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

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DOI: 10.18203/2320-1770.ijrcog20170591
Cite this publication
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
%
Negative Beta-HCG
59.3
Single pregnancy
27.2
Twin pregnancy
7.4
Ectopic pregnancy
2.5
Abortion
3.7
Total
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.
  • ... pregnancy may be a marker for designating the outcome in future phases of the pregnancy. [7][8][9] Cutoff studies are also conducted so the post-IVF initial β-hCG value can be used in the prediction of pregnancy success. 8,9 Processes of implantation, achieving pregnancy and maintenance of pregnancy are ensured with sufficient trophoblastic activity in the beginning of the pregnancy. ...
    ... 13 β-hCG levels may be very high in uncontrolled trophoblastic invasion and low initial β-hCG levels may indicate that pregnancies cannot be implanted. 7,14 In the light of this information, the fact that as BMI increased, hCG levels decreased in this study shows parallelism with the negative effect of BMI on implantation. There are studies which stated that endometrial receptivity and reproductive outcome are broken as BMI increases. ...
  • ... There is a narrow margin between the amount of gonadotrophine that is necessary to achieve ovulation in the infertile patient and the amount that will cause multiple follicle development and multifoetal pregnancies. Sofia Andrade de Oliveira et al. (2017) [21] concluded, 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. And said that B-HCG values above 139.5 mIU / ml were associated with a good prognosis gestational. ...
  • Article
    Research question: Do pregnancy, obstetric and perinatal outcomes differ according to initial maternal serum human chorionic gonadotrophin (HCG) level measured on day 11 after single blastocyst transfer? Design: Vitrified-warmed single blastocyst transfer cycles (n = 640) were collected between 1 January 2013 and 30 April 2017 with positive HCG values and retrospectively analysed by receiver operating characteristic curves to predict clinical pregnancy, ongoing pregnancy and delivery. Cycles were divided into a low HCG group (n = 155) and high HCG group (n = 485) based on cut-off value of live birth prediction. Cycles in the HCG group were subdivided into a low-high subgroup (n = 162), medium-high subgroup (n = 162) and high-high subgroup (n = 161) based on tertile points. Pregnancy rates and obstetric and perinatal outcomes were compared. Results: The area under curves for clinical pregnancy, ongoing pregnancy and live birth prediction were 0.95, 0.81 and 0.79, respectively; corresponding cut-off values were 152.2 IU/l, 211.9 IU/l and 211.9 IU/l; HCG less than 211.9 IU/l indicated an extremely low clinical pregnancy rate (34.84%), a high early miscarriage rate (61.11%) and a low live birth rate (12.26%). Rates of gestational diabetes mellitus (GDM) (P = 0.007) and female neonates (P = 0.001) were significantly higher in the LHG group compared with the HHG group; no significant differences were observed in the low versus high HCG group overall. Conclusions: Lower initial maternal serum HCG levels indicated poorer clinical outcomes. Within the high HCG group, a lower initial maternal HCG level was found to be associated with GDM occurrence and proportion of female neonates.
  • Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization
    • S Q Anupama
    • A Kathiresan
    • Y Cruz-Almeida
    • M J Barrionuevo
    • W S Maxson
    • D I Hoffman
    Anupama SQ, Kathiresan A, Cruz-Almeida Y, Barrionuevo MJ, Maxson WS, Hoffman DI, et al. Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization. Fert Sterility. 2011;96 (6):1362-6.
  • Early B-HCG levels predict pregnancy outcome
    • S A Fong
    • H Rodriquez-Ayala
    • M Louis
    • R Howland
    • D Mcculloh
    • P G Mcgovern
    Fong SA, Rodriquez-Ayala H, Louis M, Howland R, McCulloh D, McGovern PG, et al. Early B-HCG levels predict pregnancy outcome. J Soc Gynecol Investig. 2005;12(2):226.
  • Article
    Full-text available
    Pregnancies achieved by in vitro fertilization (IVF) are at increased risk of adverse outcome. The main objective of this study was to evaluate the predictive value of β-human chorionic gonadotrophin (β-HCG) and age of the patient for the successful outcome in IVF. A retrospective study was done in 139 pregnancies after IVF at single IVF center from June 2007 to July 2012. The age of the patient and initial serum values of β-HCG on day 14 of embryo transfer were correlated with ongoing pregnancy (>12 weeks gestation). The β-HCG level on day 14 of more than 347 mIU/ml has a sensitivity of 72.2% and specificity of 73.6% in prediction of pregnancy beyond 12 weeks period of gestation. Positive likelihood ratio (LR) is 2.74 and negative LR is 0.37, (receiver operating characteristic area = 0.79). In IVF cycles, there is a lot of stress on the couples while the cycle is going on. There was a positive correlation between the higher values of early serum β-HCG levels and ongoing pregnancy. Hence, it can be used as an independent predictor of a successful outcome of IVF cycle. We concluded from our study that early serum β-HCG can be used as a predictor of a successful outcome in IVF.
  • Article
    The predictive value of serum beta hCG level for fetal cardiac motion and pregnancy outcome after IVF was evaluated. The serum hCG level 12 days after ET is a useful predictor of subsequent presence of fetal cardiac activity and live birth and may assist clinicians in counseling patients regarding their IVF outcome.
  • Article
    We sought to estimate a standard curve of serum human chorionic gonadotropin (hCG) decline that characterizes spontaneous abortion. Data were extracted from a clinical database of women with symptomatic early pregnancies and nondiagnostic ultrasonography who required follow-up with serial hCG levels. The evaluation was restricted to women who had a pregnancy of unknown location, a decrease in serum levels, and who were ultimately diagnosed with miscarriage (a decrease in serum hCG to < 5 mIU/mL in the absence of surgical intervention or confirmation of products of conception after dilation and curettage). The starting point of the curve was the hCG concentration at presentation, with serial levels plotted until the time of definitive diagnosis. Semiparametric statistical techniques were used to characterize the shape of the curve. We present slopes for the decrease in log hCG levels and the projected rate of fall. Of the 1,543 patients, 710 were diagnosed with miscarriage. A quadratic curve for log hCG with a steeper rate of decline for large initial hCG values best described the pattern of change. One curve could not fully estimate the decline because the rate was dependent on the initial hCG level. In other words, more rapid decline was associated with a higher starting concentration. The rate of decline ranged from 21% to 35% at 2 days and 60% to 84% at 7 days, depending on initial hCG value. The rate of hCG decrease in spontaneous abortions is described by a quadratic profile, with a faster decline in hCG value with higher presentation levels. A rate of decline less than 21% at 2 days or 60% at 7 days suggests retained trophoblasts or an ectopic pregnancy.
  • Article
    Low initial serum beta hCG is a good predictor of early pregnancy failure. We sought to determine the contribution of treatment variables and the predictive value of early serum beta hCG after IVF on long-term pregnancy outcome. A retrospective case-control study. An academic IVF unit. Five hundred thirty-three IVF cycles performed between 1999 and 2004, which resulted in a positive serum beta hCG level (> 10 mIU/mL) on day 13 after embryo transfer (ET). The study group included 281 pregnancies with initial beta hCG < or = 150 mIU/mL on day 13 after ET. Randomly selected 252 IVF cycles with initial beta hCG > 150 mIU/mL comprised the control group. Characteristics of the patients and the treatment protocols were analyzed using logistic regression, Pearson's chi-square, and Fisher's exact test. Primary pregnancy outcome was defined as favorable when a fetal pulse was detected, testifying to a viable gestation. Unfavorable outcome referred to chemical or ectopic pregnancies, as well as spontaneous abortions. Additionally, the two groups were followed throughout gestation. Secondary pregnancy outcome was based on the following parameters: gestational age at delivery, method of delivery, and birth weight. Poor primary pregnancy outcome was encountered in 64.8% of the study group and in 22.2% of the control group. Predictors of unfavorable primary pregnancy outcome were older age, use of a short protocol, and shorter than anticipated crown-rump length. No difference was found in the secondary pregnancy outcome between the groups. Preterm labor was more prevalent in the study group, but the difference did not reach statistical significance. Pregnancy viability can be predicted by measuring serum beta hCG as early as on day 13 after ET. Older age, use of a short protocol, and shorter than anticipated crown-rump length are associated with early pregnancy loss. Of those who reach delivery, no significant adverse outcome is anticipated in IVF pregnancies with low initial serum beta hCG.
  • Article
    To correlate the live delivery rate with the initial level and rise of serum beta-hCG. Retrospective cohort analysis. Large private academic center for assisted reproductive technologies and infertility. Records of all patients from 1999 to 2005 undergoing IVF with detectable early serum beta-hCG after ET. None. Live delivery rate. Data from 6021 pregnancies were analyzed. Initial beta-hCG was predictive for delivery rate for all patients and for each age group. After controlling for the first beta-hCG, there were higher loss rates as age increased. Percent rise in second beta-hCG drawn 2 days later added predictive value. A decline in beta-hCG almost always resulted in a failure to deliver. There was a progressive increase in delivery rate as the percent rise in beta-hCG went from 0 to 100%; however, there was no further enhancement in delivery rates beyond the 100% rise point. While a better rise in beta-hCG was a good prognostic factor in all age groups, the differences in outcomes for the different age groups remained, even after controlling for first beta-hCG and percent rise. Initial level and rise in beta-hCG predicts live delivery rate, with oocyte age providing additional predictive value. The established logarithmic curves should provide convenient reference tools for tracking outcomes and counseling patients.