Discussion
The occurrence of clinical recognized pregnancy loss accounts for
approximately 15%–25% of all pregnancies[2]. A
considerable number of women suffer from recurrent pregnancy loss. In
early pregnancy inspection, especially for women who present with
threatened miscarriage, obstetricians and gynaecologists are committed
to identifying serum biological markers in order to predict pregnancy
outcomes. Several studies[3-6] have focused on
various biomarkers such as serum β-HCG, progesterone, estradiol, PAPP-A,
inhibin, CA125 and combination of serum biomarkers and ultrasound
features to predict pregnancy viability. Ideal biological markers are
highly predictive, detected conveniently and cost-effective. Nowadays,
the most widely used indicators are serum β-HCG and progesterone.
Progesterone is necessary in maintaining early pregnancy, playing an
important role in sustaining decidualization, reducing uterine
excitability, inhibiting uterine contraction, suppressing inflammatory
response and promoting maternal immune tolerance to the fetal
semi-allograft[7-9]. However, due to large
individual differences and insufficient evidence regarding appropriate
progesterone cut-off levels for risk stratification of spontaneous
miscarriage, its clinical value in miscarriage risk assessment remains
controversial.
HCG is a specific marker of pregnancy, synthesized in
syncytiotrophoblast cells and can be detected as early as 8–11 days
following ovulation[10]. Serum HCG level reflects
quantity of trophoblast cells, rapidly increasing at the early stage of
gestation, slowing down later, and reaching the peak at 8-10 weeks of
pregnancy. Previous studies[3,11] have proven
quantitative determinations of HCG as a valuable tool in the clinical
assessment of early pregnancy outcome. A systematic review summarized 8
studies with a total of 584 women that investigated either intact HCG or
β-HCG to predict the outcome in women with threatened miscarriage,
showing a sensitivity of 44% and a specificity of 86% through further
analysis using HSROC[6]. Liu et al. reported that
the optimal cut-off value of peak β-hCG was 88468IU/L, with a
sensitivity, specificity, positive predictive value, and negative
predictive value for successful pregnancy of 95.6%, 88.0%, 95.6%, and
89.0%, respectively[12]. Estrogen is another
highly important hormone in establishing and maintaining pregnancy.
Studies investigated that estrogen stimulated VEGF production and blood
vessel formation to enable maternal-fetal
circulation[13], and showed functions in immune
regulation[14]. It modulates the immune response
by inducing peripheral T cells to secrete the proinflammatory
cytokines[14]. Xu et al. compared sex hormone and
sex hormone metabolite levels of women in early pregnancy with and
without threatened miscarriage, and reported that serum E2 levels were
lower in women with threatened miscarriage[15].
They proposed that abnormal levels of sex hormone metabolites and
reduction of estrogen activity might result in bleeding during the first
trimester of pregnancy. Compared to progesterone and HCG, estrogen is
not as widely used in pregnancy assessment. Previous study has found
that the sensitivities of estradiol(80%) and HCG(85%) in predicting
pregnancy outcome at week 8 of gestation were better than that of serum
progesterone (56%)[16]. Pillai’s review found
similar results, but the sensitivity was heterogeneous among previous
reported studies[6].
As the levels of serum β-HCG and estradiol change over each week of
gestation, most of the previous studies did not take this into
consideration. Few reports have examined changes of E2 in early
pregnancy. The present study focused on dynamic variation of E2 and
β-HCG in early pregnancy women, examining their levels and growth rates
to help us predict the miscarriage risk accurately and timely. The
results presented that β-HCG and E2 levels of the ongoing pregnancy
group were significantly higher and increased more rapidly than those of
the inevitable abortion group. β-HCG in normal pregnancy increased
drastically within the beginning period of gestation, and from the 5th
week to 8th week, medians of the growth rate were 5.82, 1.96 and 0.75
per week. Low growth rate may predict bad pregnancy outcome.
Quantitative value and growth rate are both meaningful in early
pregnancy assessment. When β-HCG combined with E2, the prediction of
pregnancy outcome will be more accurate. Miscarriage women showed lower
E2 levels. E2 in normal pregnancy women increased 40%-60% weekly on
average. Slow growth rate and decreased E2 level are likely to predict
bad outcome. Results of our study agreed with most other studies,
moreover we provided more information about the variations and growth
rates of women with different early pregnancy outcomes.
The major limitation of our study is the relatively small sample size,
especially in the inevitable abortion group. It is a little difficult to
get large amount of data of miscarriage women due to a relatively small
number of miscarriage patients and lack of hormone values after their
abortions. So in the future study we will make more efforts to collect
larger samples to strengthen the results and hope to find more highly
predictive and cost-effective biological markers in predicting pregnancy
outcome.
In conclusion, dynamic monitoring of maternal serum E2 and β-HCG levels
has important clinical implication for early pregnancy assessment and
pregnancy outcome prediction. Low values and low growth rates of E2 and
β-HCG probably indicate bad pregnancy outcomes.