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.

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.

The treatment of male infertility by the utilization of donor insemination goes back many decades. Initially, fresh semen was used, usually brokered by a medical practitioner, the donors delivering the sperm as the recipient was about to ovulate, with the insemination being carried out by the doctor. There was no screening of the semen specimen, nor any attempt at matching for physical characteristics.

It is estimated that 50–80% of menstruating women experience some degree of physical and psychological premenstrual symptomatology and that 3–5% have symptoms of sufficient severity to disrupt social or psychological functioning. The diagnosis of clinically significant premenstrual syndrome (PMS) is applicable when at least one moderate to severe physical and psychological symptom occurs for up to two weeks prior to menses with remission by the end of the menstrual flow. Symptoms should cause functional impairment and must be documented prospectively for at least two consecutive menstrual cycles. Table 1 lists the American College of Obstetrics and Gynecology (ACOG) criteria set for the diagnosis of PMS.

According to Webster's Universal College Dictionary (Random House, 1997), normal means “conforming to the standard or the common type; usual regular, natural; free of any mental disorder; sane; free from disease or malformation”. On the basis of these various definitions, the answer to the question posed in the title of this review should be an unequivocal “no”. Incessant menstruation for years on end as it occurs today is certainly not natural, nor is it free of any mental disorder or free from disease. In fact, it conforms to no standard and it may cause serious dysphoric disorders and several diseases, of which anaemia and endometriosis are outstanding examples.