Individualised stimulation dose using ovarian reserve markers in women doing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI)
In planning an IVF cycle, doctors often decide the dose of stimulation drugs based on certain characteristics of each woman, such as their age. New tests have been developed that some specialists believe can better predict a woman's response to IVF stimulation. These are called ovarian reserve tests and are a general measure of the number of eggs available in the ovaries. It is unclear whether tailoring the doses of stimulation drugs based on the individual ovarian reserve tests can help to increase the chance of the woman getting pregnant and having a baby. It is also unclear whether the tests help to improve the safety of the IVF cycle, such as reducing the chances of a serious condition known as ovarian hyperstimulation syndrome (OHSS).
We included two types of studies in this review. Direct dose comparison studies recruited women predicted to respond to IVF stimulation either poorly, normally, or excessively based on their ovarian reserve test. Researchers then randomly assigned these women to different doses of FSH to see whether the different doses would impact on IVF outcomes.
The ORT-algorithm studies divided a broader group of women into those whose stimulation dose was based on the women's ovarian reserve test and those receiving a standard dose of stimulation medication or a dose based on another characteristic about the women (other than their ovarian reserve).
In total we included 20 randomised controlled trials involving 6088 women.
1. Direct dose comparison studies (low or very low quality evidence)
In women predicted to respond poorly or normally to stimulation based on their ovarian reserve test, increasing the dose of stimulation medication did not seem to influence the chance of getting pregnant or having a baby, or the chance of OHSS. However, the included studies were small and compared different doses of medication. This made it difficult to say for sure that there is no difference between doses. For women predicted to respond poorly, if the chance of live birth with 150 IU is 11%, then the chance with 300/340 IU would be between 3.8% to 16%. For women predicted to have a normal response, if the chance of live birth or ongoing pregnancy with 150 IU is 19%, then the chance with 200/225 IU would be between 12% to 31%.
In women predicted to have an excessive response to stimulation, reducing the stimulation dose may or may not affect the chance of having a baby. If the chance of live birth with 100 IU is 26%, then the chance with 150 IU would be between 18% to 33%. However, it may reduce the rate of OHSS. If the chance of moderate or severe OHSS with a lower dose is 1.6%, then the chance with a higher dose would be between 1.3% and 9.6%.
2. ORT-algorithm studies
Moderate quality evidence from these studies suggested that using an ovarian reserve test to decide on the stimulation dose generally did not have much effect on the chance of getting pregnant and having a baby, but there could have been a relatively small difference one way or another. It did generally appear to reduce the chance of having OHSS when compared to giving all women the same dose of stimulation medication, but this evidence was low quality. Our findings suggest that if the chance of live birth with a standard dose were 26%, the chance with dosing based on an ovarian reserve test would be between 24% and 30% and that if the chance of moderate or severe OHSS with a standard dose were 2.5%, the chance with dosing based on an ovarian reserve test would be between 0.8% and 2.5%.
Quality of the evidence
We assessed the quality of the evidence as ranging from very low to moderate, due to limitations in study design (as researchers and participants often knew which treatment was assigned) and statistical imprecision, as the studies included too few women to provide meaningful results for the most important outcomes, such as having a baby.