2. Definition

Page 2 – Definition

3. Anatomy

Page 3 – Applied Anatomy and Diagnostic Approach

Table 1. U-SSPCT–C Structural Table

Connections

Imaging Modalities

Laboratory Tests

Other Diagnostic Tools

4. Disease and Diagnosis

Page 4 – Clinical Application by Disease

IINMTM Disease Framework

Clinical Signs and Symptoms

Imaging Modalities (Clinical Integration)

Laboratory Tests

Other Diagnostic Tools

5. History and Culture

PAGE 5 – HISTORY, CULTURE, AND ART

1. History of Anatomy

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2. History of Physiology

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3. History of Diagnosis

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4. History of Imaging

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5. History of Laboratory Testing

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6. History of Therapies

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7. Cultural Meaning

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8. Artistic Representations

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9. Notable Figures and Quotes

Notable Figures

Quotes

7. MCQ's

PAGE 6 – MCQs

Basic Science MCQ 1

Which embryologic structure gives rise to the uterus?

A. Mesonephric duct
B. Cloacal membrane
C. Müllerian (paramesonephric) ducts
D. Wolffian duct

Correct Answer Table

Incorrect Answer Table

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Basic Science MCQ 2

Which layer of the uterus thickens and sheds during the menstrual cycle?

A. Myometrium
B. Endometrium
C. Perimetrium
D. Cervix

Correct Answer Table

Incorrect Answer Table

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Clinical MCQ 1

Which is the most common benign tumor of the uterus?

A. Endometrial polyp
B. Uterine fibroid
C. Adenomyosis
D. Endometrial carcinoma

Correct Answer Table

Incorrect Answer Table

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Clinical MCQ 2

What is a hallmark symptom of endometrial cancer?

A. Dyspareunia
B. Postmenopausal bleeding
C. Menorrhagia in adolescence
D. Pelvic mass on exam

Correct Answer Table

Incorrect Answer Table

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Radiologic MCQ 1

Which imaging modality best characterizes adenomyosis?

A. CT
B. Transvaginal ultrasound
C. MRI
D. X-ray

Correct Answer Table

Incorrect Answer Table

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Radiologic MCQ 2

A well-circumscribed, hypoechoic uterine mass with shadowing on ultrasound suggests:

A. Endometrial polyp
B. Submucosal fibroid
C. Adenomyosis
D. Malignancy

Correct Answer Table

Incorrect Answer Table

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Radiologic MCQ 3

Which finding on hysterosalpingography suggests intrauterine adhesions (Asherman syndrome)?

A. Tubal spasm
B. Beaded fallopian tubes
C. Filling defects within endometrial cavity
D. Peritoneal spillage of contrast

Correct Answer Table

Incorrect Answer Table

8. Memory Image

Page 7 – Memory Image

9. Other

Learning Objectives

 

Describe the basic anatomy including the fundus, body, cervix and Fallopian tubes

Discuss the physiology of the uterus

Describe the endometrium, the myometrium, and the serosa

Locate and identify the structures

Definition

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.

Structurally, it is characterized by its pear shape and its unique muscular structure that undergoes profound changes during different reproductive events. Though it is a pelvic structure, it enlarges many times over to become an intra-abdominal organ during pregnancy and returns to its pre-pregnancy state after child birth. Superiorly, the gracile fallopian tubes open on each side into uterine cavity, and inferiorly it communicates with the vagina through the cervix. The urinary bladder lies anterior to it and the rectum is posterior to it.

Functionally, it provides a nutritional and protective environment for a fertilized embryo to embed, and accommodates a growing embryo until child birth.

The Fallopian tubes are gracile structures that are only appreciated by hysterosalpingography, though when enlarged are also seen by other imaging modalities.

Overview

Structurally, in the non gravid state, the mature uterus is about the size of a woman’s fist, and measures about 8cm X 6cm X 4cm with a volume of about 75-200 ccs, and it weighs 100-200gms. It is a pear or pyriform-shaped muscular organ and is situated between the bladder anteriorly and the rectum posteriorly. It is a muscular organ with a hollow; endometrial cavity. Superiorly the fallopian tubes open on each side into the uterine cavity; inferiorly it communicates with the vagina via the cervix. It consists of a fundus, body (corpus), and neck (cervix).

Histologically, the inner endometrial lining consists of a single layer of columnar cells supported by a thin layer of connective tissue. The middle layer is the thickest and is called the myometrium. It consists of smooth muscle and has different layers with various orientations of the fibers. The myometrium proliferates during pregnancy. There is a loose connective tissue layer next which is called the perimetrium and then the outer lining which is a cover and is called the peritoneum and is part of a serosal layer. The cyclical changes of the menstrual cycle present a continual change of events controlled by a series of integrated hormonal events. During the follicular phase (proliferative phase) which occurs in the first half of the cycle and after the shedding of the endometrial lining, there is a rise in estrogen which causes the endometrial lining to start to thicken. In mid cycle after ovulation, luteinizing hormone is released which heralds in the luteal phase (also know as (aka) the secretory phase). Progesterone now rises and further proliferation of the endometrium occurs. In the absence of pregnancy progesterone and estrogen levels fall and the endometrium sheds.

In Part 2 of Applied Anatomy of the Uterus, we will cover disease processes and diagnosis. Common diseases 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 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.

Principles of the Uterus

The uterus is a muscular, pyriform structure specifically designed structurally and physiologically to allow implantation of the embryo and to accommodate a growing fetus until childbirth. The stroma and muscle develop from surrounding mesoderm. The uterus undergoes many changes during a woman’s lifetime, especially during pregnancy and childbirth. After menopause it becomes atrophic and may lose its support resulting in prolapse.

Principles of the Uterus: Basic Universal Principles

There are some basic, universal principles that apply to all living structures (also known as biological units) whether they are a cell or a person and they apply equally to the organ under consideration – the uterus.  These include the need to be functionally and structurally independent, but they need to also be linked to other structures in order to survive. All biological structures undergo change with time, need to occupy space, require an ability to convert one form of energy to another and apply or invoke certain forces to perform their functions.

As a Biological unit

The uterus is an important reproductive organ and has unique features like its lining of endometrium that changes with each menstrual cycle to allow implantation of the fertilized embryo and the criss-cross myometrium to stretch to accommodate a growing fetus.  The criss-cross myometrium also acts as living ligatures to minimize blood loss during and after child birth. The fallopian tubes act as a conduit for the unfertilized ovum to be transported to the endometrial cavity to enable fertilization.

Dependence and Independence

The uterus, along with the ovaries form the female reproductive system which is an independent unit. However, the function of the uterus is under a complicated system of hormones which are secreted by the ovaries which in turn are controlled by the pituitary hormones. Some pituitary hormones also have a direct effect on the uterus. This constitutes a pituitary-ovarian-uterine axis.

Links and Connections

The uterus is connected to the fallopian tubes superiorly and to the vagina inferiorly. It is a pelvic organ and lies between the urinary bladder anteriorly and the rectum posteriorly. It has an independent blood and lymphatic supply. It has unique ligaments and a muscular sling that helps in maintaining its position and preventing uterine prolapse. It is intimately connected to the endocrine system via circulating hormones, particularly estrogen and progesterone.

Time Growth and Aging

During organogenesis a pair of Mullerian ducts arise from coelomic epithelium and subsequently fuse to form the uterus. The proximal portions form the fallopian tubes and distal portions form the body and cervix of the uterus and upper 4/5ths of the vagina.

Spaces

The non gravid uterus is a pelvic organ.  However, a gravid uterus becomes an abdominal organ occupying a large area in the abdomen almost up to the tip of the xiphisternum at term. It is also only partially covered by peritoneum on its superior aspect.

Forces

Uterine contractions can occur in the non pregnant state. During the menses, contractions occur to help eject the shedded endometrium.  During pregnancy the uterus undergoes painless contraction called Braxton Hicks, which increase as the pregnancy advances. During parturition, uterine contractions have two separate effects in the upper uterine segments.  There is one set of contractions which gradually create a downward force and shortening of the muscle fibers which tend to get smaller by a process called retraction, causing descent of the fetus and rotation of the fetal head. The second effect is on the cervix and lower uterine segment which dilates as the upper uterine segment contracts.

Interactions

The uterus, ovaries and pituitary form a sophisticated unit playing an important part in ovulation, conception and child birth. The uterus, along with the fallopian tubes and cervix are the structural pillars of this unit.

State of Health and Disease

Uterine problems are very common, manifesting as fibroid disease, dysfunctional uterine bleeding, structural anomalies and uterovaginal prolapse.

Structure of the Uterus

The uterus is a hollow, muscular structure consisting macroscopically of a fundus, body, cervix and Fallopian tubes, continuing above with the peritoneal cavity and below with the vagina.  As a hollow, muscular organ it conforms to a basic histological pattern of all the hollow organs. In pursuit of understanding the structure of the uterus, we will initially explore its histological makeup and then progress to the anatomy and physiology. Finally we will explore disease entities as they apply to the anatomy, histology and physiology. Entities such as the menstrual cycle and pregnancy have implications at the histological, anatomical, physiological and at the level of diseases. These aspects are repeated from the different perspectives of histology, anatomy, physiology, imaging and disease.

Structure of the Uterus: Histology

The uterus has three basic histological layers:
endometrium – (also known as the mucosa) which is the inner layer abutting the lumen
myometrium – which is the middle and thickest layer
serosa – the superficial layer

Structure of the Uterus: Endometrium (Mucosa)

The endometrium is a dynamic structure and in the reproductive female is turned over every thirty days. It is subject to the influences of the hormonal changes of the menstrual cycle.

The endometrium is divided into two zones: a thinner basal layer called the stratum basalis and a thick superficial functional layer called the stratum functionalis.

The stratum functionalis is considered a temporary tissue and since it comes and goes in 28 days it has an “unfinished” appearance. The stroma resembles embryonic tissue and does not have a characteristic appearance of a lamina propria.
The stratum basalis has a more permanent appearance characterized by mature appearing stromal tissue, together with the deep tips of the glands.

The epithelium (or cellular lining) is made of simple tubular glands that dip down like test tubes into the stroma. The epithelium contains ciliated columnar cells and secretory cells embedded in a highly cellular, connective tissue with numerous lymphatics, vessels and uterine glands. The mucosa folds inward to form simple, tubular, uterine glands that extend deep into the stroma.

The stroma consists of vessels, lymphatics and connective tissue.

During the cycle, both the epithelium and the stroma undergo significant change. At the time of menstruation the superficial functional layer, which is sensitive to hormonal influences, sloughs and the basal layer remains intact to enable regeneration during the next cycle.

The mucosa continues into the Fallopian tubes and opens into the peritoneum. It also continues downstream into the vagina through the external os.

Structure of the Uterus: Simple Tubular Glands

A single layer of ciliated, columnar cells line the glands of the endometrium. They are cemented to the stroma by a basement membrane.

The stratum functionalis is the layer that sheds at menstruation and the stratum basalis remains to assist in the regrowth of the stratum functionalis. The spiral arteries run within the stratum functionalis and are the potential nourishment for the implanted fertilized egg if pregnancy occurs. They are branches of the arcuate arteries.

Structure of the Uterus: Cyclical Changes of the Endometrium

The three major phases of the cycle that manifest in the endometrium are the proliferative (follicular), secretory (luteal), and menstrual phases. The follicular phase occurs just after the shedding of the endometrium ending with ovulation and is followed by the secretory phase. The secretory phase is the period that follows ovulation preparing the uterus for implantation, and ends with the menstruation or the menstrual phase if implantation does not occur.

In the cervix the mucous membrane is sharply differentiated from that of the uterine cavity. The cervical mucosa is thrown into numerous oblique ridges. The mucous membrane secretes a clear, viscid alkaline mucus. The upper two thirds of the cervix is composed of a ciliated, cylindrical epithelium which gradually transforms into stratified, squamous epithelium. On the vaginal surface of the cervix the epithelium is similar to the vaginal epithelium.

Structure of the Uterus: The Muscular Layer

The muscular layer forms the bulk of uterus. It is thick in the fundus and the middle part of the body and thin at the entry point of the Fallopian tubes. There are three component muscular layers: internal, middle, and external.

The internal or deep layer is like muscularis mucosa; the fibers are arranged in circular fashion like two hollow cones with apices at uterine tube orifices and bases intermingling in the middle of the body. The fibers at the internal os are arranged in circular fashion like a sphincter.

The middle layer has no regular arrangement of the fibers; they are disposed longitudinally, obliquely and transversely in criss-cross fashion. This layer has the largest number of blood vessels. After parturition, these layers act as living ligatures and limit blood loss.

The external layer consists of fibers which pass transversely across the fundus and converge at each lateral angle of the uterus. They continue on to the Fallopian tube, the round ligament, and the ligament of the ovary. Some of the fibers pass on each side into the broad ligament, and some continue backward from the cervix into the sacrouterine ligaments.

During pregnancy the muscles undergo both hyperplasia (more smooth muscle cells) and hypertrophy (larger muscle cells).

Structure of the Uterus: The Serosa

The serosa does not cover the uterus completely. It is derived from the peritoneum; it invests the fundus and the whole of the posterior intestinal surface of the uterus, but covers the urinary bladder surface only as far as the junction of the body and cervix. In the lower fourth of the posterior surface, the serosa is loosely attached to the uterus separated by connective tissues. The reflection of intestinal peritoneum from the uterus to the intestine forms the pouch of Douglas. This is the area where a pelvic collection, such as an abscess, can accumulate and can be drained vaginally.

The Anatomy – Parts

The uterus is divided into two parts by a constriction called isthmus, midway between apex and base. The portion above the isthmus is called corpus or body of the uterus and the portion below the isthmus is called the cervix. The isthmus corresponds to the internal orifice of the uterus. The portion of the body above the opening of the fallopian tubes is called the fundus.

Conceptual Framework

The conceptual framework provides a simple framework from which to start understanding the structure of the uterus.  Simple lines and vectors are used much like the initial foundation or a framework of a building on which the detail will be built.

Coronal Plane

In the coronal plane the uterus has features reminiscent of the letter “T”.

The “T” can be further subdivided into 3 main parts including the fundus superiorly, the body, and the cervix inferiorly.  The fundus is connected to the fallopian tubes and the cervix to the vagina.

The form of the uterus and genital tract is more complex than a simple foundation “T” shape, being broad and muscular and triangular in form in the body region, cylindrical and fibrous in the cervical region and having thin and delicate Fallopian tubes.

 

In the Sagittal Plane 

In the sagittal plane the uterus has a structure reminiscent of an “L”.

The Anatomy – Parts : Applied Anatomy

This section combines the anatomy of the uterus with images as viewed with imaging including ultrasound, CT and MRI. The sagittal view consistently provides an excellent overview of the uterine size, shape and position.

The fundus and body of the uterus (also known as corpus uteri) form the largest portion of the uterus which gradually narrows to meet the cervix inferiorly.

The anterior surface is flattened and covered by peritoneum which reflects onto the bladder to form the vesicouterine space. The intestinal or posterior surface is convex transversely and is covered by peritoneum down to the cervix and vagina.  Between the posterior surface of the uterus and the rectosigmoid colon is the pouch of Douglas, also called the cul de sac. It is the most posterior and inferior space in the abdomen and the place where fluid first collects when the patient is in the supine or upright position.  The lateral margins of the uterus are usually convex. At the upper end of each lateral margin, the fallopian tubes, the uterine wall, below and in front of it, is the attachment of round ligament, while posterior to it is the attachment of the ligament of ovary. The peritoneum is reflected off the uterine wall and invests the fallopian tubes.  These folds are called the broad ligaments.

The Anatomy – Parts : Endometrium

The endometrium is a dynamic structure subject to the fluxes of the hormones. Its size and character varies with age, being thin in the young prepubertal female and in the elderly postmenopausal female. In the female of reproductive age, it ranges in size between about 2-3 mm in the post menstrual phase up to 16 mm in the premenstrual phase about 28 days later.

The endometrium is best evaluated using ultrasound for its macroscopic in vivo evaluation. In the young and old it is echogenic and with proliferation and accumulation of secretions in the glands, it initially becomes trilaminar. Following ovulation it becomes homogeneously echogenic.

In the postmenopausal female it should not measure more than 4 mm on ultrasound. There are profound changes in the endometrium during the menstrual cycle and pregnancy and these in part have been discussed in the histology section and will be revisited in the menstrual cycle section.

The Anatomy – Parts : Myometrium

The myometrium, the middle and thickest layer as stated consists of three layers:
the internal or deep layer is like muscularis mucosa. The fibers are arranged in circular fashion.
the middle layer is the thickest layer and the fibers are arranged in criss cross fashion.
the external layer consists of fibers which pass transversely across the fundus and converge at each lateral angle of the uterus.
From an imaging perspective two major layers are identified: the sub-endometrial layer (also known as the junctional zone) and the thicker outer layer.

The junctional zone is sub-endometrial smooth muscle that is more compacted and contains less water in comparison to the outer myometrium. (McCarthy)

The junctional zone is also functionally different from the outer myometrium. For example, myometrial contractions in a non-pregnant woman originate exclusively from the junctional zone.  The amplitude, frequency, and direction depend on the phase of the menstrual cycle.

The Anatomy – Parts : Fallopian Tubes

The Fallopian tubes (also known as the salpinges, oviducts) are a pair of tubular structures that are part of the female reproductive system and also part of the genitourinary system. They are characterized by their delicate and gracile nature and functional importance in fertilization.

Structurally, they are usually about 10 cm long (range 7-14 cm) and are funnel-shaped. The widest portion of the funnel is situated laterally, is called the infundibulum and is open to the peritoneal cavity. The fimbriae are delicate finger-like processes that surround the opening. Medial to the infundibulum is the middle and longest portion called the ampulla. It continues to taper as it progresses medially and it takes up half the length of the tube with a maximum outer diameter of 1-2 cm. More medial to the ampulla is the isthmus which is also slightly tapered, constitutes about 1/3 of the length and has an outer diameter of 0.5 to 1 cm. There is a 1 cm long medial intramural portion of the tube called the interstitial portion or cornual portion that connects the tube to the uterus and has an internal diameter of 1 mm.

Histologically, the tubes are structured like many other tubular organs of the body. There are three layers: an inner mucosa, intermediate muscular layer and an outer serosa which is continuous with the peritoneum.

Functionally, the tubes act as the site which allows fertilization to take place and also acts as the transport system that carries the fertilized egg (gamete) to the uterus.

Common diseases include pelvic inflammatory disease and ectopic pregnancy. Primary tumors of the tubes are rare.

Treatments are based on the cause of disease. Surgical procedures include tubal ligation, salpingolysis, resection and anastomosis and neosalpingectomy.

The Anatomy – Parts : Cervix

The cervix is the lower constricted segment of the uterus. It is somewhat conical in shape with its truncated apex directed downwards and backwards. The cervix projects through the anterior wall of the vagina which divides it into the supravaginal and vaginal portions.

The supravaginal portion is related to the bladder anteriorly and separated by fibrous tissue called parametrium. This extends laterally and the uterine arteries enter the cervix through it. The ureters run downward and forward in it about 2 cms from the margin of the cervix.

The vaginal portion (portio vaginalis) projects free into the vagina through the anterior wall, dividing it into anterior and posterior fornices. The external orifice is a circular aperture bounded by an anterior and posterior lip.

The cavity of the uterus is triangular in shape, slit-like in size and flattened anteroposteriorly. The base of the triangle is formed by the internal surface of the fundus and the apex by the internal orifice.

The cavity of the cervix is a fusiform, broader in the middle part of the canal. It communicates with the uterine cavity through the internal orifice and with the vagina through the external orifice. It has a posterior and anterior ridge from which the mucosa is thrown into palmate folds giving it a tree-like appearance in cross section. This appearance is reminiscent of a tree and is thus called the arbor vitae uterina.

Size

The nature and structure of the uterus allows it to change its size dramatically based on age and physiological state. The mature, adult uterus has been described as about the size of a small pear or an avocado. It is slightly smaller than the heart. In the non gravid state it is confined to the deep pelvis but is able to reach the epigastrium and subxiphoid region when at peak pregnancy.

The mature, non gravid uterus measures about 8 cm in length, 4 cm in A-P dimension by nearly 6 cm in transverse dimension; it weighs from about 35 gms in the virgin state up to 200 gms in the postpartum state. The volume of the uterus ranges between 75-200 cc. The myometrium measures between 1.5-2.5 cm in thickness and the endometrium measures from 1-10 mms but sometimes can be greater than 10 mm in the secretory phase.

Size: Size Continued

At Birth
At birth the dimensions of the body of the uterus are similar to the size of the cervix. Its overall length is between 2.3-4.6 cms (Nabaloff).

Prepubertal State
In the virgin state the uterus is flattened antero-posteriorly and is pyriform in shape with the apex directed downward and backward.

The prepubertal uterus measures about 2-4.4 cms in the craniocaudad (C-C) span.

The Mature Uterus
The nulliparous uterus measures between 6-8.5 cms in the craniocaudad span, 2-4 cms in the anteroposterior (A-P) dimension and 3-5 cms in the transverse dimension.

The multiparous uterus usually measures about 8-10.5 cms in the C-C span, 3-5 cms in the A-P dimension and 4-6 cms in the transverse dimension.

Size: The Gravid Uterus

In the gravid state the uterus rises out of the pelvis and enters the abdominal cavity gently displacing other abdominal structures.

Size: Post Partum Uterus

The mean size of the uterus 24 hours after delivery is 14 X 7cms. (Garagiola)

Size: The Uterus in Old Age

Size: Endometrial Size

Size and the Menstrual Cycle

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.

The measurement is taken from echogenic border to echogenic border in the midsagittal plane.

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

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).

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 its thickest in mid secretory phase and has a typical homogeneously, echogenic appearance. It usually measures between 7-16 mms. (Nalaboff).

Premenstrual Endometrium – End of Secretory Phase
The normal sagittal view of the uterus in a transvaginal ultrasound about 4 weeks after menstruation and just prior to the next menstruation when the endometrium is overripe. It demonstrates that the uterus and more specifically the endometrium are more complex than just a simple columnar epithelium. This is an example of the hyperechoic, homogeneous, thick endometrium characteristic of the secretory phase. It is during this time that progesterone is the dominant hormonal influence and estrogen influence is minimal. The endometrium in this case measures 1.2 cm.
Images courtesy of Ashley Davidoff, M.D.As luteinizing hormone levels fall in the latter phase of the cycle, the level of progesterone falls and there is shedding of the endometrium.

Size: The Post Menopausal Endometrium

The postmenopausal stripe in the absence of hormonal replacement therapy should measure <5 mms (Nalaboff). In a patient with post menopausal bleeding if the stripe measures <5 mms it is unlikely that the patient has endometrial cancer.

 

Shape

Overall, the uterus is pear-shaped and usually bent anteriorly (anteflexed) between the cervix and body.

The cavity is roughly triangular or “T” shaped. The cervix is cylindrical prior to puberty.

Shape of the Body of the Uterus

Applied Anatomy

An abnormal shape of the body of the uterus is most commonly caused by the presence of a fibroid uterus.

Shape of the Endometrium and Endometrial Cavity

The shape of the endometrium in the sagittal view is also pear-shaped or tear drop-shaped.

Depending on the phase of the menstrual cycle this shape will change but its pear shape is best appreciated in the secretory phase when the endometrium is thickest.
Shape of the Endometrium in the Coronal Plane

In the coronal plane the endometrial cavity is almost triangular in shape.

An arcuate uterus is a variant of normal where the base of the triangle is slightly convex.

Shape: Hysterosalpingogram: Defining the Shape of the Endometrial Cavity

Hysterosalpingogram involves the injection of contrast into the uterine cavity that enables the evaluation of the cavity as well as the patency of the fallopian tubes.

Shape: Applied Anatomy

Position

The uterus lies in the pelvis between the bladder and the rectum, and it projects supero-anteriorly over the urinary bladder.

The position of the uterus is described in two ways: if the uterus is bent forward it is called anteverted and if it is bent backward it is called retroverted. When the body of the uterus is bent anteriorly on the cervix, resulting in different angles for the body and the cervix, it is called anteflexion. Similarly when the body is flexed on the cervix and they are angled posteriorly at different angles, it is called retroflexion.

In the case above the uterus is anteverted – the uterus is bent forward. The long axis of the vagina forms a ninety degree angle with the axis of the cervix, which is directed posteriorly and inferiorly. The position of the uterus is significantly altered by the volume of urine in the bladder.

In the following case the bladder is moderately full and the angle formed by the uterus with the vagina is just under 90 degrees. However, the body appears to be bent on the cervix so there is both anteversion and anteflexion.

When the uterus is flexed backward the position is called retroversion and the cervix is directed anteriorly and inferiorly. The whole uterus is bent back and the vector of the body is aligned with the vector of the cervix and therefore, retroflexion is not present. This is sometimes the normal position of the uterus.

Character

Character implies the look and feel of the uterus on macroscopic evaluation.  The uterus has a smooth, external surface.  It is relatively hard to palpate since it is a fibromuscular organ.  It has a hollow endometrial cavity.  The fundus and body are muscular and the cervix is harder, more rigid and fibrous. The body of uterus is mobile, while the cervix is relatively fixed, though it can bend or flex.

Character – by Ultrasound

The outer myometrium by ultrasound is usually homogeneous, while the inner myometrium – the junctional zone – is hypoechoic.  The junctional zone is best appreciated in the late secretory phase and early menstrual phase when it is most prominent under the influence of progesterone.

The character of the endometrium also changes significantly over the menstrual cycle.  During the menstrual phase (days 1- 4) the endometrium is thin and typically is seen as a single echogenic line by ultrasound examination and measures between 1-4 mm in thickness, reflecting the early development of glands and stroma (Nalaboff).  These changes were exemplified in the section on the size of the endometrium but are sufficiently important to repeat at this time to emphasize the changes in character during the 28 day cycle.

The preovulatory endometrium is highly characteristic with trilaminar appearance of a central thin line of echogenicity, followed by a thicker hypoechoic zone and then a thin echogenic line again.

When the glands are full and the endometrium is thickest in the late secretory phase the endometrium becomes homogeneously echogenic, occasionally with a few cystic areas of early breakdown.

Character: Character – CT and MRI

The character of the uterus is dependent on many aspects including the age, time of the month and the way the angle of the uterus is scanned.

Characterization by MRI

T2-weighted imaging and contrast enhanced; T1-weighted image best evaluates the character of the uterus.

Blood Supply

The blood supply of the uterus is from the uterine artery, a branch of the internal iliac artery and ovarian artery, a branch of the aorta. The uterine artery passes inferiorly from its origin into the pelvic fascia and reaches the junction of the cervix and uterus by passing superiorly. It is superiorly related to the ureter which passes the pelvic brim to the urinary bladder and crosses the bifurcation of the common iliac artery. The uterine artery anastomoses with the ovarian artery superiorly and vaginal artery inferiorly.

The uterine artery runs along the lateral wall of the uterus and then penetrates the myometrium and divides in general into anterior and posterior branches. As they course toward the center they are called the arcuate arteries whose direction in general is circumferential to the uterus. They give rise to the radial arteries which course almost at right angles toward the endometrium.

Blood Supply: At the Mucosal Level

Branches from these arteries pass to the endometrium. As they enter the endometrium they run a straight course and supply the stratum basalis and as they enter the superficial layer of the stratum functionalis they become coiled and are called the spiral arteries. The straight arteries do not undergo cyclic changes and they supply stable unchanging blood supply to the stratum basalis which does not shed at the menses. The spiral arteries in the stratum functionalis, on the other hand, are subject to significant change with hormonal fluxes. Just before menstruation the spiral arteries coil and initially vasodilate and then there is an intense vasoconstriction causing ischemia and subsequent ischemia and destruction of the stratum functionalis which sheds as a result.

As they enter the endometrium they become the spiral arteries and their capillaries. The superficial layer of the endometrium (functionalis) is shed during menstruation. A basal layer, the basalis, is permanent and it regenerates after each menstruation. At the onset of menstruation the spiral arteries coil and initially vasodilate and then follow an intense vasoconstriction at the time of shedding.

 Venous Drainage

The venous drainage of the uterus is via the uterine veins, which in general parallel the course of the arterial supply and eventually drain into a branch of the internal iliac vein as well as into ovarian veins which drain into the IVC and left renal vein.

 Lymphatic Drainage

The lymphatics of the uterus also, in general, follow the arteries. As is usual among the other lymphatics of the body there are extensive interconnections between all the lymphatics of the pelvis. The lymphatic system of the cervix drains to the sacral nodes and the body, fundus and fallopian tubes drain toward the external iliac nodes. There is some drainage toward the internal iliac nodes as well. Lymphatics may also reach the superficial inguinal nodes along the round ligament.

 

Nerve Supply

The innervation of the uterus is entirely autonomic, arising from the inferior, hypogastric plexus (sympathetic) and the pelvic, splanchnic nerves (parasympathetic from S2,3, 4). The afferent fibers travel with the sympathetic efferents to T10-12 and L1 spinal cord segments.

In the sympathetic chain there is an intermediary step between the viscera and spinal cord – a “halfway house” if you will, that runs alongside the spinal cord and it is called the sympathetic chain. There is therefore, a neuron that carries the signal from the spinal cord to the sympathetic chain called the preganglionic neuron and one that carries the signal between the ganglion of the chain to the organ called the post ganglionic neuron. In general T1 goes to the head, T2- T6 the thorax and T7 -T11 the abdomen. T12, L1 and L2 go to the legs. This is an approximation and there is a large cross over. The innervation depends on the embryological origin.

Most of the afferent fibers ascend through the inferior, hypogastric plexus and enter the spinal cord via T10-12 and L1 spinal nerves.

The nerve supply to the uterus is derived from the hypogastric and ovarian plexuses and from the third and fourth sacral nerves.

Capsule of the Uterus

The uterus is covered by peritoneum anteriorly and posteriorly to the level of the isthmus. The peritoneal covering of the uterus is reflected posteriorly off the rectum in the region of the fornix of the vagina, creating a pouch called the recto-uterine pouch (also known as the cul de sac or pouch of Douglas or recto-vaginal pouch). This pouch is very important because it is the most posterior and inferior space of the peritoneal cavity and in the supine or upright position it will be the region where fluid will first accumulate. Anteriorly the peritoneal reflection is not as deep but a pouch is also formed called the utero-vesical (also known as the vesico-uterine) pouch.

Ligaments

The uterus remains in its pelvic position by virtue of its positions and various ligaments that keep it in position. These supports can lose strength with multiple vaginal childbirths, menopause and age and cause utero-vaginal position.

The anterior ligament consists of the vesicouterine fold of peritoneum, which is reflected onto the bladder from the front of the uterus, at the junction of the cervix and body.

The posterior ligament consists of the rectovaginal fold of peritoneum, which is reflected from the back of the posterior fornix of the vagina onto the front of the rectum. It forms the bottom of the recto-uterine pouch; laterally it is bound and the folds are called sacrogenital or rectouterine folds which have condensed fibrous tissue which attach to the sacrum and constitute the uterosacral ligaments.

The two lateral or broad ligaments (ligamentum latum uteri) pass from the sides of the uterus to the lateral walls of the pelvis. The portion of the broad ligament which stretches from the uterine tube to the level of the ovary is known as the mesosalpinx. Between the fimbriated extremity of the tube and the lower attachment of the broad ligament is a concave rounded margin called the infundibulopelvic ligament.

The round ligaments (ligamentum teres uteri) are two flattened bands between 10 and 12 cm. in length, situated between the layers of the broad ligament, in front of and below the uterine tubes.

The cardinal, Mackenrodt or transverse ligaments are attached to the side of the cervix uteri and to the vault and lateral fornix of the vagina. They are continuous externally with the fibrous tissue, which surrounds the pelvic blood vessels.

Conclusion
In Part 2 of “Applied Anatomy of the Uterus’ we will discuss common diseases, which can be congenital or acquired, benign or malignant tumors. Systemic disease, especially infections, can also affect the uterus and uterine cavity.

From a clinical perspective, we will describe the more common ailments manifesting as infertility, menorrhagia, acute or chronic abdominal pain, urinary complaints, and recurrent abortions. The module will conclude with a overview of diagnosis and treatment options.

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.