Endocrine and therapeutic aspects of infertile women with the polycystic ovary syndrome

Abstract: Fertility treatment with gonadotrophins in infertile clomiphene resistant women with the polycystic ovary syndrome (PCOS) is troublesome with an unpredictive ovarian response. The purpose of this study was to elucidate aspects of ovarian sensitivity and to evaluate treatment efficiency and costs of ovulation induction (OI) and in vitro fertilisation (IVF), as well as pregnancy outcome after infertility treatment in patients with PCOS. Infertile women with PCOS, defined as polycystic ovaries (PCO) in combination with amenorrhea/oligomenorrhea underwent OI with FSH in a low-dose step up regimen combined with down regulation with gonadotrophin releasing hormone (GnRH) agonist. Alternatively, the patients underwent treatment by in vitro fertilisation (IVF) with a long protocol down regulation and controlled ovarian hyperstimulation (COH) with FSH. The OI cycles were monitored by serum samplings of FSH and estrogen and by ultrasound. FSH threshold levels for continuous follicle growth were calculated. The effect of adrenal suppression by glucocorticoids on the intrafollicular androgen environment and oocyte/embryo quality was investigated in a double-blind, randomised control trial of adjuvant prednisolone in PCOS and control women undergoing IVF. Glucose metabolism in ovaries from PCOS and normal women in women undergoing IVF treatment was studied by investigating the effects of insulin on lactate accumulation in cultured granulosa-luteal cells. Following randomisation to OI or IVF, treatment cycles were compared with respect to conversion or cancellation of cycles, pregnancy and delivery rates, directs costs (treatments and drugs) and indirect costs (e.g. care in connection with hyperstimulation, miscarriage, maternity care and delivery). The course and outcome of pregnancies achieved by assisted reproduction techniques, as well as perinatal and neonatal complications was studied in a group of PCOS patients and compared to that seen in non PCOS patients. The FSH threshold levels for continuous follicular growth was found to vary more between patients than between repeated cycles in the same patient. Obese patients with PCOS had different kinetics of resorption/elimination of s.c. administered exogenous FSH compared to lean patients with PCOS, resulting in lower serum FSH levels for a given dose. A decreased ovarian sensitivity to insulin, measured as lactate accumulation in cultured granulosa-luteal cells was seen in PCO as compared to normal ovaries. Adjuvant corticosteroid treatment during COH for IVF in patients with PCOS resulted in a reduction of serum concentrations of DHA and DHAS, and of follicular fluid DHAS, but no beneficial effects on oocyte quality, fertilisation, cleavage and implantation rates were found. In obese patients with PCOS, no difference in the proportion of successfully completed treatments of OI or IVF was found. The cumulative pregnancy rate after five cycles was 33% in OI cycles and 62% in IVF cycles (77%, if cycles with thawed embryos were included). The cost per started cycle was lower for OI than for IVF but the cost per obtained pregnancy was twice as high for OI cycles as for IVF cycles. During pregnancy and labour it was found that women with PCOS had a higher risk of developing hypertension and/or preeclampsia. In conclusion, ultrasound monitoring is the most important tool for monitoring treatment cycles of OI and determinations of FSH threshold levels are of limited clinical value. In PCOS women, decreased insulin sensitivity is also seen in follicular cells of the ovary. Adjuvant corticosteroid therapy does not improve oocyte and embryo quality in IVF treatment of PCOS patients. Antenatal care of women with PCOS should focus on blood pressure since these women seem to have an increased risk of hypertension/preeclampsia during pregnancy. Finally, for obese patients with clomiphene resistant PCOS, IVF seem a cost-effective treatment.