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- Title
A patient-centred approach to IVF stimulation.
- Authors
Fauser, B. C. J. M
- Abstract
The history of IVF has been characterized by profound ovarian stimulation protocols, in an attempt to optimise pregnancy rates per cycle. These approaches, aiming at generating as many oocytes as possible, were meant to counterbalance shortcomings in in-vitro oocyte fertilization, embryo culture conditions, as well as embryo selection for transfer. Another reason often put forward to justify profound stimulation is the cryostorage of surplus embryos, providing additional pregnancy chances in subsequent unstimulated cycles. Over the years ovarian stimulation protocols have become extremely complex and time consuming, associated with much patient discomfort and considerable complication rates. Moreover, costs of applied medication may outweigh the cost of IVF treatment itself. High doses of exogenous gonadotrophins are usually combined with extended suppression of endogenous pituitary function using GnRH agonist. In many centres, ovarian stimulation is preceded by the suppression of ovarian function using steroid contraceptives, aiming at 'synchronizing' follicle development and also for logistic reasons. Consequently, ovarian stimulation usually takes 1 to 2 months, and associated patient discomfort and cost are substantial. Moreover, much time is required in between IVF cycles to allow for the ovary to recover, and patient drop-out rates are high even in countries where IVF is reimbursed. The stimulation of numerous dominant follicles increases chances for the rare but dangerous ovarian hyperstimulation syndrome, the retrieval of many oocytes may be more time consuming and painful, the large oocyte numbers generated may potentially affect oocyte quality (and related aneuploidy rates of embryos). Moreover, abnormal follicular phase endocrinology associated with multiple dominant follicle development may give rise to decreased endometrial receptivity (reducing pregnancy chances). Finally, the true benefit of embryo cryostorage remains limited. The aim of milder forms of ovarian stimulation is to render stimulation less complex, less time consuming and less costly while improving patient acceptability by reducing side effects. This may result in the improvement of the cost effectiveness of IVF (hopefully resulting in augmented access to IVF) and may also reduce drop-out rates. These women may be exposed to additional chances to achieve a pregnancy in subsequent IVF cycles. Only in this context can mild ovarian stimulation be appreciated, since the overall pregnancy rate for a given IVF cycle will be slightly reduced (especially in case where mild ovarian stimulation is combined with the transfer of a single embryo). Therefore, the concept of mild ovarian stimulation (just like the transfer of a single embryo) can only be developed further in a holistic perspective of IVF, involving healthy children as primary outcome, in the context of overall patient discomfort, chances for complications and cost per IVF treatment over a given period of time (which may involve multiple IVF cycles). The introduction of GnRH antagonists into the clinic (where the period of administration can be restricted to the period at risk for a premature LH rise) allowed for an IVF cycle to commence with a physiological recruitment of a limited number of follicles in the beginning of the cycle, as occurs under normal conditions. Therefore, the use of GnRH antagonists has facilitated the further development of mild stimulation applying low doses of exogenous FSH during the mid- to late-follicular phase aiming to interfere with single dominant follicle selection. Initial proof of principle studies by our group has further explored this concept. Subsequently, a large effectiveness trial comparing a mild (mild stimulation along with single embryo transfer) with a conventional approach has been performed showing similar cumulative term live birth rates at lower cost, less patient discomfort, reduced drop-out rates and a dramatic reduction in multiple pregnancies. Moreover, it has been shown that mild ovarian stimulation is associated with a reduced proportion of aneuploid embryos as assessed by preimplantation genetic screening.
- Subjects
FERTILIZATION in vitro; PREGNANCY
- Publication
Reproductive BioMedicine Online (Reproductive Healthcare Limited), 2008, Vol 16, Issue S2, pS-6
- ISSN
1472-6483
- Publication type
Abstract