Medical Approaches to Ovarian Stimulation for Infertility

Ovarian stimulation is an integral part of many different infertility treatments. Since the 1970s, ovarian stimulation has been applied in ovulatory women diagnosed with unexplained infertility aiming to increase the number of developing follicles and the number of oocytes for fertilization in vivo. Ovarian stimulation is often combined with intrauterine insemination of sperm. Since the early 1980s, ovarian stimulation has become an essential part of in vitro fertilization (IVF) aiming to improve pregnancy rates by providing the laboratory multiple oocytes for fertilization and early embryo development. Medical ovulation induction has now matured providing good cumulative live birth rates. In skillful hands and with proper ovarian response monitoring, chances for complications are low for ovulation induction. The aim of this intervention is to mimic physiologic circumstances in anovulatory women, hence, single dominant follicle development and ovulation. However, a tendency to hyperrespond to ovarian stimulation is a well-known feature of polycystic ovary syndrome (PCOS). Moreover, recent studies have shown the usefulness of novel drugs such as the aromatase inhibitor, letrozole, next to the antiestrogen clomiphene citrate or exogenous gonadotropins. In everyday practice, ovulation induction is often ignored in favor of IVF, although no direct comparative trials have been reported to date.Any form of ovarian stimulation increases the chances of pregnancy per cycle, but it is at the expense of increased complication rates, most importantly multiple pregnancies and ovarian hyperstimulation syndrome (OHSS). This holds especially true for ovarian stimulation aiming at maturing multiple dominant follicles for fertilization either in vivo. Various strategies may significantly reduce chances for OHSS.Regarding IVF, numerous new treatment modalities have been introduced over the years-often with insufficient evidence of safety and efficacy-using different compounds and dose regimens for ovarian stimulation, gonadotropin-releasing hormone analogue cotreatment, oocyte maturation trigger, interventions preceding stimulation, and luteal phase supplementation. The most important clinical challenge is to find the right balance between improving chances for success (birth of a healthy child) with reasonable cost, acceptable patient discomfort, and a minimal complication rate. New developments are rendering ovarian stimulation less intense and more individualized.