The Female Genital System
E. Stanton Adkins III
Department of Pediatrics and Surgery, University of South Carolina School of Medicine, Palmetto Health Children’s Hospital, Columbia, South Carolina 29203.
The pediatric general surgeon often confronts problems ranging from disorders in the development of the female genital system to infections, tumors, and sexual abuse. Endoscopic techniques such as urethroscopy, vaginoscopy, and laparoscopy, as well as improvements in radiologic imaging, have advanced our ability to evaluate and treat children with disorders of the genital system.
EMBRYOLOGY
The ovary arises from genital ridge mesenchyme and is populated by germ cells (1). The fallopian tubes, uterus, and upper vagina develop from the müllerian ducts. The lower vagina and external genitalia are derived from the urogenital sinus and ridge. Some minor structures are attributable to the wolffian ducts (2).
THE OVARY
The ovary consists of germ cells and the supporting stroma. Germ cells may be found in a 24-day embryo in the caudal portion of the yolk sac near the allantoic stalk. During the fifth week of gestation, these germ cells migrate dorsally along the wall of the yolk sac and the gut until by the end of the week they reach the genital ridge. Once the genital ridge becomes populated with germ cells, the gonad forms. By the seventh week, it differentiates into a recognizable ovary.
The genital ridge develops into the supporting stroma of the ovary. The coalescence of mesenchyme from the ventral medial aspects of the mesonephros and overlying coelomic epithelium form the genital ridge. Germ cells follow the gradient of stem cell factor from the yolk sac to the gonad (3). Germ cells are likewise necessary for the differentiation of gonadal stroma into an ovary or testis. Arrest of the migration of germ cells leads to failure of the ovary to develop.
As the embryo grows, epithelial cords of cells, the sex cords, grow into the mesenchyme. By the eighth week, some differentiation has occurred. In males, the sex cords develop into seminiferous tubules and the rete testis; in females, the sex cords regress. Testis determining factor (SRY) appears to be the necessary element for growth and differentiation of the sex cords. In its absence, the sex cords in the medullary portion of the gonad regress over several months.
Once germ cells reach the ovary, they are termed oogonia. At approximately the 15th week, oogonia enter into prophase of the first meiosis and are termed oocytes.
The oocytes become enclosed or encased with granulosa cells and mesenchymal theca cells. Follicles deep within the ovary become atretic, whereas superficial follicles (those formed most recently) are preserved to form the ovarian cortex. At puberty with each estrous cycle several of the primary follicles mature and complete the first meiosis with ovulation. The second meiosis does not occur until after ovulation when a sperm encounters the ovum.
MÜLLERIAN DUCT
The müllerian ducts appear in embryos of both sexes late in the sixth week. Each duct originates as a groove lateral to the developing gonad and kidney that tubularizes as the edges of the groove come together.
The paired müllerian ducts lie lateral to the wolffian ducts cranially and, at the more caudal extent, are medial to the wolffian ducts. Soon after their development, the caudal portion of the müllerian ducts fuse to form a single canal. As the fusion proceeds cranially, the müllerian duct system develops first a Y and then a T shape.
The müllerian duct fuses with the urogenital sinus at the ninth week and forms a single tube by the third month. As the embryo grows, the point of fusion with the urogenital sinus elongates. This portion has no lumen and gives rise to the vagina. The vagina itself develops when this vaginal plate recanalizes at approximately the sixth month. The proximal two-thirds of the vaginal plate is of müllerian duct origin and the lower one-third is of urogenital sinus origin.
The uterus, cervix, and fallopian tubes arise from the persistently patent portions of the müllerian duct. The tubes originate from the unfused lateral extensions of the müllerian ducts. The uterine body and cervix develop from the fused portion of the müllerian ducts. A small constriction indicates the division between the uterus and the cervix.
UROGENITAL SINUS
The urogenital sinus gives rise to the external genitalia and the lower one-third of the vagina. External genitalia arise starting at the fourth week from the cloacal membrane. On the anterior margins of this membrane are two genital swellings; on the posterior margins are paired anal swellings. The cloacal membrane remodels to become a groove between urogenital folds at the sixth week. At this stage, the perineal body forms separating the anus from the urethral groove. The fusion anterior to the groove becomes the phallus. During the eighth week, labioscrotal swellings lateral to the phallus move caudally to form the labia minora. The clitoris develops from the phallus and extends posteriorly into two corpora cavernosa of erectile tissue.
WOLFFIAN DUCT
The wolffian duct originates as the duct system for the primitive kidney, the pronephros. It becomes associated with the mesonephros, the first functional kidney, sometime after the fifth week of life. The duct connects with the urogenital sinus and persists as a defined structure for only a short time in the female. By the mid-fourth month the opening into the urogenital sinus closes. Although some structures of wolffian origin persist into adulthood, one structure, Gartner’s canal, persists in the wall of the cervix and upper vagina in approximately 20% of adults, and may become an ectopic opening for the ureter.
ANATOMY, GROWTH, AND DEVELOPMENT
The ovary migrates from the genital ridge to the pelvic brim in the third month of gestation. It remains an abdominal structure until birth and then descends into the pelvis. The uteroovarian ligament attaches the ovary to the uterus. The round ligament extends from the upper uterine cervix out through the inguinal ring and terminates diffusely in the labia majora.
The uterus is a muscular organ with a normal position anteflexed relative to the cervix and anteverted relative to the vagina. The adnexa consist of the fallopian tubes, ovaries, and broad ligaments that are lateral on either side. The fallopian tubes lie anterior to the uteroovarian ligament and posterior to the round ligament of the uterus. They are enveloped in the broad ligament. The broad ligament extends from the uterus to the pelvic sidewall.
The vagina lies just posterior to the bladder and urethra. It extends from the vestibule to the uterine cervix and is lined with squamous epithelium. The course of the vagina parallels that of the pelvic brim and is essentially horizontal. The cervix penetrates the anterior wall of the vagina near its apex. The surface of the vagina forms a collapsed H-shaped tube, which when distended possesses a series of horizontal folds or rugae.
The external genitalia consist of the labia majora that extend from the mons pubis anteriorly and posteriorly to the labial commissure at the perineal body. The labia majora are covered with skin. The labia minora lie medial to the labia majora and are covered with squamous mucosa. Anteriorly, the labia minora join to form the prepuce of the clitoris. The labia minora define the lateral margins of the vestibule. Within the vestibule, one finds the urethra in the anterior midline. Slightly posterior to that is the vaginal orifice that is covered by a membrane, the hymen.
In the infant, the labia majora, labia minora, and clitoris are relatively larger and more prominent than they are later in life. With the onset of puberty, the labia majora and mons pubis become covered with hair. The vagina is moistened with cervical mucus because the vagina has no glands of its own. With puberty, the vagina becomes colonized by Lactobacillus acidophilus, which lowers the pH of the vagina.
At birth, when the female child leaves the maternal environment, estrogen levels, which had been high, begin to fall. The levels stay low until shortly before puberty. Growth of the genitalia is hormonally governed and therefore does not parallel the linear growth of the child.
The ovary doubles in size in the first 6 weeks of life. Thereafter, it grows very slowly until just before puberty when the growth rate increases. The newborn ovary often has follicles present and may have some follicular cysts. In most situations, the cysts resolve by the time the girls are several months old.
VASCULAR SUPPLY
Ovarian arteries arise from the aorta bilaterally. The ovarian veins connect to the vena cava on the right and the renal vein on the left. The ovarian vessels travel with the ureters initially and cross the iliac vessels at the iliac bifurcation. The remaining blood supply of the deep organs comes from the hypogastric arteries with the largest branch being the
uterine artery, which proceeds toward the uterine cervix and then branches to send one marginal artery along the lateral aspect of the uterus and one along the vagina. The external pudendal artery (a branch of the external iliac), the internal pudendal artery (a branch of the hypogastric), and the hemorrhoidal vessels supply the vulva and lower one-third of the vagina. With the exception of the ovarian veins, the genital venous drainage parallels that of the arterial supply.
uterine artery, which proceeds toward the uterine cervix and then branches to send one marginal artery along the lateral aspect of the uterus and one along the vagina. The external pudendal artery (a branch of the external iliac), the internal pudendal artery (a branch of the hypogastric), and the hemorrhoidal vessels supply the vulva and lower one-third of the vagina. With the exception of the ovarian veins, the genital venous drainage parallels that of the arterial supply.
LYMPHATIC VESSELS
The perineum, vulva, and lower anterior abdomen drain toward the ipsilateral subinguinal and inguinal nodes, first entering the superficial nodes and then draining more deeply to the deep inguinal nodes. From there, drainage proceeds up the iliac chain. The internal drainage proceeds to the ipsilateral hypogastric, common iliac, and occasionally aortic or periaortic nodes. Only occasionally do the pelvic viscera drain to the inguinal nodes.
PUBERTY
Puberty is the transition from childhood to adulthood during which a child develops into a physically mature and reproductively capable adult. Maturation of the primary sexual characteristics, genitals and gonads, is heralded by the appearance of axillary and pubic hair and the development of breast buds. The hormonal control of puberty begins with the release of an increased amount of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which stimulates the pituitary to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These in turn stimulate the ovary. Estrogen and progesterone synthesis and secretion increase markedly with the onset of puberty. It is these steroids that lead to the development of the secondary sexual characteristics.
Precocious Puberty
Precocious puberty is defined as the development of secondary sexual characteristics before the age of 8 years or the onset of menarche before the age of 10 years. Precocious puberty may be either central, which is GnRH dependent; peripheral, which is GnRH independent; or incomplete, which involves the expression of some primary or secondary sex characteristics but not others.
Central precocious puberty may be idiopathic, but is generally due to a central nervous system dysfunction. The dysfunction may originate from congenital defects, tumors, other space-occupying lesions, hydrocephalus, inflammation, trauma, or radiation. Central precocious puberty is always isosexual. It is diagnosed by performing a GnRH challenge and seeing marked increases in both serum FSH and LH. It may be treated surgically to remove the inciting cause or medically using a GnRH analogue to suppress pituitary release of LH and FSH.
Peripheral, GnRH-independent precocious puberty is due to the presence of inappropriate levels of circulating sex steroids. These steroids may be either exogenous or endogenous. Exogenous steroids include oral contraceptives, anabolic steroids, and rarely estrogen-like environmental chemicals. The endogenous causes include ovarian tumors or cysts, as well as some feminizing adrenal tumors. Peripheral precocious puberty may be isosexual or heterosexual, depending on which steroids are present in greatest concentration. Serum LH and FSH levels are normal or low for age. Once exogenous sources of steroids have been ruled out, workup involves search for a tumor. The tumor may arise from the ovary or adrenal gland. Imaging with computed tomography (CT) scan or magnetic resonance imaging (MRI) can locate and define the lesion. Surgical resection of the tumor is usually curative. Adjuvant chemotherapy or radiation may be necessary for malignancies.
Incomplete sexual precocity may involve premature thelarche, premature pubarche, or premature menarche. Premature thelarche or early breast development presents with subareolar nonprogressive breast development that may be unilateral or bilateral. There are no areolar changes associated with this self-limited process. If the breast development is progressive or does not show signs of regression after 1 to 2 years, an endocrine evaluation is indicated. Premature pubarche involves the early development of pubic hair and is a sign of androgen excess. Pubarche does not normally occur before the age of 8, although some African Americans may have a normal physiologic pubarche several months earlier. If the age of onset is sufficiently early or signs of virilization should appear, endocrine evaluation is indicated. Androgen-producing tumors or adrenal hyperplasia may be responsible.
Premature menarche or vaginal bleeding is a normal event in some newborns with the withdrawal of maternal estrogen stimulation. Estrogen-producing cysts may lead to bleeding when they rupture and estrogen levels fall. Otherwise, isolated menarche is rare. Vaginal bleeding from nonendocrine causes such as vulvovaginitis, trauma, abuse, or malignancy is more common and must be excluded.
OVARY
Ovarian disorders typically present with pain or a mass. Pain is often due to rupture of a cyst and requires no therapy. Occasionally, pain is a symptom of torsion of the ovary and requires emergent surgery. Ovarian masses may be found on physical examination during ultrasound or
CT examination. Rapid assessment and intervention may prevent ovarian loss and preserve fertility.
CT examination. Rapid assessment and intervention may prevent ovarian loss and preserve fertility.
Ovarian Cysts
Functional ovarian cysts occur when a follicle or corpus luteum fails to regress. In the perinatal period, ovarian cysts are often discovered during maternal ultrasound. Following these cysts with serial ultrasound shows resolution of the cyst as newborn hormone levels fall. In pubertal females, cysts 3 to 8 cm in diameter may be seen. Observation over two menstrual cycles of cysts less than 5 cm in diameter will often show regression. If enlargement occurs or the cyst persists beyond 3 months with a diameter of 5 cm or greater, surgical resection is indicated to prevent torsion. The incidence of infertility following ovarian cystectomy is high. Use of atraumatic technique and meticulous hemostasis to minimize adhesion formation may lessen the incidence of infertility thereafter. When performed laparoscopically, a stripping technique with bipolar cautery for hemostasis has been effective.
Ovarian Torsion
Ovarian torsion is one of the few gynecologic emergencies a pediatric surgeon encounters. Prompt diagnosis and treatment can salvage a viable ovary in up to 70% of patients. Although torsion of a normal ovary is possible, the vast majority of torsed ovaries are enlarged with cyst(s) or a tumor.
Ovarian torsion presents with acute onset of intense lower abdominal pain. There is sometimes a history of similar pain that resolved spontaneously. Anorexia or nausea often accompanies the pain. Focal tenderness and a mass may be appreciated on pelvic exam. Plain radiographs sometimes reveal the calcifications of a teratoma and nonspecific ileus. When further information is required, ultrasound with color flow Doppler can demonstrate the mass and occasionally demonstrate loss of perfusion. Unfortunately, the presence of flow within the mass does not prove the converse, that the adnexa are not torsed.
At operation, the involved ovary is detorsed. If perfusion is questionable, fluorescein can demonstrate reperfusion in a viable ovary. When tumor is present, salpingo-oophorectomy is indicated. Cysts should be resected, the ovary repaired, and oophoropexy performed. The contralateral ovary must be inspected. As contralateral torsion with consequent infertility has been described, many surgeons recommend fixation of the opposite ovary.
Ovarian Tumors
Ovarian tumors in childhood may originate in any of the three components that comprise the ovary. Ninety percent of these are of germ cell origin of which two-thirds are benign teratomas. Approximately 4% are of stromal origin derived from the sex cords—granulosa-theca cell tumors and androblastomas. Only 3% are of epithelial origin. This contrasts with the adult experience in which 90% of all ovarian tumors are epithelial in nature (4).
Germ Cell Tumor
Tumors develop from germ cell precursors. These tumors are located at any point in the migration of germ cells from the yolk sac to the ovary and occasionally beyond the normal migration path.
The majority of these tumors arise spontaneously. However, there are well-described instances of familial germ cell tumors. Within a given family the tumors may not necessarily be of the same histologic type. The Li-Fraumeni cancer family syndrome has been associated with germ cell tumors in addition to bone and soft-tissue sarcomas. Other conditions such as 46XY gonadal dysgenesis and mosaic Turner syndrome are highly associated with the development of gonadoblastomas.
The germ cell tumors are histologically classified based on the developmental stage they most closely resemble. The ontogeny of the germ cell tumors is described in Table 100-1.
Germinoma
Germinoma is the current terminology designating the most primitive of the germ cell tumors. Germinomas are present in 10% of all ovarian tumors in children. They are rarely found in pure form, more often in combination with other germ cell tumors. The cells resemble primordial germ cells. Placental alkaline phosphatase is present in most germinomas. Markers for alpha-fetoprotein (AFP) and beta human chorionic gonadotropin (hCG) are negative in pure germinomas.
TABLE 100-1 Ontogeny of Germ Cell Tumors. | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||||||||||||||||
Embryonal Carcinoma
Embryonal carcinoma is histologically poorly differentiated with anaplastic elements and extensive necrosis. The tumors are uniformly negative for AFP, but may be focally positive for placental alkaline phosphatase and hCG. Chemotherapy occasionally causes these tumors to mature.
Endodermal Sinus Tumor (Yolk Sac Tumor)
The endodermal sinus tumor is the most common malignant germ cell tumor of childhood. In infants, it is most frequently involved with sacrococcygeal teratomas. The ovarian location is seen more frequently in later childhood and adolescence. Gross appearance is that of a pale tan-yellow slimy tumor with foci of necrosis. The tumors are very friable. The pathology may be papillary, reticular, solid, or polyvesicular. AFP is typically elevated in this lesion.
Choriocarcinoma
Choriocarcinoma histologically resembles placental tissue with two components, cytotrophoblasts and syncytiotrophoblasts. There are frequent foci of hemorrhage and necrosis. hCG is produced by these tumors.
Gonadoblastoma
Gonadoblastoma is a tumor that arises in dysgenetic gonads in association with the Y chromosome karyotype. The patients are phenotypic females with either a 46XY or mosaic 46XY/45XO karyotype. One-third of these patients will develop gonadoblastomas. Pure gonadoblastomas do not metastasize; however, one-third of the tumors are associated with germinomas, which do metastasize. No markers are known for this tumor.
Teratoma
The teratoma is the most common germ cell tumor of childhood and is benign in more than 90% of cases. The most common sites are the sacrococcygeal area and the ovary. The tumor is composed of endoderm-, mesoderm-, and ectoderm-derived tissues foreign to the organ or anatomic site from which they originate. Teratomas may be grouped into three subtypes—mature, immature and teratomas with malignant components. Mature teratomas show fully developed tissues such as brain, skin with hair, teeth, and the aerodigestive tract. Immature teratomas differ in that they possess neuroglial or neuroepithelial elements, which are not fully differentiated. The incidence of malignancy is associated with degree of immaturity of the tumor.
The malignancies most commonly found within teratomas are germinomas or other germ cell tumors. Occasionally, somatic cell malignancies may be found. Prognosis and therapy are based on whether the histology shows malignant cells and the tissue type of the malignancy. A mature teratoma does not manufacture AFP or hCG. These tumor markers may be found in tumors with malignant germ cell elements.
Surgical Considerations
Simple ovarian cysts are benign and may be treated by drainage without oophorectomy. Solid and complex masses are potentially malignant. Tumors are staged according to Children’s Oncology Group (COG) guidelines (Table 100-2). Small masses may be treated with excisional biopsy and frozen section. Large tumors should be managed according to COG surgical guidelines (Table 100-3). Occasionally, a benign-appearing teratoma will be found to have immature or malignant elements within it after completion of the operation. In such a case, reexploration for staging is required.
Although laparoscopy is being used with increasing frequency for most procedures, its applicability to tumors is still uncertain. Obstetricians routinely remove “dermoids” laparoscopically and believe that rupture can be controlled with vigorous irrigation (5). If the tumor is found to be malignant, the situation becomes more complex. Unless a tumor is removed intact, it cannot be accurately staged. All tumors not removed intact are therefore treated as stage II and receive chemotherapy. Stage I tumors of the ovary can be treated with resection alone. In addition, the potential for spill of tumor while morcellizing it in a pouch is unknown. It cannot be recommended as standard therapy until these questions are resolved.
TABLE 100-2 Staging of Ovarian Germ Cell Tumors. | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||||||||||||||||||
TABLE 100-3 Surgical Guidelines for Ovarian Germ Cell Tumors. | ||
|---|---|---|
|
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
