The smallest unit of inheritance coded by DNA. Generally, a single gene codes for a single protein. Genes come in pairs of alleles (one inherited from each parent) in all tissues except the haploid cells, particularly the spermatozoon.

Strictly, the process by which follicles are first formed in the ovaries before birth; in the woman, it means the growth of a primordial follicle into an early tertiary follicle -- a transition that confers receptiveness of the follicle to follicle stimulating hormone (FSH) The stimulus for initiation of follicular development and its timing for individual follicles remains a mystery.

The multiplication (by the process of mitosis) of ova, or eggs, in the ovaries of the fetus.

Can occur when an egg (as a secondary oocyte) undergoes activation (by itself, with some non-specific stimulus, or through fertilisation by a sperm) and starts to divide (it undergoes cleavage), but the male chromosomes are not incorporated and the egg remains haploid; its further development will soon stop, probably well before implantation. Can be the cause of apparent (but false) late fertilisation in the IVF lab.

(PGD) Genetic diagnosis of an IVF embryo before embryo transfer. Made possible by removing one or two cells of the embryo (embryo microbiopsy). Typically performed on day 3 of embryo development in vitro, at the 8-cell stage, prior to compaction, or on day 5, as an expanding blastocyst.

(RTF) A protein produced by the trophoblast that reduces the tendency of the mother's immune system to reject the pregnancy, apparently by increasing levels of interleukin 10, and thus reducing the tendency for miscarriage.

Development of a sperm cell, in the tubules of the testes (the testicular tubules), from spermatogonium and spermatocyte to spermatozoon (the last part of this process, from spermatid to spermatozoon, is called spermiogenesis). The process of spermatogenesis takes 56 days. At any one location in a tubule there are cells at four different stages of maturity, so mature sperm are released from a particular location into the lumen of the testicular tubules every 14 days. A systematic interruption of spermatogenesis results in azoospermia and is called maturation arrest.

The final part of the formation of a mature sperm cell, in which the round, early spermatid (already with a haploid number of chromosomes) loses its round shape to acquire the features of the mature, elongated spermatozoon. Contrast with spermatogenesis, which encompasses spermiogenesis as it's completed.

An abnormal condition of the uterus in which glands from the endometrium grow into the muscle of the wall of the uterus (the myometrium), causing local or general enlargement of the uterus, pain with periods, and perhaps heavier periods. A localised area of adenomyosis is called an adenomyoma and can be hard to distinguish from a fibroid on transvaginal ultrasound, although an increase in the serum CA 125 antigen level can point to the correct diagnosis. Unlike a fibroid it is not easily removed at surgery, because it's not clearly separable from surrounding tissue. There's no satisfactory long term treatment for adenomyosis: hysterectomy may be chosen if symptoms are bad enough. GnRH-agonists give just temporary relief.

Because genes come in pairs, one on each of the chromosomes that make up a chromosome pair, the two genes of the pair are not always identical. The manydifferent forms that a particular gene can take (and still function, for better or for worse, as a gene within that gene's job description) are referred to as its alleles. If the alleles are identical, you are homozygous for that gene; if they are not, you are heterozygous. Abnormal alleles cause genetic disease or disability: if one allele is enough to cause abnormality then the gene is dominant (inherited with dominant inheritance) and the abnormality is present in the heterozygous and the homozygous state; if two alleles are needed to cause abnormality, then the gene is recessive (inherited with recessive inheritance) and the abnormality is present in the homozygous state and in a state where the two alleles are different but both are harmful (called compound heterozygosity. In the case of alleles found on X-chromosomes (see sex chromosome) but not on Y-chromosomes, which are smaller, a recessive gene will be unopposed in males (and so will act as a dominant gene), whereas female carriers of the allele will be unaffected except in the extremely unlikely event that they inherit (or gain by mutation) a second abnormal allele; this mode of inheritance is called sex-linked recessive inheritance.

Irregular and generally heavy bleeding caused by anovulatory cycles. The underlying causes and how to prevent the sometimes harmful consequences, including endometrial hyperplasia.

The word for what scientists call programmed cell death, or cellular suicide. This is a normal -- rather altruistic! -- thing for a cell to do, as it purposefully switches on some special genes that then alter its metabolism to dismantle itself and die, for the greater good of the tissue or organ that it's a part of. Pathologists distinguish apoptosis from necrosis. Examples of apoptosis include follicular atresia.

Process by which a tissue stops growing, loses its function and degenerates. Synonymous with atrophy.

A complete absence of sperm (spermatozoa) in the semen. Detectable only by performing a sperm count, as semen looks the same whether it contains sperm or not. Due either to an obstruction (usually in the epididymis or vas deferens), and called obstructive azoospermia, or to failure of sperm to form or to mature in the testis (called maturation arrest). See also spermatogenesis and testicular sperm extraction (TESE).

Remember chromosomes occur in pairs in all cells except sperm and eggs. If part of one chromosome is found connected to a completely different chromosome it's "translocated". For that person there is no net gain or loss of genetic material, so the translocation is "balanced" and there is no problem. But when that person makes eggs or sperm, some of these will have too much or too little genetic material. The same will be true for an embryo that results. The chromosomal translocation will then be "unbalanced" and the embryo will sooner or later usually result in a miscarriage. If the two particular chromosomes have swapped parts, we call it a balanced reciprocal translocation.

(BMI) An estimate of the amount of fat a person has, calculated by dividing his or her weight (expressed in kilograms) by the square of the height (expressed in meters). Normally between about 20 and 25, although the upper limit is higher with age. A BMI below 20 generally causes oligomenorrhea, then amenorrhea, through anovulation.

The condition when an individual shows two or more genetically different cell lines that are derived from different zygotes, because of intermingling (see microchimerism). Chimerism on a micro scale is more common than generally appreciated, in the sense that most mothers who have had a child will, on careful investigation, be shown to have some white blood cells derived from their fetus or fetuses. See also mosaicism and mixoploidy, although most cases of chimerism do not cause an abnormality of the karyotype.

Generic name for recombinant human chorionic gonadotropin.

A tongue of tissue within the placenta composed of chorion and containing capillaries connected to the blood circulation in the fetus that laps the mother's blood in the uterus, exchanging oxygen, nutrients and waste products between the fetus's blood vessels (in the villi) and the mother's blood. This tissue is sampled for genetic testing with a CVS (or chorionic villus sampling. See also intervillous space. Plural: chorionic villus.

(CVS) A test done at about 9 weeks pregnancy at which, under the guidance of transvaginal ultrasound, a catheter is passed through the cervix of the pregnant uterus to obtain a small sample of tissue from the placenta (the afterbirth) for genetic testing, such as a karyotype.

Remember that the ordinary cells of the body have 46 chromosomes in 23 pairs. The members of each of the pair don't contain the same genes (this is why you can carry a gene for recessive inheritance without being sick, but if you have both genes there's trouble). During the cell divisions that produce the germ cells (the process of meiosis), the 46 chromosomes first double to 92 before they end up with the 23 present in an egg or a sperm. Two of the four sibling chromosomes (we call them chromatids) then randomly exchange bits of themselves: there's a "cross-over". The points of junction where this happens are called chiasmata. Nature is jumbling up where the genes will end up so that in the long run you don't always have to inherit two particular genes together just because they live next door to each other on a chromosome. Cross-over does not mean that genes can end up in any chromosome they like: unless "translocated", they will remain in pairs (of alleles) within a particular pair of chromosomes. Chromosomal crossover is the origin of what geneticists call hybrid vigor.

When the embryo or fetus is abnormal because of a mistake in its number of chromosomes (see aneuploid and polyploid), with too much or too little genetic material. Usually causes miscarriage. Revealed by performing a karyotype on the products of conception.

The mixture of a single (but double stranded) long string of genetic material (DNA) wound around supporting proteins. There are 46 chromosomes (23 pairs) in every normal human cell (other than the germ cells). Each cell therefore contains all the genetic information needed to make a human being. But it's only in the first few days of the embryo that all of a cell's DNA is accessible: once cells differentiate to have special purposes only the DNA they need remains unmasked. Chromosomes are located in the cell's nucleus and come in pairs, so that each cell has two alleles of each gene.

Originally a botanical term meaning asexual reproduction, or reproduction by "budding" rather than by genetic recombination involving an egg and a sperm. Animals can be cloned either by splitting an embryo during cleavage (nature does this in producing monozygotic twinning) or by inserting an adult cell nucleus into a suitably primed secondary oocyte, a process called somatic cell nuclear transfer (and generally still very inefficient, resulting in a new developing embryo in at most a few percent of attempts). See also therapeutic cloning and reproductive cloning.

Process by which the separate cells of the early embryo fuse together to form, for the first time, a tissue. Typically occurs at the stage called the morula. With compaction, it becomes difficult to detach a cell for preimplantation genetic diagnosis.

(CGH) A molecular DNA diagnostic technique whereby a set of chromosomes (a genome) is compared with a standard set using different colored dyes (typically red and green), so that any areas that do not exactly match will appear green or red instead of brown; a sensitive technique that can be applied to preimplantation genetic diagnosis as well as to chorionic villous sampling, or CVS, and to amniocentesis for prenatal diagnosis, yielding results much faster than is possible with a formal karyotype and more comprehensively than is possible with fluorescent in situ hybridisation.

A heterozygous state in which the inherited alleles of the particular gene are different and both harmful, with clinical effects similar to a homozygous state.

An adjective meaning that something, especially an abnormality or anomaly, is present from birth. The cause for such a condition can be hereditary (genetic) or it can be an environmental factor operating before birth.

Abnormal development of a body part during the life of the embryo or fetus, usually but not always apparent at or soon after birth. It can be genetically inherited or be acquired by exposure to a physical or chemical insult, such as the action of a teratogen (a drug or other substance in the environment), during development in the mother's uterus. Few congenital abnormalities can be associated with a specific cause, and an apparent cause might not be the true one.

Congenital (present from birth) absence of the two vasa deferentia, which conduct sperm from the testes to the ejaculate; hence a cause of obstructive azoospermia. Because the vas deferens is usually affected on both sides, the word "bilateral" is often inserted, as CBAVD. Infertility is inevitable, but can be overcome using in vitro fertilisation with testicular sperm extraction. The cause, however, is usually the presence among the man's genes of one of the serious alleles for the genetic disease cystic fibrosis (which, having recessive inheritance, results when there are two such alleles present); it can also come about when there are one or two of the less serious abnormal alleles for this condition. The more common of the abnormal alleles should therefore be screened for (using a specially set up polymerase chain reaction on white blood cells): should an abnormal allele be present (delta F508 is the most common seriously abnormal one), the woman should be screened too, to predict the chance of cystic fibrosis occurring in the offspring.

(CAH) Enlargement and abnormal function of the adrenal glands, usually from before birth, owing to a genetically determined, partial block in the production of cortisol, the adrenal glands' main hormone, resulting in overproduction of subsidiary hormones, including androgens, tending to virilise the female fetus, which can present at birth with intersex. In mild forms does not manifest until puberty, when the symptoms of oligomenorrhea and hirsutism mimic those of polycystic ovary syndrome. See also serum 17-hydroxyprogesterone.

The fluid in which cells or tissues, including eggs, sperm and embryos, are grown. It consists of water, salts and nutrients. Different media have turned out best for different purposes. In the early days of in vitro fertilisation, several different media seemed to produce equal results: examples included Ham's F10, Whittingham's T6. Quinn's medium (said to be based on human tubal fluid, though in reality different to the fluid in the fallopian tube) produced better results than the first generation media. Today's third generation media, or stage specific media, give superior results and are used increasingly. Plural: culture media.

A serious genetic disease (with a recessive inheritance pattern) characterised by a major disturbance of the body's mucus secretions, and thus a cause of incapacitating disease of the lungs. Important in our context because the heterozygous (or carrier) state in men can manifest with azoospermia due to congenital absence of the vasa deferentia -- the infertility of which is nowadays able to be overcome with testicular sperm extraction and ICSI, thus risking inadvertent transmission.

The part of a cell that is not the nucleus (the nucleus contains the chromosomes). The cytoplasm is contained by the cell's plasma membrane and contains all the other cellular structures, including the mitochondria. Genetic inheritance is mostly by way of the nucleus (with a contribution from mother and father); a small part is by way of the cytoplasm (with a contribution only from the mother). It is the cytoplasm of the egg (as a secondary oocyte) into which a sperm cell (spermatozoon) is injected in the process of intracytoplasmic sperm insertion. See also mtDNA.

The commonest of the alleles to result in cystic fibrosis (when two delta F508 alleles are present) or (can occur when one F508 allele is present in a man). A woman heterozygous for this gene (with one F508 allele) will be a carrier for cystic fibrosis (and for CBAVD) but will herself be otherwise normal. There are however many other faulty alleles that can also contribute to these clinical conditions. The most common alleles can be looked for at preimplantation genetic diagnosis (PGD).

The stuff of which genes are made. DNA is an abbreviation of deoxyribonucleic acid, a molecule made of a variable sequence of units, the nature and order of which forms the genetic code. DNA is located chiefly in the chromosomes, which form a cell's nucleus. A small amount of DNA (coding for about 13 genes) is found in the mitochondria (for which see also mtDNA).

A pattern of inheritance of a characteristic (such as brown eye color) or abnormality in which just one gene or allele is needed to confer the characteristic or abnormality, in contrast to recessive inheritance, which requires two abnormal genes.

Painful menstruation. Can be primary, present in teenagers, generally in spasms around the start of the period; or it can be secondary, developing as a woman gets older, and then typically lasting more than a day or so into the period, with prolonged aching as well as spasms. Primary dysmenorrhea might have no medical importance beyond the suffering the pain causes, and typically gets better as a woman reaches her 20s; severe or persistent cases, however, warrant investigation. Secondary dysmenorrhea can signify, for example, endometriosis, fibroids, adenomyosis or peritubal adhesions.

The percentage of ectopic pregnancies among total clinical pregnancies (excluding "biochemical pregnancy"). Until a generation ago, the rate was about 0.3 percent, and this can be regarded as the incidence in normal women. The rate is increased with abnormalities of the fallopian tubes, assisted conception, and other circumstances, so that nowadays ectopic pregnancies account for about 2 percent of pregnancies in western societies.

General term for oocyte.

A form of collaborative reproduction comparable in some ways to sperm donation (see donor insemination), but different in that eggs for donation are much harder to obtain physically than ejaculated sperm are; generally the egg donor undergoes all the steps needed for in vitro fertilisation up to the stage of egg retrieval.

A biopsy, or removal of one or two cells, from an early IVF embryo for preimplantation genetic diagnosis after in vitro fertilisation.

The general name for one of the two principal female sex hormones (the other is progesterone), responsible for stimulating growth of the female reproductive system (the vagina, the cervix, the uterus and the fallopian tubes) and growth of the breasts. The main estrogen is estradiol, produced by: the developing follicle (and to a lesser extent by the corpus luteum) in the ovary; by the trophoblast of the placenta; and by the body's fat tissues (through conversion from male sex hormones, or androgens, in the blood). After the menopause the main estrogen is the weaker one, estrone, largely derived from conversion by the body's fat of the weak androgen androstenedione.

Orally effective form of estradiol that resists being converted to estrone after ingestion. Generic ('no frills') name for Estigyn and Progynon C.

A controversial and emotionally hazardous way of dealing with a higher-order multiple pregnancy (such as quadruplets, quintuplets, or higher) in which, all the embryos or fetuses are at risk of being lost before viability. The technique involves carrying out transvaginal ultrasound and injecting a lethal substance (such as air or a solution of potassium) into the visibly beating heart of one or more of the embryos, so reducing the number of surviving embryos to three, two or one. Generally regarded as a more stressful procedure than even an induced abortion, both for the person undergoing the operation and for the ultrasound doctor asked to do it. Few people regard the availability of fetal reduction to mean that the greatest care does not need to be taken to avoid higher-order multiple pregnancies in assisted conception programs. There's a hazard: loss of the remaining fetuses from miscarriage; but the risk of this, with an experienced ultrasound doctor or fetal medicine specialist, is low.

Microsurgery of the fallopian tube's fimbrial end, involving careful dissection of fimbriae that have become stuck together from adhesions. Generally gives a better outcome than salpingostomy (which must be resorted to if the fimbriae are too damaged to dissect).

Known as "FISH". A form of DNA testing for genetic diagnosis in which a special region of a chromosome is stained with a dye that emits colored light when exposed to ultraviolet light. For example, a marker for chromosome 21 will normally show two spots of light, whereas three spots of light would indicate trisomy 21 (Down syndrome). Useful because the technique is accurate with just one cell, making diagnosis possible in an IVF embryo before transfer (see preimplantation genetic diagnosis), and speeding up prenatal diagnosis while awaiting a full karyotype. Being replaced in some labs by comparative genomic hybridisation.

Normal structure in the ovary that contains the egg, or oocyte. All are formed as primordial follicles before birth and remain microscopic in size until growth starts (folliculogenesis), a month or two before the cycle in which the particular follicle will be a candidate to ovulate. About 3 mm in diameter at the start of a cycle, and about 2 cm in diameter when ready to ovulate. The follicle makes more and more estrogen (particularly estradiol) as it grows. In ovarian monitoring for assisted conception, the number growing and their rate of growth are monitored by transvaginal ultrasound.

(FSH) The hormone, or gonadotropin, produced by the pituitary gland that in women stimulates the tertiary follicle to grow; in men it stimulates spermatogenesis. Obtained from human sources in a mixture with luteinising hormone (LH) as (1) human menopausal gonadotropin (hMG), extracted from the urine of women who have been through the menopause (Humegon, Metrodin and Pergonal); and (2) human pituitary gonadotropin (hPG), from human pituitary glands removed at autopsies (now obsolete). Today, pure FSH is made synthetically with gene technology (recombinant FSH), such as Gonal-F and Puregon.

Recombinant follicle stimulating hormone made by Organon. Called Puregon in Europe, Australia and Asia. On an equivalent dose basis, produces serum FSH that are somewhat slower to rise than with the use of hMG preparations, but which are ultimately higher: in other words, follicles and serum estradiol levels take a little longer to respond than they do to Humegon, but the number of mature, preovulatory follicles available for egg retrieval is the same or more. I find that 200 U (units) of Puregon per day produces a similar result to 225 U of Humegon or Metrodin. Generically known as follitropin beta.

Generic name for recombinant FSH, as found in Gonal-F (or follitropin alpha) and Puregon (Follistim), or follitropin beta. Although there are slight differences in the two preparations, their clinical action is equivalent.

The commonest cause of severe mental retardation in males, caused by a long "triple repeat sequence" in a part of a gene for intelligence located on an X-chromosome, rendering this sex chromosome susceptible to breakage, which can be revealed either in a karyotype performed under special laboratory conditions or using a special PCR DNA test; females have two X-chromosomes and so may be carriers for this devastating condition, which will affect one-in-two of their male children; the carrier state in females can have clinical effects, namely a susceptibility to reduced numbers of ovarian follicles and hence primary ovarian failure and premature menopause, so should be looked for before assisted conception attempts are made in these clinical circumstances.

A general term for a germ cell that has been released or separated from its gonad, i.e. an egg or a sperm.

A full set of DNA code (a full set of genes) for a whole animal or organism, or for a defined component of an organism, such as a mitochondrion.

Distinct from the somatic cells that compose most of the body's tissues and organs, germ cells form the eggs and sperm that will form the next generation. Early germ cells are diploid and replicate by mitosis, but during their development they enter meiosis (for eggs this occurs before birth, for sperm it occurs after puberty), so that at the time of fertilisation the contributing sperm and egg are haploid.

A form of collaborative reproduction in which the woman who is the surrogate for the intended pregnancy receives embryos from the commissioning infertile couple, who have undergone in vitro fertilisation, then, by becoming pregnant, carries (or 'gestates') the pregnancy, gives birth, and then gives up the baby to the baby's genetic parents. In principle the practice can be done for altruistic or commercial reasons.

Generic name for Dimetriose, a drug used in the treatment of endometriosis that inhibits ovulation and blocks the action of both estrogen and progesterone; risks and side effects are similar to danazol; it is usually taken just twice weekly, by mouth.

Any hormone that switches on the function of the gonads. There are two main families of gonadotropins: (a) the gonadotropin that stimulates the growth of the follicle, or follicle stimulating hormone (FSH); and (b) those that cause ovulation from the mature follicle and stimulate the corpus luteum that results to develop and to produce progesterone, namely luteinising hormone (LH) and human chorionic gonadotropin (hCG). FSH will cause growing follicles to produce the estrogen estradiol, provided that a small amount of LH (or hCG) is present. FSH and LH are produced in the pituitary gland, whereas hCG comes from the placenta in pregnancy. In men, FSH stimulates the Sertoli cells of the testicular tubules, and hence drives spermatogenesis; LH and hCG stimulate the Leydig cells to produce testosterone.

Recombinant follicle stimulating hormone made by Serono. Generically known as follitropin alpha.

A naturally occurring 'anticoagulant', or substance that stops blood from clotting. Used in medicine generally to prevent or to treat thrombosis, and sometimes in pregnancy to reduce the risk of miscarriage in someone who has had recurrent miscarriages by improving blood flow in the placenta. Administered by injection under the skin.

An adjective to describe the genetic state when the pair of genes under consideration consists of two alleles that are different. Disease or disability can follow if one of the alleles is at once seriously abnormal and dominant (see dominant inheritance) over the other allele, or if the alleles are different but both are deleterious (a state called compound heterozygosity).

An adjective to describe the genetic state when the pair of genes under consideration consists of two alleles that are the same. Disease or disability can follow if both alleles are seriously abnormal -- a condition known as recessive inheritance (and a good example of which is cystic fibrosis).

(hCG) A gonadotropin produced by the placenta in pregnancy (specifically it's produced by the trophoblast of the chorionic villi); the hormone measured in performing a pregnancy test. The generic (no frills') name for Pregnyl and Profasi, which are preparations of hCG obtained by extracting it from the urine of pregnant women, and Ovidrel, which is made by recombinant gene technology. Mimics the action of luteinising hormone (LH), but has a very much longer duration of action -- and this gives hCG considerable advantages over LH in clinical use. Given as an injection to lead to ovulation from a mature follicle 38 hours after the injection; or to stimulate ongoing function of the corpus luteum, particularly its production of progesterone. So it is typically given after a course of follicle stimulating hormone (FSH) in assisted conception (IVF or GIFT) programs and ovulation induction programs 36 hours before the expected time of egg retrieval (or before having sex or IUI), and then sometimes in further, smaller doses to support the luteal phase that follows. Sometimes used with clomiphene. Ovarian monitoring is needed for its correct use with FSH or with clomiphene. hCG treatment can precipitate the ovarian hyperstimulation syndrome (OHSS).

An examination of the endometrial cavity of the uterus by a thin fiberoptic instrument, similar to the instrument used for laparoscopy. Hysteroscopy can be done in the office, with or without sedation, to make a diagnosis, or in the operating room under general anesthesia, often in association with laparoscopy or to carry out a hysteroscopic operation, such as removal of an endometrial polyp, submucous fibroid or uterine septum.

A disease syndrome caused by abnormal sub-microscopic structure of cilia, which therefore do not function properly during embryonic life, childhood and adulthood. The consequences are situs inversus, in which the developing internal organs in the embryo rotate randomly (so that 50% of affected people have their heart on the right side of the chest and their liver on the left side of the abdomen), abnormal sinuses, a bad form of chronic bronchitis called bronchiectasis, because mucus is not cleared from lungs properly, and male infertility because the sperm tail (the flagellum) has the same sub-microscopic structure as the cilia and cannot propel the spermatozoon. Curiously, female fertility is often normal or adequate: it seems the cilia of the fallopian tube's fimbrial end still make useful contact with the cumulus mass at ovulation, stopping the egg from getting lost and giving the muscular contractions of the tube the chance to carry the egg down to the ampullary-isthmic junction. Also called Kartagener's syndrome, after the Swiss physician Manes Kartagener, who first described a triad of situs inversus, abnormal sinuses and bronchiectasis.

A protein hormone produced in women by developing follicles as well as by the corpus luteum, and in men by the testis in the presence of spermatogenesis, and acting on the pituitary gland to inhibit the production of follicle stimulating hormone. In women, falling levels occur as the number of developing follicles reduces to low numbers leading up to menopause, thus causing the elevation of serum FSH and shortening of the follicular phase that characterises the premenopause. In men, appreciable levels of serum inhibin B, a subclass of the inhibin family, predicts the presence of at least a small amount of sperm production.

A distressing dysfunction of the intestines, in which there's both overactivity of the involuntary contractions of the intestines' muscular wall and increased pain signals coming from those contractions. Treatment is based on decreasing the contractions (with a diet high in fibre, sometimes with antispasmodic drugs) and attempting to reduce the action of the pain-carrying nerves, both by sedating them (this means general sedation too, so it's often not very acceptable) and by re-educating them to be less sensitive. Treatment is time consuming and, ultimately, not always satisfactory. The symptoms of the irritable bowel syndrome are often confused with those of endometriosis; they are sometimes made worse with, and at the time of, premenstrual tension, or, in my experience of patients with it, by performance of a laparoscopy. Typically (but not always), there is an alternating tendency towards diarrhea or constipation; sometimes there is nausea with the spasms.

A reproductive strategy where survival of a species is optimised by placing a premium on individual survival despite fluctuations of the environment. Favors large animals (and large animals favor this strategy) -- animals that get pregnant more than once and the offspring of which require postnatal care before sexual maturity is reached. Spacing of pregnancy is important for survival of mother and offspring, and thus favors the evolution of a genetic basis for subfertility. The opposite reproductive strategy to r-selection. The word comes from the environment's Karrying capacity.

A "minimally invasive" surgical operation at which instruments are passed through the wall of the abdomen: (1) for the diagnosis of abnormalities of the abdominal or pelvic organs (such as the fallopian tubes, ovaries and uterus) and to diagnose endometriosis; or (2) therapeutically, to reach the fallopian tubes for certain assisted conception procedures (see gamete intrafallopian transfer and zygote intrafallopian transfer). Carries the risks of surgery (damage to internal organs, hemorrhage, infection) and the risks of general anesthesia.

Read chromosomal cross-over first, then come back. Because it can take lots of cross-overs (i.e. lots of generations) to send two genes that live as neighbours on a chromosome into different directions (i.e. they end up in different people), we can do family studies to work out how closely people are related by seeing how long the runs are of identical genes.

Early experience with superovulation for in vitro fertilisation, particularly at the original US program in Norfolk VA, saw women patients classified into three classes of responders, depending on how many eggs were obtained at egg retrieval. Poorer than usual outcomes could occur with either a low response or a high response (the high responders generally have polycystic ovaries, with a risk of ovarian hyperstimulation syndrome (OHSS). Many maneuvers have been used to try and retrieve more eggs among low responders, such as starting high dose FSH on day 1, the adding of growth hormone, the avoidance of GnRH-agonists etc., all generally without improving the results. Day 3 serum FSH levels can be high in low responders, indicating a depletion of eggs in the ovaries.

Generic name for recombinant luteinising hormone.

An area of the genome where genes are found that determine your 'tissue type', important in determining whether, for example, you can accept or will reject an organ transplant from someone else. The genes in this area are tightly packed, show extreme polymorphism, and tend to be inherited together as a group.

An instrument for carrying out laparoscopy that is just a few millimeters in diameter, making it possible to perform such operations in an ambulatory setting, without general anesthesia. The reliability of diagnoses made this way will need careful evaluation, especially if done to exclude endometriosis, which can be difficult to find even with conventional laparoscopy.

An abnormal state of the chromosomes seen on a karyotype in which cells from an individual display two or more genetically different chromosome pattern. Can be the result of mosaicism or chimerism.

The condition when an individual shows two or more genetically different cell lines (generally with different karyotypes) that are derived from one zygote.

Mitochondrial DNA. The small amount of DNA found in the mitochondria. mtDNA is the genetic code for 13 proteins involved in metabolism. Because mtDNA is much less stable than the DNA in the chromosomes (where the huge bulk of genetic code is stored), mutations accumulate with time at a greater rate than that for chromosomal DNA -- and eventually limit how well a particular cell or tissue can function with increasing age. Because all of the mtDNA you have you inherited from your mother (you derive your mitochondria from the egg you came from), we could have an explanation: (1) why all eggs are formed before birth (so the mitochondria don't have to keep on dividing too often and risking genetic errors); and (2) why miscarriages and infertility get commoner with age (as the egg's several thousand mitochondria begin to succumb to genetic errors).

In medicine generally it may be best for tests to be negative (like tests for brain tumors or tests for sexually transmitted diseases such as HIV -- as for 'histories', compare negative history), but this is not always so in infertility. Infertility tests are generally better if they're positive, like the postcoital test, tests for ovulation, tests for tubal patency, and (not least) a pregnancy test.

Central structure within a cell that contains the chromosomes. The non-nuclear part of the cell is called the cytoplasm -- which thus contains other cellular structures, including the mitochondria. Genetic inheritance is mostly by way of the nucleus (with a contribution from mother and father); a small part is by way of the cytoplasm (with a contribution only from the mother).

Strictly, oligozoospermia, meaning a reduced number of sperm cells (spermatozoa) in the ejaculate (compared with azoospermia, which means no sperm in the ejaculate). More generally, a decrease in normal, motile sperm, and more or less encompassing laborious terms such as 'asthenozoospermia' (weak motility) and 'teratozoospermia' (abnormal sperm), and even more laborious ones, such as 'oligoasthenoteratozoospermia', which do not reward the effort of concocting them.

Heavy but generally regular bleeding caused either by pathology in the uterus, such as fibroids, or by a generalised bleeding disorder, such as thrombocytopenia (a low platelet count), von Willebrand's disease (can run in families), or treatment with anticoagulant drugs. The formal term for it is menorrhagia.

The general abdominal cavity in which lie the stomach, the intestines, and the uterus, ovaries and fallopian tubes, each covered by a thin, moist, slippery surface layer, the peritoneal serosa (or peritoneum). An examination of the peritoneal cavity is called a laparoscopy.

(PCR) A method of amplifying (increasing in number) a single piece of DNA (the stuff of genes) to get enough of it to analyze physically or chemically for DNA testing. A machine is used that uses alternate cycles of high temperature (to separate DNA's two strands) and medium temperatures (to combine each of the two single strands with free nucleic acids to make new complementary strands), doubling the amount of DNA in the machine's soup each cycle. A few hours in the machine automatically creates millions of identical DNA molecules from just one specimen. Needless to say, it's extremely important that you start with the right bit of DNA, so you're not inadvertently amplifying a bit of contamination! In the film Jurassic Park, PCR was used to amplify bits of dinosaur DNA recovered from the bellies of contemporary insects, which had been trapped and preserved for millions of years inside pieces of amber. A biopsy of a single cell from an embryo after IVF can, with PCR, produce enough DNA to test it for certain genes that cause serious genetic disease.

Forms of a gene (that is, alleles) that are too prevalent in the population to be called mutations or even, sometimes, to be regarded as abnormal. Often they confer an advantage in some special circumstance.

In medicine, it might generally be best for tests to be negative (like tests for brain tumors or tests for sexually transmitted diseases, such as HIV -- as for medical histories, compare positive history) -- but not so in infertility. Infertility tests, such as the postcoital test, tests for ovulation, tests for tubal patency, and (not least) a pregnancy test, are generally better if they're positive.

(PMT) A distressing group of symptoms usually timed for the lead up to a period, then relieved as menstruation takes place, although many women experience different timing; includes downheartedness or depression (certainly an absence of well-being), aggression, fluid retention and weight gain, painful breasts ('mastalgia'), headaches and pain in the pelvis; caused by a periodic fall in the brain's endorphins, in turn usually precipitated by falling levels of progesterone in the second half of the luteal phase, although similar symptoms often accompany the use of progestogens, especially in older women; may be better during superovulation cycles because of generally higher hormone levels, but this is not always the case and PMT at the end of an unsuccessful cycle of assisted conception is particularly hard to put up with. Usually treated (up to a point) symptomatically, with perhaps fluid tablets (diuretics) and analgesics, although it's claimed that the drug Prozac has a specifically beneficial effect on mood, and encouragement of endorphin release with exercise can also be useful. Because progesterone and progestogens are the culprits, an operation to remove the ovaries (plus hysterectomy to simplify estrogen replacement therapy without needing progestogens) is usually curative, but drastic.

Failure of the ovaries to produce enough follicles, because of a problem in the ovary itself, and resulting in depletion of eggs before the age of 40 years (known as premature menopause, a cause of secondary amenorrhea), or maybe even before the age puberty is expected (causing failure of puberty to happen, including primary amenorrhea). Sometimes occurs in spite of good numbers of primordial follicles that (inexplicably, so far) won't develop. The younger the woman, the more likely that an aneuploidy will be found if a karyotype is done on blood or on a biopsy of the ovary. Estrogen replacement therapy is important to prevent general jeopardy to health, including prevention of osteoporosis.

The form of the sperm cell (or male gamete) at the first stage of spermatogenesis, by which spermatogonia enter meiosis to start to reduce the number of chromosomes for the more mature sperm cells (the spermatozoa) that will eventuate.

Recombinant follicle stimulating hormone made by Organon. Called Follistim in the US. Generically known as follitropin beta.

Recombinant follicle stimulating hormone made by Organon. Called Follistim in US. On an equivalent dose basis, produces serum FSH that are somewhat slower to rise than with the use of hMG preparations, but which are ultimately higher: in other words, follicles and serum estradiol levels take a little longer to respond than they do to Humegon, but the number of mature, preovulatory follicles available for egg retrieval is the same or more. Professor Jansen, medical director of SIVF, notes that 200 U (units) of Puregon per day produces a similar result to 225 U of Humegon or Metrodin. Generically known as follitropin beta.

A pattern of inheritance of a characteristic (such as blue eye color) or abnormality (such as congenital absence of the vas deferens) in which two abnormal genes or alleles are needed to confer the characteristic or abnormality, in contrast to dominant inheritance, which requires just one abnormal gene. In the case of alleles found on X-chromosomes but not on the smaller Y-chromosomes, a recessive gene will be unopposed (and so will act as a dominant gene) in males, whereas female carriers of the allele will be unaffected except in the extremely unlikely event that they inherit (or gain by mutation) a second abnormal allele; this mode of inheritance is called sex-linked recessive inheritance.

(rFSH) Follicle stimulating hormone derived from genetic engineering instead of being extracted from the urine of postmenopausal women (human menopausal gonadotropin, or hMG) or from the pituitary glands of cadavers (human pituitary gonadotropin, or hPG). Produced and marketed by the two pharmaceutical companies Organon (as Puregon), or Fertinex in the US and Serono (as Gonal-F) to replace their hMG preparations. Has the advantage over hMG (and its purified derivatives) of being standard in biological structure and activity, and of not being of a human source (hPG -- but not hMG -- having been implicated in transmission of Creutzfeldt-Jakob disease).

(rLH) luteinising hormone derived from genetic engineering technology instead of being extracted from the urine. Marketed by Serono as Luveris.

The chance of having something or being affected by something compared with people in a comparable situation. Usually given as a ratio, a proportion or a percentage as in the chance of having endometriosis; if your sister has it, you have a relative risk of 7:1 -- or seven times the risk -- compared with the general population of women of the same age; your relative risk of developing cancer of the ovaries if you've accumulated 10 years on the oral contraceptive pill is 1:5, 0.2 or 20.

The use of somatic cell nuclear transfer or embryo splitting to secure pregnancy and a new individual intended to be virtually genetically identical to the person who donated the cell nucleus used or genetically identical to siblings resulting from embryo splitting (which in effect is the intentional creation of identical twins, or triplets etc.). Practiced in animals, especially farm animals. Considered ethically abhorrent because of strong ethical arguments within the fields of deontological ethics (including a duty not to intentionally violate the biological principle of sexual reproduction involving genetic reassortment and individual difference), teleological ethics (including the very high risk of severe birth defects with SCNT) and utilitarian ethics (where arguments are based on considerations by and for society generally).

The form of the sperm cell in the second stage of spermatogenesis (through which the sperm cells are formed in the testes), produced from primary spermatocytes in the first cell division of meiosis, and giving rise to spermatids, which have just half the normal cell's complement of chromosomes, through the second division of meiosis; enveloped by Sertoli cells in the testicular tubules.

Estimation of sperm antibodies circulating in the blood. Generally not as useful as estimating semen sperm antibodies (for men) or cervical mucus sperm antibodies (for women), as these fluids have more immediate contact with sperm cells.

A general term used by obstetricians or pediatricians to refer to a fetus or newborn baby that seems smaller than it should be for the assumed duration of the pregnancy so far. The three main causes are a genetic abnormality of the fetus; insufficient nutrition for an otherwise normal fetus; and an incorrect calculation of the dates, maybe because ovulation and conception took place later than the usual two weeks after the last menstrual period. Recent research shows that women with infertility might be at higher risk of small-for-dates babies when they do get pregnant.

(SCNT) Transfer of the nucleus of a somatic cell into a secondary oocyte or zygote from which the egg or zygote's chromosomes have been removed, in such a way that cleavage still occurs, in effect causing the cell's nucleus to 'bud', or reproduce without genetic recombination, and hence a form of asexual reproduction or cloning now commonly used for reproductive cloning in animals and, it is hoped, for therapeutic cloning to create embryonic stem cells for treatment of serious degenerative disease and cancers.

The replicating phase of the sperm cell in the testis, equivalent to the oogonium in the ovaries, but, unlike the oogonia, spermatogonia normally persist until old age. Located among the supporting cells (Sertoli cells) in the testicular tubules. Divides by the process of mitosis until it begins to undergo meiosis by changing into the primary spermatocyte, the first step in the process of sperm cell formation, or spermatogenesis. Plural: spermatogonia.

A fibroid (or myoma) that grows from the outside surface of the uterus, into the cavity of the abdomen, or peritoneal cavity. The least likely of any sort of fibroid to affect reproduction, but can cause symptoms of pressure or pain should it twist or degenerate suddenly.

(TFTs) Usually two tests: a serum thyroxine (low for underactivity, high for overactivity) and a serum thyroid stimulating hormone (TSH, high for underactivity based primarily in the thyroid gland, low for overactivity based primarily in the thyroid gland and low for underactivity based in the pituitary gland). As a screening test for malfunction of the thyroid gland a serum TSH will generally be enough.

Surrogacy in which the woman who is the surrogate for the intended pregnancy provides the eggs (through her own ovulation); is impregnated by assisted insemination; carries (or 'gestates') the pregnancy; gives birth; and then gives up the baby to the person who commissioned the surrogacy arrangement. Also known as genetic-plus-gestational surrogacy. The surrogate is as much the biological mother of the child as if she had conceived in natural circumstances, except that the male by whom she has been impregnated has no prior social relationship with her. No countries other than the US, where commercial surrogacy can be legal, have encouraged the practice, whether for altruistic or commercial reasons.

The combination of primary ovarian failure with constitutional (that is, genetically determined) shortness; often with other clinical abnormalities, including 'webbing' of the neck; an increased 'carrying angle' at the elbow; short fourth metatarsal (feet) and metacarpal (hand) bones (the bone within the hand that leads to the ring finger), and sometimes abnormalities of the heart and the thyroid gland. Associated with a karyotype that is 45,X (a monosomy, with one sex chromosome missing) or with partial loss ('deletion') of one of a pair of X-chromosomes. The single X-chromosome present can come from the mother or the father -- and, interestingly, it behaves differently: if it comes from the mother the girl is likely to be rather socially disruptive (the way little boys typically are), whereas if the X-chromosome comes from the father her behavior tends to be closer to normal for that of a girl!

Generic name for FSH derived from the urine of menopausal women sources. FSH of recombinant (synthetic) origin is called follitropin.

(VEGF) A growth factor (or local hormone) needed for new blood vessels to form in, for example, the corpus luteum, as it turns into an efficient hormone-producing gland making and releasing progesterone about a week after ovulation. Because such new blood vessels are rather leaky, excess VEGF from multiple corpora lutea during ovulation induction or superovulation using gonadotropins can be associated with new blood vessels trying to form in the general peritoneal cavity, leakage of fluid from which causes fluid to build up in the abdomen, a potentially dangerous condition known as the ovarian hyperstimulation syndrome. VEGF is also important in the formation of the placenta, so mutations of VEGF or its target proteins can cause recurrent miscarriage.

Vasectomy reversal, the operation for reversing a sterilisation operation (a vasectomy) in a man involving removal of the blocked part of each vas deferens, in the upper part of the scrotum, and joining by microsurgery one cut end or the vas to the other cut end. Generally not as successful at returning fertility as the equivalent operation in women (tubal anastomosis): the development of sperm antibodies increases with the length of time since sterilisation and limits the effective sperm count after the reversal. Many clinics now carry out cryostorage of some sperm obtained at vasectomy reversal so that if pregnancy does not happen, or azoospermia persists, in vitro fertilisation (IVF) can be carried out with ICSI without requiring a later operation (for MESA) on the man. MESA with ICSI and IVF can be used as an alternative to vasovasostomy.