Learning Objectives

Describe the physiology of time and aging

Discuss pregnancy, ectopic pregnancy and spontaneous abortion

Describe how anatomy applies in clinical situations

Describe common disease conditions and symptoms

Explain how pathological conditions affect the uterus

Discuss treatment options

Introduction
The uterus, also known as the womb, is a hollow muscular organ that is part of the genitourinary system. It is characterized by its important role in the female reproductive system.

Part 2 of ‘Applied Anatomy of the Uterus’ will discuss common diseases to include alterations in the structure, which can be congenital or acquired, benign or malignant tumors. Systemic disease, especially infections, can also affect the uterus and uterine cavity. Diseases include fibroid disease, polyps, adenomyosis, cervical stenosis, and carcinoma. The more common disorders are the functional disorders that relate to cyclical events including menstrual cramps, endometriosis, dysmenorrhea, amenorrhea, and menorrhagia. Pain relating to the placement of an intrauterine device is also relatively common.

The developmental uterine anomalies may hinder conception and normal child birth. The changes in position could give rise to chronic pelvic pain. During childbirth there is a risk of injury to the urinary bladder as well as the anal sphincter as the uterus is anatomically closely related to these structures. The uterus may lose its support with age, repeated pregnancies and post menopause and may give rise to uterovaginal prolapse. Uterine fibroids are the most common benign tumors arising from the uterine myometrium. Uterine endometrium can stray and become ectopically placed in the myometrium giving rise to adenomyosis and when positioned in the ovaries or pelvis causing a condition called endometriosis.

The diagnosis of uterine diseases is dependent initially on clinical evaluation, while the most useful imaging modality is ultrasound. Clinically, symptoms include infertility, recurrent abortions, menorrhagia, acute or chronic abdominal pain and urinary complaints. The imaging modalities commonly used include ultrasound, MRI,  hysterosalpingography, hysteroscopy and diagnostic laparoscopy.

Treatment options are guided by the disease process and may include hormonal treatment, minimally invasive surgery or open surgery.

The Uterus and Its Neighbors

Time and Aging

In the fetus the uterus is contained in the abdominal cavity, projecting beyond the superior inlet of the pelvis and the cervix is considerably bigger then the body.

At puberty the uterus is pyriform in shape and weighs from 14 to 17 gm. It has descended into the pelvis, the fundus being just below the level of the superior aperture of this cavity.

The position of the uterus in the adult is prone to considerable variation, depending chiefly on the condition of the bladder and rectum. When the bladder is empty the entire uterus is directed forward and is at the same time bent on itself at the junction of the body and cervix, so that the body lies upon the bladder. As the latter fills, the uterus gradually becomes more and more erect, until, with a fully distended bladder, the fundus may be directed backward toward the sacrum.

During menstruation the organ is enlarged, more vascular, and its surfaces rounder; the external orifice is rounded, its labia swollen and the lining membrane of the body thickened, softer and of a darker color.

During pregnancy the uterus becomes enormously enlarged and in the eighth month reaches the epigastric region. The increase in size is partly due to growth of preexisting muscle and partly to development of new fibers.

After parturition the uterus nearly regains its usual size, weighing about 42 gms but its cavity is larger than in the virgin state; its vessels are tortuous and its muscular layers are more defined; the external orifice which was round in the nulliparous state may become slit like with one or more fissures.

In old age the uterus becomes atrophied and paler and denser in texture; a more distinct constriction separates the body and cervix.

Time and Aging: Embryology

In females, in the absence of MIS (Mullerian inhibiting substance) and androgens, the nephric (Wolffian) ducts degenerate and the paramesonephric (Mullerian) ducts give rise to the fallopian tubes, uterus, and upper two thirds of the vagina. The remnants of nephric ducts are found in the mesentery of the ovary as the epoöphoron and paroöphoron and near the vaginal introitus and anterolateral vaginal wall as Gartner’s duct cysts. The distal tips of the paramesonephric ducts adhere to each other just before they make contact with the posterior wall of the urogenital sinus. The wall of the urogenital sinus at this point forms a small thickening called the sinusal tubercle. As soon as the fused tips of the paramesonephric ducts connect with the sinusal tubercle, the paramesonephric ducts begin to fuse in a caudal to cranial direction, forming a tube with a single lumen. This tube, called the uterovaginal canal, becomes the superior portion of the vagina and the uterus. The unfused, superior portions of the paramesonephric ducts become the fallopian tubes (oviducts) and the funnel-shaped superior openings of the paramesonephric ducts become the infundibula.

Time and Aging: Function

The uterus has a vital role in reproduction. In the “receive process export” model it receives the fertilized ovum, enables the growth and development of the fetus and then delivers the baby.

More specifically, the genital tract provides a system that allows the transport of the sperm, while the fallopian tubes provide a tract for the ovum and a site for fertilization; the endometrium provides a site for implantation; the uterus protects and accommodates the growing fetus until child birth and the placenta acts as a secondary endocrine organ and a liaison between mother and child to enable nourishment and removal of waste. During childbirth the muscular layer of the uterus helps in parturition.

The menstrual cycle is the system that allows for cyclical preparation of the endometrium for potential implantation. Although we have discussed this important event throughout the module we will repeat the discussion in the context of pregnancy, discuss more complex changes in the cervix during the cycle and will add clinical entities that reflect disordered menstrual cycles.

Time and Aging: Menstrual Cycle and Applied Physiology

The cyclical changes of the menstrual cycle present a continual change of events controlled by a series of integrated hormonal events. These changes are most easily observed in the endometrium by ultrasound. When performing a pelvic ultrasound, it is of the utmost importance to record the patient’s menstrual history.

Applied Physiology
During the menstrual phase (days 1- 4) the endometrium is thin and typically is seen as a single echogenic line by ultrasound examination, and measuring between 1-4 mm thick reflecting the early development of glands and stroma (Nalaboff).  The junctional zone is irregularly thick and the myometrium loses water and thins.

Preovulation – Proliferative Phase
In the proliferative phase (day 4-14) the endometrium thickens to 5-7 mm and becomes more echogenic than the myometrium. This reflects growth of the endometrial glands, blood vessels and stroma, stimulated by estrogen production by the ovarian follicles. This proliferative endometrium is structurally and functionally preparing for implantation of the fertilized egg. In the late proliferative phase (periovulatory phase) the endometrium becomes multilayered with an echogenic basal layer, hypoechoic inner functional layer and a thin echogenic line alongside the junctional zone of the myometrium and measures up to 11 mms. (Nalaboff).

Time and Aging: Changes in the Cervix – Pre Ovulation

The cervix is generally soft in the preovulatory phase and the external os is open and the mucus is like egg white – thin and watery.

Time and Aging: Ovulation

Following ovulation the endometrium is under the influence of progesterone secretion by the corpus luteum. The endometrial glands fill up with mucus. The resulting appearance of the endometrium is a thick, echogenic structure (secretory phase). During the secretory phase (days 15-28) the endometrium is at it’s thickest in the mid-secretory phase and has a typical homogeneously, echogenic appearance. It usually measures between 7-16 mms. (Nalaboff)

The following series is taken in the postovulatory phase as the endometrium evolves into a secretory endometrium.

Thus in summary, the cyclical changes of the endometrium range from a thin, echogenic line progressing to a multi-layered appearance in the preovulatory phase, becoming thick and homogeneously echogenic and then shedding. The changes in the cervix at the time of ovulation show a thin, simple fluid with an open external os. Just prior to menstruation the cervical fluid is thick and dry and complex appearing on ultrasound, but is echogenic and the external os is closed.

Time and Aging: Outer Myometrial Changes during Menstrual Cycle

The myometrium is thickest in the second half of the cycle – the mid-secretory phase, due to mild edema, but this is not easily observed by imaging techniques.

Junctional Zone Changes
During the mid-secretory phase the junctional zone thins out. It is most prominent when under the influence of progesterone and best seen during the menses and the earliest phases of the proliferative phase.

Menstruation
The menstrual cycle is a physiological process of the uterus caused by the cyclic rise and fall of estrogen and progesterone levels.

The result is growth and maturation of the endometrium followed by endometrial degeneration and shedding at menses.
The endometrium consists of two layers: the stratum basalis and stratum functionalis. It is the stratum functionalis that will either receive the fertilized ovum or shed. If there is no implantation then luteinizing hormone levels fall in the latter phase of the cycle and the level of progesterone falls, resulting in shedding of the endometrium.

Time and Aging: Imaging the Tampon

Time and Aging: Disorders of Menstruation

Amenorrhea
Amenorrhea is a lack of normal menses. A woman who has never had a menstrual period has primary amenorrhea, while a woman whose menstrual periods have ceased has secondary amenorrhea.

There are many causes of amenorrhea. Primary amenorrhea is usually due to a condition present at birth. The most common cause of secondary amenorrhea is pregnancy.

The common result is cessation or lack of menses.

The structural and functional changes vary depending on the cause.

Women with primary amenorrhea generally present clinically in young adulthood when they fail to undergo menarche. Women may present with secondary amenorrhea anytime between menarche and menopause.

Diagnosis is based on clinical history. Secondary amenorrhea is diagnosed after cessation of menses for >6 months.

Treatment depends on the cause found at evaluation.

Oligomenorrhea
Oligomenorrhea is a term used for infrequent menstrual bleeding. The menses may be regular at long intervals or irregular.

There are many causes of oligomenorrhea, but the most common are chronic anovulation and polycystic ovarian syndrome (PCOS).

The result is menstrual bleeding occurring >35 days apart.

Structural and functional changes vary depending on the cause.

Women present clinically with infrequent menses. Women early in pregnancy may present with oligomenorrhea after they begin missing menstrual periods.

Diagnosis is based on clinical history and treatment is based on the cause found at evaluation.

Dysmenorrhea
Menstrual cramps or dysmenorrhea are cramps that occur during menses or more simply painful menstruation. They are caused by uterine muscle contractions which serve to evacuate the denuded mucosa and blood clots from the endometrial cavity. Primary dysmenorrhea is more common but dysmenorrhea may be associated with other pelvic disorders such as endometriosis, adenomyosis, pelvic inflammatory disease (PID) and adhesions in which case the dysmenorrhea may be more severe or prolonged.

Many women experience tolerable discomfort or pain but the pain can become incapacitating. Dysmenorrhea may be associated with excessive blood loss and this is known as menorrhagia.

From a structural standpoint the pain is caused by pressure receptors that sense the increased pressure during muscle contractions or by chemical receptors that may be incited by ischemia when contractions are excessive and temporary ischemia results.

Functionally, muscle contractions of the uterus are normal and are usually not felt. If the contractions are sufficiently strong, pressure receptors are activated or ischemia is induced by obstruction of the intramural arteries, causing the pain.

Clinically the pain presents as cramps during menses in the lower abdomen, usually in the suprapubic region, but may be periumbilical, left or right abdomen or may radiate down the thighs or occur in the back. Associate symptoms include nausea, vomiting, headache, weakness or even fainting. If the pain pattern changes or becomes more severe or the pelvic examination is abnormal then secondary causes should be sought and is best done by starting with an ultrasound of the pelvis.

Treatment is commonly with NSAIDS (non steroidal anti inflammatory agents) or a COX-2 inhibitor. For some patients hormonal contraceptives prove effective. Secondary causes of dysmenorrhea may require surgery.

Time and Aging: Disorders of Menstruation Continued

Menorrhagia
Menorrhagia is excessive bleeding at menses with multiple causes.

The most common causes of menorrhagia are benign uterine polyps or fibroids. However, menorrhagia may also have more serious causes including bleeding disorders or uterine cancers.

The result is a prolonged period of menstruation (>7 days) or excessive blood flow at menses (>80 cc/cycle).

Structural changes vary depending on cause.

Functional changes also vary with cause, but always include excessive bleeding, giving women their common clinical presentation. Women with menorrhagia often describe soaking through a menstrual pad every hour during menses.

Diagnosis is based on clinical history and treatment depends on the cause found at evaluation.

Metrorrhagia
Metrorrhagia is uterine bleeding between menses with multifactorial causes including benign endometrial and cervical polyps, as well as endometrial and cervical cancers.

The result is uterine bleeding between menses in an amount less than or equal to menstrual flow.

Structural and functional changes vary depending on cause. Women present clinically due to their bleeding between menses.

Diagnosis is based on clinical history and treatment depends on the cause found at evaluation.

Pregnancy

Pregnancy is a physiologic process caused by the fusion of two gametes after sexual intercourse.

This fusion, called fertilization, takes place in the fallopian tubes and the result is a zygote, a diploid cell that will grow into an embryo.

The function of every biological unit in the body is based on its ability to receive a product, process it and deliver the new product efficiently and effectively to where it is used and needed. The primary function of the uterus is to receive the fertilized egg, support its growth and development throughout gestation and ultimately deliver a well-formed, viable neonate.

Fertilization begins with the ovum being released from the ovary. At the time of ovulation the ovum is fixed within the process of meiosis at the metaphase II stage. It is surrounded by the zona pellucida, a layer of mucopolysaccharide and the cumulus oophorus, a layer of granulosa cells from the ovarian follicle. The ovum is swept up by the fimbriae of the fallopian tubes. If sexual intercourse occurs around the time of ovulation, sperm are released and move from the vagina through the cervical mucus into the uterus and fallopian tubes. The sperm move toward the ovum through a chemical attraction called chemotaxis. In the uterus, the sperm undergo capacitation, a reaction that makes the sperm membrane more permeable and better able to fuse with the oocyte membrane. When the sperm reach the ovum in the fallopian tube they undergo the acrosome reaction, releasing enzymes from the sperm head that allow it to pass through the zona pellucida.

The sperm membrane fuses with the oocyte membrane and the sperm head, containing the gamete’s genetic material, passes into the cytoplasm of the oocyte. The oocyte completes its second meiotic division and the result is a diploid zygote containing two pronuclei, membrane bound structures each containing a maternal or paternal set of chromosomes. The membranes of these pronuclei dissolve and the chromosomes from the sperm and oocyte pair in preparation for the zygote’s first mitotic division. This cell will divide multiple times as the embryo travels through the fallopian tube into the uterine cavity. This process usually takes 3-4 days after fertilization.

As the embryo travels into the uterus, its cells grow, divide and begin to differentiate. The first cells to differentiate are the trophoblastic cells, cells that will become the placenta. Enzymes from the endometrial glands digest the remaining zona pellucida in order to allow these cells to attach to and invade the endometrium. These cells proliferate within the endometrium, invading the small capillaries to form the vascular sinuses of the early placenta. Through these venous sinuses, the cells of the growing placenta secrete progesterone and HCG, which allows detection of the pregnancy with laboratory testing.

After implantation the embryo grows and the cells continue to differentiate. Around the third week of gestation, the cells differentiate into ectoderm, endoderm and mesoderm. The endoderm will develop into the gastrointestinal and respiratory tracts. The mesoderm will differentiate into the cardiovascular, genitourinary and musculoskeletal systems. The ectoderm will form the nervous system, skin and sensory organs. Organogenesis occurs between the 4th and 7th week of gestation. After the 8th week of gestation, the embryo is called a fetus. This fetus will grow and develop within the uterus over 40 weeks of pregnancy. The placenta will grow and invade the arterioles of the endometrium to connect maternal and fetal circulation.

Uterine physiology is influenced by hormones from the hypothalamus-pituitary-ovarian axis. The uterus undergoes many functional changes in pregnancy in the processes of implantation, gestation and childbirth.

 

Pregnancy: Imaging Pregnancy

As early as the 4th week of pregnancy the gestational sac may be visualized by transvaginal ultrasound. At this stage the gestational sac already contains the yolk sac, embryonic disk and amnion but these structures are too small to be visualized. An echogenic ring surrounding the cystic gestational sac represents the decidua.

Using transvaginal ultrasound the sac may be seen at ß-HCG levels as low as 800 mIU/mL but should be identified when the level is 2,000 mIU/mL (Paul).

Using the transabdominal technique the gestational sac should be visualized when the ß-HCG level is approximately 3,600 mIU/mL (Nyberg, Dashefsky).

Beta HCG levels usually double approximately every 2 days for the first four weeks of pregnancy (Ashitaka). Subsequently by 6 to 7 weeks gestation beta HCG levels may take as long as 3 1/2 days to double (Pittawy). In 15% of normal pregnancies doubling time in early pregnancy may be more than 2 to 3 days. On the other hand in ectopic pregnancy, normal doubling times may be present.

During gestation, as the myometrium hypertrophies it also becomes more contractile. In the first trimester the uterus begins having infrequent uncoordinated contractions. These contractions are mild and usually go unnoticed. As pregnancy progresses the contractions increase in intensity and frequency. These contractions become more regular toward the end of the third trimester and become rhythmic as labor begins.

Pregnancy: Processing: Growth and Nourishment

Throughout gestation the uterus grows to accommodate the developing fetus. The myometrium becomes more muscular and elastic. The uterus stretches to 500 times in size, thinning the uterine wall. As the nutritional needs of the fetus increase, the uterine blood supply hypertrophies to increase blood flow in the maternal-fetal circulation.

 

Pregnancy: Labor

Labor is uterine contractions leading to cervical changes caused by contraction of the myometrium in response to the hormone oxytocin. The result is delivery of the fetus and placenta. Between the 36th and 40th week of gestation the irregular contractions of the myometrium become rhythmic. The membranes surrounding the fetus and amniotic fluid rupture. The cervix effaces and dilates up to 10 cm in diameter. As the cervix dilates, the plug of cervical mucus is expelled resulting in the bloody show. The fetus descends into the pelvis and rotates as the strengthening, rhythmic contractions of the uterus propel the fetus through the birth canal. After delivery of the neonate, uterine contractions continue delivering the placenta.

During labor and delivery the uterus undergoes several important structural and functional changes. The cervix dilates and effaces allowing the fetus to pass. The myometrium contracts rhythmically to deliver the neonate and placenta. After childbirth, the uterine vasculature constricts and the myometrium contracts to stop postpartum bleeding.

As labor begins, there is an increase in the number of oxytocin receptors on the myometrial smooth muscle cells. Release of the hormone oxytocin from the posterior pituitary stimulates the strong rhythmic contractions of the myometrium. There is also an increase in the number of gap junctions connecting the smooth muscle cells. As a result, the contraction of the myometrial smooth muscle cells becomes more coordinated. In the cervix, increased prostaglandin levels lead to increased expression of enzymes called matrix metalloproteinases. These enzymes break down cross-linking bonds between collagen fibers.

Simultaneously, cervical hyaluronic acid content increases. These processes cause the softening, effacement and dilation of the cervix. Once the cervix is dilated, rhythmic myometrial contractions move the fetus through the birth canal. The ligaments of the pelvis relax to allow widening of the pelvic outlet, allowing the fetus to pass. After the delivery of the neonate and separation of the placenta, constriction of the uterine vasculature prevents maternal blood loss. Contraction of the myometrium also compresses the arterioles that fed the placenta to prevent blood loss.

Pregnancy: Childbirth

At child birth there is an increasing concentration of oxytocin secreted by the posterior pituitary. There is an increased concentration of prostaglandins while PGE2 brings about softening of the cervix; PGF2 cause contractions. Oxytocin causes the rhythmic contractions manifested as labor pains. The intermittent nature of these contractions helps in child birth without jeopardizing the blood supply to the uterus. Uterine fibers are in different layers: the external layer is arranged transversely, the middle layer is irregular, while the inner layer is like a submucosal muscular layer. The lower segment and cervix are in circular formation. During labor the upper uterine segment contracts and retracts which essentially means that fibers get smaller after each contraction. This action propels the fetus downwards. The lower segments and cervix, on the other hand, dilate with each contraction.

Pregnancy: Post Partum

During the postpartum period the middle muscular layer, which has oblique fibers and a maximum number of vessels, prevents excessive blood loss as criss cross fibers across the vessels act as living ligatures.

Some disorders resulting from aberrant fertilization and implantation include infertility, miscarriage and ectopic pregnancy. Diagnosis is made based on clinical history, physical exam and imaging with ultrasound. Treatment of infertility can include induction of ovulation with hormones, intrauterine insemination or in vitro fertilization. Miscarriage may require no treatment, but dilation and curettage is often used to ensure full removal of the products of conception. Ectopic pregnancy may be treated medically, with methotrexate or surgically with removal of the ectopic gestation.

Pregnancy: Complications

Pregnancy complications that occur around or during labor and delivery include placental bleeding, uterine rupture, premature rupture of membranes or labor, cephalopelvic disproportion and malpresentation. Diagnosis of these conditions is made based on clinical history, exam and imaging with ultrasound. Treatment of placental bleeding (placenta previa or placental abruption) depends on the severity of bleeding. Premature rupture of membranes is often treated with antibiotics and sometimes induction of labor. Preterm labor is treated with tocolysis and steroids to promote fetal lung maturity. Uterine rupture is a medical emergency treated with immediate laparotomy and cesarean delivery. Cephalopelvic disproportion and malpresentation both often require cesarean delivery.

Congenital Disorders
There are many congenital disorders resulting from aberrant growth and development of the fetus. Some disorders resulting from uterine dysfunction during gestation include spontaneous abortion and cervical insufficiency. Diagnosis of these conditions is made by clinical history and exam combined with ultrasound imaging during pregnancy. Often no treatment is necessary for spontaneous abortion. Women with recurrent abortions should be tested for uterine structural abnormalities as well as gynecologic infections. Cervical insufficiency may be treated expectantly with steroids to promote fetal lung maturity and bed rest. Cervical cerclage may also be used to treat cervical insufficiency.

Ectopic Pregnancy

Ectopic Pregnancy is a disorder where a gestation is located in a location other than the uterus, most commonly in a fallopian tube, but can occur on an ovary or intra-abdominally. It is characterized by pelvic pain associated with vaginal bleeding and a positive pregnancy test. Predisposing factors include previous ectopic pregnancy and pelvic infections (such as Pelvic Inflammatory Disease (PID)).

The most common location of an ectopic pregnancy is in a fallopian tube, most commonly in the ampullary portion but can occur in the adnexa or rarely in the peritoneal cavity.

Ectopic pregnancy can result in serious complications including hemodynamic instability and death.

The classic clinical presentation of ectopic pregnancy includes amenorrhea (no periods for more than 6-7 weeks), pelvic pain and vaginal bleeding. Many patients do not have this classic presentation, however. Anytime a woman presents with pelvic or abdominal pain associated with amenorrhea, one must consider ectopic pregnancy. A positive pregnancy test along with a normal or slightly enlarged, often tender uterus or adnexal mass is highly suggestive of ectopic pregnancy. However, no combination of physical findings can definitively diagnose an ectopic pregnancy.

The diagnosis is suspected clinically by a positive pregnancy test, pelvic pain and/or vaginal bleeding. It is confirmed by characteristic changes in the f Beta-HCG levels and ultrasound findings.

An ectopic is suspected if the HCG is greater than 1500 and there is no evidence of an intrauterine gestational sac on transvaginal ultrasonography. On transvaginal ultrasonography an ectopic is suspected if an intrauterine pregnancy is not detected with an HCG level of greater than 6500. In a normal pregnancy the HCG level typically will double every 48 hours in early pregnancy but will not in ectopic pregnancy. Typically, the HCG will go do down in spontaneous abortion (SAB). Sometimes, a serum progesterone level can also be helpful in determining the viability of a pregnancy but generally is not considered as reliable a marker as an HCG.

The differential diagnosis includes multiple conditions which can cause acute pelvic pain including pelvic inflammatory disease (PID), spontaneous abortion (SAB), appendicitis and kidney stones. In pelvic inflammatory disease, kidney stones and appendicitis, pregnancy testing is typically negative and vaginal bleeding is less likely. Perhaps most difficult to differentiate are spontaneous abortions from ectopic pregnancies. On physical exam, there may be pregnancy tissue present in the os in a spontaneous abortion which is typically not the case with an ectopic pregnancy. Also, the ultrasound findings may be different and the serum HCG level typically falls more quickly with a SAB.

Ectopic Pregnancy : Imaging

Ectopic Pregnancy : Treatment and Management

There are several treatment options and the appropriate selection depends on the clinical conditions. The options include expectant management, medical management and surgical management. Expectant management: sometimes if the pregnancy is early (with a serum HCG of < 1000 and declining) and the gestation is small (less than 3 cm) and there is an absent fetal heartbeat, expectant management with close follow-up may be considered. If the patient is hemodynamically stable, it may be possible to treat the ectopic medically. Medical management typically involves methotrexate. Methotrexate is a chemotherapeutic agent which inhibits folate metabolism, therefore inhibiting the growth of rapidly dividing cells such as a new gestation. Surgical intervention typically involves laparoscopic surgery and most recently tubal incision to remove the gestation. Surgery is chosen for the unstable patient, larger, more advanced pregnancies and for medical treatment failures.

Generally, the prognosis of ectopic pregnancy is good if it is diagnosed in a timely fashion. However, this serious condition is also one of the most common causes of maternal death and infertility.

Spontaneous Abortion

Spontaneous abortion is the expulsion of a non viable embryo or fetus usually caused by chromosomal aberrations or environmental factors, occurring before the 20th week, though most occur before 12 weeks.

Structural changes that can lead to spontaneous abortion include uterine septae and anatomic anomalies like bicornuate uterus. Spontaneous abortions in the first trimester usually occur due to chromosomal anomalies of the fetus.

However, functional changes due to maternal infection or toxin exposure can lead to spontaneous abortion in the second trimester.

There are 4 clinical entities including threatened, inevitable, incomplete and complete spontaneous abortion.

Clinically threatened abortion is diagnosed and characterized by some bleeding and sometimes accompanied by pain in the first trimester. About half of these patients will recover and proceed to full term pregnancies.

When the symptoms are accompanied by a dilated cervix then abortion becomes “inevitable”. Bleeding and cramps are usually more prominent with inevitable abortion. The presence of products of conception in the discharged blood warrants examination by ultrasound. If products of conception are identified in the endometrial cavity the diagnosis is compatible with incomplete abortion and their absence confirms the diagnosis of a complete spontaneous abortion. Pain and bleeding subside when the abortion is complete.

Treatment depends on the stage of the the spontaneous abortion. A complete abortion requires no further treatment. An incomplete or inevitable abortion before 13 weeks is treated with suction dilatation and curettage though medical therapy (misorostol) can be used.

Diseases

We will now review diseases of the cervix, uterus and fallopian tubes.

Diseases of the Uterus and Cervix: Fibroids

Uterine fibroids (leiomyomas) are benign tumors of the myometrium and are the most common female reproductive tract tumor. They occur in women of reproductive age.

Fibroids are caused by clonal proliferation of a single smooth muscle cell in response to estrogen and progesterone. Because their growth is hormone-responsive, they typically regress with menopause.

The structural changes are characterized by single or multiple masses of smooth muscle cells, with some fibrous tissue, within the myometrium. The masses may protrude into the uterine or abdominal cavities. Fibroids vary greatly in size and rarely may grow large enough to fill the abdomen and compress the abdominal organs.

The functional changes are variable and depend on fibroid location and size. For many women the functional change is minimal. However, fibroids that project into the uterine cavity and distend the endometrium may cause increased menstrual bleeding as well as infertility.

Clinically, many women with fibroids are asymptomatic and present clinically with incidental findings on imaging. However, women with multiple or larger fibroids may present with menorrhagia, pelvic pain, infertility or an irregular abdominal mass. Fibroids that outgrow their blood supply can undergo infarction and necrosis causing sudden severe pain.

Imaging evaluation of fibroids is usually done with ultrasound. MRI is useful in evaluation if ultrasound is non-diagnostic.
Diagnosis is made with findings on physical exam and imaging.

Treatment is variable depending on size and symptoms. Asymptomatic women with small fibroids can be managed with observation. Fibroids causing pain or infertility can be removed with laparoscopic or open myomectomy. The blood supply of large individual fibroids can be targeted with uterine artery embolization. Women with large or symptomatic fibroids who have finished childbearing may be treated with hysterectomy.

Diseases of the Uterus and Cervix: Fibroids Impinging on the Endometrium – MRI

Fibroids are common and most commonly located only in the muscular portion of the uterus. When they are purely intramural they do not cause dysfunctional uterine bleeding (DUB).  When they impinge on the endometrium they can be the cause of both DUB and infertility if large enough.

Diseases of the Uterus and Cervix: Small Submucosal Fibroid Demonstrated by Sonohysterogram

A sonohysterogram is performed by inserting a small catheter into the endometrial cavity via the cervix and injecting normal saline into the endometrial cavity, which acts as a contrast agent to outline the cavity and then, using ultrasound to evaluate the cavity. Normally the cavity is smooth. Abnormal bleeding is usually the indication for the sonohysterogram and defects caused by polyps or submucosal fibroids become obvious even when small.

Diseases of the Uterus and Cervix: Fibroids – Hysterosalpingogram

A hysterosalpingogram is performed by inserting a small catheter into the endometrial cavity via the cervix and injecting water soluble contrast into the endometrial cavity, which acts as a contrast agent to outline the cavity and then using fluoroscopy to evaluate the cavity and integrity of the fallopian tubes. Normally the cavity is smooth and the contrast spills into the peritoneal cavity, confirming patency. Infertility is usually the indication for the sonohysterogram and obstructed tubes or other causes such as congenital abnormalities or submucosal fibroids become obvious even when small.

Diseases of the Uterus and Cervix: Hyperplasia Ultrasound
Endometrial hyperplasia is a proliferative growth of the endometrium usually caused by high levels of estrogens combined with insufficient levels of progesterone. The excessive estrogen may be exogenous or endogenous. The association between tamoxifen, an anti estrogen hormone used in the treatment of estrogen dependent breast cancer, can result in endometrial hyperplasia and has been associated with the development of endometrial cancer. Endometrial hyperplasia is precancerous and therefore must be diagnosed and treated when recognized. The diagnosis is suggested by a thickened endometrium. In the post menopausal woman the endometrium should not be thicker than 4 mms. The diagnosis is confirmed by dilation and curettage (D&C). It is treated hormonally but when the histology is concerning for atypia or cancer then it is treated like endometrial cancer and hysterectomy may be performed.

Diseases of the Uterus and Cervix: Polyps

Endometrial polyps are benign growths of the endometrium which occur most commonly in middle-aged women.
The cause of most endometrial polyps is unknown. However, they have been associated with the use of the drug Tamoxifen, as well as hypertension and obesity.

The result is a growth of endometrial glands and stroma projecting from the internal uterine surface. The structural change is characterized by a mass of endometrial glands and fibrous stroma that surrounds a core of large vascular channels. This mass usually arises from the uterine fundus and projects from a stalk into the uterine cavity.

The functional change associated with endometrial polyps may be minimal or limited to abnormal uterine bleeding. However, there is some evidence that removal of endometrial polyps may improve fertility.

Endometrial polyps present clinically with abnormal uterine bleeding. This bleeding is most often light bleeding between periods (metrorrhagia), but can also manifest as heavy or extended bleeding at menses (menorrhagia).

Imaging with ultrasound is useful in the initial investigation of abnormal uterine bleeding, and sonohysterography is the most effective imaging modality for endometrial polyps.

Diagnosis of a benign polyp depends on histologic examination to rule out malignancy.

Treatment of endometrial polyps is surgical excision with hysteroscopy, followed by curettage. Although endometrial polyps are benign, there is a small risk of malignancy arising in a polyp, so removal of large (>1 cm) or symptomatic polyps is recommended.

Diseases of the Uterus and Cervix: Endometrial Carcinoma

Endometrial carcinoma is a malignant disease of the inner lining of the uterus usually occurring in postmenopausal women.

Most endometrial cancers are caused by excess exposure to estrogen without the opposing influence of progesterone. However, the cause for some endometrial cancers is multifactorial or unknown.

The result is uncontrolled growth of the endometrium.

The structural changes are characterized by proliferation of glands within the endometrium. These glands are filled with tightly packed malignant cells. The functional changes are characterized by growth of the endometrium after menopause, a time when the endometrium usually atrophies since estrogen levels decrease.

When endometrial carcinoma occurs in a premenopausal woman, the functional change is characterized by endometrial growth not regulated by the menstrual cycle.

In both cases, the result is a clinical presentation of abnormal bleeding. This bleeding can be at an abnormal time, for example after menopause or not during menses, or in an abnormally increased amount.

Imaging is useful in the initial evaluation of a patient with abnormal vaginal bleeding by pelvic ultrasound and sonohysterography.

Diagnosis is made by endometrial biopsy and staging is based on findings at lymph node dissection during surgery.
Treatment of endometrial carcinoma is surgical, with total hysterectomy as well as removal of both ovaries and fallopian tubes. As stated above, the pelvic lymph nodes are also removed for staging. Radiation therapy is used for patients who are not candidates for surgery, as well as after surgery for patients with advanced disease. Hormone therapy with progesterone and chemotherapy are used for patients with disease recurrence. Most endometrial carcinomas present with bleeding early in disease progression. As a result, with early treatment, patients often have a good prognosis.

Diseases of the Uterus and Cervix: Congenital Abnormalities

Congenital abnormalities are most often associated with anomalies of the Mullerian ducts which are a pair of embryonic structures that are precursors to the fallopian tubes, uterus and upper two thirds of the vagina.

The Mullerian duct disorders, including unicornuate, bicornuate and didelphys uteri are characterised by anomalies in the development, fusion or septal regression of the Mullerian ducts.

Structurally the full volume of the uterus and endometrial cavity is compromised, often resulting functionally and clinically with infertility.

The diagnosis is best accomplished with MRI or hysterosalpingography.

Diseases of the Uterus and Cervix: Adenomyosis – Abnormal Junctional Zone

Adenomyosis is a disease of the myometrium caused by misplaced or ectopic endometrium in the myometrium, resulting in myometrial hyperplasia and smooth muscle hypertrophy, clinically manifesting as pelvic pain and uterine enlargement. The entity can be focal or diffuse.

The exact cause of the displacement is not known but it is presumed that a breach in the endometrial myometrial barrier enables a small amount of endometrium to translocate and remain viable. There is a high prevalence rate with about 40% of hysterectomy specimens displaying the entity.

Clinically the patient presents with dysmenorrhea and menorrhagia and on exam the uterus is enlarged.

The diagnosis is best made by MRI which shows a thickened junctional zone (>10-12 mms) of the uterus. The deposition of acute blood, blood degradation products such as iron, or the presence of fluid filled microglandular deposits in the junctional zone make the MRI findings highly specific for the diagnosis.

Treatment options include pain management with NSAIDS and hormonal manipulation. Surgery with hysterectomy is the only current option for cure.

Diseases of the Uterus and Cervix: Hydrosalpinx

Hydrosalpinx is literally a fallopian tube filled with water. This is usually caused by an obstruction of the distal Fallopian tube most often related to pelvic inflammatory disease.

The entity is often bilateral. When the blood distends the fallopian tubes it is called hematosalpinx and when pus is the cause it is called pyosalpinx.

Diseases of the Uterus and Cervix: Benign Cervical Stenosis and Distended Cervical Canal

Diseases of the Uterus and Cervix: Cervical Cancer

Cervical carcinoma is a malignant disease of the uterine cervix.

Most cases of cervical carcinoma are caused by infection with the human papilloma virus (HPV).
The result is uncontrolled growth of the cervical epithelium.

The structural changes are characterized by proliferation of malignant, squamous, epithelial cells at the junction between the outer cervix and the endocervical canal.

The functional changes may be minimal, but in advanced cases can be characterized by abnormal bleeding or obstruction of the endocervical canal.

The PAP smear is an extremely effective screening tool for premalignant lesions of the cervix and allows many cases of cervical carcinoma to be prevented. As a result, most women in the U.S. present clinically while still asymptomatic during screening pap smears. However, in developing countries, where routine screening is less accessible, women with advanced disease can present with abnormal or post-coital bleeding or pain.

Diagnosis is made by biopsy after a positive pap smear and examination with colposcopy.

Imaging with MRI or CT can be used to evaluate the extent of advanced disease. Chest x-ray to look for distant metastasis is used for staging.

Treatment of premalignant lesions is local excision with a loop electrosurgical excision procedure. Early disease can be treated with radiation therapy or radical hysterectomy with similar results. Advanced disease is treated with chemotherapy and radiation.

Diseases of the Uterus and Cervix: Conclusion

The uterus is essential for the survival of our species. The reproductive age of a female starts at about the age of 12 or 13 years and generally lasts till the age of about 52 years.

Every month for approximately 40 years the uterus undergoes preparation for implantation of the fertilized ovum. This equates to almost 500 menstrual cycles and on the average worldwide, results in 2 successful pregnancies per woman. It seems like a significant and time consuming focus of energy and resources of nature with low net result but the low net result is essential for our survival.

It is essential to understand the menstrual cycle and the structural changes that result. The uterus is a small organ but can enlarge to 500 times its size during pregnancy. The organization of its parts allows the receipt and transport of the sperm, unfertilized and fertilized ova, implantation, nourishment and protection of the early pregnancy and developing fetus and the ability to expel and deliver the fetus. The anatomy and physiology is simply a miracle of life.