Endometrial scratching: A systematic review and meta-analysis

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Endometrial scratching for subfertility: A survey of current practice

Chapter overview

Background Endometrial scratching is currently being proposed as a technique to increase the probability of implantation in women undergoing IVF. While available evidence is in favour of this procedure, uncertainty remains about both the extent of any beneficial effect and the subgroups of women most likely to benefit.
Aim To determine the proportion of fertility staff across Australia, New Zealand and the United Kingdom that offer or recommend endometrial scratching to subfertile women seeking conception.
Methods An online survey was distributed to all fertility clinics across Australia, New Zealand and the United Kingdom between August and October 2015. All clinicians, nurses and embryologists were eligible to take part. A total of 143 responses were analysed.
Results Eighty three percent of clinicians responding to the survey recommended endometrial scratching to women undergoing IVF, and 92% of these reported to recommend endometrial scratching to women with RIF. Very few clinicians reported to offer this procedure to women undergoing IUI (3%). Most respondents agreed that the procedure is beneficial in women with RIF undergoing IVF (73%), and disagreed that the procedure is beneficial for women undergoing their first IVF cycle (53% disagreed).
Strengths and limitations The response rate for the survey was 36% per clinic; it was not possible to calculate an individual response rate. Fertility staff who recommend endometrial scratching may be more likely to respond to the survey and this could exaggerate the use of the procedure reported here. This study was conducted across three countries and may be generalisable to similar settings.
Conclusion The majority of clinicians responding to this survey offer endometrial scratching, most commonly to women with RIF undergoing IVF. In spite of serious deficiencies in the quality of available studies, this procedure is already being recommended by the majority of respondents at the time of this survey.

Publications

A report of this survey has been published Lensen, L. Sadler, C. Farquhar; Endometrial scratching for subfertility: everyone’s doing it, Human Reproduction, Volume 31, Issue 6, 1 June 2016, Pages 1241–1244 (313)

Statement on the contribution by others

Cindy Farquhar assisted with the design and piloting of this survey, and Lynn Sadler assisted with the data analysis.

Introduction

Endometrial scratching has been proposed as a technique to increase the probability of implantation in women undergoing IVF. A Cochrane review concluded that endometrial scratching increases the chance of pregnancy in the IVF population, and that this effect is most apparent in women with RIF: that is, women who have failed to conceive from multiple previous embryo transfers (302). However, many of the available studies are associated with a high risk of bias, and as such the true extent of any beneficial effect remains controversial (302,304,314-316).

Aims

The aim of this survey was to determine the current practices of offering or recommending endometrial scratching in fertility clinics in Australia, New Zealand and the United Kingdom, and to survey fertility clinic staff about their opinions on the beneficial effect of endometrial scratching.

Methods

Survey design and participants

A list of all fertility clinics across Australia, New Zealand and the United Kingdom was compiled from a combination of sources, including the Human Fertilisation and Embryology Authority and Fertility Society of Australia websites, lists utilised in previous surveys, and prior knowledge of existing clinics (317). Identification of the Clinical Directors at each clinic was made by website search or an email or phone call to the clinic reception. A link to a web-based survey was distributed by email to the Clinical Director or their equivalent at each clinic with an explanatory cover letter. The email requested the recipient to forward the survey link on to all eligible staff within their organisation. Eligible participants were fertility staff: specifically, clinicians, nurses and embryologists. The survey was intended to be completed by multiple staff at each clinic as it was not clear a priori whether individuals in the same clinic would have similar practices, and it was intended to get as many responses as possible. One reminder email was sent approximately three weeks later.
The survey was piloted on a small group of fertility staff in Auckland, New Zealand, as part of the survey design process. The survey had a total of 24 questions. Conditions were built into the logic such that not all participants answered all questions, for example questions were skipped based on the participants’ profession or answer to a prior question. There was an option to opt-out of the survey and the questionnaire was open online from August 2015 to October 2015. Ethics approval was obtained from the University of Auckland Human Participants Ethics Committee (Reference 014785).

Statistical analysis

Data were anonymised and analysed using Microsoft Excel and chi squared tests were carried out in OpenEpi (318). In cases of missing data, the denominator for that field was reduced to the number of respondents answering the question.

Results

Response rates and demographics

Survey invitations were sent to 189 clinics, and at least one fertility staff member responded from 68 clinics (36%). The response rates per clinic in each country were 41% (40/97) in Australia, 43% (3/7) in New Zealand, and 29% (25/85) in the United Kingdom. Multiple responses were received per clinic in 33 cases, with a range of one to eight responses per clinic and a median of one. Due to the method of distributing the survey, the number of individuals who received the survey link is unknown and therefore it is not possible to calculate an individual response rate. Of the 152 responses received, nine were excluded (five duplicates, two incomplete with no useable information, two ineligible staff members) leaving 143 eligible responses. Most of the responses were from Australian clinicians with more than 20 years’ experience (Table 3.1).

Clinic policies

The majority of respondents report that the use of endometrial scratching in their clinic is at the discretion of individual clinicians, however it was also common for fertility clinics to have clinic-level agreements, guidance or protocols to advise staff on use of endometrial scratching (Table 3.2). Responses varied across countries: most respondents from the United Kingdom reported to follow “written guidance that describes when endometrial scratching can/should be offered or recommended” (58%), whereas respondents from Australia and New Zealand were more likely to report that it is at the “discretion of the individual fertility clinician whether to offer or recommend endometrial scratching to a patient” (83% and 61% respectively).
Clinicians were requested to provide information about their practices of recommending endometrial scratching. Of the 100 clinicians completing the survey, 83% reported to “currently offer or recommend endometrial scratching” and 77% (64/83) of these reported to “currently offer or recommend endometrial scratching prior to, or as part of, an IVF cycle”. Additionally, 86% (55/64) of clinicians offering the procedure before IVF, offer it to women undergoing frozen embryo transfers. Of those not recommending endometrial scratching (17/100), the majority had “not decided whether to offer or recommend it to patients yet” (47%), however a number reported that they have “previously offered scratching and no longer do” (29%), or that their clinic has a policy to not offer scratching (6%). Endometrial scratching was introduced in some clinics as early as January 2010. The most recent reported introduction was in 2015. During that time five respondents also started and subsequently stopped offering the procedure.
The most common indication for endometrial scratching was RIF (92%). However, free-text definitions provided for a diagnosis of RIF were variable. While some clinicians included the number of previous transfers (e.g. “more than three good quality embryos”), others included the number of previous cycles (e.g. “after two failed cycles”), some included both (e.g. “women who fail to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles”), and all included at least one or the other. The number of previously transferred embryos needed to meet the definition ranged from 0-5, with an average of 2.5. The quality of the embryos transferred was frequently included (58%), however the stage of the embryos and age of the recipient were less common (23% and 9%, respectively). Other indications for scratching included recurrent miscarriage (28%) and advanced age (16%), while 6% of clinicians indicated that they offer scratching to all women undergoing IVF (Table 3.3). There did not appear to be a relationship between the country of the respondent and their indications for endometrial scratching (data not provided).
The most common timeframe for performing endometrial scratching was the luteal phase of the cycle prior to the embryo transfer cycle (89%), however a small number of clinicians conduct the procedure in the follicular phase of both the prior cycle (3%) and the embryo transfer cycle (9%). No respondents perform the procedure on the day of oocyte retrieval or embryo transfer.

Endometrial scratching in IUI or natural cycles

Only 3.6% of clinicians “offer or recommend endometrial scratching to couples trying to conceive from sexual intercourse or IUI.” All three respondents view women with recurrent miscarriage as an indication for scratching, and perform endometrial scratching in the luteal phase of the cycle prior to the IUI/attempted conception cycle.

Cost

Many respondents from Australia and the United Kingdom reported that the procedure is government funded for eligible patients. The average cost for private patients was reported as $145 NZD (Range $100-$295 NZD), £187 (Range £100-£400) and $140 AUD (Range $130-$465).

Opinions of fertility staff

All participants (clinicians, nurses and embryologists) were asked their opinion on the benefit of endometrial scratching in different patient populations (Table 3.4). Most respondents agreed that the procedure is beneficial in women with RIF undergoing IVF (73%) and disagreed that the procedure is beneficial for women undergoing their first IVF cycle (53% disagreed). New Zealand fertility staff responded more neutrally regarding the benefit of endometrial scratching in women trying to conceive from intercourse or IUI, while those from the United Kingdom were more likely to disagree that the procedure is beneficial in these groups. Respondents were mostly neutral regarding whether they had noticed an increased pregnancy rate following endometrial scratching in their own clinic (Table 3.4).

Discussion

Key results

Eighty three percent of clinicians responding to the survey reported to offer endometrial scratching to their fertility patients, with 77% offering endometrial scratching to women undergoing IVF, most commonly in the case of RIF. Similarly, 73% of all fertility staff (clinicians, nurses and embryologists) agree that this procedure is beneficial in women with RIF undergoing IVF. However, the definitions of RIF varied widely between respondents, suggesting the practice of recommending this procedure is varied. Respondents were generally neutral or did not agree that endometrial scratching is beneficial in women undergoing their first IVF cycle, or in women trying to conceive from intercourse or IUI.

Interpretation of results

While the available studies appear favourable for women with RIF undergoing IVF, the aggregate evidence has been criticised due to the potential for bias associated with many of the available studies (314,315). One of the largest and most robust studies published reported a lack of benefit from endometrial scratching, and subgroup analysis even demonstrated a detrimental effect in women with RIF (250). In the context of this controversy it is surprising that the majority of clinicians who responded to this survey currently offer this procedure to their patients and that so few disagreed with the use of this procedure.
Although endometrial scratching appears to be widely used in women with RIF, an agreed definition for RIF continues to elude us; this survey reports a wide variation in the characteristics required for a diagnosis of RIF. This finding is similar to that reported by a systematic review of definitions of RIF used in fertility studies (72). A number of suggestions have been made as to a formal definition of RIF but there has been no official consensus (69-73). While it is understandable that RIF may be viewed along a continuum rather than as a binary entity, an agreed definition would greatly benefit the research and clinical community alike.
Most clinicians stated that they recommend endometrial scratching in the luteal phase of the cycle prior to the IVF cycle. At this point in the menstrual cycle the endometrium is at its thickest and is therefore optimal for sampling. This time also represents the window-of-implantation, and there appears to be some belief that scratching during this window will therefore have an optimal effect during the equivalent window in the subsequent cycle, at the time that the embryo transfer takes place, as discussed further in Chapter 4. It is not surprising that none of the respondents recommend the procedure be conducted on the day of oocyte retrieval or embryo transfer, as this has been reported to result in a detrimental effect on pregnancy rate (239).
Few clinicians reported to offer the procedure to women undergoing IUI or trying to conceive naturally, although several trials report a beneficial effect of endometrial scratching in this population (260,263,264) (Chapter 2). It may be that this evidence is less widely known as these trials have been conducted more recently, or that the trials are deemed to be of low-quality.

Strengths and limitations of this study

The major limitation of this survey was the low clinic-level response rate of 36%, which is lower than or similar to other surveys in this area (317,319,320). The ethics approval did not allow direct communication with individual fertility clinic staff; the survey was emailed directly to the Clinical Director for distribution and only one reminder email was permitted. The low response rate is of concern as it may introduce a bias; endometrial scratch enthusiasts may have been more likely to respond to the survey, which could have inflated the use of the procedure reported here. Lower response rates are more common with online surveys (321,322); however, a paper-based survey was not feasible for this study due to its international scope. This survey was distributed to all fertility clinics across Australia, New Zealand and the United Kingdom and this multi-national reach may have increased the generalisability of the results compared to single-country surveys. There was a large variation in the response rate per clinic, with a range of 0-8 responses per invited clinic. As it was common for the use of endometrial scratching to be at the discretion of individuals, it may be most appropriate that responses were not restricted to one per clinic; however, this may also have introduced a clustering effect.

Conclusion

The large majority of clinicians and fertility staff offer endometrial scratching to women with RIF undergoing IVF and consider that the procedure is beneficial in this population. This does not appear to reflect the conflicting evidence and concern about the low quality of studies available in the literature. Further, the definition for RIF appears to vary widely and a consensus definition is overdue and would be much welcomed.

Table of Contents
Abstract 
Acknowledgements 
Table of contents 
Glossary 
Chapter 1: Background 
1.1 Chapter overview
1.2 Subfertility
1.3 In vitro fertilisation (IVF)
1.4 The endometrium
1.5 Endometrial scratching
Chapter 2: Endometrial scratching: A systematic review and meta-analysis
2.1 Chapter overview
2.2 Background
2.3 Aim
2.4 Methods
2.5 Results
2.6 Discussion
2.7 Conclusion
Chapter 3: Endometrial scratching for subfertility: A survey of current practice 
3.1 Chapter overview
3.2 Introduction .
3.3 Aims
3.4 Methods
3.5 Results
3.6 Discussion
3.7 Conclusion
Chapter 4: The Pipelle for Pregnancy (PIP) study: a randomised controlled trial 
4.1 Chapter overview
4.2 Design rationale
4.3 Aim
4.4 Methods
4.4.16 Protocol amendments
4.5 Results
4.6 Discussion
4.7 Conclusion
Chapter 5: Placebo procedure for endometrial scratching 
5.1 Chapter overview
5.2 Background
5.3 The PIP study
5.4 Placebo design
5.5 Aims
5.6 Methods
5.7 Results
5.8 Discussion
5.9 Conclusion .
Chapter 6: Evidence-based sample size calculations for endometrial scratching 
6.1 Chapter overview
6.2 Background
6.3 Aims
6.4 Methods
6.5 Results
6.6 Discussion
6.7 Conclusion
Chapter 7: Summary
References
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Endometrial scratching for subfertility

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