Endometrial Scratch Trial
A Multicentre Randomised Controlled Trial of Induced Endometrial Scratch in Women Undergoing First Time IN Vitro Fertilisation (IVF)
The challenges
In vitro fertilisation (IVF), with or without intracytoplasmic sperm injection (ICSI), is a widely used reproductive technique in women unable to conceive naturally. An array of expensive ‘add-on’ treatments are often offered, many of which lack robust evidence to support their use. One such add-on is the endometrial scratch (ES) procedure, where the endometrium is abraised prior to embryo transfer, which is hypothesised to increase the chances of live birth by improving embryo implantation. However, in women undergoing their first IVF cycle, several controlled trials have identified contradictory evidence, with the most recent systematic review concluding that there is a lack of high-quality evidence. Many of these previous studies included both women undergoing their first IVF cycle, and women undergoing subsequent cycles, and were therefore not powered to detect clinically worthwhile effects in those undergoing their first IVF cycle.
Fertility treatment has a significant cost burden to the National Health Service (NHS) and patients, with the cost to the NHS estimated to be around £68 million per year (based on 2013 costs). The number of first IVF cycles funded by the NHS has been decreasing over recent years, with 58% of first cycles funded by the NHS in 2017, reducing to 52% in 2018. Given that the average patient receives three cycles of IVF, and a single IVF cycle can cost £5000, the cost of IVF treatment is a significant burden to patients. Additionally, loss of productivity due to the emotional and physical effects of IVF treatment has been estimated at £540 (€596, converted in 2020) per woman per IVF cycle in one study. The cost of IVF is increased further if the couple decide to undergo the ES procedure, despite a lack of evidence to suggest it is effective or safe. The ES is estimated to cost £325 per cycle – a cost that does not take into account the potential pain of receiving the procedure and potential health care contacts if the procedure is in fact unsafe. Therefore, any increase in LBRs in the first cycle of IVF will prevent patients from receiving subsequent IVF cycles, therefore reducing this burden.
A high-quality randomised controlled trial (RCT) was required to definitively conclude if the ES procedure is clinically effective, cost effective and safe.
The research
The trial was a pragmatic, two-arm, superiority, open-label, parallel-group, multicentre, individually RCT undertaken at 16 fertility units in the United Kingdom, two of which were run privately. Participants were randomised to receive either the ES procedure followed by usual care, or usual IVF care only (treatment as usual (TAU)).
1048 female participants aged 18 to 37 years (inclusive) and undergoing their first cycle of IVF were recruited (other eligibility criteria were also applied).
The ES procedure was performed by a doctor or nurse in the mid-luteal phase of the menstrual cycle preceding IVF. ES was performed by inserting a speculum into the vagina. A pipelle or similar device was then inserted into the cavity of the uterus and negative pressure was applied by withdrawal of the plunger. The sampler was rotated and withdrawn three to four times so that tissue appeared in the transparent tube.
TAU participants received IVF treatment (with or without ICSI) according to the usual care practice of their fertility unit. ES participants received the ES procedure followed by TAU.
The results
Although the live birth rate was 1.5% higher in the endometrial scratch group (38.6%) compared to the control group (37.1%), the difference was not large enough to show any benefit of having the procedure. Other outcomes did not differ significantly between the two groups. However, the procedure was safe and tolerable. We found that the costs were on average £316 more expensive for those that received the endometrial scratch, compared to the control group; the difference was not large enough to show that receiving endometrial scratch was more cost-effective. We combined the results of this trial with previous trials that looked to answer a similar question, showing that, overall, the endometrial scratch does not enhance the chances of achieving a live birth.
The impact
We recommend that ES should not be undertaken in women undergoing their first cycle of IVF. However, the HFEA ‘traffic light’ currently remains amber (https://www.hfea.gov.uk/treatments/treatment-add-ons/endometrial-scratching/).
The results of the trial were presented by Mostafa Metwally at the European Society of Human Reproduction and Embryology (ESHRE) conference in July 2020. A press release was also undertaken by ESHRE: https://www.eshre.eu/ESHRE2020/Media/2020-Press-releases/Metwally.
There were other press releases from Sheffield Teaching Hospitals and the NIHR:
New research suggests IVF ‘scratch’ offers no benefit to women undergoing IVF for the first time
Publications
Daily Mail article: “'SCRATCH' TREATMENT MAKES NO DIFFERENCE TO IVF SUCCESS RATES, STUDY FINDS”.
Project team
- Project Team
-
Name Role Site Contact Chief Investigator Sheffield Teaching Hospitals mmetwally@nhs.net
01142 268092
Trial Manager The University of Sheffield R.chatters@sheffield.ac.uk
0114 2222969
Clare Pye RN
Lead Research Nurse Sheffield Teaching Hospitals Clare.Pye@sth.nhs.uk
0114 2268194
Sub Study Investigator Sheffield Hallam University s.m.laird@shu.ac.uk
Data Management Team The University of Sheffield endo-scratch-dm-group@sheffield.ac.uk Senior Statistician The University of Sheffield s.j.walters@sheffield.ac.uk
0114 222 0730
Statistician The University of Sheffield m.dimairo@sheffield.ac.uk
0114 222 5204
Health Economics The University of Sheffield t.a.young@sheffield.ac.uk
0114 222 0837
CTRU Advice The University of Sheffield 0114 222 0870
Kate Brian
PPI Lead Lamiya Mohiyiddeen
Clinical Advice Manchester University Hospitals lamiya.mohiyiddeen@cmft.nhs.uk
Clinical Advice University of Southampton y.cheong@soton.ac.uk