Carole Gilling-Smith

Insulin action in the normal and polycystic ovary

Insulin has a stimulatory effect on steroidogenesis by granulosa cells of normal and polycystic ovaries and interacts with gonadotropins in an additive or, as in the case of LH, a synergistic manner. These actions seem to be mediated specifically by the insulin receptor rather than by cross-reaction with the type I IGF receptor, even in tissue obtained from women with PCOS with biochemical evidence of insulin resistance. The authors suggest that hyperinsulinemia makes a significant contribution to premature arrest of follicle growth, which is characteristic of anovulation in women with PCOS, and that the interaction of insulin with LH is a key element in this process. Insulin may also have a role in amplifying LH-induced androgen production by theca cells, which may help explain the prominence of symptoms of hyperandrogenism in obese subjects with PCOS. The results of recent clinical studies of insulin-sensitizing agents such as metformin and the thiazoladinedione troglitazone in PCOS have provided encouragement that improvement of insulin sensitivity and consequent lowering of circulating insulin levels by these agents may be of therapeutic value in the management of both anovulation and hirsutism.

HIV and reproductive care—a review of current practice

In developed countries, antiretroviral treatment has increased life quality and expectancy of HIV‐infected individuals and led to a drop in mother‐to‐child transmission (MCT) risk to below 1%. Fertility has been shown to be reduced in both men and women with HIV. As a result of these factors, the demand for reproductive care in this population is rising. In discordant couples where the man is positive, sperm washing significantly reduces viral transmission risk to the uninfected female partner over unprotected intercourse. Positive women do not necessarily need specialised fertility treatment but should be monitored closely during pregnancy to minimise MCT risk.

Sperm DNA fragmentation in subfertile men: the effect on the outcome of intracytoplasmic sperm injection and correlation with sperm variables.

To present the first UK data on sperm DNA fragmentation levels in subfertile men and fertile controls, the correlation with semen variables, and to assess the effect on the outcome of intracytoplasmic sperm injection (ICSI).

A decade of the sperm-washing programme: correlation between markers of HIV and seminal parameters

The aim of the study was to use a decade of experience of sperm washing to assess the effect of HIV disease on semen parameters and to highlight the continuing importance of risk reduction when some controversially advocate the safety of timed unprotected intercourse for conception in the ‘stable’ HIV‐positive man.

A decade of sperm washing: clinical correlates of successful insemination outcome

BACKGROUND Since 1999, we have treated HIV-positive men with sperm washing as part of a risk-reduction programme. METHODS Retrospective analysis of the sperm-washing database from the treatment of 245 couples with 439 cycles of intrauterine insemination assessed the effects of patient factors (age, maternal FSH, rank of attempt), markers of HIV-disease [time since diagnosis, CD4 count, viral load (VL), use of highly active antiretroviral therapy (HAART)], cycle factors (natural versus stimulated, number of follicles, fresh versus frozen sperm) and sperm parameters on clinical (CPR) and ongoing pregnancy rate (OPR). RESULTS Overall 111-245 (45.4%) couples achieved a clinical pregnancy (CPR: 13.5% and OPR: 9.6% per insemination) with no seroconversions. The mean duration since HIV diagnosis was 5.8 years, 73% of men were on antiretroviral therapy, there was an undetectable VL in 64% and the median CD4 was 409 cells/mm(3). A significantly decreased OPR and a non-significantly increased miscarriage rate (MR) was observed after the female age of 40. Similarly, there was a significant increased OPR and decreased MR for women with a mean cycle maternal FSH of <6.4 IU/l. There was no effect of VL, CD4 count, use of HAART or time since diagnosis on the outcome. Nor was there a difference in the OPR according to paternal age, rank of attempt, cycle regime or number of follicles. Semen volume, sperm concentration, total count and progressive motility and post-wash concentration, progressive motility and total motile count inseminated were significantly higher in successful cycles. The use of frozen sperm had a significant negative impact on outcome. CONCLUSIONS This study of the potential safe and successful reproductive options available to HIV-positive men demonstrates that maternal age and semen quality, rather than HIV factors, remain the most important determinants of cycle success.

Polycystic ovary syndrome : evidence for a primary disorder of ovarian steroidogenesis

Polycystic ovary syndrome (PCOS) is a very common endocrinopathy of uncertain aetiology in which the most consistent biochemical abnormality is hypersecretion of androgens. In this review, evidence is presented to support the view that a primary abnormality of ovarian androgen biosynthesis provides the basis for the syndrome. PCOS is a familiar disorder and we demonstrate, in molecular genetic studies, that CYP11a, the gene coding for P450 side chain cleavage, is a key susceptibility locus for development of hyperandrogenism.

HIV, hepatitis B and hepatitis C and infertility: Reducing risk

Summary Fertility units should base their decision on whether or not to treat patients infected with HIV, HBV or HCV on the basis of the facilities they can provide, in line with these guidelines, and the views of their local ethics committee and staff members. The decision to treat a couple should be assessed purely in terms of the welfare of the child, and if risk-reduction treatment cannot be provided locally, a referral should be made to a specialist clinic that can provide care according to the standards described in the above guidelines.

Does the cause of obstructive azoospermia affect the outcome of intracytoplasmic sperm injection: a meta-analysis.

To define whether the outcome of intracytoplasmic sperm injection (ICSI) using sperm surgically retrieved from men with obstructive azoospermia (OA) depends on the cause of obstruction.

Pathogenesis of polycystic ovary syndrome: Evidence for a genetically determined disorder of ovarian androgen production

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. It is the major cause of anovulatory infertility and of hirsutism but its aetiology remains uncertain. The most consistent biochemical abnormality is hypersecretion of androgens. In this review, evidence is presented to support the view that a genetically determined abnormality of ovarian androgen secretion is the primary cause of the syndrome. Molecular genetic studies have demonstrated that CYP11a, the gene encoding P450 cholesterol side chain cleavage, is a major susceptibility locus for development of hyperandrogenism in PCOS.

HIV infection and subfertility

With the improvements in life expectancy and quality of life for HIV-infected individuals in the developed world, and the increasing rates of HIV transmission among heterosexuals, reproductive issues are becoming increasingly important. We discuss the management of conception and pregnancy in HIV-infected couples. Couples where one or both partners are HIV infected may also experience subfertility and in this article we review the methods available to treat subfertility in this population and the current guidelines for the use of these techniques. HIV-infected couples can enjoy normal, healthy lives and should have access to the same investigation and treatment as their HIV-negative counterparts. Current inequities in the treatment available must be addressed.