P-335 How to define recurrent implantation failure and when to start investigating the endometrium? Lessons from three years’ experience in a dedicated unit
Authors: Rahmati M , Ripanelli A , Nair S , Gill A , Linara-Demakakou E , Ahuja K , Macklon N 
Published: June 2022

Abstract

Study question
Should we always define recurrent implantation failure (RIF) after three unsuccessful transfers and only then start investigating the endometrium?

Summary answer
Endometrial investigations can be beneficial for patients with RIF. However, waiting for three previous failures before instituting assessment might not be appropriate in every situation.

What is known already
The definition of unexplained recurrent implantation failure (RIF) continues to be debated. This usually implies a lack of embryo implantation after the transfer of three good quality blastocysts on an apparently responsive and anatomically normal endometrium. To deal with this frustrating and distressing situation for both the patient and the clinician, additional empirical interventions are often blindly used. This approach may exacerbate rather than ameliorate any underlying aetiology. There is a need therefore to base interventions on diagnostic rationale wherever possible.

Study design, size, duration
In order to base advice and any interventions for RIF on diagnostic rationale, we created a referral unit dedicated to the investigation and treatment of patients meeting the traditional criteria for RIF. Over three years, 395 patients were referred to this unit and 237 completed their investigations. Here we present the clinical outcomes and insights obtained over these three years.

Participants/materials, setting, methods
Blood sampling for serum progesterone level and endometrial pipelle biopsy were performed after five days of luteal support in a standardised substituted cycle. The samples underwent dating by gene expression (ERA test) and immune assessment describing the recruitment and activation of the uterine Natural Killer cells (MLI test, Matrice Lab Innove). A personalised treatment plan was thus derived and suggested to the referring clinician. The outcomes after the subsequent personalised single embryo transfer were monitored.

Main results and the role of chance
The patients referred had an average of 4.3 previous good quality blastocysts transferred in the past. 58% of the referred patients had used their own eggs, including 49% after conventional IVF or ICSI, and 9% after using PGT-A. 42% of the referred patients had used donor eggs. To date, 237 patients completed their endometrial assessment. 92% of the tested patients revealed at least one disrupted endometrial marker. With the subsequent personalised single embryo transfer, an implantation rate of 58% was observed. The ongoing pregnancy rate at 12 weeks was reported at 39%.

Limitations, reasons for caution
While confirmatory prospective controlled studies are required, these data indicate that more targeted rather than blind usage of simple known therapeutics could be beneficial for patients experiencing RIF. The clinical context these referred was highly variable, including patients undergoing PGT-A and egg donation.

Wider implications of the findings
Given the higher implantation rates to be expected in some groups, waiting for at least three embryos to fail before investigating the endometrium may be inappropriate and underlie the relatively high miscarriage rate observed. The investigation of implantation failure should be driven by context rather than arbitrary definition.

Trial registration number
Not Applicable