First B-HCG predict pregnancy outcome after in-vitro fertilization

Abstract

Background: About 22% of IVF-conceived pregnancies result in spontaneous abortion. Therefore, it is important to predict the complicated and poor pregnancy outcome. Serum human chorionic gonadotrophin levels after 2 weeks of embryo transfer is a reliable marker to predict the pregnancy outcome in patients of IVF. Objective was to correlate the evolution curve of B-HCG after embryo transfer in assisted human reproduction techniques and the pregnancy outcome.Methods: A prospective and observational study. In patients who underwent embryo transfer, a collection of quantitative B-HCG in 12th day after transfer was made. In patients who had beta-HCG positive value (beta-HCG>5.0 mUI/ml), there were two new collections of beta-HCG 48 hours and 72 hours after the first collection. All results have been filed and all pregnancies were accompanied to the final outcome.Results: It was found that B-HCG values above 139.5 mIU / ml were associated with a good prognosis gestational.Conclusions: Larger studies are needed to improve these findings and give better information regarding the prognostic value of early pregnancy hCG levels.

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March 2017 · Volume 6 · Issue 3 Page 1093
International Journal of Reproduction, Contraception, Obstetrics and Gynecology
de Oliveira SA et al. Int J Reprod Contracept Obstet Gynecol. 2017 Mar;6(3):1093-1096
www.ijrcog.org
pISSN 2320-1770 | eISSN 2320-1789
Original Research Article
First B-HCG predict pregnancy outcome after in-vitro fertilization
Sofia Andrade de Oliveira*, Fernanda Silveira Seguro de Carvalho, Julio Elito Júnior
INTRODUCTION
Early pregnancy loss is common during the first
trimester, meanly in pregnancies achieved by in vitro
fertilization (IVF).1 About 22% of IVF-conceived
pregnancies result in spontaneous abortion.2 Therefore, it
is important to predict the complicated and poor
pregnancy outcome.1 Although transvaginal ultrasound is
a useful tool in assessing early pregnancies, its utility is
limited before 5 to 6 weeks of pregnancy.2 Early markers
with an abnormal rise pattern will allow a clinician to
follow a patient more closely and can expedite diagnosis
of an ectopic or abnormal intrauterine pregnancy.3
Several early-pregnancy serum markers have been
evaluated to ascertain outcome, including serum beta-
human chorionic gonadotrophin (B-HCG), estrogen,
luteinizing hormone (LH) and progesterone.3 B-HCG
levels after 2 weeks of embryo transfer is a reliable
marker to predict the pregnancy outcome in patients of
IVF.1 Low levels of serum B-HCG in early pregnancy
have been reported as a predictor of poor pregnancy
outcome such as chemical and ectopic pregnancies as
well as spontaneous miscarriage 3. However, during the
IVF treatment, the embryo can be transferred at different
developmental stages and it can impact initial B-HCG
levels and the majority of studies investigating the
prognostic value of B-HCG thresholds did not separate
their analyses according to day of ET.4
The goals of this study are: describe the evolution curve
of B-HCG after embryo transfer in assisted human
reproduction techniques and the pregnancy outcome:
abortion, ectopic pregnancy, molar trophoblastic
pregnancy, twin pregnancy and single pregnancy and,
establishing a cutoff point to differentiate an evolutionary
pregnancy from a non-evolutionary pregnancy.
Department of Gynecology, Federal University of São Paulo, São Paulo, Brazil
Received: 10 January 2017
Revised: 15 January 2017
Accepted: 08 February 2017
*Correspondence:
Dr. Sofia Andrade de Oliveira,
E-mail: sofia.gineco@gmail.com
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background: About 22% of IVF-conceived pregnancies result in spontaneous abortion. Therefore, it is important to
predict the complicated and poor pregnancy outcome. Serum human chorionic gonadotrophin levels after 2 weeks of
embryo transfer is a reliable marker to predict the pregnancy outcome in patients of IVF. Objective was to correlate
the evolution curve of B-HCG after embryo transfer in assisted human reproduction techniques and the pregnancy
outcome.
Methods: A prospective and observational study. In patients who underwent embryo transfer, a collection of
quantitative B-HCG in 12th day after transfer was made. In patients who had beta-HCG positive value (beta-HCG>5.0
mUI/ml), there were two new collections of beta-HCG 48 hours and 72 hours after the first collection. All results
have been filed and all pregnancies were accompanied to the final outcome.
Results: It was found that B-HCG values above 139.5 mIU / ml were associated with a good prognosis gestational.
Conclusions: Larger studies are needed to improve these findings and give better information regarding the
prognostic value of early pregnancy hCG levels.
Keywords: HCG - beta, In vitro fertilization, Pregnancy outcome
DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20170591

de Oliveira SA et al. Int J Reprod Contracept Obstet Gynecol. 2017 Mar;6(3):1093-1096
International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 6 · Issue 3 Page 1094
METHODS
It was a prospective and observational study and it was
done in patients who underwent an embryo transfer in the
period from 04th February 2014 to 23rd September 2014 in
the São Paulo Hospital, São Paulo, Brazil. It was made a
collection of quantitative B-HCG in 12th day after the
transfer. All collections and laboratory analyzes were
made at the central laboratory of the São Paulo Hospital.
In patients who had positive value of B-HCG (B-HCG
>5.0 mUI/ml), they were performed two new collections
of B-HCG 48 hours and 96 hours after the first collection.
They were included, in this study, all patients on IVF
Assisted Reproduction treatment who underwent embryo
transfer and who agreed to participate of the study
through voluntary signature on a consent form explaining
all the steps and the study goals.
All results have been filed and all pregnancies were
accompanied until the final outcome: abortion, ectopic
pregnancy, molar pregnancy, twin pregnancy or single
pregnancy.
The monitoring finished after the last birth, in June 2015,
of the last embryo transferred in September 2014.
To produce this article, we follow the “strengthening the
reporting of observational studies in epidemiology”
(STROBE) statement.
Statistical analysis
After collecting all B-HCG values and after all pregnancy
outcomes, it was performed an evolution curve of B-
HCG titles using the Friedman test. After that, statistic
correlations were made between the curve of evolution of
beta-HCG and the outcome found. The program used to
do the curves was used R version 3.2.1 software.
In order to find a cut-off of the B-HCG value to
discriminate outcome, a ROC curve was performed.
Ethical considerations
The study was conducted in Human Reproduction
Department of the Federal University of São Paulo-
UNIFESP, in Brazil and approved by the Research Ethics
Committee of UNIFESP with approval number: CAAE
08835313.0.0000.5505. All participants assigned a
consent form explaining all the steps and the study goals.
RESULTS
Eighty-six patients, in the period from 02nd April 2014 to
23rd September 2014, agreed to participate. After twelve
days from the embryo transfer, was performed a blood
collection for B-HCG analysis and among the 86 patients,
48 patients had negative results. Among the 38 patients
with positive results, five patients did not do the second
blood collection and were excluded from the study.
Thirty-three patients collected two other blood samples,
48 and 96 hours after the first collection and the results
were then analyzed as present below. Table 1 is a
summary of the observed frequencies for each outcome
during the period of observation after positive B-HCG
result. Table 2 is a summary of beta-HCG measures in
three days (12th, 14th, 16th) stratified by outcome.
Table 1: Frequency and percentage observed for the
outcome variable.
Outcome
n
%
Negative Beta-HCG
48
59.3
Single pregnancy
22
27.2
Twin pregnancy
6
7.4
Ectopic pregnancy
2
2.5
Abortion
3
3.7
Total
81
100.0
Table 2: Summary quantitative variables stratified by outcome (beta-HCG in mUI/mL).
Outcome
N
Minimum
Mean
Median
Maximum
SD
Negative
BHCG 1
48
0.10
0.56
0.50
3.90
0.52
Single
Pregnancy
BHCG 1
22
31.50
1459.15
979.70
9806.00
2047.89
BHCG 2
22
82.00
2729.64
1780.00
16305.00
3434.18
BHCG 3
22
142.00
5225.55
3300.00
30416.00
6480.41
Twin pregnancy
BHCG 1
6
874.70
3373.62
2402.00
9562.00
3208.81
BHCG 2
6
2600.00
6215.17
4705.50
15000.00
4719.07
BHCG 3
6
5000.00
11689.83
9060.00
28145.00
8811.45
Ectopic
pregnancy
BHCG 1
2
124.70
1086.85
1086.85
2049.00
1360.69
BHCG 2
2
132.00
1199.50
1199.50
2267.00
1509.67
BHCG 3
2
90.00
1105.50
1105.50
2121.00
1436.13
Abortion
BHCG 1
3
20.00
43.00
51.20
57.80
20.19
BHCG 2
3
1.00
35.67
3.00
103.00
58.32
BHCG 3
3
0.00
43.00
2.00
127.00
72.75

de Oliveira SA et al. Int J Reprod Contracept Obstet Gynecol. 2017 Mar;6(3):1093-1096
International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 6 · Issue 3 Page 1095
Table 3: Odds ratio of the variable beta HCG (cutoff)
considering the variable outcome single or twin) as the
response variable.
Variable
Odds
ratio
C.I 95% for OR
p
value
Inferior
Superior
BHCG
≤139.5
-
-
-
-
BHCG
>139.5
52.000
3.781
715.062
0.003
We present for each outcome, the average evolution of B-
HCG along with the confidence interval (95%) in Figure
1. For single pregnancy outcome, there were significant
diferences (p<0.05) in each of the three times, that is, we
have evidence of differences between the 12th and 14th
days, 12th and 16th days and between 14th and 16th days.
However, in twin pregnancy outcome, the difference was
in relation to 12th and 16th days. While for the ectopic
pregnancy and abortion outcomes no significant
difference was found between the three moments. It can
see a rise of developments in B-HCG to the outcome
single pregnancy and twin pregnancy. On the other hand,
for ectopic pregnancy outcomes and abortion average
developments are relatively stable behavior. It was not
possible to evaluate the percentage change of B-HCG
values among the first, second and third collections due
to low sample numbers.
Table 4: Results of the first beta-HCG value among evolutionary pregnancy and not evolutionary pregnancy.
Beta HCG value (mUI/ml)
Outcome
Total
Single and twin
pregnancy
Ectopic pregnancy and
abortion
BHCG1
≤ 139.5
n
2
4
6
% in Outcome
7.1%
80.0%
18.2%
>139.5
n
26
1
27
% in Outcome
92.9%
20.0%
81.8%
Total
n
28
5
33
% in Outcome
100.0%
100.0%
100.0%
In order to find a cut-off for the first B-HCG value to
discriminate outcome, a ROC curve was performed. In
the Figure 2 there is the ROC curve, and Table 3 a test
summary, containing the area under the curve (accuracy)
and the p value of the argument.
Figure 1: Evolution and average confidence interval
95% of BHCG for endpoints.
A ROC curve was performed (Figure 2) to choose a cut-
off value of B-HCG serum in the 12th that evidence the
evolution of a pregnancy to evolutionary pregnancy and
not evolutionary pregnancy. The point of the ROC curve
that maximizes the sensitivity and specificity
simultaneously was the value 139.5 mUI/ml. (Table 3 and
Table 4). Considering the value of cut-off, the sensitivity
obtained was 92.9% and specificity was 80%.
Figure 2: ROC Curve.
Thereby, women who have B-HCG >139.5 mUI/ml has
52 times more likely to have the outcome single or twin
compared to women who have B-HCG ≤139.5 mUI/ml.
DISCUSSION
During cycles of human assisted reproduction treatments,
there is a period of great anxiety by the couple that is the

de Oliveira SA et al. Int J Reprod Contracept Obstet Gynecol. 2017 Mar;6(3):1093-1096
International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 6 · Issue 3 Page 1096
period between the result of the positive B-HCG and the
obstetric ultrasound.3 This is an important period because
there is still no information about the location of the
pregnancy, the number of implanted embryos or about
the evolution of that pregnancy. This study aimed to find
a B-HCG value that could predict the course of
pregnancy and it found that values above 139.5 mIU/ml
were associated with a good pregnancy prognosis. The B-
HCG represents the functional activity of placental
trophoblastic tissue and the low levels are associated with
early pregnancy loss or poor outcome.2 Present study
corroborates with other studies showing that low initial
hCG is correlated with no evolutionary pregnancy
outcome.5-7
CONCLUSION
Larger studies are needed to improve these findings and
give better information regarding the prognostic value of
early pregnancy hCG levels and specially information
about the percentage change of B-HCG values along the
days.
Funding: No funding sources
Conflict of interest: None declared
Ethical approval: The study was approved by the
Research Ethics Committee of UNIFESP with approval
number: CAAE 08835313.0.0000.5505
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Cite this article as: de Oliveira SA, de Carvalho
FSS, Júnior JE. First B-HCG predict pregnancy
outcome after in-vitro fertilization. Int J Reprod
Contracept Obstet Gynecol 2017;6:1093-6.