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Obstructive Reproductive Tract Anomalies

Published:September 13, 2014DOI:https://doi.org/10.1016/j.jpag.2014.09.001

      Abstract

      Background

      Approximately 7% of girls will have an anatomic abnormality in their reproductive tract, diagnosed before or after puberty.

      Objective

      It is important for providers to be aware of the obstructive reproductive tract conditions, the way in which various conditions present, and the way in which such conditions should be managed.

      Design

      Systematic review of the literature using the GRADE evidence system.

      Results

      There is limited data in most areas of obstructive reproductive tract anomalies; however, some retrospective and prospective series with small numbers are still useful to guide clinical practice.

      Conclusions

      Recommendations are based on limited or inconsistent scientific evidence. Recommendations are based primarily on consensus and expert opinion.

      Key Words

      Level of Evidence

      Recommendations

      Jennifer Dietrich, MD, MSc
      Judith Simms-Cendan, MD
      Hina Talib, MD
      Saifuddin Mama, MD, MPH
      Elise Berlan, MD, MPH
      Jennifer Bercaw, MD
      Andrea Zuckerman, MD
      Amy Sass, MD
      Mary Romano, MD, MPH

      Background

      Approximately 7% of girls will have an anatomic abnormality in their reproductive tract, diagnosed before or after puberty.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.
      These anatomic problems can occur from the level of the hymen to the uterus and result in outflow tract obstruction with pain or without pain.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.
      The anatomic differences are thought to be multifactorial in origin, and investigations into both in genetic and environmental factors continue.
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      Many mice studies suggest that a variety of genes are involved in the development of the reproductive tract and that mutations of these genes result in infertility and maldevelopment of uterine and vaginal structures. Genes of interest based on these studies include genes within the WNT, DACH, and HOX families as well as SOX9.
      • Philibert P.
      • Biason-Lauber A.
      • Rouzier R.
      • et al.
      Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study.
      Such studies have been conducted in humans as well; however, research has not found a single gene mutation responsible for müllerian anomalies (Table 1).
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      • Philibert P.
      • Biason-Lauber A.
      • Rouzier R.
      • et al.
      Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study.
      • Christopoulos P.
      • Fotopoulou G.F.
      • Gazouli M.
      • et al.
      Genetic basis for the development of mullerian abnormalities: a review of current evidence.
      • Christopoulos P.
      • Gazouli M.
      • Fotopoulou G.
      • et al.
      The role of genes in the development of Mullerian anomalies: where are we today?.
      Table 1Genes Identified as Potentially Having Impact on Müllerian Duct Development
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      • Philibert P.
      • Biason-Lauber A.
      • Rouzier R.
      • et al.
      Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study.
      • Christopoulos P.
      • Fotopoulou G.F.
      • Gazouli M.
      • et al.
      Genetic basis for the development of mullerian abnormalities: a review of current evidence.
      • Christopoulos P.
      • Gazouli M.
      • Fotopoulou G.
      • et al.
      The role of genes in the development of Mullerian anomalies: where are we today?.
      Gene InvolvedEffect on Müllerian Duct
      Partially AbnormalRudimentary StructureAbsence of Vagina or Uterus
      Dach 1
      Dach 2
      Dlg 1
      Emx 2
      Lamc 1
      Lhx 1
      Pax 2
      Pax 8
      Rar a
      Rar b
      Wnt 4
      Wnt 7a
      Wnt 9b
      Furthermore, no current literature supports risk of offspring transmission from affected females, except in the situation of syndromes, which may have a very separate and distinct underlying genetic cause. Despite extensive genetic research in this area, no causal association has been made in humans to explain the spectrum in presentation of these anomalies. Environmental factors have been hypothesized as a contributing factor; however, this has not been well established. The types of pure müllerian anomalies discussed here are distinctly different from those occurring in conjunction with disorders of sexual differentiation or cloacal malformations and therefore this clinical opinion will be limited to the pure müllerian anomaly categories.
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      • Philibert P.
      • Biason-Lauber A.
      • Rouzier R.
      • et al.
      Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study.

      Development of the Reproductive Tract

      Reproductive tract development begins at 6-7 weeks gestational age and is initially guided by the presence or absence of SRY, the sex determining gene. In the absence of the SRY gene, female anatomy ensues.
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      There is additional evidence, that a female determining factor may also be involved in regulation of the female reproductive tract. The müllerian ducts will begin to fuse around 6-7 weeks of gestational age and this fusion continues through 14 weeks. Once fusion is complete, canalization occurs to form the uterine cavity. At around 12 weeks gestational age, the most caudal portions of the müllerian ducts begin to fuse with the sinovaginal bulb, forming the vagina, with the top third originating from the müllerian ducts and the lower third originating from the urogenital sinus.
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      Subsequently, the vaginal canal must go through a process of fusion and absorption with canalization to result in a normal vaginal cavity (Table 2).
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      Table 2Reproductive Tract Development
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      Gestational Age (weeks)Developmental Stage
      6External and internal genital structures begin to form and common müllerian and wolffian systems exist
      9Urogenital sinus develops and lack of exposure to androgens allows regression of wolffian ducts and further development of müllerian ducts
      12-14Müllerian ducts fuse with urogenital sinus
      15-26Cephalic growth of sinovaginal bulb occurs
      15-26After cephalic growth occurs, fusion of sinovaginal bulb will help form the vaginal plate. Subsequently, canalization of the vagina occurs.
      Both the lower vagina and hymen therefore originate from the urogenital sinus, whereas the fallopian tube, uterus, cervix, and upper vagina originate from müllerian structures. This has led the American Society of Reproductive Medicine (ASRM) to create a detailed classification chart of anomalies (Table 3), which is the most widely used.
      • Buttram Jr., V.C.
      • Gibbons W.E.
      Müllerian anomalies: a proposed classification. (An analysis of 144 cases).
      There are other classification systems in use, based on the fact that there are some rare anomalies that may not fit into the ASRM categories, like the VCUAM (Vagina, Cervix, Uterus, Adnexa, and Associated Malformation) system (Table 4).
      • Acién P.
      • Acién M.I.
      The history of female genital tract malformation classifications and proposal of an updated system.
      These classification systems are useful for research purposes and sometimes in clinical practice. In this clinical guideline we will describe the obstructive müllerian anomalies, which can be partial or complete.
      Table 3ASRM Classification
      • Buttram Jr., V.C.
      • Gibbons W.E.
      Müllerian anomalies: a proposed classification. (An analysis of 144 cases).
      ClassMüllerian Structure Type
      IAgenesis, dysgenesis, or atresia
      IIUnicornuate uterus with or without communicating or non-communicating horn associated
      IIIDidelphic uterus
      IVBicornuate uterus or arcuate uterus
      VSeptate uterus (partial or complete)
      VIDES-exposed
      Table 4VCUAM System
      • Acién P.
      • Acién M.I.
      The history of female genital tract malformation classifications and proposal of an updated system.
      ClassSubclassMüllerian Structure Type
      11.1, 1.2Rokitansky with unilateral renal agenesis or unicornuate with unilateral renal agenesis
      22.1, 2.2, 2.3, 2.4, 2.5Didelphic, bicornuate, or unicornuate uterus with ipsilateral or unilateral renal agenesis
      33A1, 3A2, 3A3, 3A4, 3A5, 3A6, 3A7, 3B1, 3B2, 3CMüllerian agenesis, didelphic uterus, bicornuate uterus, unicornuate uterus, arcuate, septate, DES uterus without renal anomaly with or without complete or segmental atresias
      4NoneAccessory uterine masses with other gubernaculum dysfunction
      5NoneAnomalies of the urogenital sinus
      6NoneMalformative combinations

      Clinical Presentation and Diagnosis of the Obstructive Anomaly

      An obstructed reproductive tract anomaly can present in 2 distinct ways: the teenagers who present with primary amenorrhea and pain and those with menstrual periods and progressive dysmenorrhea. History and clinical examination with imaging by ultrasonography and MRI are often indicated.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.

      Primary Amenorrhea due to an Obstructed Anomaly

      Obstructive defects are generally diagnosed in puberty, in the first year after the expected menses should have occurred, so establishment of a pubertal timeline is very important.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Breech L.L.
      • Laufer M.R.
      Obstructive anomalies of the female reproductive tract.
      The inability to efflux menstrual blood results in the development of a hematocolpos or hematometrocolpos, leading to cyclic pelvic pain in the face of primary amenorrhea. These patients may present with progressively worsening episodes of abdominal pain and since teenagers may have irregular menstruation for 2-5 years, the pain episodes may or may not be monthly, but eventually they become so severe or constant that this leads to an evaluation, often in the emergency department.
      ACOG Committee on Adolescent Health Care
      ACOG Committee Opinion No. 349, November 2006: Menstruation in girls and adolescents: using the menstrual cycle as a vital sign.
      On initial imaging, a mass due to the obstruction is often noted. The outflow tract can be obstructed at several levels, giving somewhat different presentations.
      • Marcal L.
      • Nofthaft M.A.
      • Coelho F.
      • et al.
      Mullerian duct anomalies: MR imaging.
      • Golan A.
      • Langer R.
      • Bukovsky I.
      • et al.
      Congenital anomalies of the müllerian system.
      • Santos X.M.
      • Krishnamurthy R.
      • Bercaw-Pratt J.
      • et al.
      The utility of ultrasound and magnetic resonance imaging versus surgery for the characterization of mullerian anomalies in the pediatric and adolescent population.
      Hymenal abnormalities are the most common outflow tract concern, with imperforate hymen occurring in 1/2000 girls (Fig. 1).
      • Breech L.L.
      • Laufer M.R.
      Obstructive anomalies of the female reproductive tract.
      The imperforate hymen leads to a distended vagina that after several bleeding episodes becomes so enlarged that the pain becomes unbearable and the patient will present at that time. If the mass is very large the patient could present with urinary retention or bowel complaints. On abdominal exam a mass may be palpated if the obstruction has been longstanding. The diagnosis can be made by visual inspection of the vulva, which shows no hymenal opening or hymenal remnants and usually shows a hymenal membrane that is bulging or bluish (Fig. 2).
      • Breech L.L.
      • Laufer M.R.
      Obstructive anomalies of the female reproductive tract.
      The exam may be limited by the patient's discomfort, based on both her age and her physical pain. A rectal examination is usually well tolerated and with an obstructed hymen a bulge is readily felt through the rectum, just inside the anal sphincter. If no bulge is easily palpated the diagnosis of an imperforate hymen should be questioned and further imaging obtained. A pelvic or translabial ultrasonography may be helpful in the initial diagnosis of an imperforate hymen, but is not necessary if the diagnosis is confirmed visually and by rectal exam.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Breech L.L.
      • Laufer M.R.
      Obstructive anomalies of the female reproductive tract.
      The transverse vaginal septum is a much rarer type of obstructive condition (1/2,100-1/72,000), which may be located at any level of the vagina (Fig. 3).
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Breech L.L.
      • Laufer M.R.
      Obstructive anomalies of the female reproductive tract.
      • Rock J.A.
      Anomalous development of the vagina.
      It presents very similarly to the imperforate hymen, with episodes of abdominal pain increasing in severity, leading to an evaluation. Upon evaluation abdominal tenderness or an abdominal mass may be palpated. On vulvar exam a normal hymenal opening is seen, and a moistened Q-tip can sometimes be gently placed through the hymen to assess the vaginal depth. Great care should be taken to attempt to not touch the hymen as that is very sensitive in young teenagers. A transverse vaginal septum can be at any level in the vagina, but the most common (40%) is in the upper third of the vagina.
      • Rock J.A.
      Anomalous development of the vagina.
      The septum can be thin or thick and a very thick septum can be considered partial vaginal agenesis (see next paragraph). On exam the vaginal depth can range from 1 cm to 7 or 8 cm, dependent on the level of the obstruction, with corresponding vaginal length on the other side of the obstruction. On rectal exam a bulge will be felt with a low septum, but may not be able to be reached with a high vaginal septum. Initial imaging is usually performed with a pelvic and/or translabial ultrasonography, but a pelvic magnetic resonance imaging (MRI) is currently the gold standard imaging modality.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Breech L.L.
      • Laufer M.R.
      Obstructive anomalies of the female reproductive tract.
      • Rock J.A.
      Anomalous development of the vagina.
      Segmental forms of vaginal agenesis also occur in 15% of cases and this is usually referred to as complete or partial vaginal atresia (lower vaginal atresia, Fig. 4).

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      If the vagina is not developed at all, but the cervix and uterus are developed, then these patients are often in severe pain after only a few months of obstructed flow. On exam, the hymen appears normal and the vagina appears nonpatent. Nonetheless the vagina is present, but simply at a distance much higher from the perineum. However, no bulge is present on the perineum because this anomaly does not involve the urogenital sinus derivatives, but an abdominal mass can be palpated. Upon rectal exam a bulge is sometimes palpated at a variable distance from the perineum. The diagnosis is made definitively with pelvic ultrasonography and abdominal MRI.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Breech L.L.
      • Laufer M.R.
      Obstructive anomalies of the female reproductive tract.
      • Rock J.A.
      Anomalous development of the vagina.
      If the uterus is normally developed, but the cervix is not present or not open to menstrual flow, cervical agenesis or dysgenesis is present, which is a rare diagnosis. These patients present in a similar fashion to vaginal atresia with severe pain and primary amenorrhea. Diagnosis is made by ultrasonography and/or MRI imaging of the müllerian tract. These cases require careful evaluation and frequently intraoperative assessment to determine the functional nature of the cervix (for fertility and prevention of ascending infection) in the future because 50% are associated concomitantly with vaginal agenesis and 33% are associated with additional müllerian anomalies. Due to the rare presence of this condition, the exact incidence is unknown.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Breech L.L.
      • Laufer M.R.
      Obstructive anomalies of the female reproductive tract.

      Severe Dysmenorrhea in the Presence of Menstrual Cycles due to an Obstructive Müllerian Anomaly

      Adolescents may present with dysmenorrhea and menstrual cycles in the setting of an obstructive anomaly. Studies estimate 41%-91% of teenagers experience menstrual cramping.
      • Sultan C.
      • Gaspari L.
      • Paris F.
      Adolescent dysmenorrhea.
      In most cases this is not associated with any type of müllerian anomaly, but rather with primary dysmenorrhea.
      • Sultan C.
      • Gaspari L.
      • Paris F.
      Adolescent dysmenorrhea.
      In those teenagers who have severe and worsening cramping that is not adequately responsive to pain medications or cyclical hormonal treatment, however, the diagnosis of a partially obstructed müllerian tract should be considered. These obstructive defects are generally diagnosed several years after menarche; due to the fact that there is a menstrual flow and since dysmenorrhea is fairly common in teenagers, this combination of symptoms often leads to a diagnostic delay.
      • Sultan C.
      • Gaspari L.
      • Paris F.
      Adolescent dysmenorrhea.
      • Smith N.A.
      • Laufer M.R.
      Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome: management and follow-up.
      The most common of the obstructions is the obstructed hemivagina in patients who have complete duplication of the uterine horns and upper vagina. This condition is often associated with ipsilateral renal agenesis, called OHVIRA syndrome (obstructed hemivagina with ipsilateral renal agenesis), renal dysgenesis, pelvic kidney, or ectopic ureter.
      • Cox D.
      • Ching B.H.
      Herlyn-Werner-Wunderlich Syndrome: a rare presentation with pyocolpos.
      • Sanghvi Y.
      • Shastri P.
      • Mane S.B.
      • et al.
      Prepubertal presentation of Herlyn-Werner-Wunderlich syndrome: a case report.
      • Shah D.K.
      • Laufer M.R.
      Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome with a single uterus.
      Patients may present with regular or irregular periods and progressive dysmenorrhea, which does not respond well to pain medications or cyclical hormonal treatments. Since a connection between the 2 sides can be present at the cervical or uterine level, occasionally the obstructed side can become infected and the patient presents with intermittent green discharge.
      • Cox D.
      • Ching B.H.
      Herlyn-Werner-Wunderlich Syndrome: a rare presentation with pyocolpos.
      If the obstructed side can periodically empty menstrual blood, due to a connection between the 2 sides, short episodes of very heavy bleeding can be described.
      On physical examination an abdominal mass may be palpated, if the obstruction is chronic. On vulvar exam the external genitalia are normal. Only rarely can a mass be visualized in the case of a very low extending oblique septum. A digital vaginal exam can be attempted, as these girls are usually older and a lateral bulge can often be palpated in the vagina. This can be a very tense mass so that the top of the patent hemivagina cannot be entered and the normal unobstructed cervix (typically very high in the patent vagina), cannot be palpated on the exam. On rectal exam a bulge can be felt. As with the transverse septum, these septa can be more inferior or more superior in the vagina, leading to a low or high bulge on exam.
      • Sanghvi Y.
      • Shastri P.
      • Mane S.B.
      • et al.
      Prepubertal presentation of Herlyn-Werner-Wunderlich syndrome: a case report.
      • Shah D.K.
      • Laufer M.R.
      Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome with a single uterus.
      The initial imaging is usually a pelvic ultrasonography that indicates a pelvic mass, which is then followed by an MRI, leading to the correct diagnosis. Renal imaging is indicated.
      • Sanghvi Y.
      • Shastri P.
      • Mane S.B.
      • et al.
      Prepubertal presentation of Herlyn-Werner-Wunderlich syndrome: a case report.
      • Shah D.K.
      • Laufer M.R.
      Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome with a single uterus.
      An obstructed uterine horn is another situation that presents like the obstructed hemivagina. These patients present shortly after puberty with severe dysmenorrhea that is refractory to any treatment except complete suppression. On examination the vulva appears normal and on bimanual exam 1 cervix is palpated and no bulges are felt either in the vagina or on rectal exam. Ultrasonographic imaging typically reveals a mass but MRI can exactly pinpoint the anomaly with the connections of the obstructed horn to the non-obstructed uterine horn to assist with surgical planning. Renal imaging is indicated.
      • Jayasinghe Y.
      • Rane A.
      • Stalewski H.
      • et al.
      The presentation and early diagnosis of the rudimentary uterine horn.

      Diagnostic Testing

      Besides the history and physical as outlined above, imaging is an important part of the diagnostic process, since precise anatomy of the outflow tract obstruction or absent menarche dictates the management strategy.
      • Junqueira L.P.
      • Allen L.M.
      • Spitzer R.F.
      • et al.
      Müllerian duct anomalies and mimics in children and adolescents: correlative intraoperative assessment with clinical imaging.
      Usually the first imaging modality is ultrasonography. Because a transvaginal approach is often not tolerated or even possible in this population, transabdominal ultrasonography is an appropriate initial imaging modality. On occasion translabial ultrasonography can help to delineate an obstruction. Traditionally the MRI is considered the gold standard for the precise diagnosis of the anomaly, to assess the depth of the vagina, the thickness of a septum, and the extent of the distension of vagina, cervix, and uterus or tubes.
      • Santos X.M.
      • Krishnamurthy R.
      • Bercaw-Pratt J.
      • et al.
      The utility of ultrasound and magnetic resonance imaging versus surgery for the characterization of mullerian anomalies in the pediatric and adolescent population.
      More recently 3D ultrasonography has been used due to the cost and patient inconvenience associated with MRI; however, there is not enough data available to judge the comparison with MRI at this time.
      • Pellerito J.S.
      • McCarthy S.M.
      • Doyle M.B.
      • et al.
      Diagnosis of uterine anomalies: relative accuracy of MR imaging, endovaginal sonography, and hysterosalpingography.
      In any cases of reproductive tract abnormalities involving müllerian structures, there is a high incidence of renal (40%) and spinal (10%-20%) abnormalities. It is important to use additional imaging to screen for these problems depending on the underlying diagnosis. This can be accomplished by renal ultrasonography or MRI of the abdomen as well as by spinal radiography.
      • Santos X.M.
      • Krishnamurthy R.
      • Bercaw-Pratt J.
      • et al.
      The utility of ultrasound and magnetic resonance imaging versus surgery for the characterization of mullerian anomalies in the pediatric and adolescent population.

      Treatment

      Once a diagnosis of the reproductive tract obstruction has been established, this may be addressed medically or surgically. There is a higher rate of endometriosis, hematosalpinx, and pelvic inflammatory disease in these patients, due to the obstruction, so accurate diagnosis and surgical treatment or suppression is indicated.
      • Miller R.J.
      • Breech L.L.
      Surgical correction of vaginal anomalies.
      • Berger A.
      • Batzer F.
      • Lev-Toaff A.
      • et al.
      Diagnostic imaging modalities for müllerian anomalies: the case for a new gold standard.
      • Rackow B.W.
      • Arici A.
      Reproductive performance of women with mullerian anomalies.

      Medical Treatment

      Complete suppression is the goal if delaying surgical management seems appropriate at the time of initial diagnosis. This can be due to patient's young age, when her specific anomaly would necessitate her to dilate her vagina postoperatively, to other illnesses, or to the need to delay surgery to refer to an expert center.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Rackow B.W.
      • Arici A.
      Reproductive performance of women with mullerian anomalies.
      • Taylor E.
      • Gomel V.
      The uterus and fertility.
      Suppression can be accomplished with combined estrogen and progestin hormonal contraception, such as oral contraceptive pills or patches, or progestin only therapy. Alternatively, gonadotropin releasing hormone agonist-antagonist injections with add-back therapy or depot medroxyprogesterone acetate injections can be utilized. Any attempt at complete suppression can be complicated by irregular spotting that may cause significant pain. It is important to discuss this expectation and adequate pain management with teens and their families, in an attempt to reduce emergency department visits for pain episodes. If the suppression is not able to reduce pain, then surgery is indicated.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Rackow B.W.
      • Arici A.
      Reproductive performance of women with mullerian anomalies.
      • Taylor E.
      • Gomel V.
      The uterus and fertility.

      Surgical Treatment

      Imperforate Hymen

      This is usually managed surgically in an urgent fashion. In the operating room a foley catheter can be placed and the excess hymenal tissue can be excised in a cruciate or circular fashion to create a patent vaginal space. Once the membrane is removed and all menstrual contents are suctioned, the obstruction and pain sensation are relieved. There is no risk of stenosis, so no postoperative dilation is necessary. Occasionally this anomaly has been mistakenly diagnosed in a patient with vaginal agenesis. It is imperative to realize in the operating room, when no bulge is palpable and no hematocolpos egresses, that the diagnosis may be incorrect and that the surgeon should stop, reevaluate, and reimage.
      • Miller R.J.
      • Breech L.L.
      Surgical correction of vaginal anomalies.

      Transverse Vaginal Septum

      MRI becomes important to plan surgical management for cases of transverse vaginal septa presenting with hematometrocolpos. First, one must establish if the septum is low, mid or high in its presentation within the vagina. Second, the thickness of the septum must also be considered.
      • Miller R.J.
      • Breech L.L.
      Surgical correction of vaginal anomalies.
      In cases of thin septal walls, these may be excised directly with complete removal of the septal tissue. Subsequently, the normal vaginal mucosa is sewn together to anastomose the upper and lower part of the vagina. When the transverse septum is thick, a variety of techniques can be used to repair this condition.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.

      Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

      • Miller R.J.
      • Breech L.L.
      Surgical correction of vaginal anomalies.
      Often the upper vaginal part is so distended that there is enough upper vaginal mucosa that can be undermined, mobilized, and then brought together to the lower vaginal mucosa after the septum has been resected. If there is not enough normal tissue then the septum may be divided into 2 parts: a distal section and a proximal section. Each section is then marked to create triangular leaflets. It is helpful to make 1 section in an “X” fashion and the other section in a “+” fashion. The 8 leaflets that are subsequently created can then be interdigitated to bridge a larger distance while maintaining normal vaginal caliber.
      • Miller R.J.
      • Breech L.L.
      Surgical correction of vaginal anomalies.
      Regardless of the technique used for postoperative dilation, it is very important to try to prevent stenosis, which is common after a transverse septum resection. Experience has taught that the young patients in whom this is diagnosed find dilation difficult and may not comply, so that use of menstrual suppression to delay surgical repair can be considered, after discussion with the patient and her family.

      Cervical Dysgenesis and Cervico-vaginal Agenesis

      MRI is critical when attempting to establish these diagnoses. The vagina is often congenitally absent; however, a normal or small uterus with atretic or absent cervix may be seen in conjunction with hematometra. A hematosalpinx may also be present since blood may flow retrograde proximally due to the inability to travel outward distally. In the period of immediate diagnosis, it is possible to offer menstrual suppression, as discussed above. In cases, where medical management has failed, it is important to present options to the family. While recent research has looked into ways to reconstruct the cervix, outcomes associated with reconstructive cases to date have often resulted in postoperative complications, including infections, sepsis or even death. The field of transplant medicine continues to expand, and a few reports of uterine transplants have emerged. No studies have addressed uterine transplant in humans thus far. The implications and risks following a transplant with the unknown potential for childbearing would also need to be weighed. Because these options are still very much in the research realm, patients who remain symptomatic on hormonal suppressive therapy may choose to have the uterine remnant structure removed entirely, which will ultimately prevent cyclic pain episodes, but also eliminates the possibility of carrying a pregnancy.
      • Miller R.J.
      • Breech L.L.
      Surgical correction of vaginal anomalies.
      • Riberio S.C.
      • Tormena R.A.
      • Peterson T.V.
      • et al.
      Müllerian duct anomalies: review of current management.

      Obstructed Hemivagina Including OHVIRA

      This vaginal septum resection procedure is usually accomplished vaginally. Once a speculum is placed into the vagina the bulging nonperforated septum may be seen. A solitary cervix is also seen in the normally developed vagina. By placing traction sutures along the septum, the location of the septal edges can be marked prior to decompression of the space. Once the space decompresses, the anatomy is more distorted, so it is helpful to establish landmarks. The nonperforated distended septum may then be entered simply with excision or if there is concern about the oblique lie of the septum or thickness more than 1-2 cm, a spinal needle can be helpful to direct the septal excision in to the proper space. Often the cervix on the obstructed side is very dilated and the edges maybe difficult to establish. Great care needs to be taken not to injure the cervix. Once all septal tissue is safely removed, the hemivaginal mucosa is anastomed circumferentially in interrupted fashion to the vaginal mucosa of the fully developed side. In the situation where microperforation is present and the hemivagina is not distended, or with a septum, located high in the vagina, the edges of the septal cavity can be difficult to determine. It is very important to ensure the septal tissue is resected enough to maintain patency of the space, since resealing of the space, may result in ascending infection and reobstruction. It is also important to determine the location of landmarks, in order to avoid damage to surrounding structures. For this purpose, vaginoscopy can be useful to locate the microperforation. Occasionally, it is also helpful to thread a balloon or catheter into the space through the microperforation. Once the balloon is inflated, the vaginal space with the balloon can be pulled outward to better elucidate the septum and safely resect without risk of damaging surrounding tissues.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.
      • Junqueira L.P.
      • Allen L.M.
      • Spitzer R.F.
      • et al.
      Müllerian duct anomalies and mimics in children and adolescents: correlative intraoperative assessment with clinical imaging.
      • Miller R.J.
      • Breech L.L.
      Surgical correction of vaginal anomalies.
      • Heinonen P.K.
      Clinical implications of the didelphic uterus: long-term follow-up of 49 cases.

      Communicating or Noncommunicating Uterine Horns

      Non-communicating horns may become distended with menstrual products and are best demonstrated by MRI noninvasively. The non-communicating obstructed horn can be managed through minimally invasive techniques, usually with conventional laparoscopy, but the use of robotic laparoscopy technique has also been reported to improve visualization and ease of sewing defects in layers.
      • Breech L.L.
      • Laufer M.R.
      Mullerian anomalies.
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      • Berger A.
      • Batzer F.
      • Lev-Toaff A.
      • et al.
      Diagnostic imaging modalities for müllerian anomalies: the case for a new gold standard.
      In the case of a communicating horn, pain may not be the primary symptom at presentation. Nonetheless, when there is a suspicion of a communication between the uterine horns, signs of infection, persistent pain, or the anatomy is unclear on imaging, there may be a need to evaluate the reproductive structures laparoscopically and/or hysteroscopically. Hysteroscopy may be beneficial in some cases since a communicating horn can be ruled out on the basis of visualizing 1 or 2 tubal ostia. This is primarily important for surgical planning since the removal of a communicating horn, even if the communication is very small, may require oversewing the communicating area to prevent laxity of the uterine wall on the side affected when the horn is removed. This procedure is also usually performed laparoscopically. Among patients presenting with vaginal agenesis and cyclic pain, remnant noncommunicating horns should be suspected. MRI imaging can elucidate functional endometrium in the uterine remnant, resulting in cyclic pain and fluid accumulation into a closed space. Removal of these functional obstructed horns is usually indicated and can also be done laparoscopically.
      • Simpson J.L.
      Genetics of the female reproductive ducts.
      • Berger A.
      • Batzer F.
      • Lev-Toaff A.
      • et al.
      Diagnostic imaging modalities for müllerian anomalies: the case for a new gold standard.

      Lower Vagina Atresia

      In cases of lower vaginal atresia, an upper vagina is present, but no opening is present leading to the introitus.
      • Nguyen L.
      • Youssef S.
      • Guttman F.M.
      • et al.
      Hydrometrocolpos in neonate due to distal vaginal atresia.
      • Jessel R.H.
      • Laufer M.R.
      Management of lower vaginal atresia in patient with a unicornuate uterus.
      The space between the perineum and upper vagina and between the rectaovaginal and vesicovaginal spaces is fibrous. Patients typically present at puberty with progressive pain due to the upper vagina being distended with menses. A procedure known as vaginal pullthrough is performed, involving dissection of the vesicovaginal and rectovaginal spaces to expose the bulging upper vagina. Once this bulge is exposed, the vagina can be entered to expose normal vaginal mucosa above and then mobilized to the perineum, in order to join the upper vagina to the lower vaginal dimple and, subsequently, relieve the outflow tract obstruction.
      • Nguyen L.
      • Youssef S.
      • Guttman F.M.
      • et al.
      Hydrometrocolpos in neonate due to distal vaginal atresia.
      • Jessel R.H.
      • Laufer M.R.
      Management of lower vaginal atresia in patient with a unicornuate uterus.
      In approximately 40% of cases of obstructed müllerian anomalies, endometriosis is diagnosed, due to the obstruction. Although endometriosis associated with obstructive conditions is thought to improve following relief of the obstruction,
      • Rackow B.W.
      • Arici A.
      Reproductive performance of women with mullerian anomalies.
      • Silveira S.A.
      • Laufer M.R.
      Persistence of endometriosis after correction of an obstructed reproductive tract anomaly.
      • Laufer M.R.
      • Sanfilippo J.
      • Rose G.
      Adolescent endometriosis: diagnosis and treatment approaches.
      • Dovey S.
      • Sanfilippo J.
      Endometriosis and the adolescent.
      • Sanfilippo J.
      • Wakin N.G.
      • Schikler K.N.
      • et al.
      Endometriosis in association with uterine anomaly.
      the disease process should be managed in accordance with symptoms. A need for medical and/or surgical treatment of the endometriosis lesions may arise in the future, after the obstruction has been relieved, and should be discussed with the patient as it has been shown that not all cases of endometriosis regress after resolution of the obstructive anomaly.
      • Rackow B.W.
      • Arici A.
      Reproductive performance of women with mullerian anomalies.
      • Silveira S.A.
      • Laufer M.R.
      Persistence of endometriosis after correction of an obstructed reproductive tract anomaly.
      • Laufer M.R.
      • Sanfilippo J.
      • Rose G.
      Adolescent endometriosis: diagnosis and treatment approaches.
      • Dovey S.
      • Sanfilippo J.
      Endometriosis and the adolescent.
      • Sanfilippo J.
      • Wakin N.G.
      • Schikler K.N.
      • et al.
      Endometriosis in association with uterine anomaly.

      Conclusion

      In summary, obstructive müllerian anomalies carry a major theme of pain, whether the pain occurs in the setting of amenorrhea (usually diagnosed at an earlier age following breast development) or associated with menses (often leading to a delayed diagnosis). In order to elucidate the type of obstructive müllerian anomaly present, a thorough history, physical exam, along with confirmatory imaging studies are necessary. Should the need to delay surgery arise, medical therapy is helpful for menstrual suppression and to treat continued pain. Careful planning in advance is critical for surgical treatment and best achieved in a center with expertise in managing these anomalies.

      Appendix

      Level of Evidence
      • Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force:
        • I.
          Evidence obtained from at least 1 properly designed randomized controlled trial.
        • II-1.
          Evidence obtained from well-designed controlled trials without randomization.
        • II-2.
          Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than 1 center or research group.
        • II-3.
          Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.
        • III.
          Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
      • Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:
        • Level A—Recommendations are based on good and consistent scientific evidence.
        • Level B—Recommendations are based on limited or inconsistent scientific evidence.
        • Level C—Recommendations are based primarily on consensus and expert opinion.

      References

        • Breech L.L.
        • Laufer M.R.
        Mullerian anomalies.
        Obstet Gynecol Clin North Am. 2009; 36: 47
        • Simpson J.L.
        Genetics of the female reproductive ducts.
        Am J Med Genet. 1999; 89: 224
        • Philibert P.
        • Biason-Lauber A.
        • Rouzier R.
        • et al.
        Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study.
        J Clin Endocrinol Metab. 2008; 93: 895
        • Christopoulos P.
        • Fotopoulou G.F.
        • Gazouli M.
        • et al.
        Genetic basis for the development of mullerian abnormalities: a review of current evidence.
        Eur J Obstet Gynecol. 2010; 5: 7
        • Christopoulos P.
        • Gazouli M.
        • Fotopoulou G.
        • et al.
        The role of genes in the development of Mullerian anomalies: where are we today?.
        Obstet Gynecol Surv. 2009; 64: 760
        • Buttram Jr., V.C.
        • Gibbons W.E.
        Müllerian anomalies: a proposed classification. (An analysis of 144 cases).
        Fertil Steril. 1979; 32: 40
        • Acién P.
        • Acién M.I.
        The history of female genital tract malformation classifications and proposal of an updated system.
        Hum Reprod Update. 2011; 17: 693
      1. Laufer MR: Structural abnormalities of the female reproductive tract. In: Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology, 6th ed. Edited by Emans SJ, Laufer MR. 2012, p 334.

        • Breech L.L.
        • Laufer M.R.
        Obstructive anomalies of the female reproductive tract.
        J Reprod Med. 1999; 44: 233
        • ACOG Committee on Adolescent Health Care
        ACOG Committee Opinion No. 349, November 2006: Menstruation in girls and adolescents: using the menstrual cycle as a vital sign.
        Obstet Gynecol. 2006; 108: 1323
        • Marcal L.
        • Nofthaft M.A.
        • Coelho F.
        • et al.
        Mullerian duct anomalies: MR imaging.
        Abdom Imaging. 2011; 36: 756
        • Golan A.
        • Langer R.
        • Bukovsky I.
        • et al.
        Congenital anomalies of the müllerian system.
        Fertil Steril. 1989; 51: 747
        • Santos X.M.
        • Krishnamurthy R.
        • Bercaw-Pratt J.
        • et al.
        The utility of ultrasound and magnetic resonance imaging versus surgery for the characterization of mullerian anomalies in the pediatric and adolescent population.
        J Pediatr Adolesc Gynecol. 2012; 25: 181
        • Rock J.A.
        Anomalous development of the vagina.
        Semin Reprod Endocrinol. 1986; 4: 13
        • Sultan C.
        • Gaspari L.
        • Paris F.
        Adolescent dysmenorrhea.
        Endocr Dev. 2012; 22: 171
        • Smith N.A.
        • Laufer M.R.
        Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome: management and follow-up.
        Fertil Steril. 2007; 87: 918
        • Cox D.
        • Ching B.H.
        Herlyn-Werner-Wunderlich Syndrome: a rare presentation with pyocolpos.
        J Radiol Case Rep. 2012; 6: 9
        • Sanghvi Y.
        • Shastri P.
        • Mane S.B.
        • et al.
        Prepubertal presentation of Herlyn-Werner-Wunderlich syndrome: a case report.
        J Pediatr Surg. 2011; 46: 1277
        • Shah D.K.
        • Laufer M.R.
        Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome with a single uterus.
        Fertil Steril. 2011; 96: e39-e41
        • Jayasinghe Y.
        • Rane A.
        • Stalewski H.
        • et al.
        The presentation and early diagnosis of the rudimentary uterine horn.
        Obstet Gynecol. 2005; 105: 1456
        • Junqueira L.P.
        • Allen L.M.
        • Spitzer R.F.
        • et al.
        Müllerian duct anomalies and mimics in children and adolescents: correlative intraoperative assessment with clinical imaging.
        Radiographics. 2009; 29: 1085
        • Pellerito J.S.
        • McCarthy S.M.
        • Doyle M.B.
        • et al.
        Diagnosis of uterine anomalies: relative accuracy of MR imaging, endovaginal sonography, and hysterosalpingography.
        Radiology. 1992; 183: 795
        • Miller R.J.
        • Breech L.L.
        Surgical correction of vaginal anomalies.
        Clin Obstet Gynecol. 2008; 51: 223
        • Heinonen P.K.
        Clinical implications of the didelphic uterus: long-term follow-up of 49 cases.
        Eur J Obstet Gynecol Reprod Biol. 2000; 91: 183
        • Berger A.
        • Batzer F.
        • Lev-Toaff A.
        • et al.
        Diagnostic imaging modalities for müllerian anomalies: the case for a new gold standard.
        J Minim Invasive Gynecol. 2014; 21: 335
        • Rackow B.W.
        • Arici A.
        Reproductive performance of women with mullerian anomalies.
        Curr Opin Obstet Gynecol. 2007; 19: 229
        • Taylor E.
        • Gomel V.
        The uterus and fertility.
        Fertil Steril. 2008; 89: 1
        • Riberio S.C.
        • Tormena R.A.
        • Peterson T.V.
        • et al.
        Müllerian duct anomalies: review of current management.
        Sao Paulo Med J. 2009; 127: 92
        • Nguyen L.
        • Youssef S.
        • Guttman F.M.
        • et al.
        Hydrometrocolpos in neonate due to distal vaginal atresia.
        J Pediatr Surg. 1984; 19: 510
        • Jessel R.H.
        • Laufer M.R.
        Management of lower vaginal atresia in patient with a unicornuate uterus.
        J Pediatr Adolesc Gynecol. 2013; 26: e21
        • Silveira S.A.
        • Laufer M.R.
        Persistence of endometriosis after correction of an obstructed reproductive tract anomaly.
        J Pediatr Adolesc Gynecol. 2013; 26: e93
        • Laufer M.R.
        • Sanfilippo J.
        • Rose G.
        Adolescent endometriosis: diagnosis and treatment approaches.
        J Pediatr Adolesc Gynecol. 2003; 16: S3
        • Dovey S.
        • Sanfilippo J.
        Endometriosis and the adolescent.
        Clin Obstet Gynecol. 2010; 53: 420
        • Sanfilippo J.
        • Wakin N.G.
        • Schikler K.N.
        • et al.
        Endometriosis in association with uterine anomaly.
        Am J Obstet Gynecol. 1986; 154: 39