The aim of this review was to compare treatment with clomiphene citrate (CC) or letrozole (Ltz) versus gonadotropins alone for stimulation of the ovaries during in vitro fertilisation (IVF) treatment.
Gonadotropin hormonal injections are commonly used in an IVF treatment to stimulate the ovaries to produce eggs, which can then be mixed with sperm in the laboratory to create embryos for transfer into the uterus. However, these injections are expensive, inconvenient, and are associated with side effects. Calls for patient-friendly stimulation regimens have led to the use of tablets such as clomiphene or letrozole instead of injections, but it is unclear whether these are associated with similar pregnancy rates.
We included 27 studies, of which 22 studies with a total of 3599 participants had data suitable for analysis. We studied the general IVF population and those women who had fewer eggs (poor responders) during IVF separately. This is an update of a previous Cochrane Review first published in 2012. The evidence is current to 10 January 2017.
There was no clear evidence of a difference in live-birth or pregnancy rates between the groups in the general IVF population. Low-quality evidence suggests that for a typical clinic with 23% live-birth rate (LBR) using only gonadotropin hormonal injections, switching to CC or Ltz regimens would be expected to result in LBRs between 15% and 30%.
The risk of ovarian hyperstimulation syndrome (OHSS) was lower with CC or Ltz use compared to gonadotropins alone. Low-quality evidence suggests that for a typical clinic with 6% prevalence of OHSS associated with a gonadotropin hormonal injection, switching to CC or Ltz regimen would be expected to reduce the incidence to between 0.5% and 2.5%.
Among women designated as poor responders, there was no clear evidence of a difference between the groups in live-birth or pregnancy rates. Low-quality evidence suggests that for a typical clinic with 5% LBRs in poor responders using only gonadotropin hormonal injection, switching to CC or Ltz regimen would be expected to result in LBRs between 2% and 14%. The side effects of these drugs and data on foetal abnormalities following CC or Ltz protocols were poorly reported.
Quality of the evidence
The quality of the evidence for the different comparisons ranged from low to moderate. The main limitations were risk of bias associated with poor reporting of study methods, and imprecision.