Serum progesterone and serum b-HCG levels in first trimester threatened abortion

INTRODUCTION

Abortion is a fetus delivery before reaching 500 g or the age of viability. The age of viability differs between countries according to accompanying resources and supplies. The threatened abortion is detected, if pregnant woman has a vaginal bleeding in case of a closed cervix during the first 20 weeks of pregnancy.¹Progesterone facilitates implantation by preparing and supporting endometrial building process and it is helpful in quieting the uterus or minimizing the bleeding that occur with implantation and provide an important environmental support for implantation. Increased Progesterone production has a great effect on uterine smooth  muscle by suppressing its activity and contractility.  Furthermore, its significant role in suppressing the rejection of the trophoblasts by inhibit the immunological rejection of newly implanted embryo.² B_HCG secreted mainly by the syncytiotrophoblasts of the placenta after successful implantation and it is responsible for continuation of pregnancy. It has a main role in support and maintenance of the function of the corpus luteum by maintain progesterone release from the day after

implantation, by that time serum B_HCG test may be positive.³

This study aimed to declare the relation between maternal serum progesterone level and  serum B_H.C.G  level in patients with threatened abortion at gestational age 5-12 weeks and their relation to outcome of  abortion.

PATIENTS AND METHODS

The study was carried out at El Hussien and Om El Masreen hospitals during the period from June 2017 to November 2019. 200 patients on the5^th - 12^th week of gestation with first trimester threatened abortion were included in our study. All pregnant women who were included in our study signed a informed written consent to clarify their agreement to be enrolled in our study. Pregnant women who were diagnosed with twin pregnancy, ectopic pregnancy, embryonic demise, induced abortion, prior treatment with progesterone or B_HCG, diabetic patient , vesicular mole and bleeding tendency diseases were excluded in our study. All cases were subjected to history taking including personal history (name, age, parity and educational level), menstrual history (L.M.P, menarche , nature of menses), Obstetric history (number of parity, abortion, living children and history of previous sections). General examination was done to exclude general causes of bleeding while pelvic and speculum examination was done to exclude other local causes of vaginal bleeding as cervical erosion and to examine cervix opened or closed. Trans_ vaginal ultrasonographic scanning was done at the first presentation  to check fetal viability,  assess measurements, retroplacental hemorrhage and placenta previa. We assay progesterone and B_HCG levels at the time of presentation by venous blood samples collection from all cases. All cases were followed up every two weeks by ultrasound to assess fetal viability and  measurements till 20^th week gestation and according the outcome they were divided in two groups the aborted group and the continued group.

Statistical analysis:

SPSS version 24 was our chosen version . MD and SD were used to analyze data , while frequency and percentage were used with qualitative data. We compare between the continued and aborted group by Student t test, while comparing non parametric data corrected chi square was used. Our cutoff value of serum progesterone and serum beta HCG was detected by  receiver operator characteristic curve (ROC) analysis.

RESULTS

This prospective study was conducted on two hundred pregnant women on the 5- th 12th week of gestation with threatened abortion. The abortion rate is 27.5% (55 aborted cases ) till the 20th week of gestation. We divided the patients into two groups aborted group and continued group.

Table 1: Demographic and clinical variables distribution according to aborted or continued. This table revealed no considerable difference found regarding age, GA, hemoglobin and BMI between the aborted and continued groups.

Table 2: B_hCG and Progesterone distribution according to aborted or continued. Regarding median B_hCG levels were significantly lower among aborted women compared to those who continued pregnancy. Meanwhile, mean progesterone levels were low significant between the groups.

Fig 1: ROC curve for β-HCG and Progesterone for predicting abortion. The ROC curve showed that the cut off level of β-HCG 18153 gave 100% sensitivity and specificity was 98.2% and cut off level of Progesterone 23. 5 gave 83% sensitivity  and specificity was 89%.

Fig 2: ROC curve for investigated B_H.C.G and Progesterone together for predicting abortion. The ROC curve showed that progesterone and β-H.C.G combined together rises specificity up to 100%.

Table (3): Logistic Regression model for abortion. The table showed that there is significant risk for abortion in case of patients with decreasing in B_H.C.G level.

DISCUSSION

Miscarriage is an anxious thought faced by women who look for to be a mother. Miscarriage is pregnancy termination before fetus reach the age of viability. Up to 20% of all pregnant women, their  pregnancy  would ended by  miscarriage and most of them occurred during the first trimester.⁴  Early vaginal bleeding could be a predictor for miscarriage. However, there were different risk of miscarriage based on reported duration and amount of bleeding and accompanying pain symptoms.⁵

Progesterone and B_HCG were consider as reliable single markers because of their potential prediction  of miscarriage. Progesterone is one of ovarian steroid hormones secreted by the ovary and markedly related to the continuation and stabilization of pregnancy. This hormone plays important role for preparing uterus for embryo implantation. The other importance of progesterone is inhibition of uterus contraction and suppression of the maternal immune system.⁶ HCG promotes progesterone production by corpus luteal cells, promotes angiogenesis in uterine hypertrophy; aids in suppressing maternal immunity and cripples phagocytes action on implanted embryo and placental formation; increases uterine growth parallel to fetal growth; Facilitates implantation and enhances maturation of fetus organs during fetal life.⁷. Increased  progesterone levels means a well functional corpus luteum and a healthy growing placenta. Viable pregnancy have been associated with more than 55 nmol/L serum progesterone levels, meanwhile low levels less than 30 nmol/L signals to incoming pregnancy failure.⁸

Serum progesterone concentration < 5ng/ml reflect ongoing pregnancy failure, whilst healthy pregnancy is more related to values > 20 ng /ml.⁹ In our study we found that β-HCG levels were significantly lower among aborted women compared to those who continued pregnancy, meanwhile progesterone levels were low significant between the groups. In agreement with Osmanağaoğlu et al.¹⁰

study, who revealed that β-HCG levels were detected significantly lower in the aborted women than that of the group where no abortion was detected. Also, we revealed that B_ HCG and progesterone are significant in predicting pregnancy out come with a cutoff value of  B_HCG and Progesterone which was (18153 mIU/ml ,23.5 ng/ml). for B_HCG at  18153 mIU/ml were 100% and 98.2%, respectively meanwhile, for Progesterone at 23.5 ng/ml 83% and 89% respectively. and this is supported by the results of by (Maged and Mostafa ¹¹; Kim et al.¹²; Darwish et al.¹³; Duan et al.¹⁴,  and Al-Sebai et al.¹⁵).

Moreover, we warranted that β-HCG is considered as an independent factor on miscarriage. Also, we have noticed a significant   positive correlation between β-HCG and progesterone. This result agreed with that reported by Al-Sebai et al.¹⁵ who studied  the role of B_HCG  measurement in normal pregnant women and women who complained of  vaginal bleeding in their first eighteen weeks of pregnancy revealed that a single serum B_HCG measurement is greatly acceptable in the prediction of prognosis of  vaginal bleeding in  early 18 weeks of gestation. In  study of  Darwish et al.¹³

who investigated  using  progesterone in cases with recurrent abortions to predict  pregnancy outcome, they revealed that no relevant relation between progesterone  and pregnancy outcome with a 43% sensitivity and 50% specificity. Also, Kim et al. ¹²  in comparison between B_HCG, progesterone and inhibin A for prediction of threatened abortion outcome found that the single measurement of serum HCG is sufficient meanwhile, the ordinary assessment of inhibin A serum and progester­one levels seems to be unjustifiable in these patients to predict pregnancy outcomes.  Meanwhile, Verhaegen et al.¹⁶ in their recent meta-analysis study revealed that the single marker strategy for predicting the prognosis of threatened miscarriage is not preferred rather than the    combination of serum progesterone with serum B_H.C.G which is more reliable. In the contrary,  Lo and Rajuddin ¹⁷ use the cut-off point of progesterone to a level of 19.5 ng/dl gave the best sensitivity and specificity. Also Abdelazim et al.¹⁸ which found a 20 ng/dl as a cut-off point had 95.1% sensitivity and 98.9% specificity to predict viable and non-viable pregnancy. Duan et al.¹⁴concluded that there is significant relation between measuring B_HCG and progesterone in predicting outcome of threatened abortion and when using together shows great improvement over a single test. Depend on our findings, the single measurement of B_H.C.G give the best sensitivity, specificity and the best prognosis rather than progesterone. Moreover, The Combination does not add any benefit on sensitivity ,while specificity increased from 98.2% to 100%.

CONCLUSION

We revealed that B_HCG is considered as an independent factor on miscarriage. Also, we have noticed a significant  positive correlation between B_HCG and progesterone B In case of threatened abortion, using  B_HCG to anticipate the end result is more reliable than progesterone B with a cutoff value of  B_HCG 18153 mIU/ml (with sensitivity 100% and specificity 98.2%),   Progesterone 23.5 ng/ml ( with sensitivity 83% and specificity 89%). Depend on our results, the single measurement of B_HCG gave the best sensitivity, specificity and the best prognosis rather than progesterone. Moreover, The Combination of  B_HCG and progesterone does not add any benefits on sensitivity ,while specificity increased from 98.2% to 100%.