Imperforate Hymen: Varied Presentation, New Associations, and Management.

AIM: Imperforate hymen is an isolated and sporadic event. The aim of this study was to report varied clinical and management problems of consecutive imperforate hymen in children and to compare the genetic review with literature.
MATERIALS AND METHODS: This is a retrospective analysis of eight consecutive imperforate hymen children admitted during 2010-2015.
RESULTS: Among eight girls, two were infants and six were in the adolescent group. Clinical presentations included varied degree of genitourinary obstruction (7) and incidental finding (1). Genetic analysis of imperforate hymen suggested sporadic event (5), associations (2), and syndromic (1). Ultrasound and magnetic resonance imaging revealed the level of obstruction. Hymenectomy was done in neonate (1), adolescent (6), and one has been under observation. Abdominoperineal pull-through was done in concomitant proximal vaginal atresia.
CONCLUSIONS: Hymen development origin is variable and complex. Imperforate hymen is rarely a part of systemic/genetic anomaly. Genital examination at birth or during puberty is mandatory which often guides the timing of hymenectomy and prevents the sequelae of imperforate hymen. Hymenectomy is ideal during puberty and resolves all genitourinary obstructions.

INTRODUCTION

Hydrometrocolpos is a pathological distension of uterus and vagina with an excessive amount of fluid in the presence of vaginal outflow obstruction.[12] Imperforate hymen is the most common and distal congenital anomaly of female genital tract obstruction.[12] Imperforate hymen with/without hydrometrocolpos is detected during puberty or in newborn period and rarely antenatally.[12] Prognosis depends on the time of detection, presence of infection, surgical management, and associated anomalies.[123] Associated anomalies include the McKusick–Kaufman syndrome, mullerian dysgenesis syndrome, anorectal malformations, staphyloma of the left eye, and severe hydrops.[123] Peter plus syndrome has varied clinical presentations such as corneal opacity, glaucoma, and systemic anomalies.[4567]

We report a neonate and adolescent girls presenting with bladder outlet obstruction due to hydrometrocolpos, success of semi-elective decompression, rare association of the imperforate hymen with Peter plus syndrome, proximal vaginal atresia, bladder exstrophy and epispadias complex, and with brief embryological analysis.

MATERIALS AND METHODS

This is a retrospective, descriptive, observation analysis of imperforate hymen children admitted during 2010–2015 [Table 1].

Table 1

Clinical analysis of imperforate hymen children

RESULTS

Age at presentation varied from neonates (2) to adolescence (6) [Table 1]. Urinary retention and midline mass were the common mode of presentations. Family history was noncontributory. Informed consent and ethical issues were discussed before planning for surgery. All patients had bulging imperforate hymen except one who had the double obstruction. Ultrasound, contrast-enhanced computerized tomography (CECT), magnetic resonance imaging (MRI), and micturating cystourethrography were helpful in identifying the level of obstruction and complications of the genitourinary system. Peter plus syndrome, bladder exstrophy, and epispadias complex [Figure 1] were the new syndromes/associations that have been reported in our study. One girl also had proximal vaginal atresia [Figure 2] who required the abdominoperineal pull-through. She had trigonal injury and recovered without any sequela. She received two cycles of leuprolide acetate postoperatively, a potent gonadotropin-releasing hormone receptor agonist. She has been on regular dilatation program. Hymenectomy was successful in both the symptomatic neonate and the adolescents. Follow-up varied from 6 months to 3 years and was asymptomatic.

Figure 1

Imperforate hymen girls showing features of Peter plus syndrome {(vertical arrow-bilateral central corneal opacity)} and post operative case of bladder exstrophy-epispadias complex with imperforate hymen (horizontal arrow)

Figure 2

Magnetic resonance imaging showing hydrometra (vertical arrow), proximal vaginal atresia (left arrow), and collapse vagina (right arrow)

DISCUSSION

Incidence of imperforate hymen is 0.0014%–0.1% in newborns.[1] Cervical glands secrete mucus under the influence of pre-/post-natal maternal estrogen.[2] Imperforate hymen, transverse vaginal septum, and vaginal atresia with or without persistence of a urogenital sinus (UGS) of cloaca are the common causes of the secretory hydrometrocolpos.[12] Hymen perforation occurs commonly during fetal life or perinatal period.[12] However, there have been case reports of spontaneous hymen rupture in early years of life and adolescent period. Therefore, imperforate hymen diagnosis is made at different ages of life.

Imperforate hymen has varied clinical presentations such as incidental finding, midline lower abdominal mass with or without protruding hymen, obstructive uropathy, urinary tract infection, constipation, acute renal failure, acute abdomen with paralytic ileus, primary amenorrhea/cyclical abdominal pain, and respiratory distress.[12] Imperforate hymen protrudes or bulges on valsalva maneuver, but not in the double obstruction. Urological complications are reported in more than 50% of complex congenital vaginal malformation either in neonates or during puberty.[238910111213] Hydrometrocolpos causes acute urinary retention from urethral compression/urethral angulation or due to sacral plexuses irritation.[14] Obstructive uropathy was the common mode of presentation in our series.

Two mullerian ducts (MDs) fuse and form a single uterovaginal canal in around 8–10 weeks.[123] Vagina is developed from uterovaginal canal and sinovaginal bulb.[123] Complete patent vagina is formed around the 5th month.[2] Vagina has six different developmental phases.[9] Hymen development has dual origin from sinovaginal bulb and UGS or from isolated origin of UGS.[215] It separates the vagina from UGS cavity and vestibule.[12] Embryological defects can occur during development, differentiation, migration, apoptosis, fusion, and canalization.[3] Vaginal atresia with hydrometrocolpos may be part of complex syndromic anomalies which include Mckusick–Kaufman syndrome and Bardet–Biedl syndrome.[128] Imperforate hymen is a local fusion anomaly with defective resorption of mullerian septum, and it is a sporadic event.[123] However, the development of mesonephric ducts, paramesonephric ducts, and UGS structures is interdependent, and their paracrine actions also have a role in hymen development. Therefore, hymen anomalies may present with concomitant anomalies of the above three structures.[21112]

Homeobox gene, bone morphogenetic protein 4, sonic hedgehog, transformation-related protein P63, and retinoic acid growth factors are required for vaginal development.[12] T-box transcription factor gene alterations have been implicated in imperforate hymen.[12] There have been rare case reports of familial, polygenetic, autosomal dominant/recessive, and X-linked inheritances of imperforate hymen.[1112] Our cases are classified into Type IV B vaginal malformation except the double obstruction case.[1239] Ruggeri et al.'s classification is most useful in defining the embryological insult, understanding the pathogenesis with clinical implications and suggesting appropriate management for vaginal anomalies. Cloacal membrane premature rupture, UGS, and mesodermal abnormalities are implicated in bladder exstrophy and epispadias complex with multiple urorectogenital abnormalities. Vaginal stenosis with anterior displacement is common in exstrophy complex, but imperforate hymen association is rare. Concurrent anomalies of imperforate hymen are transverse vaginal septum and vertical septal anomalies,[129] but proximal vaginal atresia is rare. Hymen develops even in vaginal agenesis with a contribution from UGS.[15] In our case, patent distal vagina and hymen might have developed from UGS.[15] Hence, vagina is a complex embryological organ with variable developmental contributions from MDs, UGS, and all the three germ layers.[15]

Midline systemic defects such as cleft palate/lip, anal atresia, and spina bifida are reported in Peter plus syndrome. At present, we are adding imperforate hymen as a midline defect to the list of Peter plus syndrome which has not been reported in the Online Mendelian Inheritance in Man database. It is a new nonrandom occurrence of association. Craniofacial abnormalities represent a deficiency, excess, or absence of an embryonic developmental field.[7] Peters anomaly and facial dysmorphism of our case may be due to invisible or dwarf of neuromeric organization such as basal prosomeres5, r0, rl-5 mesencephalic neuromeres, and somitomeres 8–11.[7] Autocrine and paracrine actions of retinoic acid are necessary for the development of neural crest-derived periocular mesenchyme and UGS mesoderm in early embryology.[121617] Retinoic acid signaling and/or aldehyde dehydrogenases abnormality might have been the problem in our case.

History and perineal examination in frog leg position can diagnose imperforate hymen.[12] However, ultrasound, CECT scan, MRI, endoscopy, laparoscopy, echocardiography, karyotype, and infantogram have been useful in investigating patients of hydrometrocolpos and their associated congenital malformation.[1237818] These children may require comprehensive multi-surgical specialty management with lifelong follow-up.[18] Timing and types of hymenectomy/hymenotomy depend on age, symptoms, associated urogenital anomaly, hymen function, and ethical issues such as virginity-sparing surgeries.[1314] Hymenectomy is advisable and successful after the onset of thelarche, but within 2 years or just before menarche because girls will have estrogen-primed hymen, developed and well-delineated anatomical structures. Cruciate incision, hymen trimming, and marsupialization with vaginal epithelium are different types of surgical methods that keep the outlet intact for adequate functioning of the endometrium. Central circular hymenectomy leaves the intact hymen annular and solves the ethical issues of defloration.[19] It has clinically good results, but informed consent is a must.[19] Women with isolated imperforate hymen shall have normal fertility rate after early correction. Gonadotropin-releasing hormone receptor agonist suppresses the initial menstrual cycles postoperatively and allows the smooth healing of abdominoperineal pull-through surgery.

CONCLUSIONS

Imperforate hymen is a local fusion anomaly and is rarely a part of the systemic inherited disorder. Imperforate hymen is one of the new midline associations included in Peter plus syndrome. Imperforate hymen with concurrent proximal vaginal atresia is rare and explains the varied embryological origin of vagina and hymen. Genital examination should be emphasized as a routine part of newborn/well child evaluation program and in adolescent girls with urogynecological problems. Prognosis depends on early detection and treatment and the severity of associated anomalies. A thorough knowledge of embryology, proper cross-sectional imaging, and comprehensive surgical planning shall have good success in complex vaginal anomaly.

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Nil.

Conflicts of interest

There are no conflicts of interest.