A randomized controlled trial on the impact of a specialized training program on anxiety and perceived pain in infertile women undergoing hysterosalpingography.

Hysterosalpingography (HSG) is a minimally invasive procedure that can be painful. This study aimed to examine the impact of a tailored training program on anxiety and perceived pain intensity in infertile women undergoing HSG. This research was a clinical trial involving 86 infertile women who were candidates for HSG and conducted at the radiology department of the Royan Infertility Center in Tehran, Iran, between November 22, 2021, to March 11, 2023.The participants were divided into two groups:43 women in the intervention group and 43 women in the control group. The randomization of the samples was carried out using a random number table. The women in the intervention group received two face-to-face group training sessions. Data were collected using valid questionnaires. Additionally, the heart rate and blood pressure of the participants were recorded. Data analysis showed the training intervention was significantly associated with reducing anxiety levels, perceived pain, systolic blood pressure, diastolic blood pressure, and heart rate in women undergoing HSG (p < 0.05). These findings support the use of structured training interventions to improve the overall experience and outcomes for patients undergoing HSG.Trial Registration Number: IRCT20150905023897N4.

Hysterosalpingography findings in infertile Sudanese women: a cross-sectional study on tube blockage.

Introduction: infertility is a significant public health concern in Africa and Hysterosalpingography (HSG) is an affordable option for initial treatment. This study aimed to provide information about the incidence of abnormal pathology and tubal findings in HSG of Sudanese women who experienced infertility. Methods: this prospective cross-sectional study included 100 infertile patients who were requested for HSG, including age, duration of infertility, body mass index (BMI), medical history, and HSG findings collected after performing the radiographic test, which was diagnosed by an experienced radiologist. Results: one hundred infertile women (46% and 54%) experienced primary and secondary infertility, respectively. Mean age was (31.1 ± 5.2, 27.5 ± 6.0) years, and BMI was (25.1 ± 3.3, 25.7 ± 2.9) Kg/cm2 for primary and secondary infertility respectively. Abnormal findings prevalence was (29/46, 63%) and (30/54, 56%). The incidence of fallopian tube abnormality was (52/100, 52% (25/46, 54.3%), and (27/56, 50%) for primary and secondary infertility, respectively. Forty-one percent of participants had normal hysterosalpingograms. Pelvic surgery was the highest risk factor in 24% of the participants. Age and medical history were significantly associated with the infertility type (P < 0.05). Conclusion: infertile patients who underwent hysterosalpingography (HSG) were predominantly older, with secondary infertility being slightly more common, underscoring the importance of early diagnostic evaluation and care. Fallopian tube abnormalities were the most common cause of infertility, with tube blockage affecting nearly half of the participants. Additionally, this study revealed that prior pelvic surgery significantly increased the risk of infertility.

Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

STUDY QUESTION: Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? SUMMARY ANSWER: Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. WHAT IS KNOWN ALREADY: HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. STUDY DESIGN, SIZE, DURATION: This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. MAIN RESULTS AND THE ROLE OF CHANCE: School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. LIMITATIONS, REASONS FOR CAUTION: The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. STUDY FUNDING/COMPETING INTEREST(S): The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER: NCT05168228.

The effect of prior hysterosalpingo-foam sonography or hysterosalpingography on tubal patency: a secondary analysis of a randomized controlled trial.

STUDY QUESTION: Does hysterosalpingo-foam sonography (HyFoSy) prior to hysterosalpingography (HSG) or HSG prior to HyFoSy affect visible tubal patency when compared HSG or HyFoSy alone? SUMMARY ANSWER: Undergoing either HyFoSy or HSG prior to tubal patency testing by the alternative method does not demonstrate a significant difference in visible tubal patency when compared to HyFoSy or HSG alone. WHAT IS KNOWN ALREADY: HyFoSy and HSG are two commonly used visual tubal patency tests with a high and comparable diagnostic accuracy for evaluating tubal patency. These tests may also improve fertility, although the underlying mechanism is still not fully understood. One of the hypotheses points to a dislodgment of mucus plugs that may have disrupted the patency of the Fallopian tubes. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of the randomized controlled FOAM study, in which women underwent tubal patency testing by HyFoSy and HSG, randomized for order of the procedure. Participants either had HyFoSy first and then HSG, or vice versa. Here, we evaluate the relative effectiveness of tubal patency testing by HyFoSy or HSG prior to the alternative tubal patency testing method on visible tubal patency, compared to each method alone. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women aged between 18 and 41 years scheduled for tubal patency testing were eligible for participating in the FOAM study. Women with anovulatory cycles, endometriosis, or with a partner with male infertility were excluded. To evaluate the effect HyFoSy on tubal patency, we relied on HSG results by comparing the proportion of women with bilateral tubal patency visible on HSG in those who underwent and who did not undergo HyFoSy prior to their HSG (HyFoSy prior to HSG versus HSG alone). To evaluate the effect of HSG on tubal patency, we relied on HyFoSy results by comparing the proportion of women with bilateral tubal patency visible on HyFoSy in those who underwent and who did not undergo HSG prior to their HyFoSy (HSG prior to HyFoSy versus HyFoSy alone). MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, we randomized 1160 women (576 underwent HyFoSy first followed by HSG, and 584 underwent HSG first followed by HyFoSy). Among the women randomized to HyFoSy prior to HSG, bilateral tubal patency was visible on HSG in 467/537 (87%) women, compared with 472/544 (87%) women who underwent HSG alone (risk difference 0.2%; 95% CI: -3.8% to 4.2%). Among the women randomized to HSG prior to HyFoSy, bilateral tubal patency was visible on HyFoSy in 394/471 (84%) women, compared with 428/486 (88%) women who underwent HyFoSy alone (risk difference -4.4%; 95% CI: -8.8% to 0.0%). LIMITATIONS, REASONS FOR CAUTION: The results of this secondary analysis should be interpreted as exploratory and cannot be regarded as definitive evidence. Furthermore, it has to be noted that pregnancy outcomes were not considered in this analysis. WIDER IMPLICATIONS OF THE FINDINGS: Tubal patency testing by either HyFoSy or HSG, prior to the alternative tubal patency testing method does not significantly affect visible tubal patency, when compared to alternative method alone. This suggests that both methods may have comparable abilities to dislodge mucus plugs in the Fallopian tubes. STUDY FUNDING/COMPETING INTEREST(S): The FOAM study was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, or interpretation of the data. H.R.V. reports consultancy fees from Ferring. M.v.W. received a travel grant from Oxford University Press in the role of Deputy Editor for Human Reproduction and participates in a Data Safety and Monitoring Board as an independent methodologist in obstetrics studies in which she has no other role. M.v.W. is coordinating editor of Cochrane Fertility and Gynaecology. B.W.J.M. received an investigator grant from NHMRC (GNT1176437) and research funding from Merck KGaA. B.W.J.M. reports consultancy for Organon and Merck KGaA, and travel support from Merck KGaA. B.W.J.M. reports holding stocks of ObsEva. V.M. received research grants from Guerbet, Merck and Ferring and travel and speaker fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

Effects of virtual reality and nature sounds on pain and anxiety during hysterosalpingography: a randomized controlled trial.

OBJECTIVE: The objective of this study was to determine the effects of listening to nature sounds alone and virtual reality plus listening to nature sounds on pain and anxiety in hysterosalpingography. METHODS: This three-arm parallel randomized controlled trial included 135 (45 in each group) women who underwent hysterosalpingography in Turkey. The virtual reality+nature sounds group viewed a nature video with virtual reality glasses and listened to nature sounds during hysterosalpingography, whereas the nature sounds group only listened to nature sounds. The control group received only routine care. RESULTS: During hysterosalpingography, women in virtual reality+nature sounds group experienced less pain than those in control group (p=0.009). After hysterosalpingography, pain levels were lower in both virtual reality+nature sounds group and nature sounds group than in control group (p=0.000 and p=0.000, respectively), anxiety levels were lower in virtual reality+nature sounds group than in nature sounds group and control group (p=0.018 and p=0.000, respectively), and anxiety levels were lower in nature sounds group than in control group (p=0.013). CONCLUSION: Virtual reality with nature content plus listening to nature sounds and only listening to nature sounds are effective in reducing pain and anxiety related to hysterosalpingography procedures in women. Compared with only listening to nature sounds, virtual reality plus listening to nature sounds further reduced hysterosalpingography-related pain and anxiety.

Diagnostic accuracy of hysterosalpingo-foam sonography for assessment of fallopian tube patency in infertile women.

RESEARCH QUESTION: What is the diagnostic accuracy of hysterosalpingo-foam sonography (HyFoSy), using two-dimensional ultrasound in tubal patency assessment in infertile women compared with laparoscopy with dye chromotubation? DESIGN: This prospective study was conducted at My Duc Hospital, Vietnam. Infertile women aged 18 years or older, who were scheduled for laparoscopy, were included. Visual Analogue Scale (VAS) score for perception of pain during HyFoSy was used. Laparoscopy was carried out on the same day. Clinicians undertaking laparoscopy were blinded to HyFoSy results. Sensitivity, specificity, negative and positive predictive value, and 95% confidence intervals were calculated. A sample size of 455 women (n = 910 fallopian tubes) was needed to demonstrate a fluctuation hypothesis, not exceeding 6%, for sensitivity and specificity (power 0.80, two-sided alpha 5%, loss to follow-up 5%). RESULTS: Between 2019 and 2022, 455 participants were recruited. Hysterosalpingo-foam sonography was unsuccessfully carried out in six participants. Two withdrew their consent. Data analysis was conducted on the remaining 447 participants (n = 868 fallopian tubes). The sensitivity and specificity of hysterosalpingo-foam sonography compared with laparoscopy were 0.75 (95% CI 0.71 to 0.79) and 0.70 (95% CI 0.65 to 0.74), respectively. Hysterosalpingo-foam sonography gave a positive predictive value of 0.76 (95% CI 0.73 to 0.80) and negative predictive value of 0.68 (95% CI 0.64 to 0.73). A total of 42.8% of women reported a VAS score of no pain. No adverse event was reported. CONCLUSION: Compared with laparoscopy with dye chromotubation, two-dimensional HyFoSy is a well-tolerated, reliable technique for assessing tubal patency.

Iodine and other factors associated with fertility outcome following oil-soluble contrast medium hysterosalpingography: a prospective cohort study.

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM). Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG. Setting: Auckland, New Zealand (2019-2021). Sample: 196 women with primary or secondary infertility who underwent OSCM HSG. Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented. Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]. Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.

No pain relief by virtual reality during hysterosalpingography (HSG): results from a randomized controlled trial.

STUDY QUESTION: Is virtual reality (VR) an effective non-pharmacological tool to reduce procedural pain during hysterosalpingography (HSG)? SUMMARY ANSWER: An HSG with VR does not reduce procedural pain scores compared to an HSG without VR. WHAT IS KNOWN ALREADY: An HSG is often experienced as painful and uncomfortable. VR has been proven successful to reduce acute procedural pain during a variety of medical procedures and interventions. STUDY DESIGN, SIZE, DURATION: We performed a two-centre open-label randomized controlled trial between January 2021 and October 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women scheduled for HSG as part of their infertility work-up were screened for participation. After informed consent, women were randomized between HSG with or without VR. Due to the nature of the intervention, the study was not blinded. VR was administered by a head-mounted device displaying nature movies and/or relaxation exercises. The primary endpoint was procedural pain measured using VAS (scale 0.0-10.0 cm). Procedural pain was divided into overall pain score and peak pain score during the procedure. It was measured immediately after HSG. Secondary endpoints included patient satisfaction, VR preferences, and adverse effects of VR. MAIN RESULTS AND THE ROLE OF CHANCE: We included a total of 134 women, 69 to the intervention group (HSG with VR) and 65 to the control group (HSG without VR). The mean VAS for peak pain was 6.80 cm (SD 2.25) in the intervention group versus 6.60 cm (SD 2.40) in the control group (mean difference 0.28 (95% CI -0.57, 1.12), P = 0.52). The mean VAS for overall pain was 5.00 cm (SD 2.10) in the intervention group versus 4.90 cm (SD 2.13) in the control group (mean difference 0.06 (95% CI -0.71, 0.84), P = 0.88). The expectation that VR would be a good distraction from pain during HSG was correlated with both overall and peak pain scores. When correcting for this expectation, we found that women in the intervention group reported significantly higher scores, both in peak (adjusted MD 0.58 (95% CI -0.81, 1.97), P = 0.021) and overall (adjusted MD 0.43 (95% CI -0.84, 1.71), P = 0.013) pain, compared to the control group. There were no differences in the prevalence of symptoms that were considered as adverse effects of VR. LIMITATIONS, REASONS FOR CAUTION: The study was not blinded. Reasons for declining participation in the study were anxiety or wanting full control during HSG, which might have created selection bias. The distraction score possibly indicates that the level of VR immersiveness was not optimal due to the lack of sound and/or the type of VR applications. Future studies should investigate whether more immersive or interactive VR applications could decrease procedural pain scores during HSG. WIDER IMPLICATIONS OF THE FINDINGS: Since VR does not reduce procedural pain, this additional tool should not be used during HSG. STUDY FUNDING/COMPETING INTEREST(S): There was no external funding for this study. KR and AvH report receiving a travel grant from Merck outside the scope of this study. BM is supported by a National Health and Medical Research Council (NHMRC) investigator grant (GNT1176437) and BM reports consultancy for Merck, Organon, and Norgine and travel and research funding from Merck. BM holds stock for ObsEva. CL reports receiving research grants from Merck, and Ferring. KD and VM report receiving travel and speaker's fees from Guerbet and research grants from Guerbet. VM also reports research grants from Merck and Ferring. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER: The trial is registered prospectively in the Netherlands Trial Register (trialregister.nl registration number NL9203, currently accessible on trialsearch.who.int). TRIAL REGISTRATION DATE: 16-01-2021. DATE OF FIRST PATIENT'S ENROLMENT: The first participant was enrolled on 19 January 2021.

Oil-soluble contrast medium bathing attenuated endometrial inflammation and improved endometrial receptivity in women with recurrent implantation failure: a descriptive study.

BACKGROUND: The oil-soluble contrast medium used in hysterosalpingography has been shown to have a fertility-enhancing effect, but the underlying mechanism is unclear, especially regarding the role of window of implantation (WOI). This study aimed to assess the endometrial immunological impact of the WOI before and after bathing with the oil-soluble contrast medium in women with recurrent implantation failure (RIF). METHODS: This descriptive study involved two medical centers between December 18, 2019, and December 30, 2020. We included infertile women who underwent three or more transfer cycles, cumulative transplantation of at least four high-quality cleavage-stage embryos or three high-quality blastocysts without clinical pregnancy, and high-quality frozen embryos that were still available for implantation. Patients received 5 ml of ethiodized poppyseed oil bathing, endometrial biopsy around bathing, and frozen-thawed embryo transfer (FET) within four menstrual cycles after bathing. Patients were excluded if failure to complete anyone. Data on the baseline characteristics and clinical data of the FET cycles were collected, and endometrial biopsy specimens were collected in the luteal phase before and after bathing and subjected to immunohistochemistry. The number of CD56 and CD138 positive cells and H-score of expression of ανß-3 and HOXA10 in endometrium were collected. RESULTS: Thirty-four patients were initially enrolled in the study; ultimately, twelve patients with a median age of 32.5 years (range 27-40 years) completed the research. The median number of embryo transfer cycles was three (range 3-8). A total of 4 of 12 women (33.33%) were diagnosed with chronic endometritis before oil-soluble contrast bathing. After bathing, the median numbers of CD138-positive cells in endometrium decreased from 0.75 (range 0-13.5) to 0.65 (range 0-6), P = 0.035; additionally, the H-score of expression of ανß-3 in endometrium increased from 148.50 ± 31.63 to 175.58 ± 31.83, P < 0.001. The thickness of the endometrium also significantly increased (8.90 ± 1.45 mm vs.10.11 ± 1.98 mm, P = 0.005). However, no consistent changes were found in the expression of CD56 and HOXA10 in the endometrium. Five patients experienced biochemical pregnancies (41.67%), four had clinical pregnancies (33.33%), and three achieved live births following oil-soluble contrast bathing (25%). CONCLUSIONS: These results suggest that oil-soluble contrast medium bathing decreased CD138-positive cells and upregulated expression of ανß-3 during WOI in patients with RIF. This histological impact of endometrium may result in enhanced fertility during FET cycles. Investigating the ability of intrauterine bathing with lower-dosage oil-soluble contrast to improve pregnancy in the RIF population is warranted.

Contrast media for hysterosalpingography: systematic search and review providing new guidelines by the Contrast Media Safety Committee of the European Society of Urogenital Radiology.

OBJECTIVES: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. METHODS: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. RESULTS: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. CONCLUSIONS: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. CLINICAL RELEVANCE STATEMENT: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. KEY POINTS: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient.

Hysterosalpingo-foam sonography versus hysterosalpingography during fertility work-up: an economic evaluation alongside a randomized controlled trial.

STUDY QUESTION: What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER: During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference -1.2%, 95% CI: -3.4% to 1.5%; P = 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1160 infertile women (18-41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies-management based on HyfoSy results versus HSG results-the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference -1.2%; 95% CI: -3.4% to 1.5%). For the procedures itself, HyFoSy cost €136 and HSG €280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were €3307 for the HyFoSy strategy and €3427 for the HSG strategy (mean difference €-119; 95% CI: €-125 to €-114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was €10 042, meaning that by using HyFoSy instead of HSG we would save €10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION: When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS: Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S): FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting-and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

[Pregnancy after intrauterine insemination following hysterosalpingo-foam-sonography or hysterosalpingography]. / Grossesse par insémination intra-utérine après hystérosalpingo-foam-sonographie ou hystérosalpingographie.

OBJECTIVE: To compare clinical pregnancy rates following intrauterine insemination performed after hysterosalpingography (HSG) or hysterosalpingo-foam-sonography (HyFoSy). MATERIAL AND METHODS: This is a retrospective study including 242 intrauterine insemination (IUI) performed between 2015 and 2020 at the fertility center of the Reunion Island. Among these inseminations, 121 with previous HSG and 121 with previous HyFoSy were matched. The main outcome of interest was clinical pregnancy rate. Secondary outcomes were birth rate and time to pregnancy after tubal patency test. RESULTS: The pregnancy rate after insemination was 9.9% for the HSG group and 11.6% for the HyFoSy group, with no statistically significant difference between the groups (P=0.66). The live birth rate was similar in the two groups (7.4% for HSG and 10.7% for HyFoSy; P=0.37). Over half (57.1%) of the pregnancies occurred within 6 months after HyFoSy, whereas only 8.3% after HSG. CONCLUSION: IUI results are not influenced by HyFoSy compared to HSG with regard to the pregnancy rates. Use of HyFoSy in infertility assessment allows global evaluation and more rapid adapted management. This approach could optimize management of patients undergoing IUI.

Effect of Acupoint Application of Chinese Medicine Combined with a Hot Compress on Pain of Uterine and Fallopian Tube Contrast Agent in Infertile Women.

Objective: To investigate the effects of combining traditional Chinese medicine acupoint sticking with sea salt hot compress on pain relief and promoting physical and mental comfort in infertile women undergoing Hysterosalpingo contrast sonography (HyCoSy). Methods: Infertile women admitted to Zhujiang Hospital of Southern Medical University from October 2021 to December 2022 were selected and 150 of them were selected by random number table method as the main subjects of the study and divided into three groups. The control group received psychological soothing and music therapy. The hot compress group received a sea salt package hot compress at temperatures of 50-65°C in addition to psychological and music soothing. The combined group received an acupoint application of traditional Chinese medicine along with the hot compress and psychological soothing. Pain levels, assessed using the Numeric Rating Scale (NRS), were recorded at different stages of the HyCoSy procedure: cervical dilatation (T0), balloon intubation (T1), contrast medium injection (T2), 10 minutes after examination (T3), 30 minutes after examination (T4), 24 hours after examination (T5), 48 hours after examination (T6), and 1 week after examination (T7).Stacey salpingography adverse reaction grading method: Adverse reactions were evaluated using the grading method for adverse reactions in salpingography designed by Stacey, and adverse reactions were classified into 0 to 4 levels. Stacey grading was used to evaluate pain severity, and adverse reactions of the vagus nerve, anxiety status, and test comfort were also compared among the three groups. Results: Statistically significant differences in NRS scores were observed among the three groups of patients at various stages of the HyCoSy procedure (T0-T5) (P = .001, P = .001, P = .001, P = .001, P = .012,). The combined group showed a higher proportion of grade 1-2 pain (96%) compared to the control group (83%) and the hot compress group (90%), while the proportion of grade 3 pain (4%) was lower than that in the control group (17%) and the hot compress group (10%) (P < .001). There were no significant differences in anxiety scores before and 1 week after examination (P= .273, P = 1.000, P = .779). The Kolcaba comfort scores were significantly higher in the combined group (67.54±7.58) and the hot compress group (65.02±8.12) compared to the control group (58.96±7.53) (P < .001,). No complications, scalds, or severe skin allergies were reported in any of the three groups during the one-week follow-up. Conclusions: The combination of acupoint application with hot compress during HyCoSy resulted in reduced pain levels and improved physical and mental comfort in infertile women. This simple and safe approach can be effectively utilized in clinical practice to enhance the patient experience during the procedure.

Value of painless transvaginal four-dimensional hysterosalpingo contrast sonography in reducing venous intravasation: a comparative study.

OBJECTIVE: To investigate the value of painless transvaginal four-dimensional hysterosalpingo contrast sonography (TV 4-D HyCoSy) in reducing venous intravasation and its influencing factors through a retrospective comparative study on conventional TV 4-D HyCoSy. MATERIALS AND METHODS: A total of 451 patients were enrolled in this study from Jan. 2019 to Oct. 2021. There were 249 patients in the painless TV 4-D HyCoSy group and 202 patients in the conventional TV 4-D HyCoSy group. The incidence of venous intravasation and its related influencing factors were analyzed and compared between these two groups. The difficulty of image evaluation for the diagnosis was also compared. RESULTS: There was no significant difference in the baseline characteristics between the painless group and the conventional group (p > 0.05). Compared with the conventional group, the painless group had a lower incidence of venous intravasation (16.9 vs. 24.8%; p = 0.039). Painless TV 4-D HyCoSy was more effective in reducing venous intravasation in patients with primary infertility (p = 0.032) without a history of pelvic surgery (p = 0.008) or ectopic pregnancy (p = 0.018). Logistic regression analysis demonstrated that painless TV 4-D HyCoSy and endometrial thickness > 5 mm were protective factors for venous intravasation. Moreover, the diagnostic procedure was easier in the painless group than in the conventional group (p = 0.002). CONCLUSIONS: Painless TV 4D-HyCoSy may be an effective mode in reducing the incidence of venous intravasation and improving the diagnosis of patency of fallopian tubes.

Contrast Agent Reflux in Transvaginal 4-D Hysterosalpingo-Contrast Sonography: Influencing Factors and Coping Strategies.

ABSTRACT: Transvaginal 4-D hysterosalpingo-contrast sonography (TV 4-D HyCoSy) plays an important role in the detection and diagnosis of clinical female infertility. The purposes of this study were to analyze the influencing factors of TV 4murD HyCoSy complicated with contrast agent reflux and to provide evidence for clinical diagnosis and treatment. Female patients diagnosed as infertility by transvaginal hysterosalpingography from January 2021 to December 2022 were included. The characteristics of patients with and without contrast agent reflux were evaluated. Pearson correlation and logistic regression were conducted to analyze the related factors affecting the occurrence of contrast reflux. A total of 416 patients undergoing TV 4-D HyCoSy were included, and the incidence of contrast agent reflux in patients undergoing TV 4-D HyCoSy was 38.94%. Pearson correlation analysis results indicated that history of uterine cavity operation ( r = 0.556), adenomyosis of uterus ( r = 0.584), examination on less than 5 days after menstruation ( r = 0.602), endometrial thickness ( r = 0.566), and endometrial polyps ( r = 0.575) are all correlated with contrast agent reflux in patients undergoing 4-D HyCoSy (all P < 0.05). Logistic regression analysis showed that history of uterine cavity operation (odds ratio [OR], 1.109; 95% confidence interval [CI], 1.012-1.872), adenomyosis of uterus (OR, 2.026; 95% CI, 1.864-2.425), examination on less than 5 days after menstruation (OR, 2.465; 95% CI, 2.118-2.851), endometrial thickness less than 6 mm (OR, 2.866; 95% CI, 2.095-2.957), and endometrial polyps (OR, 1.587; 95% CI, 1.137-1.744) were the influencing factors of contrast agent reflux in patients undergoing (all P < 0.05). The incidence of contrast agent reflux in TV 4-D HyCoSy is high, and there are many influencing factors. Clinical medical workers should take early measures based on these influencing factors to reduce the contrast agent reflux.

Hysterosalpingography: a step up for dose reduction.

AIM: To evaluate the efficiency of last image capture in interpreting a hysterosalpingogram (HSG) when compared to conventional spot views; to confirm its validity in showing pathology; to establish its use as the preferred method; and to decrease the radiation dose to the patient. MATERIALS AND METHODS: The study population consisted of women aged ≥18 years. A standard technique was performed including additional five last image capture after each spot view. Every patient had two stacks of images, one with the exposure film and one with the last image capture. The images were interpreted separately (high-dose versus low-dose) and blindly by two radiologists with different levels of training assessing for uterine abnormalities, fallopian tube abnormalities, peritoneal spillage, and incidental findings. Inter-reading variability was calculated using Kohen's kappa. RESULTS: Discrepancies between exposure film and last image capture were detected in only a minority of cases for all variables. Except for the presence of strictures, there was at least substantial agreement between the readers and almost perfect agreement regarding peritoneal spillage and fallopian tube patency, both on exposure film and last image capture. CONCLUSION: Reduction in radiation dose without compromising the diagnostic efficacy of HSG is mandatory. If the study is of sufficient quality and deemed negative on last image capture, conventional spot view can be avoided. If further detail is required, standard spot views can still be obtained. Using last image capture instead of spot films has the potential to reduce the overall radiation dose by up to 78%.

Infertility: Evaluation and Management.

Infertility is the inability to achieve a pregnancy after 12 months of regular, unprotected sexual intercourse. Evaluation and treatment are recommended earlier than 12 months when risk factors for infertility exist, if the female partner is 35 years or older, and in the setting of nonheterosexual partnerships. A comprehensive medical history and physical examination emphasizing the thyroid, breast, and pelvic areas should be performed to help direct diagnosis and treatment. Causes of infertility in females include uterine and tubal factors, ovarian reserve, ovulatory dysfunction, obesity, and hormone-related disorders. Common male factor infertility issues include abnormal semen, hormonal disorders, and genetic abnormalities. Semen analysis is recommended for the initial assessment of the male partner. Evaluation of the female should include assessment of the uterus and fallopian tubes with ultrasonography or hysterosalpingography when indicated. Laparoscopy, hysteroscopy, or magnetic resonance imaging may be needed to evaluate for endometriosis, leiomyomas, or evidence of a previous pelvic infection. Treatment with ovulation induction agents, intrauterine insemination, in vitro fertilization, donor sperm or eggs, or surgery may be necessary. Unexplained male and female infertility can be treated with intrauterine insemination or in vitro fertilization. Limiting alcohol intake, avoiding tobacco and illicit drug use, consuming a profertility diet, and losing weight (if obese) may improve pregnancy success rates.

Diagnostic accuracy of pelvis multiparametric MRI against CT virtual hysterosalpingography: a prospective study of tubal patency through female infertility assessment.

OBJECTIVE: To evaluate the diagnostic accuracy of MRI-hysterosalpingogram (HSG) with semiquantitative dynamic contrast-enhanced perfusion, against the virtual multislice CT hysterosalpingogram (VHSG) as a reference standard. METHODS AND MATERIALS: In this prospective study, 26 women (age >18 years) searching for infertility causes and with VHSG physician request. Thereafter, the assessment performance of both techniques was determined by two reader analyses. k statistics were used for the assessment of tubal patency. Receiver operating characteristic (ROC) analysis was used to compare the capability for tubal patency assessment between both exams on a per-patient and per-tube basis. The McNemar test was used to compare the diagnostic accuracy measures. RESULTS: Tubal patency, uterine morphological, ovarian, and extrauterine abnormalities were evaluated through both exams in all 26 women. There was no significant difference between diagnostic performance measurements between the methods. The ROC curve of VHSG was 0.852 for both per-patient and per-tube analyses, and one and 0.938 for MRI-HSG. Sensitivity and specificity for per-patient and per-tube for VHSG were 95.2 and 97.7, 80 and 87.5%, and for MRI-HSG 100% for both analyses and 100 and 87.5%, respectively. CONCLUSION: This study demonstrates the feasibility of diagnosing tubal patency through MRI, using a semi-quantitative dynamic contrast-enhanced perfusion sequence, and the satisfactory diagnosing of the uterine morphology, ovarian abnormalities, and ovarian and deep endometriosis. ADVANCES IN KNOWLEDGE: Multiparametric MRI with a perfusion real-time sequence as a HSG method can be used in the evaluation not only for uterine and ovarian abnormilities but also tubal patency.

Risk Factors of Contrast Agent Intravasation With Sulfur Hexafluoride Microbubble During Hysterosalpingo-Contrast Sonography.

OBJECTIVES: To analyze the risk factors of sulfur hexafluoride microbubble contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy), and to explore a simple prediction model by the obvious clinical history. METHODS: This was a retrospective study included 299 infertility women who had undergone HyCoSy examination from July 1, 2018 to June 31, 2019. The factors were recorded, including age, endometrial thickness, balloon length, infertility type, history of intrauterine surgery, history of pelvic surgery, and tubal patency. The method of multivariate logistic regression analysis was adopted to analyze the risk factors affecting the contrast agent intravasation, and the receiver operating characteristic curves were plotted to test their efficacy. RESULTS: Secondary infertility, a history of intrauterine surgery, thin endometrial thickness, and tubal obstruction were all risk factors of the occurrence of intravasation (P < .05). And the area under the receiver operating characteristic curves of the multifactor-combined prediction model of the intravasation was significantly larger than that of single-factor. CONCLUSIONS: Sonographers and gynecologists should be familiar with the risk factors of intravasation and select the appropriate timing of HyCoSy toward reducing the occurrence of intravasation and other complications after thoroughly explaining and communicating with the patients.