Human Reproduction, Vol. 17, No. 4, 956-959,
April 2002
© 2002 European Society of Human Reproduction and Embryology
The use of intrauterine insemination in Australia and New Zealand
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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BACKGROUND: There is good evidence in the literature in favour of intrauterine insemination (IUI) as the most cost-effective treatment for unexplained and moderate male factor subfertility. However there is no published data on whether this evidence is being translated into clinical practice. METHODS: We identified fertility centres within Australia and New Zealand registered with the Reproductive Technology Accreditation Committee of the Fertility Society of Australasia. Thirty-seven of these units were then sent a postal survey to establish current clinical practice. RESULTS: Nearly a third of centres promote IVF as first-line treatment even in the presence of patent tubes and normal semen while, when semen parameters are reduced, IUI is rarely considered. One in five (20%) units remain unconvinced of the cost-effectiveness of IUI. When IUI is used, it is virtually always combined with ovarian stimulation with marginally more units using clomiphene citrate than gonadotrophins. CONCLUSIONS: Although it may take relatively more treatment cycles to achieve pregnancy, there are considerable advantages to the patient in terms of risk/benefit ratio and financial cost associated with IUI compared with IVF. In the current climate of evidence-based medicine, as clinicians we are obliged to translate this into our practice. It appears from our survey that in many units this is not happening.
Key words: intrauterine insemination/IVF
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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Involuntary subfertility is a common problem, affecting up to 15% of couples (Templeton et al., 1990
) and demand for medical treatment is increasing. In an attempt to improve spontaneous conception rates, artificial insemination techniques in various forms have been practised for almost 200 years (Brinsden and Marcus, 1997). Recently the most refined of these, intrauterine insemination (IUI), alone or in combination with controlled ovarian hyperstimulation (COH), has been the focus of a substantial amount of research. A literature search using `intrauterine insemination' as a key word identified 114 English language citations on Medline and 39 citations in the Cochrane Controlled Trials Register since 1998 alone. As a result there is now considerable evidence that the use of IUI (with or without COH) for couples with unexplained or mild to moderate male factor infertility can achieve pregnancy rates of 10.5–17.9% per cycle (Stone et al., 1999; Cohlen et al., 2000; Kaplan et al., 2000) compared with a spontaneous pregnancy rate of 2% per cycle. Despite these figures the role of IUI has remained controversial, particularly in relation to IVF. It is also apparent that there are wide variations in patient selection criteria and cycle regimens between the units that have published their results.
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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A total of 68 fertility units registered with the Reproductive Technology Accreditation Committee of the Fertility Society of Australasia were identified. Of these, satellite clinics and those units not offering IUI, IVF and/or gamete intra-Fallopian transfer (GIFT) were excluded. Satellite clinics were excluded on the basis that treatment guidelines would mirror those of the central unit. The remaining 37 centres were sent questionnaires, each with 13 questions (Table I
) relating to their practice, covering a 12 month period from January to December 1999. Each centre was provided with a pre-paid reply envelope. Non-response by a unit was followed up with a further postal questionnaire and finally a faxed questionnaire.
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Data were analysed using Fisher's exact test. A P-value
0.05 was considered statistically significant. |
Results |
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Twenty-seven (73%) units responded, although three felt unable to answer the questionnaire, leaving 24 evaluable replies. Overall, IUI made up 37% of treatment cycles (Table II
). In nearly a third of units (seven, 30.4%) at least 80% of cycles were IVF or ICSI. GIFT was relatively rarely used, comprising only 7% of total cycles with only four units performing >10% GIFT cycles. Six units (25%) performed some unstimulated cycles of IUI. In stimulated IUI, COH using FSH made up less than half the total cycles (Table II) with the remainder using clomiphene citrate. Pregnancy rates for each treatment cycle were greatest with IVF/ICSI (Table II). The two units that failed to achieve pregnancy following IUI with FSH carried out very few IUI cycles. The combined mean pregnancy rate for all IUI cycle types was 11.9% (5–21%). Overall, 15 units (65%) reported pregnancy rates of >10% per cycle.
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On average, a basic semen analysis with a sperm concentration of 12.9x106/ml (range: 2–20) and normal morphology of at least 23.4% (range: 1–95) was considered suitable for IUI. Ninety-five percent of these units set a minimum threshold for sperm concentration of at least 5x106/ml. There was a considerable variation in what constitutes an acceptable sperm preparation result, with a range from 0.1–40x106 motile sperm/ml. In the presence of normal sperm and patent tubes the majority of units routinely offer IUI as first-line treatment, although almost a third recommend IVF on the basis of superior pregnancy rates (Table III
). In the presence of reduced basic semen parameters the use of IUI fell markedly, with nearly 40% of units rarely considering IUI an option (Table III). Centres that routinely used IUI for unexplained infertility were significantly more likely to offer IUI for male factor subfertility (5 versus 0, P = 0.03). Nineteen units (82.6%) were, however, prepared to offer IUI to women >40 years old.
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Although there was a variety of drug regimens used for COH, clomiphene citrate alone was the single most popular choice (Table IV
). Only two units routinely used FSH in doses >75 IU daily. Twelve units (52.2%) monitored serum estrogen daily or on alternate days starting between days 8 and 10, five units (21.7%) performed a single measurement and six units (26.1%) did not assess estrogen. Twenty units (86.9%) attempted to detect the LH surge by blood or urine at the time of estrogen estimation (50%) or based on follicle size at ultrasound (30%).
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Most units believed that IUI is a cost-effective procedure, but five units (21.7%) were unsure or strongly disagreed (Figure 1
). A total of 80% of the units who answered limited IUI to three or four cycles before recommending a change of treatment.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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Our study provides information on the current place of IUI in clinical practice in 23 tertiary infertility centres within Australia and New Zealand, and to our knowledge is the only study of its kind. At present the majority of treatment cycles consist of IVF/ICSI with nearly a third of units recommending IVF as the first-line treatment, even in the presence of patent tubes and a normal semen analysis. When IUI is used, it is almost always in conjunction with COH. Given that there is published evidence in favour of this approach in the literature, it was interesting to us that 25% of units were prepared to undertake IUI without ovarian stimulation. This may have reflected local patient preference for `natural cycle' IUI.
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 5.2–12.6% 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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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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We would like to thank all the clinical directors of fertility centres that took the time to answer our questionnaire.
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Notes |
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3 To whom correspondence should be addressed at: 67 Klea Avenue, Clapham, London SW4 9HZ, UK. E-mail: miskry{at}hotmail.com
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References |
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Aboulghar, M.A., Mansour, R.T., Serour, G.I., Amin, Y., Ramzy, A.M., Sattar, M.A. and Kamal, A. (1999) Management of long-standing unexplained infertility: a prospective study. Am. J. Obstet. Gynecol., 181, 371–375.[Medline]
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Submitted on July 16, 2001; resubmitted on October 23, 2001; accepted on November 13, 2001.
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