Comparative Study Between Corpus Luteum Changes in Normal Pregnancy and Threatened Abortion Using Transvaginal Color Doppler Sonography

INTRODUCTION

Among different physiological factors responsible for initiating and maintaining pregnancy, corpus luteum plays a critical role in normal pregnancy. The corpus luteum produces several hormones, such as estradiol, progesterone, relaxin, inhibin A and B, as well as products such as cytokines and prostaglandins.¹

The synthesis of progesterone by corpus luteum is extremely important for the maintenance of normal pregnancy in the first seven weeks. Similarly, the production of progesterone by the placental syncytiotrophoblast increases progressively during the first weeks of gestation, so that in eight and a half weeks the placenta and corpus luteum contribute in equal amounts of progesterone. However, from the eighth week, the placental contribution is sufficient to maintain gestation. Angiogenesis in the corpus luteum occurs under physiologic circumstances in each menstrual cycle and functionally is very important for maintenance of early pregnancy.² This role implies a potential correlation between abnormal function of corpus luteum and possible abnormal pregnancy including abortion.

The introduction of Doppler ultrasound in obstetrics has allowed evaluating hemodynamic characteristics of corpus luteum from the first trimester of pregnancy. For example, Kurjak et al in one of the first studies using transvaginal pulsed-wave Doppler ultrasound in early pregnancies, identified the luteal flow characteristics in 75% of the patients.³

In fact, the use of transvaginal color Doppler sonography allows simple and precise recognition of an ovary with corpus luteum. Intensity of color corresponds with velocity of blood flow in newly formed intraovarian vessels. Color is an essential guide for pulsed Doppler exploration of such small and randomly dispersed vessels inside ovarian tissue. Without color flow, Doppler analysis would be time-consuming and potentially inaccurate. Using color Doppler sonography, it was feasible to distinguish the ovary containing an active corpus luteum from the inactive ovary. The technique is simple to use, and the results are displayed obviously.⁴

The RI of the corpus luteum vessels is apparently constant during the initial gestation, without significant changes. This can be explained by the absence of muscular tunica in the corpus luteum vessels, which provides minimal resistance, very full flow and inability to self-regulate. When compared to pathological pregnancies, RI is significantly higher in retained abortion and incomplete abortion than in normal pregnancies, and no statistical differences are found in cases of ectopic pregnancy, hydatidiform mole and anembryonic pregnancies.⁵ However, some more recent evidence reported non-significant difference in RI in threatened abortion when compared to normal pregnancy.⁶

The aim of our study is to compare the clinical and sonographic characteristics between women with threatened abortion compared to those with normal pregnancy using transvaginal color Doppler ultrasonography, to predict pregnancy outcome in first trimesteric threatened abortion pregnancies.

PATIENTS AND METHODS

This study was carried out on 200 pregnant women (divided into two groups): Group I: 100 pregnant women with normal pregnancy. Group II: 100 pregnant women with threatened abortion.

The type of the study is prospective cohort observational done at Al-Galaa Maternity Hospital.

The study population includes women admitted to the hospital with 6-12 weeks of gestation with the following criteria:

Inclusion criteria: Age between 18-35 years old, women had normal intrauterine pregnancies (confirmed by sonographic measurement), spontaneous conception and agreement to sign the informed consent to participate in the study.

Exclusion criteria: subjects were excluded from the study that have multiple pregnancies, molar pregnancy and uterine anatomic abnormalities.

Smoking.

Methods: Transvaginal ultrasound examination was carried out with a high color Doppler resolution transvaginal ultrasound, using standard techniques.

GE Voluson A6 equipped with a 5-MHz transvaginal probe. The high pass filter was set at 100 Hz and the spatial peak temporal average was 80 mW/cm² (according to the limits of security recommended by the American Food and Drug Administration for use in fetal medicine).

The ultrasonographic assessment was performed with the patient in the decubitus position.

A two-dimensional, B-mode scan was first performed to evaluate the state of the pregnancy and to determine the true gestational age. Normal pregnancy defined as an intrauterine gestational sac with live embryo (positive heart action) and crown-rump measurement correlated to menstrual age. Threatened abortion was mainly a clinical diagnosis (closed cervical os with vaginal bleeding) with sonographic findings of a prominent subchorionic anechoic area due to blood collection.

Corpus luteum blood flow was defined as random, usually semilunar in appearance, dispersed vessels with very prominent diastolic component of a cardiac cycle and consequently low impedance to blood flow.⁷

Endovaginal ultrasonography was done for 200 pregnant women starting at 6 weeks till 9 weeks menstrual age for evaluation of corpus luteum changes in normal pregnancy 100 cases and threatened abortion 100 cases as regard site, size, morphological type and growth rate (follow up after one week) as well as to evaluate the functional state by Doppler ultrasonography velocimetric analysis of CL blood flow (resistance index).

Follow up of the patients at 12 weeks GA to detect the outcome of pregnancy.

After identification of corpus luteum blood flow, pulsed Doppler sonographic sample volume was placed where highest intensity of color was visualized to obtain the flow velocity waveform, and results was applied for calculation the resistance index (RI) according to the following formula:

RI= S-D/S

Where RI is the resistance index, S corresponded to the peak systolic velocity and D corresponded to the peak diastolic velocity. RI of the corpus luteum vessels is considered as normal when less than 0.64 ⁶

Statistical analysis: recorded data were analyzed using the statistical package for social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean± standard deviation (SD). Qualitative data were expressed as frequency and percentage.

The following tests were done:

-Independent-samples t-test of significance was used when comparing between two means.

-A one-way analysis of variance (ANOVA) when comparing between more than two means.

-Chi-square (x²) test of significance was used in order to compare proportions between qualitative parameters.

-The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the p-value was considered significant as the -Probability (P-value)

-P-value

-P-value

-P-value >0.05 was considered insignificant.

                                  RESULTS

Table (1) shows no statistically significant difference between study group and control group according to age (years) gestational age (days) and the location of corpora luteal.

Table (2) shows statistically significant difference between study group and control group according to resistance index at first visit.

Table (3) shows statistically significant difference between morphological appearance and resistance index at first visit and second visit in study group and no statistically difference in control group.

Table (4) shows no statistically significant difference between abortion group and continuing group according to diameter of CL at first visit and second visit in study group but shows statistically significant difference between abortion group and continuing group according to resistance index at second visit in study group.

Table (5) shows no statistically significant difference between abortion group and control group according to diameter CL but shows statistically significant difference according to resistance index at first visit.

Table (6) shows no statistically significant difference between continuing group and control group according to diameter of CL but show statistically significant difference according to RI at first visit and second visit.

Table (7) shows statistically significant difference between study group and control group according to outcome after 12 weeks.

N.B. In study group, CL could not be seen in 20 cases but were added to the total outcome after 12 weeks of GA. In control group 10 cases were aborted after 12 weeks GA despite showing no signs of threatened abortion and they were included in control group from the beginning.

t-Independent Sample t-test;

p-value>0.05 NS; *p-value

Table (2): Comparison between study group and control group according to resistance index at first visit and second visit.

 Using: One Way Analysis of Variance; p-value

Table (3): Comparison between morphological appearance and resistance index at first visit and second visit in study group and control group.

t-Independent Sample t-test; p-value>0.05 NS;

Table (4): Comparison between abortion group and continuing group according to diameter and RI of CL at first visit and second visit in study group.

t-Independent Sample t-test; p-value>0.05 NS;

Table (5): Comparison between abortion group and control group according to diameter CL and RI at first visit and second visit.

t-Independent Sample t-test; p-value>0.05 NS;

Table (6): Comparison between continuing group and control group according to diameter of CL and RI at first visit and second visit.

x²: Chi-square test; *p-value

Table (7): Comparison between study group and control group according to outcome after 12 weeks.