Middle East Fertility Society Journal (2015) xxx, xxx–xxx
Middle East Fertility Society
Middle East Fertility Society Journal www.mefsjournal.org www.sciencedirect.com
ORIGINAL ARTICLE
3D power Doppler ultrasound characteristics of the corpus luteum and early pregnancy outcome Reda A. Ahmad *, Somayya M. Sadek, Amany M. Abdelghany Department of Obstetrics and Gynecology, Faculty of Medicine, Zagazig University, Egypt Received 24 October 2014; revised 13 April 2015; accepted 26 April 2015
KEYWORDS Corpus luteum; Three dimensional ultrasound; First trimester; Vascularization index; Pregnancy; Power Doppler
Abstract Objective: to assess the relationship of corpus luteum morphology and vascularity by 3 dimensional power Doppler ultrasound and the pregnancy outcome in early pregnancy. Design: prospective observational cohort study. Setting: Zagazig University Hospital. Materials and methods: this is a prospective observational cohort study of thirty six pregnant patients examined by two dimensional and three dimensional transvaginal sonography for corpus luteum volume, echostructure and corpus luteum vascularization index in the period after documentation of fetal heart activity and nine weeks. Results: there were 36 study women, ultrasound morphologic features of corpus luteum: volume ranged from 0.91 to 42.8 ml with median of 6.85, vascularization index ranged from 0.05 to 23.8 with a median of 6.85, echostructure was cystic in 12 women (33.3%), hemorrhagic in 18 (50%) and solid in 6 women (16.7%). The relation between CL volume and pregnancy outcome was significant (p-value was 0.02), being smaller in group of missed abortion. The relation between CL VI and pregnancy outcome was non significant (p-value was 0.229). The relation between CL echostructure and pregnancy outcome was highly significant (p-value was 0.009). The prognosis was worst in group of solid echostructure. Conclusion: the corpus luteum volume and echostructure assessed by 3D power Doppler ultrasound have statistical relationship with the early pregnancy outcome. Ó 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
1. Introduction Corpus luteum (CL) is a powerful little gland producing progesterone that is essential for regulating menses as well as for initiating and maintaining early pregnancy [1]. * Corresponding author. E-mail address:
[email protected] (R.A. Ahmad). Peer review under responsibility of Middle East Fertility Society.
Production and hosting by Elsevier
Angiogenesis is an essential factor with a major impact on the growth and regression of follicles and corpus luteum [2,3]. Doppler flow study with its indices such as pulsatility index and resistance index gives important information about uterine perfusion and angiogenesis in the ovarian follicles [4]. Three dimensional (3D) power Doppler imaging (PDI) gives the combined advantages of the improved sensitivity of two dimensional (2D) PDI to small vessels and of 3D ultrasound, so it is useful for non-invasively visualizing tissue structure and vasculature [5,6]. The histogram facility of the vocal imaging program automatically obtains 3 vascularity indices vascularization index (VI), flow index (FI) and vascularization flow index (VFI)
http://dx.doi.org/10.1016/j.mefs.2015.04.004 1110-5690 Ó 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Ahmad RA et al. 3D power Doppler ultrasound characteristics of the corpus luteum and early pregnancy outcome, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.04.004
2 which potentially can reflect the vascular density, blood flow and tissue perfusion respectively so the quantification of complete blood flow of the region of interest from the analysis of power Doppler signals can be fully studied [7]. Many authors study vascularity of the ovary using 3D power Doppler and quantify vascularity in the ovary in the late follicular phase [8], study changes in blood flow in the ovarian stroma with age [9], and compare intraovarian vascularization in polycystic ovaries with that in normal ovaries [10]. To the best of our knowledge, there are no published studies where 3D power Doppler ultrasound has been used to study the CL vascularity and its relationship with the pregnancy outcome in early first trimester till nine weeks where placental function starts. The objective of this study is to assess the CL morphology and vascularity by 3D power Doppler and its relationship with the early pregnancy outcome. 2. Material and methods 2.1. Patients 2.1.1. Study design This is a prospective observational cohort study. Our study included thirty-six women recruited from the antenatal outpatient clinic at Zagazig University Hospital between October 2012 and April 2013. The inclusion criteria were maternal age ranged from 18 to 27 years, singleton spontaneous viable pregnancy and gestational age after documentation of fetal heart activity (usually after 6 weeks gestation calculated by reliable last menstrual period, regular and no hormonal contraception at least three months before pregnancy, and/ or crown rump length measurement) and nine weeks, all patients with history of ovulation induction, multiple pregnancy or with known cause of pregnancy loss were excluded. 2.1.2. Equipment All the patients were evaluated in first trimester after documentation of fetal heart activity (usually after 6 weeks gestation), and followed up to 10 weeks gestation, by twodimensional and three-dimensional ultrasound using a MyLap 60 (Esaote, Italy) ultrasound machine, equipped with endocavitary high frequency convex 3D/4D transducer (BE1123). Power Doppler ultrasound settings were used in all women: frequency 3–9 MHz, pulse repetition frequency 1 kHz, gain 4.0 and wall motion filter ‘low 1’ (40 Hz at pulse repetition frequency 1 kHz). The women were examined in the lithotomy position with an empty bladder. 2D ultrasound was applied first to obtain confirmation of pregnancy, its location, number of gestational sacs; gestational age and fetal heart activity then the CL morphology and its power Doppler flow were examined. After this, the 3D ultrasound mode was switched on. The woman was asked to remain as still as possible, and a 3D power Doppler data set of the CL was acquired. The power Doppler box was placed on the maximum longitudinal plane of the CL, covering completely its whole surface. When an adapted device free color sign was obtained, we placed the 3D box to obtain the volume on region of interest.
R.A. Ahmad et al. All the analyses of stored ultrasound volumes were done off-line by one author. The volumes were processed by the VOCAL imaging program (Virtual Organ Computer-Aided Analysis). The contours of the CL were drawn manually following the outer contour of the thick color ring surrounding it. The analyzed parameters were: the corpus luteum volume (CLV), corpus luteum echostructure and corpus luteum vascularization index (VI). Vascularization index (VI) measures the number of color voxels in the ovarian volume, representing the number of ovarian vessels expressed as a percentage [11]. 3. Results In this study of the 36 selected pregnant women, it was possible to visualize the CL in 36 of them (100%). The age of the women in whom it was possible to distinguish the CL was in the range of 18–27 years. The average age was 22.2 years with a standard deviation of ±2.8 years. The study included 32 pregnant women with no history of prior abortion, two cases gives history of abortion once and two cases aborted twice before. Pregnancy outcome was good in 72.2% (n = 26) (26/36) and missed abortion occurred in 27.8% (n = 10) (10/36). The most common morphologic type was the hemorrhagic CL in 50% (n = 18) (18/36), followed by CL with cystic echostructure in 33.3% (n = 12) (12/36) and solid in 16.7% (n = 6) (6/36). Regarding CL morphology by 3D US, the relation between CL echostructure and pregnancy outcome was highly significant (p-value was 0.009). The prognosis was worst in group of solid echostructure, Table 1. The CL had an average volume ranged from 0.91 to 42.8 ml with median of 6.85 ml. It was observed that pregnant women with smaller size CL had more incidence of abortion than those with larger one this difference was statistically significant. Regarding the Doppler study of CL blood flow the average vascularization index (VI) ranged from 0.05 to 23.8 with a median of 6.85. By comparing the vascular characteristic (VI) between those who aborted and those with good outcome no significant difference was found (p-value was 0.229), Table 2.
Table 1 The relationship between CL echostructure and pregnancy outcome. Prognosis/echostructure
Cystic
Hemorrhagic
Solid
P value
Good: 72.2% (26/36) Poor: 27.8% (10/36).
12 0
12 6
2 4
0.009
Table 2 The relation between corpus luteum volume and vascularization index and pregnancy outcome. Prognosis
Volume (ml) Range (median)
Vascularization index Range (median)
Good: 72.2% (26/36) Poor: 27.8% (10/36). P value
0.91–42.8 (3.4) 0.9–3.5 (1.9) 0.02
0.05–23.8 (6.4) 1.5–21.8 (10.2) 0.229
Please cite this article in press as: Ahmad RA et al. 3D power Doppler ultrasound characteristics of the corpus luteum and early pregnancy outcome, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.04.004
Doppler ultrasound characteristics and early pregnancy outcome 4. Discussion It is known that abortion is a frequent event, occurring in more than half of all conceptions, and approximately 15% of clinically recognized pregnancy. However the incidence is between 2% and 6% after documentation of cardiac activity [1]. Many ultrasound findings in early pregnancy have been described as associated with abortions, one of them is CL characteristics, it has been postulated that some cases of early abortion may result from inadequate function of the CL [3]. Currently, it is possible to identify the sonographic and Doppler characteristics of CL and we can study it during pregnancy [4]. The studies seek to define gestational CL sonographic parameters as morphology, size and volume, as well as evaluating the vascularity with color Doppler velocimetry, always in search of the definition of normal CL and association between morphology and function. In this study we attempted to identify sonographic and Doppler characteristics of the CL that might be associated with spontaneous pregnancy loss during the first trimester using 3D ultrasound. In this study, we described the morphological and vascular characteristics of CL in 36 pregnant women with single fetus with gestational age in the period after documentation of the fetal heart activity and nine weeks and pregnancies followed up to 10th weeks’ gestations. Detection of CL in this study was 100%. Among results reported in the literature, which report rates between 75.2% [12] and 98% [5], while another study point to an average rate of 82% [13]. The higher rate of detection in our study compared with other studies as they have included patients at up to 12 weeks’ gestational age [5,8]. The likelihood of identifying the CL decreases as pregnancy progresses through the first trimester, and our study was limited to pregnancies earlier than 10 weeks’ gestation. Another explanation may be that in patients with noncystic corpora lutea, the addition of color Doppler imaging may have improved confidence for visualization of a solid CL that, if small in size, could have been questionable on gray scale sonography alone. The morphology of the CL in early pregnancies is variable according to its echographically grayscale. In our study we found that the most common morphologic types were the hemorrhagic CL in 50% (n = 18) (18/36), followed by CL with cystic echostructure in 33.3% (n = 12) (12/36) and solid in 16.7% (n = 6) (6/36) and the relation between CL echostructure and pregnancy outcome was highly significant (p-value was 0.009). The prognosis was worst in group of solid echostructure. On the contrary other authors studied the sonographic appearance of CL and first trimester pregnancy outcome and they described four types of CL, simple cyst, thickened wall cyst, complex cyst and hypoechoic and they found no association between sonographic morphologic appearance of CL and first trimester pregnancy outcome [14,15]. Da Silveira et al. [16] founded that the most common morphologic types identified was the CL with the thick wall and dense hypoechoic center (48%), followed by CL looking hypoechoic (42.5%). The hypoechoic CL was more common among women who have aborted, but presented no significant difference compared to the other types.
3 Durfee et al. [17] found the most common appearance was a round hypoechoic structure (34%). Other appearances included a cyst with a thick wall and anechoic center (27%), a cyst containing internal debris (23%), and a thin-walled simple cyst (15%). The importance of the size of the CL is controversial. It is known that maintenance of embryo implantation depends on progesterone secretion, under the effect of human chorionic gonadotropin (HCG) stimulation, by the CL. Most authors found no relationship between the gland enlargement and increased serum progesterone [18,19]. The relation between CL volume and pregnancy outcome was significant (p-value was 0.02). Being smaller in those that spontaneously aborted during the first trimester. Few studies describe the size of CL. In the study by Da Silveira et al. and Glock et al. the average volume of CL found was, 4.2 ± 1.9 cm3 and 3.7 ± 1.7 cm3 respectively[16,15]. Others use the value of the largest diameter measured averaged 21.8 mm and it is among the values described in the literature of 19.0 ± 0.6 mm [14]. Our results were in accordance with Da Silveira et al. [16], when comparing the mean values of the larger diameter and volume of the CL of pregnant women with those who aborted, found lower volume in cases of abortion, a figure that approached statistical significance. On contrary Frates et al. [14] found that CL size in pregnancies that survived the first trimester, similar to the size in those that spontaneously aborted during first trimester, however volumes calculated using 3D ultrasound (a method that we used) are more accurate than those calculated using a mathematical formula including diameters measured by 2D ultrasound [20,21]. 3D power Doppler is a new method of studying vascularization. What 3D power Doppler might add is more accuracy, so we used it to study CL morphology and its vascularization. In 2D spectral Doppler ultrasound studies, blood flow velocity is measured in one or possibly a few subjectively selected vessels. With 3D ultrasound, vascularity indices in a whole organ are calculated. It seems likely that the results of 3D power Doppler ultrasound examinations better reflect true vascular changes in an organ than those of 2D color or spectral Doppler ultrasound examinations. The inter- and intraobserver reproducibility of calculations of ovarian volume and ovarian vascular indices using 3D ultrasound have been shown to be acceptable [22–25]. In agreement with this study that found no association between the vascularization index (VI) 3D US of normal pregnant women and those who progressed to miscarriage, some authors found no difference in resistance index 2D US CL of normal pregnant and miscarriage [5,8–10,19,16, 17,26]. In contrast another study found that the mean RI from the CL blood flow was higher in patients of missed abortion than in women with normal pregnancy [27]. 5. Conclusion The CL characteristics namely volume and echostructure assessed by 3D power Doppler ultrasound have statistical relationship with the early pregnancy outcome, so it can be used as one of the predictors of pregnancy outcome, while vascularization of CL had no impact on pregnancy outcome.
Please cite this article in press as: Ahmad RA et al. 3D power Doppler ultrasound characteristics of the corpus luteum and early pregnancy outcome, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.04.004
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Please cite this article in press as: Ahmad RA et al. 3D power Doppler ultrasound characteristics of the corpus luteum and early pregnancy outcome, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.04.004