1. SERUM PROGESTERONE LEVEL IN PREDICTING THE OUTCOME OF THREATENED MISCARRIAGE  
THUZAR THWE,KHIN LATT,SAN SAN MYINT
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY,
UNIVERSITY OF MEDICINE(1),
YANGON,MYANMAR

2. Introduction
Threatened miscarriage- common early pregnancy complication(30%)
Serial serum beta hcg – for prediction the outcome
Single serum progesterone- essential for continuation of pregnancy
- keep the uterus in relax state
-promote endometrial decidualization
-important role in matainig the early stage of
pregnancy

3. Aim
To predict the outcome of threatened miscarriage by serum progesterone level at early gestation(6-14wks).

4. Methods
. A total of 109 patients attending the Gynaecological OPD and admitted to the Gynaecology wards of Central Women’s Hospital, Yangon were recruited.
history taking and physical examination
datas were collected by direct questionnaires according to proforma
Ultrasound (TAS and TVS) examination was done to confirm maturity, viability and intra or extra uterine pregnancy
Blood sample (3ml)
Pregesterone level was measured by cobas e 411 analyzer which was made in Germany
The principle of competitive immunoassay with analyte liberation method was used

5. managed according to hospital guideline and followed up every 4 weeks if there was no complication
If they had any of vaginal bleeding, lower abdominal pain and something passed per vagina, recheck ultrasound was done. These patients were managed according to hospital guideline depending on the viability
If there was no complication, clinical examination and ultrasound was done at 22 weeks and 28 weeks gestation to confirm the outcome of pregnancy
Different cut off point for progesterone level for prediction of viability was determined by using the ROC curve
Chi-square test was used to find the association between basal progesterone level and outcome of early pregnancy threatened miscarriage.

6. Results
Demographic characteristics of study population
In patient 25years and below, 70% went into non-viable pregnancy and only 30% had ongoing pregnancy
In more than 35 years of age patient, 80% went into non-viable pregnancy and 20% had ongoing pregnancy
the association of age and non-viable pregnancies were statistically significant ( P value 0.016)
The association of non-viable pregnancies and educational status was not statistically significant (P value ).

7. Gestational age (weeks)
No. of patients with different progesterone levels (ng/ml)
Total
≤20
21-40
41-60
>60
≤ 8 weeks 30 10 4 1 45
>8 to 10 weeks 24 2 6 33
>10 to 12 weeks 5 3 11
>12 to 14 weeks 21 64 16 19
110
Table (1) Progesterone level of study population at different gestational age

8. Gestational age(weeks)
Progesterone level ≤20ng/ml
non-viable pregnancies
Ongoing pregnancies
Total
No.
Percent
≤ 8 weeks 27
90% 3
10% 30
>8 to 10 weeks 23
95% 1 5% 24
>10 to 12 weeks 5
100% 0%
>12 to 14 weeks 4
80%
20% 58
93% 7% 63
Table (2) Outcome of threatened miscarriage of study patient with progesterone level ≤20ng/ml at different gestational age .

9. Gestational age (weeks)
Progesterone level >60ng/ml
No. of Non-viable pregnancies
No. of Ongoing pregnancies
Total
≤ 8 weeks 1
>8 to 10 weeks 2 4 6
>10 to 12 weeks
>12 to 14 weeks 3 8 11 5 14 19
Table (3) Outcome of threatened miscarriage of study patient with progesterone level >60ng/ml at different gestational age .

10. Non-viable pregnancies
Progesterone level (ng/ml)
outcome
Total
Ongoing pregnancies
Non-viable pregnancies
No.
Percent
≤20 5 8% 58
92% 63
57%
21 to 40 15
93% 1 7% 16
14%
41 to 60 10
83% 2
17% 12
10%
>60 14
73%
27% 19
19% 44
40% 66
60%
110
100%
Table (4) Association of progesterone level and outcome of threatened pregnancy

11. Miscarriage
Ongoing pregnancy
Total
No. 60 50
110
Percent (%) 54 46
100
Table (5) Outcome of threatened miscarriage among the study population at 22 weeks gestation

12. Non-viable pregnancy
Ongoing pregnancy
Total
No. 66 60
110
Percent (%) 44 40
100
Table (6) Outcome of threatened miscarriage among the study population at 28 weeks gestation
The above table showed the outcome of threatened miscarriage among the study population. More than half of the population, 66cases (60%), ended up with non-viable pregnancy and the rest 44 cases (40%) went into the ongoing pregnancy.

13. Cut off point
Sensitivity
Specificity
PPV
NPV
Efficiency
≤10
81.19
95.45
59.42
77.77
87.27
≤20
87.88
88.36
92.06
82.98
88.18
≤30
79.54
86.56
81.39
84.45
≤40
89.39
54.54
75.64
72.72
75.45
≤50
92.42
38.63
69.32
77.27
70.90
≤60
31.81
67.03
73.68
68.18
Table (7) Different cut off points of early pregnancy progesterone level for the prediction of pregnancy loss

14. Asymptotic 95% Confidence Interval
Figure (1) ROC curve showing the serum progesterone level and outcome of threatened miscarriage
Area
Std. Error
Asymptotic Sig.b
Asymptotic 95% Confidence Interval
Lower Bound
Upper Bound
.911
.030
.000
.852
.970

15. 7. Discussion
 Non-viable pregnancy is more common over the age of 35years and ≤25 years than the other age group
Extreme maternal ages were statistical significant with non-viable pregnancies

16. at 6-8 weeks gestation, 30 cases - serum progesterone level of ≤20ng/ml. (27 cases - non-viable and 3 cases - ongoing pregnancy)
10 cases - serum progesterone level 21-40ng/ml at 6-8 weeks gestation (9 cases have ongoing pregnancy , one patient loss her pregnancy
>60ng/ml at that gestation only one case is found and it undergoes ongoing pregnancy
higher level of progesterone can predict the chance of ongoing pregnancy at 6- 8 weeks gestation

17. At the gestation of >8-10 weeks gestation, total 33 cases
24 cases had serum progesterone level of ≤20 ng/ml (23 cases - non- viable pregnancy and only one case - ongoing pregnancy)
only two cases - serum progesterone level of 21-40ng/ml at >8-10 weeks gestation
one case at serum progesterone level of 41-60ng/ml and had ongoing pregnancy
At the serum progesterone level of >60ng/ml, total 6 cases are found (4 cases - ongoing pregnancy and 2 cases - non-viable pregnancies)
So, it can say the outcome of threatened miscarriage is improved with the higher level of the serum progesterone level.

18. Total 11 cases are found at the gestation of >10-12 weeks gestation
5/ 11 cases - serum progesterone level of ≤20 ng/ml - all are non- viable pregnancy
2/11 cases- serum progesterone level of 21-40ng/ml
3/11 cases - serum progesterone level of 41-60ng/ml
1/11 case - serum progesterone level of >60ng/ml
all of these are ongoing pregnancy.
At week gestation- 21 cases
5/21 cases - ≤20 ng/ml (3 cases are non-viable pregnancy)
2/21 cases at 21-40ng/ml and 3/21 cases at 41-60ng/ml and all are ongoing pregnancy.
11/21 at >60 ng/ml and all ended as non-viable pregnancy.

19. - total 110 cases- 44cases (40%) ongoing pregnancy
- 66 cases (60%) non-viable pregnancy
at the cut off level of single serum progesterone 10ng/ml -sensitivity % , specificity 95.45% , positive predictive value 59.42% , negative predictive value 77.77% and efficiency of 87.27% .
at the single serum progesterone level of 20ng/ml sensitivity of 87.88%, specificity of 88.36% , positive predictive value of 92.06% , negative predictive value of 82.98% and efficiency of 88.18%
Serum progesterone level of 20ng/ml has higher sensitivity, positive predictive value and negative predictive value than the serum progesterone level of 10ng/ml.
So the most efficient cut off value of serum progesterone of prediction of the outcome of threatened miscarriage was 20ng/ml.

20. The best cut off value of serum progesterone level is 20ng/ml which is the same with the study of Abdelazim et al,2012. Both of the studies had the same inclusion and exclusion criteria and outcomes were determined by the ultrasound in both studies
In Jorine et al 2012, the cut off level of serum progesterone level is 3.2 to 6ng/ml and 10ng/ml which is lower than the cut off value of this recent study because there are many differences in the numbers of the studied populations.
According to the RCOG(2006), the cut off level to predict the outcome of threatened miscarriage was still conflicting.

21. In comparison of the outcome of threatened miscarriage at 22 weeks gestation and 28 weeks gestation 45%(50 cases) and 40% (40cases) ongoing pregnancy respectively.
There are only 5 cases(4%) ended up with non-viable pregnancy after 22weeks gestation.So, it can be concluded that the outcome of threatened miscarriage was good after 22 weeks gestation.
In recent study 63cases (69.3%) have serum progesterone level of ≤20ng/ml and 5cases (7.9%) are viable and 58 cases (92%) are failed.
Nigh teen cases (17%) are serum progesterone level of >60ng/ml, 14 cases (73%) are viable and 5 cases (26%) failed pregnancy.
So that , higher level of serum progesterone level is associated with the viable pregnancy

22. 9. REFERENCES
Abdelazim , Ibrahim A (2012) Relation between single serum progesterone assay and viability of the fitsr trimester pregnancy, Obstetrics and Gynaecology , Aim Shams University, Caris,Egypt, 1:80, 1-5.
Ash monga, Stephen Dobbs (2011), Gynaecology by ten teacher, 19th Edition,
David J, Cahill, Rebecca Swingler, Peter G (2011), Bleeding and pain in Early Pregnancy, High Risk Pregnancy,
Elecsus (2010), Electrochemiluminescence immunoassay(ECLIA) for the in vitro quantitatie determination of progesterone in human serum and plasma, available from [accessed on 20 July 2015].
Hinshaw K, Fayyad A, Munjuluri P (2006) The management of early pregnancy loss. Royal College of Obstetricians and Gynaecologists (Green-top guideline No 25).

23. THANK YOU