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: 8.66). 02/2010; 17(2):184-96. DOI: 10.1093/humupd/dmq041
Source: PubMed

ABSTRACT 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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    Journal of GLBT Family Studies 11/2014; DOI:10.1080/1550428X.2014.891088
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    ABSTRACT: From the early ages of assisted reproductive technologies (ARTs), different protocols have been developed with different gonadotropin preparations at different dosages with or without gonadotropin releasing hormone agonist or antagonist cotreatment. Various adjuvants have also been incorporated in controlled ovarian hyperstimulation (COH) protocols in an attempt to increase the efficacy and safety. The "best" protocol for COH should minimize stimulation burden while maintain the highest healthy, singleton, term live birth rates. Understandably, the one that meets all these expectations may not exist and COH should be individualized. Currently, there are worldwide differences in COH protocols and gonadotropin dose algorithms used depending on the country, demographics, funding stream, and existing guidelines/legislations. In 2014, despite efforts to individualize COH, currently, many of the protocols employ lack of high-quality evidence-based data. The aim of this review is to overview the efficacy and safety of available COH protocols, in normal responders, poor responders, and hyperresponders from evidence-based medicine perspective.
    Seminars in Reproductive Medicine 07/2014; 32(4):262-271. DOI:10.1055/s-0034-1375178 · 3.00 Impact Factor
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    ABSTRACT: Objective To evaluate the dose–response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial anti-Müllerian hormone (AMH) concentrations. Design Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0–14.9 pmol/L [0.7–<2.1 ng/mL]; high: 15.0–44.9 pmol/L [2.1–6.3 ng/mL]) trial. Setting Seven infertility centers in four countries. Patient(s) Two hundred sixty-five women aged ≤37 years. Intervention(s) Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle. Main Outcome Measure(s) Number of oocytes retrieved. Result(s) The number of oocytes retrieved increased in an rhFSH dose–dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose–response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2–0.7) and 1.0 (95% confidence interval 0.7–1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum. Conclusion(s) Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level. Clinical Trial Registration Number NCT01426386.
    Fertility and Sterility 09/2014; DOI:10.1016/j.fertnstert.2014.08.013 · 4.30 Impact Factor


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Dec 1, 2014