External structures

Testes

The testes (see Figure 31-2) are the source of both sperm and the male sex hormone, testosterone. There are usually two testes, oval in shape and approximately 4–5cm long, located outside the body cavity in the scrotum (a pouch of skin). The cremaster muscles in the scrotum can raise the testes closer to the body (in a cold environment) or lower them further from the body (in a hot environment). The temperature in the scrotum is approximately 3°C lower than normal core body temperature (see Figure 31-3) — this is essential for the survival of sperm. During fetal development, the testes develop in the upper body cavity and at 7 months’ gestation they move through the inguinal canal to the scrotum together with the spermatic cord.

FIGURE 31-2 The testes.

A The scrotum. B The tubules of the testis and epididymis.

FIGURE 31-3 The heat exchanger of the testis.

As blood descends from the body through the testicular artery, heat is transferred into nearby venous blood, so the arterial blood cools as it descends. The blood that reaches the testes is approximately 3°C cooler than blood in the rest of the body.

Each testis is divided into about 250 internal compartments called lobules, each of which contains 1 to 3 long, thin tightly coiled hollow tubes called seminiferous tubules. The seminiferous tubules are the sites of sperm production and contain two major types of cells: (1) spermatogonia, which are germ cells that line the walls and develop into spermatozoa; and (2) sustentacular (Sertoli) cells, which support this process. Adjacent sustentacular cells form tight junctions in which the walls of two adjacent cells are ‘stuck’ together very firmly. These tightly joined cells create a blood–testis barrier, which prevents immune blood cells from entering the seminiferous tubules. This barrier is required because the developing sperm have surface antigens that could be recognised as foreign by the immune system; in the absence of the barrier, an immune attack would be mounted against the sperm, causing inflammation and possible male sterility.

Located between the tightly packed seminiferous tubules are cells called interstitial (Leydig) cells. These cells secrete testosterone when stimulated by luteinising hormone (LH).

Penis

The human male penis (see Figure 31-4) performs two major functions: (1) the elimination of urine; and (2) the delivery of mature spermatozoa and associated fluids to the female reproductive tract. The structure of the penis is such that it is a small soft organ for the majority of the time, but becomes greatly enlarged and stiffened for the purpose of reproduction.

FIGURE 31-4 A cross-section of the penis.

The penis contains 3 cylindrical columns of erectile tissue — that is, ‘spongy’ tissue that becomes rigid when congested with blood (supplied to the penis from the internal iliac artery via the internal pudendal or penile artery). On each side of the penis there is an erectile corpus cavernosum and medially there is the corpus spongiosum, the tip of which is enlarged to form the glans penis. The penile urethra runs through the corpus spongiosum and the glans is covered by a double fold of skin, the prepuce (foreskin).

The nerve supply to the penis is from the second, third and fourth sacral spinal nerves, through the pelvic plexuses and the internal pudendal nerve. These are the nerves that are involved in the different stages of the male sexual response. These nerves can be damaged through trauma (often car or motorcycle accidents) and can result in altered sexual function.

Internal structures

Accessory glands

The male reproductive system includes three accessory glands (see Figure 31-5). These glands produce the fluids that that are added to the sperm to produce the final mixture known as semen.

Seminal vesicles. These two pouches behind the bladder, alongside the ampullae, secrete and store the seminal fluid. The seminal fluid is viscous and alkaline, and it helps to neutralise the acid environment of the female vagina. The fluid also contains fructose (a sugar energy source for sperm) and fibrinogen (to clot the semen and attach it to the wall of the vagina). The fluid is emptied into the ejaculatory ducts to join the sperm from the ductus deferens and forms a major part of the ejaculate (60% of semen volume).

Prostate gland. This gland is located at the base of the bladder, surrounding the first part of the urethra. It may be palpated through the rectum in a prostate examination. The prostate is often enlarged in old age (obstructing the flow of urine from bladder). The prostate gland secretes a milky, slightly acidic fluid that contains acid phosphatase, clotting enzymes and fibrinolysin (which breaks the clot of sperm to allow sperm to move into the uterus). This contributes to sperm motility and viability and makes up about 25% of semen volume. Many small ducts within the prostate deliver this fluid to the urethra.

FIGURE 31-5 Anatomy of the prostate gland and seminal vesicles.

It is important to note the spelling (and hence pronunciation) of the word prostate, as it is sometimes confused with the word prostrate, which means lying face-down.

Bulbourethral glands (Cowper’s glands). These glands are the size of peas and lie immediately below the prostate. The ducts empty into the penile urethra below the prostate. The fluid produced by these glands is clear, mucous and alkaline and makes up 10% of the semen. This small volume of secretion is released shortly before ejaculation, serving to neutralise the acidic pH of the penile urethra.

The remaining 5% of semen volume consists of the sperm.

FOCUS ON LEARNING

1. Describe the structure of the testes and penis.

2. Discuss the progression of sperm from the testes through the spermatic ducts and penis.

3. Discuss the roles of the male accessory glands.

4. List the components of semen.

External structures

The vulva is the collective name for the external female genitalia comprising the mons pubis, clitoris, vestibule, introitus (entrance), Bartholin’s glands and the labia (lips) majora and minora (see Figure 31-7).

FIGURE 31-7 External female genitalia.

The mons pubis is a pad of fat that covers and protects the pubic symphysis. The clitoris is erectile tissue and it is the female equivalent of the male penis, in that it arises from the same embryonic tissue, has a similar (but much smaller) structure and becomes engorged with blood during arousal. It consists of a spongy tissue that becomes rigid when congested with blood (during arousal) and is highly innervated, being the major site of female sexual stimulation and orgasm. The vestibule contains the openings of the urethra, vagina and Bartholin’s glands (which produce lubricating secretion). The introitus is the vaginal orifice itself, and is covered by a thin membrane (hymen) in females prior to their first sexual encounter.

The labia majora (plural; singular = labium majorum) are two folds of skin that extend from the mons pubis to the fourchette. They are highly sensitive to temperature, touch, pressure and pain and are homologous to the male scrotum. Sebaceous glands on the medial (inner) surfaces secrete lubricants and the labia protect the structures of the vulva. The labia minora (plural; singular = labium minorum) are two smaller and thinner folds of skin within the labia majora. They form the prepuce (foreskin) of the clitoris, are hairless and secrete a bactericidal lubricant. When aroused, the labia become flushed with blood and enlarge slightly. The labia minora are also highly innervated and provide stimulation during coitus (sexual intercourse).

Posterior to the vestibule are the perineum and anus, the perineum being the area of skin lying between the vaginal orifice and the anus — it has very little subcutaneous fat, little hair and sebaceous glands.

Internal structures

The internal structures of the female reproductive system (see Figure 31-6) are the vagina, cervix, uterus, fallopian tubes and ovaries.

Vagina

The vagina is an elastic, fibromuscular canal that is 9–10 cm in length. It extends up and back from the introitus to the lower portion of the uterus. As Figure 31-6 shows, the vagina lies between the urethra (and part of the bladder) and the rectum. Mucosal secretions from the upper genital organs, menstrual fluids and products of conception leave the body through the vagina, which also receives the penis during coitus. During sexual excitement, the vagina lengthens and widens and the anterior third becomes congested with blood.

The vaginal wall consists of a mucous membrane lining of squamous epithelial cells that allows the vagina to stretch during coitus and childbirth. There is also a thick layer of smooth muscle that assists with these functions.

The upper part of the vagina surrounds the cervix, the lower end of the uterus (see Figure 31-8). The recessed space around the cervix is called the fornix of the vagina. The posterior fornix is deeper than the anterior fornix because of the angle at which the cervix meets the vaginal canal, which is usually about 90°. A pouch called the cul-de-sac separates the posterior fornix and the rectum.

FIGURE 31-8 A cross-section of the uterus, fallopian tube and ovary.

The vagina’s elasticity and relatively sparse nerve supply enhance its function as the birth canal. During sexual arousal, however, the vaginal wall becomes engorged with blood, like the labia minora and clitoris. Engorgement pushes some fluid to the surface of the mucosa, enhancing lubrication. The vaginal wall does not contain mucus-secreting glands; rather, secretions drain into the vagina from the endocervical glands or enter from the vestibule from the Bartholin’s glands.

Ovaries

The ovaries are the female gonads responsible for the production of the gametes, as well as the production of the major female sex hormones, oestrogen and progesterone (see Figure 31-9). There are two small, oval-shaped ovaries, one on each side of the uterus. In women of reproductive age, each ovary is 3–5 cm long, 2.5 cm wide and 2 cm thick and weighs 4–8 g. Size and weight vary somewhat from phase to phase of the menstrual cycle. Each ovary is secured by ligaments, including the mesovarian, ovarian and suspensory ligaments, while the blood supply comes from the ovarian artery.

FIGURE 31-9 A cross-section of an ovary during the reproductive years.

Breast structure

The female breast is composed of 15–20 pyramid-shaped lobes that are separated and supported by Cooper’s ligaments (see Figure 31-10). Each lobe contains 20–40 lobules, which subdivide into many functional units called acini (plural; singular = acinus). Each of these is lined with epithelial cells capable of secreting milk and subepithelial cells that contract to squeeze milk from the acinus. The acini empty into a network of ducts that reach the skin surface through openings (pores) in the nipple. The lobes and lobules are surrounded by muscle strands and fatty connective tissue. The amount of fatty connective tissue varies from individual to individual, depending on weight, genetic and endocrine factors.

FIGURE 31-10 The female breast.

An extensive capillary network surrounds the acini, with supply from the internal and lateral thoracic arteries and intercostal arteries, while venous return follows the arterial supply and empties into the superior vena cava. Lymphatic drainage of the breast occurs largely through axillary nodes, but approximately 25% occurs through transpectoral and internal mammary routes. The breasts receive sensory innervation from branches of the second to sixth intercostal nerves and the cervical plexus. This accounts for the fact that breast pain may be referred to the chest, back, scapula, medial arm and neck.

The nipple is a pigmented, cylindrical structure, which has multiple openings, one from each lobe. The areola is the pigmented, circular area around the nipple. A number of sebaceous glands, the glands of Montgomery, are located within the areola and aid in lubrication of the nipple during lactation (milk production). The nipple and areola contain smooth muscles, which receive motor innervation from the sympathetic nervous system. Sexual stimulation, breastfeeding and exposure to cold cause the nipple to become erect.

At the onset of puberty in the female, oestrogen secretion stimulates mammary growth. Breast development, or thelarche, is usually the first sign of puberty. During the reproductive years, the breast undergoes cyclic changes in response to changes in the levels of oestrogen and progesterone associated with the menstrual cycle. Oestrogen promotes development of the lobular ducts; progesterone stimulates development of cells lining the acini. Lactation occurs after childbirth in response to increased levels of prolactin. Prolactin secretion increases by continued breastfeeding. Oxytocin, another hormone released after delivery, controls milk ejection (let down) from acini cells.

During the proliferative phase of the menstrual cycle, high oestrogen levels increase the vascularity of breast tissue and stimulate proliferation of ductal and acinar tissue. This effect is sustained into the luteal phase of the cycle. During this phase, progesterone levels increase and contribute to the breast changes induced by oestrogen. Specific effects of progesterone include dilation of the ducts and conversion of the acinar cells into secretory cells. Most women experience some degree of premenstrual breast fullness, tenderness and increased breast nodularity. Breast volume may increase as much as 10–30 mL. Because the length of the menstrual cycle does not allow for complete regression of new cell growth, breast growth continues at a slow rate until approximately 35 years of age. Because of the cyclic changes that occur in breast tissue, breast examination should be conducted at the conclusion of or a few days after the menstrual cycle, when hormonal effects are minimal and breasts are at their smallest.

The function of the female breast is primarily to provide a source of nourishment for the newborn. Physiologically, breast milk is the most appropriate nourishment for newborns. Not only does its composition change over time to meet the changing digestive capabilities and nutritional requirements of the infant, but it also contains specific immunoglobulins, especially IgA, and nonspecific antimicrobial factors, such as lysosomes and lactoferrin, that protect the infant against infection. During lactation, high prolactin levels interfere with hypothalamic-pituitary hormones that stimulate ovulation. This mechanism suppresses the menstrual cycle and prevents ovulation.⁵ In underdeveloped countries, breastfeeding is the major means of contraception.

The effects of testosterone in males

Testosterone is a very powerful hormone causing major changes in the male body. Testosterone is essential for spermatogenesis and the changes seen in the young male when puberty commences. After puberty, it is necessary to maintain the function and size of the reproductive organs. The effects of castration (removal of the testes, also known as orchidectomy) include both depression of sexual function and a reduction in the size of the accessory organs; this is evidence of the necessity for the continued production of testosterone throughout adult life.

Testosterone stimulates the development and maintenance of the male secondary sex characteristics of hair growth (facial, pubic and axillary or underarm), growth of the larynx resulting in a deepening of the voice, secretion of skin oil glands, the male pattern of fat distribution and the male libido (sex drive). In individuals with a genetic predisposition, higher levels of testosterone are thought to be associated with baldness. Higher levels of testosterone also cause negative feedback to the hypothalamus and anterior pituitary (to lower the secretion of GnRH, FSH and LH).

A major function of testosterone is to drive anabolism — namely, increased muscle and bone growth. These effects have been exploited by athletes who use anabolic steroids (similar to testosterone) to gain muscle mass and hence sports controlling bodies commonly test for anabolic steroids. An increased level of aggression is often associated with testosterone; however, this is a hotly debated topic and there is no clear evidence to show that high levels of testosterone lead to violent tendencies. Note that androgens are the male sex hormones, the main one being testosterone.

The effects of oestrogen and progesterone in females

Oestrogen and progesterone are powerful hormones that cause major changes in the female body. Unlike testosterone, they are not required to be produced in the fetus to develop a female reproductive anatomy, so the absence of testosterone in a fetus results in female development. (Remember that the sex of the fetus is determined at conception by the combination of chromosomes from the mother and father, and the hormones are produced to match this sex.

Oestrogen is analogous with testosterone in that it stimulates the growth of the ovaries and primordial follicles (germ cells that become oocytes, the immature eggs). In addition, it stimulates the growth of smooth muscle and the proliferation of the epithelial linings of the reproductive tract, growth of the external genitalia and breast growth (particularly the lactiferous ducts and fat deposition). Oestrogen promotes development of the female body configuration (narrow shoulders, broad hips), the female fat distribution pattern and the development of pubic, axillary and body hair. Another effect is on bone growth, and oestrogen is protective against osteoporosis. Oestrogen is the main hormone referred to although it also usually indicates oestradiol as well.

Progesterone is predominantly a sexual cycle hormone, as it stimulates the endometrial glands of the uterus during the menstrual cycle induces the production of thick sticky cervical mucus, decreases contractions of the uterine tubes and myometrium (essential for the prevention of miscarriage), stimulates breast growth (particularly glandular tissue) and has feedback effects on the hypothalamus and anterior pituitary to maintain control of the sexual cycles.

General principles

Adult males and females produce a set of specialised reproductive cells called gametes. Cells that give rise to gametes undergo a different type of cell division in which the amount of genetic material received by each daughter cell is halved. This type of division is called meiosis and it occurs solely in the gonads (see Figure 31-12). Thus gametes contain one half of the genetic material of somatic cells: one copy of each type of chromosome. The total number of chromosomes in all other body cells is 46, comprising 22 pairs of autosomes and 2 sex chromosomes: XX in females (homologous) and XY in males.

FIGURE 31-12 Meiosis.

Source: Based on Patton KT, Thibodeau GA. Anatomy & physiology. 7th edn. St Louis: Mosby; 2010.

In the gametes, the egg (ovum) and sperm cells each contain half of the genetic material of all other body (somatic) cells, as they have only 23 chromosomes instead of 23 pairs of chromosomes. When an ovum (from the mother) and sperm (from the father) combine to undergo fertilisation, a new cell with the full human genetic complement is produced (that is, with 23 pairs of chromosomes). This cell is called a zygote and it then undergoes many cycles of cell division to give rise to a new individual. At each cycle, genetic material is precisely copied for transmission to the new daughter cells. Products of any one cell division are genetically identical to each other, to their parent cell and to the original fertilised egg (zygote). This type of cell division is known as mitosis and it continues throughout life in growth, turnover and repair (see Chapter 5).

Meiosis

Meiosis can essentially be thought of as two rounds of mitosis in which the synthesis phase (namely, replication of the chromosomes) is skipped in the second round, resulting in a halving of the genetic material. The phases of the cell cycle are shown in Figure 31-12 and you can see that the second round of division (meiosis II) begins immediately after telophase I without the duplication of chromosomes so that the daughter cells each receive only half the chromosome number. In males this meiotic event is called spermatogenesis and in females it is called oogenesis. Gamete formation in both males and females is controlled by the sex hormones. In both sexes the same set of hormones triggers the process and the end result is the production of sperm and testosterone in the male and the production of ova, oestrogen and progesterone in the female. In addition, in females the hormones that trigger oogenesis are also responsible for the changes of uterine thickness during the menstrual cycle.

Spermatogenesis

Spermatogenesis is the formation of spermatids and it takes place in the seminiferous tubules of the testes under the influence of testosterone (see Figures 31-13 and 31-14). Spermatogonia (plural; singular = spermatogonium) are primitive germ cells that line the walls of the seminiferous tubules. They progress through various stages of development to become more developed spermatocytes; each spermatocyte then undergoes meiosis to give rise to four spermatids that reach the lumen of the seminiferous tubules. These four spermatids are immature sperm cells and are not free-swimming. They need to mature in a process called spermiogenesis to ultimately give rise to four mature free-swimming spermatozoa (commonly abbreviated to sperm). It takes about 2 months for spermatogonia to become mature sperm and a healthy adult male will produce several million mature sperm each day; these mature sperm are stored in the ductus deferens (including the ampulla) awaiting ejaculation.

FIGURE 31-13 Seminiferous tubule.

Section shows process of meiosis and sperm cell formation.

FIGURE 31-14 Hormonal control of spermatogenesis in a sexually mature male.

ABP = androgen-binding protein; LH= luteinising hormone; FSH = follicle-stimulating hormone; GnRH = gonadotropin-releasing hormone.

Mature sperm have named parts each with a specific function (see Figure 31-15): the head contains the genetic material, the midpiece contains mitochondria, which provide energy for sperm movement; and the tail provides locomotion.

FIGURE 31-15 Anatomy of a mature sperm cell.

The pathway of sperm from the testes to the tip of the penis is shown in Figure 31-16. The transport of sperm from the epididymis to the ductus deferens is due to peristalsis of smooth muscle in the epididymis and ductus deferens, rather than the sperm’s own motility. Mature sperm, together with other components of semen, are ejaculated by contraction of smooth muscle in the epididymis, ductus deferens, ejaculatory ducts, prostate and seminal vesicles (sympathetic stimulation). Each ejaculate is a volume of about 3 mL containing about 300 million sperm.

FIGURE 31-16 The pathway of sperm from the seminiferous tubules to the tip of the penis.

The complete process, from hormonal roles through to spermatogenesis, is shown in Figure 31-17.

FIGURE 31-17 Hormonal changes and sperm production.

In response to signals from the hypothalamus, follicle-stimulating hormone (FSH) and luteinising hormone (LH) are released, which in turn stimulate the testes to produce testosterone necessary for sexual maturation, as well as spermatogenesis. Following spermatogenesis, the spermatozoa travel through the ducts to exit via the penis. GnRH = gonadotropin-releasing hormone.

Oogenesis

The same hormones that control male sexual development control female sexual development and menstrual and ovarian cycling (see Figure 31-18). At birth, a female has all of the oocytes she will ever have — approximately 2 million. No new oocytes are subsequently produced, so a female is born with all her immature gametes already present — a situation that is in contrast to male gamete production. Most of these will degenerate so that at puberty she has 200,000–400,000 left. Over a woman’s reproductive lifetime of about 30–40 years, several hundred oocytes will complete differentiation and be released from the ovary (ovulation).

FIGURE 31-18 Hormonal control of female reproductive development.

The gametes are all present in each of the ovaries in the form of primordial follicles. The actual gamete is surrounded by a layer of cells called the granulosa cells in the cortex of the ovary. The oocyte and the granulosa cells together comprise the follicle. During a woman’s reproductive years, every month 1 follicle develops and is ovulated. In 1–2% of cycles more than 1 oocyte develops to this stage, potentially resulting in multiple births. The oocyte degenerates within a few days if it is not fertilised by sperm.

The ovarian cycle

The ovarian cycle is the series of changes in the ovarian follicles that include oocyte development and ovulation. The follicles respond to FSH by growing and maturating, such that 1 follicle bulges out from the ovary. The granulosa cells within this follicle proliferate and a zona pellucida (clear area or zone) forms between the oocyte in the middle and the surrounding granulosa cells, while a fluid-filled antrium appears. The granulosa cells increase in number and produce increasing amounts of oestrogen until the follicle bursts and the oocyte is released. Ovulation is stimulated by the surge in LH (see Figure 31-19). The oocyte is surrounded by a layer of granulosa cells (corona radiata) at ovulation and the remains of the follicle stay in the ovary and become the corpus luteum. Oestrogen and progesterone are secreted from the corpus luteum for about 10 days if a pregnancy does not occur.

FIGURE 31-19 Hormonal control of ovulation.

As the follicle matures, more and more oestrogen is produced from the larger number of granulosa cells surrounding the ovum. When the concentration of oestrogen in the blood reaches a certain level it has a positive feedback action on the hypothalamus (1) triggering a ‘burst’ in production of GnRH (2) and a consequent rapid increase in LH concentration. This rise in LH concentration is essential for the wall of the follicle to burst (3) and release the oocyte (4).

The menstrual cycle

The menstrual (or uterine) cycle lasts for approximately 28 days and is controlled by oestrogen and progesterone secreted by the ovaries (see Figure 31-20).^2,8,9 The ovarian and menstrual cycles occur in concert with each other as the developing follicle produces oestrogen, which stimulates the uterine endometrium to proliferate. This is necessary to prepare the uterus to receive a zygote (fertilised egg).

FIGURE 31-20 The menstrual cycle.

GnRH = gonadotropin-releasing hormone.

The menstrual cycle is divided into three stages:

The luteal stage is controlled by the corpus luteum and is under the influence of LH. The corpus luteum produces more progesterone than oestrogen, so this phase is dominated by progesterone. Progesterone causes the endometrial glands to fill with glycogen, the endometrial blood vessels to grow and it inhibits smooth muscle activity in the myometrium.

Changes in hormone levels are quite dramatic throughout the cycle (Figure 31-20) and can be measured to monitor the cycle and potential pregnancy. The complete process, from hormonal roles through to ovulation, is shown in Figure 31-21.

FIGURE 31-21 Hormonal changes and oocyte production.

In response to signals from the hypothalamus, FSH and LH are released, which in turn stimulate the ovaries to produce oestrogen and progesterone necessary for sexual maturation, as well as oogenesis. Following ovulation, the oocyte travels through the fallopian tube and exits the body via the vagina. The corpus luteum, which remains in the ovary, continues producing hormones for several days before degenerating.

Cervical mucus plays a role in disease prevention, contraception (to an extent) and the sexual act itself. In the menstrual and proliferative stages, which are under the influence of oestrogen, the mucus is abundant, clear and non-viscous. This is most pronounced at the time of ovulation and the freely flowing liquid allows sperm easy access from the vagina, through the uterus and to the fallopian tubes. During the luteal phase under the influence of progesterone the cervical mucus is thick and sticky. This can form a barrier to sperm movement and create a plug to seal off the uterus (and embryo if implantation occurs) from infection.

Ovarian and menstrual cycle timing

The ovarian and menstrual cycles occur in concert with each other, as the ovarian cycle drives the menstrual cycle. The developing primordial germ cells in the ovary begin releasing oestrogen in increasing amounts as their development proceeds. The granulosa cells, which produce oestrogen, increase in number throughout the development process and the endometrial layer of the uterus responds to the increasing levels of oestrogen in the blood. When a follicle is fully matured and ready to ovulate, it is producing a relatively high amount of oestrogen, which causes a positive feedback on the hypothalamus (see Figure 31-19). The hypothalamus responds by increasing the GnRH pulses and, in turn, the anterior pituitary produces large quantities of LH. This sharp rise in LH blood concentration is the trigger necessary for the oocyte to burst out of the ovary (ovulate). In assisted reproductive technology this increase in LH must be artificially created (by LH injections) to stimulate ovulation for egg collection (refer to Chapter 32).

After ovulation has occurred, oestrogen levels drop and the remains of the follicle in the ovary (the corpus luteum) produce a relatively higher concentration of progesterone. One important effect that progesterone has is to prevent muscular contraction of the myometrium (the middle layer of smooth muscle of the uterus). This is essential for the uterus to hold and carry a baby to full term; if the uterine myometrium contracts, then the zygote or more developed embryo could be expelled and the pregnancy fail.

The corpus luteum will persist in the ovary and secrete progesterone for about 10 days before it degenerates. If an egg is fertilised soon after ovulation (within hours) it will take the zygote about 5–6 days to reach the uterus and another day to become embedded in the endometrium (implantation) and produce sufficient hCG to establish the pregnancy. The hCG produced maintains the corpus luteum for a longer period until the placenta is established, at which time the placenta produces the progesterone necessary to maintain the quiet state of the myometrium. So the corpus luteum produces progesterone long enough for a possible pregnancy to establish and then degenerates into the corpus albicans (which does not produce progesterone). After 10 days, if no implantation is established, the levels of progesterone fall and the myometrium begins to contract to expel the excess endometrium, which is not needed. This is the menstrual flow. hCG will continue to be produced by an implanted embryo and this is the basis of a pregnancy test: hCG detection in the urine (or blood, for greater sensitivity) is positive 2 weeks after fertilisation.

The interplay of the ovarian and menstrual cycles may at first seem very complex, but when you focus on the reasons for the events you will see that this elegant system brings about maturation of an oocyte and prepares the uterus to receive the oocyte if it is fertilised. The hormonal interplay also seems complex, but essentially the pre-ovulation phase is dominated by oestrogen (preparing the uterus) while the post-ovulation phase is dominated by progesterone (holding the prepared uterus ready) in case fertilisation and implantation occur. If there is no fertilisation, both hormone levels are relatively low and the thickened uterus, which is not needed, is expelled.

The female sexual response

When not sexually aroused, the uterus lies in its normal anteverted position over the bladder, the vagina is relatively narrow and the labia minora are retracted (see Figure 31-22). In the excitement phase, sexual stimulation causes the uterus to stand more vertically and the inner end of the vagina dilates. The labia minora become vasocongested and may extend beyond the labia majora. A vaginal transudate moistens the vagina and vestibule. The plateau phase is a continuation of the excitement phase up to the moment of orgasm and resolution. In this phase the uterus is vertical and the cervix is withdrawn from the vagina. The clitoris is engorged and the labia are bright red and flushed with blood, and the lower third of the vagina constricts the penis. This phase can continue for a long or short time depending on the couple and the circumstances of the sexual activity. During the orgasm phase, the vagina contracts rhythmically and the uterus has peristaltic contractions. Finally, at resolution the uterus returns to its original anteverted position and the cervix protrudes into the top of the vagina; it may contact a pool of sperm as it does so, thereby allowing the sperm to gain access to the uterus and uterine tubes.

FIGURE 31-22 The female sexual response.

The male sexual response

The physiological response of the male can also be thought of in terms of four stages. Figure 31-23 details both the nerve impulses responsible and the actions they bring about in males.

FIGURE 31-23 The male sexual response.

With tactile (touch) stimulation of the genital region (the excitement phase), signals are transmitted via the internal pudendal nerve to the sacral level of the spinal column, which in turn sends efferent parasympathetic signals to the internal pudendal artery of the penis and the trabecular muscles of the erectile tissue. The trabecular muscles relax, allowing blood to flow into the erectile tissue, with the result that the penis becomes erect. A second consequence of this is the release of a small amount of fluid from the bulbourethral glands. During the plateau phase this heightened state of arousal, accompanied by widespread muscle myotonia, is maintained and built up further.

The male orgasm phase is divided into two parts: the orgasm-emission phase and the orgasm-expulsion phase. During the orgasm-emission phase sympathetic nerve signals arising in the L1–L2 level of the spinal cord induce peristaltic movement of the ductus deferens, which moves sperm from the epididymis to the ampulla and from there into the prostatic urethra. In addition, these nerve signals induce release of seminal and prostatic fluids from the seminal vesicles and prostate gland, respectively. The orgasm-expulsion phase is triggered by the presence of semen in the urethra, which is detected by sensory receptors and signalled to the central nervous system; nervous signals are integrated in the L1–S4 level of the spinal cord. Efferent sympathetic and efferent somatic signals arise from this integration of sensory input. The sympathetic signals cause further release of seminal and prostatic fluid and close the internal urethral sphincter, preventing the release of urine. The somatic signals innervate the bulbocavernosus and ischiocavernosus muscles, which contract rhythmically around the bulb and root of the penis. This rhythmical compression of the penis forces the semen out through the penile urethra (ejaculation).

Finally, during the resolution phase, efferent sympathetic signals arising from the L1–L2 level of the spinal cord cause the internal pudendal artery to contract, reducing blood flow to the erectile tissue. At the same time the trabecular muscles contract and the remaining blood is squeezed out of the penis as it returns to its flaccid state.

Fertilisation

The oocyte is ‘fertilisable’ for only a few hours after ovulation and entering the fallopian tube; however, sperm can live for 2–3 days after ejaculation into the vagina. The sperm meet the oocyte at fertilisation at the ovarian end of the fallopian tube, and the zygote implants in the uterus (see Figure 31-24). At ovulation, an oocyte completes its first meiotic division. As it is released from the ovary, it is surrounded by the zona pellucida and granulosa cells (corona radiata), both of which are a barrier to the sperm. The sperm undergo capacitation in the female tract, which ‘primes’ them for the meeting with the oocyte. It actually takes many sperm to bind to the zona pellucida to release the acrosome that gradually breaks down this barrier. When one sperm finally penetrates the zona pellucida and reaches the oocyte cell membrane, the membrane alters immediately to prevent any more sperm binding to it. This is termed the fast block and is essential to prevent the entry of more than one sperm ‘head’. The fertilised ovum now contains the oocyte nucleus (with 23 chromosomes) and the sperm nucleus (with 23 chromosomes) and these fuse together to form one cell nucleus containing the full complement of 46 chromosomes. At this stage the fertilised egg is called a zygote.

FIGURE 31-24 Fertilisation, gestation and parturition.

After sperm fertilise the oocyte within the fallopian tube, the zygote continues travelling until it reaches the uterus. Here, it implants and grows, while the placenta also develops, until parturition (labour). The fetus is expelled from the uterus through the cervix and vagina.

The zygote travels along the fallopian tube to the uterus (this takes 3–4 days) and as it does so, it undergoes a series of rapid mitotic divisions to become known as an embryo. The embryo reaches the uterine cavity as a tiny hollow ball of cells termed a blastocyst. After several more days, this implants in the uterine wall. At this stage the uterus is primed by progesterone and oestrogen (from the corpus luteum) such that the endometrium is thickened and rich in nutrients and blood flow. As discussed above, oestrogen and progesterone are vital for the maintenance of a pregnancy. When fertilisation occurs, the corpus luteum is stimulated by hCG secreted from the developing embryo to secrete oestrogen and progesterone for 2–3 months.

Implantation

Implantation is the process whereby the blastocyst adheres to and then sinks into the endometrium. Implantation is completed early in the second week (after fertilisation) and normally occurs in the upper part of the uterus; if the blastocyst implants lower, near to the cervix, there may be complications during birth (parturition). The outer cell layers of the blastocyst proliferate and ‘invade’ the endometrium. These cells produce enzymes that break down the endometrial cells, allowing the blastocyst to ‘sink’ into the endometrium until it becomes completely embedded. The blastocyst initially derives its nutrition from the endometrial cells that are broken down — the blastocyst literally ‘eats’ its way into the thickened endometrium and digests the released products to continue growing. As the blastocyst develops into an embryo, it eventually forms the placenta and obtains its nutrition from maternal blood, via the placenta.

The development and function of the placenta

The placenta is a complex organ that is derived partly from the developing embryo and partly from the maternal endometrium. The embryo-derived part is the chorion, and it is derived from the outer cells of the blastocyst. The mature placenta secretes hCG, oestrogen and progesterone. The oestrogen has negative feedback on the hypothalamus, which reduces the production of GnRH, thus reducing the production of FSH and LH. In this way, with very little FSH, there is no stimulation of the primordial germ follicles in the ovaries and the ovarian and menstrual cycles stop.

After implantation, the embryo is completely embedded in the endometrium. The continued invasion of the endometrium results in eroded spaces that become filled with maternal blood; these spaces are termed sinuses or lacunae (literally, empty spaces). Lacunae receive blood from the uterine arteries and drain into the uterine veins. Nutrients, gases and wastes thus diffuse to and from the embryo and maternal blood across a layer of blastocyst cells (now termed chorionic cells), but without direct connection between the two circulations — at this and all subsequent stages of development, maternal blood is separated from embryonic and fetal tissues, including embryonic blood, by a layer of chorion.

By the end of the second week after fertilisation, chorionic villi (projections of the chorion) have grown over the entire surface of the embedded embryo and the menstrual period is missed. During the third week, embryonic blood vessels begin to appear in the chorionic villi and soon establish connections with the blood vessels developing in the embryo itself via the umbilical blood vessels (in the umbilical cord). By the end of the third week, when the embryo’s heart begins to beat, blood begins to circulate from the embryo, through the umbilical arteries to capillaries in the chorionic villi.

Up to the eighth week of gestation, chorionic villi cover the entire surface of the embryonic sac. After this time, they begin to disappear, eventually remaining only where they form the fetal part of the mature placenta; the rest of the chorion becomes smooth as the villi disappear.

As the embryo and its sac grow, they begin to bulge from the uterine wall into the uterine cavity, and by the end of the tenth week the fetus completely obliterates the uterine cavity.

Formation of the placenta is completed by the end of the first trimester. The fetal component of the placenta is that part of the chorion that retained its villi — these branch as they continue to grow, providing a large surface area for diffusional exchange between fetal and maternal blood (see Figure 31-25). The maternal component of the placenta is the endometrium. Over the second and third trimesters, the placenta increases in size, in the degree of branching of the villi and in the volume of the intervillous space (i.e. the continuous space between the villi, filled with maternal blood). At term, the placenta weighs 500–600 g and is 18–20 cm in diameter.

FIGURE 31-25 Structural features of the placenta.

The close placement of the fetal blood supply and maternal blood supply permits diffusion of nutrients and other substances. It also forms a thin barrier to prevent diffusion of most harmful substances. No mixing of fetal and maternal blood occurs. A Diagram showing a cross-section of the placental structure. B Photograph of a normal, full-term placenta (fetal side) showing the branching of the placental blood vessels.

Source: Patton KT, Thibodeau GA. Anatomy & physiology. 7th edn. St Louis: Mosby; 2010.

Transfer (exchange) across the placenta

The welfare of the fetus depends above all else on adequate bathing of its chorionic villi by maternal blood. If maternal placental circulation is reduced, fetal hypoxia, growth retardation or fetal death may ensue.

Most blood-borne substances can cross the placental ‘barrier’ between the fetal and maternal bloodstreams. Many large molecules, such as immunoglobulin G (IgG), pass the barrier readily, but a few such as heparin and immunoglobulin M are excluded. Transfer of the following occurs readily by a variety of mechanisms:

water

oxygen

carbon dioxide

nutrients (e.g. glucose)

wastes (e.g. urea)

electrolytes

hormones

some antibodies such as IgG, which serve to confer passive immunity to a variety of pathogens on the newborn (but which can also harm the baby in the case of Rhesus incompatibility)

alcohol

most drugs, including those used for the management of labour

many infectious agents — bacterial, viral and protozoal.

From the perspective of the fetus, the placenta acts as a lung (gas exchange), gut, liver (nutrient absorption and metabolism) and kidney (excretion, water and electrolyte homeostasis) — the main limiting factor for the efficiency of all these functions being the maternal placental circulation.

The embryonic sac

From the time the embryonic (amniotic) sac begins to bulge into the uterine cavity until the time it completely occupies the cavity some 10 weeks after fertilisation, it has the following three layers:

The innermost layer of the sac is the amnion. Extensions of the amnion cover the fetal surface of the placenta and the umbilical cord. The amnion is continuous with the skin of the fetus at the umbilicus.

The middle layer is the chorion, termed the chorion laeve.

The outermost layer is the decidua capsularis.

These membranes constitute a barrier to infection of the fetus through the vagina and cervix. Within the sac, the fetus floats freely in amniotic fluid, anchored through the umbilical cord.

Note that all the cells derived from the fertilised egg, which includes the fetus itself, the fetal components of the placenta and the fetal membranes other than the decidua capsularis, are genetically identical to each other, but genetically different from the mother. Thus, if a biopsy sample of the chorionic villi is taken, we can look at the karyotype and genetic composition of the baby, enabling prenatal testing for genetic diseases.

The origin, composition and significance of amniotic fluid

Amniotic fluid is derived in part as a filtrate of maternal blood and in part from fetal urine. At term, about 1 L of amniotic fluid is present in the sac. The composition of amniotic fluid is similar to that of extracellular fluid, with the addition of:

hormones, enzymes and other fetal metabolites — many of these metabolites can be measured in a sample of amniotic fluid derived by amniocentesis to give a prognosis of the health of the baby (e.g. alpha (α)-fetoprotein as an indicator of neural tube disorder, bilirubin as an indicator of haemolysis)

cells shed from the fetus — some of these are viable and can be cultured for genetic and biochemical analysis.

The functions of the amniotic fluid are of significance in terms of the normal development of the fetus. The fluid mechanically cushions the fetus from external shock and the mother’s physical activity (walking, exercise, etc.), and it also helps maintain a constant temperature of 37°C. But perhaps one its most important functions involves allowing the external growth of the fetal limbs and the free movement essential for musculoskeletal development.

As the fetal central nervous system develops, reflex actions of swallowing and urination begin and the amniotic fluid circulates through the fetus as well as surrounding it. Circulation of the amniotic fluid involves exchange between 3 fluid compartments: the amniotic cavity, the fetus (gastrointestinal tract, blood, urinary tract) and the mother (blood). This circulation is essential to the normal development of the fetus, and the level of amniotic fluid (checked by ultrasound) can be diagnostic for the development of the fetus.

The mother’s adaptations to pregnancy

Changes in reproductive and other organs during gestation

The uterus and breasts increase in size in the pregnant female, but the degree of increase depends on a variety of factors. For example, a small baby will not expand the uterus quite as much as a larger baby.

Uterus

The uterus expands to contain the ever-growing fetus. At 12 weeks the height of the fundus of the uterus is at the level of the pubic symphysis, by 20 weeks it is at the level of the umbilicus and between 36 and 40 weeks it is at the level of the xiphoid process of the sternum. The uterus enlarges mainly by hypertrophy (enlargement) of existing cells. In late pregnancy, stretching leads to thinning of the uterine wall. Irregular contractions of the uterine muscle occur throughout pregnancy; these are known as Braxton-Hicks contractions.

Cervix

The cervix enlarges and softens, and the cervical canal is filled by a mucous plug (operculum). The operculum not only helps to hold the fetus and placenta within the uterus, but it also acts as a physical barrier to infection. At the onset of labour the operculum is expelled as a ‘show’ and is a clear indication of impending parturition.

Breasts

There is hyperproliferation of breast tissue, increasing the size of the breasts. This is physiologically normal growth, not to be confused with the rapid growth of breast tissue experienced in breast cancer (see Chapter 32). This growth may be accompanied by a feeling of fullness and tenderness. There will also be dilation of the veins, a deepening in colour of the nipples and areola, and the appearance of Montgomery follicles (enlarged sebaceous glands) in the areola.

Respiratory changes

In pregnancy, there is an increase in the depth of breathing (at rest), without an increase in the rate of breathing. This change leads to better clearance of carbon dioxide and improved oxygenation of maternal blood; this is clearly favourable for fetal gas exchange in the placenta. Progesterone acts on the respiratory centre in the medulla of the brain to increase its sensitivity to carbon dioxide: the result is an increase in tidal volume, thereby increasing the depth of breathing. Thus ventilation increases, without an increase in respiratory rate. This is aided by the relaxing effect of progesterone on the smooth muscle of the airways (reducing airway resistance).

Late in pregnancy, the growing uterus lifts up the diaphragm, leading to more effective ‘emptying’ of the lungs (lower lung residual volume), improving clearance of carbon dioxide from the maternal blood. In addition to increased concentrations of oxygen (and reduced concentrations of carbon dioxide), oxygen carriage by maternal blood is increased because the blood volume and the total number of erythrocytes (oxygen-carrying red blood cells) are increased in pregnancy.

Cardiovascular changes

The cardiovascular changes of pregnancy ensure increased blood flow to the placenta and uterus. The fundamental change is a large increase in blood volume. Plasma volume increases (by 45%) to a greater extent than does the number of erythrocytes (by 25%); thus there are apparent falls in values for red blood cells and haemoglobin (haemodilution), with an actual increase in oxygen-carrying capacity. Haemodilution is beneficial in that it results in better circulation of the blood. One of the effects of this improved circulation is more efficient loss of heat, from both the fetus and the mother, through the mother’s skin. The increased blood volume automatically causes increased cardiac output, as both stroke volume (blood ejected from each ventricle at each contraction) and heart rate increase. While increased blood flow to the placenta and the uterus is effected in this way, it is achieved without corresponding increases in blood pressure, as the relaxing effect of progesterone on the smooth muscle of the arterioles leads to reduced peripheral resistance. Thus blood pressure does not in general change with pregnancy and may in fact fall slightly due to the vasodilative effect of progesterone.

Fetal blood has a higher concentration of haemoglobin than does maternal blood, and fetal haemoglobin has a greater affinity for oxygen than does adult haemoglobin: these differences favour the transfer of oxygen from maternal blood to fetal blood in the placenta.

Water and electrolytes

In pregnancy there are increases in both body water content and urine output. The increase in body water comprises increases in plasma volume and increased extracellular fluid (i.e. widespread oedema). With the increased blood volume, there is increased renal blood flow and thus the glomerular filtration rate increases. This leads to increased urine output, even though aldosterone causes reabsorption of sodium and antidiuretic hormone causes reabsorption of water at markedly high levels during pregnancy. Increased urine output, of course, leads to a greater frequency of micturition. Another contributor to this effect is the increasing pressure of the growing uterus on the bladder. Increased thirst and drinking in pregnancy maintain the supply of water for these processes.

Nutrition and metabolism

In pregnancy food intake increases, as does anabolism, and there is some increase in the basal metabolic rate. In early pregnancy the mother may experience nausea, but appetite and thirst subsequently increase to high levels and these are maintained throughout pregnancy. The increase in food intake supplies the required nutrients for:

growth of the fetus

the increase in the mother’s basal metabolic rate

laying down of fat stores in the mother, to be drawn upon for lactation

laying down of fat and glycogen stores in the fetus, late in pregnancy — at the beginning of independent life glycogen stores are used as metabolic fuels and the fat as insulation.

There may also be some problems associated with nutrition in pregnancy:

If the increased requirements for special nutrients (e.g. calcium, iron, folic acid) are not met, these may be reflected in abnormal development, such as congenital defects of the spinal chord.

A reduction in gut motility, caused by the relaxing effect of progesterone on smooth muscle, can lead to constipation.

Stomach reflux and heartburn may be frequent as the lower oesophageal sphincter has reduced tone (an effect of progesterone) and the stomach is ‘crowded’ by the uterus.

Unusual food cravings and food aversions may develop — these are highly individual and do not occur in all women.

Blood glucose may rise, as insulin is antagonised by placental lactogen, and glycosuria may occur, due to increased blood glucose and an increased glomerular filtration rate (hence tubular reabsorption of filtered glucose may be incomplete).

Fetal development

The fetus’ organ systems are established by the end of the eighth week after fertilisation. In the following 30 weeks the fetus changes in proportion, as growth of the body ‘catches up’ to the relatively large head. In addition the fetus also grows in size — the increase in length is especially marked from 9 to 16 weeks and the increase in weight is especially marked in the last few weeks of pregnancy.

In the first half of pregnancy, all babies grow at the same rate, so measurement of size, by ultrasound, gives accurate dating of the pregnancy within this period. However, in the second half of pregnancy, individual differences in the sizes of different fetuses appear.

Some features of the fetal period:

9–12 weeks

• Body length (measured as ‘crown–rump’ length) increases faster than head size; thus, at the end of the period, the head is proportionally smaller than at its beginning.

• Ossification centres appear in many bones.

• External genitalia, which are not obviously differentiated at the beginning of the period, achieve their mature forms in the twelfth week.

• Urine begins to form, making its contribution to amniotic fluid.

17–20 weeks

• Overall growth slows, as final proportions are reached.

• Fetal movements are felt by the mother although they are evident on ultrasound well before this time.

• The skin is covered in vernix caseosa (a cheese-like fatty secretion that acts as a ‘barrier cream’ or moisturiser) and lanugo (fine hair).

• Brown fat is deposited around the neck and shoulders: these deposits are used for heat production in the newborn.

From 20 weeks onwards

• The fetus is considered (legally) viable: birth before this time is recorded as miscarriage or abortion, but after 20 weeks it is recorded as birth or stillbirth. Medically, the baby is considered potentially viable from 22 weeks gestation or from 400 g in weight.

21–25 weeks

• The fetus is lean, with little subcutaneous fat; skin is red and wrinkled.

• Surfactant begins to be secreted in the fetal lungs, but babies born at this age usually die because of respiratory immaturity.

26–29 weeks

• If born at this age, the baby moves energetically and cries; the lungs are not mature, but are capable of breathing air and the baby can survive with intensive care.

• The central nervous system has matured such that temperature homeostasis and rhythmic breathing are possible.

30–38 weeks

• Weight doubles; subcutaneous fat is laid down in quantity such that at birth fat constitutes 16% of body weight.

• The newborn also has extensive glycogen reserves; it will utilise both fat and glycogen reserves in the first few days after birth and lose weight.

The average pregnancy is 266 days (38 weeks) after conception or 40 weeks after the last menstrual period. Pregnancy may be prolonged up to 2 weeks; a baby born this late will be thin, with dry skin (‘postmature’).

The neonate

Surgical sterilisation

Sterilisation procedures involve surgical interruption of the reproductive ducts in either the male or the female. Overall, they should be considered as permanent, as they cannot be reliably reversed.

Vasectomy in males is the removal of part of the ductus deferens, which was previously known as the vas deferens — hence the term vasectomy refers to the severing of this duct. This procedure is performed under local anaesthetic as an outpatient. The ejaculate is free of sperm after 2–3 months; otherwise, sexual function remains unchanged. There may be adverse effects, such as leakage from the cut end of the ductus deferens, which may cause chronic inflammation and tenderness; and leakage of sperm into the blood, which may elicit an (auto-) immune response resulting in inflammation and a danger of destruction of the spermatocytes. Males are often worried about a vasectomy and fear that they will become impotent; this may stem from the mistaken belief that infertility results in impotence.

Tubal ligation in females is essentially interruption of the fallopian tubes by ligation (tying), electrocoagulation or surgical section (cutting). It is usually performed laparoscopically under general anaesthetic. This operation prevents sperm from reaching the oocyte and the oocyte from travelling down the fallopian tubes into the uterus. The adverse effects are associated with surgical trauma and anaesthetics.

The Essure method of tubal interruption is an alternative permanent sterilisation technique. A catheter-like instrument is guided through the cervix and uterus into the fallopian tubes. A microinsert (a soft, springlike coil made of polyester fibres and nickel titanium alloy) is placed in each fallopian tube. The microinsert has an inner coil and an outer coil and polyethylene fibres in a tightly wound configuration. Once in place, the outer coil expands to anchor the microinsert in the fallopian tube. Over a period of approximately 3 months, tissue grows into the coil to permanently block the fallopian tube and hence the oocyte can no longer meet the sperm. An X-ray is taken 3 months after the procedure to assess whether the blockage is complete. The first clinical trial of this technique in Australia showed the method to be safe and highly acceptable to women with 100% efficacy.¹¹ Although there is at least one report of failure,¹² this is a safer method than tubal ligation, as it does not involve laparoscopic surgery.

Barrier methods

Barrier methods of contraception are designed to prevent sperm from reaching the oocyte and are reliable only if properly used.

The condom needs to be put on the penis prior to physical contact between the penis and vagina; its reliability can be increased by concurrent use of a spermicide. The condom has the added advantage of providing protection for both partners against sexually transmitted infections.

The cervical cap fits around the cervix and is held there by suction. Similarly, the diaphragm has a sprung margin that allows it to block the top of the vagina as well as the cervix itself. Both the cap and diaphragm can be inserted a considerable time before intercourse and must be left in place for 6 hours after intercourse as the sperm will remain in the vagina for some time. The cap or diaphragm should be used only in combination with a spermicide, since they are unreliable on their own. Spermicides contain a chemical in either a cream or a foam that will kill sperm. The spermicide must be applied shortly before intercourse and does not provide reliable contraception on its own.

The disadvantages of the cap or diaphragm plus spermicide include: they need to be in place before sexual intercourse and so forethought is required; the cap and diaphragm must be carefully fitted to prevent sperm accessing the uterus; and spermicides can cause irritation of the vagina and cervix.

Hormonal methods

Oral contraceptive medications are referred to as the contraceptive pill (or ‘the pill’). Combined oral contraceptives contain both oestrogen and progesterone. These hormones suppress ovulation by feeding back on the hypothalamus and anterior pituitary to inhibit the secretion of FSH and LH. Thus follicles do not mature (lack of FSH) and oocytes are not released (lack of LH). The hormones in the combined pill thus mimic the actions of the corpus luteum in the luteal phase of a normal cycle or of the placenta in pregnancy. Typically, the pill is taken for 21 days, during which FSH and LH are suppressed and follicle development does not occur; however, the endometrium develops and is maintained by the steroids in the pill. For the next 7 days, no active pills are taken and the endometrium breaks down in a ‘simulation’ of normal menstruation.

Progesterone alone has a number of contraceptive effects: it inhibits ovulation in some (but not all) cycles; it inhibits the development of the endometrium under the influence of oestrogen (as seen in the proliferative phase of the menstrual cycle); and, most importantly, it causes thickening of the cervical mucus, making it impenetrable by sperm. The minipill contains progesterone only. The contraceptive action on cervical mucus lasts only 22–26 hours, so the pill must be taken at the same time each day (successive pills no more than 24 hours apart).

Other means of delivery of progesterone-only preparations are by implantation, such as Norplant capsules or Depot injection (e.g. Depo-Provera). Norplant implants may last for 5 years, while Depo-Provera lasts for 3 months.

The most significant side effects of oral contraceptives are an increased risk of blood clotting and hypertension in women who smoke or have a history of cardiovascular disease. The risk was higher in older forms of combined contraceptives, which incorporated much higher hormone concentrations than are currently used. Irregular bleeding is often associated with the use of progesterone-only preparations. The association of steroid contraceptives with cancers of the breast and reproductive system is controversial. Major life-threatening side effects are rare.

Contraceptives for men containing testosterone are in the experimental stage. Testosterone feeds back on the hypothalamus and anterior pituitary to inhibit the secretion of FSH and LH. Without FSH, sustentacular cells cannot carry out their crucial functions in supporting spermatogenesis; thus sperm concentrations in semen fall below those required for fertility. This method of contraception appears effective, with minor side effects of weight gain and acne; long-term effects on the prostate gland are under investigation.

Other methods of contraception

Coitus interruptus (withdrawal) requires the penis to be withdrawn prior to ejaculation. If practised diligently, there is some contraceptive effect. However, often the penis is either not withdrawn at all or only partially withdrawn, and this practice will almost inevitably lead to a high failure rate.

In the rhythm method, the couple monitors the female’s menstrual cycle over a few months to ensure a good record of the cycle. They then pick the point of the cycle where they are relatively certain that they will have little chance of fertilising an oocyte. This could be at least 6 days before ovulation (sperm can survive for up to 5 days inside the female body) or 2 days post-ovulation (when the oocyte is no longer capable of being fertilised). The problem with this method of contraception is that few couples really understand the female cycle well enough to successfully chart the progress. Furthermore, most women do not have an absolutely regular cycle and, since timing is crucial, the failure rate is high.

The intrauterine device (IUD) acts as foreign body in the uterus to produce a low-grade, chronic inflammatory response. In this state, the uterus inhibits sperm transport and prevents successful implantation of a fertilised egg. Modern IUDs are now made of plastic rather than copper. Adverse effects of IUDs include cramping and bleeding and increased risk of infection. If pregnancy occurs, there is an increased risk that it may be ectopic.

The ‘morning after’ pill interferes with transport of the fertilised egg and with implantation. A combined pill is given in two doses, 12 hours apart.

Mifepristone (also known as RU486) is a progesterone antagonist that blocks progesterone receptors in the uterus. This progesterone-blocking action in the endometrium could prevent implantation; however, the more significant use of this drug is to produce early abortion. Administration of the drug within 2 months of conception causes erosion of the endometrium and increased contraction of the myometrium. The administration of RU486 is followed after 48 hours by administration of prostaglandin, to complete the process of expulsion of the embryo.

The failure of contraception

Failure rates for contraception are shown in Table 31-3. Several of the techniques in Table 31-3 are quite reliable, with sterilisation procedures being the most successful. However, sterilisation procedures are often avoided due to the difficulty in reversing them at a later stage. Oral contraceptive pills and implants based on hormones are widely used, as they are effective and can be ceased relatively easily if conception is desired. The only completely reliable method of preventing conception is abstinence (avoiding sexual intercourse). If no method is used at all, the failure rate is 80–90% in women under the age 35 and 40–50% in women over the age of 35.

Table 31-3 FAILURE RATES FOR CONTRACEPTION (NUMBER OF PREGNANCIES PER 100 WOMEN PER YEAR)