REPRODUCTIVE TRACT ANOMALIES Prof. M.C.Bansal MBBS., MS., FICOG., MICOG. Founder Principal & Controller, Jhalawar Medical College & Hospital Jjalawar. MGMC & Hospital , sitapura ., Jaipur
Developmental anomalies of the reproductive system represent some of the most fascinating disorders that obstetricians and gynecologists encounter. The mullerian ducts are the primordial anlage of the female reproductive tract. They differentiate to form the fallopian tubes, uterus, the uterine cervix, and the superior aspect of the vagina. A wide variety of malformations can occur when this system is disrupted. They range from uterine and vaginal agenesis to duplication of the uterus and vagina to minor uterine cavity abnormalities.
TERMINOLOGY Hematometra -The distension of the uterus with blood or menstrual fluid. Hematometrocolpos-The distension of the uterus and vagina with blood or menstrual fluid; because the vaginal wall is more distensible, the vagina will preferentially fill before the uterus. Hydrocolpos-The distension of the vagina with fluid; often seen in infants with complex reproductive anomalies. Metroplasty -Uterine reconstructive procedure. Uterine anlagen -An underdeveloped uterine structure that is a remnant of a single embryologic mullerian duct.
Indifferent Embryo Genotype of embryo 46XX or 46XY is established at fertilization At 1-6 wks it is sexually indifferent or undifferentiated stage; that is genetically female and male embryos are phenotypically indistinguishable AT Week 7 begins phenotypic sexual differentiation Week 12 female or male characteristics of external genitalia can be recognized Week 20 phenotypic differentiation is complete.
In utero photograph of a 56-day embryo showing continued growthof the genital tubercle and elongation of the urethral folds that have not yet initiated fusion. The genital swellings remain indistinct.
UROGENITA L SYSTEM INTERMEDIATE PRIMITIVE UROGENITAL SINUS MESODERM VESICO DEFINITIVE URETHRAL UROGENITAL SINUS CANAL hasCRANIAL CAUDAL PELVIC PHALLIC PART PART PART PART PRIMITIVE VAGINALURINARY PLATE URETHRABLADDER FEMALE URETHRA
Indifferent Embryo Components which form the adult female and male reproductive systems are: 1. Gonads ovaries or testes 2. Genital Duct Systems Paramesonephric and Mesonephric Ducts 3. External Genitalia
After the folding of the embryonic disc and the formation of the peritoneal cavity,the intermediate mesoderm forms a bulging on the posterior abdominal wall,lateral to the attachment of the dorsal mesentry of the gut . This bulging is now called the NEPHROGENIC CORD. Its surface is covered by the epithelium lining the peritoneal cavity-COELOMIC EPITHELIUM
Genital Duct Development After about 37 days of fertilization, two pairs of genital ducts appear Mesonephric Duct extending from the mesonephros to the cloaca (urogenital sinus) referred to as the Wolffian system Second duct arises as a longitudinal invagination of coelomic epithelium on the anterolateral surface of the urogenital ridge, known as Paramesonephric or Mullerian Duct.
Paramesonephric Duct Cranial uterine tubes Caudal portions fuse and form the uterovaginal primordium and bring together two peritoneal folds, the broad ligament. Initially they remain separated by a septum but later they fuse to form the uterus.
Paramesonephric Duct Paramesonephric ducts do not make contact with the urogenital sinus. Paramesonephric ducts fuse with the medial wall of the mesonephric ducts. Below the caudal tip of the uterine primordium and above the dorsal wall of the urogenital sinus, with the mesoneprhic ducts lying laterally, a collection of paramesonephric cells forms constituting the Mullerian tubercle.
Female Genital Duct Formation In ovary the absence of testosterone inhibits the development of the mesonephric ducts. The atretic remains form the epoophoron, paraoophoron and Gartner’s ducts. In absence of AMH, paramesonephric ducts form the female internal genital tract.
A-Genital ducts in the female at the end of the second month. B. Genital ducts after descent of the ovary. The only partsremaining from the mesonephric system are the epoophoron, paroophoron, and Gartners cyst
Embryology of Vagina Embryology controversial Derived paramesonephric ducts vs. mesonephric ducts vs. urogenital sinus, or a combination. Most accepted, superior part derived fusion paramesonephric , while inferior part arises from urogenital sinus.
The lower part of the utero-vaginal canal comes in close contact with the dorsal wall of the phallic part of the urogenital sinus The utero-vaginal canal and the urogenital sinus are soon separated from each other by the formation of a solid plate of cells called the VAGINAL PLATE
The endodermal cells of the urogenital sinus proliferate to form 2 swellings called sino- vaginal bulbs These bulbs soon fuse to form 1 mass Most of the vaginal plate is formed from these sino-vaginal bulbs The part of the vaginal plate near the future cervix is derived from mesodermal cells of the utero-vaginal canal.
The vagina is formed by the development of a lumen within the vaginal plate The hymen is situated at the junction of the lower end of the vaginal plate with the uroge
A-uterovaginal canal (mesoderm)in contact with lining ofUGS(endoderm) B-sino-vaginal bulbs are formed by proliferation of endodermal lining C-solid vaginal plate partly derived fromendoderm of sinovaginal bulbs D-vagina formed by canalization of vaginal plate
Inductor role of mesoneprhic duct on vagina sinovaginal bulbs are caudal segments of mesonephric ducts. Between these bulbs and caudally to the paramesonephric ducts, a solid epithelial structure is located contacting the dorsal wall of the urogenital sinus…the mullerian tubercle.
Theory of Mullerian Tubercle. Mullerian tubercle -cellular condensation b/w inferior part of fused paramesonephric ducts and urogenital sinus. Sinovaginal bulbs develop, constitute vaginal plate. Cavity formed is lined with paramesonephric epithelium, opens into the urogenital sinus
Formation of the uterus and vagina. A. 9 weeks. Note the disappearance of the uterine septum. B. At the end of the third month. Note the tissue of the sinovaginal bulbs. C. Newborn. The fornices and the upper portion of the vagina are formed byvacuolization of the paramesonephric tissue, and the lower portion of the vagina is formed by vacuolization of the sinovaginal bulbs.
Mesonephric duct induction Vagina derived from fused mesonephric ducts and Mullerian tubercle. Paramesonephric ducts form uterus to external cervical os and adequate formation is induced by mesonephric ducts. Mesonephric ducts regress cranially but at cervical os, they enlarge and form the sinovaginal bulbs. The paramesonephric cellular condensation (mullerian tubercle ) incorporates itself in the vaginal plate formed by fusion of the two bulbs. Cavitation allows the paramesonephric cells to line the primitive vaginal cavity with paramesonephric epithelium.
Agenesis of mesonephric duct As ureteral bud sprouts from the opening of the mesonephric ducts in the urogenital sinus, the absence or distal agenesis of a mesonephric duct would result in an absence of its opening to the sinus ( the origin of the blind vagina) and in an absence of the ureteral bud on that side. Thus, the definitive kidney would fail to develop (ipsilateral renal agenesis)
Development external genitalia Early, similar in both sexes 6th wk, three external protuberance surround cloacal membrane, the left and right genital swellings meet anteriorly to form the genital tubercle. 12th wk identify difference. Genital swelling labioscrotal folds scrotum or labia major Genital tubercle phallus penis or clitoris
Development of External GenitaliaAnlage Male FemaleGenital Tubercle Glans and shaft Glans and shaft of of penis clitorisUrogenital Sinus Penile urethra Vestibule of vaginaUrethral fold Penis Labia MinoraLabioscrotal fold Scrotum Labia Major
American Fertility SocietyClassification of Mullerian Anomalies
AMERICAN FERTILITY SOCIETY CLASSIFICATION OF UTEROVAGINAL ABNORMALITIES CLASS 1 DYSGENESIS OF MULLERIAN DUCTS CLASS 2 DISORDERS OF VERTICAL FUSION OF THE MULLERIAN DUCTS A) assymetric obstructed disorder of uterus or vagina,usually associated with ipsilateral renal agenesis 1-unicornuate uterus with a non communicating rudimentary anlage or horn
2-unilateral obstruction of a cavity of a double uterus 3-unilateral vaginal obstruction associated with a double uterus B) symmetric unobstructed 1-didelphic uterus a)complete longitudinal vaginal septum b) partial longitudinal vaginal septum c) no longitudinal vaginal septum
Abnormalities in the formation or fusion of the mullerian ducts results in a variety of anomalies of the uterus and vagina: single, multiple, combined, or separate. Failure of development of a mullerian duct is associated with failure of development of a ureteric bud from the caudal end of the wolffian duct. Thus, the entire kidney can be absent on the side ipsilateral to the agenesis of a mullerian duct.
Depending on the timing of the teratogenic influence, renal units can be absent, fused, or in unusual locations in the pelvis. Ureters can be duplicated or can open in unusual places, such as the vagina or uterus polygenic or multifactorial inheritance. Hox-9, 10, 11, 13 are expressed along the length of mullerian ducts. Alteration of HOX genes may give rise to mullerian anomalies involvement of the Y chromosome in the pathogenesis of mÃ¼llerian anomalies has not been considered.
Disorders of Ineffective Suppression of Mullerian Ducts Ambiguous external genitalia frequently are accompanied by a small rudimentary uterus or a partially developed vagina. Additionally, when there is a genetic loss of cytoplasmic receptor proteins within androgenic target cells, such as occurs in the androgen insensitivity syndrome (formerly called testicular feminization syndrome), the vagina is incompletely developed because the existing male gonads suppress the development of the mullerian ducts. genetically male patients ,BUT seen clinically as phenotypic XY females without a completely formed vagina
OTHER EXAMPLES Congenital rectovaginal fistula, imperforate (covered) anus, hypospadias, and other anatomic variants of cloacal dysgenesis These anomalies can be associated with maldevelopment of the mullerian and mesonephric duct derivatives.
CONGENITAL ABSENCE OF MULLERIAN DUCTS include congenital absence of the vagina and uterus. referred as congenital absence of the vagina (vaginal agenesis) accurately labeled aplasia (or dysplasia) of the mullerian ducts because the lower vagina generally is normal, but the middle and upper two thirds are missing. uterus absent rudimentary uterine primordia are present Tubes and ovaries are generally are normal.
CHARESTICS OF WOMEN WITH MULLERIAN AGENESIS Congenital absence of the uterus and vagina (small rudimentary uterine bulbs are usually present with rudimentary fallopian tubes) Normal ovarian function, including ovulation Sex of rearing: female Phenotypic sex: female (normal development of breasts, body proportions, hair distribution, and external genitalia) Genetic sex: female (46,XX karyotype) Frequent association of other congenital anomalies (skeletal, urologic, and especially renal)
Mayer-Rokitansky-Kuster-HauserSyndrome (utero-vaginal agenesis) 15% of primary amenorrhea Normal secondary development & external female genitalia Normal female range testosterone level Absent uterus and upper vagina & normal ovaries Karyotype 46-XX 15-30% renal, skeletal and middle ear anomalies
First seen by a gynecologist at age 14 to 15 years, when the absence of menses causes concern. - Have a normal complement of chromosomes (46,XX) - Usually have normal ovaries and secondary sex characteristics, including external genitalia. - Menstruation does not appear at the usual age because the uterus is absent, but ovulation occurs regularly. - There are some exceptions to the rule of normal ovaries. For example, polycystic ovaries and gonadal dysgenesis have been reported in patients with congenital absence of the vagina. - Additionally, nested polymerase chain reaction demonstrated the presence of testis-specific protein 1-Y- linked (TSPY) gene in two women
Associated Urologic and Renal Anomalies Incidence-47% includes unilateral renal agenesis, unilateral or bilateral pelvic kidney, horseshoe kidney, hydronephrosis, hydroureter, and a variety of patterns of ureteral duplication.
Associated Skeletal and Other Anomalies spine (wedge vertebrae, fusions, rudimentary vertebral bodies, and supernumerary vertebrae), the limbs and ribs also can be involved. Other anomalies include syndactyly, absence of a digit, congenital heart disease, and inguinal hernias,
Vertical Fusion Defects: obstructive and non-obstructive Incomplete cavitation of the vaginal plate formed by the down-growing mullerian ducts and the up-growing urogenital sinus. Can be considered in two categories: 1.Imperforate Hymen 2.Transverse Vaginal Septum
VAGINAL ABNORMALITIESDevelopmental abnormalities of the normal single vagina include: Vaginal agenesis Vaginal atresia Double vagina Longitudinal vaginal septum Transverse vaginal septum
TRANSVERSE VAGINAL SEPTUM Vertical fusion - complete cavitation of the vaginal plate between the sinovaginal bulbs and uterovaginal canal. Transverse vaginal septum may be caused by a failure of this process incidence of 1 in 70,000 females. The septum may be obstructive, with accumulation of mucus or menstrual blood, or may be non-obstructive, allowing for flow of mucus and blood. Transverse vaginal septum can develop at any level within the vagina but is more common in the upper portion, that is, at the junction between the sinovaginal plate and the caudal end of the fused müllerian ducts 46 percent of septa were located in the upper vagina, 35 percent in the middle, and 19 percent in the lower portion of the vagina. The thickness of the septum may be variable, and thicker septa tend to be located nearer the cervix. Typically, a septum is thin (average thickness of 1 cm
In neonates and infants, obstructive transverse vaginal septum causes fluid and mucus collection in the upper vagina, resulting in a mass that that may be large enough to compress abdominal or pelvic organs limit diaphragmatic movement, and neonatal deaths have been reported. pyomucocolopos, pyometria, and pyosalpinges may develop . In contrast to other defects of the mullerian ducts, transverse vaginal septum is fortunately associated with few urologic abnormalities.
Patients with obstructive transverse vaginal septum usually present during adolescence with cyclic lower abdominal pain Amenorrhea gradual development of a central pelvic mass.Patients with nonobstructive transverse vaginal septum typically complain of abnormal menstrual flow pain with intercourse, difficulty in placing or removing tampons obstructed labor.
Longitudinal vaginal septum Results from defective lateral fusion and incomplete reabsorption of the paired müllerian ducts. These septa are generally seen with partial or complete duplication of the cervix and uterus. Pt complain of difficulty with intercourse or with complaints of vaginal bleeding In an obstructive variety of longitudinal vaginal septum -patient presents in adolescence with normal menarche, but reports worsening monthly unilateral vaginal and pelvic pain . On examination, a patent vagina and cervix is noted, but a unilateral vaginal and pelvic mass can be seen. The mass represents obstruction of one of the hemivaginas associated with uterine duplication.
Vaginal Agenesis Females with vaginal atresia lack the lower portion of the vagina, but otherwise have normal external genitalia. The embryonic origin of this condition is presumed to involve failure of the urogenital sinus to contribute its expected caudal portion of the vagina . As a result, the lower portion of the vagina, usually one fifth to one third of the total length, is replaced by 2 to 3 cm of fibrous tissue. In some individuals, vaginal atresia may extend to near the cervix.
condition doesn’t becomes apparent until the time of expected menarche. cyclic pelvic pain due to hematocolpos or hematometra. On physical examination, normal breast and pubic hair development is present. The perineum is usually normal, with normal secondary sex characteristics with a hymeneal ring and beyond the ring, a vaginal dimple or small pouch. A rectoabdominal examination confirms the presence of midline structures
sonographic or MR imaging will display upper reproductive tract organs. MR imaging is a more accurate diagnostic tool, as the length of the atresia, the amount of upper vaginal dilatation, and the presence or absence of a cervix can be identified. Laparoscopy, is necessary for diagnosis when the anatomy cannot be fully evaluated with radiographic studies.
OBSTETRICAL SIGNIFICANCE OF VAGINAL ABNORMALITIES Complete mullerian agenesis – pregnancy is impossible because uterus and vagina is absent About one third of women with vaginal atresia have associated urological abnormalities Complete vaginal atresia – precludes pregnancy by vaginal intercourse unless corrected operatively In most cases of partial atresia, because of pregnancy- induced tissue softening, obstruction during labor is gradually overcome.
By the 12th week, the paramesonephric ducts and/or upper vagina joins with the vaginal plate, which canalizes beginning caudally and creates the lower vagina. By the fifth month of gestation, the canalization of the vagina is complete. The hymen is formed from the proliferation of the sinovaginal bulbs, becoming perforate before or shortly after birth. An imperforate hymen results when this "sheet" of tissue fails to completely canalize. Varying degrees of perforation result in findings such as a cribiform or septate hymen.
Imperforate Hymen: Diagnosis/ Treatment Classic appearance of bulging, blue-domed, translucent membrane Cyclic pelvic pain due to hematocolpos hematometria, or hematosalpinx Bulging hymeneal membrane or a blind-ending pouch on exam. Pelvic/Rectal exam, U/S, MRI Rarely urologic anomalies. Tx: Cruciate incision
Lateral Fusion Defects:obstructive and non-obstructive
Lateral Fusion Defects Most common type of mullerian defects The resulting organs are either asymmetric or symmetric and obstructed or nonobstructed. Result from failure of formation of one mullerian duct, migration of a duct, fusion of the mullerian ducts, or absorption of the intervening septum. Defective resorption of the septum between the fused mullerian ducts results in a uterine septum, which may extend either partially down the uterus or the full length to the cervix. This is the most common uterine defect.
Obstructive Defect of Lateral Fusion: Failure of lateral fusion of two mullerian ductsand failure of one duct to communicate with the outside, thus unilateral obstruction. Uterus didelphys with obstructed hemivagina with ipsilateral renal agenesis
Obstructed Lateral Fusion: Presentation Dysmenorrhea, abd pain, vaginal masses, intermittent foul odor, mucopurulent discharge, endometriosis IVP generally shows renal agenesis on obstructed side. diagnosis is difficult: U/S, HSG, MRI treatment: excision of septum or excise obstructed uterine horn to prevent endometriosis or pregnancy in rudimentary horn
Uterine didelphys Two mullerian ducts fail Generally have good to fuse, thus duplication of reproductive system. outcomes. Generally limited to uterus A septated vagina may and cervix (uterine didelphys and bicollis occur in 75% of cases (two cervices), although and may cause duplication of vulva, difficulty with bladder, urethra, vagina intercourse or vaginal and anus may also occur delivery.
This anomaly is distinguished from bicornuate and septate uteri by the presence of complete nonfusion of the cervix and hemiuterine cavity Except for ectopic and rudimentary horn pregnancies, problems associated with uterine didelphys are similar but less frequent than those seen with unicornuate uterus Complications may include - preterm delivery (20%) - fetal growth restriction (10%) - breech presentation (43%) - cesarean delivery rate (82%)
Uterine didelphys with complete vaginal septum Resection of septum: metroplasty or hysteroscopic resection of septum Obstructed hemivagina and ipsilateral renal agenesis will have regular menses, but pain.
Unicornuate Uterus Reproductive potential is essentially normal high risk for infertility, endometriosis, Risk for spontaneous abortions,Pre term labour, IUFD,breech presentations No septum, no intervention. Asymmetric lateral fusion defect. One cavity normal with fallopian tube and cervix, while the failed mullerian duct has various configurations. Affected mullerian duct may not develop or develop partially as horn or an anlager. It may or may not communicate. Most rudimentary horns are asymptomatic, others contain functional endometrium that is shed cyclically. If the rudimentary horn is obstructed (without communication to the other uterus or cervix), the women may develop cyclic pain and may require surgical excision of the obstructed horn. DX: HSG, IVP, U/S, MRI, no treatment.
1. Unicornuate 2. Unicornuate with uterine horn (not containing an endometrial cavity) not fused to unicornuate uterus
1. Unicornuate with uterine horn (no endometrial cavity)fused to unicornuate uterus 2. Unicornuate uterus with noncommunicating horn containing endometrial cavity not fused
Bicornuate and Septate Uteri Bicornuate: Septate: – Fundus indented – Normal external surface, – Partial fusion of mullerian need laparoscopy to dx ducts – Defect in canalization or – Variable degree of resorption of midline septum separation of uterine horns between mullerian ducts. that can be complete, – Septum can cause infertility, partial or minimal recurrent midtrimester loss – HSG won’t dx, need – Tx: resection of septum laparoscopy hysteroscopically or – Minimal reproductive problems, however can hysteroscopic metroplasty have pregnancy loss, PTL, etc.
BICORNUATE UTERUS Marked increase in miscarriages that is likely due to the abundant muscle tissue in the septum Pregnancy losses in the first 20 weeks 70 percent for bicornuate 88 percent for septate uteri There also is an increased incidence of preterm delivery, abnormal fetal lie, and cesarean delivery.
DES RELATED ABNORMALITIES Development of rare vaginal clear cell adenocarcinoma. Increased risk of developing cervical intraepithelial neoplasia small-cell cervical carcinoma vaginal adenosis, non-neoplastic structural abnormalities
Structural Abnormalities: transverse septa, circumferential ridges involving the vagina and cervix cervical collars s smaller uterine cavities shortened upper uterine segments T-shaped and irregular oviduct abnormalities
Reproductive Performance Women exposed to DES in utero in general have impaired conception rates possibly associated with cervical hypoplasia and atresia Their incidences of miscarriage, ectopic pregnancy, and preterm delivery are also increased, especially in women with structural abnormalitiesTransgenerational Anomalies Genital tract anomalies have been described in the offspring of women exposed to DES when they were a fetus
CERVICAL ABNORMALITIESAtresia. The entire cervix may fail to develop. This may be combined with incomplete development of the upper vagina or lower uterusDouble cervix. Each distinct cervix results from separate müllerian duct maturation. Both septate and true double cervices are frequently associated with a longitudinal vaginal septum. Many septate cervices are erroneously classified as double.Single hemicervix. This arises from unilateral müllerian maturation.Septate cervix. This consists of a single muscular ring partitioned by a septum. The septum may be confined to the cervix, or more often, it may be the downward continuation of a uterine septum or the upward extension of a vaginal septum.
VULVAR ABNORMALITIESAtresia Complete atresia of the vulva includes atresia of the introitus and lower third of the vagina. In most cases, however, atresia is incomplete and results from adhesions or scars following injury or infection The defect may present a considerable obstacle to vaginal delivery, deep perineal tears may result. Labial Fusion Most commonly due to congenital adrenal hyperplasia.