The Cochrane Database of Systematic Reviews, CD003357, 2012
Abstract
Background
In vitro fertilisation (IVF) is a widely accepted treatment for unexplained infertility (NICE 2004), which affects up to a third of all infertile couples. With estimated live birth rates (LBRs) per cycle varying from 33.1% in women aged under 35 years down to 12.5% in women aged between 40 and 42 years (HFEA 2011), its effectiveness has not been rigorously evaluated in comparison with other treatments. With increasing awareness of the role of expectant management, less-invasive procedures such as intrauterine insemination (IUI), and concerns about multiple pregnancies and costs associated with IVF, it is important to evaluate the effectiveness of IVF against other treatment options in couples with unexplained infertility.
Objectives
To evaluate the effectiveness and safety of IVF compared to expectant management, clomiphene citrate, IUI alone and intrauterine insemination plus controlled ovarian stimulation (IUI+SO).
Search Methods
Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, first quarter), MEDLINE (1970 to July 2011), EMBASE (1985 to July 2011) and reference lists of articles were searched. Relevant conference proceedings were handsearched. Authors were contacted.
Selection Criteria
Randomised controlled trials (RCTs) were included. LBR per woman was the primary outcome.
Data Collection and Analysis
Two review authors independently assessed eligibility and quality of trials.
Main Results
Six RCTs were included in the final analysis. LBR per woman was significantly higher with IVF (45.8%) than expectant management (3.7%) (odds ratio (OR) 22.00, 95% confidence interval (CI) 2.56 to 189.37, 1 RCT, 51 women). There were no comparative data for clomiphene citrate. There was no evidence of a significant difference in LBR between IVF and IUI alone (OR 1.96, 95% CI 0.88 to 4.36, 1 RCT, 113 women), 40.7% with IVF versus 25.9% with IUI. In studies comparing IVF versus IUI+SO, LBR per woman did not differ significantly between the groups among treatment-naive women (OR 1.09, 95% CI 0.74 to 1.59, 2 RCTs, 234 women) but was significantly higher in a large RCT of women pretreated with IUI + clomiphene citrate (OR 2.66, 95% CI 1.94 to 3.63, 1 RCT, 341 women). These three studies could not be pooled due to high heterogeneity (I(2) = 84%). There was no evidence of a significant difference in multiple pregnancy rate (MPR) or ovarian hyperstimulation syndrome (OHSS) between the two treatments (OR 0.64, 95% CI 0.31 to 1.29, 3 RCTs, 351 women; OR 1.53, 95% CI 0.25 to 9.49, 1 RCT, 118 women, respectively). AUTHORS'
Conclusions
IVF may be more effective than IUI+SO. Due to paucity of data from RCTs the effectiveness of IVF for unexplained infertility relative to expectant management, clomiphene citrate and IUI alone remains unproven. Adverse events and the costs associated with these interventions have not been adequately assessed.
Topics
IVF unexplained subfertility Cochrane systematic review, in vitro fertilisation versus IUI unexplained infertility, unexplained infertility IVF expectant management comparison, live birth rate IVF versus intrauterine insemination, randomized controlled trial IVF unexplained subfertility effectiveness, IVF versus IUI controlled ovarian stimulation unexplained, Pandian Bhattacharya Cochrane IVF unexplained infertility, cost effectiveness IVF unexplained subfertility, multiple pregnancy risk IVF versus IUI ovarian hyperstimulation, clomiphene citrate IUI IVF treatment naive unexplained infertility
PMID 22513911 22513911 DOI 10.1002/14651858.CD003357.pub3 10.1002/14651858.CD003357.pub3
Cite this article
Pandian, Z., Gibreel, A., & Bhattacharya, S. (2012). In vitro fertilisation for unexplained subfertility. The Cochrane database of systematic reviews, CD003357. https://doi.org/10.1002/14651858.CD003357.pub3
Pandian Z, Gibreel A, Bhattacharya S. In vitro fertilisation for unexplained subfertility. Cochrane Database Syst Rev. 2012:CD003357. doi:10.1002/14651858.CD003357.pub3
Pandian, Zabeena, et al. "In vitro fertilisation for unexplained subfertility." The Cochrane database of systematic reviews, no. 4, 2012, pp. CD003357.
Keywords
Fertility Agents, Female, Clomiphene
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Other comparisons Due to lack of evidence and very low-quality data there is uncertainty whether there is a difference for any LOD with IVF versus IVF, LOD with second-look laparoscopy versus expectant management, monopolar versus bipolar LOD, and adjusted thermal dose versus fixed thermal dose. AUTHORS' Laparoscopic ovarian drilling with and without medical ovulation induction may decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical ovulation induction alone. But the sensitivity analysis restricted to only RCTs at low risk of selection bias suggests there is uncertainty whether there is a difference between the treatments, due to uncertainty around the estimate. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancy. 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