About 1 million immature ova are present in each ovary at birth, but only about 200 per ovary mature to be released at ovulation. A fertilized ovum develops into an embryo.
About 1 million immature ova are present in each ovary at birth, but only about 200 per ovary mature to be released at ovulation. A fertilized ovum develops into an embryo.
Menstruation depends upon a functioning ovary (see OVARIES) and this upon a healthy PITUITARY GLAND. The regular rhythm may depend upon a centre in the HYPOTHALAMUS, which is in close connection with the pituitary. After menstruation, the denuded uterine ENDOMETRIUM is regenerated under the in?uence of the follicular hormone, oestradiol. The epithelium of the endometrium proliferates, and about a fortnight after the beginning of menstruation great development of the endometrial glands takes place under the in?uence of progesterone, the hormone secreted by the CORPUS LUTEUM. These changes are made for the reception of the fertilised OVUM. In the absence of fertilisation the uterine endometrium breaks down in the subsequent menstrual discharge.
Disorders of menstruation In most healthy women, menstruation proceeds regularly for 30 years or more, with the exceptions connected with childbirth. In many women, however, menstruation may be absent, excessive or painful. The term amenorrhoea is applied to the condition of absent menstruation; the terms menorrhagia and metrorrhagia describe excessive menstrual loss – the former if the excess occurs at the regular periods, and the latter if it is irregular. Dysmenorrhoea is the name given to painful menstruation. AMENORRHOEA If menstruation has never occurred, the amenorrhoea is termed primary; if it ceases after having once become established it is known as secondary amenorrhoea. The only value of these terms is that some patients with either chromosomal abnormalities (see CHROMOSOMES) or malformations of the genital tract fall into the primary category. Otherwise, the age of onset of symptoms is more important.
The causes of amenorrhoea are numerous and treatment requires dealing with the primary cause. The commonest cause is pregnancy; psychological stress or eating disorders can cause amenorrhoea, as can poor nutrition or loss of weight by dieting, and any serious underlying disease such as TUBERCULOSIS or MALARIA. The excess secretion of PROLACTIN, whether this is the result of a micro-adenoma of the pituitary gland or whether it is drug induced, will cause amenorrhoea and possibly GALACTORRHOEA as well. Malfunction of the pituitary gland will result in a failure to produce the gonadotrophic hormones (see GONADOTROPHINS) with consequent amenorrhoea. Excessive production of cortisol, as in CUSHING’S SYNDROME, or of androgens (see ANDROGEN) – as in the adreno-genital syndrome or the polycystic ovary syndrome – will result in amenorrhoea. Amenorrhoea occasionally follows use of the oral contraceptive pill and may be associated with both hypothyroidism (see under THYROID GLAND, DISEASES OF) and OBESITY.
Patients should be reassured that amenorrhoea can often be successfully treated and does not necessarily affect their ability to have normal sexual relations and to conceive. When weight loss is the cause of amenorrhoea, restoration of body weight alone can result in spontaneous menstruation (see also EATING DISORDERS – Anorexia nervosa). Patients with raised concentration of serum gonadotrophin hormones have primary ovarian failure, and this is not amenable to treatment. Cyclical oestrogen/progestogen therapy will usually establish withdrawal bleeding. If the amenorrhoea is due to mild pituitary failure, menstruation may return after treatment with clomiphene, a nonsteroidal agent which competes for oestrogen receptors in the hypothalamus. The patients who are most likely to respond to clomiphene are those who have some evidence of endogenous oestrogen and gonadotrophin production. IRREGULAR MENSTRUATION This is a change from the normal monthly cycle of menstruation, the duration of bleeding or the amount of blood lost (see menorrhagia, below). Such changes may be the result of an upset in the balance of oestrogen and progesterone hormones which between them control the cycle. Cycles may be irregular after the MENARCHE and before the menopause. Unsuspected pregnancy may manifest itself as an ‘irregularity’, as can an early miscarriage (see ABORTION). Disorders of the uterus, ovaries or organs in the pelvic cavity can also cause irregular menstruation. Women with the condition should seek medical advice. MENORRHAGIA Abnormal bleeding from the uterus during menstruation. A woman loses on average about 60 ml of blood during her period; in menorrhagia this can rise to 100 ml. Some women have this problem occasionally, some quite frequently and others never. One cause is an imbalance of progesterone and oestrogen hormones which between them control menstruation: the result is an abnormal increase in the lining (endometrium) of the uterus, which increases the amount of ‘bleeding’ tissue. Other causes include ?broids, polyps, pelvic infection or an intrauterine contraceptive device (IUD – see under CONTRACEPTION). Sometimes no physical reason for menorrhagia can be identi?ed.
Treatment of the disorder will depend on how severe the loss of blood is (some women will become anaemic – see ANAEMIA – and require iron-replacement therapy); the woman’s age; the cause of heavy bleeding; and whether or not she wants children. An increase in menstrual bleeding may occur in the months before the menopause, in which case time may produce a cure. Medical or surgical treatments are available. Non-steroidal anti-in?ammatory drugs may help, as may tranexamic acid, which prevents the breakdown of blood clots in the circulation (FIBRINOLYSIS): this drug can be helpful if an IUD is causing bleeding. Hormones such as dydrogesterone (by mouth) may cure the condition, as may an IUD that releases small quantities of a PROGESTOGEN into the lining of the womb.
Traditionally, surgical intervention was either dilatation and curettage of the womb lining (D & C) or removal of the whole uterus (HYSTERECTOMY). Most surgery is now done using minimally invasive techniques. These do not require the abdomen to be cut open, as an ENDOSCOPE is passed via the vagina into the uterus. Using DIATHERMY or a laser, the surgeon then removes the whole lining of the womb. DYSMENORRHOEA This varies from discomfort to serious pain, and sometimes includes vomiting and general malaise. Anaemia is sometimes a cause of painful menstruation as well as of stoppage of this function.
In?ammation of the uterus, ovaries or FALLOPIAN TUBES is a common cause of dysmenorrhoea which comes on for the ?rst time late in life, especially when the trouble follows the birth of a child. In this case the pain exists more or less at all times, but is aggravated at the periods. Treatment with analgesics and remedying the underlying cause is called for.
Many cases of dysmenorrhoea appear with the beginning of menstrual life, and accompany every period. It has been estimated that 5–10 per cent of girls in their late teens or early 20s are severely incapacitated by dysmenorrhoea for several hours each month. Various causes have been suggested for the pain, one being an excessive production of PROSTAGLANDINS. There may be a psychological factor in some sufferers and, whether this is the result of inadequate sex instruction, fear, family, school or work problems, it is important to o?er advice and support, which in itself may resolve the dysmenorrhoea. Symptomatic relief is of value.... menstruation
Once ejaculated during intercourse the spermatozoon travels at a rate of 1·5–3 millimetres a minute and remains mobile for several days after insemination, but quickly loses its potency for fertilisation. As it takes only about 70 minutes to reach the ovarian end of the uterine tube, it is assumed that there must be factors other than its own mobility, such as contraction of the muscle of the womb and uterine tube, that speed it on its way.... spermatozoon
Methods of contraception include total or periodic abstinence from sexual intercourse (see contraception, natural methods of); barrier methods (see contraception, barrier methods of); coitus.
The male condom is one of the most widely used barrier contraceptives. Female condoms (see condom, female) are similar to, but larger than, male condoms. Other female barrier methods include the diaphragm (see diaphragm, contraceptive), a hemispherical dome of thin rubber with a metal spring in the rim to hold it in place against the vaginal wall, blocking the entrance to the cervix. It is used with a spermicide. A cervical cap (see cap, cervical) is an alternative to the diaphragm. The contraceptive sponge, which is a disposable, circular, polyurethane foam sponge impregnated with spermicide, is inserted high in the vagina and left in place for at least 6 hours after intercourse.
Spermicides, in the form of aerosol foams, creams, gels, and pessaries, are placed in the vagina as close as possible to the cervix shortly before intercourse.
Some spermicides should not be used with rubber barrier devices.
Mechanical and chemical means used together correctly can be highly effective in preventing conception.... contraception
Fertilization may also occur as a result of semen being artificially introduced into the cervix (see artificial insemination) or may take place in a laboratory (see in vitro fertilization).
fetal alcohol syndrome A rare condition consisting of a combination of congenital defects that result from the continuous consumption of excessive amounts of alcohol by the mother throughout pregnancy. The affected baby has diminished growth, delayed mental development, a small head, a small brain, and small eyes. He or she may have a cleft palate, a small jaw, heart defects, and joint abnormalities. As a newborn, the baby sucks poorly, sleeps badly, and is irritable as a result of alcohol withdrawal. Almost one-fifth of affected babies die during the first few weeks of life; and many who survive are, to some degree, mentally and physically handicapped.... fertilization
The woman is given a course of fertility drugs to stimulate release of eggs from the ovary. This is followed by ultrasound scanning to check the eggs, which are collected by laparoscopy immediately before ovulation. They are then mixed with sperm in the laboratory. Two, or sometimes more, fertilized eggs are replaced into the uterus. If they become safely implanted in the uterine wall, the pregnancy usually continues normally.
Only about 1 in 10 couples undergoing in vitro fertilization achieves pregnancy at the 1st attempt, and many attempts may be needed before a successful pregnancy is achieved. Modifications of the technique, such as gamete intrafallopian transfer (GIFT), are simpler and cheaper than the original method. in vivo Biological processes occurring within the body. (See also in vitro.)... in vitro fertilization
Every cell consists essentially of a cell-body of soft albuminous material called cytoplasm, in which lies a kernel or nucleus which seems to direct all the activities of the cell. Within the nucleus may be seen a minute body, the nucleolus; and there may or may not be a cell-envelope around all. (See also MITOCHONDRIA.) Each cell nucleus carries a set of identical CHROMOSOMES, the body’s genetic instructions.
Cells vary much in size, ranging in the human body from 0·0025 mm to about 0·025 mm.
All animals and plants consist at ?rst of a single cell (the egg-cell, or ovum), which begins to develop when fertilised by the sperm-cell derived from the opposite sex. Development begins by a division into two new cells, then into four, and so on till a large mass is formed. These cells – among them stem cells (see STEM CELL) which have the potential to develop into a variety of specialised cells – then arrange themselves into layers, and form various tubes, rods, and masses which represent in the embryo the organs of the fully developed animal. (See FETUS.)
When the individual organs have been laid down on a sca?olding of cells, these gradually change in shape and in chemical composition. The cells in the nervous system send out long processes to form the nerves; those in the muscles become long and striped in appearance; and those which form fat become ?lled with fat droplets which distend the cells. Further, they begin to produce, between one another, the substances which give the various tissues their special character. Thus, in the future bones, some cells deposit lime salts and others form cartilage, while in tendons they produce long white ?bres of a gelatinous substance. In some organs the cells change little: thus the liver consists of columns of large cells packed together, while many cells, like the white blood corpuscles, retain their primitive characters almost entire.
Thus cells are the active agents in forming the body, and they have a similar function in repairing its wear and tear. Tumours, and especially malignant tumours, have a highly cellular structure, the cells being of an embryonic type, or, at best, forming poor imitations of the tissues in which they grow (see TUMOUR).... cells
Adrenal glands These two glands, also known as suprarenal glands, lie immediately above the kidneys. The central or medullary portion of the glands forms the secretions known as ADRENALINE (or epinephrine) and NORADRENALINE. Adrenaline acts upon structures innervated by sympathetic nerves. Brie?y, the blood vessels of the skin and of the abdominal viscera (except the intestines) are constricted, and at the same time the arteries of the muscles and the coronary arteries are dilated; systolic blood pressure rises; blood sugar increases; the metabolic rate rises; muscle fatigue is diminished. The super?cial or cortical part of the glands produces steroid-based substances such as aldosterone, cortisone, hydrocortisone, and deoxycortone acetate, for the maintenance of life. It is the absence of these substances, due to atrophy or destruction of the suprarenal cortex, that is responsible for the condition known as ADDISON’S DISEASE. (See CORTICOSTEROIDS.)
Ovaries and testicles The ovary (see OVARIES) secretes at least two hormones – known, respectively, as oestradiol (follicular hormone) and progesterone (corpus luteum hormone). Oestradiol develops (under the stimulus of the anterior pituitary lobe – see PITUITARY GLAND below, and under separate entry) each time an ovum in the ovary becomes mature, and causes extensive proliferation of the ENDOMETRIUM lining the UTERUS, a stage ending with shedding of the ovum about 14 days before the onset of MENSTRUATION. The corpus luteum, which then forms, secretes both progesterone and oestradiol. Progesterone brings about great activity of the glands in the endometrium. The uterus is now ready to receive the ovum if it is fertilised. If fertilisation does not occur, the corpus luteum degenerates, the hormones cease acting, and menstruation takes place.
The hormone secreted by the testicles (see TESTICLE) is known as TESTOSTERONE. It is responsible for the growth of the male secondary sex characteristics.
Pancreas This gland is situated in the upper part of the abdomen and, in addition to the digestive enzymes, it produces INSULIN within specialised cells (islets of Langerhans). This controls carbohydrate metabolism; faulty or absent insulin production causes DIABETES MELLITUS.
Parathyroid glands These are four minute glands lying at the side of, or behind, the thyroid (see below). They have a certain e?ect in controlling the absorption of calcium salts by the bones and other tissues. When their secretion is defective, TETANY occurs.
Pituitary gland This gland is attached to the base of the brain and rests in a hollow on the base of the skull. It is the most important of all endocrine glands and consists of two embryologically and functionally distinct lobes.
The function of the anterior lobe depends on the secretion by the HYPOTHALAMUS of certain ‘neuro-hormones’ which control the secretion of the pituitary trophic hormones. The hypothalamic centres involved in the control of speci?c pituitary hormones appear to be anatomically separate. Through the pituitary trophic hormones the activity of the thyroid, adrenal cortex and the sex glands is controlled. The anterior pituitary and the target glands are linked through a feedback control cycle. The liberation of trophic hormones is inhibited by a rising concentration of the circulating hormone of the target gland, and stimulated by a fall in its concentration. Six trophic (polypeptide) hormones are formed by the anterior pituitary. Growth hormone (GH) and prolactin are simple proteins formed in the acidophil cells. Follicle-stimulating hormone (FSH), luteinising hormone (LH) and thyroid-stimulating hormone (TSH) are glycoproteins formed in the basophil cells. Adrenocorticotrophic hormone (ACTH), although a polypeptide, is derived from basophil cells.
The posterior pituitary lobe, or neurohypophysis, is closely connected with the hypothalamus by the hypothalamic-hypophyseal tracts. It is concerned with the production or storage of OXYTOCIN and vasopressin (the antidiuretic hormone).
PITUITARY HORMONES Growth hormone, gonadotrophic hormone, adrenocorticotrophic hormone and thyrotrophic hormones can be assayed in blood or urine by radio-immunoassay techniques. Growth hormone extracted from human pituitary glands obtained at autopsy was available for clinical use until 1985, when it was withdrawn as it is believed to carry the virus responsible for CREUTZFELDT-JAKOB DISEASE (COD). However, growth hormone produced by DNA recombinant techniques is now available as somatropin. Synthetic growth hormone is used to treat de?ciency of the natural hormone in children and adults, TURNER’S SYNDROME and chronic renal insu?ciency in children.
Human pituitary gonadotrophins are readily obtained from post-menopausal urine. Commercial extracts from this source are available and are e?ective for treatment of infertility due to gonadotrophin insu?ciency.
The adrenocorticotrophic hormone is extracted from animal pituitary glands and has been available therapeutically for many years. It is used as a test of adrenal function, and, under certain circumstances, in conditions for which corticosteroid therapy is indicated (see CORTICOSTEROIDS). The pharmacologically active polypeptide of ACTH has been synthesised and is called tetracosactrin. Thyrotrophic hormone is also available but it has no therapeutic application.
HYPOTHALAMIC RELEASING HORMONES which affect the release of each of the six anterior pituitary hormones have been identi?ed. Their blood levels are only one-thousandth of those of the pituitary trophic hormones. The release of thyrotrophin, adrenocorticotrophin, growth hormone, follicle-stimulating hormone and luteinising hormone is stimulated, while release of prolactin is inhibited. The structure of the releasing hormones for TSH, FSH-LH, GH and, most recently, ACTH is known and they have all been synthesised. Thyrotrophin-releasing hormone (TRH) is used as a diagnostic test of thyroid function but it has no therapeutic application. FSH-LH-releasing hormone provides a useful diagnostic test of gonadotrophin reserve in patients with pituitary disease, and is now used in the treatment of infertility and AMENORRHOEA in patients with functional hypothalamic disturbance. As this is the most common variety of secondary amenorrhoea, the potential use is great. Most cases of congenital de?ciency of GH, FSH, LH and ACTH are due to defects in the hypothalamic production of releasing hormone and are not a primary pituitary defect, so that the therapeutic implication of this synthesised group of releasing hormones is considerable.
GALACTORRHOEA is frequently due to a microadenoma (see ADENOMA) of the pituitary. DOPAMINE is the prolactin-release inhibiting hormone. Its duration of action is short so its therapeutic value is limited. However, BROMOCRIPTINE is a dopamine agonist with a more prolonged action and is e?ective treatment for galactorrhoea.
Thyroid gland The functions of the thyroid gland are controlled by the pituitary gland (see above) and the hypothalamus, situated in the brain. The thyroid, situated in the front of the neck below the LARYNX, helps to regulate the body’s METABOLISM. It comprises two lobes each side of the TRACHEA joined by an isthmus. Two types of secretory cells in the gland – follicular cells (the majority) and parafollicular cells – secrete, respectively, the iodine-containing hormones THYROXINE (T4) and TRI-IODOTHYRONINE (T3), and the hormone CALCITONIN. T3 and T4 help control metabolism and calcitonin, in conjunction with parathyroid hormone (see above), regulates the body’s calcium balance. De?ciencies in thyroid function produce HYPOTHYROIDISM and, in children, retarded development. Excess thyroid activity causes thyrotoxicosis. (See THYROID GLAND, DISEASES OF.)... endocrine glands
The ?rst ‘test-tube baby’ – to use the popular, and widely used, term for such a child – was born by CAESAREAN SECTION in England on 25 July 1978. Many other children conceived in this manner have since been born, and, though only 10 per cent of women conceive at the ?rst attempt, the overall success rate is improving. Embryo transplantation and research are controversial procedures and in many countries, including the UK, are controlled by legislation. Embryo transfer and research using embryos are regulated by the Human Fertilisation & Embryology Authority (see ASSISTED CONCEPTION; APPENDIX 7: STATUTORY ORGANISATIONS).... embryo transfer
The embryo develops upon one side of the ovum, its ?rst appearance consisting of a groove, the edges of which grow up and join to form a tube, which in turn develops into the brain and spinal cord. At the same time, a part of the ovum beneath this is becoming pinched o? to form the body, and within this the endoderm forms a second tube, which in time is changed in shape and lengthened to form the digestive canal. From the gut there grows out very early a process called the allantois, which attaches itself to the wall of the uterus, developing into the PLACENTA (afterbirth), a structure well supplied with blood vessels which draws nourishment from the mother’s circulation via the wall of the womb.
The remainder of the ovum – which within two weeks of conception has increased to about 2 mm (1/12 inch) in size – splits into an outer and inner shell, from the outer of which are developed two covering membranes, the chorion and amnion; while the inner constitutes the yolk sac, attached by a pedicle to the developing gut of the embryo. From two weeks after conception onwards, the various organs and limbs appear and grow. The human embryo at this stage is almost indistinguishable in appearance from the embryo of other animals. After around the middle of the second month, it begins to show a distinctly human form and then is called the fetus. The property of ‘life’ is present from the very beginning, although the movements of the fetus are not usually felt by the mother until the ?fth month.
During the ?rst few days after conception the eye begins to be formed, beginning as a cup-shaped outgrowth from the mid-brain, its lens being formed as a thickening in the skin. It is very soon followed by the beginnings of the nose and ear, both of which arise as pits on the surface, which increase in complexity and are joined by nerves that grow outward from the brain. These three organs of sense have practically their ?nal appearance as early as the beginning of the second month.
The body closes in from behind forwards, the sides growing forwards from the spinal region. In the neck, the growth takes the form of ?ve arches, similar to those which bear gills in ?shes. From the ?rst of these the lower jaw is formed; from the second the hyoid bone, all the arches uniting, and the gaps between them closing up by the end of the second month. At this time the head and neck have assumed quite a human appearance.
The digestive canal begins as a simple tube running from end to end of the embryo, but it grows in length and becomes twisted in various directions to form the stomach and bowels. The lungs and the liver arise from this tube as two little buds, which quickly increase in size and complexity. The kidneys also appear very early, but go through several changes before their ?nal form is reached.
The genital organs appear late. The swellings, which form the ovary in the female and the testicle (or testis) in the male, are produced in the region of the loins, and gradually descend to their ?nal positions. The external genitals are similar in the two sexes till the end of the third month, and the sex is not clearly distinguishable till late in the fourth month.
The blood vessels appear in the ovum even before the embryo. The heart, originally double, forms as a dilatation upon the arteries which later produce the aorta. These two hearts later fuse into one.
The limbs appear at about the end of the third week, as buds which increase quickly in length and split at their ends into ?ve parts, for ?ngers or toes. The bones at ?rst are formed of cartilage, in which true bone begins to appear during the third month. The average period of human gestation is 266 days – or 280 days from the ?rst day of the last menstrual period. The average birth weight of an infant born of a healthy mother (in the UK) is 3,200 g (see table).
The following table gives the average size and weight of the fetus at di?erent periods:
(See also PREGNANCY AND LABOUR.)... fetus
Checking a hormone pro?le in the woman’s blood will help in the diagnosis of ovulatory disorders like polycystic ovaries, an early menopause, anorexia or other endocrine illnesses. Ovulation itself is best assessed by ultrasound scan at mid-cycle or by a blood hormone progesterone level in the second half of the cycle.
The FALLOPIAN TUBES may be damaged or blocked in 20–30 per cent of infertile women. This is usually caused by previous pelvic infection or ENDOMETRIOSIS, where menstrual blood is thought to ?ow backwards through the fallopian tubes into the pelvis and seed with cells from the lining of the uterus in the pelvis. This process often leads to scarring of the pelvic tissues; 5–10 per cent of infertility is associated with endometriosis.
To assess the Fallopian tubes adequately a procedure called LAPAROSCOPY is performed. An ENDOSCOPE is inserted through the umbilicus and at the same time a dye is pushed through the tubes to assess their patency. The procedure is performed under a general anaesthetic.
In a few cases the mucus around the cervix may be hostile to the partner’s sperm and therefore prevent fertilisation.
Defective production is responsible for up to a quarter of infertility. It may result from the failure of the testes (see TESTICLE) to descend in early life, from infections of the testes or previous surgery for testicular torsion. The semen is analysed to assess the numbers of sperm and their motility and to check for abnormal forms.
In a few cases the genetic make-up of one partner does not allow the couple ever to achieve a pregnancy naturally.
In about 25 per cent of couples no obvious cause can be found for their infertility.
Treatment Ovulation may be induced with drugs.
In some cases damaged Fallopian tubes may be repaired by tubal surgery. If the tubes are destroyed beyond repair a pregnancy may be achieved with in vitro fertilisation (IVF) – see under ASSISTED CONCEPTION.
Endometriosis may be treated either with drugs or laser therapy, and pregnancy rates after both forms of treatment are between 40–50 per cent, depending on the severity of the disease.
Few options exist for treating male-factor infertility. These are arti?cial insemination by husband or donor and more recently in vitro fertilisation. Drug treatment and surgical repair of VARICOCELE have disappointing results.
Following investigations, between 30 and 40 per cent of infertile couples will achieve a pregnancy usually within two years.
Some infertile men cannot repair any errors in the DNA in their sperm, and it has been found that the same DNA repair problem occurs in malignant cells of some patients with cancer. It is possible that these men’s infertility might be nature’s way of stopping the propagation of genetic defects. With the assisted reproduction technique called intracytoplasmic sperm injection, some men with defective sperm can fertilise an ovum. If a man with such DNA defects fathers a child via this technique, that child could be sterile and might be at increased risk of developing cancer. (See ARTIFICIAL INSEMINATION; ASSISTED CONCEPTION.)... infertility
Two types of sperm cells are produced: one contains 22 autosomes and a Y sex chromosome (see SEX CHROMOSOMES); the other, 22 autosomes and an X sex chromosome. All the ova, however, produced by normal meiosis have 22 autosomes and an X sex chromosome.
Two divisions of the NUCLEUS occur (see also CELLS) and only one division of the chromosomes, so that the number of chromosomes in the ova and sperms is half that of the somatic cells. Each chromosome pair divides so that the gametes receive only one member of each pair. The number of chromosomes is restored to full complement at fertilisation so that the zygote has a complete set, each chromosome from the nucleus of the sperm pairing up with its corresponding partner from the ovum.
The ?rst stage of meiosis involves the pairing of homologous chromosomes which join together and synapse lengthwise. The chromosomes then become doubled by splitting along their length and the chromatids so formed are held together by centromeres. As the homologous chromosomes – one of which has come from the mother, and the other from the father – are lying together, genetic interchange can take place between the chromatids and in this way new combinations of GENES arise. All four chromatids are closely interwoven and recombination may take place between any maternal or any paternal chromatids. This process is known as crossing over or recombination. After this period of interchange, homologous chromosomes move apart, one to each pole of the nucleus. The cell then divides and the nucleus of each new cell now contains 23 and not 46 chromosomes. The second meiotic division then occurs, the centromeres divide and the chromatids move apart to opposite poles of the nucleus so there are still 23 chromosomes in each of the daughter nuclei so formed. The cell divides again so that there are four gametes, each containing a half number (haploid) set of chromosomes. However, owing to the recombination or crossing over, the genetic material is not identical with either parent or with other spermatozoa.... meiosis
In recent years, however, the position has been altered by the introduction of the so-called fertility drugs, such as CLOMIPHENE, and human menopausal gonadotrophin which, through the medium of the PITUITARY GLAND, stimulate the production of ova (see OVUM). Their wide use in the treatment of INFERTILITY has resulted in an increase in the number of multiple births, a recognised hazard of giving too large a dose.
Twins may be binovular or uniovular. Binovular, or fraternal, twins are the result of the mother’s releasing two ova within a few days of each other and both being fertilised by separate spermatozoa (see SPERMATOZOON). They both develop separately in the mother’s womb and are no more alike than is usual with members of the same family. They are three times as common as uniovular, or identical, twins, who are developed from a single ovum fertilised by a single spermatozoon, but which has split early in development. This is why they are usually so remarkably alike in looks and mental characteristics. Unlike binovular twins, who may be of the same or di?erent sex, they are always of the same sex.
So far as fraternal, or binovular, twins are concerned, multiple pregnancy may be an inherited tendency; it certainly occurs more often in certain families, but this may be partly due to chance. A woman who has already given birth to twins is ten times more likely to have another multiple pregnancy than one who has not previously had twins. The statistical chance of a third pair of twins is 1:512,000. Identical twins do not run in families.
The relative proportion of twins of each type varies in di?erent races. Identical twins have much the same frequency all over the world: around 3 per 1,000 maternities. Fraternal twins are rare in Mongolian races: less than 3 per 1,000 maternities. In Caucasians they occur two or three times as often as identical twins: between 7 (Spain and Portugal) and 10 (Czech and Slovak Republics and Greece) per 1,000 maternities. They are more common in Afro-Caribbeans, reaching 30 per 1,000 maternities in certain West African populations.
Rarely, uniovular twins may not develop as separate individuals, being physically joined in some way. They are called conjoined or (traditionally) Siamese twins. Depending on the extent of common structures shared by the infants – this ranges from a common umbilical cord to twins with conjoined heads or a common liver – the infants may be successfully separated by surgery. (See CONJOINED TWINS.)
Parents of twins, triplets, etc. can obtain advice and help from the Twins and Multiple Births Association (TAMBA).... multiple births
Pregnancy lasts about 280 days and is calculated from the ?rst day of the last menstrual period – see MENSTRUATION. Pregnancy-testing kits rely on the presence of the hormone beta HUMAN CHORIONIC GONADOTROPHIN (b HCG) which is excreted in the woman’s urine as early as 30 days from the last menstrual period. The estimated date of delivery can be accurately estimated from the size of the developing fetus measured by ULTRASOUND (see also below) between seven and 24 weeks. ‘Term’ refers to the time that the baby is due; this can range from 38 weeks to 41 completed weeks.
Physical changes occur in early pregnancy – periods stop and the abdomen enlarges. The breasts swell, with the veins becoming prominent and the nipples darkening. About two in three women will have nausea with a few experiencing such severe vomiting as to require hospital admission for rehydration.
Antenatal care The aim of antenatal care is to ensure a safe outcome for both mother and child; it is provided by midwives (see MIDWIFE) and doctors. Formal antenatal care began in Edinburgh in the 1930s with the recognition that all aspects of pregnancy – normal and abnormal – warranted surveillance. Cooperation between general practitioners, midwives and obstetricians is now established, with pregnancies that are likely to progress normally being cared for in the community and only those needing special intervention being cared for in a hospital setting.
The initial visit (or booking) in the ?rst half of pregnancy will record the history of past events and the results of tests, with the aim of categorising the patients into normal or not. Screening tests including blood checks and ultrasound scans are a routine part of antenatal care. The ?rst ultrasound scan is done at about 11 weeks to date the pregnancy, with a further one done at 20 weeks – the anomaly scan – to assess the baby’s structure. Some obstetric units will check the growth of the baby with one further scan later in the pregnancy or, in the case of twin pregnancies (see below), many scans throughout. The routine blood tests include checks for ANAEMIA, DIABETES MELLITUS, sickle-cell disease and THALASSAEMIA, as well as for the blood group. Evidence of past infections is also looked for; tests for RUBELLA (German measles) and SYPHILIS are routine, whereas tests for human immunode?ciency virus (see AIDS/ HIV below) and HEPATITIS are being o?ered as optional, although there is compelling evidence that knowledge of the mother’s infection status is bene?cial to the baby.
Traditional antenatal care consists of regular appointments, initially every four weeks until 34 weeks, then fortnightly or weekly. At each visit the mother’s weight, urine and blood pressure are checked, and assessment of fetal growth and position is done by palpating the uterus. Around two-thirds of pregnancies and labours are normal: in the remainder, doctors and midwives need to increase the frequency of surveillance so as to prevent or deal with maternal and fetal problems.
Common complications of pregnancy
Some of the more common complications of pregnancy are listed below.
As well as early detection of medical complications, antenatal visits aim to be supportive and include emotional and educational care. Women with uncomplicated pregnancies are increasingly being managed by midwives and general practitioners in the community and only coming to the hospital doctors should they develop a problem. A small number will opt for a home delivery, but facilities for providing such a service are not always available in the UK.
Women requiring more intensive surveillance have their management targeted to the speci?c problems encountered. Cardiologists will see mothers-to-be with heart conditions, and those at risk of diabetes are cared for in designated clinics with specialist sta?. Those women needing more frequent surveillance than standard antenatal care can be looked after in maternity day centres. These typically include women with mildly raised blood pressure or those with small babies. Fetal medicine units have specialists who are highly skilled in ultrasound scanning and specialise in the diagnosis and management of abnormal babies still in the uterus. ECTOPIC PREGNANCY Chronic abdominal discomfort early in pregnancy may be caused by unruptured ectopic pregnancy, when, rarely, the fertilised OVUM starts developing in the Fallopian tube (see FALLOPIAN TUBES) instead of the uterus. The patient needs hospital treatment and LAPAROSCOPY. A ruptured ectopic pregnancy causes acute abdominal symptoms and collapse, and the woman will require urgent abdominal surgery. URINARY TRACT INFECTIONS These affect around 2 per cent of pregnant women and are detected by a laboratory test of a mid-stream specimen of urine. In pregnancy, symptoms of these infections do not necessarily resemble those experienced by non-pregnant women. As they can cause uterine irritability and possible premature labour (see below), it is important to ?nd and treat them appropriately. ANAEMIA is more prevalent in patients who are vegetarian or on a poor diet. Iron supplements are usually given to women who have low concentrations of HAEMOGLOBIN in their blood (less than 10.5 g/dl) or who are at risk of becoming low in iron, from bleeding, twin pregnancies and those with placenta previa (see below). ANTEPARTUM HAEMORRHAGE Early in pregnancy, vaginal bleedings may be due to a spontaneous or an incomplete therapeutic ABORTION. Bleeding from the genital tract between 24 completed weeks of pregnancy and the start of labour is called antepartum haemorrhage. The most common site is where the PLACENTA is attached to the wall of the uterus. If the placenta separates before delivery, bleeding occurs in the exposed ‘bed’. When the placenta is positioned in the upper part of the uterus it is called an abruption. PLACENTA PRAEVIA is sited in the lower part and blocks or partly blocks the cervix (neck of the womb); it can be identi?ed at about the 34th week. Ten per cent of episodes of antepartum bleeding are caused by placenta previa, and it may be associated with bleeding at delivery. This potentially serious complication is diagnosed by ultrasound scanning and may require a caesarean section (see below) at delivery. INCREASED BLOOD PRESSURE, associated with protein in the urine and swelling of the limbs, is part of a condition known as PRE-ECLAMPSIA. This occurs in the second half of pregnancy in about 1 in 10 women expecting their ?rst baby, and is mostly very mild and of no consequence to the pregnancy. However, some women can develop extremely high blood pressures which can adversely affect the fetus and cause epileptic-type seizures and bleeding disorders in the mother. This serious condition is called ECLAMPSIA. For this reason a pregnant woman with raised blood pressure or PROTEIN in her urine is carefully evaluated with blood tests, often in the maternity day assessment unit. The condition can be stopped by delivery of the baby, and this will be done if the mother’s or the fetus’s life is in danger. If the condition is milder, and the baby not mature enough for a safe delivery, then drugs can be used to control the blood pressure. MISCARRIAGE Also called spontaneous abortion, miscarriage is the loss of the fetus. There are several types:
threatened miscarriage is one in which some vaginal bleeding occurs, the uterus is enlarged, but the cervix remains closed and pregnancy usually proceeds.
inevitable miscarriage usually occurs before the 16th week and is typi?ed by extensive blood loss through an opened cervix and cramp-like abdominal pain; some products of conception are lost but the developing placental area (decidua) is retained and an operation may be necessary to clear the womb.
missed miscarriages, in which the embryo dies and is absorbed, but the decidua (placental area of uterine wall) remains and may cause abdominal discomfort and discharge of old blood.
THERAPEUTIC ABORTION is performed on more than 170,000 women annually in England and Wales. Sometimes the woman may not have arranged the procedure through the usual health-care channels, so that a doctor may see a patient with vaginal bleeding, abdominal discomfort or pain, and open cervix – symptoms which suggest that the decidua and a blood clot have been retained; these retained products will need to be removed by curettage.
Septic abortions are now much less common in Britain than before the Abortion Act (1967) permitted abortion in speci?ed circumstances. The cause is the passage of infective organisms from the vagina into the uterus, with Escherichia coli and Streptococcus faecalis the most common pathogenic agents. The woman has abdominal pain, heavy bleeding, usually fever and sometimes she is in shock. The cause is usually an incomplete abortion or one induced in unsterile circumstances. Antibiotics and curettage are the treatment. INTRAUTERINE GROWTH RETARDATION describes a slowing of the baby’s growth. This can be diagnosed by ultrasound scanning, although there is a considerable margin of error in estimates of fetal weight. Trends in growth are favoured over one-o? scan results alone. GESTATIONAL DIABETES is a condition that is more common in women who are overweight or have a family member with diabetes. If high concentrations of blood sugar are found, e?orts are made to correct it as the babies can become very fat (macrosomia), making delivery more di?cult. A low-sugar diet is usually enough to control the blood concentration of sugars; however some women need small doses of INSULIN to achieve control. FETAL ABNORMALITIES can be detected before birth using ultrasound. Some of these defects are obvious, such as the absence of kidneys, a condition incompatible with life outside the womb. These women can be o?ered a termination of their pregnancy. However, more commonly, the pattern of problems can only hint at an abnormality and closer examination is needed, particularly in the diagnosis of chromosomal deformities such as DOWN’S (DOWN) SYNDROME (trisomy 21 or presence of three 21 chromosomes instead of two).
Chromosomal abnormalities can be de?nitively diagnosed only by cell sampling such as amniocentesis (obtaining amniotic ?uid – see AMNION – from around the baby) done at 15 weeks onwards, and chorionic villus sampling (sampling a small part of the placenta) – another technique which can be done from 12 weeks onwards. Both have a small risk of miscarriage associated with them; consequently, they are con?ned to women at higher risk of having an abnormal fetus.
Biochemical markers present in the pregnant woman’s blood at di?erent stages of pregnancy may have undergone changes in those carrying an abnormal fetus. The ?rst such marker to be routinely used was a high concentration of alpha-fetol protein in babies with SPINA BIFIDA (defects in the covering of the spinal cord). Fuller research has identi?ed a range of diagnostic markers which are useful, and, in conjunction with other factors such as age, ethnic group and ultrasound ?ndings, can provide a predictive guide to the obstetrician – in consultation with the woman – as to whether or not to proceed to an invasive test. These tests include pregnancy-associated plasma protein assessed from a blood sample taken at 12 weeks and four blood tests at 15–22 weeks – alphafetol protein, beta human chorionic gonadotrophin, unconjugated oestriol and inhibin A. Ultrasound itself can reveal physical ?ndings in the fetus, which can be more common in certain abnormalities. Swelling in the neck region of an embryo in early pregnancy (increased nuchal thickness) has good predictive value on its own, although its accuracy is improved in combination with the biochemical markers. The e?ectiveness of prenatal diagnosis is rapidly evolving, the aim being to make the diagnosis as early in the pregnancy as possible to help the parents make more informed choices. MULTIPLE PREGNANCIES In the UK, one in 95 deliveries is of twins, while the prevalence of triplets is one in 10,000 and quadruplets around one in 500,000. Racial variations occur, with African women having a prevalence rate of one in 30 deliveries for twins and Japanese women a much lower rate than the UK ?gure. Multiple pregnancies occur more often in older women, and in the UK the prevalence of fertility treatments, many of these being given to older women, has raised the incidence. There is now an o?cial limit of three eggs being transferred to a woman undergoing ASSISTED CONCEPTION (gamete intrafallopian transfer, or GIFT).
Multiple pregnancies are now usually diagnosed as a result of routine ultrasound scans between 16 and 20 weeks of pregnancy. The increased size of the uterus results in the mother having more or worse pregnancy-related conditions such as nausea, abdominal discomfort, backache and varicose veins. Some congenital abnormalities in the fetus occur more frequently in twins: NEURAL TUBE defects, abnormalities of the heart and the incidence of TURNER’S SYNDROME and KLINEFELTER’S SYNDROME are examples. Such abnormalities may be detected by ultrasound scans or amniocentesis. High maternal blood pressure and anaemia are commoner in women with multiple pregnancies (see above).
The growth rates of multiple fetuses vary, but the di?erence between them and single fetuses are not that great until the later stages of pregnancy. Preterm labour is commoner in multiple pregnancies: the median length of pregnancy is 40 weeks for singletons, 37 for twins and 33 for triplets. Low birth-weights are usually the result of early delivery rather than abnormalities in growth rates. Women with multiple pregnancies require more frequent and vigilant antenatal assessments, with their carers being alert to the signs of preterm labour occurring. CEPHALOPELVIC DISPROPORTION Disparity between the size of the fetus and the mother’s pelvis is not common in the UK but is a signi?cant problem in the developing world. Disparity is classi?ed as absolute, when there is no possibility of delivery, and relative, when the baby is large but delivery (usually after a dif?cult labour) is possible. Causes of absolute disparity include: a large baby – heavier than 5 kg at birth; fetal HYDROCEPHALUS; and an abnormal maternal pelvis. The latter may be congenital, the result of trauma or a contraction in pelvic size because of OSTEOMALACIA early in life. Disproportion should be suspected if in late pregnancy the fetal head has not ‘engaged’ in the pelvis. Sometimes a closely supervised ‘trial of labour’ may result in a successful, if prolonged, delivery. Otherwise a caesarean section (see below) is necessary. UNUSUAL POSITIONS AND PRESENTATIONS OF THE BABY In most pregnant women the baby ?ts into the maternal pelvis head-?rst in what is called the occipito-anterior position, with the baby’s face pointing towards the back of the pelvis. Sometimes, however, the head may face the other way, or enter the pelvis transversely – or, rarely, the baby’s neck is ?exed backwards with the brow or face presenting to the neck of the womb. Some malpositions will correct naturally; others can be manipulated abdominally during pregnancy to a better position. If, however, the mother starts labour with the baby’s head badly positioned or with the buttocks instead of the head presenting (breech position), the labour will usually be longer and more di?cult and may require intervention using special obstetric forceps to assist in extracting the baby. If progress is poor and the fetus distressed, caesarean section may be necessary. HIV INFECTION Pregnant women who are HIV positive (see HIV; AIDS/HIV) should be taking antiviral drugs in the ?nal four to ?ve months of pregnancy, so as to reduce the risk of infecting the baby in utero and during birth by around 50 per cent. Additional antiviral treatment is given before delivery; the infection risk to the baby can be further reduced – by about 40 per cent – if delivery is by caesarean section. The mother may prefer to have the baby normally, in which case great care should be taken not to damage the baby’s skin during delivery. The infection risk to the baby is even further reduced if it is not breast fed. If all preventive precautions are taken, the overall risk of the infant becoming infected is cut to under 5 per cent.
Premature birth This is a birth that takes place before the end of the normal period of gestation, usually before 37 weeks. In practice, however, it is de?ned as a birth that takes place when the baby weighs less than 2·5 kilograms (5••• pounds). Between 5 and 10 per cent of babies are born prematurely, and in around 40 per cent of premature births the cause is unknown. Pre-eclampsia is the most common known cause; others include hypertension, chronic kidney disease, heart disease and diabetes mellitus. Multiple pregnancy is another cause. In the vast majority of cases the aim of management is to prolong the pregnancy and so improve the outlook for the unborn child. This consists essentially of rest in bed and sedation, but there are now several drugs, such as RITODRINE, that may be used to suppress the activity of the uterus and so help to delay premature labour. Prematurity was once a prime cause of infant mortality but modern medical care has greatly improved survival rates in developing countries.
Labour Also known by the traditional terms parturition, childbirth or delivery, this is the process by which the baby and subsequently the placenta are expelled from the mother’s body. The onset of labour is often preceded by a ‘show’ – the loss of the mucus and blood plug from the cervix, or neck of the womb; this passes down the vagina to the exterior. The time before the beginning of labour is called the ‘latent phase’ and characteristically lasts 24 hours or more in a ?rst pregnancy. Labour itself is de?ned by regular, painful contractions which cause dilation of the neck of the womb and descent of the fetal head. ‘Breaking of the waters’ is the loss of amniotic ?uid vaginally and can occur any time in the delivery process.
Labour itself is divided into three stages: the ?rst is from the onset of labour to full (10 cm) dilation of the neck of the womb. This stage varies in length, ideally taking no more than one hour per centimetre of dilation. Progress is monitored by regular vaginal examinations, usually every four hours. Fetal well-being is observed by intermittent or continuous monitoring of the fetal heart rate in relation to the timing and frequency of the contractions. The print-out is called a cardiotocograph. Abnormalities of the fetal heart rate may suggest fetal distress and may warrant intervention. In women having their ?rst baby (primigravidae), the common cause of a slow labour is uncoordinated contractions which can be overcome by giving either of the drugs PROSTAGLANDIN or OXYTOCIN, which provoke contractions of the uterine muscle, by an intravenous drip. Labours which progress slowly or not at all may be due to abnormal positioning of the fetus or too large a fetus, when prostaglandin or oxytocin is used much more cautiously.
The second stage of labour is from full cervical dilation to the delivery of the baby. At this stage the mother often experiences an irresistible urge to push the baby out, and a combination of strong coordinated uterine contractions and maternal e?ort gradually moves the baby down the birth canal. This stage usually lasts under an hour but can take longer. Delay, exhaustion of the mother or distress of the fetus may necessitate intervention by the midwife or doctor. This may mean enlarging the vaginal opening with an EPISIOTOMY (cutting of the perineal outlet – see below) or assisting the delivery with specially designed obstetric forceps or a vacuum extractor (ventouse). If the cervix is not completely dilated or open and the head not descended, then an emergency caesarean section may need to be done to deliver the baby. This procedure involves delivering the baby and placenta through an incision in the mother’s abdomen. It is sometimes necessary to deliver by planned or elective caesarean section: for example, if the placenta is low in the uterus – called placenta praevia – making a vaginal delivery dangerous.
The third stage occurs when the placenta (or afterbirth) is delivered, which is usually about 10–20 minutes after the baby. An injection of ergometrine and oxytocin is often given to women to prevent bleeding.
Pain relief in labour varies according to the mother’s needs. For uncomplicated labours, massage, reassurance by a birth attendant, and a warm bath and mobilisation may be enough for some women. However, some labours are painful, particularly if the woman is tired or anxious or is having her ?rst baby. In these cases other forms of analgesia are available, ranging from inhalation of NITROUS OXIDE GAS, injection of PETHIDINE HYDROCHLORIDE or similar narcotic, and regional local anaesthetic (see ANAESTHESIA).
Once a woman has delivered, care continues to ensure her and the baby’s safety. The midwives are involved in checking that the uterus returns to its normal size and that there is no infection or heavy bleeding, as well as caring for stitches if needed. The normal blood loss after birth is called lochia and generally is light, lasting up to six weeks. Midwives o?er support with breast feeding and care of the infant and will visit the parents at home routinely for up to two weeks.
Some complications of labour All operative deliveries in the UK are now done in hospitals, and are performed if a spontaneous birth is expected to pose a bigger risk to the mother or her child than a specialist-assisted one. Operative deliveries include caesarean section, forceps-assisted deliveries and those in which vacuum extraction (ventouse) is used. CAESAREAN SECTION Absolute indications for this procedure, which is used to deliver over 15 per cent of babies in Britain, are cephalopelvic disproportion and extensive placenta praevia, both discussed above. Otherwise the decision to undertake caesarean section depends on the clinical judgement of the specialist and the views of the mother. The rise in the proportion of this type of intervention (from 5 per cent in the 1930s to its present level of over 23 per cent
P
of the 600,000 or so annual deliveries in England) has been put down to defensive medicine
– namely, the doctor’s fear of litigation (initiated often because the parents believe that the baby’s health has suffered because the mother had an avoidably di?cult ‘natural’ labour). In Britain, over 60 per cent of women who have had a caesarean section try a vaginal delivery in a succeeding pregnancy, with about two-thirds of these being successful. Indications for the operation include:
absolute and relative cephalopelvic disproportion.
placenta previa.
fetal distress.
prolapsed umbilical cord – this endangers the viability of the fetus because the vital supply of oxygen and nutrients is interrupted.
malpresentation of the fetus such as breech or transverse lie in the womb.
unsatisfactory previous pregnancies or deliveries.
a request from the mother.
Caesarean sections are usually performed using regional block anaesthesia induced by a spinal or epidural injection. This results in loss of feeling in the lower part of the body; the mother is conscious and the baby not exposed to potential risks from volatile anaesthetic gases inhaled by the mother during general anaesthesia. Post-operative complications are higher with general anaesthesia, but maternal anxiety and the likelihood that the operation might be complicated and di?cult are indications for using it. A general anaesthetic may also be required for an acute obstetric emergency. At operation the mother’s lower abdomen is opened and then her uterus opened slowly with a transverse incision and the baby carefully extracted. A transverse incision is used in preference to the traditional vertical one as it enables the woman to have a vaginal delivery in any future pregnancy with a much smaller risk of uterine rupture. Women are usually allowed to get up within 24 hours and are discharged after four or ?ve days. FORCEPS AND VENTOUSE DELIVERIES Obstetric forceps are made in several forms, but all are basically a pair of curved blades shaped so that they can obtain a purchase on the baby’s head, thus enabling the operator to apply traction and (usually) speed up delivery. (Sometimes they are used to slow down progress of the head.) A ventouse or vacuum extractor comprises an egg-cup-shaped metal or plastic head, ranging from 40 to 60 mm in diameter with a hollow tube attached through which air is extracted by a foot-operated vacuum pump. The instrument is placed on the descending head, creating a negative pressure on the skin of the scalp and enabling the operator to pull the head down. In mainland Europe, vacuum extraction is generally preferred to forceps for assisting natural deliveries, being used in around 5 per cent of all deliveries. Forceps have a greater risk of causing damage to the baby’s scalp and brain than vacuum extraction, although properly used, both types should not cause any serious damage to the baby.
Episiotomy Normal and assisted deliveries put the tissues of the genital tract under strain. The PERINEUM is less elastic than the vagina and, if it seems to be splitting as the baby’s head
moves down the birth canal, it may be necessary to cut the perineal tissue – a procedure called an episiotomy – to limit damage. This is a simple operation done under local anaesthetic. It should be done only if there is a speci?c indication; these include:
to hasten the second stage of labour if the fetus is distressed.
to facilitate the use of forceps or vacuum extractor.
to enlarge a perineum that is restricted because of unyielding tissue, perhaps because of a scar from a previous labour. Midwives as well as obstetricians are trained
to undertake and repair (with sutures) episiotomies.
(For organisations which o?er advice and information on various aspects of childbirth, including eclampsia, breast feeding and multiple births, see APPENDIX 2: ADDRESSES: SOURCES OF INFORMATION, ADVICE, SUPPORT AND SELF-HELP.)... pregnancy and labour
In a highly signi?cant advance in research, a scienti?c team in the United States obtained stem cells from newly formed human embryos
– donated by women who had become pregnant after successful in vitro fertilisation – and successfully cultivated these cells in the laboratory. This achievement opened the way to replicating in the laboratory, the various specialised cells that develop naturally in the body. UK government legislation constrains the use of human embryos in research (see ETHICS) and the ethical aspects of taking this stem-cell culture technique forwards will have to be resolved. Nevertheless, this discovery points the biological way to the use of genetic engineering in selecting di?erentiated specialised cells from which replacement tissues could be grown for use as transplants to rectify absent or damaged tissues in the human body.
Research into potential use of stem cells has raised expectations that in the long term they may prove to be an e?ective regenerative treatment for a wide range of disorders including PARKINSONISM, ALZHEIMER’S DISEASE, type-2 diabetes (see under DIABETES MELLITUS), myocardial infarction (see HEART, DISEASES OF), severe burns, osteoporosis (see under BONE, DISORDERS OF) and the regeneration of blood to replace the need for BONE MARROW TRANSPLANT. Recent research has shown that adult stem cells may also be stimulated to produce new cell lines. If successful, this would eliminate the need to use embryos and thus resolve existing ethical dilemmas over the use of stem cells.... stem cell
Meiosis produces egg (see ovum) and sperm cells that differ from their parent cells in that they have only half the normal number of chromosomes.... cell division
Sometimes during cell division chromosomes may be lost or duplicated, or abnormalities in the structure of individual chromosomes may occur. The surprising fact is the infrequency of such errors. About one in 200 live-born babies has an abnormality of development caused by a chromosome, and two-thirds of these involve the sex chromosomes. There is little doubt that the frequency of these abnormalities in the early embryo is much higher, but because of the serious nature of the defect, early spontaneous ABORTION occurs.
Chromosome studies on such early abortions show that half have chromosome abnormalities, with errors of autosomes being three times as common as sex chromosome anomalies. Two of the most common abnormalities in such fetuses are triploidy with 69 chromosomes and trisomy of chromosome 16. These two anomalies almost always cause spontaneous abortion. Abnormalities of chromosome structure may arise because of:
Deletion Where a segment of a chromosome is lost.
Inversion Where a segment of a chromosome becomes detached and re-attached the other way around. GENES will then appear in the wrong order and thus will not correspond with their opposite numbers on homologous chromosomes.
Duplication Where a segment of a chromosome is included twice over. One chromosome will have too little nuclear material and one too much. The individual inheriting too little may be non-viable and the one with too much may be abnormal.
Translocation Where chromosomes of different pairs exchange segments.
Errors in division of centromere Sometimes the centromere divides transversely instead of longitudinally. If the centromere is not central, one of the daughter chromosomes will arise from the two short arms of the parent chromosome and the other from the two long arms. These abnormal daughter chromosomes are called isochromosomes.
These changes have important bearings on heredity, as the e?ect of a gene depends not only upon its nature but also upon its position on the chromosome with reference to other genes. Genes do not act in isolation but against the background of other genes. Each gene normally has its own position on the chromosome, and this corresponds precisely with the positon of its allele on the homologous chromosome of the pair. Each member of a pair of chromosomes will normally carry precisely the same number of genes in exactly the same order. Characteristic clinical syndromes, due to abnormalities of chromosome structure, are less constant than those due to loss or gain of a complete chromosome. This is because the degree of deletion, inversion and duplication is inconstant. However, translocation between chromosomes 15 and 21 of the parent is associated with a familial form of mongolism (see DOWN’S (DOWN) SYNDROME) in the o?spring, and deletion of part of an X chromosome may result in TURNER’S SYNDROME.
Non-disjunction Whilst alterations in the structure of chromosomes arise as a result of deletion or translocation, alterations in the number of chromosomes usually arise as a result of non-disjunction occurring during maturation of the parental gametes (germ cells). The two chromosomes of each pair (homologous chromosomes) may fail to come together at the beginning of meiosis and continue to lie free. If one chromosome then passes to each pole of the spindle, normal gametes may result; but if both chromosomes pass to one pole and neither to the other, two kinds of abnormal gametes will be produced. One kind of gamete will contain both chromosomes of the pair, and the other gamete will contain neither. Whilst this results in serious disease when the autosomes are involved, the loss or gain of sex chromosomes seems to be well tolerated. The loss of an autosome is incompatible with life and the malformation produced by a gain of an autosome is proportional to the size of the extra chromosome carried.
Only a few instances of a gain of an autosome are known. An additional chromosome 21 (one of the smallest autosomes) results in mongolism, and trisomy of chromosome 13 and 18 is associated with severe mental, skeletal and congenital cardiac defects. Diseases resulting from a gain of a sex chromosome are not as severe. A normal ovum contains 22 autosomes and an X sex chromosome. A normal sperm contains 22 autosomes and either an X or a Y sex chromosome. Thus, as a result of nondisjunction of the X chromosome at the ?rst meiotic division during the formation of female gametes, the ovum may contain two X chromosomes or none at all, whilst in the male the sperm may contain both X and Y chromosomes (XY) or none at all. (See also CHROMOSOMES; GENES.)... sex chromosomes
The ovum is then placed in the uterus.... (icsi)
Sperm are produced within the seminiferous tubules of the testes and mature in the epididymis.
Production and development of sperm cells is dependent on testosterone and on gonadotrophin hormones secreted by the pituitary gland.
Sperm production starts at puberty.... sperm
The manner of sterilising bedding, furniture, and the like, after contact with a case of infectious disease, is given under DISINFECTION; whilst the sterilisation of instruments, dressings, and skin surfaces, necessary before surgical procedures, is mentioned in the same article and also under ANTISEPTICS, ASEPSIS, and WOUNDS. For general purposes, one of the cheapest and most e?ective agents is boiling water or steam.
Bacteriological sterilisation may be e?ected in many ways, and di?erent methods are used in di?erent cases.
Reproductive sterilisation In women, this is performed by ligating (cutting) and then tying the FALLOPIAN TUBES – the tubes that carry the OVUM from the ovary (see OVARIES) to the UTERUS. Alternatively, the tubes may be sealed-o? by means of plastic and silicone clips or rings. The technique is usually performed (by LAPAROSCOPY) through a small incision, or cut, in the lower abdominal wall. It has no e?ect on sexual or menstrual function, and, unlike the comparable operation in men, it is immediately e?ective. The sterilisation is usually permanent (around 0·05 pregnancies occur for every 100 women years of use), but occasionally the two cut ends of the Fallopian tubes reunite, and pregnancy is then again possible. Removal of the uterus and/or the ovaries also sterilises a woman but such procedures are only used when there is some special reason, such as the presence of a tumour.
The operation for sterilising men is known as VASECTOMY.... sterilisation
Hard plastic lenses give good vision, are long-lasting and durable, inexpensive, and easy to maintain. However, they are sometimes difficult to tolerate and may fall out. Hard gas-permeable lenses are more comfortable because they allow oxygen to pass through to the eye, but are less durable. Soft lenses are the most comfortable because of their high water content. Disposable soft lenses are for single-use only; extended wear lenses are worn for up to a month.
Other types of lenses include rigid, scleral lenses that cover the whole of the front of the eye and are used to disguise disfigurement due to injury or disease; bifocal contact lenses; and interruptus; hormonal methods, including the use of oral contraceptives, implants, and injections (see contraceptives, injectable); intrauterine devices (see IUDs); postcoital methods (see contraception, emergency); or sterilization of the male (see vasectomy) or female (see sterilization, female).
contraception, barrier methods of
The use of a device and/or a chemical to stop sperm reaching an ovum, preventing fertilization and pregnancy. Barrier methods also help prevent the sexual transmission of diseases such as AIDS, genital herpes (see herpes, genital), and viral hepatitis (see hepatitis, viral).
toric contact lenses with an uneven sur- face curvature to correct astigmatism.
Hard plastic contact lenses may cause abrasion of the cornea if they are worn for too long. Soft lens wearers sometimes develop sensitivity of the eyes and lids. Other problems that may occur with any type of contact lens include infections and redness of the eye.... contact lenses
A man’s fertility depends on the production of normal quantities of healthy sperm in the testes (see testis), which, in turn, depends on adequate production of gonadotrophin hormones by the pituitary gland at the base of the brain. Fertility in males is also dependent on the ability to achieve an erection and to ejaculate semen into the vagina during sexual intercourse. Males become fertile at puberty and usually remain so, but to a lesser degree, well into old age.A woman’s ability to conceive depends on normal ovulation (the monthly production of a healthy ovum by 1 of the ovaries) and the ovum’s unimpeded passage down a fallopian tube towards the uterus; on thinning of the mucus surrounding the mouth of the cervix to enable sperm to penetrate; and on changes in the lining of the uterus which prepare it for the implantation of a fertilized ovum. These processes are in turn dependent on normal production of gonadotrophins by the pituitary gland, and of the sex hormones oestrogen and progesterone by the ovaries. Women become fertile at puberty, and they remain so until the menopause around the age of 40 to 50. (See also fertility drugs; infertility.)... fertility
It occurs about 6 days after fertilization, when the blastocyst (early embryo) comes into contact with the wall of the uterus.
As the cells of the developing embryo continue to divide, the outer cell layer penetrates the lining of the uterus to obtain oxygen and nutrients from the mother’s blood; later, this layer develops into the placenta.
The embryo usually implants in the upper part of the uterus; if it implants low down near the cervix, placenta praevia may develop.
Rarely, implantation occurs outside the uterus, possibly in a fallopian tube, resulting in an ectopic pregnancy.... implantation, egg
There are 2 types of nucleic acid: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). In all plant and animal cells, including human cells, DNA permanently holds the coded instructions, which are translated and implemented by RNA. DNA is the main constituent of chromosomes, which are carried in the nucleus (central unit) of the cell.
DNA and RNA are similar in structure, both comprising long, chain-like molecules. However, DNA usually consists of 2 intertwined chains, whereas RNA is generally single-stranded.
The basic structure of DNA has been likened to a rope ladder, the chains forming the 2 sides, with interlinking structures in between forming the rungs.
The ladder is twisted into a spiral shape called a double helix.
Each DNA chain has a “backbone” consisting of a string of sugar and phosphate chemical groups. Attached to each sugar is a chemical called a base, which can be any of 4 types (adenine, thymine, guanine, and cytosine) and forms half a rung of the DNA ladder. The 4 bases can occur in any sequence along the chain. The sequence, which may be many millions of individual bases long, provides the code for the activities of the cell (see genetic code).
RNA is like a single strand of DNA; the main difference is that the base thymine is replaced by another base, uracil.
When a cell undergoes mitotic (see mitosis) division, identical copies of its DNA must go to each of the 2 daughter cells. The 2 DNA chains separate, and 2 more chains are formed, side by side with the original chains. Because only certain base pairings are possible, the new double chains are identical to the original DNA molecule. Each of a person’s cells carries the same DNA replica that was present in the fertilized ovum, so the DNA message passes from one generation of cells to the next.... nucleic acids
A normal pregnancy lasts around 40 weeks from the first day of the woman’s last menstrual period. It is divided into 3 stages (trimesters) of 3 months each. For the first 8 weeks of pregnancy, the developing baby is called an embryo; thereafter it is called a fetus.
In the 1st trimester the breasts start to swell and may become tender. Morning sickness is common. The baby’s major organs have developed by the end of this stage. During the 2nd trimester, the mother’s nipples enlarge and darken and weight rises rapidly. The baby is usually felt moving by 22 weeks. During the 3rd trimester, stretch marks and colostrum may appear, and Braxton Hick’s contractions may be felt. The baby’s head engages at about 36 weeks.
Common, minor health problems during pregnancy include constipation, haemorrhoids, heartburn, pica, swollen ankles, and varicose veins. Other common disorders include urinary tract infections, stress incontinence (see incontinence, urinary), and candidiasis.Complications of pregnancy and disorders that affect it include antepartum haemorrhage; diabetic pregnancy; miscarriage; polyhydramnios; pre-eclampsia; prematurity; and Rhesus incompatibility. (See also childbirth; fetal heart monitoring; pregnancy, multiple.)... pregnancy
Ova (eggs) are released at monthly intervals from the 2 ovaries, which also secrete oestrogen hormone; and progesterone hormones that control the reproductive cycle. The ova travel through the fallopian tubes to the uterus. Fertilization takes place if a sperm released into the vagina during sexual intercourse travels through the cervix and uterus to penetrate an ovum while it is in the fallopian tube.... reproductive system, female
Complex organisms are built up of millions of cells that are specially adapted to carry out particular functions. The process of cell differentiation begins early on in the development of the embryo and cells of a particular type (e.g. blood cells, liver cells) always give rise to cells of the same type. Each cell has a particular number of *chromosomes in its nucleus. The sex cells (sperm and ova) always contain half the number of chromosomes of all the other cells of the body (see meiosis); at fertilization a sperm and ovum combine to form a cell with a complete set of chromosomes that will develop into the embryo.... cell