Background Establishing the subgroup analysis of the fallopian tubes (tubes) is a commonly undertaken diagnostic investigation for women with subfertility. This is usually achieved by flushing contrast medium through the tubes and visualising patency on radiographs, ultrasonography or laparoscopy. Many women were noted to conceive in the first three to six months after tubal flushing, raising the possibility that tubal flushing could also be a treatment for infertility. There has been debate about which contrast medium should be used (water-soluble or oil-soluble media) as this may influence pregnancy rates. An important adverse event during tubal flushing is intravasation (backflow of contrast medium into the blood or lymphatic vessels),which could lead to embolism although it is asymptomatic in most cases. Objectives To evaluate the effectiveness and safety of tubal flushing with oil-soluble contrast media (OSCM) and water-soluble contrast media (WSCM) on subsequent fertility outcomes in women with subfertility. Search methods We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, MEDLINE, Embase, CENTRAL, PsycINFO, reference lists of identified articles and trial registries. The most recent search was conducted in April 2020. Selection criteria Randomised controlled trials (RCTs) comparing tubal flushing with OSCM, WSCM with each other or with no treatment, in women with subfertility. Data collection and analysis Two review authors independently selected the trials, assessed risk of bias and extracted data. We contacted study authors for additional information. The overall quality of the evidence was assessed using GRADE methods. Main results Fifteen trials involving 3864 women were included in this systematic review. Overall, the quality of evidence varied from very low to moderate: the main limitations were risk of bias, heterogeneity and imprecision. OSCM versus no treatment Four studies (506 women) were included in this comparison. Tubal flushing with OSCM may increase the odds of live birth (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.57 to 6.85, 3 RCTs, 204 women, I2 = 0, low-quality evidence). This suggests that if the chance of live birth following no treatment is assumed to be 11%, the chance following tubal flushing with OSCM would be between 16% and 46%. Tubal flushing with OSCM may increase in the odds of clinical pregnancy (OR 3.54, 95% CI 2.08 to 6.02, 4 RCTs, 506 women, I2 = 18%, low-quality evidence). This suggests that if the chance of clinical pregnancy following no treatment is assumed to be 9%, the chance following tubal flushing with OSCM would be between 17% and 37%. No study measured intravasation or other adverse events such as infection, haemorrhage and congenital abnormalities. WSCM versus no treatment Only one study (334 women) was included in this comparison. We are uncertain whether tubal flushing with WSCM increase live birth compared to no treatment (OR 1.13, 95% CI 0.67 to 1.91, 1 RCT, 334 women, low-quality evidence). This suggests that if the chance of live birth following no treatment is assumed to be 21%, the chance following tubal flushing with WSCM would be between 15% and 33%. We are uncertain whether tubal flushing with WSCM increases clinical pregnancy compared to no treatment (OR 1.14, 95% CI 0.71 to 1.84, 1 RCT, 334 women, low-quality evidence). This suggests that if the chance of clinical pregnancy following no treatment is assumed to be 27%, the chance following tubal flushing with WSCM would be between 29% and 40%. One case with pelvic infection was reported in the WSCM group and no case with infection in the no treatment group in a one study (334 women). Meta-analysis was not performed due to the rare events. No study measured intravasation or other adverse events such as infection, haemorrhage and congenital abnormalities. OSCM versus WSCM Six studies (2598 women) were included in this comparison. Three studies reported live birth, including two with higher live birth in the OSCM group (OR 1.64, 95% CI 1.27 to 2.11, 1119 women; OR 3.45, 95% CI 1.97 to 6.03, 398 women); and one with insufficient evidence of a difference between groups (OR 0.92, 95% CI 0.60 to 1.40, 533 women). Given the substantial heterogeneity observed (I2 = 86%), meta-analysis was not performed. Tubal flushing with OSCM probably increased in the odds of intravasation (asymptomatic) compared to tubal flushing with WSCM (OR 5.00, 95% CI 2.25 to 11.12, 4 RCTs, 1912 women, I2 = 0, moderate-quality evidence). This suggests that if the chance of intravasation following tubal flushing with WSCM is assumed to be 1%, the chance following tubal flushing with OSCM would be between 2% and 9%. Tubal flushing with OSCM may increase the odds of clinical pregnancy (OR 1.42, 95% CI 1.10 to 1.85, 6 RCTs, 2598 women, I2 = 41%, low-quality evidence). This suggests that if the chance of clinical pregnancy following tubal flushing with WSCM is assumed to be 26%, the chance following tubal flushing with OSCM would be between 28% and 39%. We are uncertain whether tubal flushing with OSCM decreases the odds of infection (OR 0.22, 95% CI 0.04 to 1.22, 2 RCTs, 662 women, I2 = 0, very low-quality evidence) or haemorrhage (OR 0.65, 95% CI 0.40 to 1.06, 2 RCTs, 662 women, I2 = 0, very low-quality evidence). Three neonates with congenital abnormalities were reported in the OSCM group while no congenital abnormality was reported in the WSCM group in one study (1119 women). No meta-analysis was performed due to the rare events. Authors' conclusions The evidence suggests that compared to no treatment, tubal flushing with OSCM may increase the chance of live birth and clinical pregnancy, while it is uncertain whether tubal flushing with WSCM improves those outcomes. Compared to tubal flushing with WSCM, OSCM may improve clinical pregnancy while meta-analysis was impossible for live birth due to heterogeneity. Evidence also suggests that OSCM is associated with an increased risk of asymptomatic intravasation. Overall, adverse events, especially long-term adverse events, are poorly reported across studies.

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Tubal flushing for subfertility

mainresultsandtheroleofchance: Of the 4221 citations identified, 30 studies were eligible. Of the latter, 28 reported results per individual tube and were included in the meta-analysis, representing a total of 1551 women and 2740 tubes. In nine studies, all participants underwent HSG in addition to sono-HSG and laparoscopy, allowing direct comparison of the accuracy of sono-HSG and HSG. Pooled estimates of sensitivity and specificity of sono-HSG were 0.92 (95% CI: 0.82 –0.96) and 0.95 (95% CI: 0.90 –0.97), respectively. In nine studies (582 women, 1055 tubes), sono-HSG and HSG were both compared with laparoscopy, giving pooled estimates of sensitivity and specificity of 0.95 (95% CI: 0.78 –0.99) and 0.93 (95% CI: 0.89 –0.96) for sono-HSG, and 0.94 (95% CI: 0.74 –0.99) and 0.92 (95% CI: 0.87 –0.95) for HSG, respectively. Doppler sonography was associated with significantly greater sensitivity and specificity of sono-HSG compared with its non-use (0.93 and 0.95 versus 0.86 and 0.89, respectively, P ¼ 0.0497). Sensitivity analysis regarding methodological quality of studies was consistent with these findings. We also found no benefit of the commercially available contrast media over saline solution in regard to the diagnostic accuracy of sono-HSG. limitations, reasons for caution: Methodological quality varied greatly between studies. However, sensitivity analysis, taking methodological quality of studies into account, did not modify the results. This systematic review did not allow the distinction between distal and proximal occlusion. This could be interesting to take into account in further studies, as the performance of the test may differ for each localization. wider implications of the findings: Given our findings and the known benefits of sono-HSG over HSG in the context of subfertility, sono-HSG should replace HSG in the initial workup of subfertile couples.

Hysterosalpingosonography for diagnosing tubal occlusion in subfertile women: a systematic review with meta-analysis

Background This study was conducted to describe the first experiences with hysterosalpingo-foam sonography (HyFoSy) as a first step routine office procedure for tubal patency testing. Methods A prospective observational cohort study was started in a university affiliated teaching hospital. In 2010, 73 patients with subfertility and a low risk of tubal pathology were examined. A non-toxic foam containing hydroxymethylcellulose and glycerol was applicated through a cervical applicator for contrast sonography (HyFoSy). Tubal patency was determined by transvaginal ultrasonographic demonstration of echogenic dispersion of foam in the Fallopian tube and/or the peritoneal cavity. Only in case patency could not be demonstrated, a hysterosalpingography (HSG) was performed as a control. Results In 67 out of 73 (92%) patients, a successful procedure was performed. In 57 out of 73 (78%) cases, there was no further need for a HSG. In five patients (5/73; 7%) tubal occlusion was confirmed by HSG and in five patients (5/73; 7%) there was discordance between HyFoSy and HSG. Of 73 patients, 14 (19%) conceived within a median of 3 months after the procedure. Conclusions HyFoSy is a successful procedure to demonstrate tubal patency as a first step office procedure.

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First experiences with hysterosalpingo-foam sonography (HyFoSy) for office tubal patency testing

Contrast Ultrasonography for Tubal Patency

Objectives
To evaluate the spectrum of diagnostic findings in hysterosalpingography (HSG) examinations performed at our institution between 2006–2010 and their prognostic significance for treatment decisions and fertility outcomes

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Hysterosalpingography in the workup of female infertility: indications, technique and diagnostic findings

Tubal assessment is an integral part of female fertility evaluation. While diagnostic laparoscopy is gold standard, it is not suitable to be used as a screening test. Hysterosalpingogram (HSG) has been advocated as first-line investigation historically. With advances in diagnostics, more tests are available, such as hysterosalpingo contrast sonography (HyCoSy) and Chlamydia antibody titre (CAT) are available. The CAT test is much cheaper, less invasive and can be performed at any time during the cycle. The CAT test can also be used as a means of identifying which patients need further evaluation. HyCoSy has same diagnostic accuracy as HSG, without exposing women to radiation. We argue that HSG is out of date and has no place in a modern infertility evaluation. We also suggest a pathway (based on history, clinical and ultrasound evaluation) for investigations to screen for and diagnose tubal pathology.

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Zaid Hasafa

Papers

Should a hysterosalpingogram be a first-line investigation to diagnose female tubal subfertility in the modern subfertility workup?