In the current study, the overall sensitivity and specificity of HSG in diagnosing uterine cavity abnormalities were 90.8% and 96.5%, respectively. Wide ranges of sensitivity (21% to 81%) and specificity (70% to 98%) have been reported in the literature [10,11,12,13,14,15] Taskin et al. [10] attributed their low sensitivity to the predominant malefactor of infertility in the couples visiting their clinic. Nigam et al. [11] reported a 70% PPV with 12.96% false negative rate. Shakya B [12] reported a 90% accuracy with 83.3% false negative rate, and false positive rate close to zero. These conflicting results may be related to the variable sample size and prevalence of each pathology.
We demonstrated the highest false negative rate of 2.5% (5/200) in diagnosing uterine luminal filling defect (submucous fibroid/polyps) confirmed by hysteroscopy; these data are in agreement with the data of Soares SR et al. [3]. In our opinion, early views of the uterus are essential to avoid missing small filling defects that may become obscured with advanced opacification of the uterine cavity. A combination of HSG and MR imaging can provide a road map for fibroid locations and to guide fertility-restoring therapy [16].
Interestingly, HSG has high PPV (98.2%) in diagnosing abnormal uterine contour in our study, similarly [12].
Further, 39.3% (11/28) patients with abnormal contour had adenomyosis and pelvic endometriosis on laparoscopy and underwent surgery. Seven cases showed deep pelvic endometriosis with adhesions/tethering between the torus uterinus and rectal serosa, which would be amenable to shaving. Five cases showed a large complex mass involving the posterior myometrial wall and infiltrating into the bowel wall, which would require segmental resection of the involved bowel. In our opinion, MRI is recommended in cases with abnormal uterine contour on HSG and specifically in radiographic appearance suggestive of adenomyosis (irregularity of the uterine contour with small outpouchings of contrast media). MRI can provide more information about disease burden before surgery and allows disease monitoring after the intervention [16].
Good correlation between HSG and hysteroscopy in diagnosing intrauterine adhesions has been previously reported [3, 13]. Fortunately, in our study, HSG has high specificity (96.3%) with a false positive rate of 3% (6/200). We attribute our false positive results to abnormality misclassification of adhesions induced deformed cavity. Two cases with unilateral scarring of one half of the uterine cavity diagnosed as having a unicornuate uterus on HSG and four cases with synechiae indenting the cavity diagnosed as septate uterus on HSG. Ahmadi et al. [17] reported that HSG appearance of intrauterine adhesions varies with the scar sites and severity [17]. HSG can provide a road map for the location and extent before hysteroscopic adhesiolysis, and interval HSG can be used to track the progression of the adhesions [16].
Highest sensitivity of HSG was demonstrated in diagnosing congenital uterine abnormalities. This finding corroborated the results of the previous study [18]. This finding is in disagreement with the data reported by Soares SR et al. [3] due to the high incidence of arcuate uteri in their study (which is a discrete malformation, more subtle and difficult to detect). Diagnostic accuracy of HSG seems to depend on the type of uterine abnormality; HSG is more sensitive in diagnosing uterine malformations with a more aggressive morphologic expression [3].
As expected, differentiation between septate and bicornuate uterus is a common diagnostic dilemma in HSG, similarly [18]. The present study estimated that seven cases diagnosed as having bicornuate uterus at HSG had a complete uterine septum (four cases), partial septum (two cases), and arcuate uterus (one case) at hysteroscopy.
It is known that the appearance of the external fundal contour represents the primary difference (septate uterus will show a normal convex uterine fundus). In most cases, further evaluation with MRI is required; the septate uterus can be discriminated from the bicornuate uterus by the presence of fundal cleft less than 1 cm [16]. In addition, it allows characterization of the septal nature (fibrous or muscular). Hysteroscopic metroplasty is recommended for the fibrous component of the septum without resection of the muscular part due to the high risk of bleeding [16].
It is our belief that MRI is recommended for evaluation of double uterine cavity abnormalities on HSG. It provides accurate characterization, which is essential for treatment decision and prediction of pregnancy outcomes.
The current study demonstrated that HSG is accurate (97.7%) in predicting bilateral tubal patency with a false negative rate of 1.6% (2/128). One case had unilateral tubal obstruction at laparoscopy; we attribute our false negative results to pelvic diffusion of contrast media from the only patent tube, which was misinterpreted as bilateral tubal patency. The other case had bilateral tubal obstruction at laparoscopy; contrast intravasation into uterine and ovarian veins during HSG was mistaken for tubal filling. In our opinion, fluoroscopic observation of dynamic filling and spillage can reduce such diagnostic errors.
Differentiation of proximal tubal occlusion from transient spasm may be challenging in some cases. In the current study, HSG falsely diagnosed bilateral proximal tubal occlusion in three cases. In our opinion, if a proximal tubal occlusion is suspected at HSG, tubal spasm should be considered as the possible cause (if there are tapering and smooth cornual margin). A spasmolytic agent should be administered to relieve tubal spasm then we can inject additional 1–2 ml of contrast media until the tube fills and spills if not; proximal tubal obstruction is suggested (cornual margin is pointed or blunt and irregular), at that time, selective trans-cervical tubal recanalization under fluoroscopic guidance could be recommended.
The reported accuracy differed between studies concerning tubal obstruction (level and side of obstruction) [19,20,21,22]. It was more accurate in distal than proximal tubal obstruction [19] and in bilateral than unilateral tubal obstruction [22].
Tvarijonavičienė E and coworkers [22] reported that the choice of laparoscopy as a “gold standard” procedure in diagnosing tubal occlusion is questionable (the 3-year cumulative pregnancy rate in patients diagnosed to have bilateral tubal occlusion at LS was 2%). It indicates that laparoscopy is not real reference standard, but it is the best we have. Waheed S et al. [6] reported that HSG is significantly superior in predicting tubal patency (68% of patients had bilateral tubal patency on HSG, compared to 28% on laparoscopy). B. Berker et al. [21] recommended laparoscopy in patients with tubal obstruction (unilateral or bilateral) on HSG; they reported a change in the management plan from artificial reproductive technologies (ART) to intrauterine insemination in 12 patients with bilateral tubal obstruction on HSG but confirmed tubal patency by laparoscopy. Recently, fertiloscopy was analyzed as a procedure of choice for tubal status evaluation [23], but further studies are needed to assess the accuracy of this procedure.
Interestingly, HSG is specific (90.2%) in diagnosing peritubal adhesions in our study by using more than one of the reported radiographic signs with a false positive rate of 8.6% (11/128). Valentini et al. [24] reported accuracy (89.2%) with false positive rate 11.7% and false negative rate 9%. They recommended shortening of the 6-month interval between HSG and laparoscopy in cases with a radiographic diagnosis of peritubal adhesions; at least radiographic suspicion can simplify the laparoscopic procedure and obviating diagnostic laparoscopy before surgical intervention. We recommend HSG before surgical intervention in peritubal adhesions.
Our results are in line with previously published findings [24], which emphasize the good accuracy of HSG in the diagnosis of pelvic adhesions. Lower accuracy has been reported [6, 25,26,27]. Goynumer G et al. [25] described high PPV of HSG in cases with severe pelvic disease; however, due to its low NPV, suspicious and even normal HSG should undergo diagnostic laparoscopy [25]. Waheed S et al. [6] reported that laparoscopy is more accurate than HSG in diagnosing pelvic adhesions; both laparoscopy and HSG are complementary. S Tanahatoe et al. [28] concluded that laparoscopy may reveal normal findings or abnormalities not requiring ART in patients with abnormal HSG even with bilateral pathology.
The American Society for Reproductive Medicine (ASRM) states that HSG is the standard test for tubal patency. Laparoscopy is indicated for women with risk factors for peritoneal disease (pelvic pain, moderate or severe endometriosis, previous pelvic infection, or surgery) or an abnormal HSG or US who do not require assisted reproductive technique, e.g., severe male factor infertility. Laparoscopy is not recommended for routine infertility work up in the absence of pelvic pathology or another specific indication (i.e., severe dysmenorrhea) [29].
Based on our study and results of previous literature [6, 20, 21, 30, 31], we can conclude that HSG is a valuable imaging modality for evaluating the genital tract of an infertile female; invasive procedures like laparoscopy and hysteroscopy are not indicated in patients with normal HSG findings and patients may be managed conservatively. Patients who had a pelvic disease or showing tubal obstruction on HSG needs further evaluation by laparoscopy.
We should emphasize that HSG performance could be influenced by the faulty technique and artifacts (e.g., inadvertent insertion of the cannula, insufficient uterine pressure due to vaginal reflux, premature ending of the procedure). In addition, there is an unavoidable possibility of objectiveness involved in the interpretation of results. Minimization of misdiagnosis can be achieved by understanding technique limitations, being thoughtful and highly consistent in interpretations (we observed that consultant and fellow radiologists are more consistent than resident, which may be attributed to their better visual memory to remember cases rather than increased learning curve in between reading rounds). Finally, HSG should be interpreted in association with the findings of clinical examination and symptomatology, as well as other imaging modalities (e.g., transvaginal echography).
Strengths of our study include using uniform radiographic signs among three radiologists with different experience and comparison to the gold standard test. We included suboptimal HSG examinations to decrease concordance between readers and to represent day-to-day practice.
Limitation of our study includes its retrospective nature; the radiologist was given HSG snapshot series and did not look at the real-time HSG while it was being done to be able to observe dynamic filling and spillage. Although, no limitation to either group, which will not affect inter-reader variability. Now, most clinicians prefer not to be present at HSG time and read post hoc films later to make clinical decisions. The second reading in our study might be affected by training effect and detection bias as a consequence of the first reading; to overcome this, we ensured a gap of at least 3 months between the two readings. The duration between HSG and hysteroscopy or laparoscopy may possibly contribute to bias. In the future, we encourage future research to develop a guideline with exact definitions of what should be judged as HSG.