Bailliere's clinical obstetrics and gynaecology最新文献

High tonic serum concentrations of luteinizing hormone (LH) in the follicular phase, frequently witnessed in polycystic ovary syndrome, have been associated with decreased reproductive function. Impaired rates of fertilization, conception and miscarriage are obtained when LH levels are high before oocytes are collected, during ovulation induction or in women with regular cycles. Conversely, treatment that decreases LH concentrations, such as gonadotrophin-releasing hormone analogue or laparoscopic ovarian puncture, eases induction of ovulation and pregnancy and improves miscarriage rates. Tonic hypersecretion of LH appears to induce premature oocyte maturation, causing the problems with fertilization and miscarriage.

The objective of this chapter is to review the role of surgical management of polycystic ovarian syndrome in infertile women. Pertinent studies and their references were identified through computer medline search. To date there is no standardization of the technique of laparoscopic ovarian drilling. However, it appears that the results are promising, with a high ovulation rate ranging between 70% and 90% and a pregnancy rate of 70%. Clomiphene citrate remains the first line of treatment to induce ovulation in infertile women with polycystic ovarian syndrome. Laparoscopic ovarian drilling can be offered to clomiphene-resistant women, especially to those who have also failed to respond to gonadotrophin treatment or who have experienced ovarian hyperstimulation syndrome. It appears that the pregnancy rate after ovarian drilling is comparable with that for gonadotrophin therapy. However, until more complete and long-term data are available, caution must be exercised when offering this type of treatment.

The rationale of ovulation induction is to achieve the development of a single follicle and ultimately a singleton healthy baby. Problems faced by women with anovulatory polycystic ovary syndrome are the sensitivity of the ovary to stimulation and health issues such as obesity. This chapter will discuss medical management including strategies to lose weight, address hyperinsulinaemia with insulin-sensitizing agents, such as metformin, and outline methods of ovulation induction from the usual first-line therapy of clomiphene citrate and the subsequent use of gonadotrophin therapy in clomiphene-resistant patients. Appropriately directed surgical ovulation induction with laparoscopic ovarian diathermy appears to be as efficacious as gonadotrophin therapy but will not be discussed in the context of this chapter.

Numerous case-control, cohort studies, case reports and reviews have been published during the last 5 years regarding the association between infertility and induction of ovulation and epithelial ovarian cancer. Despite this amount of published material, final conclusions regarding direct linkage between these different aspects of infertility and ovarian cancer, as well as any data relating to a putative pathogenetic mechanism, cannot be drawn. In this review we summarize the available data as well as update a previous review by Shoham published in 1994. We outline some of the information that has become available from basic research which may help to direct investigators to suitable clinical research models that may eventually serve to clarify this enigma. Finally we share ideas that focus on specific high-risk cohorts.

Luteinizing hormone releasing hormone (LHRH) agonists have been used in conjunction with gonadotrophins, and occasionally with pulsatile LHRH, for ovulation induction in women with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS) and also for superovulation for in vitro fertilization (IVF) and gamete intrafallopian transfer in women with PCOS. In IVF, LHRH agonists given by the ‘long protocol’ before gonadotrophins are commenced have consistently shown higher pregnancy rates and higher live birth rates. Although the optimal time to commence LHRH agonist is not clearly determined, commencement in the early follicular phase possibly with pre-treatment with the combined oral contraceptive pill would avoid the risk of inadvertent administration during early pregnancy. The role of LHRH agonists in ovulation induction is less clear cut, although there may be some advantages in patients with refractory PCOS. The role of LHRH agonists in ovarian hyperstimulation syndrome and recurrent miscarriage is also discussed.

We review three complications of ovarian stimulation, namely ovarian hyperstimulation syndrome, thromboembolic disease in relation to fertility treatment and multiple pregnancy. Current views on the ovarian hyperstimulation syndrome emphasize its association with the presence of polycystic ovaries. We review here the pathophysiological background of this association and focus on the central role of vascular endothelial growth factor (VEGF). Overexpression of VEGF in the polycystic ovary is thought to contribute to its characteristic multifollicular response to gonadotrophic stimulation. Release of large amounts of VEGF into the circulation is thought to account for the development of the clinical syndrome of ovarian hyperstimulation. The implications of this understanding are explored and the clinical features of the condition and its management are described. Thromboembolic disease is increasingly recognized as a serious if rare complication of infertility treatment. The subject is reviewed here with special reference to two recently published and important papers. The most concerning complication of infertility treatment is multiple pregnancy. Few doctors seem to be aware of the dire statistics: every index of obstetric outcome is adversely affected. The survival, health and family circumstances of children born as the result of multifetal gestation are all impaired. Infertility patients need a clear understanding of the risks involved so that they can appreciate the need for intensive monitoring of ovarian stimulation. In our opinion a knowledge of the rate of multiple pregnancy is quite as important as knowing the clinic's ‘success’ rate.

Polycystic ovarian disease (PCOD) is characterized by anovulation, eventually high luteinizing hormone (LH) levels, with increased LH pulse frequency, and hyperandrogenism. As the aetiology of the disease is still unknown, gonadotrophin-releasing hormone (GnRH) antagonists, competitive inhibitors of GnRH for its receptor, are interesting tools in order to study and treat the role of increased LH levels and pulse frequency in this disease. Their administration provokes a rapid decrease in bioactive and immunoactive LH followed by a slower decrease in follicle-stimulating hormone (FSH). In patients with PCOD, the suppression of gonadotrophin secretion eradicates the symptoms of the disease as long as the treatment lasts. Several authors have suggested that increased plasma LH levels have deleterious effects on the fertility of women with PCOD. Indeed, fewer spontaneous pregnancies with more miscarriages are observed when plasma LH levels are high. Assisted reproduction techniques such as in vitro fertilization (IVF) have provided other clues to the role of the LH secretory pattern in women with PCOD. The number of oocytes retrieved, the fertilization rate and the cleavage rate are lower in PCOD patients undergoing IVF and this is inversely correlated with FSH:LH ratio. These abnormalities are corrected when endogenous secretion of LH is suppressed. On the other hand, implantation and pregnancy rates after IVF are similar to those observed in control women. New GnRH antagonists are devoid of side effects and suppress LH secretion within a few hours without a flare-up effect. This action lasts for 10–100 hours. When GnRH antagonists are associated with i.v. pulsatile GnRH, this combination both suppresses the effect of endogenous GnRH and because of the competition for GnRH receptors restores a normal frequency of LH secretion. We have studied two women with PCOD, administering first 10 mg s.c. every 72 hours for 7 days of the GnRH antagonist