Doppler assessment of uterine and intraovarian blood flow in patients with genital endometriosis

Materials and methods. The research included 65 women with diagnosis of external genital endometriosis who formed the Ist group. 38 women with internal genital endometriosis were included into the IInd group. Control group involved 30 women without genital endometriosis. Doppler study was set in both phases of menstrual cycle with determination of uterine and intraovarian pulsatility index, resistance index and systolic/diastolic ratio in uterine arteries.

In recent years the problem of endometriosis began to occupy the first places in gynecological practice.The spread of the disease among women of reproductive age is 5-10 % [1], but some scientists indicate about more prevalence of endometriosis among females of reproductive age -up to 45 % [2].In addition, about 50 % of women with infertility have this pathology [3].Increase of frequency of endometriosis is most likely associated with more advanced diagnostic capabilities.However, lifestyle habits, metabolic changes, deterioration of ecological situation, genetic background factors and other aspects are important in the development of the disease [4].Pain syndrome, menstrual disorders in the form of hemorrhagic syndrome, infertility are dominating clinical manifestations of endometriosis.This pathology significantly affects the quality of life of patients, leading to impairment of relations in the family and with other people, reducing professional and daily activities [5].
Clinical management of patients with endometriosis is still a debate process.Various groups of medications from symptomatic treatment till hormonal drugs, agonists of gonadotropin-releasing hormones, gonadotropin medications, aromatase inhibitors and so on are proposed for treatment.However, surgical operations of endometriosis in recent years are very successful.Therefore, it should be mentioned, that complete examination of patient with endometriosis is basic for choosing effective kind of treatment.In practical medicine Doppler assessment of blood flow in vessels of pelvic organs by endometriosis is not widely spread.Mostly attention is paid to changes of sizes and structure of internal genital organs by ultrasound echography.But it ought to re-member that forming of endometrioid foci commonly begins from development of new blood vessels [6].So, changes of hemodynamics in vessels that can be determined by Doppler are important for complete diagnosis of endometriosis.

Aim of research
To evaluate the uterine and intraovarian hemodynamic changes in women with internal and external endometriosis.

Materials and methods
The research included 65 women with diagnosis of external genital endometriosis who formed the I st group.38 women with internal genital endometriosis were included into the II nd group.This group also included patients with adenomyosis in combination with small myoma nodes (diameter less than 1.5-2.0cm Оригинальные исследования 16-40 points; IV -severe endometriosis, more than 40 points).Internal endometriosis was also classified according to stages: I -pathological process is limited by submucous membrane of uterine body; II -pathological process involves myometrium; III -pathological process is located in whole myometrium till serous membrane of uterus; IV -involvement in pathological process, except uterus, parietal peritoneum of pelvis and nearby organs [7].
Ultrasound and Doppler examinations of pelvic organs were set in both phases of menstrual cycle (on 6-8 th and 22-24 th days) using 3.5, 7.5 and 9 MHz transabdominal and transvaginal transducers (ultrasound machine PHILLIPS HD7).We determined uterine and intraovarian pulsatility index (PI), resistance index (RI) and systolic/diastolic ratio (S/D ratio) in uterine arteries.
Fоr stаtistical аnаlysis we used program Stаtistica 6.0.We cаlculated arithmetic mean vаlue, stаndard error of the mеаn, criterion χ 2 (Yates corrected Chi-square), рrobаbility of differences results of research (p).To compare two independent groups on one feature we used nonparametric Mann-Whitney test, to compare two dependent groups -Wilcoxon test.The difference between the values comparing considered reliable at p < 0.05.

Results
The average age of women in the I st and II nd groups was statistically different -27.88 ± 0. Using clinical and instrumental examinations external genital endometriosis of the I and II stages were diagnosed in 25 women (38.46 %), the III stage -in 15 (23.08 %).Among patients in the IInd group 9 (23.68 %) women had I stage of disease, 10 (26.32 %) -II and 19 (50.00 %) -III.
The leading complaints in patients with external and internal endometriosis were algomenorrhea (69.23 % and 86.84 % respectively) and dyspaureniya (43.08 % and 42.11 %), which was determined by the severity of pain index (Table 1).Obviously, level of pain index in patients with external endometriosis did not indicate the extent of the disease, whereas in patients with internal endometriosis it reflected severity of the disease and was most pronounced in diffuse myometrium injury.Women from the IInd group suffered from pain which was not connected with menstrual cycle more often, than in the Ist group (χ 2 = 4.73, P < 0.05).
Disorders of menstrual cycle like spot dark blood discharges before or after menses, hyperpolymenorrhae were more frequent in women with internal endometriosis (χ 2 = 7.64, P < 0.01) comparers to external one.10.8 % per-sons with external endometriosis had no complaints against none patients with internal endometriosis (χ 2 = 4.84, P < 0.05).
In both groups among general complaints the most spread were unmotivated weakness (78.5 % in I group and 92.0 % -in II), malaise (64.5 % and 84.0 % respectively), increased fatigue (48.0 % and 64.0 %).Most patients suffered from irritability, emotional liability, sleep disturbances, increased anxiety.It was established that common symptoms are often in various combinations and met with equal frequency in all stages of genital endometriosis.
Infertility was diagnosed in 24 (36.92 %) women with external endometriosis and 16 (42.11%) -with internal one.In I group quantity of patients with primary infertility (83.33 %) was more than with secondary one (16.67%).And in the contrary, in II group secondary infertility (75.00 %, χ 2 = 11.29,P < 0.001 compared to I group) was more often than primary (25.00 %, χ 2 = 11.29,P < 0.001 compared to I group).Differences between spreading of type of infertility according to stage of disease were not found.
Results of Doppler examination of uterine and ovarian arteries demonstrated that in healthy women there were decrease of indexes of vessels resistance during menstrual cycle by reducing of peak systolic flow and the simultaneous increase of maximum final velocity diastolic flow (Тable 2).There was no significant difference in blood circulation between right and left uterine arteries in different phases of cycle.This pattern of blood flow is ensured by adequate hormonal ovarian function.Estrogens have vasodilatation effect and progesterone has the opposite one.
In patients with endometriosis we found hemodynamic disturbances in uterine arteries of varying degrees which were depended on localization of the pathological process and its stages.In women of I group with I and II stages of external endometriosis indices of peripheral vascular resistance were not differ significantly by from parameters of control group.In persons with III stage there was moderate increase of vascular resistance indices higher over healthy women (P < 0.05).Thus, in patients with III stage of external endometriosis, despite the absence of objective instrumental data for internal endometriosis, there are predisposing factors for its development -increased indices of peripheral vascular resistance in the uterine arteries.
By all stages of internal endometriosis we found increase of peripheral vascular resistance, which grew rapidly according to severity of pathological process (Тable 3).Thus, in patients of I stage these indexes were similar to controls,

Original research
II-III stages -difference was significant higher over healthy women.Similar changes were determined in both uterine arteries.Critical changes in blood flow can be manifested in the form of dicrotic notch between diastolic peak systolic velocity and maximum one that reaches baseline.Critical changes of circulation were detected in 6 (31.58 %) of patients with III stage of the disease.In half of all cases dicrotic notches were symmetrical in both uterine arteries.In addition, in 7 (36.84%) of patients with III degree of internal endometriosis negative blood flow in diastole phase was determined.It can mean significant changes in blood supply of uterus.In the second phase of the menstrual cycle, in contrast to the control group, there is no gradual decrease in peripheral vascular resistance indices in persons with internal endometriosis.In patients with II and III stages these parameters remained high and differ significantly from physiological ones.
It is worth to mention that all patients with critical changes of blood velocity had such parameters with negative values in diastole phase of menstruation in both phases of menstrual cycle.This can be criterion of decompensation of arterial blood flow in uterus.Such patients had complains on hemorrhagic syndrome and severe pain syndrome that was not stopped from receiving non-narcotic analgesics.
We did not determine significant important difference of RI and PI between healthy women and patients with internal and external endometriosis.However, in control group in follicle phase of menstrual cycle RI was 0.51 ± 0.01, PI 0.70 ± 0.03, in luteal phase -0.43 ± 0.02 and 0.59 ± 0.02 respectively.Obviously, at 6-8th days of menses there were increased levels RI and PI, but mostly in women with external endometriosis (I group -0.54 ± 0.03 and 0.80 ± 0.03, II group -0.52 ± 0.02 and 0.78 ± 0.02).In the second phase of menstrual cycle we found increase of these indices in patients from the Ist (0.50 ± 0.03 and 0.65 ± 0.04) and the IInd groups (0.46 ± 0.03 and 0.63 ± 0.02 respectively).In patients with external endometriosis indices of peripheral vascular resistance of intraovarian velocity were fairly higher than those in patients with internal.Women with endometriod cysts had RI in intraovarian circulation in both phases of the menstrual cycle over 0.55 (P < 0.05).
Thus, the obtained results prompt to evaluate importance of complete Doppler examination of uterine and ovarian arteries for differentiated treatment of patient with genital endometriosis and indications for surgical management.The presence of decompensation of blood circulation in uterine arteries in both phases of menstrual cycle may be the basis for deciding about possibility of surgical treatment of this pathology.

Conclusions
1. Doppler studies of uterine blood velocity during menstrual cycle in patients with genital endometriosis demonstrated equally direction of hemodynamic disorders in patients with external (III stage) and internal (II-III stages) endometriosis -highly resistant blood flow compared to healthy women (P < 0.05).Decompensated changes in blood velocity in uterine arteries were observed only in cases of the IIIrd stage of internal endometriosis.
2. Doppler indices of intraovarian blood velocity during menstrual cycle were increased in patients with endometriod cysts.
).Control group involved 30 women of reproductive age without diagnosis of genital endometriosis and other hormonal or acute gynecological and extragenital pathologies.Verification of diagnosis was performed in accordance with Order # 319 of Ministry of Health of Ukraine [1].Diagnosis was based on the combination of clinical manifestations and specific methods of examinations (ultrasound, laparoscopy, hysteroscopy, morphology).Stages of external genital endometriosis were performed according to American Fertility Society classification, based on calculation of the total area and depth of endometrioid heterotopy, expressed in points (I -minimal endometriosis, 1-5 points; II -mild endometriosis, 6-15 points; III -moderate endometriosis,

Table 1 .
Clinical manifestations of patients with endometriosis

Table 2 .
Uterine artery indices in patients with external endometriosis in both phases of menstrual cycle probability of the difference of indicator relative to control group (P < 0.05). *:

Table 3 .
Uterine artery indices in patients with internal endometriosis in both phases of menstrual cycle ‫:٭‬ probability of the difference of indicator relative to control group (P < 0.05).