Background: In vitro fertilisation (IVF) is now a widely accepted treatment for unexplained infertility (RCOG 1998). However, with estimated livebirth rates per cycle varying between 13% and 28%, it's effectiveness has not been rigorously evaluated in comparison with other treatments. With increasing awareness of the role of expectant management and less invasive procedures such as intrauterine insemination, concerns about multiple complications and costs associated with IVF, it is extremely important to evaluate the effectiveness of IVF against other treatment options in couples with unexplained infertility.
Objectives: The aim of this review is to determine, in the context of unexplained infertility, whether IVF improves the probability of livebirth compared with 1. expectant management 2. clomiphene citrate (CC) 3. intra uterine insemination (IUI) alone 4. IUI with controlled ovarian stimulation and 5. Gamete IntraFallopian Transfer (GIFT).
Search strategy: RCTs were identified using the search strategies developed for the Menstrual Disorders and Subfertility Group. See Review group for more information.
Selection criteria: Only randomised controlled trials were included. Livebirth rate per woman was the primary outcome of interest.
Data collection and analysis: Two reviewers independently assessed eligibility and quality of trials.
Main results: Nine randomised controlled trials were identified. In two we could not extract data separately for unexplained infertility cases, two were non-randomised, one reported no valid rates (included in the review and not in the meta-analysis), leaving four trials for analysis. One trial compared two different interventions (IVF versus IUI with or without ovarian stimulation) and one study compared three interventions (IVF versus IUI with ovarian stimulation and GIFT). The number of trials assessing the effectiveness of IVF with the other treatments were as follows: IVF versus expectant management (one), IVF versus IUI (one), IVF versus IUI with ovarian stimulation (two) and IVF versus GIFT (three). Livebirth rate per woman was reported in two studies and three studies determined clinical pregnancy rate per woman. Multiple pregnancy rate was reported in three trials. Two studies reported ovarian hyperstimulation syndrome (OHSS) as an outcome measure. There were no comparative data for clomiphene citrate, and no comparative data on livebirth rates for expectant management or GIFT. There was no evidence of a difference in livebirth rates between IVF and IUI either without (OR 0.51, 95% CI 0.23 to 1.1) or with (OR 0.87, 95% CI 0.42 to 1.8) ovarian stimulation. There was no evidence of a difference in clinical pregnancy rates between IVF and expectant management. There was no significant difference in the clinical pregnancy rates between IVF and GIFT (OR 0.47, 95% CI 0.24 to 0.92). There was no evidence of a difference in the multiple pregnancy rates between IVF and either IUI with ovarian stimulation (OR 1.59, 95% CI 0.68 to 3.70) or GIFT (OR 0.47, 95% CI 0.08 to 0.58). Clinical heterogeneity was present among the studies included. However, there was no evidence of statistical heterogeneity, which allowed the studies to be combined for statistical analysis.
Reviewer's conclusions: Any effect of IVF relative to expectant management, clomiphene citrate, IUI with or without ovarian stimulation and GIFT in terms of livebirth rates for couples with unexplained subfertility remains unknown. The studies included are limited by their small sample size, so that even large differences might be hidden. Livebirth rates are seldom reported. Adverse effects such as multiple pregnancies and ovarian hyperstimulation syndrome have also not been reported in most studies. Larger trials with adequate power are warranted to establish the effectiveness of IVF in these women. Future trials should not only report rates per woman /couple but also include adverse effects and costs of the treatments compared as outcomes. Factors that have a major effect on these outcomes such as fertility treatment, female partner's age, duration of infertility and previous pregnancy history should also be considered.