[Twenty years of in vitro fertilization: realization and questions for the future]

IVF is a well-established procedure for the treatment of longstanding infertility due to tubal disease, endometriosis, unexplained infertility or certain types of infertility involving a male factor. IVF can also be applied to couples requiring oocyte donation. Conventional IVF involves several related procedures: patient selection, ovarian stimulation, oocyte retrieval, semen preparation, insemination of cumulus-oocyte complexes, assessment of fertilization, assessment of embryo cleavage, replacement to the uterus of mostly two or three embryos, cryopreservation of excess embryos and establishment of pregnancy. GIFT and ZIFT are related techniques, suitable in couples with at least one healthy Fallopian tube. Conventional IVF is a potentially successful procedure in patients with tubal and unexplained infertility. However, fertilization may fail in couples with certain forms of andrological infertility, especially those in which sperm function is severely deficient. Techniques of assisted fertilization--partial zona dissection (PZD) and subzonal insemination (SUZI)--have been used with limited success to treat couples with severe andrological infertility who could not be helped by conventional IVF. ICSI--the injection of a single spermatozoon into the cytoplasm of a fertilizable metaphase II oocyte--has proved to be more efficient than PZD and SUZI for the alleviation of severe male-factor infertility. Nowadays ICSI can be considered as an infertility treatment, providing similar results in male infertility as conventional IVF in female-factor or idiopathic infertility. The ICSI treatment involves several related steps: selection of patients for ICSI, ovarian stimulation and oocyte handling, evaluation and preparation of spermatozoa, the ICSI procedure itself, oocyte damage and pronucleus formation after ICSI, embryo development and replacement and cryopreservation of excess embryos. The audit of IVF and ICSI results is hampered by the way these data are registered in different countries and different centers. A correct and reliable analysis is possible in the United Kingdom; the UK data bank was used to study the factors influencing the outcome of IVF--especially the female age has a determining role. Infertility treatments have induced a sharp increase in the number of multiple pregnancies. Reducing the number of multiple gestations should be considered as a future major challenge for all infertility centers. Since its introduction in 1991 questions have been raised concerning the safety of ICSI, a novel and efficient assisted fertilization procedure. A careful follow-up of the ICSI pregnancies and children is therefore indicated. At the VUB this prospective follow-up of genetic counseling, the possibility of prenatal diagnosis, the problems during pregnancy, the occurrence of (major) congenital malformations as well as a further medical and psychomotor follow-up. The results of 1437 fetal karyotypes indicate that in comparison with a control group there is after ICSI a slight but significant increase of sex chromosomal aneuploidies and de-novo structural aberrations. The percentage of ICSI children (n = 2840) with major congenital malformations was similar to the malformation rate in children from conventional IVF (n = 2955) or natural conception. This prospective follow-up study should be continued much longer--if possible until adulthood to assess the fertility of these children.