O-203 Comparing viable and non-viable IVF early pregnancy measurements: does knowledge of gestational age using date of ET potentially change miscarriage diagnosis guidelines in IVF patients
Authors: Murugesu S , Shearer A , Linton-Reid K , Balfoussia D , Mittal M , Stalder C , Aboagye E , Saso S , Saravelos S , Bourne T 
Published: July 2024

Abstract

Study question
In IVF pregnancies with known embryo transfer (ET) dates, can gestational age as well as ultrasound measurements be used to diagnose miscarriage?

Summary answer
Early pregnancy measurements vary at fixed gestational ages based on ET. However, there is a specific time cut-off where an empty gestational sac indicates miscarriage.

What is known already
Current guidelines state that when ultrasound findings show a pregnancy of unknown viability, a repeat scan must be performed either 7 or 14 days later (depending on the presence of an embryo or gestation sac size) to confirm viability, irrespective of the LMP based gestational age. This definition only considers ultrasound measurements, and even when the pregnancy dates thought to be certain and based on day of ET date, there are no exceptions to this guidance.

Study design, size, duration
This was a retrospective cohort study within a London tertiary unit, Wolfson Clinic, Hammersmith Hospital, Imperial College Healthcare NHS Trust over a 36-month time period. We collated data from both fresh and frozen cycle IVF pregnancies over four years: Jan 1st 2019 to December 31st 2021.

Participants/materials, setting, methods
In this unit, patients undergoing fresh or frozen IVF cycles, have an embryo transfer at Day3-6 of development. We included any patient with a confirmed intrauterine pregnancy at first scan (5-8 weeks gestation) for analysis of pregnancy outcomes. The data collected included date of embryo transfer (ET), embryo age at transfer, and early pregnancy measurements using ultrasound. The endpoint was viability at the 11-14 week dating scan.

Main results and the role of chance
1161 IVF embryo transfers were included in the study, 677 (58.3%) frozen and 484 (41.7%) fresh cycles. 892 (76.8%) remained viable at 11-14 weeks and 269 (23.2%) were non-viable. Pregnancies resulting in viable pregnancies had a range of CRL (≤16mm) and empty mean gestation sac diameter (MSD) (≤11mm) measurements at each expected age by ET date (≤8 weeks gestation). At 49 days CRL varied from 1mm to 17mm, and at 42 days empty MSD measurements varied from 7 to 18mm. This shows that a range in embryo and gestation sac sizes will be seen in subsequently shown to be viable pregnancies despite the apparent exact gestation being known based on ET. This may relate to both differing embryo growth rates and timing of implantation. A Kolmogorov-Smirnov test was applied to compare the viable and miscarriage cohort CRL measurements in relation to expected age by ET. The result: 0.610, p-value=1.33 x10-15, demonstrated a significant difference in embryo size between viable and non-viable pregnancies with known ET dates. All pregnancies where the scan showed an empty gestational sac (n = 157) at 47 days gestation by ET date, had a 100% positive predictive value with a 100% specificity (CI:90.1-100.0) for miscarriage.

Limitations, reasons for caution
The sample was powered to 0.9, significance level 0.05. Analysis demonstrated 100% positive predictive value with 100% specificity (CI:90.1-100.0), to confirm miscarriage with an empty gestation sac ≥47days age by ET date. A larger cohort size from different centres is needed to reduce the confidence interval and confirm the findings.

Wider implications of the findings
There is significant variation in CRL and MSD size between viable pregnancies of the same gestational age by ET. However, we found &gt;47 days gestation an empty gestation sac resulted in miscarriage. If confirmed in larger studies this may permit women to be given an earlier definitive diagnosis of miscarriage.

Trial registration number
Audit registration GRM_104 Imperial Healthcare NHS Trust