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Three-dimensional power Doppler imaging in the diagnosis of polycystic ovary syndrome
International Journal of Gynecology and Obstetrics 105 (2009) 36–38
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
CLINICAL ARTICLE
Three-dimensional power Doppler imaging in the diagnosis of polycystic ovary syndrome ☆ Yedla M. Mala ⁎, Sharda B. Ghosh, Reva Tripathi Maulana Azad Medical College, Lok Nayak Hospital, Delhi, India
a r t i c l e
i n f o
Article history: Received 4 August 2008 Received in revised form 18 November 2008 Accepted 19 November 2008 Keywords: 2D Doppler 3D power Doppler Polycystic ovary syndrome
a b s t r a c t Objective: To determine the role of three-dimensional (3D) power Doppler imaging in the diagnosis of polycystic ovary syndrome (PCOS). Methods: Pulsatility index (PI) and resistance index (RI) of the uterine artery and ovary were measured by two-dimensional (2D) Doppler imaging, while vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured by 3D power Doppler in 25 patients with PCOS and 25 women with normal menstrual cycles used as a control group. Results: Uterine artery PI and RI were significantly higher (P b 0.001) and ovarian PI and RI were significantly lower (P b 0.001) in women with PCOS compared with controls. Ovarian VI and VFI were significantly higher in women with PCOS compared with the control group (P b 0.001). Conclusion: 3D power Doppler indices were higher in women with PCOS than in the control group and were positively correlated with 2D color Doppler indices, and clinical and hormonal parameters. High 3D power Doppler indices may be useful as one of the diagnostic criteria for PCOS. © 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Materials and methods
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of chronic anovulation and androgen excess that occurs with a prevalence of approximately 4%–7% in the female population [1]. Women with PCOS typically present for health care because of irregular bleeding, infertility, and/or symptoms of androgen excess. Despite the criteria for PCOS [2], physicians can find the condition difficult to diagnose because patients may not present with all of the typical features of the disease. More accurate diagnosis of various conditions has been achieved using color Doppler ultrasound [3]. Among the newest technological advances is the ability to evaluate the vascular flow and pattern using threedimensional (3D) power Doppler ultrasound, in which blood flow and vascularization are measured with histogram software analysis [4]. Power Doppler ultrasound is superior to frequency-based color Doppler ultrasound particularly for low-velocity blood flow [5], and has the potential to detect alterations in blood flow [6]. The present study was conducted to determine the role of color Doppler imaging and 3D power Doppler imaging in the diagnosis of PCOS, and the correlation of various clinical and hormonal parameters with the ultrasound findings.
Twenty-five women with PCOS diagnosed on the basis of clinical, hormonal, and ultrasound parameters using the Rotterdam criteria [2] were recruited to the study. A control group consisted of 25 women of similar reproductive age with normal menstrual cycles, normal ovaries on transvaginal ultrasound (TVS), and without any gynecological symptoms, who attended a family welfare clinic. Women who had diabetes mellitus, or had taken glucocorticoids or oral contraceptive pills during the previous 3 months, or had endocrinopathies that caused amenorrhea, such as thyroid disorder and pituitary insufficiency, were excluded from the study. Institutional Review Board approval was obtained for the study and informed consent was obtained from the participants. A thorough medical history including menstrual and obstetric details was taken followed by a physical examination, which included determining body mass index (BMI, calculated as weight in kilograms divided by the square of the height in meters) and obtaining a FerrimanGallwey score (FGS) for hirsutism. Serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured on days 2 to 5 of the menstrual cycle. Androgen levels were not measured and hirsutism was taken as an indicator of androgen excess. Women with amenorrhea were given norethisterone acetate (5 mg three times a day for 5 days) to induce withdrawal bleeding before the measurement of hormonal status. Between day 2 and day 5 of the menstrual cycle TVS was performed, and the ovarian volume was measured using the prolate ellipsoid formula: D1× D2 × D3. Follicles were counted in both stroma and cortex in multiplanes, and a total of 12 or more follicles measuring
☆ Paper presented at the 15th World Congress on Ultrasound in Obstetrics and Gynecology, held September 25–29, 2005, in Vancouver, Canada; and published as an abstract in Ultrasound Obstet Gynecol 2005; 26(4):341. ⁎ Corresponding author. H. No. C-12, First floor, Green Park Main, New Delhi 110 016, India. Tel.: +91 9868899082. E-mail address: [email protected] (Y.M. Mala).
0020-7292/$ – see front matter © 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2008.11.042
Y.M. Mala et al. / International Journal of Gynecology and Obstetrics 105 (2009) 36–38
37
2–9 mm in diameter were counted in the PCOS patients [7]. The color Doppler flow imaging parameters measured in the uterine artery and ovary were pulsatility index (PI) and resistance index (RI). The ascending branch of the uterine artery was visualized in the transverse section lateral to the uterus at the cervico–uterine junction. Ovarian blood vessels were visualized within the ovarian stroma away from the ovarian surface. The blood vessel that showed maximum blood flow velocity was used for the measurements. Three-dimensional power Doppler ultrasound was performed using conventional equipment (ATL HDI 1500) to measure vascularization index (VI), flow index (FI), and vascularization flow index (VFI). The entire ovary excluding the supplying vessels was observed. During observation, patients were asked to hold their breath to eliminate body movements. After determining the total color percentage and flow amplitudes in the total volume, virtual organ computer-aided analysis (VOCAL) software was used for histogram analysis algorithms to form indices of blood flow and vascularization [8,9]. VI, expressed as a percentage, allows an estimation of vessel density, whereas FI, expressed as a percentage, gives the average intensity of the flow. VFI indicates both flow intensity and vessel density [8]. At least 3 readings were taken for each variable and the mean was calculated. All the quantitative measurements were done by a single observer to eliminate interobserver error. As there was no significant difference between values from the right or left side, the mean of the two was used. Data obtained from PCOS and control groups were compared using independent sample t test. Pearson and Spearman correlations were used to determine the correlation between the variables.
(P b 0.01), and LH/FSH ratio (P b 0.01). The mean uterine artery RI was also significantly higher in the PCOS group than in the control group. Of the women in the PCOS group, 96% had an RI of more than 0.80, and 32% in the control group had an RI of less than 0.80. A significant correlation was seen between uterine artery RI and LH/FSH ratio (P b 0.01), ovarian volume (P b 0.01), and uterine artery PI (P b 0.01). The PI and RI values of the ovary were lower in the PCOS compared with the control group (P b 0.001) (Table 1). Pearson correlation showed a significant inverse correlation between PI and RI of the ovary and LH/FSH ratio (P b 0.01), and number of follicles (P b 0.01) in the ovary. Three-dimensional power Doppler VI of the ovary was found to be significantly higher in the PCOS group compared with the controls: mean values were 6.07 and 1.87, respectively. In the PCOS group, 72% of women had a VI of more than 4, and 100% of patients in the control group had a VI of less than 3.99. The 3D power Doppler FI was not significantly different between the PCOS and control groups. 3D power Doppler VFI was significantly higher in the PCOS group compared with the control group (P b 0.001). In the PCOS group, 60% of women had a VFI of more than 2, and 96% of patients in the control group had a VFI of less than 1.99. The VI of the ovary of the women in the PCOS group showed a strong correlation with LH/FSH ratio (P b 0.01), volume of ovary (P b 0.01), uterine artery PI and RI (P b 0.01), and VFI (P b 0.01). VFI of the ovary in the PCOS group showed a strong correlation with BMI (P b 0.01), LH/FSH ratio (P b 0.01), ovarian volume (P b 0.01), number of follicles (P b 0.01), uterine artery PI (P b 0.01), and uterine artery RI (P b 0.05).
3. Results
4. Discussion
The mean ages of the women in the PCOS and control groups were 23.92 ± 3.81 and 23.88 ± 3.02 years, respectively. Most patients with PCOS (92%) had menstrual irregularities. Amenorrhea was present in 28%, oligomenorrhea in 56%, and dysfunctional uterine bleeding in 8% of patients in the PCOs group. Primary infertility was present in 84% of the women in the PCOS group, and 8% had secondary infertility. The women in the control group had regular, normal menstruation (days 25–35) and at least one live birth. The clinical and hormonal profile and Doppler indices are shown in Table 1. Uterine artery PI was higher in the PCOS group compared with the control group. Of the women in the PCOS group, 88% had a uterine artery PI of more than 3, and 92% of women in the control group had a PI of less than 3. There was a significant correlation between high uterine artery PI and BMI (P b 0.05), FGS (P b 0.05), ovarian volume
Doppler ultrasound has been used for several years to study the pattern of blood flow in fetal and maternal vessels. Recently, color Doppler imaging and 3D power Doppler imaging have been used to diagnose various gynecological disorders. In the present study in which color Doppler flow imaging was done in the early follicular phase of the menstrual cycle, the uterine artery PI and RI were significantly higher in the PCOS group compared with the control group. Battaglia et al. [3] also showed high uterine PI (3.58 ± 0.34) in patients with PCOS and showed a positive correlation with LH/FSH ratio, but no significant correlation was found between uterine artery PI and ovarian morphology. The elevated uterine artery RI was correlated with androstenedione levels. In the present study, a strong positive correlation was seen between uterine artery PI and ovarian volume and LH/FSH ratio (P b 0.01). Some authors [3,10] also observed significantly elevated PI in the uterine artery associated with a low RI of the ovary in patients with PCOS. The PI was positively correlated with the LH/FSH ratio, and the RI was negatively correlated. The high RI and PI in the uterine arteries may be due to low serum estrogen levels. Estrogen influences uterine and ovarian vascularity, and estrogen levels are inversely correlated with uterine PI [11]. This effect seems to be mediated by a reduced function of periarteriolar vasoconstrictor nerves [12]. As the estrogen level increases in a normal menstrual cycle, the resistance to blood flow decreases, but because of the absence of ovulation in patients with PCOS and thus a continued low level of estrogen (estradiol), this change is not seen [10]. Horwitz et al. [13] showed that androgens have direct vasoconstrictor effects on vascular tissues, mediated by specific receptors present in arterial blood vessel walls. Doppler flow measurements of the ovarian artery were studied in women with PCOS and in women with normal menstruation who were undergoing in vitro fertilization and embryo transfer after ovulation induction with clomiphene citrate and human menopausal gonadotropin. They concluded that the levels of LH, estradiol, and 17αhydroxyprogesterone on the day of ovulation in patients with normal menstrual cycles are much higher than those of PCOS patients. Moreover with a rise in estradiol levels, the PI of the ovarian artery decreased to reach a nadir on the day of ovulation. Patients with PCOS had higher
Table 1 Clinical and hormonal profiles and Doppler indices of women with PCOS and women without PCOS a Characteristic
Women with PCOS (n = 25)
Women without PCOS (n = 25)
P value
BMI FGS LH/FSH ratio Ovarian volume, cm3 Number of follicles Uterine artery PI Uterine artery RI PI of ovary RI of ovary VI of ovary FI of ovary VFI of ovary
27.42 ± 4.52 13.68 ± 3.99 2.84 ± 1.22 12.16 ± 3.06 9.62 ± 1.78 3.74 ± 1.01 0.87 ± 0.04 2.64 ± 0.97 0.56 ± 0.08 6.07 ± 3.26 20.97 ± 4.31 2.39 ± 0.86
22.68 ± 2.04 2.96 ± 1.54 0.78 ± 0.22 5.19 ± 1.40 1.94 ± 0.48 2.43 ± 0.36 0.80 ± 0.06 3.08 ± 0.56 0.60 ± 0.07 1.87 ± 2.17 19.46 ± 3.75 1.16 ± 0.59
b 0.001 b 0.001 b 0.011 b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 NS b 0.001
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); FGS, Ferriman-Gallwey score; LH, luteinizing hormone; FSH, follicle-stimulating hormone; PI, pulsatility index; RI, resistance index; VI, vascularization index; FI, flow index; VFI, vascularization flow index; NS, not significant. a Values are given as mean ± SD.
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Y.M. Mala et al. / International Journal of Gynecology and Obstetrics 105 (2009) 36–38
estradiol values during the proliferative phase, and despite hormonal stimulation the blood flow in the patient did not improve [14]. Zaidi et al. [15] studied the intraovarian vasculature and found a higher intensity of color flow in the ovarian stroma of patients with PCOS. There was no significant difference in the impedance to blood flow in patients with PCOS and controls, i.e., mean ovarian stromal PI was not significantly different between the two groups. They postulated that the increased ovarian stromal blood flow velocity in combination with a relatively unchanged impedance to blood flow may reflect increased ovarian perfusion and thus a greater delivery of gonadotropins to the granulosa cells of the developing follicles. This theory may help to explain the greater likelihood of a multifollicular response and a greater incidence of ovarian hyperstimulation syndrome in patients with PCOS. The presence of stromal ovary vascularization with low resistance had generally high diagnostic value for PCOS. Color Doppler imaging illustrates only the direction of flow, colorcoded mean velocities, and the range of mean velocities. Power Doppler ultrasound adds a fourth parameter, which is amplitude or energy [16]. Power Doppler ultrasound has the advantage of being more sensitive to low blood flow, and thus overcomes the angle dependence and aliasing of standard color Doppler [16]. It displays the total flow in a confined area, giving an impression similar to that of angiography. This implementation of a 3D display permits the physician to see the interactivity of the 3 dimensions on the screen [8]. The size of the ovaries makes them ideal organs for using transvaginal 3D power Doppler ultrasound to measure the Doppler signals within the entire ovary. Three-dimensional power Doppler ultrasound is more accurate than the methods previously used to measure blood flow changes in PCOS [3,10,15]. 3D power Doppler histogram analysis can quantify the whole ovarian stromal Doppler signal via a 3D reconstructive figure, which can reflect the stromal flow data, whereas 2D power Doppler cannot [8]. With the use of 3D power Doppler ultrasound, different indices can be calculated. Pan et al. [4] studied 3D power Doppler parameters in women undergoing in vitro fertilization in a control group and a PCOS group. The mean VI in women with PCOS was 3.99 ± 2.38, the mean FI was 50.26± 3.02, and the VFI at 2.10 ± 1.32 was significantly higher than in the control group. The present study also showed that the 3D power Doppler parameters VI and VFI were significantly higher in the PCOS group compared with the control group. The FI appeared to be higher in the PCOS group compared with the control group, but the difference was not statistically significant. VI and VFI of the ovary performed by 3D power Doppler ultrasound showed a strong correlation with 2D color Doppler indices, and clinical and hormonal parameters. Ng et al. [9] compared ovarian stromal blood flow between fertile women with normal ovaries and infertile women with PCOS. They reported that fertile controls and women with PCOS had similar total ovarian 3D power Doppler flow indices. Women with PCOS and of normal body weight had significantly
higher total ovarian 3D power Doppler flow indices than women with PCOS who were overweight [9]. In conclusion, 3D power Doppler parameters could be used as a diagnostic tool for PCOS. However, large-scale studies are necessary to define the normal cut-off values. Three-dimensional power Doppler ultrasound may also assist in defining the severity, progression, or regression of the disease. References [1] Polson DW, Adam J, Wadsworth J, Franks S. Polycystic ovaries -- a common finding in normal women. Lancet 1988;8590(1):870–2. [2] The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Hum Reprod 2004;19(1):1–47. [3] Battaglia C, Artini P, D'Ambrogio G, Genazzani AD, Genazzani AR. The role of color Doppler imaging in the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol 1995;172(1):108–13. [4] Pan HA, Wu MH, Cheng YC, Li CH, Chang FM. Quantification of Doppler signal in polycystic ovary syndrome using three-dimensional power Doppler ultrasonography: a possible new marker for diagnosis. Hum Reprod 2002;17(1):201–6. [5] Rubin JM, Bude RO, Carson PL, Bree RL, Adler RS. Power Doppler US: a potentially useful alternative to mean frequency-based color Doppler US. Radiology 1994;190 (3): 853–6. [6] Rubin JM, Adler RS, Fowlkes JB, Spratt S, Pallister JE, Chen JF, et al. Fractional moving blood volume: estimation with power Doppler US. Radiology 1995;197 (1): 183–90. [7] Balen AH, Laven JS, Tan SL, Dewailly D. Ultrasound assessment of the polycystic ovary: international consensus definitions. Hum Reprod Update 2003;9(6):505–14. [8] Pairleitner H, Steiner H, Hasenoehrl G, Staudach A. Three-dimensional power Doppler sonography: imaging and quantifying blood flow and vascularization. Ultrasound Obstet Gynecol 1999;14(2):39–43. [9] Ng EH, Chan CC, Yeung WS, Ho PC. Comparison of ovarian stromal blood flow between fertile women with normal ovaries and infertile women with polycystic ovary syndrome. Hum Reprod 2005;20(7):1881–6. [10] Aleem FA, Predanic M. Transvaginal color Doppler determination of the ovarian and uterine blood flow characteristics in polycystic ovary disease. Fertil Steril 1996;65(3): 510–6. [11] Killam AP, Rosenfeld CR, Battaglia FC, Makowski EL, Meschia G. Effect of estrogens on the uterine blood flow of oophorectomized ewes. Am J Obstet Gynecol 1973;115(8): 1045–52. [12] Ford SP, Reynolds LP, Farley DB, Bhatnagar RF, Van Orden DE. Interaction of ovarian steroids and periarterial alpha 1-adrenergic receptors in altering uterine blood flow during the estrous cycle of gilts. Am J Obstet Gynecol 1984;150(5):480–4. [13] Horwitz KB, Horwitz LD. Canine vascular tissues are targets for androgens, estrogens, progestins and glucocorticoids. J Clin Invest 1982;69(4):750–8. [14] Schurz B, Schön HJ, Wenzl R, Eppel W, Huber J, Reinold E. Endovaginal Doppler flow measurements of the ovarian artery in patients with a normal menstrual cycle and with polycystic ovary syndrome during in vitro fertilization. J Clin Ultrasound 1993;21(1): 19–24. [15] Zaidi J, Campbell S, Pittrof R, Kyei-Mensah A, Shaker A, Jacobs HS, et al. Ovarian stromal blood flow in women with polycystic ovaries – a possible new marker for diagnosis? Hum Reprod 1995;10(8):1992–6. [16] Meyerowitz CB, Fleischer AC, Pickens DR, Thurman GB, Borowsky AD, Thirsk G, et al. Quantification of tumor vascularity and flow with amplitude color Doppler sonography in an experimental model. J Ultrasound Med 1996;15(12):827–33.
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
CLINICAL ARTICLE
Three-dimensional power Doppler imaging in the diagnosis of polycystic ovary syndrome ☆ Yedla M. Mala ⁎, Sharda B. Ghosh, Reva Tripathi Maulana Azad Medical College, Lok Nayak Hospital, Delhi, India
a r t i c l e
i n f o
Article history: Received 4 August 2008 Received in revised form 18 November 2008 Accepted 19 November 2008 Keywords: 2D Doppler 3D power Doppler Polycystic ovary syndrome
a b s t r a c t Objective: To determine the role of three-dimensional (3D) power Doppler imaging in the diagnosis of polycystic ovary syndrome (PCOS). Methods: Pulsatility index (PI) and resistance index (RI) of the uterine artery and ovary were measured by two-dimensional (2D) Doppler imaging, while vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured by 3D power Doppler in 25 patients with PCOS and 25 women with normal menstrual cycles used as a control group. Results: Uterine artery PI and RI were significantly higher (P b 0.001) and ovarian PI and RI were significantly lower (P b 0.001) in women with PCOS compared with controls. Ovarian VI and VFI were significantly higher in women with PCOS compared with the control group (P b 0.001). Conclusion: 3D power Doppler indices were higher in women with PCOS than in the control group and were positively correlated with 2D color Doppler indices, and clinical and hormonal parameters. High 3D power Doppler indices may be useful as one of the diagnostic criteria for PCOS. © 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Materials and methods
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of chronic anovulation and androgen excess that occurs with a prevalence of approximately 4%–7% in the female population [1]. Women with PCOS typically present for health care because of irregular bleeding, infertility, and/or symptoms of androgen excess. Despite the criteria for PCOS [2], physicians can find the condition difficult to diagnose because patients may not present with all of the typical features of the disease. More accurate diagnosis of various conditions has been achieved using color Doppler ultrasound [3]. Among the newest technological advances is the ability to evaluate the vascular flow and pattern using threedimensional (3D) power Doppler ultrasound, in which blood flow and vascularization are measured with histogram software analysis [4]. Power Doppler ultrasound is superior to frequency-based color Doppler ultrasound particularly for low-velocity blood flow [5], and has the potential to detect alterations in blood flow [6]. The present study was conducted to determine the role of color Doppler imaging and 3D power Doppler imaging in the diagnosis of PCOS, and the correlation of various clinical and hormonal parameters with the ultrasound findings.
Twenty-five women with PCOS diagnosed on the basis of clinical, hormonal, and ultrasound parameters using the Rotterdam criteria [2] were recruited to the study. A control group consisted of 25 women of similar reproductive age with normal menstrual cycles, normal ovaries on transvaginal ultrasound (TVS), and without any gynecological symptoms, who attended a family welfare clinic. Women who had diabetes mellitus, or had taken glucocorticoids or oral contraceptive pills during the previous 3 months, or had endocrinopathies that caused amenorrhea, such as thyroid disorder and pituitary insufficiency, were excluded from the study. Institutional Review Board approval was obtained for the study and informed consent was obtained from the participants. A thorough medical history including menstrual and obstetric details was taken followed by a physical examination, which included determining body mass index (BMI, calculated as weight in kilograms divided by the square of the height in meters) and obtaining a FerrimanGallwey score (FGS) for hirsutism. Serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured on days 2 to 5 of the menstrual cycle. Androgen levels were not measured and hirsutism was taken as an indicator of androgen excess. Women with amenorrhea were given norethisterone acetate (5 mg three times a day for 5 days) to induce withdrawal bleeding before the measurement of hormonal status. Between day 2 and day 5 of the menstrual cycle TVS was performed, and the ovarian volume was measured using the prolate ellipsoid formula: D1× D2 × D3. Follicles were counted in both stroma and cortex in multiplanes, and a total of 12 or more follicles measuring
☆ Paper presented at the 15th World Congress on Ultrasound in Obstetrics and Gynecology, held September 25–29, 2005, in Vancouver, Canada; and published as an abstract in Ultrasound Obstet Gynecol 2005; 26(4):341. ⁎ Corresponding author. H. No. C-12, First floor, Green Park Main, New Delhi 110 016, India. Tel.: +91 9868899082. E-mail address: [email protected] (Y.M. Mala).
0020-7292/$ – see front matter © 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2008.11.042
Y.M. Mala et al. / International Journal of Gynecology and Obstetrics 105 (2009) 36–38
37
2–9 mm in diameter were counted in the PCOS patients [7]. The color Doppler flow imaging parameters measured in the uterine artery and ovary were pulsatility index (PI) and resistance index (RI). The ascending branch of the uterine artery was visualized in the transverse section lateral to the uterus at the cervico–uterine junction. Ovarian blood vessels were visualized within the ovarian stroma away from the ovarian surface. The blood vessel that showed maximum blood flow velocity was used for the measurements. Three-dimensional power Doppler ultrasound was performed using conventional equipment (ATL HDI 1500) to measure vascularization index (VI), flow index (FI), and vascularization flow index (VFI). The entire ovary excluding the supplying vessels was observed. During observation, patients were asked to hold their breath to eliminate body movements. After determining the total color percentage and flow amplitudes in the total volume, virtual organ computer-aided analysis (VOCAL) software was used for histogram analysis algorithms to form indices of blood flow and vascularization [8,9]. VI, expressed as a percentage, allows an estimation of vessel density, whereas FI, expressed as a percentage, gives the average intensity of the flow. VFI indicates both flow intensity and vessel density [8]. At least 3 readings were taken for each variable and the mean was calculated. All the quantitative measurements were done by a single observer to eliminate interobserver error. As there was no significant difference between values from the right or left side, the mean of the two was used. Data obtained from PCOS and control groups were compared using independent sample t test. Pearson and Spearman correlations were used to determine the correlation between the variables.
(P b 0.01), and LH/FSH ratio (P b 0.01). The mean uterine artery RI was also significantly higher in the PCOS group than in the control group. Of the women in the PCOS group, 96% had an RI of more than 0.80, and 32% in the control group had an RI of less than 0.80. A significant correlation was seen between uterine artery RI and LH/FSH ratio (P b 0.01), ovarian volume (P b 0.01), and uterine artery PI (P b 0.01). The PI and RI values of the ovary were lower in the PCOS compared with the control group (P b 0.001) (Table 1). Pearson correlation showed a significant inverse correlation between PI and RI of the ovary and LH/FSH ratio (P b 0.01), and number of follicles (P b 0.01) in the ovary. Three-dimensional power Doppler VI of the ovary was found to be significantly higher in the PCOS group compared with the controls: mean values were 6.07 and 1.87, respectively. In the PCOS group, 72% of women had a VI of more than 4, and 100% of patients in the control group had a VI of less than 3.99. The 3D power Doppler FI was not significantly different between the PCOS and control groups. 3D power Doppler VFI was significantly higher in the PCOS group compared with the control group (P b 0.001). In the PCOS group, 60% of women had a VFI of more than 2, and 96% of patients in the control group had a VFI of less than 1.99. The VI of the ovary of the women in the PCOS group showed a strong correlation with LH/FSH ratio (P b 0.01), volume of ovary (P b 0.01), uterine artery PI and RI (P b 0.01), and VFI (P b 0.01). VFI of the ovary in the PCOS group showed a strong correlation with BMI (P b 0.01), LH/FSH ratio (P b 0.01), ovarian volume (P b 0.01), number of follicles (P b 0.01), uterine artery PI (P b 0.01), and uterine artery RI (P b 0.05).
3. Results
4. Discussion
The mean ages of the women in the PCOS and control groups were 23.92 ± 3.81 and 23.88 ± 3.02 years, respectively. Most patients with PCOS (92%) had menstrual irregularities. Amenorrhea was present in 28%, oligomenorrhea in 56%, and dysfunctional uterine bleeding in 8% of patients in the PCOs group. Primary infertility was present in 84% of the women in the PCOS group, and 8% had secondary infertility. The women in the control group had regular, normal menstruation (days 25–35) and at least one live birth. The clinical and hormonal profile and Doppler indices are shown in Table 1. Uterine artery PI was higher in the PCOS group compared with the control group. Of the women in the PCOS group, 88% had a uterine artery PI of more than 3, and 92% of women in the control group had a PI of less than 3. There was a significant correlation between high uterine artery PI and BMI (P b 0.05), FGS (P b 0.05), ovarian volume
Doppler ultrasound has been used for several years to study the pattern of blood flow in fetal and maternal vessels. Recently, color Doppler imaging and 3D power Doppler imaging have been used to diagnose various gynecological disorders. In the present study in which color Doppler flow imaging was done in the early follicular phase of the menstrual cycle, the uterine artery PI and RI were significantly higher in the PCOS group compared with the control group. Battaglia et al. [3] also showed high uterine PI (3.58 ± 0.34) in patients with PCOS and showed a positive correlation with LH/FSH ratio, but no significant correlation was found between uterine artery PI and ovarian morphology. The elevated uterine artery RI was correlated with androstenedione levels. In the present study, a strong positive correlation was seen between uterine artery PI and ovarian volume and LH/FSH ratio (P b 0.01). Some authors [3,10] also observed significantly elevated PI in the uterine artery associated with a low RI of the ovary in patients with PCOS. The PI was positively correlated with the LH/FSH ratio, and the RI was negatively correlated. The high RI and PI in the uterine arteries may be due to low serum estrogen levels. Estrogen influences uterine and ovarian vascularity, and estrogen levels are inversely correlated with uterine PI [11]. This effect seems to be mediated by a reduced function of periarteriolar vasoconstrictor nerves [12]. As the estrogen level increases in a normal menstrual cycle, the resistance to blood flow decreases, but because of the absence of ovulation in patients with PCOS and thus a continued low level of estrogen (estradiol), this change is not seen [10]. Horwitz et al. [13] showed that androgens have direct vasoconstrictor effects on vascular tissues, mediated by specific receptors present in arterial blood vessel walls. Doppler flow measurements of the ovarian artery were studied in women with PCOS and in women with normal menstruation who were undergoing in vitro fertilization and embryo transfer after ovulation induction with clomiphene citrate and human menopausal gonadotropin. They concluded that the levels of LH, estradiol, and 17αhydroxyprogesterone on the day of ovulation in patients with normal menstrual cycles are much higher than those of PCOS patients. Moreover with a rise in estradiol levels, the PI of the ovarian artery decreased to reach a nadir on the day of ovulation. Patients with PCOS had higher
Table 1 Clinical and hormonal profiles and Doppler indices of women with PCOS and women without PCOS a Characteristic
Women with PCOS (n = 25)
Women without PCOS (n = 25)
P value
BMI FGS LH/FSH ratio Ovarian volume, cm3 Number of follicles Uterine artery PI Uterine artery RI PI of ovary RI of ovary VI of ovary FI of ovary VFI of ovary
27.42 ± 4.52 13.68 ± 3.99 2.84 ± 1.22 12.16 ± 3.06 9.62 ± 1.78 3.74 ± 1.01 0.87 ± 0.04 2.64 ± 0.97 0.56 ± 0.08 6.07 ± 3.26 20.97 ± 4.31 2.39 ± 0.86
22.68 ± 2.04 2.96 ± 1.54 0.78 ± 0.22 5.19 ± 1.40 1.94 ± 0.48 2.43 ± 0.36 0.80 ± 0.06 3.08 ± 0.56 0.60 ± 0.07 1.87 ± 2.17 19.46 ± 3.75 1.16 ± 0.59
b 0.001 b 0.001 b 0.011 b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 b 0.001 NS b 0.001
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); FGS, Ferriman-Gallwey score; LH, luteinizing hormone; FSH, follicle-stimulating hormone; PI, pulsatility index; RI, resistance index; VI, vascularization index; FI, flow index; VFI, vascularization flow index; NS, not significant. a Values are given as mean ± SD.
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estradiol values during the proliferative phase, and despite hormonal stimulation the blood flow in the patient did not improve [14]. Zaidi et al. [15] studied the intraovarian vasculature and found a higher intensity of color flow in the ovarian stroma of patients with PCOS. There was no significant difference in the impedance to blood flow in patients with PCOS and controls, i.e., mean ovarian stromal PI was not significantly different between the two groups. They postulated that the increased ovarian stromal blood flow velocity in combination with a relatively unchanged impedance to blood flow may reflect increased ovarian perfusion and thus a greater delivery of gonadotropins to the granulosa cells of the developing follicles. This theory may help to explain the greater likelihood of a multifollicular response and a greater incidence of ovarian hyperstimulation syndrome in patients with PCOS. The presence of stromal ovary vascularization with low resistance had generally high diagnostic value for PCOS. Color Doppler imaging illustrates only the direction of flow, colorcoded mean velocities, and the range of mean velocities. Power Doppler ultrasound adds a fourth parameter, which is amplitude or energy [16]. Power Doppler ultrasound has the advantage of being more sensitive to low blood flow, and thus overcomes the angle dependence and aliasing of standard color Doppler [16]. It displays the total flow in a confined area, giving an impression similar to that of angiography. This implementation of a 3D display permits the physician to see the interactivity of the 3 dimensions on the screen [8]. The size of the ovaries makes them ideal organs for using transvaginal 3D power Doppler ultrasound to measure the Doppler signals within the entire ovary. Three-dimensional power Doppler ultrasound is more accurate than the methods previously used to measure blood flow changes in PCOS [3,10,15]. 3D power Doppler histogram analysis can quantify the whole ovarian stromal Doppler signal via a 3D reconstructive figure, which can reflect the stromal flow data, whereas 2D power Doppler cannot [8]. With the use of 3D power Doppler ultrasound, different indices can be calculated. Pan et al. [4] studied 3D power Doppler parameters in women undergoing in vitro fertilization in a control group and a PCOS group. The mean VI in women with PCOS was 3.99 ± 2.38, the mean FI was 50.26± 3.02, and the VFI at 2.10 ± 1.32 was significantly higher than in the control group. The present study also showed that the 3D power Doppler parameters VI and VFI were significantly higher in the PCOS group compared with the control group. The FI appeared to be higher in the PCOS group compared with the control group, but the difference was not statistically significant. VI and VFI of the ovary performed by 3D power Doppler ultrasound showed a strong correlation with 2D color Doppler indices, and clinical and hormonal parameters. Ng et al. [9] compared ovarian stromal blood flow between fertile women with normal ovaries and infertile women with PCOS. They reported that fertile controls and women with PCOS had similar total ovarian 3D power Doppler flow indices. Women with PCOS and of normal body weight had significantly
higher total ovarian 3D power Doppler flow indices than women with PCOS who were overweight [9]. In conclusion, 3D power Doppler parameters could be used as a diagnostic tool for PCOS. However, large-scale studies are necessary to define the normal cut-off values. Three-dimensional power Doppler ultrasound may also assist in defining the severity, progression, or regression of the disease. References [1] Polson DW, Adam J, Wadsworth J, Franks S. Polycystic ovaries -- a common finding in normal women. Lancet 1988;8590(1):870–2. [2] The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Hum Reprod 2004;19(1):1–47. [3] Battaglia C, Artini P, D'Ambrogio G, Genazzani AD, Genazzani AR. The role of color Doppler imaging in the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol 1995;172(1):108–13. [4] Pan HA, Wu MH, Cheng YC, Li CH, Chang FM. Quantification of Doppler signal in polycystic ovary syndrome using three-dimensional power Doppler ultrasonography: a possible new marker for diagnosis. Hum Reprod 2002;17(1):201–6. [5] Rubin JM, Bude RO, Carson PL, Bree RL, Adler RS. Power Doppler US: a potentially useful alternative to mean frequency-based color Doppler US. Radiology 1994;190 (3): 853–6. [6] Rubin JM, Adler RS, Fowlkes JB, Spratt S, Pallister JE, Chen JF, et al. Fractional moving blood volume: estimation with power Doppler US. Radiology 1995;197 (1): 183–90. [7] Balen AH, Laven JS, Tan SL, Dewailly D. Ultrasound assessment of the polycystic ovary: international consensus definitions. Hum Reprod Update 2003;9(6):505–14. [8] Pairleitner H, Steiner H, Hasenoehrl G, Staudach A. Three-dimensional power Doppler sonography: imaging and quantifying blood flow and vascularization. Ultrasound Obstet Gynecol 1999;14(2):39–43. [9] Ng EH, Chan CC, Yeung WS, Ho PC. Comparison of ovarian stromal blood flow between fertile women with normal ovaries and infertile women with polycystic ovary syndrome. Hum Reprod 2005;20(7):1881–6. [10] Aleem FA, Predanic M. Transvaginal color Doppler determination of the ovarian and uterine blood flow characteristics in polycystic ovary disease. Fertil Steril 1996;65(3): 510–6. [11] Killam AP, Rosenfeld CR, Battaglia FC, Makowski EL, Meschia G. Effect of estrogens on the uterine blood flow of oophorectomized ewes. Am J Obstet Gynecol 1973;115(8): 1045–52. [12] Ford SP, Reynolds LP, Farley DB, Bhatnagar RF, Van Orden DE. Interaction of ovarian steroids and periarterial alpha 1-adrenergic receptors in altering uterine blood flow during the estrous cycle of gilts. Am J Obstet Gynecol 1984;150(5):480–4. [13] Horwitz KB, Horwitz LD. Canine vascular tissues are targets for androgens, estrogens, progestins and glucocorticoids. J Clin Invest 1982;69(4):750–8. [14] Schurz B, Schön HJ, Wenzl R, Eppel W, Huber J, Reinold E. Endovaginal Doppler flow measurements of the ovarian artery in patients with a normal menstrual cycle and with polycystic ovary syndrome during in vitro fertilization. J Clin Ultrasound 1993;21(1): 19–24. [15] Zaidi J, Campbell S, Pittrof R, Kyei-Mensah A, Shaker A, Jacobs HS, et al. Ovarian stromal blood flow in women with polycystic ovaries – a possible new marker for diagnosis? Hum Reprod 1995;10(8):1992–6. [16] Meyerowitz CB, Fleischer AC, Pickens DR, Thurman GB, Borowsky AD, Thirsk G, et al. Quantification of tumor vascularity and flow with amplitude color Doppler sonography in an experimental model. J Ultrasound Med 1996;15(12):827–33.