27
Fetal loss in threatened abortion after embryonic/fetal heart activity Y. Tannirandorn , , S. Sangsawang, S. Manotaya, B. Uerpairojkit, P. Samritpradit , D. Charoenvidhya Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Received 2 December 2002; revised 23 January 2003; Accepted 29 January 2003. Available online 26 March 2003. Abstract Objectives : To study the incidence of fetal loss in threatened abortion after detection of embryonic/fetal heart activity. Methods: A prospective study was performed on pregnant women with clinically diagnosed threatened abortion between 6 and 14 weeks of gestation. All had a good menstrual history and the calculated gestational age using crown–rump length in the first trimester ultrasound was in agreement. Embryonic/fetal heart rate measurements were obtained by a 5 MHz vaginal probe using M-mode and real- time B mode imaging. All cases were followed up with respect to pregnancy outcomes. The data were analyzed using the SPSS computer program. Results: Eighty-seven pregnant women were included in the study. There were three pregnancies (3.4%) which resulted in fetal loss before 20 weeks of gestation. In viable pregnancies, the mean embryonic/fetal heart rate increased with advancing gestational age. The individual values of embryonic/fetal heart rate for fetal losses were within the reference range. Conclusions: The incidence of fetal loss in threatened abortion after detection of embryonic/fetal heart activity was 3.4%. There was no evident pattern of bradycardia or tachycardia that signaled the incipient of viability. Keywords: Threatened abortion; Fetal loss, Ultrasound

Fetal Loss in Threatened Abortion After Embryonic

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Page 1: Fetal Loss in Threatened Abortion After Embryonic

Fetal loss in threatened abortion after embryonic/fetal heart activity

Y. Tannirandorn  ,  , S. Sangsawang, S. Manotaya, B. Uerpairojkit, P. Samritpradit, D. Charoenvidhya

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Received 2 December 2002; revised 23 January 2003; Accepted 29 January 2003. Available online 26 March 2003.

Abstract

Objectives: To study the incidence of fetal loss in threatened abortion after detection of embryonic/fetal heart

activity. Methods: A prospective study was performed on pregnant women with clinically diagnosed threatened

abortion between 6 and 14 weeks of gestation. All had a good menstrual history and the calculated gestational age

using crown–rump length in the first trimester ultrasound was in agreement. Embryonic/fetal heart rate measurements

were obtained by a 5 MHz vaginal probe using M-mode and real-time B mode imaging. All cases were followed up

with respect to pregnancy outcomes. The data were analyzed using the SPSS computer program. Results: Eighty-

seven pregnant women were included in the study. There were three pregnancies (3.4%) which resulted in fetal loss

before 20 weeks of gestation. In viable pregnancies, the mean embryonic/fetal heart rate increased with advancing

gestational age. The individual values of embryonic/fetal heart rate for fetal losses were within the reference

range. Conclusions: The incidence of fetal loss in threatened abortion after detection of embryonic/fetal heart activity

was 3.4%. There was no evident pattern of bradycardia or tachycardia that signaled the incipient of viability.

Keywords: Threatened abortion; Fetal loss, Ultrasound

Pregnancy Outcome of Patients Complicated by Threatened Abortion

Pregnancy Outcome of Patients Complicated by Threatened Abortion

G Mustafa MD 

Registrar

Department of Obstetrics and Gynaecology

Government Medical College & Associated L.D. Hospital Srinagar Kashmir 

Rabia Khurshid MD 

Registrar

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Department of Obstetrics and Gynaecology

Government Medical College & Associated L.D. Hospital Srinagar Kashmir 

Mushtaq 

Postgraduate

Department of Obstetrics and Gynaecology

Government Medical College & Associated L.D. Hospital Srinagar Kashmir 

Irfan ul shamas 

Postgraduate

Department of Obstetrics and Gynaecology

Government Medical College & Associated L.D. Hospital Srinagar Kashmir 

Shahida Mir MD 

HOD

Department of Obstetrics and Gynaecology

Government Medical College & Associated L.D. Hospital Srinagar Kashmir 

Citation: G. Mustafa, R. Khurshid, Mushtaq, I. ul shamas & S. Mir : Pregnancy Outcome of

Patients Complicated by Threatened Abortion. The Internet Journal of Gynecology and

Obstetrics. 2010 Volume 14 Number 1

Keywords: Abortion | bleeding per vaginum | pregnancy.

Abstract

The study was conducted among 100 pregnant women who presented with

vaginal bleeding before 20 weeks of gestation, 34% of women aborted,

Page 3: Fetal Loss in Threatened Abortion After Embryonic

21.2% had preterm delivery, 23.4% had low birth weight babies, apgar

score was less than 7 in 20.3% babies and perinatal mortality was 3%.

Serum T3, T4levels were in lower range in patients who aborted as

compared to those patients who continued with pregnancy.

Introduction

Uterine bleeding during pregnancy represents a definite threat to the

developing embryo and is often followed shortly by termination of the

gestation1,2. Clinical diagnosis of threatened abortion is presumed when any

bloody discharge or vaginal bleeding appears during first half of pregnancy

50% of women with vaginal bleeding in 1st trimesters of pregnancy abort

and 50% continue pregnancy2. There is increased risk of suboptimal

pregnancy outcome in the form of preterm delivery, low birth weight and

unexplained intrauterine death in these cases4-12. It has been suggested that

gestational bleeding and little or no symptomatology is almost always the

consequence of marginal separations of placenta. Gestational bleeding no

associated with placenta previa involved permanent deciduoplacental

damages leading to impairment of oxygen transfer and fetal nutrition13.

Hypothyroidism in pregnancy is associated with adverse fetal outcome as

well as increase in obstetric complications. Women with hypothyroidism

have a lower rate of pregnancy and a high rate of spontaneous miscarriages

compared to normal population14-20.

Material and Methods

To know the outcome of pregnancy complicated by threatened abortion the

study was conducted in Government Lal Ded Hospital, an associated

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hospital of Government Medical College Srinagar with eligible mothers in

childbearing age taken from 19-34 years. As quoted by Shaw Committee

(1996), number of abortions per annum is 10% of total live births i.e. seven

million per annum. The prevalence of patients coming with bleeding per

vaginum before 20 weeks of gestation in Government Lal Ded Hospital,

Srinagar is around 1800 per annum and the sample size of the study

population was accordingly calculated to be 100 by systematic random

sampling. The study was conducted in 100 women with early pregnancy

bleeding (before 20 weeks of gestation); a group of 100 pregnant women

who had no history of bleeding per vaginum during their pregnancy

delivered in LDH were taken as control. The patients were selected in OPD

of Lal Ded Hospital from January 2001 to May 2003. Women from same

socio-cultural and ethnic groups from plains of Kashmir valley were taken in

study group. Women with gestational age less than 20 weeks and as closed

were included in study. Exclusion criteria – cervical erosion, bleeding

disorders, hydatidiform mole, cardiac diseases, diabetes mellitus, hepatic

disease multiple gestation, eclampsia and severe PET.

A detailed obstetrical and medical history was taken, timing and intensity of

bleeding was noted, thorough examination was done which included general

physical examination, signs of anaemia, detection of icterus, pulse, blood

pressure recorded, P/A examination, P/S examination and P/V was done.

Baseline investigations including Hb, blood grouping and typing, BT, CT,

PC, TLC, DLC, urine examination, blood sugar, thyroid profile, ECG and

USG for gestational age, fetal viability and placental localization were done.

Patients of threatened abortion wee given bed rest, sedation for two weeks,

subsequently they were allowed to resume some activity but not to travel

and go for coitus. Patients were followed by thereafter during antenatal,

intranatal and up to one week postnatal period. Sub-optional pregnancy was

Page 5: Fetal Loss in Threatened Abortion After Embryonic

described as birth weight less than 2501gms or gestational age less than 37

weeks and still birth.

Observations

In the study group 34% aborted, of these 23.5% were missed abortions,

25.2% were incomplete abortions, 17.6% had complete abortions and 23.5%

had inevitable abortions, of the rest 66%, 21.2% had preterm delivery and

in control group, there were 7% preterm deliveries and the incidence of

preterm delivery in cases was 3.85 times more than controls which was

significant (p < 0.05) Table-1. In the study group apgar score was < 7 in

20.3% babies and in control group it occurred in 13.2%. In the study group

78.8% of babies were born full term and in control group term deliveries

occurred in 93% of cases which was significant. In the study group, 23.4%

babies were born with low birth weight while as in controls low birth was

seen in8.1% babies. The average birth weight in term and low birth weight

babies in study group was 2.18 to 2.0kgs and in control group it was

2.30kgs, the difference was significant (p < 0.05) table-2. In study group

heavy bleeding was reported in 33% and slight bleeding in 67%. Abortions

occurred in 45.4% among heavy bleeders and 28.45% in slight bleeders

(table-3). Preterm deliveries occurred in 18.2% of heavy bleeders and 11.9%

of slight bleeders. Low birth weight occurred in 43.8% among heavy

bleeders and 16.6% of slight bleeders (table-3).

Among aborters mean serum T3 levels were 0.88 + 0.27ng/ml while as

among non-aborters the levels were 1.52 + 0.41ng/ml. The mean serum

T4levels among aborters was 5.93 + 0.94 ng/dl and among non-aborters it

was 8.46 + 1.06 ng/dl (table-4). The difference in the mean serum TSH

levels between aborters and non-aborters was not significant.

Page 6: Fetal Loss in Threatened Abortion After Embryonic

 

Table – 1 - Outcome of pregnancy in cases of threatened abortion

comparing with non-bleeders

 

Table – 2 - Comparative assessment of effect of early pregnancy bleeding on

the neonatal birth weight

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Table – 3 - Effect of severity of bleeding on pregnancy outcome

 

Table – 4 - Comparison of Serum T3, T4 and TSH in bleeding P/V cases

(n=100) before 20 weeks of gestation

Page 8: Fetal Loss in Threatened Abortion After Embryonic

Discussion

First trimester vaginal bleeding is an important predictor of adverse fetal

outcome12 with increased risk of preterm delivery, delivery of low birth

weight infant, and abortion4-12.

In our study we found in women with bleeding before 20 weeks of

gestations, 34% aborted and total foetal loss (abortions + perinatal death)

was 37%. The study is consistent with the studies of Adelusi B. et al3, Lipitz

et al21, Queekin et al22, Karim et al11.

In our study 21.2% of women had preterm delivery which is consistent with

the studies of Strobino et al2, William S et al8, Sipila P et al23, Ananth CV et

al9. Low birth weight was seen in 23.4% of study cases; heavy bleeding was

associated with an increased risk of low birth weight (odds ratio 2.2).

Mau G24, Yang et al25, Hertzits et al7 in their study did not show any increase

in frequency of small for gestational age infants in pregnancies complicated

by early gestational bleeding. The results of studies conducted by Beetzofin

JH et al6, Berkowitz GS et al5, Ananth CV9, Verma et al26, Hohlweg-Majenl P

et al were consistent with our study. In present study we found 3%

incidence of congenital malformations which was supported by the study of

Sipila et al23, Ananth CV et al9 and other studies2,4,8 did not observe any

congenital malformations.

In our study the serum T3and T4 levels were at a lower range of normal in

bleeders who subsequently aborted, there was no change in TSH level in

any patients. Maruo T et al18 and Bolz M19 concluded that women with

hypothyroidism have a high rate of spontaneous miscarriages compared to

normal populations. This indicated that maternal thyroid hormones may

have some possible role in maintaining pregnancy.

Page 9: Fetal Loss in Threatened Abortion After Embryonic

Correspondence to

Dr. Irfan ul shamas 

Saderbal syed sahib 

Hazratbal 

([email protected])

References

1. Charles H. Peckham. Uterine bleeding during pregnancy when not

followed by immediate termination of pregnancy. Obstet Gynecol 1970; 35:

937-41. (s)

2. Strobino B, Pantel-Silverman J. Gestational vaginal bleeding and

pregnancy outcome. Am J Epidemiol 1989; 129: 806-15. (s)

3. Adelusi B, Dada OA. Prognosis of pregnancies after threatened abortion.

Int J Gynaecol Obstet 1980; 18: 444-7. (s)

4. SJ Funderburk D, Burthrie. Outcome of pregnancies complicated by early

vaginal bleeding. Brit J Obstet Gynaecol 1980; 87: 100-105. (s)

5. Berkowitz GS, harlap S, Beck GJ, Freeman DH, Balas M. Early gestational

bleeding and pregnancy outcome: a multivariable analysis. Int J Epidemiol

1983; 12: 165-173. (s)

6. Batzofin JH, Fielding WL, Friedman EA. Effect of vaginal bleeding in early

pregnancy on outcome. Obstet Gynecol 1984; 63: 515-8. (s)

7. hertz JB, Heisterberg L. The outcome of pregnancy after threatened

abortion. Acta Obstet Gynecol San 1985; 64: 151-6. (s)

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8. Williams MA, Mitten Drof, Leibermine E. Adverse infant outcome

associated with first trimester vaginal bleeding. Obstet Gynecol 1991; 78:

14-8. (s)

9. Ananth CV, Savitz DA. Vaginal bleeding and adverse reproductive

outcomes: a meta-analysis. Paediatric Perinat Epidemiol 1999; 8: 62-78. (s)

10. Fournl. Takparal, Zohoun T. Pregnancies complicated by haemorrhage

and birth of low birth weight infants in cotonon (Bemin). Sante 1994; 407-

11. (s)

11. Karim SA, Bakhtawar I, Butta AT, Jalil M. Effects of first and second

trimester vaginal bleeding on pregnancy outcome. J Pak Med Associ 1998;

48: 40-2. (s)

12. Arfa M, Abdul Fataeh M, Zeid HA. Outcome of pregnancies complicated

by early vaginal bleeding. East Mediters Health J 2000; 6: 457-64. (s)

13. Dickey RP, Olar TT, Curde DN, Taylor SN. Relationship of first trimester

subchorionic bleeding detected by color Doppler ultrasound to subchorionic

fluid, clinical bleeding and pregnancy outcome. Obstet Gynaecol 1992; 82:

415-20. (s)

14. Winikeff D, Malinek M. The predictive value of thyroid “test profile” in

habitual abortion. Br J Obstet, Gynaecol 1975; 82: 760-6. (s)

15. Smith SC, Bold AM. Interpretation of in-vitro thyroid function tests

during pregnancy. Zentralbe Gynaecol 1984; 106: 18-25. (s)

16. Davis Le, Leveno KJ, Luningham FG. Hypothyroidism complicating

pregnancy. Obstet Gynaecol 1998; 72: 108-12. (s)

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17. Kuller JA, Laifer SA, Portney DL, Rulin Mc. The frequency of

transplacental haemorrhage in patients with threatened abortion. Gynaecol

Obstet Invest 1994; 37: 229-31. (s)

18. Maruo T, Katayama K, Maturo H. The role of maternal thyroid hormones

in maintaining early pregnancy in threatened abortion. Acta Endocrinol

1992; 127: 118-22. (s)

19. Bolz M, Nagel H. The course of pregnancy in congenital thyroid gland

aplaria. Case report with a special reference of maternal hypothyroidism.

Zentral bl Gynaecol 1994; 116: 515-21. (s)

20. Allan WC, Haddow, Palomaki GE, Williams JR. Maternal thyroid

deficiency and pregnancy complications. Implications for population

screening. J Med Screen 2000; 7: 127-30. (s)

21. Lipitz S, Adman D, Manczes J. Mid-trimester bleeding-variables which

effect the outcome of pregnancy. Gynaecol Obstet Invest 1991; 32: 24-7. (s)

22. Queek M, Berle P. Spontaneous abortion after vaginal haemorrhage in

intact early pregnancy an aetiologic analysis. Geburtshilfe Frauenheil 1992;

52: 553-6. (s)

23. Sipila P, Hastikainen, Sorri AL, Oja H. Perinatal outcome of pregnancies

complicated by vaginal bleeding. Br J Obstet Gynaecol 1992; 99: 959-63. (s)

24. Man G. Risk of prematurity and reported bleeding in pregnancy. Z

Guburtshilfe Perinatal 1997; 181: 17-9. (s)

25. Yang J, Savitz DA. The effect of vaginal bleeding during pregnancy on

preterm and small for gestational age births: US National Maternal and

Infant Health Survey 1988 Paediatr. Perinat Epidemiol 2001; 13: 34-9. (s)

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26. Verme SK. Premi HR, et al. Perinatal outcome of pregnancies

complicated by threatened abortion. J Indian Med Assoc 1994; 92: 364-5. (s)

This article was last modified on Fri, 15 Oct 10 23:25:56 -0500

Slow fetal heart rate may predict pregnancy outcome in first-trimester threatened abortion

Apichart Chittacharoen M.D.a,  , a,  , Yongyoth Herabutya F.R.C.O.G.a, a

a Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Received 2 December 2003; revised 2 December 2003; Accepted 2 December 2003. Available online 2 July 2004.

Abstract

Two hundred forty pregnant women presented with first-trimester threatened abortion were examined by transvaginal

ultrasound. Women with a slow fetal heart rate of less than 120 beats per minute may eventually be at increased risk

for pregnancy loss.

Article Outline

Reprint requests: Apichart Chittacharoen, M.D., Department of Obstetrics and Gynecology, Faculty of Medicine,

Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand (FAX: 66-2-2011416).

Progestogen for preventing miscarriage

Progestogen therapy in early-to-mid pregnancy does not prevent miscarriage. Four small studies included in this review suggest that progestogen therapy may be beneficial for women who have experienced recurrent miscarriages. This finding should be interpreted with caution until it is confirmed in large, well-designed trials.

RHL Commentary by Thach TS

1. INTRODUCTION

Progesterone plays a key part in preparing the uterus for implantation of the newly fertilized egg. It has been suggested that some women who experience spontaneous abortions may not be producing enough progesterone, so by administering exogenous progesterone it may be possible to prevent miscarriage. In Viet Nam, where induced abortion is available on request since 1960, unsafe abortion and miscarriage are together still the fourth leading cause of maternal mortality (1). Doctors in Viet Nam widely prescribe progestogens for the

Page 13: Fetal Loss in Threatened Abortion After Embryonic

treatment of threatened miscarriage. Widespread use of progestogens is not limited to under-resourced settings. In France, for example, progesterone is among the most frequently prescribed drug during pregnancy (2), and almost one third of women with threatened abortion are prescribed progestogen in Italy (3). Unlike in developed countries, most health-care workers and policy-makers in developing countries do not have easy access to the latest reliable information on effective care (4). Therefore, it is likely that in developing countries the extent of progestogen use during pregnancy is much greater than in developed countries. The objective of this review was to determine the efficacy and safety of progestogens as a preventative therapy against miscarriage.2. METHODS

The review authors searched all relevant databases for randomized and quasi-randomized controlled trials that had compared progestogens with placebo or no treatment for preventing miscarriage. Where necessary the review authors contacted authors of papers to obtain information. They also contacted experts in the field to identify any unpublished works. Two review authors independently assessed the quality of the available trials.3. RESULTS

The current updated review (5) was published in April 2008. It analysed data from 15 randomized controlled trials involving 2118 women who were perceived to be at an increased risk of miscarriage (previous miscarriage, threatened abortion, having undergone a uterine procedure such as amniocentesis, etc.). In this update, new data were included from a trial (6) in which 180 women with recurrent miscarriage were randomized to receive oral dydrogesterone, intramuscular human chorionic gonadotrophin or no treatment (controls).Overall, there was no statistically significant difference in the risk of miscarriage between groups receiving a progestogen or a placebo/no treatment [Peto odds ratio (Peto OR) 0.98; 95% confidence interval (CI) 0.78–1.24]. Also, the route of administration of progestogen (oral, intramuscular, or vaginal) appeared not to be associated with a statistically significant difference in miscarriage rates. Interestingly, four small trials (three of them published 40 year ago and one published in 2005) reported that progestogen administration was associated with a statistically significant decrease in miscarriage rate compared with placebo (OR 0.37; 95% CI 0.17–0.91) in a subgroup of women who had experienced recurrent miscarriage. The confidence interval suggests that the difference in miscarriage rate between progestogen administration and placebo may be either small or large.Progestogen therapy was not associated with any adverse effects on the woman. Although slightly more fetal/neonatal adverse events (fetal abnormalities and neonatal deaths) were identified among women receiving progestogen, the numbers were far too small − partly because of the rarity of such events − to qualify as a potential risk.Threatened miscarriage − the most common clinical diagnosis necessitating progestogen treatment − was analysed separately in another review (7), which includes only 84 participants from two rather methodologically poor studies. There was no evidence of effectiveness of vaginally given progesterone in reducing the risk of miscarriage for women with threatened miscarriage (RR 0.47; 95% CI 0.17−1.30).4. DISCUSSION

Progestogens do not prevent miscarriage in early-to-mid pregnancy. Results from the four small trials showing a positive effect of progestogens in the subgroup of women with recurrent miscarriage should be interpreted with caution because of the small number of

Page 14: Fetal Loss in Threatened Abortion After Embryonic

subjects in those trials and the wide confidence interval. Moreover, the methods used in the three older trials were inadequate and the 2005 trial (6) was neither placebo-controlled nor blinded nor well randomized. Also, the operative definition of recurrent miscarriage was not consistent between the trials. Finally, the Le Vine trial (8) had a post-randomization dropout rate of 46.4%.4.1 APPLICABILITY OF THE RESULTS

Despite the fact that all trials included in the review were conducted in developed countries, there is no biological basis to believe that the findings of this review may not be applicable to developing countries.4.2 IMPLEMENTATION OF THE INTERVENTION

Progestogen should be removed from the treatment list for preventing miscarriage. To do that, the most important step will be to increase awareness among policy-makers, health-care providers and patients about the fact that the practice is not based on evidence. Furthermore, proper counselling will need to be provided to all women presenting with threatened miscarriage. To institute the use of progestogen therapy for recurrent miscarriage, treatment protocols for reproductive health care will need to be standardized and periodically updated by appropriate authorities, using an evidence-based approach.4.3 IMPLICATIONS FOR RESEARCH

Even though the endocrinological basis of recurrent miscarriage has been studied extensively, there are still gaps in knowledge about physiopathological mechanisms of miscarriage. The long-term maternal and neonatal/fetal adverse effects of progestogen administration in early pregnancy also warrant further investigation. Further large randomized controlled trials are needed to answer to the following questions: What is the efficacy of progesterone treatment in terms of increasing live birth rate among women with recurrent miscarriage? What alternative treatments may be used to treat threatened abortion, especially recurrent miscarriage?References

1. Maternal mortality in Viet Nam 2000–2001: an in-depth analysis of cause and determinants. Manila: World Health Organization Regional Office for Western Pacific; 2005.

2. Beyens MN, Guy C, Ratrema M, and Ollagnier M. Prescription of drugs to pregnant women in France: the HIMAGE study. Therapie 2003;58:505–511.

3. Donati S, Baglio G, Spinelli A, and Grandolfo ME. Drug use in pregnancy among Italian women. European Journal of Pharmacology 2000;56:323–328.

4. Villar J, Gulmezoglu AM, Khanna J, Carroli G, Hofmeyr GJ, Schulz K, et al. Evidence-based reproductive health in developing countries. The WHO Reproductive Health Library, No. 8. Geneva: World Health Organization.

5. Haas DM, Ramsey PS. Progestogen for preventing miscarriage. Cochrane Database of Systematic Reviews 2008; Issue 2. Art. No.: CD003511; DOI: 10.1002/14651858.

6. El-Zibdeh MY. Dydrogesterone in the reduction of recurrent spontaneous abortion. Journal of Steroid Biochemistry & Molecular Biology 2005;97(5):431–434

7. Wahabi HA, Abed Althagafi NF, Elawad M. Progestogen for treating threatened miscarriage. Cochrane Database of Systematic Reviews 2007; Issue 3. Art. No.: CD005943; DOI: 10.1002/14651858.

8. LeVine L. Habitual abortion. A controlled clinical study of progestational therapy. Western Journal of Surgery 1964;72:30–36.

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This document should be cited as: Thach TS. Progestogen for preventing miscarriage : RHL commentary (last revised: 2 February 2009). The WHO Reproductive Health Library; Geneva: World Health Organization.

Abortions

Uteroplacental circulation in patients with first-trimester threatened abortion

Presented in part at the VIth World Congress of Ultrasound in Obstetrics and Gynecology, Rotterdam, the

Netherlands, October 27–31, 1996.

Juan Luis Alcázar M.D.a,  , a,  , Maria Luisa Ruiz-Perez M.D.a, a

a Department of Obstetrics and Gynecology, Clı́Enica Universitaria de Navarra, School of Medicine, University of Navarra, Pamplona, Spain

Received 17 May 1999; revised 11 August 1999; Accepted 11 August 1999. Available online 29 December 1999.

Abstract

Objective: To assess uteroplacental circulation in patients with first-trimester threatened abortion with a living embryo.

Design: Prospective, cross-sectional study.

Setting: Tertiary care university hospital.

Patient(s): Forty-nine patients with first-trimester threatened abortion and a living embryo and 129 women with

singleton, low-risk, normally developing first-trimester pregnancies recruited as controls.

Intervention(s): Transvaginal color Doppler ultrasound measurement of the peak systolic velocity and pulsatility index

of the uterine arteries and the spiral arteries.

Main Outcome Measure(s): Uteroplacental blood flow and pregnancy outcome.

Result(s): There was a significant relation between gestational age and the peak systolic velocity and pulsatility index

in the uterine arteries and between gestational age and the peak systolic velocity and pulsatility index in the spiral

arteries in controls. There were no differences in any Doppler parameter assessed between the study group and the

controls, even in those pregnancies that ended in spontaneous abortion.

Conclusion(s): No apparent alteration occurs in the early uteroplacental circulation in patients with threatened

abortion with a living embryo. The use of transvaginal color Doppler ultrasound is not helpful for predicting pregnancy

outcome in these cases.

Keywords: Uteroplacental circulation; Doppler ultrasound; first trimester; threatened abortion

Page 16: Fetal Loss in Threatened Abortion After Embryonic

Article Outline

Materials and methods

o Patients and study design

o Ultrasound examinations

o Statistical analysis

Results

Discussion

Acknowledgements

References

Reprint requests: Juan Luis Alcázar, M.D., Department of Obstetrics and Gynecology, Clı́Enica Universitaria de

Navarra, Avenida Pio XII, 36, 31008 Pamplona, Spain (FAX: 34-948-172294

Purchase

Copyright © 1999 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Estimation Of CA-125 Level In First Trimester Threatened Abortion

Batool Mutar Mahdi MB.Ch.B, M.Sc., FICMS 

Assistant Professor

Department Of Microbiology

Baghdad University   

Baghdad Iraq 

Citation: B. Mahdi : Estimation Of CA-125 Level In First Trimester Threatened

Abortion. The Internet Journal of Gynecology and Obstetrics. 2010 Volume 12 Number 2

Page 17: Fetal Loss in Threatened Abortion After Embryonic

Keywords: Ca-125 | Abortion | Pregnancy.

Abstract

Objective: Serum level of CA-125 turned out to be a valuable parameter

not only as a marker of ovarian carcinoma but also in other fields of

obstetrics and gynecology. Earlier work suggested that highest level of CA-

125 could be detected in the sera of women with threatened

abortion. Design: A prospective study.Setting: Private hospital and clinics

in Baghdad.Subjects: The study population comprised of 42 pregnant

women who were recruited from August 2004 to September 2007 and had a

vaginal bleeding in the first trimester ending in abortion. The controls were

20 pregnant women who had normal pregnancy without

complications. Intervention: Blood was collected and level of CA-125

antigens (Ags) was estimated in the serum of these women by Enzyme

Linked Immuno Sorbent Assay (ELISA) in Immunological laboratories in

Central Public Health Laboratories and Teaching Laboratories in Medical

city in Baghdad. Ultrasound confirmation of fetal heart activity was

done. Main outcome measure: Pregnancy outcome and CA-125 level in

the serum.RESULTS: In spite of increasedlevel ofCA-125 in aborted

patients in first trimester. There was no significant difference between two

groups. CONCLUSIONS: CA-125 can not be used as a predictor of outcome

of early pregnancy complicated by vaginal bleeding

Page 18: Fetal Loss in Threatened Abortion After Embryonic

Introduction

Spontaneous abortion is one of most common complication of pregnancy.

The diagnosis of spontaneous abortion currently depends on a combination

of ultrasonography and nine hormonal methods (serum human chorionic

gonadotropin (HCG), estradiol (E2), estrone, estriol, progesterone, human

placental lactogen, cortisol, urine HCG and urine estrogen (1).

Another parameter used as a predictive marker for a spontaneous abortion

or subsequent outcome of pregnancy is Cancer Antigen-125 (CA-125). This

antigen is a cell surface high molecular weight glycoprotein; synthesis is not

restricted to malignant transformation and ovarian tumors (2,3). It is also

expressed in normal tissues such as endometrium, endocervix, fallopian

tubes, and mesothelial cells lining adult plura, pericardium and peritoneum

(4). There is a cyclic changes in the serum concentration of CA-125 in

normal menstruating women seems that it's a product of normal

endometrium (5). In other reports, it was suggested that ovaries were the

main source of CA-125 (6). Generation of potential immunogenic peptide

(YTLDrDSLYV) derived from CA-125 that bind to human leukocyte antigen

(HLA A2,1) leading to elicit peptide – specific human cytotoxic T

lymphocytes that effectively kill ovarian tumors expressing CA-125 antigen

(7).

During pregnancy, CA-125 was presented in tissues derived from embryonic

coelomic epithelium (8) and through out gestation, significant quantities

seen in the deciduas and chorion which is the main source of it (9). CA-125

had been found in high concentration in human amniotic fluid and the

amnion was a major source of it (10).

During pregnancy, disruption of the epithelial basement membrane of the

fetus membrane or disruption of the decidua could theoretically leads to a

Page 19: Fetal Loss in Threatened Abortion After Embryonic

rise in the maternal serum CA-125 level; this increase may be a predictor of

subsequent spontaneous abortion of the fetus (11).

A study was initiated to investigate a rise in the serum CA-125 level might

predict spontaneous abortion or ongoing pregnancy in pregnant women

with vaginal bleeding in first trimester and compare it with normal

pregnant Iraqi women.

Materials And Methods

The study population comprised of 42 Iraqi pregnant women who had

vaginal bleeding in first trimester ended with abortion confirmed by

ultrasound and some of them dilatation and curettage done for them. The

women were recruited from private hospitals and clinics in baghdad from

August 2004 to September 2007. Gestational ages were calculated

according to the last menstrual period confirmed by ultrasound.

The control group comprised 20 pregnant women who had normal

pregnancy in first trimester and who had continued their pregnancy

confirmed by antenatal care and follow–up.

Maternal blood samples were taken in the first trimester and the serum was

separated and measurement of CA-125 was done in the Central Public

Health - Department of Immunology and Teaching Laboratories –

Department of Immunology in Baghdad using Enzyme Linked Immuno

Sorbent Assay (ELISA).

Statistical Analysis

Data was expressed as mean ± SEM. Statistical analysis was done using

student t-test.

Page 20: Fetal Loss in Threatened Abortion After Embryonic

Results

Forty-two pregnant women were recruited for this study. Their ages ranged

from 16-33 years old (mean 23 years), gravidity ranged (1 - 6) (mean 2.51).

Number of previous abortions were (0-3) (mean 0.55). All of them were not

smoker.

While the measurement of CA-125 showed higher mean value for the group

that ended with abortion, there was no significant difference between two

groups as shown in Table 1.

 

Table 1. Level of CA-125 in the serum of pregnant women expressed as

mean ± standard error mean.

Discussion

The ultrasound, serum β-HCG and progesterone titers are widely used to

assess the risk of miscarriage at the early stages of pregnancy (12). They

are not considered as satisfactorily sensitive tests during the first three

months of pregnancy, therefore their value is limited. Evaluation of serum

levels of CA-125 antigens has been considered as a useful marker in

diagnosis and monitoring of some ovarian carcinoma (13) but there are

Page 21: Fetal Loss in Threatened Abortion After Embryonic

some studies suggesting its predictive value when estimating the risk of

miscarriage at early stages of pregnancy (14). Women with threaten

abortion revealed higher values of serum CA-125 antigen than those in the

control group and those patients who had presented the highest values of

the antigen later miscarried (15). This high level is likely due to tropho-

decidual origin of this marker and invasion of deciduas by chorionic villi.

This decidual disruption is associated with vaginal bleeding (16-17).

Our results showed no significant difference between groups I who end with

abortion and group II that had ongoing pregnancy in spite of its higher

values 39.9±15.4 . Our results were in agreement with Hornstein et al 1995

(18) and Vavilis et al 2001(19), who found that there was no statistically

significant difference in CA-125 levels of patients who aborted compared

with those women that continued pregnancies. Poliklinik et al 2000(20) was

in agreement with our results who reported that CA-125 could not serve as

an accurate predictor of pregnancy outcome due to the wide overlap of the

ranges.

However, there are also contradictory reports which showed that it may be

useful. Some reports demonstrated the prognostic significance of the

maternal serum CA-125 measurement in the threatened abortion because it

determined the extent of decidual destruction which is directly related to

the outcome of pregnancy and its usefulness in predicting early abortion

(20, 21). One report showed that all patients who eventually aborted had

values of CA-125 more than 125IU/ml while the control had a value not

more than 93 IU/ml (22).

One report showed the distribution of CA-125 during pregnancy was highest

in first trimester than second and third trimester (5, 9, and 11). This may be

due to the secretion of CA-125 and placenta protein 14 (PP14) by the

glandular epithelium of the endometrium (5,23). Serum concentration of

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these parameters may increase during the first trimester of pregnancy as

the concentration of progesterone rise to a maximum in the first trimester

(24). This observation suggest that CA-125 is synthesized by normal

endometrium in non pregnant female and by deciduas in pregnant women

(25).

An observation that suggest CA-125 correlates less well with endometrial

development in women suffering from recurrent miscarriage (26). One

report demonstrated that concentration of CA-125 in the pregnant women

who subsequently aborted were higher than those who did not, thus

suggesting that serum CA-125 are not so important in maintaining

successful pregnancy (27). CA-125 may be useful in the assessment of

endometrial development in recurrent miscarriage patients and this

suggested the importance in preparing the endometrium for embryo

implantation (28). High level of serum CA-125 with high lactate

dehydrogenase indicates more extensive trophoblastic tissue damage (29).

Some found that single serum CA-125 level determinations is valuable in

women with imminent abortion presenting with abdominal pain, vaginal

bleeding or both (30,31). Our results are in disagreement. In our opinion

this may possibly be attributed to the method of CA-125 measurement. In

above reports used radioimmunoassay while we used enzyme immune

sorbent assay method.

Acknowledgement

I would like to thank all the staff of Immunological Department in Central

Public Health Laboratory and Teaching Laboratories in Medical City

especially Sanna' Halabia, Dr. Nahla Ghanim, Dr. Leen Al-Galabi, Abdul-

majeed Haji and Salah Hussin for their help and assistance.

Page 23: Fetal Loss in Threatened Abortion After Embryonic

Correspondence to

Dr. Batool Mutar Mahdi 

Department Of Microbiology 

Al-Kindi College Of Medicine 

Baghdad University 

AL-Nahda Square –Baghdad- Iraq 

Mobile:00 964 1 077 02 553215 

E-mail:[email protected]

Title Combined maternal serum inhibin A and embryonic/ fetal heart rate for the prediction of pregnancy outcome in a first-trimester threatened abortion.

Author(s) Phupong V, Hanprasertpong T 

Institution Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. [email protected]

Source J Med Assoc Thai 2011 May; 94(5):529-34.

MeSH

Abstract To examine the value of combined maternal serum inhibin A and embryonic/fetal heart rate to predict the pregnancy outcome in a first-trimester threatened abortion.This was a prospective observational study. The authors measured maternal serum inhibin A and the embryonic/fetal heart rate in women with a clinical diagnosis of a threatened abortion and in normal pregnant women. The main outcome measured was ongoing normal pregnancies.Thirty women with threatened abortions and 30 normal pregnant women were followed. Three women with threatened abortions ended in failed pregnancies. The mean embryonic/fetal heart rate and the median of serum inhibin A in the threatened abortion group were not different from the control group. In women with threatened abortions and failing pregnancies, the embryonic/fetal heart rate (101.7 +/- 20.1 beats/min) was significantly lower than in women with threatened abortions but ongoing pregnancies (163.3 +/- 19.7 beats/min, p = 0.024). Serum inhibin A in women with threatened abortions and failing pregnancies was not different from women with threatened abortions but ongoing pregnancies (median) 274.0 vs. 559.9 pg/mL, p = 0.388). When using serum inhibin A combined with embryonic/fetal heart rate, or only embryonic/fetal heart rate, the sensitivity and specificity for predicting an ongoing pregnancy were 100% and 50% or 100% and 100%, respectively.Combined

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maternal serum inhibin A and embryonic/fetal heart rate is not better than embryonic/fetal heart rate for predicting the pregnancy outcome in a first-trimester threatened abortion.

Language Eng

Pub Type(s) Journal ArticleResearch Support, Non-U.S. Gov't

PubMed ID 21675439