P-479 Prognosis for ongoing pregnancy after recurrent implantation failure (RIF) following IVF/ICSI treatment
Authors: Stevens Brentjens L , Roumen R , Romano A , Van Golde R , Den Hartog J 
Published: June 2023

Abstract

Study question
What is the cumulative ongoing pregnancy rate within one year after visiting the RIF outpatient clinic in patients with RIF after IVF/ICSI treatment?

Summary answer
The cumulative ongoing pregnancy rate was 42.9% with a mean time to pregnancy of 8.8 months (95% CI 7.5-10.1 months).

What is known already
An estimated portion of 10-15% of IVF patients experience RIF. Multiple add-on treatments have been proposed, however, evidence for effective clinical therapeutic options still remain scarce. Although it is described that RIF patients might eventually benefit most from a ‘keep calm and carry on’ approach, in practice patients often seek clearer answers on their pregnancy chance and request further investigations/interventions. It would be helpful to give patients insight in their chances of achieving pregnancy after RIF, but at this moment little is known about their prognosis. This is further complicated by the lack of consistency in the definition of RIF.

Study design, size, duration
A prospective cohort study on 42 RIF patients after one-year follow-up was performed, as part of the MURIM (Multidisciplinary Research on Repeated Implantation Failure and Recurrent Miscarriages) study. Baseline characteristics including an endometrial assessment and ReceptIVFity (vaginal microbiome) test were collected at the RIF outpatient clinic. After a follow-up duration of minimal one year participants were asked to complete a questionnaire regarding fertility treatment and pregnancy outcome. Missing information was received via medical files.

Participants/materials, setting, methods
RIF patients aged 18 to 38 years old visiting the RIF outpatient clinic at Maastricht University Medical Centre+ between April 2019 until September 2021 were included. RIF was defined as consecutive implantation failure of three high quality embryos or ten embryos without a quality criterion. Clinical characteristics, pregnancy outcome and time to pregnancy was analyzed by survival analysis and cox hazard regression analysis via SPSS version 20.0. A p-value of &lt; 0.05 was considered statistically significant.

Main results and the role of chance
Forty-two out of 44 contacted patients responded to the questionnaire (response rate = 95.5%). The ongoing pregnancy rate was 42.9% (Standard Deviation (SD): 0.50%) during the first year after visiting the RIF outpatient clinic. Mean time to ongoing pregnancy was 8.8 months (95%-CI: 7.5-10.1 months). The mean amount of embryo transfers (ETs) during this year was 2 (SD: 1.78). The ongoing pregnancy rate per ET (by survival analysis) for the first, third and sixth ET was 33.1%, 49.3% and 63.8%, respectively. To correct for a possible overestimation of the cumulative ongoing pregnancy rate per ET by normal survival analysis, pregnancy rates were calculated again using the number at risk of the total group during the first ET (pessimistic cumulative pregnancy rate). The pessimistic cumulative ongoing pregnancy rates were 33.1%, 42.9% and 48.6%, respectively.
When comparing baseline characteristics by univariable cox hazard regression between women with and without ongoing pregnancy, no significant differences were found. Nineteen pregnancies were reported during the one-year follow-up, one conceived spontaneously (5.3%); four via fresh ET (IVF=15.8% and ICSI=5.3%); and 14 by frozen ET (IVF=26.4% and ICSI=47.4%). The pregnancies resulted in 14 livebirths (73.7%); one miscarriage (5.3%); one stillbirth (5.3%); and three ongoing pregnancies (15.8%).

Limitations, reasons for caution
Although this is the first study that prospectively describes pregnancy prognosis after RIF, it is limited by the short follow-up period and relatively small sample size. The RIF outpatient clinic consultation might have contributed to the obtained pregnancy results but the proportionality is unclear as there is no control group.

Wider implications of the findings
The obtained ongoing pregnancy prognosis after RIF is encouraging and justifies a conservative approach after three failed ETs. Furthermore, the high pregnancy rate indicates the need of well-defined, individualized diagnostic criteria to define RIF and to be able to deviate between couples with 'bad luck' and an underlying (treatable) cause.

Trial registration number
NL66835.068.18/METC18-040