Economic evaluation of endometrial scratching before the second IVF/ICSI treatment: a cost-effectiveness analysis of a randomized controlled trial (SCRaTCH trial)

Abstract

Study question: Is a single endometrial scratch prior to the second fresh IVF/ICSI treatment cost-effective compared to no scratch, when evaluated over a 12-month follow-up period?

Summary answer: The incremental cost-effectiveness ratio (ICER) for an endometrial scratch was €6524 per additional live birth, but due to uncertainty regarding the increase in live birth rate this has to be interpreted with caution.

What is known already: Endometrial scratching is thought to improve the chances of success in couples with previously failed embryo implantation in IVF/ICSI treatment. It has been widely implemented in daily practice, despite the lack of conclusive evidence of its effectiveness and without investigating whether scratching allows for a cost-effective method to reduce the number of IVF/ICSI cycles needed to achieve a live birth.

Study design, size, duration: This economic evaluation is based on a multicentre randomized controlled trial carried out in the Netherlands (SCRaTCH trial) that compared a single scratch prior to the second IVF/ICSI treatment with no scratch in couples with a failed full first IVF/ICSI cycle. Follow-up was 12 months after randomization.Economic evaluation was performed from a healthcare and societal perspective by taking both direct medical costs and lost productivity costs into account. It was performed for the primary outcome of biochemical pregnancy leading to live birth after 12 months of follow-up as well as the secondary outcome of live birth after the second fresh IVF/ICSI treatment (i.e. the first after randomization). To allow for worldwide interpretation of the data, cost level scenario analysis and sensitivity analysis was performed.

Participants/materials, setting, methods: From January 2016 until July 2018, 933 women with a failed first IVF/ICSI cycle were included in the trial. Data on treatment and pregnancy were recorded up until 12 months after randomization, and the resulting live birth outcomes (even if after 12 months) were also recorded.Total costs were calculated for the second fresh IVF/ICSI treatment and for the full 12 month period for each participant. We included costs of all treatments, medication, complications and lost productivity costs. Cost-effectiveness analysis was carried out by calculating ICERs for scratch compared to control. Bootstrap resampling was used to estimate the uncertainty around cost and effect differences and ICERs. In the sensitivity and scenario analyses, various unit costs for a single scratch were introduced, amongst them, unit costs as they apply for the United Kingdom (UK).

Main results and the role of chance: More live births occurred in the scratch group, but this also came with increased costs over a 12-month period. The estimated chance of a live birth after 12 months of follow-up was 44.1% in the scratch group compared to 39.3% in the control group (risk difference 4.8%, 95% CI -1.6% to +11.2%). The mean costs were on average €283 (95% CI: -€299 to €810) higher in the scratch group so that the point average ICER was €5846 per additional live birth. The ICER estimate was surrounded with a high level of uncertainty, as indicated by the fact that the cost-effectiveness acceptability curve (CEAC) showed that there is an 80% chance that endometrial scratching is cost-effective if society is willing to pay ∼€17 500 for each additional live birth.

Limitations, reasons for caution: There was a high uncertainty surrounding the effects, mainly in the clinical effect, i.e. the difference in the chance of live birth, which meant that a single straightforward conclusion could not be ascertained as for now.

Wider implications of the findings: This is the first formal cost-effectiveness analysis of endometrial scratching in women undergoing IVF/ICSI treatment. The results presented in this manuscript cannot provide a clear-cut expenditure for one additional birth, but they do allow for estimating costs per additional live birth in different scenarios once the clinical effectiveness of scratching is known. As the SCRaTCH trial was the only trial with a follow-up of 12 months, it allows for the most complete estimation of costs to date.

Study funding/competing interest(s): This study was funded by ZonMW, the Dutch organization for funding healthcare research. A.E.P.C., F.J.M.B., E.R.G. and C.B. L. reported having received fees or grants during, but outside of, this trial.

Trial registration number: Netherlands Trial Register (NL5193/NTR 5342).

Keywords: ART; ICSI; IVF; cost-effectiveness; economic analysis; endometrial injury; endometrial scratch; live birth.

Figure 1.

Cost-effectiveness acceptability plane of the chance of pregnancy leading to live birth after 12 months of follow-up.^a The red triangles are the differences between scratch and control in the chance of achieving a live birth and the difference in average costs from individual bootstrap samples. The black lines indicate the 95% CI for these differences. The black dot represents the point estimate for the averages that is used to calculate the point estimate for the ICER. The spread of the triangles indicates the uncertainty around the differences in live birth and costs, and thus, in the ICER. While most triangles are in the upper right quadrant, indicating that scratching is more expensive and yields a higher chance of achieving a live birth, some triangles are also in the upper left quadrant (more expensive and less effective), bottom left quadrant (less expensive and less effective) and bottom right quadrant (less expensive and more effective). ^aThe ongoing pregnancy status had to be reached within 12 months after randomization; live birth could have resulted after 12 months of follow-up. EUR, European euro (€).

Figure 2.

Cost-effectiveness acceptability curve for the chance of pregnancy leading to live birth after 12 months of follow-up.^a The cost-effectiveness acceptability curve is shown for increasing monetary value for each additional live birth that society is willing to pay, with calculations ranging from €1 to €50 000. The line indicates the probability that endometrial scratching is cost-effective at varying monetary values for each additional live birth. ^aThe ongoing pregnancy status must be reached within 12 months after randomization; live birth could have resulted after 12 months of follow-up. EUR, European euro (€).

Figure 3.

Cost-effectiveness acceptability plane of the chance of pregnancy leading to live birth from the 2nd fresh IVF/ICSI treatment. The red triangles are the differences between scratch and control in the chance of achieving a live birth and the difference in average costs from individual bootstrap samples. The black lines indicate the 95% CI for these differences. The black dot represents the point estimate for the averages that is used to calculate the point estimate for the ICER. The spread of the triangles indicates the uncertainty around the differences in live birth and costs, and thus, in the ICER. Although scratching was more expensive than control in all bootstrap samples, this did not always yield a positive difference in the chance of achieving a live birth. EUR, European euro (€).

Figure 4.

Cost-effectiveness acceptability curve for the chance of pregnancy leading to live birth from the second fresh IVF/ICSI treatment. The cost-effectiveness acceptability curve is shown for increasing monetary value for each additional live birth that society is willing to pay, with calculations ranging from €1 to €50 000. The line indicates the probability that endometrial scratching is cost-effective at varying monetary values for each additional live birth that originates from the second fresh IVF/ICSI treatment. EUR, European euro (€).