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.

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.

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.

Diagnostic Approaches in Nuclear Medicine for Reproductive Health Assessment: Hysterosalpingography in Radiology versus hysterosalpingoscintigraphy.

Background: Infertility is a significant aspect of reproductive health and evaluating degree of tubal pathology is essential for determining appropriate management plans. Aims and Objectives: To assess the role of hysterosalpingoscintigraphy (HSSG) as a tubal patency test in nuclear medicine and compare it with hysterosalpingography (HSG) in radiology in infertile women and study pain perception in both tests as well. Materials and Methods: A prospective study was conducted on 50 infertility patients undergoing infertility evaluation at a tertiary care hospital. Both HSG and HSSG procedures were performed during proliferative phase of menstrual cycle. Results: Our study demonstrated the potential of HSSG as a tool for evaluating tubal patency in infertility workup. It showed good accuracy in detecting tubal patency compared to HSG. Conclusion: HSG is a radiological procedure valued for its ability to provide detailed anatomical information of uterus and patency of fallopian tubes. In contrast, HSSG provides dynamic information on the functional aspects of the reproductive system using nuclear medicine techniques. Both HSG and HSSG are vital tools in the diagnostic armamentarium for assessing female reproductive health, offering complementary information that aids in comprehensive patient management.

Hysterosalpingographic Findings Among Ghanaian Women with Infertility: A Five-year Trend Analysis.

Objectives: To understand the pattern of hysterosalpingographic (HSG) findings and annual trends among Ghanaian women with infertility over a five-year period. Methods: We retrospectively evaluated the hospital medical records of women with infertility who underwent HSG at a major tertiary center in Ghana between January 2018 and December 2022. The data was statistically analyzed. Results: The subjects comprised of 2324 Ghanaian women diagnosed with clinical infertility. HSG identified 1685 (72.5%) with primary infertility and they were also younger women with a mean age of 32.2±4.5 years. The remaining 639 (27.5%) women had secondary infertility and were older (34.2±5.3 years; p < 0.001). Primary infertility rate decreased with increasing age (p < 0.001). Bilateral tubal blockage was seen in 701 (41.6%) women with primary infertility and 365 (57.1%) women with secondary infertility. Hydrosalpinx was present in 236 (10.2%) women, fimbrial adhesions in 444 (19.1%), Asherman's syndrome in four (0.2%), and bilateral beaded tubes/tubercular salpingitis in five (0.2%). HSG was unable to detect infertility-related abnormalities in 513 (22.1%) women despite their clinical infertility. The majority of patients (1502; 64.6%) had tubal blockage: bilateral in 1066 (45.9%) and unilateral in 436 (18.8%). Conclusions: Infertility rates among Ghanaian women increased at an accelerating rate over the years. Primary infertility was significantly more prevalent among younger women. Tubal and cervical abnormalities were the most prevalent HSG findings.

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.

Severe Pain and Postoperative Effects during Hysterosalpingography: A Meta-Analysis.

Background: We aimed to evaluate the impact of pain on patients during Hysterosalpingography (HSG). Methods: PubMed, PMC and other journals were searched for randomized controlled trials (RCTS) on HSG. Appropriate articles were selected for inclusion and reasonable exclusion according to keywords. Following a thorough review of the relevant literature, the process of literature screening was conducted in accordance with the aforementioned criteria. The methodological quality of the studies was assessed using the risk of bias assessment tool developed by the Cochrane Collaboration. Meta-analysis was conducted using RevMan 5.4.1 software. Results: Twelve studies were included, including 1530 cases in the experimental group and 1545 cases in the control group. The literature summarizes the basic information of patients during HSG and makes statistics on the differences in visual analog scale (VAS) and pain perception. The findings from the HSG examination revealed a lack of significant association between patients' pain sensation and their age and BMI. However, the duration of pregnancy in patients decreased following HSG treatment (95%CI (-18.84 to -3.58), P=0.004).Compared with conventional testing, HSG could effectively reduce the pregnancy time of patients (95%CI (-18.84, -3.58), P=0.004), reduce the VAS of patients (95%CI (-4.73, -1.51), P=0.0001), and increase the number of patients without pain (95%CI (1.80, 10.43), P=0.001). Conclusion: During the HSG examination, acceptable pain avoidance is generated and can be relieved over time. At present, there is no effective alternative method, so the patient should cooperate with the doctor to complete the examination, to relieve the pain.

Diagnostic accuracy of transvaginal ultrasonography and hysterosalpingography in the detection of uterine cavity pathologies among infertile women.

Background: Uterine cavity pathology may affect the endometrium or myometrium, resulting in distortion of the uterine cavity, and is responsible for 2%-5% of infertility. The methods for its assessment usually involve imaging modalities like pelvic ultrasonography, often transvaginal-(TVS), and hysterosalpingography-(HSG), with hysteroscopy-(HSC) as the gold standard. However, HSC is not readily available in resource-poor-settings. Purpose: To determine and compare the diagnostic accuracy of TVS and HSG in detecting uterine cavity pathology using HSC as a gold standard. Materials and Methods: A cross-sectional analytical study of consenting infertile women for evaluation of the uterine cavity using transvaginal-ultrasonography, hysterosalpingogram, and hysteroscopy. The primary-outcome-measures were the sensitivity, specificity, and accuracy of TVS and HSG in detecting uterine cavity abnormalities using HSG as the gold standard. Results: Eighty-eight participants were analysed for this study. The lesions confirmed on HSC were intrauterine-adhesions (43.1%), endometrial polyps (14.8%), submucous fibroids (18.2%), intrauterine-septum (13.6%), and cavity distortion (14.8%). The overall sensitivity with TVS was 57.7%, with a specificity of 97.6%, a positive-predictive-value (PPV) of 88.2%, and a negative-predictive-value (NPV) of 88.2%, giving a percentage-accuracy of 88.2%. In comparison, HSG had a sensitivity of 72.1%, a specificity of 99.4%, a PPV of 97.4%, and an NPV of 92.0%, giving an overall accuracy of 92.9%. The detection rates of TVS and HSG in this category were: fibroids (97.7% vs 89.8%; p = .0004) and adhesions (73.9% vs 87.5%; p = .0002), respectively. Conclusion: HSG appears to be the superior modality for detection of obliterative uterine cavity pathologies, while TVS is better suited for myometrium and endometrial lesions.

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.

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.

Effect of radiation on serum anti-Müllerian hormone during hysterosalpingography in female infertility.

RESEARCH QUESTION: Does radiation exposure during hysterosalpingography (HSG) negatively affect serum anti-Müllerian hormone (AMH) levels in infertile women? DESIGN: Prospective cohort study conducted at Songklanagarind Hospital, Thailand, between April 2021 and May 2023. Thirty-two infertile women and 34 control participants were enrolled. Serum AMH levels were assessed in the infertile group at baseline before the HSG procedure and at 1 and 3 months after the procedure. Control participants, who self-reported no medical conditions, underwent the same AMH level assessments. Changes in serum AMH levels were compared. RESULTS: Infertile women had a mean age of 32.4 ± 3.8 years, body mass index of 21.2 ± 2.0 kg/m2 and baseline mean AMH level of 3.66 ng/ml (95% CI 3.00 to 4.32), which did not significantly differ from the control group. One month after HSG, mean AMH level significantly declined (0.33 ng/ml, 95% CI -0.65 to -0.01; P = 0.045) in the infertile group. The change in serum AMH levels between baseline and 1 month was significantly different in the HSG group compared with controls (-0.33 ng/ml, 95% CI -0.65 to -0.01 versus 0.36 ng/ml, 95% CI 0.06 to 0.67; P = 0.002). Changes in serum AMH levels from baseline to 3 months did not differ between the two groups. CONCLUSIONS: One month after the HSG, infertile women experienced a significant decrease in serum AMH levels compared with controls. The change in serum AMH levels between baseline and 3 months after HSG did not significantly differ from that of the control group.

Outpatient hysteroscopy impact on subsequent assisted reproductive technology: a systematic review and meta-analysis in patients with normal transvaginal sonography or hysterosalpingography images.

BACKGROUND: Standard management for intrauterine lesions typically involves initial imaging followed by operative hysteroscopy for suspicious findings. However, the efficacy of routine outpatient hysteroscopy in women undergoing assisted reproductive technology (ART) remains uncertain due to a lack of decisive high-quality evidence. This study aimed to determine whether outpatient hysteroscopy is beneficial for infertile women who have unremarkable imaging results prior to undergoing ART. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines, incorporating data up to May 31, 2023, from databases such as PubMed, Embase, and the Cochrane Library. The primary outcome assessed was the live birth rate, with secondary outcomes including chemical pregnancy, clinical pregnancy rates, and miscarriage rates. Statistical analysis involved calculating risk ratios with 95% confidence intervals and assessing heterogeneity with the I2 statistic. RESULTS: The analysis included ten randomized control trials. Receiving outpatient hysteroscopy before undergoing ART was associated with increased live birth (RR 1.22, 95% CI 1.03-1.45, I2 61%) and clinical pregnancy rate (RR 1.27 95% CI 1.10-1.47, I2 53%). Miscarriage rates did not differ significantly (RR 1.25, CI 0.90-1.76, I2 50%). Subgroup analyses did not show a significant difference in clinical pregnancy rates when comparing normal versus abnormal hysteroscopic findings (RR 1.01, CI 0.78-1.32, I2 38%). We analyzed data using both intention-to-treat and per-protocol approaches, and our findings were consistent across both analytical methods. CONCLUSIONS: Office hysteroscopy may enhance live birth and clinical pregnancy rates in infertile women undergoing ART, even when previous imaging studies show no apparent intrauterine lesions. Treating lesions not detected by imaging may improve ART outcomes. The most commonly missed lesions are endometrial polyps, submucosal fibroids and endometritis, which are all known to affect ART success rates. The findings suggested that hysteroscopy, given its diagnostic accuracy and patient tolerability, should be considered in the management of infertility. DATABASE REGISTRATION: The study was registered in the International Prospective Register of Systemic Review database (CRD42023476403).

Successful pregnancy outcome via in-vitro fertilization and laparoscopic resection of non-communicating rudimentary horn pregnancy containing early pregnancy: a case report.

BACKGROUND: Non-communicating rudimentary horn pregnancy (NCRHP) lead to life-threatening condition for both mother and fetus. Early diagnosis of NCRHP and laparoscopic resection is important to prevent catastrophic conditions. However, delayed diagnosis until the second or third trimester makes it difficult to accurately diagnose between NCRHP and bicornuate uterine pregnancy, as both conditions present uterine rupture and massive hemoperitoneum. Furthermore, these rare cases are challenging in pregnancy trials and associated with adverse outcomes in subsequent pregnancies. CASE PRESENTATION: A 31-year-old gravida 1 para 0 Korean woman visited our infertility center with a confirmed positive urine pregnancy test after timed intercourse. Before she was scheduled to have timed intercourse, a unicornuate uterus with a non-communicating right uterine horn was suspected based on an ultrasound scan and hysterosalpingography during the initial infertility workup. A gestational sac was observed in the right non-communicating rudimentary horn at 5 weeks of gestation. Serum beta-human chorionic gonadotropin (b-hCG) level was 2052.0mIU/mL. An elective laparoscopic resection of the right rudimentary horn containing a gestational sac, along with ipsilateral salpingectomy, was performed with no adverse event. After 3-month of recovery period and three cycles of conceptional trials involving timed intercourse and intrauterine insemination, in-vitro fertilization (IVF) was performed using the antagonist protocol, and successful pregnancy was confirmed. The patient had been hospitalized from 21 + 6 weeks to 35 + 6 weeks of gestation, underwent cerclage placement and tocolytics with corticosteroid treatment. She delivered an early-term male baby by cesarean section. CONCLUSION: In this rare case, the successful pregnancy achieved through IVF following the appropriate management of NCRHP under laparoscopy underscores the critical importance of early diagnosis and intervention in cases of NCRHP. Timely identification and management of NCRHP are vital to prevent the occurrence of catastrophic conditions and to enhance the prognosis of a successful pregnancy through assisted reproductive technology (ART). Therefore, a high index of suspicion for NCRHP is important and employs a range of diagnostic modalities.

A Prospective Study to Evaluate the Role of Combined Diagnostic Laparoscopy and Hysteroscopy in the Management of Female Infertility.

Introduction Infertility affects approximately 10-15% of couples worldwide. Hysteroscopy and laparoscopy are two newer modalities available for the evaluation of infertility and are complementary rather than mutually exclusive. Each provides useful information that the other may not have and each has its advantages. Materials and methods A total of 75 patients of female infertility (study group) in the age group of 18-40 years from the Outpatient Department (OPD) were recruited. Infertility was defined as one year of unprotected intercourse without pregnancy. Hysteroscopy and laparoscopy were carried out in each patient at the follicular phase of the menstrual cycle. Hysteroscopic findings were compared with laparoscopic findings for uterine and tubal pathology. Hysteroscopy as a procedure was also compared with laparoscopy as a one-step procedure for diagnostic accuracy in investigating a case of female infertility. The data was analyzed by Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 29.0, Armonk, NY). Observations and results In our study, out of a total of 75 cases evaluated for infertility, primary infertility patients were 48 (64%) and secondary infertility patients were 27 (36%). In our study, both tubes were patent on chromopertubation in primary infertility (PI) vs secondary infertility (SI) in 49.33% vs 21.33% of total cases. Both tubes were blocked in PI vs SI in 9.33% vs 8% of total cases. In our study, 20 patients (26.66%) underwent hysteroscopic intervention. Adhesiolysis was the commonest procedure required in seven (9.33%) followed by hysteroscopic cannulation in six (8%). In our study, a total of 30 procedures were performed in 20 patients during laparoscopy. The most common procedure required was ovarian drilling in 22.66% (17/75) followed by surgery for endometriosis in 10.66% (8/75). Adhesiolysis was required in 5/75 (6.66%). Both laparoscopy and hysteroscopy were normal in 44/75 cases for uterine findings. Conclusion Thus, hysterolaparoscopy as "one step" had various advantages in our study, more accuracy in the findings and therapeutic intervention in the same sitting reducing the cost. The addition of hysteroscopy to laparoscopy is invaluable in the infertility workup as it has a definite edge in the detection of uterine pathology, as well as being therapeutic at the same time. More accuracy in the diagnostic findings and therapeutic intervention in the same setting will help in reducing the time and cost of treatment.

Assessment of contrast intravasation in patients investigated by fluoroscopic hysterosalpingograms: A two-year retrospective audit in Western Australia.

INTRODUCTION: Intravasation on hysterosalpingogram (HSG) is defined by the flow of injected contrast from the uterine cavity into adjacent myometrial vessels. Evidence suggests intravasation can result in consequences such as pulmonary and cerebral embolisms. However, adverse events are poorly reported across published studies. Reported intravasation ranges from 0.0% to 13%, with higher rates attributed to oil-soluble contrast medium (OSCM) use. Recent reviews of OSCM's fertility-enhancing benefits have prompted rapid clinical uptake by fertility specialists worldwide. This instigates increased concern for intravasation and its associated sequelae. We aim to assess the prevalence of intravasation in fluoroscopic HSGs and its reporting in Western Australia (WA). METHODS: A two-year retrospective analysis of all fluoroscopic HSGs in one public teaching hospital within WA was conducted. All HSGs were retrieved from the public radiology information system and a blinded method was utilised to verify the presence and grading of intravasation in captured HSG images. Grading of intravasation was attributed by anatomical spread: 1 to myometrium, 2 to parametrium and 3 to para-iliac vessels. Results were subsequently compared with reported intravasation to assess for discrepancies. RESULTS: Of 308 successful HSGs, an intravasation rate of 7.1% was identified. Of these cases, 45% were reported and 32% were graded. Majority (73%) of intravasation events were classified as grade 1, with 9.0% and 18% of cases classified as grade 2 and 3, respectively. CONCLUSION: Under-reporting of intravasation emphasises a need for increased vigilance of radiologists. Standardised classification can provide interpretational consistency and should be considered to improve safety in future practice.

Sequential-contingent strategy for fallopian tube evaluation using hysterosalpingo foam sonography: a cost analysis.

Background: Tubal pathology is the etiological factor in 20% of couples with female infertility. Historically, diagnostic evaluation of the fallopian tubes has been performed by means of hysterosalpingography (HSG). Hysterosonosalpingography with EXEM® foam is a recent technique with supposedly comparable effectiveness to HSG, but with better tolerability for patients. Methods: Tubal patency was assessed in patients who were candidates for intrauterine insemination (IUI) between January 2020 and July 2021. (I) Hysterosonosalpingography with EXEM® foam. (II) If the patient had both tubes patent, IUI was proposed. In case of inconclusive or pathological results, HSG was performed. (III) If the HSG concludes tubal patency, IUI is proposed. On the other hand, if it results in tubal obstruction, in vitro fertilization (IVF) is proposed. Results: Assessment of tubal patency by HSG showed concordance with previous Hysterosonosalpingography with EXEM® foam results in 45.5% (n=15) of cases of unilateral obstruction and 66.7% (n=6) of cases of bilateral obstruction. When we compare the total cost of HSG (€54,899.46) with the sum of patients who only required Hysterosonosalpingography with EXEM® foam together with those who underwent both tests (€45,575.96), it shows that the latter represents a cost benefit strategy (cost difference €9,323.50). Conclusions: Our results suggest a benefit of €9,323.50 when performing the contingent sequential strategy, in case of pathological or inconclusive results, compared to performing a systematic HSG in all patients. Patients with an obstructive hysterosalpingogram with EXEM® and a patent hysterosalpingogram will be the subgroup that will benefit the most, as IUI can be proposed instead of IVF. In addition, there is a benefit in terms of optimizing the medical procedure, hospital visits and speeding up the time to start assisted reproductive technology (ART).

Fertility and anatomical outcomes following hysteroscopic adhesiolysis: An 11-year retrospective cohort study to validate a new classification system for intrauterine adhesions (Urman-Vitale Classification System).

OBJECTIVE: To propose a new classification system (Urman-Vitale Classification System) for intrauterine adhesions (IUAs) and to evaluate anatomical and fertility outcomes after hysteroscopic adhesiolysis accordingly. METHODS: A retrospective analysis of consecutive patients treated over 11 years by a single operator in a tertiary care hospital. Women with sonographic suspicion of IUAs were scheduled for hysterosalpingography (HSG) and hysteroscopy for confirmation and treatment. IUAs were divided into five classes according to symptoms, ultrasound, HSG findings, and postsurgical hysteroscopic appearance. Hysteroscopic adhesiolysis was performed using a bipolar cutting electrode in an office setting. Evaluated outcomes were restoration of the uterine cavity, clinical pregnancy, pregnancy loss, and live birth rates. RESULTS: A total of 227 patients (479 procedures) were included. Mean number of hysteroscopies increased in frequency with class of adhesions from Class 1 to Class 5 (1.0 ± 0.2 vs 2.3 ± 0.5; P = 0.001). Full restoration of the cavity was achieved in 100% of patients with Class 1 compared with 18.5% for Class 5 (43/43 vs 5/27; P = 0.001). Clinical pregnancy (Class 1 vs Class 4: P = 0.034; 1 vs 5: P = 0.006; 2 vs 5: P = 0.024) and live birth (Class 1 vs Class 4: P = 0.001; 1 vs 5: P = 0.006; 2 vs 4: P = 0.007; 2 vs 5: P = 0.0208) rates decreased with increasing severity of IUAs. Pregnancy loss rate was related to IUA severity (Class 1 vs Class 4: P = 0.012; 1 vs 5: P = 0.003: 2 vs 4: P = 0.014; 2 vs 5: P = 0.021). CONCLUSION: A classification based on symptoms, imaging findings, and postsurgical macroscopic appearance of the uterine cavity could be useful in predicting prognosis and fertility in women with IUAs.

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

SUMMARY 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.

Utility of Repeat Uterine Cavity Evaluation in the Infertility Workup.

Background: Uterine cavity abnormalities contribute to infertility. The purpose of this study was to evaluate the incidence, recurrence rates, and risk factors for uterine cavity abnormalities in women undergoing infertility workup and treatment, focusing on the utility of routinely repeated imaging. Methods: Retrospective cohort study at single academic medical center of 833 infertile women who had uterine cavity evaluations performed at least 9 months apart. Results: Of 833 eligible patients, 664 (79.7%) had normal initial imaging and 169 (20.3%) had abnormal initial imaging. Among the former, 10% had abnormal uterine cavity on repeat saline infusion sonohysterography (SIS); among the latter, 32% had abnormal repeat SIS [Chi-square p < 0.0001, risk ratio 2.30 (95% confidence interval 1.85-2.86)]. On average, 23.1 ± 13.6 months passed between studies. Regardless of initial imaging findings, women with abnormal repeat SIS were older than those with normal repeat SIS, with no difference in time elapsed between studies. There were no associations between repeat imaging outcomes and body mass index, uterine instrumentation, number of treatment cycles, or maximum peak estradiol levels in a single cycle between studies. There was no difference in live birth rate among cycles started within 1 year after repeat SIS across groups. Conclusions: Uterine cavity abnormalities were found in 10% of patients on repeat imaging despite initially normal testing. No risk factors for cavity abnormality on repeat imaging were identified besides age and prior abnormality. It would be prudent to continue performing routine repeat uterine cavity evaluation for women undergoing fertility treatment, particularly if corrective measures had been taken in the past.