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Objective: To compare a so-called mild in-vitro fertilisation (IVF) treatment strategy with the standard IVF treatment on the following aspects: the chance of a pregnancy resulting in full-term live birth within 1 year, patient discomfort, multiple pregnancies, and costs., Design: Randomised, open-label, prospective trial (www.controlledtrials.com, number ISRCTN35766970)., Method: 404 patients were assigned to undergo either a mild treatment, consisting of ovarian stimulation with a gonadotrophin releasing hormone (GnRH) antagonist combined with single embryo transfer, or the standard treatment consisting of prolonged stimulation with a GnRH agonist combined with the transfer of two embryos. The primary outcome measures were: (1) the percentage of cumulative pregnancies within one year after randomisation leading to full-term live birth; (2) total costs per couple and child up to 6 weeks after expected delivery; and (3) overall patient discomfort. Analysis was done according to the intention-to-treat principle and was intended to show that the mild treatment was not inferior to the standard treatment; the non-inferiority threshold was -12.5%., Results: The proportion of cumulative pregnancies resulting in full-term live birth after 1 year was 43.4% in the mild and 44.7% in the standard treatment group. The lower limit of the one-sided 95% confidence interval was equal to -9.8%. The respective proportion of couples with multiple pregnancies was 0.5% versus 13.1% (p < 0.0001), and the average total costs were Euro 8,333.- versus Euro 10,745.- (difference: Euro 2,412.-, 95% CI: 703-4,131). There were no statistically significant differences between the groups with regard to anxiety, depression, physical discomfort, and sleep quality., Conclusion: After 1 year of treatment, the cumulative percentage of pregnancies leading to full-term live birth and the total patient discomfort were the same for the mild treatment (average 2.3 IVF-cycles) and the standard treatment (average 1.7 IVF-cycles). The mild treatment significantly reduced the number of multiple pregnancies and the overall costs.

Preimplantation genetic screening (PGS) is a diagnostic procedure using fluorescence in situ hybridisation to detect aneuploidy in cleavage-stage embryos from in-vitro fertilisation (IVF) before transfer into the uterus. It has been suggested that the use of PGS may improve the effectiveness of IVF in women of advanced maternal age. Recently, a Dutch study was published showing that PGS did not increase but instead significantly reduced the rates of ongoing pregnancies and live births after IVF in women of advanced maternal age. This is in contrast to the results of a comparable study from Belgium indicating that there was no difference in pregnancy rates between IVF with or without PGS. Embryo mozaicism, leading to discordant PGS results in 2 cells from the same embryo, might explain the discrepancy in the results of these studies. PGS should not be applied in IVF until the technique has been further developed.

An increasing number of women are delaying childbirth until an age when their fertility has significantly declined. Oocyte donation provides the opportunity for women to successfully conceive regardless of age. In The Netherlands, in 1997 the age limit for oocyte donation treatment was set at 45 years. The most important objections to pregnancy in older women are the medical risks for mother and child, the application of fertility treatments beyond the natural reproductive age and the psychosocial consequences for the child. However, based on international experience and recent data concerning the risks of pregnancy after oocyte donation in older women, it is proposed to increase the maximum age limit for this procedure to 50 years.

The young specialty of reproductive medicine has developed tremendously in barely 30 years and has taken a prominent place in the field of obstetrics and gynaecology. In addition to the diagnosis and treatment of infertility, reproductive medicine comprises a large number of medical activities, most of which affect women in almost all phases of life, from shortly after puberty to old age. A key role is played by the pathophysiology of ovarian function and ovarian hormones. Requests for medical assistance concern: disorders of sexual development, the consequences for health in the short- and long-term of overweight and anovulation early in life, premature menopause and the need for hormone replacement, damage to the ovaries as a result of radio- or chemotherapy for cancer, the hormonal aspects of breast cancer, the hormonal aspects of sexuality and well-being, and counselling regarding contraception or menopausal symptoms and hormone replacement.

Women with an androgen deficiency complain about a loss of libido and a lack of well-being. It is difficult to link these symptoms to low circulating androgen levels in blood. This is because these complaints often arise during a period of life characterized by major psychosocial changes. Furthermore, coinciding oestrogen deficiency may give rise to similar symptoms. Another problem is the assessment of androgen deficiency. The androgen assay used is designed for men presenting with levels much higher than normal. Finally, concentrations in the peripheral blood are a poor reflection of intracellular androgen receptor stimulation. Patients with complaints suggestive of a relative androgen deficiency (based on the pattern of complaints and low serum androgen concentrations) should first of all be counselled for psychosocial problems. Oestrogen deficiency should subsequently be ruled out or substituted. If the complaints still persist then androgen substitution can be considered.

In order to obtain high pregnancy rates per IVF cycle, ovarian stimulation is employed to produce multiple embryos. The best embryos are transferred into the uterus and the remainder are frozen for possible use in later cycles. Despite limiting the number of transferred embryos, more than half of all IVF babies are the result of multiple pregnancies. The associated morbidity and costs have led to calls for the adoption of single embryo transfer. New techniques such as pre-implantation genetic screening for aneuploidy have enabled better embryo selection with optimal chances of a healthy child. Milder ovarian stimulation protocols may further reduce the morbidity and costs of IVF cycles. Improved cryopreservation techniques should improve the chances of pregnancies in subsequent cycles using excess embryos. The definition of success in IVF should be changed from number of children per IVF cycle to number of children born after singleton pregnancies per IVF treatment started.

For the first time, the results from all 13 in vitro fertilisation (IVF) centres in the Netherlands have been published in the scientific literature. The Dutch IVF system is unique in many respects, especially with regard to the limited number of high-volume centres, the widespread use of transport IVF and the complete coverage by health insurance companies. IVF is frequently applied, resulting in an amazing I IVF child out of every 60 children born in the Netherlands. The reported ongoing pregnancy rates per started IVF cycle (21%) are comparable with those in other European countries, but lower than in the United States. However, the number of embryos transferred is relatively low (a maximum of 2), resulting in a very low risk of higher order multiple pregnancies. Even twin pregnancies remain the most dangerous health issue associated with IVF. In order for IVF to move forward, a shift in paradigms is urgently required. The surrogate endpoint of 'pregnancies per treatment cycle' should be replaced by the alternative measure of 'healthy children born per started IVF treatment' in relation to patient discomfort, side effects, chances for (long-term) health risks, and costs.

The hypothalamic gonadotrophin-releasing hormone (GnRH) stimulates synthesis and secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) by the gonadotrophic cells of the pituitary. The mechanisms of action of GnRH antagonists and of agonists is completely different. Due tot competitive blockage of GnRH receptors by antagonist administration, LH (and to a lesser extent FSH) levels drop rapidly. Moreover pituitary function normalizes immediately following cessation of medication. The direct and rapid action of GnRH antagonists, the dose dependent suppression of LH and FSH and the rapid restoration of hypophyseal function after cessation of the use of antagonists may shorten and simplify in-vitro fertilization, with less chance of side effects or complications. Further studies are required to decide whether antagonists can usefully be applied for other gynecological indications such as the polycystic ovary syndrome. The possibilities of profitable long term treatment will increase considerably if it proves possible to develop a sustained action formulation.