Ovarian folliculogenesis is an exponential process marked by dramatic proliferation and differentiation of the somatic and germ cell elements of the follicle. Although the central roles of gonadotropins and of gonadal steroids in this explosive agenda are well accepted, the variable fate of follicles afforded comparable gonadotropic stimulation suggests the existence of additional intraovarian modulatory systems. Accordingly, consideration must be given to another set (or sets) of regulatory principles that may provide these missing modulatory loops. The work of multiple contributors favors the hypothesis that these modulatory loops are comprised of a host of peptidergic principles which engage in situ in the modulation of ovarian growth and function. In its capacity as an intraovarian regulator, a given agent may be acting independently of, as an amplifier of, as an attenuator of, or even as a mediator of, gonadotropin action. Together, gonadotropins, steroids, and locally derived peptidergic principles form a triad that modulates the growth and differentiation of ovarian follicles (Figure 1).

It has been clearly demonstrated that GnRHa is a powerful suppressant of ovarian steroidogenesis and, as a result, provides alternative strategies in dealing with certain gynaecological disorders. A concern for the deleterious effects of oestrogen deprivation is underscored by the potential long-term application of these compounds. Available studies indicate that concomitant HRT, whether physiological or pharmacological, may be utilized with good results. However, there is a great need to further explore the benefit and risks of supplementation therapy.

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.

Ovulation is the result of an integrated action of the hypothalamus, pituitary and ovaries. During the process, gonadal steroids, peptides and growth factors are produced and influence the synthesis and release of gonadotropin-releasing hormone (GnRH), follicle stimulating hormone (FSH) and luteinizing hormone (LH). These latter compounds play a crucial role in folliculogenesis and are frequently used in the management of infertility.

The present review demonstrates that the availability of bioactive FSH and LH in PCOS is normal and that granulosa cells of PCO are not apoptotic and instead hyperexpress functional FSH receptors and may possess intact aromatase activity. Consequently, these cells respond excessively to exogenous FSH stimulation and produce high amounts of oestradiol both in vivo and in vitro. The altered developmental capacity of follicles from PCO in vivo is most likely due to the abnormal follicular milieu of PCO and the culminating effects of intrafollicular inhibitors and stimulators. The failure of ovarian oestradiol production and follicular maturation to dominance in vivo may be due to a mechanism that interferes with the function of FSH, such as intraovarian steroids and growth factors. It has previously been shown that EGF and TGFα have inhibitory actions on follicular development, aromatization and LH receptor formation. In contrast, EGF enhances early follicular recruitment and growth. Therefore, it is hypothesized that EGF/TGFα may have a causal relationship in the mechanisms of anovulatory infertility in women with PCOS. Thus, an aberration in the regulation of follicular fluid EGF and/or TGFα may result in reduced numbers of granulosa cells, cessation of follicle selection and ultimately in the creation and maintenance of PCOS. The exact mechanism by which the hyperfunction of EGF/TGFα occurs and the trigger for this hyperactivity in the ovary remain to be determined. An experimental animal model may be required to assist such investigations in the future.

Whereas the direct action of sex steroids, namely of androgens, on prostate cell division was questioned as early as in the 1970s, and remains so, the interest in prostatic growth factors (GFs) is rather recent but has expanded tremendously in the last five years. This lag period can be partly explained by the fact that, at the time, androgen receptors had just been discovered, and newly developed hormonal regimens or strategies to treat patients with prostate carcinoma (PCa) or epithelioma had generated great enthusiasm and hopes in the medical and scientific community. Another point to consider was the difficulty in maintaining prostate tissues in organ cultures and the relative novelty of culturing prostate epithelial cells in monolayers. Failures of sex steroids to elicit a direct positive response on prostate cell division in vitro, as seen in vivo, were interpreted as resulting from inappropriate models or culture conditions. However, the increasing number of reports confirming the lack of mitogenic activity of sex steroids in vitro, coupled with the powerful mitogenic activity of GFs displayed in other systems, the discovery of GF receptors (GF-Rs), and the elucidation of their signalling pathways showing sex steroid receptors as potential substrates of GF-activated protein kinases gradually led to an increased interest in the putative role of GFs in prostate physiopathology. Of utmost importance was the recognition that hormone refractiveness was responsible for PCa progression, and for the poor outcome of patients with advanced disease under endocrine therapies. This problem remains a major issue and it raises several key questions that need to be solved at the fundamental and clinical levels.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication induced by exogenous administration of substances that are used to stimulate follicular growth and ovulation. There has only been one reported incidence of a spontaneous occurrence of OHSS and that was in 1992. The crucial event in the development of the syndrome is the administration of human chorionic gonadotropin (HCG), although several studies have reported the onset of OHSS after gonadotropin stimulation despite withholding HCG. OHSS is represented by a broad spectrum of clinical and laboratory manifestations which, in the severest form, can induce a life-threatening condition.

There has been an increase in the incidence of ectopic pregnancy to epidemic proportions in many developed countries in the past two decades. In 1989, ectopic pregnancy accounted for 1.6% of all pregnancies in the United States of America. This trend may be explained by an increase in the incidence of established risk factors as well as a dramatic improvement in diagnostic tools and advances in reproductive technology. Technologic advances such as highly sensitive radioimmunoassays for the β-subunit of human chorionic gonadotropin (βhCG), the development of high-resolution ultrasound and a heightened physician awareness have revolutionized the clinical management of ectopic pregnancy, leading to earlier and more consistent diagnoses and consequently reduced maternal mortality rates. 1,3–13 Unfortunately, ectopic pregnancy is still associated with a significant morbidity and mortality and contributes substantially to health-care costs. For example ectopic pregnancy complications accounted for 13% of all pregnancy-related deaths and were the leading cause of maternal mortality in African- American women in 1989. Financially, an estimated 1.1 billion dollars was spent in the United States of America alone for the management of ectopic pregnancy in 1990.

The formation of adhesions is a significant clinical problem. Complications like bowel obstruction and chronic pelvic pain are known to be related to adhesion formation. Besides these complications, adhesions do play an additional role in the gynaecological patient. Interference with the functioning of the fallopian tubes and ovaries disturbs ovum pickup and sperm transport and may compromise the fertility of patients.

The first attempts at in vitro fertilization (IVF) of human oocytes were performed during cycles utilizing human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). These early cycles resulted in a successful conception, which unfortunately ended as a tubal gestation. The birth of Louise Brown in 1978, the first successful IVF birth, was actually achieved following fertilization during a spontaneous cycle in which ovulation was triggered with endogenous luteinizing hormone (LH).However, due to the greater margin for error afforded by larger numbers of follicles, the practice of IVF rapidly evolved towards the use of controlled ovarian hyperstimulation (COH) to achieve higher pregnancy rates. It is easy to understand why this approach evolved. Oocyte harvesting was accomplished primarily by laparoscopy. Since oocyte yield per follicle was less than 100% and fertilization rates were limited, the relatively traumatic follicle aspiration process was more likely to result in embryo transfer if a greater number of follicles was present.

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.

A brief look at the history of cytokine research shows that the term ‘lymphokine’ was first described in 1969 as the product of sensitized lymphocytes exposed to specific antigens. To eliminate the incorrect notion that such proteins can be produced only by lymphocytes, Cohen et al. (1974) proposed the term ‘cytokines’ to indicate their production also by nonlymphoid cells.2 After a long-persisting reluctance, it seems that ‘cytokine’ is becoming the prevalent term for these proteins. Meanwhile, a group of participants at the Second International Lymphokine Workshop held in 1979 proposed the term ‘interleukin’ in order to develop, ‘a system of nomenclature based on the protein's ability to act as communication signals between different populations of leukocytes’.3 They introduced the names IL-I and IL-2 for two important cytokines. Since then the number of described interleukins reached 16 and this number may increase. Furthermore, notwithstanding this previous notion, interleukins are now known to be produced in a variety of tissues other than leucocytes and affect the functions of many and diverse somatic cell types (e.g. IL-1 or IL-6). Therefore, while many cytokines are now termed as interleukins, others continue to be known by their old names [e.g. tumour necrosis factor-alpha (TNF-α)], suggesting that they had been recognized earlier, but all of them are included under the generic name of cytokines.