Misdiagnosis in patients with obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome: a retrospective study of 164 cases

This single-center retrospective study included all patients diagnosed with OHVIRA syndrome who were admitted for treatment to the Department of Obstetrics and Gynecology at Peking Union Medical College Hospital (PUMCH) between January 2000 and December 2023. Patients were eligible for inclusion if they met the following inclusion criteria: (a) a definitive diagnosis of OHVIRA syndrome established through pelvic examination and imaging examinations; (b) confirmation of the clinical classification via surgical findings; and (c) availability of complete medical records, including admission notes, operative reports and outpatient follow-up documentation. The study protocol was reviewed and approved by the Ethics Committee of PUMCH (Project No. ZS-1858). All cases were identified and retrieved from the Hospital Information System (HIS) by the medical records department staff at PUMCH, based on the diagnostic code listed on the home page of the medical records. Two general gynecologists independently reviewed the collected medical records and excluded cases with incomplete documentation or missing surgical notes, patients who had not undergone surgery, and those who were incorrectly diagnosed with OHVIRA syndrome. For cases meeting the inclusion criteria, all available charts were thoroughly reviewed to extract demographic and disease-related information, including age at symptom onset, age at the first diagnosis, clinical classification, degree of obstruction, lateral location of the septum, clinical manifestations, complications, and imaging modalities used prior to the primary diagnosis (ultrasound or magnetic resonance imaging). For patients who had experienced a misdiagnosis, additional details were collected, including the initial incorrect diagnosis, the management provided following that diagnosis, and the time interval between the misdiagnosis and the eventual correct diagnosis. Descriptive statistics were expressed as the mean values ± standard deviations (SD) or medians with interquartile ranges for continuous variables, and as frequencies and percentages for categorical variables. Comparisons between the proper diagnosis group and the misdiagnosis group were conducted using Pearson’s χ 2 test or Fisher’s exact test for categorical variables, while independent-sample t-tests or Mann–Whitney U tests were applied for continuous variables, depending on data distribution. To identify potential risk factors for misdiagnosis, variables deemed clinically relevant or those with P  < 0.15 in the univariate analysis were included in a binary logistic regression model. P  < 0.05 was considered statistically significant. All statistical analyses were performed using the IBM ® SPSS ® 30.0 statistical package (SPSS Inc., Chicago, Illinois, USA).

As illustrated in the flowchart in Fig.  1 , a total of 182 patients diagnosed with OHVIRA syndrome were initially identified from the HIS. Of these, 9 patients were excluded due to incomplete medical records, 5 were excluded because they had not undergone surgery, and 4 were excluded after chart review revealed alternative diagnoses of other genital tract malformations. Consequently, 164 patients met the inclusion criteria and were enrolled for further analysis. Fig. 1 The flowchart of enrollment of patients with OHVIRA syndrome The flowchart of enrollment of patients with OHVIRA syndrome Table 1 presents the demographic characteristics and disease-related information of the enrolled patients. The mean onset age of these patients was 17.13 ± 6.17 years, while the mean age at first diagnosis was 19.39 ± 7.82 years old. Among the patients, 71 (43.3%) patients were classified as type 1 OHVIRA syndrome, 57 (34.8%) as type 2, 14 (8.5%) as type 3, and 22 (13.4%) as type 4. Based on the extent of obstruction, 93 (56.7%) cases were categorized as completely obstructed, whereas 71 (43.3%) cases were incompletely obstructed. The lateral distribution of the septum favored the right side in 91 (55.5%) patients and the left in 73 (44.5%) patients. Regarding clinical manifestations, 134 (81.7%) patients reported dysmenorrhea, 59 (36.0%) had irregular bleeding, and 54 (32.9%) experienced abnormal vaginal discharge, often purulent or foul-smelling. Additionally, 50 (30.5%) patients had a history of PID, and 43 (26.2%) patients were complicated with pelvic endometriosis. In terms of imaging modalities used, pelvic ultrasound was performed in all patients, while only 93 (56.7%) patients underwent pelvic MRI prior to their primary diagnosis. Table 1 Demographics and disease related information of patients with OHVIRA syndrome OHVIRA patients ( N  = 164) Proper diagnosis group ( N  = 137) Misdiagnosis group ( N  = 27) P value Onset age (yr) 17.13 ± 6.17 16.99 ± 6.39 17.85 ± 4.92 0.510 Age at first diagnosis (yr) 19.39 ± 7.82 19.78 ± 7.85 17.38 ± 7.52 0.145 Clinical classification  Type 1 71 (43.3%) 64 (46.7%) 7 (25.9%) 0.052  Type 2 57 (34.8%) 47 (34.3%) 10 (37.0%)  Type 3 14 (8.5%) 12 (8.8%) 2 (7.4%)  Type 4 22 (13.4%) 14 (10.2%) 8 (29.6%) Obstruction extent  Complete obstruction 93 (56.7%) 78 (56.9%) 15 (55.5%) 0.895  Incomplete obstruction 71 (43.3%) 59 (43.1%) 12 (44.4%) Lateral distribution  Left 73 (44.5%) 61 (44.5%) 12 (44.4%) 0.994  Right 91 (55.5%) 76 (55.5%) 15 (55.6%) Clinical manifestation  Dysmenorrhea 134 (81.7%) 108 (78.8%) 26 (96.3%) 0.061  Irregular bleeding 59 (36.0%) 56 (40.9%) 3 (11.1%) 0.003*  Abnormal discharge 54 (32.9%) 44 (32.1%) 10 (37.0%) 0.619 Complications  Pelvic inflammation 50 (30.5%) 38 (27.7%) 12 (44.4%) 0.085  Endometriosis 43 (26.2%) 30 (21.9%) 13 (48.1%) 0.005* Imaging examination  Pelvic ultrasound 164 (100.0%) 137 (100.0%) 27 (100.0%) N/A  Pelvic MRI 93 (56.7%) 88 (64.2%) 5 (18.5%)  < 0.001* Data are shown as mean ± standard deviation or N (%). *stands for P  < 0.05 Demographics and disease related information of patients with OHVIRA syndrome Data are shown as mean ± standard deviation or N (%). *stands for P  < 0.05 Among all patients diagnosed with OHVIRA syndrome, 27 (16.5%) patients had experienced misdiagnosis, leading to unnecessary surgeries or procedures. A comparative analysis between the properly diagnosed group and the misdiagnosed group revealed that the latter had a significantly lower proportion of cases presenting with irregular bleeding ( P  = 0.003) and a higher proportion of cases complicated by endometriosis ( P  = 0.005). Additionally, the proportion of patients who underwent pelvic MRI prior to the primary diagnosis was markedly higher in the proper diagnosis group compared to the misdiagnosis group (64.2% vs. 18.5%, P  < 0.001). Although not statistically significant, trends were observed in other measures: patients in the misdiagnosis group tended to be younger at diagnosis ( P  = 0.145), showed differences in clinical classification distribution ( P  = 0.052), and had higher rates of dysmenorrhea ( P  = 0.061) and PID ( P  = 0.085). All 27 misdiagnosed cases are summarized in Table  2 . The mean age at the time of the initial incorrect diagnosis was 17.38 ± 7.52 years, while the mean age at the time of the correct diagnosis was 20.02 ± 8.18 years. The median interval between their primary and correct diagnosis was 14.03 (5.03–48.00) months. Table 2 The diagnosis and management of misdiagnosed patients Misdiagnosis patients ( N  = 27) Age at primary diagnosis (yr) 17.38 ± 7.52 Age at proper diagnosis (yr) 20.02 ± 8.18 Diagnosis interval ( m ) 14.03 (5.03–48.00) Primary diagnosis  Pelvic abscess 8 (29.6%)  Ovarian cyst 7 (25.9%)  Rudimentary uterine horn 3 (11.1%)  Uterine didelphys 2 (7.4%)  Hydrosalpinx/hematosalpinx 2 (7.4%)  Cervical dysplasia 2 (7.4%)  Imperforate hymen 1 (3.7%)  Vaginal hematocele 1 (3.7%)  Vaginal wall abscess 1 (3.7%) Management after primary diagnosis  Pelvic abscess removal 5 (18.5%)  Simple drainage of abscess/cyst 5 (18.5%)  Ovarian cystectomy 5 (18.5%)  Adnexectomy 1 (3.7%)  Salpingostomy 2 (7.4%)  Ipsilateral hysterectomy 2 (7.4%)  Hysteroplasty 1 (3.7%)  Cervicoplasty 2 (7.4%)  Drainage of hematocele 3 (11.1%)  Incision of imperforate hymen 1 (3.7%) Data are shown as mean ± standard deviation/median and interquartile range or N (%) The diagnosis and management of misdiagnosed patients Data are shown as mean ± standard deviation/median and interquartile range or N (%) Among the misdiagnosed cases, 8 (29.6%) cases were initially diagnosed with pelvic abscess and 7 (25.9%) with ovarian cyst. Other patients were misdiagnosed with various genital tract malformations, including rudimentary uterine horn (3/27, 11.1%), uterine didelphys (2/27, 7.4%), cervical dysplasia (2/27, 7.4%) and imperforate hymen (1/27, 3.7%). In some instances, gynecologists focused solely on the obstructive manifestations and diagnosed conditions such as hydrosalpinx/hematosalpinx (2/27, 7.4%), vaginal hematocele (1/27, 3.7%), or vaginal wall abscess (1/27, 3.7%). Based on their primary diagnoses, several additional interventions were undertaken. Specifically, 5 (18.5%) patients underwent transabdominal or laparoscopic pelvic abscess removal, 5 (18.5%) underwent simple drainage of abscess or cyst, and 3 (11.1%) underwent drainage of hematocele. Among patients diagnosed with ovarian cysts or hydrosalpinx/hematosalpinx, 5 (18.5%) received ovarian cystectomy, 1 (3.7%) underwent adnexectomy, and 2 (7.4%) underwent salpingostomy. For those misdiagnosed with rudimentary uterine horn, uterine didelphys or cervical dysplasia, 2 (7.4%) patients received ipsilateral hysterectomy, 1 (3.7%) received hysteroplasty and 2 (7.4%) received cervicoplasty surgery. To further investigate factors associated with misdiagnosis in patients with OHVIRA syndrome, a binary logistic regression analysis was conducted (Table 3 ), incorporating variables with P  < 0.15 in the univariate analysis, including onset age, clinical classification, dysmenorrhea, irregular bleeding, pelvic inflammation, endometriosis, and pelvic MRI prior to the primary diagnosis. For clinical classification, Type 1 was designated as the reference (dummy) variable. The results suggested that complicating with pelvic endometriosis was a potential risk factor for misdiagnosis (OR 3.267, 95% CI 1.010–10.660). Conversely, presenting with irregular bleeding (OR 0.193, 95%CI 0.047–0.800) and undergoing pelvic MRI prior to diagnosis (OR 0.157, 95% CI 0.050–0.486) were identified as potential protective factors against misdiagnosis in patients with OHVIRA syndrome. Table 3 Factors associated with misdiagnosis based on a logistic regression analysis Variables OR OR (95% CI) P value Lower Upper Age at first diagnosis 0.934 0.850 1.027 0.161 Clinical Classification  Type 1 0.525  Type 2 2.543 0.533 12.142 0.242  Type 3 3.540 0.440 28.495 0.235  Type 4 1.856 0.432 7.974 0.406 Clinical manifestation  Dysmenorrhea 2.674 0.288 24.816 0.387  Irregular bleeding 0.193 0.047 0.800 0.023* Complications  Pelvic inflammation 2.128 0.571 7.928 0.261  Endometriosis 3.267 1.010 10.660 0.048* MRI before primary diagnosis 0.157 0.050 0.486 0.001* OR Odds ratio; CI Confidence interval; * stands for P  < 0.05 Factors associated with misdiagnosis based on a logistic regression analysis OR Odds ratio; CI Confidence interval; * stands for P  < 0.05

Many patients with OHVIRA syndrome experience misdiagnosis, particularly those with coexisting pelvic endometriosis, and are frequently treated as cases of pelvic abscess, ovarian cyst, or other genital tract malformations. Performing pelvic MRI prior to diagnosis substantially reduce the risk of misdiagnosis and improve the accuracy of clinical assessment in OHVIRA syndrome.

This retrospective study conducted a thorough and comprehensive review of 164 cases from a tertiary medical center, demonstrating that misdiagnosis is relatively common in the clinical practice of OHVIRA syndrome, often resulting in multiple referrals, unnecessary medical procedures or surgeries, and consequently increasing the complexity and risks associated with subsequent diagnosis and treatment. Furthermore, the study identified coexisting pelvic endometriosis as a potential risk factor for misdiagnosis, while performing pelvic MRI in suspected cases prior to diagnosis emerged as a protective factor, underscoring the importance of thorough pre-diagnostic imaging in improving diagnostic accuracy. OHVIRA syndrome is a rare congenital urogenital tract malformation disease with a reported prevalence of 0.1–3.8% [ 19 ]. Despite its rarity, it remains the most common obstructive Müllerian anomaly diagnosed in adolescents after menarche [ 12 ]. While the classic presentation involves didelphys uterus, obstructed hemivagina, and ipsilateral renal agenesis, OHVIRA syndrome encompasses a wide spectrum of anatomical variants. Other rare anatomical variants were also observed in clinical practice. Fedele et al. reported 10 cases with septate uterus, 9 with bicornuate uterus and 4 with unilateral cervical atresia by retrospectively reviewing 87 cases at their center [ 20 ]. Large-scale systemic reviews and multicentric retrospective studies also confirmed the existence of multiple variations in the anatomy of the uterus, cervix, and renal anomalies [ 8 , 16 , 17 ]. The new ASRM Müllerian Anomalies Classification 2021 system adopt inclusive variations of OHVIRA syndrome as well, including uterus didelphys, complete septate uterus, bicornuate uterus, duplicated cervices, septate cervix and atresic cervix [ 21 ]. This broad anatomical diversity results in a wide range of clinical presentations. While most patients with completely obstructed hemivagina present with dysmenorrhea and pelvic mass after menarche, atypical symptoms are common in those with incomplete obstruction, such as intermittent mucopurulent vaginal discharge, irregular vaginal bleeding, acute PID and secondary endometriosis. Additionally, some patients with OHVIRA syndrome initially seek medical service due to urinary problems, infertility, dyspareunia, or digestive complaints, while others are entirely asymptomatic and receive a diagnosis incidentally [ 22 – 24 ]. This heterogeneity in anatomical anomalies and clinical manifestations contributes significantly to the risk of misdiagnosis and delayed diagnosis in OHVIRA syndrome. Our study findings strongly support this inference, with an interesting observation that irregular bleeding appears to serve as a protective factor against misdiagnosis. Abnormal uterine bleeding (AUB) is a common issue among adolescents, accounting for nearly half of all gynecologic visits in this population, with the most frequent causes being ovulatory dysfunction and coagulopathy [ 25 ]. Müllerian anomalies, by contrast, represent only a small fraction of AUB cases [ 26 ]. We speculate that irregular bleeding prompts gynecologists to conduct imaging examinations such as pelvic ultrasound, which may lead to the incidental detection of underlying genital tract anomalies. Furthermore, our regression analysis also suggested that coexisting pelvic endometriosis may increase the likelihood of misdiagnosis in OHVIRA syndrome. Given the rarity of OHVIRA syndrome, general practitioners may have limited familiarity with this anomaly, and the presence of complications such as pelvic abscess or pelvic endometriosis can be misleading, causing clinicians to focus on the apparent pathology while overlooking the underlying congenital abnormality. In our study, more than half of the misdiagnosed patients were initially diagnosed with pelvic abscess or ovarian cyst. Therefore, when a pubertal girl presents with a pelvic mass or pelvic inflammation shortly after menarche, gynecologists should consider the possibility of OHVIRA syndrome or other obstructive müllerian anomalies, as these conditions can cause retrograde menstrual flow and subsequently lead to endometriosis or PID. It is noteworthy that this study identifies performing pelvic MRI prior to diagnosis as a protective factor against misdiagnosis in OHVIRA syndrome. While ultrasound remains the most commonly used imaging modality for its diagnosis, followed by pelvic MRI [ 27 ], ultrasound is typically the first-line screening tool since it’s non-invasive, readily available, cost-effective, and provides real-time imaging. Transvaginal ultrasound has been reported to be sufficiently sensitive for detecting uterine contour anomalies [ 28 ], and three-dimensional ultrasound can produce high-quality images comparable to MRI for diagnosing congenital uterine anomalies. However, transvaginal ultrasound is often unsuitable for adolescents who are not sexually active. MRI, with its superior soft-tissue resolution, is considered the gold standard for accurately diagnosing OHVIRA syndrome [ 29 ], as it offers detailed visualization of complex anatomical variations in OHVIRA syndrome, including ipsilateral cervical atresia, communicating uteri, and various uterine anomalies. Moreover, MRI not only provides a more comprehensive depiction of pelvic anatomy but also facilitates the detection of both acute and chronic complications [ 30 , 31 ]. In light of previous research and our findings, we recommend that pelvic MRI should be performed in patients with a high clinical suspicion of OHVIRA syndrome to ensure an accurate preoperative diagnosis, reduce the risk of misdiagnosis,· and guide optimal surgical management. Despite the rarity of OHVIRA syndrome, it is crucial for gynecologists, pediatricians, and radiologists to maintain a high level of awareness. The syndrome should be suspected in adolescents presenting with dysmenorrhea, pelvic or abdominal pain with or without fever, abnormal vaginal discharge, or pelvic mass, particularly in cases of unexplained pelvic inflammation or endometriosis. When OHVIRA syndrome is suspected, pelvic examination along with pelvic and urinary tract ultrasound should be performed, and, when feasible, preoperative MRI should be obtained to more accurately assess the clinical type and associated complications. In addition, early recognition of the association between renal agenesis and genital tract malformations is important for timely diagnosis. Several case series have reported early detection of OHVIRA syndrome in prepubertal patients with unilateral renal agenesis [ 32 – 34 ], highlighting the need to consider this syndrome in female neonates or girls incidentally found to have renal agenesis, thereby preventing complications that could compromise fertility or renal function. However, if clinicians lack related experience in diagnosing or managing OHVIRA syndrome, prompt referral to experienced medical institution and specialists in pediatric and adolescent gynecology is recommended. Interim management options, including pain control, antibiotics, or menstrual suppression, may be employed to stabilize the patient while arranging appropriate referral [ 35 ]. This study represents the largest investigation to date focusing on the misdiagnosis status of patients with OHVIRA syndrome, providing clinicians with valuable insights into the incidence, underlying causes, and potential risk and protective factors associated with misdiagnosis in OHVIRA cases. Nevertheless, the retrospective nature of the study imposes certain limitations, including incomplete information regarding the primary diagnosis, such as the level of the medical institution and the specialty of the diagnosing clinician. The extended timespan of case collection may also affect the accuracy of descriptive data. Additionally, while we employed the four-subtype new classification system in this study, which has been utilized in several systematic reviews and retrospective studies, its application in routine clinical practice remains limited compared with the ESGE or the new ASRM classification systems.

Obstructed Hemivagina and Ipsilateral Renal Anomaly (OHVIRA) syndrome, also referred to as Herlyn-Werner-Wunderlich Syndrome (HWWS) [ 1 ], is a rare congenital malformation of the female reproductive system characterized by the triad of uterine didelphys, obstructed hemivagina and ipsilateral renal anomaly. This condition accounts for approximately 6.2–8.3% of all female genital tract malformations [ 2 , 3 ]. Based on the degree of vaginal obstruction, OHVIRA syndrome is broadly categorized into completely obstructed and incompletely obstructed subtypes. In 2015, a more refined classification system was introduced, incorporating both anatomical variations and the extent of obstruction [ 4 ]. This system delineates four subtypes: Type 1, completely obstructed hemivagina with isolated uteri; Type 2, partial reabsorption of the vaginal septum; Type 3, completely obstructed hemivagina with communicating uteri; and Type 4, cervicovaginal atresia. Due to the obstruction of menstrual flow, patients with OHVIRA syndrome usually present with symptoms such as dysmenorrhea, irregular bleeding or abnormal vaginal discharge in adolescence, sometimes occurring shortly after menarche [ 5 ]. They are also at an increased risk of developing complications such as endometriosis and pelvic inflammatory disease (PID) [ 6 – 8 ]. For individuals who receive an early and accurate diagnosis of OHVIRA syndrome, timely surgical resection of the vaginal septum can effectively relieve the obstruction and help preserve fertility [ 9 – 11 ]. However, in clinical practice, a significant proportion of patients experience delayed diagnosis after repeated referrals and, in some cases, undergo additional surgical procedures, thereby increasing surgical risks and imposing both physical and psychological burdens. Several case reports and case series have documented this issue in patients with obstructive Müllerian anomalies [ 12 – 15 ]. Although an increasing number of large-scale studies have examined the anatomical variations, clinical characteristics and complications of OHVIRA syndrome [ 8 , 16 – 18 ], there remains a lack of in-depth research with relatively large sample sizes specifically addressing the prevalence, causes and risk factors associated with misdiagnosis. While many gynecologists recognize that the misdiagnosis is common in patients with OHVIRA syndrome, the exact incidence, underlying reasons, and contributing factors are still unclear. In this study, we aim to summarize the current status of misdiagnosis in OHVIRA syndrome and further investigate potential related risk factors through a retrospective review of cases in a tertiary medical center.