Is trophoblastic thickness at the embryonic implantation site a new sign of negative evolution in first trimester pregnancy?

J. Bajo, F.J. Moreno-Calvo1, L. Martinez-Cortés, F.J. Haya and J. Rayward

Department of Obstetrics and Gynecology, Hospital Universitario Getafe, 28905 Madrid, Spain


    Abstract
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In this study a new sign to evaluate the evolution of pregnancy is described: the trophoblastic thickness at the embryonic implantation site. A prospective, observational study of 592 normal pregnancies with no known risk factors was carried out from January 1998 to February 1999. Serial ultrasound scans were performed from week 5 to week 12 of pregnancy. Trophoblastic thickness was measured at the embryonic implantation site to determine the significance of a difference in gestational age in weeks and a trophoblastic thickness of >=3 mm in predicting poor prognosis in pregnancy outcome. The sensitivity of this sign in the prediction of spontaneous abortion was 82%, the specificity was 93%, the positive predictive value was 63% and the negative predictive value was 97%.

Key words: early pregnancy/spontaneous abortion/trophoblast


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The most critical time in the life of an individual is during the first trimester of pregnancy when placentation and the development of the embryo that will become a new human being take place. This is the time of most sensitivity to external aggression and when most pathological conditions begin.

It is estimated that of every 100 potential pregnancies only 31 progress, taking into account failures of fertilization (Barri, 1997Go). If we take into consideration pregnancies starting at the implantation stage, the frequency of spontaneous abortion is 30–40% (Knudsen et al., 1991Go; De La Fuente, 1997Go). For this reason and in view of the anxiety a couple may undergo waiting for a successful outcome, many authors have studied the prognosis of pregnancy based on ultrasound criteria obtained prior to the eighth week of pregnancy.

The aim of this study was to determine the prognostic value of a new sign, the trophoblastic thickness at the embryonic implantation site, on the progression of pregnancy during the first trimester.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
A prospective, observational study was carried out from January 1998 through February 1999 of 592 normal pregnancies with no known risk factors. Patients that presented any pathological condition that could negatively affect the progression of pregnancy were excluded (Table IGo). All of the pregnant women had regular periods and had not had any previous spontaneous abortions. Also excluded from the study were those women whose first ultrasound scan showed indications of poor prognosis, e.g. gestational sac anomalies, bradycardia, small-for-date embryo, yolk sac anomalies, bleeding or retrochorionic haematoma. Gestational age was determined by crown–rump length in all pregnancies at week 6.


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Table I. Exclusion criteria
 
Serial ultrasounds were performed on all pregnant women from week 5 to 12 of amenorrhoea. The same physician (F.J.M.-C.) using the same ultrasound scanner carried out all examinations. The trophoblastic thickness at the site of embryonic implantation, which can be found at week 5–6 by locating the yolk sac and omphalomesenteric canal, was measured. This finding confirms the existence of an embryo because without it there is no yolk sac (Gonzalez-de-Agüero et al., 1998Go). The yolk sac has a stalk and it is this embryonic stalk (from which the umbilical cord originates) in its parietal extremity that indicates (Figure 1Go) the embryonic implantation site where the placenta subsequently develops. At this site, peritrophoblastic resistances are lower than in the rest of the trophoblastic corona (Barco et al., 1989). The implantation site of the cord was easily seen with conventional B-mode ultrasound in most cases. In some pregnancies, however, at week 7 the embryonic implantation site of the cord was not easily located and was confirmed by colour Doppler imaging but only with informed consent of the patient.



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Figure 1. Pregnancy at 7 weeks. The arrows show the site of the embryonic stalk where the trophoblastic thickness should be measured. The size of the yolk sac, shown with `x', is normal. E = embryo.

 
A thinning of the trophoblast was defined as when the numerical difference between gestational age in weeks and the trophoblastic thickness in millimeters was 3 or more.

Trophoblastic thickness was recorded at each week of gestation and this was subsequently related to gestational age. The progressing of each pregnancy was followed through to week 12 to determine whether the trophoblastic thinning at the site of implantation in comparison to the gestational age in the terms described was a risk factor for spontaneous abortion.

The ultrasound scanner used was an Aloka 2000 (Tokyo, Japan) with a 10 MHz vaginal probe and a colour-coding system of blood flow in real time. The repetition frequency of pulses was 4.1 to 15 kHz. The frequency filter was placed at 50 Hz and the acoustic power (SPTA) was constantly lower than 94 mW/cm2, which is recommended by the US Food and Drug Administration, Rockville, MD, USA for the use of colour Doppler in embryo study. Maximum study time was 5 min without Doppler. The statistical analysis was carried out using the {chi}2-test. All women were informed of the study and gave their written consent.


    Results
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In 88 pregnancies (15% of the total) the difference between the gestational age in weeks and trophoblastic thickness was >=3 mm (Table IIGo). Of these, 56 (64%) women who still presented an embryo with heartbeat at the moment of the scan, miscarried between 1 and 7 days later. On the other hand, 36% (32 pregnancies) did not miscarry in the first trimester even though they also presented a difference between gestational age (weeks) and trophoblastic thickness (mm) of 3. Of these 32 pregnancies with a thin trophoblast that progressed, there was a constant relationship between the trophoblast and the gestational age. Two of these miscarried at 18 and 20 weeks.


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Table II. Contingency tables. Progression of pregnancies according to tophoblastic thickness
 
Of the 504 pregnancies that presented a difference of <=3 mm between gestational age and trophoblastic thickness, only 12 (2%) resulted in spontaneous abortion. The remaining 492 (98%) pregnancies progressed favourably to week 12. Of the 56 pregnancies with a thin trophoblast that ended in miscarriage, 15 were diagnosed at week 6, presenting a trophoblast of <=3 mm. In 20 pregnancies a thin trophoblast was diagnosed at week 7 (their thickness being <=4 mm). Six were found at week 8 (with a trophoblastic thickness of <=5 mm), five at week 9 with a thickness of <=6 mm and 10 pregnancies at week 10 with a trophoblastic thickness of <=7 mm. Normal values of trophoblastic thickness at these gestational ages are greater than those quoted above for `thin' trophoblast. Heartbeat was found to be normal for gestational age in all these pregnancies when trophoblastic thinning was diagnosed.

According to our data, a difference of >=3 mm between gestational age (weeks) and trophoblastic thickness at the site of embryonic implantation was statistically significant (P < 0.001). When used as the only sign in predicting poor pregnancy outcome in the first trimester, it presented a sensitivity of 82%, a specificity of 93%, a positive predictive value of 63% and a negative predictive value of 97% (Table IIGo).


    Discussion
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The discovery of early ultrasound signs that give a correct prognosis of the outcome of a pregnancy has given rise to many studies that aim to determine which pregnancies will fail to progress.

The following series of ultrasound signs found in early pregnancy predicting poor prognosis have been described: (i) gestational sac anomalies (Bromley et al., 1991Go; Nazari et al., 1991Go; Dickey et al., 1992Go); (ii) early bradycardia (Laboda et al., 1989Go; May and Sturtevant, 1991Go; Stefos et al., 1998Go); (iii) yolk sac anomalies (Lidsay et al., 1992Go; Fadda et al., 1993Go; Stampone et al., 1996Go; Sza1bo et al., 1996; Cepni et al., 1997Go; Rempen, 1998Go); (iv) subchorionic haematomas (Bennet et al., 1996Go; Kurjak et al., 1996Go); (v) slow embryonic growth (Koornstra and Exalto, 1991Go; Bessho et al., 1995Go).

Alterations of thickness, echogenicity and structure of the trophoblastic corona have always been associated with poor prognosis in pregnancy. However, as far as we can see, never before has the relationship between trophoblastic thickness at the embryonic implantation site and the gestational age in weeks been studied as a possible risk factor.

Until the seventh week of amenorrhoea, the corona has uniform thickness of 7–10 mm. At week 8 the trophoblast starts growing more unequally at the embryonic implantation site. Growth is progressive and, according to our study, proportional to gestational age. Consequently in those pregnancies presenting a difference between gestational age in weeks and trophoblastic thickness of >=3 mm (i.e. disproportional), close ultrasound monitoring should be carried out because of greater risk of spontaneous abortion.

Nevertheless, we do not fully understand the relationship between this ultrasound sign and the subsequent loss of pregnancy although from our observations we can deduce that a decrease in thickness at the site of the future placenta could indicate `early placental insufficiency' and a placenta that cannot meet the nutritional requirements of the embryo.

In the light of our study, we consider that a difference of >=3 between correct gestational age in weeks and trophoblastic thickness in mm at the embryonic implantation site should be seen as an indication that closer monitoring of the pregnancy is required since, as seen in our results, this could mean a poor outcome.


    Notes
 
1 To whom correspondence should be addressed at: Servicio de Obstetricia y Ginecología, Hospital Universitario de Getafe, Ctra. Madrid-Toledo, Km 12 500, 28905 Madrid, Spain. E-mail: fmorenoc{at}sego.es Back


    References
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
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Submitted on November 22, 1999; accepted on March 29, 2000.