In vitro fertilisation (IVF) is the treatment of last resort for many subfertile couples and a very costly one, partly due to the use of expensive drugs, i.e. gonadotrophins, needed for controlled ovarian hyperstimulation (COH) . COH is an essential part of IVF which is needed to obtain a reasonable yield of oocytes which can then be fertilised in vitro. In clinical practice physicians often rely on their clinical experience and judgement when selecting an appropriate starting dose of follicle stimulation hormone (FSH). There is neither international nor nationwide consensus about COH programmes. Defining the optimal dose of FSH to retrieve an acceptable number of oocytes remains complicated. The problem herewith is that women show marked differences in their ovarian reserve and, as a consequence, in their ovarian response to medication [2, 3]. Women who respond poorly to ovarian stimulation have poorer pregnancy prospects than women with a normal ovarian response . Frequently, the occurrence of an insufficient response will urge the clinician to cancel the cycle which is obviously very stressful to the couple and may lead to withdrawal from further treatment. In a subsequent stimulation cycle higher dosages of FSH are usually given, although these may also be inadequate, leading to another cancellation of the cycle or even to hyperresponse with risk of ovarian hyperstimulation syndrome (OHSS). The result is that the poor responder may go through a series of treatment cycles with an overall poor prospect for pregnancy.
On the other end of the spectrum, women with a hyperresponse to ovarian stimulation are at risk of increased patient discomfort, cycle cancellation and development of OHSS. This condition may lead to severe illness requiring hospitalisation and intensive care with thromboembolic phenomena or multiple organ failure which are potentially life threatening complications. Mild and moderate forms of OHSS occur in respectively 20–33% and 3–6% of all ovarian stimulation cycles, while the severe form of the syndrome has been reported to occur as frequently as 0.1–2% .
In view of the tight relationship between hyperresponse and OHSS, prevention of hyperresponse is one of the key elements in preventing OHSS. Accurate prediction of ovarian response is now possible by using an ovarian reserve test (ORT) . Various ORTs are available, of which basal FSH is the oldest whereas the antral follicle count (AFC) and serum level of anti-Müllerian hormone (AMH) have been introduced more recently. Previous systematic reviews by our group have shown that both AFC and AMH provide an optimal balance between sensitivity and specificity, are superior to basal FSH, and are able to predict ovarian response to COH, allowing for studies on the value of adjustment of the FSH dosage based on these parameters [6–10]. It should be emphasised that our reviews showed that ORTs can predict ovarian response after COH, but not the occurrence of pregnancy after IVF treatment.
Previous research has shown that dose adjustment after ORTs resulted in a higher rate of normal ovarian response and significantly higher pregnancy rates . However, this study had several weaknesses. First of all, the power calculation was not based on the outcome ‘pregnancy’ but on the outcome ‘appropriate response’. Furthermore, participants with possible extremes in ovarian response were excluded, FSH dosage was only fixed until stimulation day 8, and the used algorithm was complicated and impractical for daily clinical use. Before definitive conclusions can be drawn about dose adjustment after ORTs, these results need to be confirmed in a large randomised controlled trial (RCT). Based upon these data, we hypothesize that the use of an ORT as predictor of ovarian response followed by an individualised FSH regime, will lead to a reduction in the occurrence of an inappropriate ovarian response, a reduction in the amount of cycle cancellations, reduction in the number of withdrawals from treatment, reduction in the occurrence of OHSS, reduction in the application of cycles with poor prospects for success, improvement in overall pregnancy rates and improvement of overall cost-effectiveness of IVF programs.