Male infertility is a frequent cause of childlessness, and, indeed, a comparison of the contributions to conception failure made by male and female factors shows them to be equally frequent. In practice, male infertility appears to be resistant to most treatments. However, the major reason for this may be that often attempts are carried out without knowing the cause of the problem. Unlike in women, obstructions and hormonal disorders are rare in male infertility. Rather, it would appear that sperm disorders are the most common cause, reflecting a variety of pathogenetic mechanisms. Defects in sperm morphology, defective sperm movement, deficient development or functional failure of the acrosome, and the excessive generation of reactive oxygen species are changes that are often seen in infertile semen, but little is known about their aetiology. In 5–10% of men being treated for infertilty, an autoimmune reaction against spermatozoa is observed. Although the correlation between the presence of systemic antisperm antibodies and fertility potential is poor, the appearance of sperm-bound antibodies of immunoglobulin class IgA in semen seems to be closely associated with infertility. Studies in laboratory animals and humans have shown that complementary adhesion molecules are located on the surface of oocytes and spermatozoa. These molecules interact and lead to gamete fusion. Abnormalities in these molecules on the sperm surface might be expected to contribute to male infertility. However, their clinical significance has not yet been documented, and the molecular basis of human gamete interaction is far from being understood. Therefore, the key to understanding male infertility may lie in basic research which directly targets the fundamental cellular and molecular biology of the human spermatozoon.

Mammalian fertilization, whether it takes place within the female reproductive tract or within a laboratory dish, is comprised of many processes which must follow a specific sequence. The spermatozoon must bind to and pass through the zona pellucida, fuse with the oolemma and become incorporated into the cytoplasm of the oocyte. Fusion of the two gametes triggers oocyte activation, resulting in exocytosis of the cortical granules and completion of the second meiotic division of the oocyte. A block in one or more of these processes, due either to abnormalities in the spermatozoon or oocyte, may result in fertilization failure.

Amongst men who attend fertility problems clinics, just over 10% are diagnosed to be oligospermic (< 5 × 106 sperm per ml) or azoospermic, with no known aetiological explanation. Amongst the many possible causes of impaired sperm production there is a genetic component, a pointer to the possible location of some of the responsible genes being found in 1976 when Tiepolo and Zuffardi discovered six azoospermic individuals with a deleted Y chromosome. In each individual, the long arm of the Y chromosome had lost its distal fluorescent segment as well as part of the nonfluorescent euchromatin lying proximal to it (Figure 1). They hypothesized that factors important in spermatogenesis might lie at the interface between fluorescent and nonfluorescent material. The locus, AZFor ‘azoospermia factor’, was subsequently mapped, using collections of deleted Y chromosomes, to interval six of the long arm and it lies within cytological band Yq11.23 (Figure 2).

Consideration of the function of the epididymis has undergone profound changes over the last century during which it has moved from a largely neglected male reproductive organ to one that is an increasingly exploited source of sperm for assisted reproduction strategies. From histological studies in the lizard1 it was considered that, ‘…the cells lining the epididymal canal produce a material necessary for the spermatozoa during their passage through the organ …’ whereas a fertility study with guinea-pigs stated boldly that, ‘… changes undergone [by spermatozoa in the epididymis] are not conditioned by some specific action of epididymal secretion …’. The former view found favour in a review of the literature which concluded that, ‘… there are specific epididymal secretions necessary for sperm maturation and survival …’, although the nature of the secretions were not then known. However, this concept, currently held by most of those studying the epididymis of animals, was again contradicted on the basis of clinical work: ‘… it certainly is possible for sperm that have never passed through any length of the epididymis at all to mature on their own …’.

Experimental animal models have shown that the in vitro embryo culture involved in many treatments for infertility results in a dramatic reduction in embryo viability. Recent advances in methodology such as RT-PCR for localization and quantitation of cytokines and their receptors, are revealing the role that this group of growth factors plays in the basic physiology of embryo development and the process of implantation itself. These studies offer the likelihood of dramatically improving in vitro embryo culture in humans and other species by supplementation of culture medium with growth factors or antagonists to improve embryo viability and hence implantation rates.

Of all the assisted reproductive technologies in current use, artificial insemination has by far the longest history. While the earliest verifiable reports using this technique date to the eighteenth century for nonhuman artificial insemination and to the nineteenth century for human artificial insemination, systematic use of this approach to assist reproduction did not occur until the early part of this century. During the early 1900s, in Russia, Ivanov developed methods for semen collection from and insemination of horses. These techniques were later modified to apply to other agriculturally important species so that by the 1930s, millions of horses, cattle and sheep were being bred using artificial insemination. The adaptation of widespread use of artificial insemination (primarily in cattle) in agriculture extended to Britain in the early 1940s and to the USA in the 1950s. Corresponding implementation of artificial insemination in human reproductive medicine closely followed these innovations in the animal husbandry field.

With hysteroscopic surgery, specific endoscopic approaches can be applied in selected cases avoiding the need for classical open surgery or even hysterectomy. The development of these surgical procedures has resulted in an increasing interest in the use of diagnostic hysteroscopy in order to identify that intrauterine pathology which is suitable for endoscopic treatment.

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.

In an effort to summarize the potential risks of therapeutic insemination by donor (TID), including a review of cases of disease attributed to donor semen, a MEDLINE literature search was conducted to identify all published case reports of transmissible diseases occurring in donor semen recipients published in English between 1975 and 1992. The reference list for each article was reviewed to locate additional published case reports. Pertinent case reports were compiled according to disease agent and classified into viral, bacterial and other categories.

Oral contraceptives remain the most widely used form of contraception in North America and Europe today. In spite of the concerns of many women relating to the potential risks of these preparations, recent data have demonstrated that currently available oral contraceptives are safe, with no increased risk of cardiovascular disease or cancer in nonsmoking women. The present review will focus on the impact of oral contraceptive use in the older woman, including a discussion of the noncontraceptive health benefits of oral contraceptives.

Late-onset or nonclassic hyperandrogenic congenital adrenal hyperplasia (CAH) is an attenuated deficiency of 21-hydroxylase, 3β-ol-hydroxysteroid dehydrogenase or 11β-hydroxylase which presents during childhood or adolescence and leads to an increased secretion of adrenal androgens. Many reviews of the genetic or hormonal characteristics of these syndromes have been published, but relatively little attention has been paid to the pathogenesis and treatment of hirsutism which, in most young women, is the main complaint. In fact, it is generally assumed that the hirsutism is strictly related to the increased secretion of adrenal androgens and that glucocorticoids are the treatment of choice. However, some recent studies have shown that the ovary contributes to the hyperandrogenism of these patients and some alternative therapies have been proposed. This forms the matter of the present review.

The ability to bypass the oviduct by fertilizing human oocytes in vitro and then transferring the ensuing embryos into the uterine environment to produce pregnancies that can be carried to term (assisted reproductive technology, ART) has made the real functional significance of the fallopian tube come under debate. The question has been raised as to whether the oviduct is a simple conduit, providing for the transport of gametes and embryos, or whether it has any functional relevance to early conception. In the field of ART, some reports claim that transfer of embryos either to the uterus or to the oviduct yield similar results, while a greater amount of evidence confirms that tubal transfers are associated with higher pregnancy and take home baby rates, suggesting that unknown factors in the oviduct favour fertilization and embryo viability. This review attempts to provide some answers to questions about the role of oviductal cells in vivo during early conception and in vitro in the field of ART.

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.

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.

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.