There have been a number of reviews on this topic over the past decade, starting with Carlsen et al. and including Irvine et al. and Murray et al., concerning declining male fertility. The most exhaustive has perhaps been that of Toppari et al. The main findings of these reviews are: (1) that in some countries of the world sperm production has halved in the last 60 years, (2) rates of testicular cancer have doubled, (3) rates of malformation of the male reproductive tract, such as hypospadias, have doubled, (4) rates of testicular maldescent have risen sharply and (5) these effects are largely linked geographically. Typically, endocrine disrupting chemicals (EDCs) in the environment have been regarded as the main candidates for these effects. A consistent problem with the field, however, is the difficulty in determining the accuracy of data relating to changes in men's health over the latter half of the 20th century. Advances in diagnosis and changing attitudes to the emotive issues surrounding deformity and male infertility inevitably render some of the mass of collected data suspect. Indeed a recent review of testicular and prostate cancer concluded that while the incidence of prostate cancer had increased, the epidemiological data were not suitable for concrete conclusions about causation to be drawn. However, in the case of testicular cancer the data suggested a limited number of major risk factors. In addition, assessing urogenital malformation retrospectively from patient notes is subject to considerable variation in classification. A recent review does however find evidence to suggest that trends of increasing incidences of hypospadias on a temporal and geographical basis may reflect an actual increase in incidence and require further study. On the other hand, there is a considerable body of evidence for EDC disruption of reproduction in wildlife (reviewed by Guillette & Gunderson, 2001).

Erectile dysfunction (formerly known as impotence) is defined as the consistent inability to achieve or maintain an erection suitable for intercourse. Until recently, most of the information on the prevalence of erectile dysfunction has been based on small studies of selected population samples. More reliable data became available with the completion of the Massachusetts Male Aging Study. Data from this study indicate that erectile dysfunction is a common condition with an estimated incidence rate of 26 cases per 1000 man-years. In 1993, the National Institutes of Health Consensus Conference estimated that 10 to 20 million men in the USA have problems with erection.

Ectopic pregnancy occurs when the conceptus implants outside the normal site within the uterine cavity. The most common site is within the Fallopian tube (98.3%), followed by abdominal (1.4%), ovarian (0.15%) and cervical (0.15%) implantation. Considering tubal ectopic pregnancies, 80% occur at the ampulla and 12% at the isthmus; 6% are fimbrial and 2% are interstitial. Approximately 5% to 5.7% of all clinical pregnancies from assisted reproductive technology (ART) in 1988–92 were ectopic; however, in 1995 the incidence was less at 2.8%. A meta-analysis of risk factors that predispose to ectopic pregnancy is depicted in Table 1. However, this meta-analysis does not control for the interplay of risk factors (multivariate analysis), including the impact of control group data and consequent problems of data collection (e.g. the incidence of pelvic inflammatory disease (PID) in the ectopic group is laparoscopically derived whereas it is derived from the history in the control group).

Male infertility, while having a variety of causes, is generally discussed in terms of semen parameters. While the World Health Organization (WHO) have been able io set limits for semen parameters below which a male can be considered subfertile (20 million/ml; >50% motility; >50% morphologically normal forms), it is well documented that in vivo conceptions have been achieved where semen quality falls well outside these limits, and that infertile men may have normal semen parameters. Macleod and Gold in comparing 1000 fertile men and 1000 infertile men, found that significantly more infertile men had sperm densities below 20 million/ml, but also that 60% of infertile men had sperm densities of 60 million or more. Jouannet and Feneaux have shown that the conception rate in vivo only apparently falls significantly at sperm concentrations of less than five million/ml. Although the cause of subnormal semen analysis is unknown in the majority of cases, there is no reason to suppose that abnormal semen parameters on their own are the cause of infertility. Rather the problem may be caused by failure of sufficient numbers of sperm traversing the female tract and reaching the oocyte. Unfortunately, lack of defined diagnoses lead to a lack of direct treatment for subnormal semen parameters. The development of in vitro fertilization (IVF) resulted in a method that could be used to circumvent the problem since it requires relatively low numbers of sperm and these are placed in the immediate vicinity of the oocyte. It should also be pointed out that normal semen parameters do not imply fertility, since these parameters cannot directly identify dysfunction. IVF offers the advantage that sperm-oocyte interractions can be observed, and in cases of fertilization failure, the point at which sperm dysfunction manifests itself may potentially be identified – if not the nature of the dysfunction. Techniques have now been developed that may overcome certain types of dysfunction, using both biochemical and mechanical means.

The insulin-like growth factors IGF-I and -II have effects on metabolism, growth, proliferation and differentiation in many tissues and cell types and are therefore important modulators of multiple aspects of physiology. IGF actions are largely mediated via the type 1 IGF receptor, though both peptides, particularly IGF-II, can bind to a second receptor known as the type 2 IGF/mannose-6-phosphate receptor. Access to these receptors is controlled by a family of six highly specific binding proteins (IGFBPs 1–6). Originally, the IGFBPs were thought of as IGF inhibitors, since their affinity for ligand is substantially higher than that of the receptors. More recently however, it has become apparent that modification of the binding proteins, for example proteolyis, phosphorylation or association with extracellular matrix, can influence IGFBP affinity for IGF and therefore IGF bioavailability and function.

It is estimated that as many as 10% of couples worldwide suffer from infertility or reduced fertility, and that in approximately half of these cases this results from defective spermatogenesis. In 60% of these infertile men, the failure to produce mature germ cells (i.e. azoospermia) or the formation of low numbers of sperm (i.e. oligozoospermia) can be ascribed a genetic aetiology. Few of the loci associated with male infertility have been mapped in humans; however, several genetic models of defective germ-cell development and differentiation have been described in mice. The schematic in Figure 1 summarizes the main features of spermatogenesis in humans.

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.