 infertile patients undergoing hysterosalpingography was performed. After a hysterosalpingogram with water-soluble contrast demonstrated tubal patency, 30 patients were randomized to receive oil-soluble contrast medium (oil group) and 26 patients received no additional contrast medium (control group). The outcome was pregnancy and timing of pregnancy in relation to hysterosalpingography. There were 18 (64%) pregnancies in the oil group and 14 (56%) pregnancies in the control group. Mean time to achieve pregnancy was shorter in the oil group: 3.8 months in the oil group compared with 6.1 months in the control group (P =.06) There was a clinically meaningful improvement in pregnancy rates between the oil group and the control group at 1 month postprocedure (relative risk [RR] 2.1, 95% confidence interval [CI] 0.6, 7.2). However, at 12 months postprocedure, the advantage was diminished. (RR 1.3, CI 0.8, 2.1)Eighteen months after hysterosalpingography, contrast does not appear to influence cumulative pregnancy rates; however, the addition of oil-soluble contrast medium to water-soluble contrast medium may have the potential to reduce the time to conception.

[Effect of contrast media used in hysterosalpingography (HSG) on phagocytosis of spermatozoa by peritoneal macrophages in female rats]. / Wpllw srodków kontrastujacych stosowanych w histerosalpinogografii (HSG) n fagocytoze pelmników przez makrofagi otrzewnowe samic szczurzych.

It is apparent from numerous communications that hysterosalpinogography (HSG), besides its diagnostic value, may also claim therapeutic activity. After such examinations, more frequent pregnancies were recorded in previously infertile women without resorting to supplementary treatment. Pregnancies were more numerous when applying oil-based contrast media than water-based contrast ones. Hypothesis has been put forward as to the possibility of modulating activity of these agents exerted upon the peritoneal and oviductal macrophages. Increased amount of these cells as well as excessive phagocytosis of spermatozoa was shown in case of endometriosis, one of the most frequent causes of infertility. It is supposed that excessive phagocytosis of spermatozoa by peritoneal macrophages (PM) may be the cause of infertility. Studies were performed to determine the effect of oil- and water-soluble contrast media, on sperm phagocytosis by PM in vitro. PM were obtained from Wistar female rats. Subsequently, the cells were centrifuged, washed and suspended in culture medium. Next 1 million PM were allowed to attach to the cover glass for one hour under standard conditions of incubation. Dilutions of 0.25%, 0.5%, 1.0% Lipiodol Ultra--Fluid (Byk Gulden Konstanz) and Uropolinum 60% (Polfa) were added to chambers with incubated PM for next one hour. The controls were cultured in the same conditions without contrast medium added. Sperm were isolated from the epididymal cauda of male rats and subsequently suspended in culture medium at a concentration 1 million/ml and added to equivalent volume of cultured macrophages for 1.5 hours. After the exposure time the cultures were washed and stained. The spermiophagic index (SPI) was determined. SPI = number of phagocytosed sperm cells/number of macrophages x 100. Statistical analysis was performed by means of Student t-test. Additional histochemical reactions were made and scanning as well as transmission electron microscopy studies were accomplished. The established results (Fig. 1-9) indicate that lipiodol inhibits phagocytosis of spermatozoa by PM stronger (1% lipodol SPI = 1.99 + 0.94 < 0.0001) than uropolinum (1% uropolinum SPI = 5.07 +/- 1.02 p < 0.0001). In control studies, without contrast medium added, SPI was equal to 14.66 +/- 3.12 (p < 0.00001). Marked inhibition involving phagocytosis of spermatozoa was detected already after the treatment with lipiodol in low concentration (0.25% lipiodol SPI = 3.73 +/- 0.89 p < 0.0001). It failed to be so distinct after treating macrophages with uropolinum in low concentration (0.25% uropolinum SPI = 8.34 +/- 1.50 p < 0.0001). Scanning electron microscopy studies have disclosed that in the cultures of macrophages with spermatozoa, the macrophages spread well over the glass bottom. The macrophages' cytoplasmic membrane was highly folded with numerous protrusions different in size and shape. They covered the digested parts of spermatozoon causing its fragmentation. In cultures of macrophages with spermatozoa and 1% uropolinum, the structure of macrophages was similar to that in the control group. Accumulations and conglomerations of a large number of macrophages with spermatozoa were additionally revealed. In cultures of macrophages with spermatozoa and 1% lipiodol, the macrophages were not spread, but rather spherical. Also the cytoplasmic membrane protrusions were small, short, fine and appeared in smaller number. Occasionally areas of smooth cytoplasmic membrane without any folds were seen. Such macrophages did not phagocytose sperm. Transmission electron microscopy studies of macrophages cultured with sperm have disclosed that the macrophages' cytoplasmic membrane was highly folded with numerous protrusions different in size and shape. The latter encircled and closed parts of sperm (head, midpiece or tail) inside inside endosomes, finally linking the latter with lysosomes. The ultrastructure of macrophages cultured with spermatozoa and 1% uropolinum was s

A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result?

OBJECTIVE: To evaluate the therapeutic effect of oil-soluble contrast media compared with water-soluble contrast media after hysterosalpingography (HSG) in infertile couples. DESIGN: Meta-analysis of four randomized clinical trials (RCTs) and six nonrandomized controlled studies evaluating pregnancy rates after the use of oil- or water-soluble contrast media during HSG. SETTING: Institute of Epidemiology and Health Services Research, Leeds, United Kingdom. PATIENTS: Four identified RCTs studied 800 patients and six nonrandomized studies comprised an additional 1,806 patients, all experiencing primary or secondary infertility. INTERVENTION: Hysterosalpingography as part of infertility investigation. MAIN OUTCOME MEASURE: Pregnancy rates after HSG. RESULTS: Pregnancy rates were significantly higher in the oil-soluble contrast media group compared with the water-soluble contrast media group in the RCTs. Inclusion of the six nonrandomized studies did not alter this conclusion. This apparent benefit was greatest for patients with unexplained infertility. CONCLUSIONS: Oil-soluble contrast media have a therapeutic effect compared with water-soluble media and this effect is greatest for patients who have been diagnosed as having unexplained infertility. New techniques for the evaluation of tubal patency support the hypothesis that tubal "plugs" may be involved in proximal tubal blockage.

[Hysterosalpingography using iotrolan--a new contrast medium]. / Hysterosalpingographie mit Iotrolan--Ein neues Kontrastmittel.

Iotrolan was investigated as a new contrast medium for hysterosalpingography. Fertility rates and side-effects were registered in a series of 108 consecutive patients. The results indicate a higher fertility rate after hysterosalpingography with iotrolan than after the use of other water-soluble contrast media but a lower fertility rate when compared to lipiodol. As for side-effects, the study indicates that the frequencies of low abdominal pain and vaginal bleeding after hysterosalpingography are equal for iotrolan and lipiodol but higher for other, water-soluble contrast media. A prospective, randomized study is recommended for the clarification of these aspects.

Pregnancy rates after the use of oil-based and water-based contrast media to evaluate tubal patency.

Hysterosalpingography (HSG) has assumed a diagnostic and possibly therapeutic role in the evaluation of the infertile couple. The procedure is done using either an oil-based (OBCM) or a water-based (WBCM) contrast medium. Data from several retrospective studies suggest that higher pregnancy rates may be achieved when OBCM is used. Interpretation of these results, however, may be confounded by various methodologic flaws in study design and comparisons of heterogeneous populations. We sought to compare the therapeutic benefit of OBCM and WBCM in a prospective randomized study of infertile patients, controlling for pelvic anatomy by laparoscopic assessment. We used ethiodized oil (Ethiodol) or iothalamate meglumine (Conray 60) for tubal lavage at the time of laparoscopy only in patients with normal pelvic anatomy. Of the 225 patients who had diagnostic laparoscopy in the evaluation of infertility, 40 (18%) had normal pelvic anatomy and an otherwise unremarkable evaluation. Adequate follow-up was available on 29 patients randomized to receive either OBCM (n = 15) or WBCM (n = 14). A significant difference in pregnancy rates was noted between OBCM (40%) and WBCM (14%) by chi-square analysis. No short- or long-term adverse reactions were noted. Results of this study suggest that in patients with normal pelvic anatomy as assessed laparoscopically, OBCM may offer a therapeutic benefit not evident with WBCM.

[Evaluation of hysterography in the diagnosis of choriocarcinoma and invasive mole].

From 1963 through 1985, 181 hysterography were performed for 101 patients. The diagnostic accuracy of hysterography was 92.3%. There were no false positive findings, though a negative result may be obtained in patients whose intramural lesion does not communicate with the uterine cavity, as proved by operative findings. Three types of abnormalities were observed on the hysterogram: (1) filling defect, (2) intramural invasion of the uterine wall by the contrast medium and (3) extravasation of the contrast medium into the pelvic veins. The filling defect was usually observed in patients with (1) residual molar tissue in the uterine cavity, (2) intramural lesion and (3) intrauterine adhesions. The above three conditions can be differentiated by the characteristic shape of the filling defect. If it is used in combination with either or both of the other two procedures, ie., B-ultrasound and pelvic arteriography the accuracy of diagnosis will be further improved.

Oil or aqueous contrast media for hysterosalpingography: a prospective, randomized, clinical study.

In this prospective randomized clinical study the pregnancy rate and the quality of the images obtained by hysterosalpingography (HSG) in 175 women with fertility problems have been compared using an oil-soluble contrast medium and an aqueous contrast medium. After the HSG there was a follow-up period of 6 months. No statistically significant difference in pregnancy rate was found. With both contrast media good images were obtained. The oil-soluble contrast medium gave a more sharply outlined uterine cavity, the aqueous contrast medium showed more tubal details. Furthermore, the control picture with the aqueous contrast medium can be prepared after ten minutes. We conclude that the use of an aqueous contrast medium for routine HSG is preferable.