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A review published in the Cochrane Database of Systematic Reviews looks at preparation techniques prior to embryo transfer in IVF.
Prof Dusko Ilic, Professor of Stem Cell Science, King’s College London, said:
“Absence of reliable evidence is not evidence of absence of benefit. This review tells us primarily how weak the research is, not that these techniques do not work.
“For several comparisons, the trials were small, at high risk of bias, and did not report the outcomes that matter most to patients, particularly live birth and adverse events.
“The review also covers only a limited group of preparatory practices, rather than embryo-transfer technique as a whole. Some measures, such as bladder filling or afterloading, may still make catheter placement easier in selected patients, even if a direct improvement in pregnancy rates has not been demonstrated. These findings support selective, clinically justified use rather than routine use based solely on tradition.”
Miss Sesh K Sunkara, Consultant Gynaecologist and Subspecialist in Reproductive Medicine and a Senior Clinical Lecturer in Reproductive Medicine at King’s College London, said:
“It would be more appropriate to use the phrases “uncertain evidence” rather than “no clear evidence.” The phrase “common embryo transfer techniques” is also not accurate, as several interventions are currently not routine practices either during or before embryo transfer. These include changing the woman’s position, flushing the endocervical canal, flushing the endometrial cavity with culture media, using a tenaculum to straighten the cervix, and cervical dilatation.
“The review is undertaken following the right methodology. However, the primary studies included have limitations which has been highlighted by the authors (small underpowered studies, old studies with some from over 20 years ago). There isn’t robust evidence to make to make firm conclusions from the existing low-quality studies analysed in this Cochrane review; the author’s have highlighted that “the certainty of evidence was low or very low” and “most outcomes in the review were graded as low or very low certainty of evidence”. The review is not a primary study, it is a qualitative and quantitative synthesis of the existing studies and evidence.
“The review concluded that “the evidence is very uncertain about the effect of a full bladder on pregnancy rate compared with an empty bladder” and “low-certainty evidence suggests that embryo afterloading may result in little to no difference in pregnancy rate compared with direct embryo transfer”. As firm or robust conclusions could not be drawn, we cannot say whether these interventions are helpful or not helpful to improve live birth or pregnancy rates.
“A point to note is there would be no harm to patients or extra costs from the common practice of embryo transfer with full bladder or from the use of embryo afterloading. In the absence of harm and with uncertain evidence whether they are helpful or not, the evidence from this review is unlikely to impact current practice.”
Dr Alison Campbell, Chief Scientific Officer, Care Fertility, said:
“This research describes both a lack of standardisation and lack of high-quality research in the preparation of the patient for embryo transfer during IVF treatment, which is not surprising, but it can be considered reliable based on the methodology used. It is challenging to conduct trials which involve varying practices that may impact treatment outcomes one way or the other, so studies are limited. Outcomes are strongly influenced by embryo quality, patient factors and laboratory performance, so very large trials would be needed to detect a benefit from a difference in practice or preparation with so many variables to account for.
“Such preparation techniques described in this review are longstanding and based on reasonable assumptions such as the catheter containing the precious embryo will more easily reach the desired location in the uterus (womb) if these simple measures are taken. They are performed in good faith and practitioners consider they may help the procedure despite the lack of high quality evidence.
“Expertise and compassion are crucial during embryo transfer such that the patient has the best chance of success and feels as supported as possible during the process.
“Following preparation, the actual embryo transfer itself is also subject to variability based on several factors including patient, embryo quality, equipment, environment and medical and laboratory practitioners.
“The future may see increased automation in IVF, including embryo transfer, but high-quality evidence and data are required to enable the development of such new technologies and unfortunately, as described in this Cochrane review, this is still lacking with regard to preparation for this important step of the IVF process.”
Prof Alastair Sutcliffe, Professor of General Paediatrics, University College London (UCL), said:
“This paper has valid methodology and is welcomed. It is of value in that it informs practitioners whose main aim is to increase successful pregnancy rates. It also is research in an area where a lot of non-evidence-based claims are made.”
The review ‘Techniques for preparation prior to embryo transfer’ by Cochrane. was published in the Cochrane Database of Systematic Reviews at 01:00 UK time on Thursday 6th August.
Declared interests
Prof Dusko Ilic: “No CoIs to declare.”
Dr Alison Campbell: Minor shareholder in Care Fertility. [Care Fertility: Care Fertility does use some of the preparatory procedure described in this review publication.]
Prof Alastair Sutcliffe: “None”
For all other experts, no reply to our request for DOIs was received.