Clinical outcomes in relation to the daily dose of recombinant follicle-stimulating hormone for ovarian stimulation in in vitro fertilization in presumed normal responders younger than 39 years: A meta-analysis

Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
Human Reproduction Update (Impact Factor: 10.17). 02/2010; 17(2):184-96. DOI: 10.1093/humupd/dmq041
Source: PubMed


The optimal ovarian stimulation dose to obtain the best balance between the probability of pregnancy and the risk of complications, while maximizing cost-effectiveness of in vitro fertilization (IVF) treatment, is yet to be established.
A systematic search of the electronic databases PubMed, EMBASE and Cochrane library, from 1984 until October 2009 for randomized controlled trials comparing different doses of recombinant FSH in IVF, was performed.
Ten studies (totaling 1952 IVF cycles) were included in the present meta-analysis, comprising patients younger than 39 years with regular menstrual cycle, normal basal FSH levels and two normal ovaries. Comparison was made between studies using a daily dose of 100 versus 200 IU recFSH, and between 150 versus 200 IU recFSH or higher. Although oocyte yield was greater in the >200 IU/day dose group, pregnancy rates were similar compared with lower dose groups. The risk of insufficient response to ovarian stimulation was greatest in the 100 IU/day dose group. The risk of developing ovarian hyperstimulation syndrome was greater in the >200 IU/day dose group. The number of embryos available for cryopreservation was lowest in the 100 IU/day group, but similar comparing the 150 IU/day and the >200 IU/day dose groups.
This meta-analysis suggests that the optimal daily recFSH stimulation dose is 150 IU/day in presumed normal responders younger than 39 years undergoing IVF. Compared with higher doses, this dose is associated with a slightly lower oocyte yield, but similar pregnancy and embryo cryopreservation rates. Furthermore, the wide spread adherence to this optimal dose will allow for a considerable reduction in IVF costs and complications.

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Available from: F.J.M. Broekmans, Dec 01, 2014
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    • "This could be compared to a lesbian-competent clinic in Denmark, where women in their mid-thirties on average need six or seven inseminations to become pregnant (StorkKlinik, n.d.). While insemination is a rather simple medical process, IVF is highly technical and involves risks for the patient going through hormonal treatment and egg retrieval (Humaidan, Quartarolo & Papanikolaou, 2010; Sterrenburg et al., 2011). Rapidly moving from insemination to IVF seems reasonable from a different-sex couple's perspective, where deficient fertility has brought them to treatment after years of trying to conceive through intercourse. "
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    • "With regard to a step-down or fixed dose of FSH, a meta-analysis of 10 studies (1952 IVF cycles) comparing a daily dose of 100 IU versus 200 IU rFSH and 150 IU versus 200 IU rFSH or higher showed that although the oocyte yield was greater in the >200 IU/day dose group, the pregnancy rates were similar when compared with the lower dose groups. The risk of an insufficient response to ovarian stimulation was greatest in the 100 IU/day dose group and the risk of developing OHSS was greater in the >200 IU/day dose group [8]. The authors concluded that the optimal daily rFSH stimulation dose is 150 IU in presumed normal responders aged <39 years undergoing IVF. "
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    ABSTRACT: We sought to determine the impact of treatment flexibility on clinical outcomes in either a corifollitropin alfa or recombinant follicle-stimulating hormone (rFSH) protocol. Post hoc analysis of a prospective, multicenter, randomized, double-blind, double-dummy non-inferiority clinical trial (Engage). Efficacy outcomes were assessed on patients from the Engage trial who started treatment on menstrual cycle day 2 versus menstrual cycle day 3, patients who received rFSH step-down or fixed-dose rFSH, patients who received rFSH on the day of human chorionic gonadotropin (hCG) compared with those who did not, and patients who received hCG when the criterion was reached versus those with a 1-day delay. The effect of each of the treatment flexibility options on ongoing pregnancy rate was not significant. The estimated difference (95% confidence interval) in ongoing pregnancy rate was -4.3% (-9.4%, 0.8%) for patients who started ovarian stimulation on cycle day 2 versus day 3, 1.8% (-4.1%, 7.6%) for patients who received hCG on the day the hCG criterion was met versus 1 day after, 3.2% (-2.1%, 8.6%) for patients who received rFSH on the day of hCG administration versus those who did not, and -5.8% (-13.0%, 1.4%) for patients who received a reduced versus fixed-dose of rFSH from day 8. Treatment flexibility of ovarian stimulation does not substantially affect the clinical outcome in patients’ treatment following initiation of ovarian stimulation with either corifollitropin alfa or with daily rFSH in a gonadotropin-releasing hormone antagonist protocol. Trial registration Trial was registered under identifier NCT00696800.
    Full-text · Article · Jun 2013 · Reproductive Biology and Endocrinology
    • "A milder IVF treatment protocol also reduces the multiple pregnancy rate and overall costs (Heijnen et al., 2007). A recent meta-analysis showed that 150 IU/day of rec FSH in normal responders ,39 years is the optimal daily dose for the best balance between a high pregnancy rate and a low risk of complications, thus maximizing the cost-effectiveness of an ART cycle (Sterrenburg et al., 2011). Although evidence in favor of milder ovarian stimulation for IVF is accumulating, it also has been argued that this protocol is associated with lower ongoing pregnancy rates and higher cancelation rates (Hohmann et al., 2003; Heijnen et al., 2007). "
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