Reproductive Medicine
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TABLE OF CONTENTS Preface........................................................................................................ 1 Chapter 1: Anatomy of the Reproductive Tract ............................................ 4 Anatomical Planes ........................................................................................................... 5 Female Reproductive Anatomy ....................................................................................... 7 Male Reproductive Anatomy ......................................................................................... 16 Key Takeaways: .............................................................................................................. 23 Practice Questions: Chapter 1 ........................................................................................ 24 Chapter 2: Reproductive Hormones .......................................................... 26 Hypothalamic-Pituitary-Gonadal Axis .......................................................................... 26 The HPG Axis in Males .................................................................................................. 26 The HPG Axis in Females .............................................................................................. 29 Steroid Hormones .......................................................................................................... 31 Steroid Hormone Synthesis ....................................................................................... 31 Androgen Metabolism and Function ............................................................................. 36 Actions of Steroid Hormones on a Cellular Level ......................................................... 38 Congenital adrenal hyperplasia (CAH) ......................................................................... 40 Key Takeaways: .............................................................................................................. 47 Practice Questions: Chapter 2 ....................................................................................... 48 Chapter 3: Embryology ............................................................................. 50 Indifferent Stage of Development to Differentiation .................................................... 51 Summary of Male Reproductive Embryology ............................................................... 53 Summary of Female Reproductive Embryology ........................................................... 54
Disorders of Genetic Sex ................................................................................................ 54 X0 – Turner Syndrome .............................................................................................. 55 XXY – Klinefelter Syndrome ...................................................................................... 55 Other Disorders of Embryological Development .......................................................... 56 Bicornuate Uterus .......................................................................................................... 56 Ambiguous Genitalia ..................................................................................................... 57 Key Takeaways: .............................................................................................................. 60 Practice Questions: Chapter 3 ....................................................................................... 61 Chapter 4: Female Reproductive Physiology ............................................. 65 Puberty ........................................................................................................................... 65 Menstrual Cycle ............................................................................................................. 69 Hormonal Issues in the Menstrual Cycle ...................................................................... 73 Effects on the Endometrium.......................................................................................... 76 Menopause ..................................................................................................................... 77 Detecting Menopause Biochemically ............................................................................ 79 Key Takeaways: .............................................................................................................. 81 Practice Questions: Chapter 4 ....................................................................................... 82 Chapter 5: Disorders of Female Reproductive Physiology ......................... 85 Luteal Phase Defect........................................................................................................ 85 Polycystic Ovarian Syndrome ........................................................................................ 86 Endometriosis ................................................................................................................88 Dysmenorrhea ................................................................................................................ 89 Amenorrhea ................................................................................................................... 90 Anti-sperm Antibodies................................................................................................... 92
Anti-phospholipid Syndrome ........................................................................................ 93 Key Takeaways: .............................................................................................................. 94 Practice Questions: Chapter 5. ...................................................................................... 95 Chapter 6: Male Reproductive Physiology and Pathophysiology ................ 97 Normal Male Reproductive Physiology ......................................................................... 97 Puberty ........................................................................................................................... 98 Disorders of Male Reproductive Physiology ................................................................. 99 Aging and Male Fertility .............................................................................................. 104 Anti-sperm Antibodies................................................................................................. 107 Key Takeaways: .............................................................................................................110 Practice Questions: Chapter 6 ...................................................................................... 111 Chapter 7: Fertility and Infertility Issues.................................................. 114 Human Fertilization ..................................................................................................... 114 Infertility Overview ....................................................................................................... 118 Evaluating Infertility in an Infertile Couple ................................................................. 118 Male Infertility .............................................................................................................. 121 Female Infertility ......................................................................................................... 123 Ovulation Disorders ..................................................................................................... 124 Structural Factors ........................................................................................................ 125 Key Takeaways: .............................................................................................................127 Practice Questions: Chapter 7...................................................................................... 128 Chapter 8: Natural Enhancement of Fertility ........................................... 131 Ovulation Detection Methods ....................................................................................... 131 Fertility Nutrition ........................................................................................................ 134
Fertility Herbal Strategies for Men and Women ......................................................... 138 Fertility Massage and other Treatments ..................................................................... 140 Key Takeaways: ............................................................................................................. 141 Practice Questions: Chapter 8 ..................................................................................... 142 Chapter 9: Assisted Reproductive Technologies ...................................... 145 Sperm Collection .......................................................................................................... 145 Ovulation Induction ..................................................................................................... 146 Controlled Ovarian Hyperstimulation......................................................................... 148 Intrauterine Insemination (IUI).................................................................................. 149 In vitro Fertilization (IVF) ........................................................................................... 150 Intracytoplasmic Sperm Injection (ICSI) .................................................................... 153 Uterine Transplant....................................................................................................... 154 Key Takeaways: .............................................................................................................155 Practice Questions: Chapter 9 ..................................................................................... 156 Chapter 10: Contraception ...................................................................... 159 Overview....................................................................................................................... 159 Hormone-based Contraceptives ................................................................................... 161 Long Acting Reversible Contraceptives (LARC) ......................................................... 163 Barrier and Other Contraceptives ............................................................................... 164 Surgical Contraception ................................................................................................ 165 Emergency Contraception ........................................................................................... 166 Key Takeaways: ............................................................................................................ 167 Practice Questions: Chapter 10 ................................................................................... 168 Summary ................................................................................................. 171
Course Questions and Answers ................................................................ 176 Answers to Quiz ...................................................................................... 220 Answers to Practice Questions: Chapter 1 ...................................................................220 Answers to Practice Questions: Chapter 2 .................................................................. 221 Answers to Practice Questions: Chapter 3 .................................................................. 222 Answers to Practice Questions: Chapter 4 .................................................................. 223 Answers to Practice Questions: Chapter 5. ................................................................. 224 Answers to Practice Questions: Chapter 6 .................................................................. 225 Answers to Practice Questions: Chapter 7................................................................... 226 Answers to Practice Questions: Chapter 8 .................................................................. 227 Answers to Practice Questions: Chapter 9 .................................................................. 228 Answers to Practice Questions: Chapter 10................................................................. 229 Answers to Course Questions and Answers ................................................................ 230
PREFACE Reproductive Medicine is the study of human fertility and reproduction. Clinically, Reproductive Medicine deals with the anatomy, physiology, diagnosis, and treatment of a variety of reproductive disorders, including infertility. The advent of Assisted Reproductive Technology (or A-R-T) has led to a rapid expansion in the field of Reproductive Medicine. Reproductive Medicine is often considered one of the more challenging topics for medical students and clinicians. Reproductive Medicine requires an understanding of the anatomy, physiology, and pathophysiology of both the male and female reproductive tract. The purpose of this lecture will be to review the basic concepts of human reproduction and discuss the etiology, diagnosis, and treatment of common reproductive disorders. This course will provide listeners with a foundation to approach simple and complex clinical scenarios in Reproductive Medicine. In chapter one, we will review the basic anatomy of the male and female reproductive systems. We will begin by discussing the anatomy of the female reproductive tract, which includes the ovaries, fallopian tubes, uterus, cervix, and vagina. Next, we will review the anatomy of the major organs of the male reproductive tract, including the testis, efferent duct, epididymis, urethra and penis. While not all disorders of fertility are related to abnormalities of the anatomical structures of the reproductive tract, any abnormality that exists will automatically impair fertility. In humans, reproduction is dependent upon hormone signaling. The purpose of chapter two will be to discuss reproductive hormones. Reproductive hormones are part of the Hypothalamic-Pituitary-Gonadal Axis. The hypothalamus regulates hormone secretion from the pituitary gland. The hypothalamus synthesizes and secretes GonadotropinReleasing Hormone (or GNRH). GNRH is released from the hypothalamus in a pulsatile fashion. GNRH stimulates secretion of follicle stimulating hormone (or FSH) and luteinizing hormone (or LH) from the pituitary. Both FSH and LH play a role in steroid
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hormone synthesis and secretion. The reproductive steroid hormones include Testosterone, Dihydrotestosterone (or DHT), Estrogens, and Progesterone. Reproductive tract development will be covered in chapter three. Gonadal development begins around the seventh week of gestation. There are two basic embryologic structures that develop into the reproductive tract – the mesonephric ducts (also called the Wolffian ducts) and the paramesonephric ducts (also called Mullerian ducts). The male reproductive tract develops from the mesonephric or Wolffian ducts, and the female reproductive tract develops from the paramesonephric or Mullerian ducts. In chapter four, we will discuss female reproductive physiology. This chapter will cover the physiology of female puberty, ovulation, menstruation, and menopause. Female reproductive physiology is complex and involves multiple changes that occur in puberty as part of female reproductive development, the different changes that happen as part of the normal menstrual cycle, and the changes a woman goes through as she reaches menopause. The different ways in which menopause is diagnosed are covered in this chapter. Chapter five will include a discussion of female reproductive diseases, including endometrial and myometrial disorders, fertility-related issues, and causes of amenorrhea (or lack of menstruation) and dysmenorrhea. Each of these disorders will affect the menstrual cycle, menstruation, and fertility in different ways, which will be covered in the chapter. In chapter six, we will switch gears to male reproductive physiology and pathophysiology. Chapter six will provide a general overview of male reproductive physiology and cover topics such as puberty and spermatogenesis. Because male reproductive physiology is generally less complex than female reproductive physiology, chapter six will also cover disorders of male reproduction, including congenital disorders and hypogonadism. The purpose of chapter seven will be to review the principles of fertility and conception. We will also discuss the etiology and diagnosis of male and female infertility in this chapter. The normal fertilization of human oocytes to make a zygote is covered in this chapter along with how to work up infertility in the couple who cannot conceive. The
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different types of fertility issues seen in both men and women are also discussed in this chapter. Chapter eight in the course is devoted to issues related to the natural enhancement of fertility. While these are not often used in mainstream medicine for fertility enhancement, many infertile couples and naturopathic doctors promote things like natural ways to detect ovulation, issues related to optimizing nutrition for better fertility, herbal remedies for fertility enhancement, and even massage techniques designed to promote fertility. These are all covered as part of the discussion in this chapter. Assisted reproductive technologies will be covered in chapter nine, including intrauterine insemination, in vitro fertilization, and intracytoplasmic injection of sperm. These techniques are advanced therapies for a variety of infertility issues and have been found to be effective in attaining a pregnancy when it would otherwise be essentially impossible under natural circumstances. We will conclude this lesson by covering contraception (or birth control) in chapter ten of the course. Understanding available forms of contraception are critical to providing comprehensive reproductive care. Most are based on manipulating the hormonal milieu in women desiring to avoid pregnancy, although there are barrier methods and intrauterine methods, such as an IUD, that will effectively prevent pregnancy.
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CHAPTER 1: ANATOMY OF THE REPRODUCTIVE TRACT In this chapter, we will review basic reproductive anatomy in both males and females. This discussion will involve an overview of both male and female reproductive anatomy. In both genders, many of the major reproductive organs are contained within the pelvis. The pelvis is a circular region created by the joining of the pelvic bones with the sacrum. Figure 1 shows the bony pelvis, which has the major purpose with regard to the reproductive system of protecting these vital structures:
Figure 1.
For clinical purposes, it is important to understand that the shape of the pelvis differs in males and females. In general, females have a wider pelvic inlet to facilitate childbirth. There are actually many differences between these two anatomical structures that
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impact the ability of the female in particular to have a successful childbirth. Let’s review these: •
Pelvic size—the male pelvis tends to be smaller than the female pelvis, even though the bones are thicker. The female has lighter bones but a bigger pelvis overall, which gives a woman wider hips.
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Sacrum—the sacrum forms the broad base of the vertebral column and is a posterior structure the fetus must pass near during childbirth. In males, the sacrum is more curved, longer, and narrower. In females, the sacrum is shorter, wider, and less curved. Too great a curvature in females would impact the ability of the fetus to pass through the pelvis in the birth process.
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Pelvic inlet and outlet—the pelvic inlet is the first bony barrier to effective passage of the fetus in childbirth. In females, the pelvic inlet is roughly oval in shape, while in males, this structure is heart-shaped. The pelvic outlet is below the inlet and is narrower in males than it is in females. Again, the goal is to have a birth passage that is more efficient in females than it is in males.
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Coccyx—this is the small triangular lower tip of the vertebral column. In males, the coccyx is immobile and is projected inward. In females, the coccyx is straighter and is considerably more flexible than in males.
Again, each of these pelvic bone structures represents an evolutionary difference between men and women that together account for the ability of the female sex to give birth much more efficiently than the male sex. Women who, for whatever reason, were born with a more android-shaped pelvis will not necessarily have more difficulty getting pregnant but will have a harder time achieving a vaginal birth.
ANATOMICAL PLANES Let’s start our discussion of reproductive anatomy by reviewing standard anatomical planes. The body can be divided up into three distinct planes – the sagittal plane, the coronal plane, and the transverse plane. Figure 2 shows what these common anatomical planes look like:
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Figure 2.
The three anatomical planes are perpendicular to each other and are based on the standard anatomical position. The standard anatomical position assumes an individual is standing, facing forward, with the palms of his or her hands facing forward as well. •
In standard anatomical position, the sagittal plane divides the body in half creating a left side and a right side. The sagittal plane runs vertically from head to toe.
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The parasagittal plane is any vertical plane that is on either side of the central sagittal plane. It does not divide the body into two equal halves.
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Like the sagittal plane, the coronal plane also runs from head to toe. However, the coronal plane divides the body into front and back.
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The transverse plane, which is also called the horizontal plane, divides the body into superior and inferior sections – or top and bottom sections. The transverse plane runs parallel to the ground in a person in standard anatomical position.
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In order to avoid confusion, there are a few other anatomical terms we should review: •
Anterior is used to describe a structure that is towards the front. For example, the heart is largely anterior to the lungs.
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Posterior is used to describe a structure that is towards the back. For example, the lungs are largely posterior to the heart.
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Superior is used to describe a structure that is towards the head. For example, the eyes are superior to the mouth.
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Inferior is used to describe a structure that is towards the feet. For example, the mouth is inferior to the eyes.
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Medial is used to describe structures in relation to the midline of the body.
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Lateral is used to describe structures further from the midline of the body. In females, the ovaries are the most lateral anatomical structures.
To review – anterior means front, while posterior means back. Superior means top (or closer to the head), while inferior means bottoms (or closer to the feet). The term medial is used to describe structures closer to the midline, while lateral is used to describe structures further from the midline. These terms will be helpful in understanding the relationship of the reproductive organs to one another.
FEMALE REPRODUCTIVE ANATOMY The female reproductive system consists of the ovaries, fallopian tubes, uterus, cervix, and vagina. The ovaries, fallopian tubes, uterus, cervix and upper two-thirds of the vagina are located in the pelvis, which means that the vast majority of the system is protected by this bony structure. It is useful to keep in mind that these organs share space in the pelvis with the structures of the urinary and gastrointestinal systems. Figure 3 shows these major female reproductive structures:
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Figure 3.
To understand where the organs of the female reproductive system are located within the pelvis, let’s first consider the coronal plane. Figure 4 shows these structures in the coronal plane:
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Figure 4.
Recall that the coronal plane runs from head to toe and separates the body into anterior and posterior segments – or front and back segments. The coronal planes allow us to consider how the organs of the pelvis relate to the midline. In this view, we can appreciate that the uterus, cervix, and vagina are midline structures. The fallopian tubes extend laterally on both sides of the uterus. The fallopian tubes are hollow structures contiguous with the smooth muscle of the uterus. The fallopian tubes open to the ovaries. The ovaries are connected to the uterus by the ovarian ligament. In the coronal view, you can see the close association of the female reproductive system to the urinary bladder and female rectum. Most of the time, this does not affect fertility but, as you’ll see, things like endometriosis affect the uterus, bladder, and rectum or even the sigmoid colon, leading to bladder or GI symptoms often seen in this disorder. 9
In addition, the fact that the bladder is a hollow structure that can be kept full of urine makes it helpful in using ultrasonography to better visualize the female reproductive structures using a transabdominal view of the uterus and ovaries. The uterus, cervix and vagina form a hollow continuum located immediately behind the bladder, and the rectum is the most posterior structure in this view. This orientation also helps explain why pregnant women often have to urinate frequently. The bladder – the most anterior structure in this view – sits between the pubic bone and the uterus. As the uterus grows during pregnancy, it can put pressure on the bladder. Let’s next consider the sagittal plane. Recall, that the sagittal plane is a vertical plane that divides the body in half into left and right segments. This view allows you to see how the organs of the pelvis relate to one another. In this view, the bladder is the most medial structure and that the vagina, cervix, and uterus, are also medial. The furthest lateral structures are the ovaries, which are paired structures on either side of the uterus. Let’s now consider each of the organs of the female reproductive tract individually. The ovaries are the gonadal structures of the female reproductive system. Females have two ovaries – a right ovary and a left ovary. The ovaries are oval shaped, and each ovary is about the size of an almond. The ovaries are held in place by the broad ligament. The ovaries are attached to the uterus by the ovarian ligament. The blood supply to the ovary comes from the ovarian artery. The right and left ovarian arteries branch directly off of the abdominal aorta right below the level of the renal artery. Figure 5 shows the major ligaments of the female reproductive system:
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Figure 5.
The ovaries contain two general populations of cells – germ cells and follicle cells. Germ cells migrate into the gonadal tissue very early in embryonic development. Follicular cells (which are also referred to as granulosa cells) act as support cells for the germ cells. We will discuss the function of these cell populations in a few minutes. The fallopian tubes – also called the uterine tubes – are tubular structures extending from the uterine fundus, bilaterally. The fallopian tubes transport eggs from the ovary to
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the uterus. The fallopian tubes are contiguous with the uterus and consist of an inner mucosal layer and an outer smooth muscle layer. The mucosal layer contains ciliated cells that help propel the egg towards the uterus. Similarly, the smooth muscle layer contracts to facilitate egg transport. The fallopian tubes can be divided into four sections – the isthmus, the ampulla, the infundibulum, and the fimbriae. The isthmus extends off the uterus and is the most medial part of the tube. The ampulla of the fallopian tube is lateral to the isthmus. The ampulla is a curved section of the tube, and it is the location of fertilization. The infundibulum is the funnel-shaped portion of the tube that opens to the ovary. Fimbriae are attached to the infundibulum. Fimbriae function by sweeping released eggs from the ovary into the infundibulum. From the infundibulum, the egg can then travel through to the ampulla, isthmus, and into the uterine cavity. The fallopian tube is the major site of fertilization of the female egg, after which it is the zygote that gets transported to the uterus. While fertilization can occur anywhere along the fallopian tube, the most common site for this process is the ampulla. You need to realize that much of the fallopian tube interiorly is very narrow. The total length of each fallopian tube is 7 to 12 centimeters, while the external diameter is less than 1 centimeter. The narrowest part of the fallopian tube is the part where it opens into the uterus. At this point, it is just 1 millimeter in internal diameter. In the ampulla, the internal diameter is about six millimeters in diameter. The fimbriae represent the lateral ends of the fallopian tube. These form fingers that essentially wrap around the ovaries in order to give the ruptured egg the best opportunity to flow into the fallopian tube. While the relationship between the fimbriae and ovary is a close one, this structure actually is not enclosed but opens directly into peritoneal cavity itself. It provides a portal through which menstrual blood and tissue, ascending infectious organisms, or pus can pass out of the female reproductive tract in order to enter the pelvis. In addition, the narrowness of the fallopian tube in parts makes it easy for this structure to impact fertility. If an infection occurs that scars the fallopian tube, this greatly impairs fertility by blocking the passage of the egg or zygote, leading to an increased chance of an ectopic pregnancy.
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The fallopian tube has multiple layers. The inner epithelial layer has four types of cells within it. There are secretory cells that do not have cilia and ciliated cells that contain the cilia, which beat in the direction of the uterus. There are intercalary cells sometimes called peg cells spaced between other cells. Small cells called indifferent cell make up the fourth type of epithelial cell in the fallopian tube. The numbers and appearance of these cells depend greatly on the estrogen and progesterone levels of the female, which means they function differently depending on the menstrual phases, pregnancy status, and menopausal status of the woman. This alone may play a significant role in fertility. The uterus is a hollow organ that functions as the womb in human reproduction. The uterus is comprised of three layers – the endometrium, the myometrium, and the perimetrium. The perimetrium is the outermost layer. The perimetrium is a serous membrane covering similar to the peritoneum and pericardium. The myometrium is the middle layer. The myometrium is comprised of smooth muscle and functions to expel the neonate during labor and delivery. The innermost layer is the endometrium, which is the layer involved in the female menstrual cycle. Before we discuss the endometrium and myometrium separately, let’s first discuss the uterus as a whole. The uterus is located within the pelvic cavity and is contiguous with the fallopian tubes superiorly and the cervix inferiorly. Within the pelvis, the uterus is supported by a variety of muscles and ligaments. The pelvic floor muscles support the uterus nearly as much as the supporting ligaments. Women with pelvic floor dysfunction will not have the musculature to support the uterus and uterine prolapse through the vagina may occur. Laxity of the supporting ligaments also affects uterine prolapse. Among the different supporting ligaments of the uterus are the round ligaments that connect the anterior and superior surface of the uterus to the labia majora, passing through the internal inguinal rings and the inguinal canal. These stretch as the uterus grows in pregnancy. The second set of ligaments is the uterosacral ligaments that fan out from the lateral uterus to the sacrum. These contain muscle fibers, blood vessels, parasympathetic nerve fibers, and lymphatics. There are also the paired transverse or cardinal cervical ligaments that extend from the cervix and insert into the fascia near the
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levator ani muscles and obturator muscles. The broad ligament comes from peritoneal folds that cover the fallopian tubes, housing the major uterine structures. The upper part of the uterus is more muscular, while the lower part of the uterus, including the cervix, is more fibrous. The portion above the fallopian tubes is called the fundus. The next lowest portion is the corpus or body. The lower part is the cervix or isthmus. The majority of the endometrial cavity is contained within the corpus. The myometrium is layered in the uterus. The outer layer is longitudinal along the vertical axis of the uterus. The vascular layer has interlacing spiral groups of smooth muscle fibers and is very vascular. The inner layer is both oblique and longitudinal. These layers together allow for maximum uterine contractions in all directions. The uterus itself can be in several different positions. Most of the time, the woman who has never been pregnant has a uterus slightly bent in the anterior direction and its axis is also tilted forward. A lesser number of women will have a retroflexed uterus, which is backward curvature, or retroversion, which is backward tilted with respect to the axis. Others are mid-position, with a vertical axis. There is no evidence that any of these positions affects fertility, bleeding patterns, or pain patterns of the woman, even though this was once a common misperception. The outer layer of the uterus is called the perimetrium, which is an extension of the peritoneum. This is a thin layer of fascia that lies over the uterus on all sides. It has no muscular or secretory activity but largely separates the external border of the uterus. The endometrium is very important and changes with the different phases of the menstrual cycle. There are three layers, including the pars basalis, the zona spongiosa, and the superficial zona compacta. There are straight branches of the uterine radial arteries that end in the pars basalis. There are spiral branches that penetrate further to make lakes of dilations of the end capillaries. The endometrium proliferates because of the influence of estrogen, while maturation of this tissue is under the influence of progesterone. In the follicular phase or proliferative phase, the lining thickens up until the time of ovulation. After ovulation is the secretory or luteal phase. The menstrual phase is when the most superficial layer sheds because estrogen and progesterone levels are low. The spiral arteries proliferate in the luteal 14
phase but clot off in the menstrual phase in order to shed the superficial zona compacta. Menstrual cramps come from ischemia of the uterine lining as the spiral arteries fail. The blood supply of the uterus is derived from the uterine artery. The uterine artery is a branch off of the internal iliac artery. The uterus also receives blood from the ovarian artery. The ovarian artery arises from the abdominal aorta. The uterine and ovarian arteries often have small connections – or anastomoses - between them. The uterus receives both sympathetic and parasympathetic innervation. The sympathetic innervation to the uterus is derived from the uterovaginal plexus. The uterovaginal plexus arises from the inferior hypogastric plexus. The parasympathetic innervation to the uterus comes from the pelvic splanchnic nerves. The pelvic splanchnic nerves arise from S2 through S4. There is the inferior aspect of the uterus called the cervix. It is about 2 to 3 centimeters long. There is an intravaginal part called the portio vaginalis, which has nonkeratinizing squamous epithelium on its surface with mucus glands. Below that is the endocervical canal, which is 2 centimeters long. The external os is the opening of the cervix into the vagina. The endocervical canal is lined with columnar epithelium and contains endocervical glands. At the junction of the ectocervix and the endocervix is the squamocolumnar junction. Its features depend on the hormonal environment. This is where cervical cancer originates. The cervix is contiguous with the body of the uterus. The cervix connects the uterus to the vagina. The cervix is comprised of two distinct regions – the ectocervix and the endocervix. The ectocervix is the inferior region of the cervix that projects into the vagina. The opening of the ectocervix is called the external os. The endocervical canal is the more superior portion of the cervix. The internal os is the opening between the endocervical canal and the body of the uterus. The uterine artery supplies blood to the cervix. The cervix is innervated by the pelvic splanchnic nerves arising from S2 through S4. The vagina is a muscular tube that extends from the cervix. The vagina consists of four layers – an outermost fibrous layer, a fibromuscular layer, an elastic layer, and an innermost epithelial layer. The blood supply to the vagina comes from the uterine
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arteries and vaginal arteries. The vagina is innervated by the pelvic splanchnic nerves. Somatic innervation of the vagina comes from the pudendal nerve.
MALE REPRODUCTIVE ANATOMY In this section, we will review the anatomy of the male reproductive tract. Figure 6 shows the major structures of the male reproductive tract:
Figure 06.
The testes are the gonads of the male reproductive system. The testes are located within the scrotum. The teste produce the male gamete, called sperm, spermatozoon, or sperm cell. The testes have both an exocrine and endocrine function. The exocrine function of the testes includes producing sperm and seminal fluid to support sperm cells. The endocrine function of the testes is to synthesize and secrete steroid hormones, such as testosterone and dihydrotestosterone. The endocrine function of the testes will be
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discussed in length in chapter two. Blood to the testes is supplied by the testicular arteries. The testicular arteries arise from the abdominal aorta. Each testis is about 4 to 5 centimeters in length, surrounded by two separate layers of connective tissue. The outermost layer is called the tunica vaginalis, which itself has a parietal and visceral layer. Inside the tunica vaginalis is the tunica albuginea, which is tough, fibrous, and white in color. This inner layer forms multiple septa that divides each testis into about 300 to 400 lobules. Within the lobules are the seminiferous tubules. Figure 7 shows the structure of the testis:
Figure 07.
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The seminiferous tubules are tightly coiled and make up most of the testis. They are configured with ducts that have several layers each that have a central lumen. Spermatogenesis starts and ends in these tubules. We will talk about spermatogenesis in a minute. As the sperm cell is created, it enters the strait tubules or rete testes. There are a few of these ducts that have coalesced from minor ducts. These are called efferent ductules, which exit the confines of the tunica albuginea. Within the seminiferous tubules are cells of six different types. There are supporting cells known as sustentacular cells and five separate types of germ cells that start with the most immature cells at the outer basement membrane and end with the most mature but haploid cells nearest the lumen. The Sertoli cells are the sustentacular cells that secrete molecules to promote the production of sperm. They also determine if a given germ cell will survive or not. These are particularly important because they have tight junctions between them that form the blood-testes barrier. Men need this barrier to protect the developing sperm cells from outside influences and protect the body’s immune system from seeing these sperm cells as foreign, making autoantibodies against them. Should this happen, fertility can be impaired. The germ cells go from least mature to most mature in the seminiferous tubules. The least mature cells are the spermatogonia, which are just inside the basement membrane. These are essentially stem cells. They divide into primary and secondary spermatocytes, evolve into spermatids, and mature further into sperm cells. This is the process of spermatogenesis, which does not start until puberty. It takes 64 days to go from a stem cell to a formed sperm cell, with new cycles beginning every sixteen days. Spermatogonia are diploid cells having 46 chromosomes, while mature sperm cells have 23 chromosomes and are therefore haploid. The process of meiosis performs this change with a great deal of DNA crossover happening so that each sperm cell is unique. One spermatogonia creates four unique haploid sperm cells. Figure 8 shows the process of spermatogenesis:
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Figure 08.
The scrotum is an external cutaneous sac. The scrotum is located externally because spermatogenesis – or sperm production – takes place at temperatures about 2 to 4 degrees Celsius below body temperature. The scrotum has its own layers beneath the skin. There is a dartos muscle that is just beneath the skin. It extends up to make the scrotal septum, dividing the two testes. The abdominal internal oblique muscle descends to create the cremaster muscles that cover the testes. These muscles contract in cold environments in order to bring the testes closer to the core of the body. They also relax in warm weather in order to move them away from the body so as to lower their temperature. They also change the surface area of the testes to retain heat if necessary. The midline area of the scrotum on the skin is called the raphe. Mature sperm cells are very small with very little cytoplasm. About 100 to 300 million sperm cells are made each day. Each sperm cell has a distinct head, a midpiece, and a tail. The head contains the genome of the cell. It is covered with an acrosome or cap that contains enzymes to help in egg penetration. The midpiece has packed mitochondria that help provide energy for the tail to be motile. The flagellum has an
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axial filament that participates in its movement. Figure 9 shows the structure of a mature sperm cell:
Figure 09.
Once the sperm cell is made in the seminiferous tubules, they enter the epididymis for further maturation of the sperm. The epididymis is a coiled tube that would be 20 feet in length is it is straightened out and not coiled. It takes twelve days to have a sperm cell migrate through the epididymis. It is propelled through smooth muscle contractions in this structure. Eventually, these sperm cells will acquire the ability to move under their own power. They are stored in the epididymis until the time of ejaculation. Even though sperm are mature in the epididymis, they must undergo processing and must travel through a duct system in order to exit the body. The ductus deferens or vas deferens is a muscular tube that, together with nerves and blood vessels, forms the spermatic cord. This is the part of the male reproductive system that can be cut in a vasectomy to prevent a pregnancy. Sperm itself make up just five percent of semen. This means that there is more to semen, gotten from different glands and structures in the male reproductive system.
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The first place these sperm cells go is the seminal vesicles. This is where volume is added, along with a great deal of fructose. Fructose is a sugar used specifically by the mitochondria in order to provide fuel to them as the cells proceed through the male and female reproductive tract. This fluid then travels through the ejaculatory ducts to enter into the prostate gland. There is just one prostate gland that sits at the base of the bladder and surrounds the male urethra. This secretes an alkaline substance to the semen in order to allow sperm to coagulate and then decoagulate after ejaculation. Sperm must first coagulate in order to stay within the vagina and then must decoagulate in order to pass through the cervix. The bulbourethral glands is the last place where the semen travels. These are also called Cowper’s glands. There is a thick, salty substance secreted by the glands in order to lubricate and cleanse the semen as they pass through the urethra. Pre-ejaculate is the substance released prior to ejaculation as part of sexual responsiveness. While not containing much sperm, pre-ejaculate can still cause a pregnancy. The penis consists of three distinct sections – the root, the body, and the glans. The root of the penis is the most proximal portion and is located internally within the superficial perineal pouch. The body of the penis is the external portion connecting the root to the glans. The body of the penis contains three columns of erectile tissue – the corpus spongiosum and two corpus cavernosa. The corpus spongiosum is a small capillary bed that surrounds the urethra. The corpus cavernosa is a larger capillary bed that fills with blood during an erection. The glans is the most distal portion of the penis. The glans of the penis contains the external urethral opening surrounded by corpus spongiosum. Figure 10 shows the structure of the male penis:
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Figure 10.
Blood is supplied to the penis by the dorsal penile arteries, the deep penile arteries, and the bulbourethral arteries. The dorsal penile arteries, the deep penile arteries, and the bulbourethral arteries all arise from the internal pudendal artery. The penis receives sympathetic, parasympathetic, and sensory innervation. Innervation to the penis arises primarily from the S2 through S4 spinal regions. Parasympathetic input controls erection, whereas sympathetic input controls ejaculation. The mnemonic “point and shoot” is often used to help medical students remember the innervation of the penis. Point equals parasympathetic and shoot equals sympathetic. Parasympathetic input controls “pointing” or erection, while sympathetic input controls “shooting” or ejaculation.
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