Pelvic Pain in Patients with Complex Mullerian Anomalies Including Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH), Obstructed Hemi-vagina Ipsilateral Renal Anomaly (OHVIRA), and Complex Cloaca

Abstract

Caring for patients with congenital pelvic anomalies can be challenging in many ways but one crucial aspect is providing longitudinal into adulthood. Newborns with urinary, intestinal or vaginal obstruction require urgent operations to relieve obstruction followed by multiple reconstructive procedures involving the perineum. Openings are created in the pelvic floor musculature that did not exist in development. Adolescence presents further challenges for these postoperative patients while other diagnoses present for the first time in the peri-pubertal teenage years. Young adults can have new symptoms when they become sexually active and are faced with reproductive decisions. During all of these time periods, optimization of function is of paramount importance and patients who are suffering are not able to participate in school, sports or work. This study evaluates the prevalence of pelvic pain in newborns and adolescents with complex congenital pelvic anomalies, associated factors and possible treatment options.

INTRODUCTION

Chronic pelvic pain, characterized by noncyclical painful episodes lasting at least six months, has been described in patient populations with various diagnoses including genitourinary, gastrointestinal, musculoskeletal, psychological, or idiopathic disorders.^{1, 2} Chronic pelvic pain, affecting approximately 1 in 7 women, can lead to excess clinic visits with an estimated direct medical cost for outpatient visits in the U.S. of $881.5 million per year.³ In one study by Mathias and colleagues, 15% of respondents reported loss of work due to chronic pain and 45% reported reduced work productivity.³ To date, there is limited literature reporting the prevalence of pain in the Müllerian anomaly patient populations such Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH), obstructed hemivagina ipsilateral renal anomaly syndrome (OHVIRA), and cloacal anomalies.

MRKH is a rare congenital anomaly that involves aplasia or severe hypoplasia of the Müllerian structures including the upper vagina, cervix, uterus, and fallopian tubes.^{4, 5} Clinical presentation is typically primary amenorrhea in a normally developed adolescent female. On physical examination, the external genitalia appears normal with an absent or severely hypoplastic vagina and in most cases a vaginal dimple within hymenal tissue.⁴ Imaging, including ultrasonography and MRI, is useful in confirming the diagnosis and most patients have a chromosomal analysis done that reveals a normal XX karyotype. Most commonly, there is complete aplasia of the Müllerian structures; however, remnants of uterine tissue with or without the presence of endometrium have been reported. In rare cases, this can lead to pelvic pain due to obstructed menstrual flow, uterine remnant distension and retrograde menstrual flow into the peritoneal cavity causing peritoneal irritation and endometriosis.⁵ Compared to ultrasonography, MRI can be particularly useful in these cases to identify uterine remnants and the presence or absence of endometrium within the remnant.⁵ Treatment, with each individual’s goals in mind, is aimed at establishing ability to have normal sexual intercourse and preserving future fertility.

OHVIRA is a rare obstructive Müllerian anomaly that involves a triad of obstructed hemivagina, uterine anomaly usually in the form of uterus didelphys, and ipsilateral renal anomaly.⁶ The associated renal anomaly is typically renal agenesis but there have been reports of renal dysplasia, renal atrophy, and ectopic ureteral insertion into the obstructed hemivagina.^{6, 7} Furthermore, it can be associated with other anomalies such as intestinal malrotation.⁸ Most commonly, a patient will present with pelvic pain, a pelvic mass if there is obstructed menses and/or dysmenorrhea around the time of menarche.

Cloacal anomalies are a set of complex conditions where there is a persistent common channel of the gastrointestinal, urinary, and genital tracts. Variations in embryological development and anatomy lead to unique considerations in the management of these patients. In particular, these individuals may be at increased risk for developing chronic pelvic pain given their differences in pelvic anatomy and their need for multiple reconstructive procedures throughout their lifetime.

The aim of the current study is to evaluate the prevalence of pelvic pain in patients diagnosed with MRKH syndrome, OHVIRA, or cloacal anomalies. In addition, subgroup analysis was performed to explore the severity, frequency, potential anatomical, medical or surgical associations that place patients at increased risk of developing pelvic pain.

METHODS

Participant Selection

We reviewed medical records for all children birth to 17 years of age who were listed in a clinical database with a diagnosis of MRKH, OHVIRA, or cloacal anomaly. Participants were excluded if presented with acute pain (e.g. hernia). The study was reviewed by the Phoenix Children’s Hospital Institutional Review Board, acknowledged as exempt, and approved to proceed. Informed consent and assent were waived.

Study Design

A retrospective chart review was performed for patient demographics (e.g. child’s age or race), diagnosis, presence or absence of pelvic pain and characteristics surrounding pain such as whether the pain was associated with menstruation, urination or intercourse, and presence of endometriosis. Patients also completed psychological measures as part of clinical care.

Measures

Achenbach System of Empirically Based Assessment

The Achenbach System of Empirically Based Assessment (ASEBA) system is a psychometrically robust set of instruments used to measure a range of behavioral and emotional problems in children and adults.⁹ Patients completed the Youth Self Report (YSR) or Adult Self Report (ASR), respectively for their age; mothers, if available at clinic appointment, completed the Child Behavior Checklist (CBCL) for youth under 18 years of age and Adult Behavior Checklist (ABCL) for those over 18 years of age. This study used T scores from the Anxious/Depressed, Withdrawn/Depressed and Somatization scales.

Statistical Analysis

IBM SPSS Statistics (version 25, 2017, Armonk, NY: IBM Corp) was used for statistical analyses. Descriptive statistics were used to classify the presence of pain and the characteristics of pain (e.g., presence of pain during menstruation or urination). χ² analyses were performed to evaluate the relationship between diagnoses (MRKH, OHVIRA and cloaca) and the presence of pelvic pain. Independent student’s t-test was used for comparisons between presence of pelvic pain and age. One-way ANOVAs were used to compare the T scores from the ASEBA questionnaires and the three diagnoses. If a statistically significant (P<0.05) interaction effect was identified, homogeneity of variance tests were performed, and if assumed, post-hoc comparisons using the Tukey HSD test were completed.

RESULTS

A total of 81 patients from the clinical registry were included; 36 with cloacal anomalies, 33 MRKH and 11 OHVIRA. Fifty-eight patients (72%) were Hispanic, 20 (25%) were white, non-Hispanic, and one patient was listed as other, non-Hispanic; mean age was 15.7 ± 7.8 (SD) years.

The majority of participants reported no pelvic pain with only 21% reporting pain across all diagnoses (Table 1). Of those patients reporting pelvic pain, there was a statistically significant difference by diagnosis in the prevalence of pain with 63% in the OHVIRA patients, 21% in the MRKH patients, and 8% in the cloacal anomalies patients (Table 1). However, due to the low n reporting presence of pelvic pain in the cloaca group, the difference should be interpreted with caution. Further, the numbers were too small in those who reported presence of pain with menstruation, urination or intercourse vs. those who did not in order to make meaningful statistical comparisons between the three diagnoses; therefore, this data is omitted. There was a statistically significant difference between age and presence of pelvic pain (p = 0.01). Mean age for those with pelvic pain was 19.1 ± 5.9 years compared to 14.4 ± 7.7 years for those without pelvic pain.

Table 1.

Pelvic Pain Characteristics

	MRKH (n= 33)	OHVIRA (n= 11)	Cloacal anomalies (n= 36)
Pelvic Pain Present*
Yes	7 (21.2%)	7 (63.6%)	3 (8.3%)
No	26 (78.8%)	4 (36.4%)	33 (91.7%)
Menstrual Pain
Yes	1 (3%)	2 (18.2%)	0 (0%)
No	32 (97%)	9 (81.8%)	36 (100%)
Pain with Urination
Yes	1 (3%)	0 (0%)	1 (2.8%)
No	32 (97%)	11 (100%)	35 (97.2%)
Pain with Intercourse
Yes	1 (3%)	0 (0%)	1 (2.8%)
No	32 (97%)	11 (100%)	35 (97.2%)

^*p < 0.0001

With respect to the psychological measures, there was a statistically significant difference between diagnosis and patient self-reported withdrawn/depressed symptoms. Post hoc comparisons using Tukey’s HSD revealed that withdrawn/depressed symptoms were statistically significantly higher for those with an MRKH or OHVIRA diagnosis compared to those with a cloaca diagnosis (Table 2). There was no statistically significant difference between MRKH and OHVIRA. No statistically significant differences between the diagnoses and the other patient self-report or parent reported psychological variables were found (Table 2).

Table 2.

Psychological Variables

	MRKH	OHVIRA	Cloacal anomalies	P Value
Patient Self-report	(n= 6)	(n= 2)	(n= 4)
Anxiety/Depression T scores	55.7 ± 8.2a	61.0 ± 15.6	52.3 ± 2.6	0.49
Depression/Withdrawal T scores	62.2 ± 4.1b	66.5 ± 0.7c	54.0 ± 5.2	0.02
Somatization T score	59.8 ± 7.6	62.5 ± 17.7	51.5 ± 1.9	0.24
Parent Proxy-report	(n= 3)	(n= 2)	(n= 14)
Anxiety/Depression T scores	50.3 ± 0.6	53.5 ± 5.0	53.6 ± 5.4	0.60
Depression/Withdrawal T scores	57.0 ± 10.4	58.0 ± 11.3	53.3 ± 5.3	0.69
Somatization T score	55.0 ± 8.7	54.5 ± 6.4	56.0 ± 7.1	0.95

^aMean ± SD

^bp = 0.05

^cp = 0.03

DISCUSSION

Chronic pelvic pain can be present for patients diagnosed with genitourinary/anorectal anomalies and can be a feature of their symptoms at any age. Each time a complaint is made, evaluation and/or imaging must be done to rule out acute anatomical causes for the pelvic pain. Conditions needing urgent attention can include reducible or incarcerated hernias, partial or complete adhesive bowel obstructions, urinary tract abnormalities such as infections or calculi, and in the case of OHVIRA or cloaca patients, obstructed reproductive organs such as hemiuteri or vaginas. In our study, we found that patients with OHVIRA reported pain more frequently than patients with MRKH and complex cloacas. We also discovered that older patients reported the presence of pelvic pain more than those who were younger. Whether the younger children eventually develop or report pain when they mature warrants further investigation.

In the MRKH population, various anatomical pathology, including uterine remnants with functioning endometrium, unilateral rudimentary remnant, and abnormally located ovaries have been shown to be associated with pelvic pain.^{5, 10–12} With this in mind, it is recommended that all MRKH patients presenting with pelvic pain undergo anatomical evaluation with an MRI to rule out an anatomical causative factor.^{5, 10} Evaluation to rule out urinary tract dysfunction is also necessary. One case report exists of a patient with undiagnosed MRKH, presenting with severe pain, dysuria, and mild hematuria after intercourse who was found to unknowingly be having urethral intercourse.¹³ There are non-surgical and surgical approaches to creating a neovagina; however, it is generally recommended that any procedure is delayed until mid to late teen years when the patient can be an active participant in the decision making process.⁵ Non-surgical creation of a neovagina involves the use of sequential vaginal dilation for approximately 20–30 minutes twice per day. The patient will progressively increase the width and length of the dilator over time with functional depth and width achieved in about 6 to 18 months. With an overall success rate of 75%−85% and low complication rate, this is considered the first line treatment.⁵ There are several surgical options which are divided into traction and graft-based methods. These include the Vecchietti procedure, Abbe-McIndoe skin graft procedure, intestinal vaginoplasty, Davydov procedure and more recently, autologous buccal mucosa graft vaginoplasty.¹⁴ Most still require the use of vaginal dilators to maintain the length and width of the neovagina following the procedure. The desired surgical method is typically based on a shared decision making process and the surgeon’s personal experience.⁵

In the OHVIRA population, physical examination of the abdomen may reveal a mass and manual pelvic examination may reveal a palpable bulge of the vaginal side wall. Diagnosis can be aided by ultrasound but MRI is the preferred imaging modality, demonstrating the obstructed hemivagina with hematometrocolpos and ipsilateral renal agenesis.^{6, 15} In some cases, a diagnostic laparoscopy may be necessary. Surgical intervention is eventually required as the hematocolpos will lead to continued pain and possibly urinary retention. Surgical options most commonly include vaginoplasty in which the vaginal septum is resected to relieve the obstruction.^{16, 17} In some cases, a hemi-hysterectomy may be required if cervical agenesis or dysgenesis is present on the obstructed side. It is important to rule out any other obstructive causes of the pelvic pain within this patient population, as in MRKH.

A cloaca is a normal transient structure during embryological development and its persistence yields an imperforate anus and a single perineal opening. The goal of early management is to detect other associated anomalies, allow for proper drainage of urine, and divert the intestinal tract with a colostomy.¹⁸ Overall, surgical reconstruction is indicated for the achievement of bowel and bladder control and normal sexual function.¹⁸ Traditionally, a posterior sagittal anorectovaginourethroplasty (PSARVUP) can be used to separate the three structures by first dissecting the rectum from the vagina using a posterior sagittal approach, then the anterior vaginal wall is dissected off of the urinary tract. The rectum and vagina can be mobilized and positioned more anatomically.^{18, 19} In a total urogenital mobilization, the rectum is separated from the vagina, similar to PSARVUP, but then the entire urogenital sinus is dissected and mobilized as one structure. This technique has been associated with less complications of urethral and vaginal strictures and has a more acceptable cosmetic outcome.¹⁸ Recently, laparoscopic-assisted cloacal repairs have been done that either completely or partially reconstruct the perineal openings.^{20, 21} Postoperative cloacal patients require imaging when evaluating new onset of pelvic pain and there are limited studies regarding the incidence of pain in the absence of one of the acute problems such as obstruction, infection, stricture or calculi.

Various interventions, used on adults with chronic pelvic pain in the absence of congenital anomalies, have been proposed to address the pelvic pain experienced by these patient populations, however there have been limited studies of hormone supplementation, botulinum toxin injections and pelvic physical therapy in the MRKH/OHVIRA/cloaca patients. Studies in adults have looked at the differences in the pituitary and steroid hormones in MRKH patients as compared to controls, finding that the MRKH patients have hormonal phases supporting ovarian function and that the differences between the groups could represent cycle phasing irregularities or the loss of the ovarian-uterine communication. Given that the hormonal differences are not significant, there is little to modify to prevent future pelvic pain.²² There are no hormone-related studies available in the OHVIRA or cloacal populations. A systematic review on physiotherapy in the treatment of chronic pelvic pain in adults found that there are many options with limited data and few randomized trials with heterogeneous data, making it difficult to make a recommendation on the option of physiotherapy and its efficacy for chronic pelvic pain.^{23, 24} No studies have been published on pelvic physical therapy in the MRKH, OHVIRA or cloacal patient populations.

Both anxiety and depression have been associated with pain in adults and psychosocial symptoms have been reported in women with MRKH.^{25, 26} In this study, withdrawn/depressed symptoms were statistically significantly higher in MRKH and OHVIRA. A limitation with our study is the small sample size. It is not clear whether the relationship of the psychological symptoms are due to the pain or to the diagnosis. This warrants further investigation with larger sample sizes.

As stated above, there can be many causes of pelvic pain in patients with congenital anomalies, some of which are more acute in nature. However, one cause can be spasm of the levator ani muscle known as levator syndrome, a chronic condition characterized by severe episodic pain in the rectum and anus. This condition has an incidence of 7.4% with about half of those occurring in women between the ages of 30–60 years old.^{27, 28} The causes are unknown with symptoms that can include irregular and spontaneous rectal pain, lasting 20 minutes or longer in duration, a dull ache in the pelvis, and sense of pressure in the rectum. Symptoms can be felt when sitting, relieved when standing or lying down, and can be unrelated to bowel movements.^{27, 29} The diagnosis is made by exclusion of other acute diagnoses. Treatment options include sitz baths, NSAIDS, sitting on a pillow to put pressure on the anus, botox injections, biofeedback, electrogalvanic stimulation, or physical therapy.^{27, 30} Few studies have researched levator syndrome in the pediatric population. Hoebeke et al. evaluated children, with a mean age of 8 years with pelvic floor syndrome, defined as pain in the perianal region without obvious trauma, and found that biofeedback therapy can successfully treat pelvic floor spasms, in conjunction with concomitant anticholinergic treatment, when detrusor hyperactivity was seen on urodynamics.³¹ More studies are needed to research levator syndrome in the pediatric population, what other diagnoses this syndrome is associated with and ways to treat this chronic condition.

Conclusion

The goals of therapy of any team of providers caring for patients with complex congenital conditions is to help them achieve success in the milestones of childhood development including sports, school and social interaction. Success in young adulthood can be defined in different ways but being able to participate in sexual activity and being able to work or go to school without being in pain should be reasonable goals. Pelvic spasms, as described by our patients, can be frustrating because the triggers are not always clear and the episodes can cluster over a short time period. The time of day does not appear to matter and patients may have to completely stop what they are doing until the pain resolves. Next steps for care of these patient populations are to better characterize the pain in terms of severity, duration, onset triggers and alleviating factors. Scoring the pain pre-procedure and post-intervention is possible in the adolescents who are undergoing reconstructions for the first time or do not undergo reconstructions at all and this may help identify inciting factors for those who experience spasms. Also, studying those patients who do not experience pain may elucidate differences from those that do and allow further solutions to make all the patients pain free. Finally, the ability to understand a pediatric and diagnosis-specific form of levator syndrome in these congenital patients allows the providers a way to explain the symptoms to the patients so they can seek care when they are experiencing these debilitating episodes. The goal of care is always to optimize function and further work should be done in this area to improve outcomes.