The maximum diameter of the pelvis through which the infant’s head can pass differs for all three planes. Initially the largest diameter is in the transverse plane (pelvic brim), but the anteroposterior diameter becomes the largest at the pelvic outlet, particularly in females who possess a classical gynaecoid pelvis where the angle of the subpubic arch is equal to or greater than 90 degrees. Measurements of the diameter of the pelvis at the brim, cavity and outlet are presented in Table 20.1.

Table 20.1 Pelvic measurements

The shape of the pelvis can vary in individuals. While the gynaecoid is most common in women, three other types have been described: the android, anthropoid and platypelloid pelvis. These are illustrated in Figure 20.7.

• The android pelvis has male type features. It is characterised by a small inlet that is somewhat heart-shaped. The side walls converge, causing the pelvis to narrow as the fetus descends. The ischial spines are prominent and the angle of the subpubic arch is less than 90 degrees. This type of pelvis is least suited to childbearing.

• In the anthropoid pelvis the anteroposterior diameter is greater than the transverse diameter, but the pelvis is generally large all over. The side walls are parallel or flare outward, ischial spines are not prominent and the subpubic angle may be normal or wide. The pelvis is so large that delivery may occur without rotation.

• In the platypelloid pelvis there is a reduced anteroposterior diameter. The side walls diverge, the cavity is shallow and the ischial spines are blunt with a wide subpubic angle. The fetus may have difficulties entering the brim, but once through here there should be no further difficulty.

The shape of the pelvis does not necessarily predict whether a successful vaginal delivery is likely; the size of the fetal head in relation to the pelvis is more important (Stables & Rankin 2005).

Figure 20.7 Shapes of the pelvic brim

(from Coad & Dunstall 2005)

Childbirth is dependent on the ability of the baby to move, to ensure that the maximum diameter of the baby’s skull moves to align with the maximum diameter of the pelvis. These manoeuvres are called the mechanism of labour and are outlined in the later chapters on this topic.

Anatomy of the male reproductive system

The structures of the male reproductive system (Fig 20.8) include the testes, penis, accessory ducts (epididymis, vas deferens or ductus deferens, ejaculatory ducts and urethra) and the accessory glands (prostate, seminal vesicles and bulbourethral glands).

Figure 20.8 Schematic sagittal section of the male pelvic region

(based on Moore & Persaud 1998)

The paired testes each contain coiled seminiferous tubules, which are the site of sperm production. The sperm are moved from the seminiferous tubules to the coils of the epididymis by peristalsis. Secretions from the Sertoli cells, adjacent to the seminiferous tubules, build up pressure and contribute to the movement of sperm (Fig 20.9).

Figure 20.9 The testis in cross-section, illustrating the seminiferous tubules and interstitial cells of Leydig

(based on Bray et al 1994)

In the epididymis, sperm mature and become motile after approximately 14–21 days. During ejaculation, peristaltic contractions move spermatozoa from the epididymis to the vas deferens, through the ejaculatory duct and into the urethra. The urethra runs from the urinary bladder to the outside of the body, with part of the urethra (spongy urethra) running through the penis. The urethra has the dual role of transporting urine and sperm to exit the body.

During sexual excitement, the three columns of erectile tissue surrounding the urethra become engorged with blood, resulting in erection. This enables the penis to enter the vagina during sexual intercourse. Further stimulation leads to ejaculation of semen (sperm and secretions).

Accessory sex glands and semen

Semen is the alkaline fluid that protects, nourishes and transports sperm during ejaculation. Two to five millilitres is ejaculated during orgasm, containing 50–100 million sperm/mL. At least 20 million sperm/mL are necessary for fertility. However, 90% of the fluid is made up of secretions from the seminal vesicles, prostate gland and bulbourethral glands.

Seminal vesicles release alkaline secretions into the ejaculatory duct that contain several chemicals, including fibrinogen, fructose and prostaglandins. Fibrinogen helps to coagulate semen just after ejaculation, and this contributes to retention of semen in the region of the uterine cervix until the sperm become motile. Fructose nourishes the sperm, and prostaglandins aid fertilisation by making the cervical mucus more receptive. Prostaglandins also stimulate uterine contractions, which suck semen into the uterus and fallopian tubes, enabling them to reach the ampulla as soon as five minutes after ejaculation, or up to six hours later. These secretions also dilute epididymal inhibitory factor, which is thought to suppress the motility of spermatozoa.

The prostate gland produces an acidic, milky fluid containing citric acid and clotting enzymes that aid coagulation, and this is emptied into the urethra. Bulbourethral (Cowper’s) glands produce alkaline fluid that neutralises the acidic urethra, along with mucus that lubricates the urethra and protects spermatozoa. Secretions travel through the ducts into the spongy urethra.

Gametogenesis

Fertilisation involves the union of two gametes—an oocyte from the female and a sperm from the male. Gametes are highly specialised sex cells (Fig 20.10). Gametogenesis (formation of the sex cells) necessarily involves halving the number of chromosomes in each cell, by a type of cell division called meiosis, and by altering the shape of the cells. In females this process is termed oogenesis and in males it is spermatogenesis. When the two gametes join at fertilisation, the full number of chromosomes is restored.

Figure 20.10 Male and female gametes. (a) Parts of the human sperm (× 1250). The head, composed mostly of the nucleus, is partly covered by the acrosome, an organelle containing enzymes. The tail consists of three regions: middle piece, principal piece and end piece. (b) Sperm drawn to about the same scale as the oocyte. (c) Human secondary oocyte or ovum (× 200) surrounded by the zona pellucida and corona radiata

(based on Moore & Persaud 1998)

Oogenesis

Oogenesis is the process by which mature female sex cells are formed. Much of this process occurs in the fetus prior to birth. Oogonia in the fetus multiply by mitotic division and develop into primary oocytes (containing 46 chromosomes). The first meiotic division also begins before birth, but is arrested until after puberty. Completion of the first meiotic division is linked to the ovarian cycle. Each month, following puberty, several primary oocytes begin to develop but only one matures to complete the first meiotic division 36–48 hours before ovulation (Blackburn 2007). This division results in a large secondary oocyte containing most of the cytoplasm, and a smaller non-functional polar body that soon degenerates. Each has 23 chromosomes (22 autosomes and 1 sex chromosome). At ovulation the secondary oocyte begins the second meiotic division, but the division is only completed if fertilisation occurs. Once again, almost all the cytoplasm goes to one cell, the mature oocyte; a second polar body is non-functional and degenerates. The cellular divisions of oogenesis are outlined in Figure 20.11.

Figure 20.11 Arrest of oocyte meiosis

(based on Coad & Dunstall 2001)

The mature oocyte is a large, immotile cell, just visible to the naked eye. Up to two million primary oocytes are usually present in the ovaries of a newborn female infant, but many regress during childhood, leaving about 40,000 at puberty. During the reproductive life of a female, about 400 oocytes mature and are released during ovulation.

Spermatogenesis

Spermatogenesis describes the development of spermatogonia (primitive germ cells) into spermatozoa. This process begins at puberty and continues into old age. At puberty, the spermatogonia increase in number by mitotic division and grow and change to form primary spermatocytes (2n chromosomes). Each primary spermatocyte undergoes the first meiotic division to form two secondary spermatocytes (n chromosomes) and the second meiotic division to result in four spermatids (n chromosomes). Spermatids undergo a considerable change in shape, in a process termed spermiogenesis, to become mature spermatozoa (sperm).

The mature sperm has relatively little cytoplasm. It is divided into a head, midpiece and tail, and is motile. The head forms most of the bulk, contains the nucleus with the chromosomes and is covered anteriorly by the acrosome, a structure containing enzymes that facilitate penetration of the ovum at fertilisation. The midpiece is rich in energy-producing mitochondria, which fuel the lashing movements of the tail. Spermatogenesis takes about two months to complete and continues throughout the reproductive life of a male (Moore & Persaud 2008). The sperm move to the epididymis, where they are stored and become functionally mature.

A comparison of oogenesis and spermatogenesis is shown in Figure 20.12.

Figure 20.12 Comparison of oogenesis and spermatogenesis

(based on Moore & Persaud 1998)

Female reproductive cycles

Females undergo monthly reproductive cycles starting at puberty and continuing through the reproductive years. These cycles are controlled by the hypothalamic–pituitary–ovarian hormones and result in changes in the ovary that lead to release of one secondary oocyte per month, and in changes in the uterus in preparation for implantation of the fertilised ovum. If fertilisation does not occur, the cycle begins again under the influence of the hypothalamic–pituitary hormones. For simplicity, the reproductive cycle is described as an average 28-day cycle. There is considerable individual variation, but the cycle length of most women is between 21 and 35 days (Blackburn 2007).

Ovarian cycle

The ovarian cycle (Fig 20.13) includes three phases: the follicular or pre-ovulatory phase, the ovulatory phase or ovulation, and the post-ovulatory or luteal phase.

Figure 20.13 The ovarian cycle

(based on Coad & Dunstall 2001)

Follicular phase

In the follicular phase, the ovarian follicles, containing an oocyte, mature. Ovarian follicles are found in the cortex of the ovary and contain a variety of cells, including primary or secondary oocytes, granulosa cells and theca cells. Oocytes are surrounded by a thick membrane, the zona pelucida, and in mature follicles there is a large fluid-filled cavity, the antrum.

Follicles are present in several forms: primordial (the most undeveloped), primary, secondary and Graafian or vesicular follicles (the most mature).

• Primordial follicles contain primary oocytes and are the type of follicle present at birth. The first meiotic division has already begun in utero, but the process is arrested partway and does not continue again until puberty, when levels of gonadotrophin-releasing hormone (GnRH), luteinising hormone (LH) and follicle-stimulating hormone (FSH) increase.

• The primary follicle is formed in response to the increased level of the hormones mentioned above. The hormones signal the cells surrounding the oocyte to proliferate and form a layer of granulosa cells. These cells allow nutrients and signalling molecules to reach the oocyte.

• The secondary follicle is formed when a layer of connective tissue, called the theca folliculi, develops around the follicle and an antrum begins to develop with it. The thecal cells, together with the granulosa cells, produce steroid hormones (mainly oestrogens with small quantities of progesterone). The secondary follicle is also characterised by the zona pellucida, which surrounds the oocyte and is released along with the oocyte at ovulation.

• Graafian or vesicular follicles are the final and most mature form of ovarian follicle. This stage of follicular development is characterised by a large antrum and a follicular size of approximately 2.5 cm diameter. Due to its size it bulges from the ovary midway through the ovarian cycle.

The completion of meiosis I, in which a secondary oocyte and the first polar body are formed, occurs 36–48 hours before ovulation (Blackburn 2007). Meiosis II continues but is not completed until fertilisation occurs. The process of meiosis results in the genetic material in each oocyte being halved from 46 chromosomes (2n) to 23 chromosomes (n).

Ovulation

The ovulatory phase begins when oestrogen levels peak and ends when the vesicular follicle ruptures, releasing the secondary oocyte surrounded by the zona pellucida and corona radiata (the crown of granulosa cells around the zona pellucida). Ovulation is under hormonal control, as follows: LH interacts with LH receptors on the granulosa cells, increasing the production of oestrogen by the dominant follicle. A rise in oestrogen levels 12–24 hours before ovulation triggers the LH surge. The high level of LH stimulates production of prostaglandins (PGF_2α and PGE₂), and allows the primary oocyte to complete the first meiotic division and become a secondary oocyte. Simultaneously, levels of oestrogen drop and proteolytic enzymes are synthesised, which break down the thecal cells and assist rupture of the vesicular follicle (Blackburn 2007).

Luteal phase

This is the final stage of the ovarian cycle. The ruptured follicle remains in the ovary and the antrum begins to fill with clotted blood. The granulosa and some thecal cells form a structure called the corpus luteum. This is an endocrine structure capable of producing progesterone and smaller amounts of oestrogen. The purpose of the corpus luteum is to provide progesterone until the placenta is adequately formed. If fertilisation does not occur, the corpus luteum degenerates into a corpus albicans and is degraded through lysosomal activity.

Uterine cycle

The uterine cycle occurs in the same timeframe as the ovarian cycle and is similarly controlled by changes in hormonal levels (Fig 20.14). It consists of three stages: the menstrual phase (days 1–5), the proliferative phase (days 6–14) and the secretory phase (days 15–28). The following is a review of each stage.

Figure 20.14 Uterine cycle and hormone levels

(based on Coad & Dunstall 2001)

Menstrual phase

Menstruation is triggered by several factors. The first is a drop in levels of progesterone and oestradiol (one form of oestrogen). The second is a change in the ratio of prostaglandins and prostacyclins (hormone-like compounds) that cause vasoconstriction and increased coiling of the spiral arterioles, leading to a decrease in blood flow to the stratum functionalis of the uterus. The cells in the stratum functionalis become ischaemic and necrosed, and slough away from the stratum basalis. The straight arterioles dilate, contributing to menstrual flow (Blackburn 2007).

Proliferative phase

In the proliferative phase, the stratum functionalis of the endometrium begins to thicken as endometrial cells proliferate. Arterioles regenerate and endometrial glands develop. These changes occur in response to increased levels of oestradiol. The mucus produced by the cervix also responds to these hormones. Its consistency becomes less viscous and less stretchy, showing little or no ferning (spinnbarkeit test), thus becoming more receptive to sperm. Variation in the length of the proliferative phase accounts for most of the variation in uterine cycles (Blackburn 2007).

Secretory phase

The secretory phase occurs following ovulation, when levels of progesterone are high. The influence of progesterone results in further thickening of the stratum functionalis, an increase in the number of blood vessels and increased coiling and dilation of blood vessels. Finally, the endometrial glands begin secreting glycogen.

Hypothalamic–pituitary–ovarian (HPO) axis

The female reproductive system is regulated by a variety of hormones produced by the brain (the hypothalamus and the pituitary gland) and the ovaries (Fig 20.15).

Figure 20.15 Control of follicular development and oestrogen secretion

(based on Bray et al 1994)

Hypothalamus

The hypothalamus produces a peptide hormone called gonadotrophin-releasing hormone (GnRH) within its neurons. This hormone stimulates the release of several hormones from the anterior pituitary gland, specifically FSH and LH.

Pituitary gland

The anterior pituitary gland produces and secretes many hormones, including FSH, LH and prolactin. LH and FSH are glycoproteins that enhance each other’s actions (act synergistically) in regulating the ovarian cycle.

FSH, along with oestrogen produced by the ovaries, acts on granulosa cells of the follicles to stimulate growth and produce FSH receptors and LH receptors. The LH receptors combine with LH during the LH surge to inhibit the growth of granulosa cells and initiate production of progesterone from the follicle. The granulosa cells of a primordial follicle undergo limited growth without FSH. Secretion of FSH peaks mid-cycle at a lower level than the LH surge (Blackburn 2007).

LH acts on thecal cells, instigating the production of androgens that are converted to oestrogens by the granulosa cells. This increases the oestrogen level and inhibits the development of other follicles by inhibiting FSH (negative feedback). At the same time, one follicle becomes dominant and secretes high levels of oestradiol, allowing granulosa cell development in that follicle. As levels of oestradiol increase, the release of GnRH is triggered by positive feedback, allowing increased levels of LH and FSH to complete the maturation of follicles, and an LH surge triggers ovulation within 12–24 hours.

Following ovulation, increasing levels of oestrogen and progesterone exert a powerful negative feedback effect, inhibiting the release of GnRH and subsequently LH and FSH. This negative feedback prevents further maturation of follicles—important if the oocyte released at ovulation was successfully fertilised. However, in most cycles, fertilisation does not occur and the corpus luteum degenerates into the corpus albicans, resulting in a decreased level of progesterone. The low progesterone levels cease to inhibit GnRH, which begins to rise, followed by an increase in LH and FSH and the beginning of the follicular phase.

Prolactin is a protein hormone that stimulates milk production. Levels of prolactin rise during pregnancy, but human placental lactogen (hPL) and progesterone prevent the binding of prolactin to receptors in the breast. After delivery, prolactin stimulates milk production.

Research activity

A review publication in the journal Drug Safety by Al-Shawaf et al (2005) suggests that as many as 15% of couples may experience problems with fertility and that pharmacological agents are now routinely used with the aim of retrieving multiple oocytes to increase the chance of pregnancy. They describe the side-effects associated with fertility drugs as changes to the ovarian cycle, ovarian hyperstimulation syndrome and congenital malformations, although they suggest this may relate to the high-risk populations studied rather than the drugs themselves. High-order multiple pregnancies are also identified as being commonly associated with the use of fertility drugs—due to multiple ovulations or more than one embryo replacement. Gonadotrophin-releasing hormone (GnRH) agonists are widely used in assisted reproduction, and while there is considerable research into the possible link of GnRH with increasing risk of ovarian cancer and possibly breast cancer, these authors suggest that this has not been substantiated.

1. Identify the physiological mechanism that explains the way in which GnRH agonists can assist fertility.

2. Suggest why fertility drugs may be associated with the side-effects outlined above.

Ovaries

The ovaries produce the oestrogens (oestradiol, oestrone and oestriol), progesterone and inhibin.

Oestrogens are produced in the ovaries by granulosa cells within the follicles and the corpus luteum. The most abundant oestrogen during a woman’s reproductive years is oestradiol, which is responsible for most of the effects of oestrogen in the female reproductive system. However, during pregnancy, oestriol becomes the main oestrogen secreted (Blackburn 2007). The stimulus for oestrogen release is primarily FSH and, to a lesser extent, LH. Oestrogens are responsible for various functions, including:

• development and maintenance of the female reproductive structures such as the endometrial lining of the uterus, and secondary sexual characteristics such as fat content of the breasts, abdomen, mons pubis and hips, voice pitch, broadness of the pelvis, distribution of underarm and pubic hair, and the development of breasts

• fluid and electrolyte balance—by influencing the action of aldosterone, sodium reabsorption in the renal tubules is stimulated and diuresis is reduced

• increasing the rate at which amino acids enter cells, thereby altering protein metabolism, allowing cells to grow and multiply. This action is supported by the influence of growth hormone.

• regulation of oxytocin and adrenergic receptors (Henderson & Macdonald 2004)

• stimulation of uterine tube contractility to assist sperm motility and to retain the ovum (Blackburn 2007).

Progesterone is produced in the ovaries by granulosa cells, primarily of the corpus luteum. Therefore progesterone levels peak in the post-ovulatory phase when the corpus luteum is active, and fall if pregnancy does not occur and the corpus luteum degenerates. LH is the stimulus for progesterone release. Progesterone has various functions, including:

• preparation of the endometrium of the uterus to receive a fertilised ovum

• prevention of sperm entry into the uterus by promoting changes in the cervical mucus

• increasing basal body temperature by influencing the thermostat located in the hypothalamus

• relaxation of the muscle of the uterine tubes during the luteal phase to assist passage of the fertilised ovum to the uterus (Blackburn 2007).

Inhibin is produced in the ovaries by granulosa cells of the follicles and corpus luteum. It exerts negative feedback controls on FSH release during the growth of the dominant follicle and the corpus luteum.

Clinical points

1. Body temperature rises after ovulation, in response to progesterone, and is used in natural family planning to indicate the fertile phases of the reproductive cycle.

2. Hormonal contraceptives contain levels of oestrogen and/or progesterone that cause feedback control on the HPO axis to prevent follicle development and ovulation. Some contraceptives use the cervical mucus-changing properties of progesterone (e.g. the mini-pill).

Summary: homeostatic control of the reproductive cycle

While the follicular phase of the cycle is characterised by the positive feedback of oestrogen prompting an LH surge, the luteal phase is characterised by negative feedback. GnRH, LH and FSH production is controlled by negative feedback mechanisms linked to the ovarian hormones in the HPO axis (oestrogens, progesterone and inhibin). If the secondary oocyte is not fertilised, the ovum dies in 24 hours and the corpus luteum deteriorates. The levels of oestrogens and progesterone therefore drop, triggering the production of GnRH, LH and FSH, which begins the reproductive cycle (ovarian and uterine cycles) again. If fertilisation and implantation occur (pregnancy), levels of oestrogen and progesterone remain elevated because the blastocyst secretes the hormone human chorionic gonadotrophin (hCG) that maintains the corpus luteum and hormone production. The placenta takes over producing oestradiol and progesterone by 6–10 weeks gestation.

Research activity

Hormone replacement therapy (HRT) has previously been suggested to reduce the risk of cardiovascular disease. A study published in the Journal of the American Medical Association in 2002 in fact identified that HRT increased the risk of cardiovascular disease in healthy postmenopausal women. The study was halted early because it was decided that these results presented an unacceptable risk for the participating women (Rossouw et al 2002). HRT has also been used to treat the symptoms of menopause.

1. Explain why HRT may reduce these symptoms.

2. What is the concern about the use of HRT?

Hypothalamic–pituitary–testicular control in the male

Hypothalamic–pituitary–testicular (HPT) control in the male is not cyclical, like HPO control in the female. The HPT axis regulates physiological changes in the testes from puberty onward. GnRH is secreted by the hypothalamus every 70–90 minutes, which triggers the anterior pituitary to secrete LH and FSH.

LH directly stimulates both the production of testosterone from cholesterol, and the process of spermatogenesis, while FSH primarily facilitates spermatogenesis.

Testosterone is produced by the Leydig (interstitial) cells in the seminiferous tubules (Fig 20.9) and diffuses across the basal membrane to directly influence the spermatogonia and Sertoli cells. Testosterone levels are maintained by negative feedback to the hypothalamus and anterior pituitary, via the HPT axis.

Summary points

• The structures of the female and male reproductive systems are designed to produce and transport gametes: ova and sperm.

• Gametogenesis involves cell divisions that halve the chromosome number: oogenesis produces ova in the ovaries, and spermatogenesis produces sperm in the testes.

• Following puberty, a single oocyte is released from the ovary each month under the control of the hormones of the HPO axis.

• Ovarian hormones stimulate monthly vascular and glandular development of the uterus in preparation for pregnancy.

• Hormones of the HPT axis stimulate sperm production from puberty onwards.

• Sperm are produced in the seminiferous tubules and stored in the epididymis until ejaculation.

• Semen released at ejaculation includes about 300 million sperm and 2–5 mL of secretions from the accessory glands to aid nourishment and support of the sperm.

EMBRYOLOGY

Embryology is described as the study of ‘the origin and development of a human being from a zygote to the birth’. (Moore & Persaud 2008, p 2). Moore and Persaud (2008) emphasise that development is a continuum that starts at fertilisation, includes birth—a dramatic event resulting in a change in environment—and continues after birth, with development of teeth, bones, reproductive structures and so on. The process finishes by about the age of 25 years.

This section is limited to antenatal development, which begins with conception. Conception refers to fertilisation that results in pregnancy (Blackburn 2007). The probability of a viable conception has been calculated at only 30% per menstrual cycle (Blackburn 2007), with spontaneous abortions resulting from a range of abnormalities. The processes needed to produce a viable oocyte and a viable sperm have been described earlier in this chapter. This section examines fertilisation and the factors that contribute to successful fertilisation, implantation, development of the embryo and fetus, and development of the placenta.