Alternative approaches to ovarian stimulation for in vitro fertilization

Abstract

In vitro fertilization (IVF), literally meaning ‘fertilization in glass’, is characterized by co-culture of aspired oocytes with spermatozoa and subsequent transfer of the embryo(s) into the uterine cavity. The original indication for this treatment was subfertility resulting from impaired function of the fallopian tubes (Steptoe 1975). Since then, indications for the usage of IVF have increased considerably (Diedrich et al. 1992; Macklon et al. 1991). The first efforts in the field of IVF in human were made in the 1940’s. By incubating surgically harvested oocytes with spermatozoa in vitro, two-cell pre-embryos were observed (Rock & Menkin 1944). These embryos were not transferred into the uterus. A major breakthrough was achieved in 1959 by the fertilization of rabbit eggs in vitro and subsequently transferring the four-cell embryos into the fallopian tubes of recipient rabbits, followed by the delivery of healthy rabbits (Chang 1959). This was the first proof that the concept of fertilizing mammalian eggs in vitro could produce normal offspring. The first attemps in IVF were characterized by the use of polyovulating agents and aspiration of human oocytes by laparoscopy resulting in an ectopic pregnancy (Steptoe & Edwards 1976). This technique failed to result in a life-born baby and was temporary abandoned. Edwards and Steptoe resorted to retrieving the single egg characteristics of the normal menstrual cycle. As a consequence, the best result was the recovery of solely one oocyte. On the 25th of July 1978 the first baby arising from IVF, Louise Brown, was born in the U.K. (Steptoe & Edwards 1978). Unfortunately, by aspirating the oocyte in the natural cycle only a few pregnancies were reported. Subsequently, the use of human menopausal gonadotropin (HMG) to stimulate multiple follicular development was re-introduced with more success (Garcia et al. 1983a; Garcia et al. 1983b).