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i320 Abstracts of the 35th Annual Meeting of the ESHRE, Vienna, Austria 24 to 26 June 2019
P-386 Evaluating the risk of ectopic pregnancy and
spontaneous abortion in early pregnancy using a serum hCG
and CA125 measurement algorithm
R. Zmuidinaite1,S.Butler
1, F. Sharara2,J.Saadeh
3, R. Iles1
1MAP Sciences, Research, Bedford, United Kingdom
2Virginia Centre for Reproductive Medicine, Embryology, Reston, U.S.A.
3Al Enaiah Medical Lab, Medical laboratory, Sharjah, United Arab Emirates
Study question: Can a mathematical algorithm based predictive model,
utilising serum biomarkers, be a viable test to predict risk of ectopic pregnancy
or spontaneous abortion?
Summary answer:Single point hCG and CA125 combined measurement
gives an accurate risk score, detecting ectopic pregnancy or spontaneous
abortion in the second month of gestation.
What is known already: About 10–15% (increasing to 18-30% for IVF
patients) of all spontaneous pregnancies end in recognised spontaneous abor-
tion and 1-2% result in ectopic pregnancy. Currently, diagnosis is based on
repeat hCG measurement and ultrasound scan and results are often inconclu-
sive, requiring repeat follow up causing patient anxiety and increased risk of
tubal rupture. Both hCG and CA125 have been used extensively in management
of viable pregnancies, spontaneous abortion and ectopic pregnancy but not in
combination with mathematical modelling following single point measurement
to predict risk.
Study design,size,duration: This was a diagnostic test study including serum
samples from 380 pregnancies. Serum samples were collected from the A&E and
EPAU at London Hospital from pregnant women (average gestational age: 7
weeks) presenting with lower abdominal pain and/or vaginal bleeding between
2002 and 2003. Serum hCG and CA125 of 137 samples were included in
the study. Outcomes were confirmed by the follow up. Analysis of data using
supervised machine learning was performed in 2017.
Participants/materials, setting, methods: There were 13 cases with 124
controls for ectopic pregnancy and 62 cases with 75 controls for spontaneous
abortion models. Multiple algorithms were built and tested from the data
which were then validated by ten-fold cross-validation to ensure reproducibil-
ity and reliability. Quadratic and linear discriminant analysis algorithms based
predictive models were built on a log normalised data. Data analysis was
performed in R.
Main results and the role of chance:Two separate models were developed
which combined serum measurements of hCG and CA125 to calculate the
relative risk for either ectopic pregnancy or spontaneous abortion. Ectopic
pregnancy test performance was 100%, 73% and 77% for sensitivity, specificity
and accuracy respectively and an ROC of 0.87. The ROC for spontaneous
abortion was 0.74 with sensitivity of 63% and specificity of 72%. This diagnostic
test reports the relative risk comparing an adjusted risk based on the results
of the general risk. Five categories of risk were modelled for both ectopic
pregnancy and spontaneous abortion which included: low, normal, moderate,
elevated and high risk.
Following the cross validation, the study resulted in a user friendly, clinical
decision making support system being created. The system requires simple
data input of serum marker values and patient information to rapidly provide
a calculated risk score. This risk score can enable clinicians to make informed
decisions regarding patient management and pregnancy advice.
Limitations, reasons for caution: This study is limited by the cohort size
and the limited number of ectopic pregnancy cases.
Wider implications of the findings:This study has shown that simple, single
point measurement test can be used quickly at the most critical time to identify
women with high risk for ectopic pregnancy or spontaneous abortion when
compared to serial measurement and ultrasound scan alone.
Trial registration number: not applicable
P-387 Evaluating the clinical utility of endometrial biopsy for
chronic endometritis screening in patients who experience
implantation failure following euploid embryo transfer
C.A. Hernandez-Nieto1,L.Sekhon1,J.Lee1,T.Alkon1, M.Luna-Rojas1,
B. Sandler2, A. Copperman2,T.Mukherjee
2
1Reproductive Medicine Associates of New York, Reproductive endocrinology and
Infertility, New York, U.S.A.
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2Icahn School of Medicine at Mount Sinai, Obstetrics- Gynecology and Reproductive
Science, New York, U.S.A.
Study question: Does endometrial biopsy (EMB) and chronic endometritis
(CE) screening oer clinical utility in patients following euploid embryo implan-
tation failure?
Summary answer: Patients, regardless of endometrial biopsy findings, have
similar IVF outcomes on a subsequent treatment cycle as compared with
patients who do not undergo endometrial biopsy.
What is known already:Chronic endometritis is a local inflammatory disease
characterized by plasmacyte infiltration within the endometrial stroma and is
found within 8-72% of tested infertile patients (Kitaya K, 2018). Recent studies
showed that CE may exert a negative eect on embryo implantation through
impairing decidualization and altering the expression of proteins involved in
endometrial receptivity (Wu D, 2017). Further study findings have suggested
that antibiotic treatment for CE can improve IVF success rates. Clinical evidence
is still scarce regarding the value of performing an endometrial biopsy for
screening CE in patients with a history of failed implantation after a euploid
blastocyst transfer.
Study design, size, duration: A retrospective, cohort study included infertile
patients who failed a euploid embryo transfer and thereafter underwent an
endometrial biopsy for CE screening, received antibiotic treatment (if indi-
cated), and had a subsequent single, euploid frozen embryo transfer from
January 2016 to December 2018. A sample size of 70 patients per group was
calculated to be necessary to detect a 15% dierence in clinical pregnancy rates
with 80% power. Alpha=0.05.
Participants/materials, setting, methods: Cohorts were segregated
into two groups (Group 1: patients who had a failed euploid embryo
implantation that underwent EMB, this group also included patients in
which EMB was negative for CE. Group 2: Control patients who had an
unsuccessful euploid embryo implantation and did not undergo EMB). For
EMB cases, CE was diagnosed using CD138 immunohistochemistry staining. All
patients in the study underwent a subsequent single, euploid frozen embryo
transfer (FET).
Main results and the role of chance: Group 1 included 241 patients of
which 42% (n=90) were diagnosed with CE and received antibiotic therapy;
while the remaining 124 patients were found to be negative for CE. Group 2
included 985 control patients.
On an unadjusted comparison, no dierences were found in age, baseline
FSH, baseline AFC, previous number of stimulation/IVF cycles, and embryonic
quality among cohorts. However, a significant dierence in AMH levels (3.3±2.9
vs 4.0±4.7, p=0.02), BMI (24.5±4.6 vs 23.5±4.2, p=0.002), and endometrial
thickness (8.6±1.3mm vs 9.0±1.6mm, p=0.03) was observed. When analyz-
ing a subsequent FET cycle, no dierences were found in clinical pregnancy
(CPR) rates 76% vs 81.1%(p=0.28), ongoing pregnancy rate (OPR) 78.8%
vs 85.9(p=0.36) clinical loss rate (CLR) 10.6% vs 17.1%(p=0.09) or multiple
pregnancy rate (MPR) 0.06% vs 1.6%(p=0.41) among Group 1 vs Group 2
respectively.
Using a logistic regression analysis fitted with a GEE model, and after adjusting
for age, BMI, endometrial thickness at FET, embryo quality, and day of embryo
biopsy, there was no positive association to performing an EMB and FET cycle
outcomes (CPR (OR 1.01 CI95% 0.7-1.4,p=0.9), OPR (OR 1.16 CI95% 0.8-1.6,
p=0.3), CLR (OR 0.6 CI95% 0.3-1.3, p=0.3) and MPR (OR 0.6 CI95% 0.05-3.3,
p=0.4)).
Limitations, reasons for caution: This study is limited by its retrospective
nature. Also, there is limited evidence and dierences in worldwide standard-
ization for the ideal time to perform an endometrial biopsy, methodology
for CE diagnosis, and treatment protocols. These caveats might reduce
this study findings generalizability. Future randomized controlled trials are
needed.
Wider implications of the findings: Understanding the clinical utility of
CE screening and the potential therapeutic advantages on embryo implanta-
tion is of critical importance for guiding patients during ART treatment. To
date, there is limited evidence to support performing endometrial biopsies
in patients with a history of failed implantation following euploid embryo
transfer.
Trial registration number: This study was approved by the Western Insti-
tutional Review Board (Study Number: 1167398).
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