The establishment of a pregnancy depends upon mechanisms of forming close contacts between embryonic/fetal and maternal tissues. The starting point is the attachment of the blastocyst to the uterine wall, and this critical step is followed by a series of different morphogenetic events leading to placentation. These processes depend on the invasive properties of extra-embryonic trophectoderm-derived cells that show their highest expression in species with haemochorial placentation, i.e. Insectivores, rodents, and primates including the human. In this review we will concentrate upon the human with occasional reference to other species.

Inhibin is a glycoprotein hormone, consisting of two dissimilar, disulphide-linked subunits, termed α (MW 20kD) and β (MW 3-15kD), which inhibits the production and/or secretion of pituitary gonadotrophins, preferentially follicle stimulating hormone (FSH). The most widely studied inhibin molecule has a molecular weight of 31-32kD, as purified and cloned from bovine, porcine, ovine, rat and human sources. Higher molecular weight forms have been identified in ovarian follicular fluids and in culture media of granulosa and Sertoli cells, and generally differ from the 31kD form in having larger α-subunits, designated by their molecular weights, e.g. α44 in 58kD inhibin. There are two forms of the β-subunit, named βA and βB and the corresponding inhibin dimers have been named inhibin A and inhibin B. Dimers of the β-subunit, which have been shown to have FSH stimulating activity, are termed activins and are designated activin A, B or AB depending on whether the dimer is a homodimer of βA or βB or a heterodimer of βA and βB (Figure 1). The major gonadal source of inhibin is the granulosa cell in the female and the Sertoli cell in the male. Other potential cellular sites of origin will be discussed below.

Research methods and knowledge in the field of male reproductive toxicology have gradually improved since reports in the late 1970s on severe impairment of spermatogenesis in workers with occupational exposure to certain chlorinated hydrocarbon pesticides (the nematocide 1,2-dibromochloropropan and the insecticide and fungicide chlordecone, but still we have only vague answers to basic questions about the overall significance of the environmental and occupational impact of these compounds on male reproductive capability.

Follicle stimulating hormone (FSH) is a glycoprotein hormone secreted by the pituitary gland that, together with luteinizing hormone (LH), controls development, maturation and function of the gonad. Like the related hormones, LH, thyroid stimulating hormone (TSH) and human chorionic gonadotropin (hCG), FSH consists of two polypeptide chains, α and β, bearing carbohydrate moieties N-linked to asparagine (Asn) residues. The α subunit is common to all members of the glycoprotein hormone family, whereas the β subunit, although structurally very similar, differs in each hormone and confers specificity of action.

It is 130 years since the first description of endometriosis and yet this enigmatic disease still continues to confound gynaecologists. In the last five years there has been evidence which suggests that endometriosis is a much more common finding in the pelvis than previously recognized and this has created conflict over the precise definition of the disease. Currently it is difficult for clinicians to be certain what constitutes endometriosis and what is the clinical and pathological significance of the visual diagnosis of the disease. This article will review the evidence about the pathological significance of the visual diagnosis of endometriosis. It will analyze the aetiological factors that predispose to the disease and evidence concerning its pathogenesis. Finally, it will discuss the evidence that points to a particular epithelium being the origin of endometriosis.

Fully mature oocytes are the rarest cells in the body. A premenopausal woman produces only one during each menstrual cycle and that survives for just a single day. Ovarian productivity is parsimonious in order that the ovulation rate matches the optimal capacity of the uterus for carrying conceptuses to full-term. But, in this new era of assisted reproductive medicine, there are many applications for which spare oocytes are needed (Table 1), and it is desirable to obtain more cells than are routinely available during superstimulated cycles. Since the great majority of ovarian oocytes undergo atresia (> 99.9%), the possibility of tapping the store of immature oocytes before they degenerate and maturing them in vitro is very attractive.

The architecture of the human endometrium is extensively remodelled during the course of each normal menstrual cycle, unlike most other tissues and organs which undergo very little change during adult life. During menstruation, when loss of most of the functionalis layer occurs, there is concomitant epithelial regrowth; repair of the luminal surface is complete almost as bleeding ceases. During the proliferative phase of the cycle and under the influence of rising oestrogen levels, the stromal cells, glands and blood vessels undergo rapid proliferation which results in tissue thickening. Following ovulation (around day 14 of the idealized 28-day cycle), the secretory phase of the cycle is characterized by increasing tortuosity of the spiral arterioles and glands and increased glandular secretory activity. After about day 22, decidualization of many of the stromal fibroblasts also occurs, the resultant decidual cells having many characteristics typical of epithelial cells. Periods of tissue oedema are apparent both in mid-proliferative (days 8–11) and mid-secretory (days 20–23) endometrium. Late in the cycle, there is regression of the tissue as menstruation is initiated.

Several conclusions can be drawn from a review of the formation, function and regression of the corpus luteum. Ovulation and luteinization encompass degenerative and growth changes. Inflammatory conditions associated with ovulation lead to the breakdown of the follicle wall and the membrana granulosa, along with initial damage to theca and granulosa cells. The early corpus luteum is, therefore, a tissue in stress. Thus, one view of the corpus luteum is that it, like the phoenix, rises from the inflammatory ashes of the postovulatory follicle to exist briefly and to be consumed by a similar process at regression. The luteinization process is associated with parenchymal cell hypertrophy and matrix remodelling, which appear to be regulated by IGFs and androgens, and with angiogenesis, which is induced mostly by bFGF. High levels of functional activity of the corpus luteum are regulated by control at the level of the LH receptor, whose activation leads to the translocation of cholesterol into the cell and mitochondria for conversion to steroids. Functional luteal regression can be considered as another inflammatory-like condition with apparent activation of the immune system, along with cytokine, reactive oxygen, and eicosanoid production. Structural luteolysis is subsequently invoked that leads to matrix dissolution and cellular degeneration. It is perhaps not surprising that the invocation of immune activation, which causes the production of DNA-damaging reactive oxygen species and cytotoxic cytokines each cycle, may increase the risk of pathologies. One example may be ovarian cancer which appears to be associated with the use of fertility-enhancing drugs and associated with the number of ovulations in a woman's lifetime.

It is a fundamental principle of laboratory tests that they are never entirely free from error. However, understanding the source and extent of such errors is a prerequisite for correct appreciation and interpretation of test results in the diagnostic process. In order to evaluate these errors, quality control (QC) has been introduced into clinical laboratory tests and has become routine practice.

Uterine growth factors appear to play a role in the regulation of pregnancy. One of these, colony stimulating factor-1 (CSF-1), synthesized by the uterine epithelium under the control of female sex steroids, has been shown to have important functions both before implantation and during the formation of the placenta. In the female reproductive tract the CSF-1 receptor, the product of the c-fms proto-oncogene, is expressed in decidual cells, trophoblasts and macrophages, indicating that these cells are the primary targets for CSF-1. This article reviews the biology of CSF-1 during gestation as well as the possible involvement of CSF-1 and its receptor in the aetiology of gynaecological tumours.

Fertilization and early embryo development take place in the oviduct in vivo. Relative to studies in other reproductive organs, the importance of the oviduct has been ignored for many years because pregnancies can be obtained in assisted reproduction treatment using in-vitro fertilization (IVF) and embryo transfer to the uterus without involving the Fallopian tube. After the reports on the beneficial effect of oviductal cells on embryo development in sheep and subsequently in human, and a practical need to improve the success rates in clinical assisted reproduction, there was a period when more research was performed on the Fallopian tube. Many of these studies used in vitro coculture systems to emulate the in vivo environment in vitro, and to search for oviduct-derived embryotrophic factors. With the recent development of sequential culture to improve embryo development in vitro, the use of coculture in assisted reproduction and its related research declined because routine use of coculture is laborious and experience-dependent.

Over the last fifty years the understanding of a number of symptomatic gynaecological conditions has crystallized to the point where a coherent framework of pathogenesis and a systematic approach to treatment can be discerned. Examples are endometriosis, menorrhagia, premenstrual syndrome and the symptoms associated with the climacteric. Chronic pelvic pain is only now reaching the stage of similar systematization, and it is interesting to speculate why this has taken so long. Two factors can perhaps be cited as relevant: in the conditions listed above, either reasonably plausible models for causation based on visible pathology have been available, as with endometriosis, or effective treatments have been readily available, for example hormone replacement therapy (HRT) for estrogen deficiency symptoms. In the case of pelvic pain, models of causation have often been speculative rather than based on research, and simple effective treatments have proved elusive. In this review current concepts of pain physiology and therapy are discussed with a view to placing in perspective the clinical problem of pelvic pain. The condition is best seen from a bio-psycho-social perspective but the main focus of the present review is the neurobiological aspect.

The first site of contact between maternal and fetal tissue at the beginning of blastocyst attachment and implantation is the plasma membrane of uterine epithelial cells. Indeed, as has been noted often, regardless of the mode of placentation which ultimately occurs, contact between this plasma membrane and that of the trophoblast is a common beginning to implantation in most species studied so far, which now range from viviparous lizards to human beings. The similarities in these early events of uterine receptivity and placentation go further than mere contact between opposing surfaces however. A considerable body of evidence indicates that the behaviour of the plasma membrane of uterine epithelial cells during early pregnancy has many common aspects across species including humans. This review pays special attention to events in the human uterus and the epithelial cells in particular, but examines them within the wider context of uterine receptivity for implantation across species.

Spermatozoa binding to the zona pellucida is an early, critical event leading to fertilization and early pre-embryo development. Fertilization involves a complex and orderly sequence of events that is completed at syngamy, which is defined as the union of the two sets of haploid chromosomes to form a new diploid fertilized ovum (zygote). In order to be able to fertilize an oocyte, spermatozoa need to undergo a process called ‘capacitation’, which is usually defined as a series of changes that renders the sperm cells capable of undergoing the acrosome reaction. This process that naturally occurs within the female genital tract is possible under in vitro conditions. However, capacitation is not the only process spermatozoa must undergo to fertilize the oocytes successfully. To fertilize an oocyte, spermatozoa must also be at least highly motile, as well as being capable of undergoing the acrosome reaction timely, penetrating through the oocyte investments and fusing with the oocyte plasma membrane properly.

Tubal factors are estimated to account for 15–20 per cent of infertility. The incidence not only depends on the patient population but is probably also underestimated since evaluation of tubai function is largely restricted to the appraisal of its patency. Consequently the treatment of tubai infertility is primarily focused on the restoration of tubai patency. That infertility frequently persists in spite of successfully restored patency and that tubal pregnancy frequently occurs after infertility surgery suggest that underlying disease has not been diagnosed.

Before sexual differentiation occurs at seven weeks, the urological ridges develop in the embryo. These contain the primitive gonads, the mesonephros (embryonic kidneys) and the paired Wolffian (mesonephric) ducts, along with the Müllerian (paramesonephric) ducts. The fundamental mechanism of fetal sexual development was elucidated by Alfred Jost and is determined by the development of the gonad: where testes form in response to the testis-determining gene, and the male testicular hormones cause development of the male phenotype. If ovaries develop or the gonads are absent, female secondary sex characteristics are produced. Recently, the cloning of the putative human testis-determining gene on the Y-chromosome was reported. Assuming this is the true controller of testicular development, an understanding of the initiation of sexual differentiation at the genetic level should emerge in the near future. Of great importance will be the isolation of the testis-determining gene product and identification of other genes that it regulates.

Epidemiological studies relating cigarette smoking to the ability to conceive and maintain a pregnancy provide information on the clinical significance of smoking on reproductive health. Cigarette smoking by females has significantly increased in the decades after World War II, and now has an average initiation at ages 18–20 years. Maternal smoking is a hazard to the general health, the reproductive health and the life of both mother and child. Gestational smoking renders the fetus a passive smoker. This can result in fetal and neonatal death and in reduced fecundity of adult daughters.

Over the past four years, major advances in the understanding of the aetiology and pathogenesis of the androgen insensitivity syndrome (AIS) have occurred. This review aims to summarize current information on clinical, diagnostic, therapeutic and molecular aspects of AIS.

Age is perhaps the most important single variable influencing outcome in the assisted reproductive technologies (ART). The effect of advancing age on clinical ART outcome is manifested not only in the pattern of ovarian response to stimulation regimens, but also in reduced implantation efficiency and an increased spontaneous abortion rate. The clinical importance of these factors is compounded by the fact that increasing numbers of older women are presenting for ART treatment. Delayed childbearing is becoming increasingly common in the western world. The availability of methods of birth control, educational and career priorities for women, and the increased rates of divorce and remarriage are some of the factors contributing to this phenomenon.

The endometrium expresses many of the same integrins displayed by other tissues. Endometrial epithelial cells maintain the ‘classic’ epithelial integrins, including α2, α3, α6, and β4, while the stroma expresses the fibronectin receptor, α5β1. During the menstrual cycle, the endometrium undergoes dynamic changes in morphology in preparation for implantation. With these histological changes are concomitant alterations in integrin expression that appear to ‘frame’ the window of implantation, by the co-expression of glandular αvβ3 and α4β1 during days 20 to 24 of the menstrual cycle. The changes in integrin expression shift from epithelial to stroma predominance late in the menstrual cycle, extending into early pregnancy. Decidual integrins that appear upregulated in pregnancy include α1β1, α3β1, α6β1 and αvβ3. Markers of uterine receptivity hold promise for a better understanding of the implantation process and may help to explain many different types of infertility. These markers will be essential for monitoring and improving infertility therapies. The importance of integrins in the human endometrium now seems well established and promises to be an area of great clinical and basic science activity in the future.