1 Department of Obstetrics and Gynaecology, St George Hospital, Kogarah, NSW, Australia 2 Present address: 67 Klea Avenue, Clapham, London SW4 9HZ, UK.
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Abstract |
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Key words: intrauterine insemination/IVF
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Introduction |
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The cost-effectiveness of IUI compared with IVF has recently been addressed by a prospective randomized controlled trial from Holland (Goverde et al., 2000). The authors reported no significant difference in cumulative pregnancy rates between IUI with COH and IVF, while the cost of IVF was more than twice that of IUI with COH. These findings agree with an evaluation of infertility treatments in the UK, which also concluded that IUI should be considered the most cost effective treatment for unexplained and moderate male factor infertility (Philips et al., 2000
). This evidence should make IUI attractive to both patients and clinicians as IUI is less invasive, requires less intensive monitoring and is associated with lower risks of hyperstimulation and multiple pregnancy. Although the evidence is there to support a policy of IUI as first-line management for idiopathic and mild/moderate male factor infertility, to our knowledge there is no published data to establish whether this is currently happening in clinical practice. In Australia, the subsidized infertility system through Medicare has led to the highest rate of IVF per head of population in the world. Against that background, the aim of this study was to examine the pattern of use of IUI within fertility units in Australia and New Zealand.
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Materials and methods |
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Results |
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Discussion |
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IUI in combination with COH in unexplained infertility is clearly associated with acceptable pregnancy rates, which is reflected by the fact that most units stated that they would offer this as the first-line treatment in appropriate cases. In general, despite the limitations of self-reported data, the results reported by units in Australia and New Zealand are consistent with those reported in the literature, with most centres achieving pregnancy rates of ~12% per cycle. Given these results, it is difficult to understand why nearly a third of the units surveyed are promoting IVF as first-line management. Although these units justify their policy on the basis of higher per cycle pregnancy rates, this ignores the fact that although it may take more treatment cycles to get pregnant following IUI, for many women IVF would become unnecessary. While with enough cycles cumulative pregnancy rates of >60% can be achieved (Matorras et al., 2000), even adopting an initial protocol of three cycles of IUI prior to IVF will allow almost 30% of patients to avoid IVF (Aboulghar et al., 1999
), which is universally accepted as being more invasive as well as more expensive to the patient, both financially and psycho-socially.
The same principle applies to those with mild/moderate semen abnormalities. Although success rates may not be as good as for idiopathic infertility, the most recent Cochrane review (Cohlen et al., 2000) reported that IUI with COH significantly increased the probability of pregnancy by a combined odds ratio of 6.0 compared with timed intercourse alone. After meta-analysis, IUI with or without COH resulted in overall pregnancy rates of 5.212.6% per completed cycle. In a recent analysis of >9000 cycles of IUI with COH, male factor subfertility was associated with a pregnancy rate of 8.2% in a population with an average female age of 39 years (Stone et al., 1999
). As for those with idiopathic infertility, an initial policy of `trial of IUI' would be expected to spare the rigours of IVF for many couples.
In order to reproduce these results it has been reported that initial sperm concentration should be at least 5x106/ml (Dickey et al., 1999), while following semen preparation at least 1x106 motile sperm should be available for insemination (Berg et al., 1997
; Goverde et al., 2000
), which is less than the threshold of 2x106 sperm with 80% motility in our survey. Despite this, only five units routinely offer IUI as first-line treatment with these type of post-preparation results when the basic semen analysis is abnormal, with 40% of centres preferring IVF/ICSI and therefore rarely offering IUI.
Paradoxically the majority of units would offer IUI to women >40 years despite evidence of low pregnancy rates in these patients (Nuojua-Huttunen et al., 1999). As with other treatment protocols, patient age is the most important predictor of success, with <5% of women aged >40 and 0.5% of women >45 years conceiving following IUI (Stone et al., 1999
). In our questionnaire we asked whether individual units would use IUI in this population, to which >80% said yes. However, we did not ask how often they did. It seems likely that use of IUI in these women would be determined by patient preference against a clinic preference for IVF.
Virtually all units routinely combined IUI with COH, with the majority of centres using clomiphene citrate rather than gonadotrophins. This strategy is reasonable as the addition of COH to increase the number of available oocytes at ovulation has been shown to as much as double the chances of pregnancy compared with IUI alone (Guzick et al., 1999), although the evidence of benefit from COH in the treatment of male infertility is not as convincing (Cohlen et al., 1998
). Units in Australia and New Zealand appear to use relatively low-dose COH regimens, with <10% using >75 IU of FSH. It is possible that these doses represent sub-optimal stimulation, which would skew results in favour of IVF/ICSI. However, although more intensive COH can be associated with higher pregnancy rates, relatively poor control of the number of ovulated oocytes increases the risk of multiple pregnancy. This is a disadvantage when IUI is compared with in-vitro techniques, which can potentially be precisely controlled by limiting the number of replaced embryos.
At present there is no clear evidence in the literature to enable us to conclude whether clomiphene citrate or gonadotrophins are superior for ovarian stimulation, with some studies promoting gonadotrophins (Manganiello et al., 1997) and others reporting no difference in pregnancy rates (Ecochard et al., 2000
). On this background a pragmatic choice by individual clinics is currently entirely reasonable. Based on the variety of drug regimes used by clinics in our survey and reported in the literature, more research is needed to establish both the drug and dose of choice for COH to improve pregnancy rates while minimizing the risks of ovarian hyperstimulation and multiple pregnancy.
In conclusion, despite good evidence of the cost-effectiveness of IUI, 20% of centres within Australia and New Zealand remain unconvinced and this is reflected in clinical practice. One in three units recommending IVF as the first-line treatment even in the presence of patent tube and normal semen reflects how infertility treatment is `sold', with IVF being promoted as the technique likely to result in pregnancy `as quickly as possible'. This ignores the considerable advantages to patients of IUI compared with IVF in invasiveness, level of monitoring, risks and financial costs. In the current climate of evidence-based medicine, it seems clear to us that IUI should be offered as the first-line treatment for unexplained and mild/moderate male factor infertility. Once provided with the right information, patients will elect which they prefer, speed versus cost and invasiveness.
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Acknowledgements |
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Notes |
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References |
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Submitted on July 16, 2001; resubmitted on October 23, 2001; accepted on November 13, 2001.