Mild ovarian stimulation for IVF
1 Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100 3584 CS, Utrecht, The Netherlands 2 Academic Department of Obstetrics and Gynaecology, St George's Hospital Medical School, Cranmer Terrace, Tooting, London SW17 0RE, UK 3 Department of Obstetrics and Gynaecology and Reproductive Medicine, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, 92141 Clamart, France 4 Centre for Reproductive Medicine, Dutch-Speaking Brussels Free University, Laarbeeklaan 101, 1090 Brussels, Belgium
5 Correspondence addressed. E-mail: m.f.g.verberg{at}umcutrecht.nl
BACKGROUND: Mild ovarian stimulation for in vitro fertilization (IVF) aims to achieve cost-effective, patient-friendly regimens which optimize the balance between outcomes and risks of treatment.
METHODS: Pubmed and Medline were searched up to end of January 2008 for papers on ovarian stimulation protocols for IVF. Additionally, references to related studies were selected wherever possible.
RESULTS: Studies show that mild interference with the decrease in follicle-stimulating hormone levels in the mid-follicular phase was sufficient to override the selection of a single dominant follicle. Gonadotrophin-releasing hormone antagonists compared with agonists reduce length and dosage of gonadotrophin treatment without a significant reduction in the probability of live birth (OR 0.86, 95% CI 0.72–1.02). Mild ovarian stimulation may be achieved with limited gonadotrophins or with alternatives such as anti-estrogens or aromatase inhibitors. Another option is luteinizing hormone or human chorionic gonadotrophin administration during the late follicular phase. Studies regarding these approaches are discussed individually; small sample size of single studies along with heterogeneity in patient inclusion criteria as well as outcomes analysed does not allow a meta-analysis to be performed. Additionally, the implications of mild ovarian stimulation for embryo quality, endometrial receptivity, cost and the psychological impact of IVF treatment are discussed.
CONCLUSIONS: Evidence in favour of mild ovarian stimulation for IVF is accumulating in recent literature. However, further, sufficiently powered prospective studies applying novel mild treatment regimens are required and structured reporting of the incidence and severity of complications, the number of treatment days, medication used, cost, patient discomfort and number of patient drop-outs in studies on IVF is encouraged.
Received on February 16, 2008; revised August 17, 2008; accepted on October 20, 2008
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