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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 4  |  Page : 1355-1358

Role of transvaginal Doppler sonography in cases of irregular uterine bleeding with depot medroxyprogesterone acetate


Department of Obstetrics and Gynacology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission26-Jul-2018
Date of Decision23-Aug-2018
Date of Acceptance28-Aug-2018
Date of Web Publication31-Dec-2019

Correspondence Address:
Mohammed Wahid Al-Sarag
Shebin El-Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_237_18

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  Abstract 


Objectives
To evaluate role of transvaginal Doppler sonography in cases of irregular uterine bleeding with depot medroxyprogesterone acetate (DMPA).
Background
Abnormal uterine bleeding is the leading cause of cessation of DMPA use. The definite mechanism of abnormal uterine bleeding has remained vague. Transvaginal Doppler is a noninvasive technique for studying Doppler changes of uterine and spiral artery in cases of abnormal uterine bleeding with DMPA.
Patients and methods
A case–control study was done on two groups of users of DMPA, one group included 21 cases with abnormal uterine bleeding, and the second group included 21 cases with amenorrhea. Transvaginal sonography was done, and endometrial thickness was measured in greatest sagittal section of the uterus. Uterine and spiral artery pulsatility index (PI) and resistance index (RI) were measured. Data were collected and tabulated.
Results
Significant changes in PI and RI of uterine and spiral arteries were detected. Uterine artery RI and PI were lower in bleeding group (P = 0.003 and 0.021, respectively), and spiral artery RI and PI were lower in bleeding group (P = 0.0007 and 0.0003, respectively).
Conclusion
Abnormal uterine bleeding with DMPA is associated with hemodynamic changes in transvaginal Doppler in form of increased blood flow in uterine and spiral arteries as indicated by significant decrease in RI and PI of both arteries.

Keywords: depot medroxyprogesterone acetate, Doppler, spiral artery, uterine artery


How to cite this article:
Essam M, Alhalabi A, Hamza H, Al-Sarag MW. Role of transvaginal Doppler sonography in cases of irregular uterine bleeding with depot medroxyprogesterone acetate. Menoufia Med J 2019;32:1355-8

How to cite this URL:
Essam M, Alhalabi A, Hamza H, Al-Sarag MW. Role of transvaginal Doppler sonography in cases of irregular uterine bleeding with depot medroxyprogesterone acetate. Menoufia Med J [serial online] 2019 [cited 2020 Jan 21];32:1355-8. Available from: http://www.mmj.eg.net/text.asp?2019/32/4/1355/274242




  Introduction Top


Depot medroxyprogesterone acetate (DMPA) is one of long-acting reversible contraception. It is safe and highly effective in preventing pregnancy [1]. DMPA is highly effective if taken every 3 months as directed. With correct and consistent use, less than 1% will experience a method failure in the first year of use. Typical users though have failure rates of ∼3% in the first year. For women who prefer an injectable contraceptive method, duration of use is not associated with any decrease in efficacy or safety. Thus, the use of DMPA does not require a rest period [2]. It acts primarily by suppression of ovulation, other ways by thickening of cervical mucous thus preventing sperm entry, or by altering endometrium so preventing implantation of fertilized egg [3]. Compared with other progesterone-only contraception, DMPA contains substantially higher level of progesterone; consequently, DMPA is associated with more adverse effects [4]. The most common adverse effects of DMPA is abnormal uterine bleeding [5]. Most women using DMPA experience disruption of menstrual bleeding patterns, which include amenorrhea, irregular or unpredictable bleeding, or spotting. One should rule out the possibility of organic pathology if there is persistent or sever abnormal uterine bleeding and appropriate treatment should be undergone [2]. The exact pathophysiological mechanisms of irregular bleeding have remained unclear. Several studies have been performed on endometrial morphology, histology, vascular microstructure, and biochemistry, such as tissue factor, lipid peroxide, vitamin E, progesterone receptors, matrix metalloproteinase, and the PGE2 and PGF2a [6]. DMPA leads to formation of new fragile superficial blood vessel embedded in collapsed stromal extracellular matrix [7]. DMPA-induced reductions in endometrial blood flow cause hypoxia-reperfusion injury and free radical production that promotes aberrant angiogenesis via enhanced expression of vascular endothelial growth factor and angiopoietin-2 and reciprocal inhibition of angiopoietin-1 as well as directly damaging blood vessels that bleed despite the surfeit of available perivascular tissue factor [8],[9],[10]. Blood flow to the endometrium comes from uterine artery, which divides before myometrial endometrial junction into basal arteries that supply the basal portion of endometrium and the spiral arteries that continue upward to the endometrial surface. Considering that blood supply to the endometrium must go through the subendometrial area, vascularization of this area may be related to endometrial perfusion and hence any consequent endometrial vascular abnormalities [11]. Transvaginal Doppler is a noninvasive technique for studying Doppler indices changes, which may reflect underlying pathology with cases of abnormal uterine bleeding with DMPA [12]. This study aimed to elucidate Doppler changes in uterine and spiral artery in DMPA users with abnormal uterine bleeding in comparison with amenorrhea cases with DMPA.


  Patients and Methods Top


This case–control study was done on two groups of users of DMPA: the first group included 21 cases with abnormal uterine bleeding, and the second group included 21 cases with amenorrhea. It was done in the period from November 2016 to August 2017 in Obstetrics and Gynecology Department, Faculty of Medicine, Menoufia University. The study protocol was approved by the Medical Ethical Committee of Faculty of Medicine-Menoufia University. An informed consent was taken from each participant before being enrolled in the study. Users of DMPA with abnormal uterine bleeding without any local or general causes were included in the study and also did not use any hormonal treatment altering bleeding pattern. A detailed menstrual and medical history was taken first. All women were assessed by the physician on duty, including general, abdominal, and local examination and investigation. The study was explained to them and an informed consent was obtained before a transvaginal ultrasound examination. The ultrasound assessment was performed by the same experienced operator. The examination was conducted with Philips HD11XE ultrasound machine (Philips, Radiological Society of North America McCormick Place, Chicago, IL, United States). Patient emptied the urinary bladder before examination, and then lied in lithotomy position. A transducer was introduced into vagina and conventional gray-scale sonography was done, where the uterus and both adnexa were scanned in longitudinal and transverse planes to exclude any abnormality, and then endometrial thickness was measured in the greatest sagittal section of the uterus. Color Doppler was switched on to determine the blood flow in the subendometrial areas. The pulse repetition for color velocity was adjusted in the range of 3 cm/s, and the color gain was changed to 80 ± 2% to optimize blood flow detection in the small vessels. Spectral wave forms were obtained from vessels of high color intensity. After confirming that wave forms were continuous, at least three cardiac cycles were selected for calculation of spiral artery pulsatility index (PI) and resistance index (RI). Angle should be kept at 0° because of the course of the small spiral arteries. The transducer was moved to lateral vaginal fornix, color Doppler was switched on, and uterine artery was visualized by color Doppler lateral to the cervix with angle of insonation less than 30°. PI and RI of uterine arteries were measured. All Doppler indices were calculated automatically using auto-trace measurements. Recorded data were analyzed using the statistical package for the social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean ± SD. Qualitative data were expressed as frequency and percentage. Student's t test was used for comparison of two groups of normally distributed variables, whereas Mann–Whitney test was used for comparison of two groups of non-normally distributed variables. The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the P value was considered significant if it is less than 0.05.


  Results Top


The demographic data of women included in the study did not differ significantly [Table 1]. The endometrial thickness did not show any significant difference between both groups (P = 0.314). The uterine volume was significantly lower in amenorrheic group (134.3 ± 12.00 mm 3) than in bleeding group (149.8 ± 20.11 mm 3), with P value of 0.001 [Table 2]. Uterine artery RI was lower in bleeding group (0.60 ± 0.07) than in amenorrheic group (0.75 ± 0.10) (P = 0.0001). Uterine artery PI was lower in bleeding group (2.00 ± 0.92) than in amenorrheic group (2.72 ± 1.25), with P value of 0.021. Spiral artery RI was lower in bleeding group (0.36 ± 0.20) than in amenorrheic group (1.40 ± 0.92), (P = 0.0007). Spiral artery PI was lower in bleeding group (0.65 ± 0.32) than in amenorrheic group (3.00 ± 1.84) (P = 0.0003) [Table 3].
Table 1: Baseline characteristics and demographic data of study groups

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Table 2: Sonographic measures of study groups

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Table 3: Doppler blood flow characteristics

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There was no significant difference in the mean uterine artery RI and PI in the bleeding group who used Depo-Provera for less than 1 year and the other group who used it for more than 1 year. Also there was no significant difference in the mean spiral artery RI and PI in the bleeding group who used Depo-Provera for less than 1 year and the other group who used it for more than 1 year. The mean uterine artery RI and PI in the amenorrhea group using Depo-Provera were measured in the group using it for less than 1 year compared with group more than 1 year, which was nonsignificant. The mean spiral artery RI and PI in the amenorrhea group using Depo-Provera measured were in the group using it for less than 1 year compared with group more than 1 year, which was nonsignificant.


  Discussion Top


Bleeding disorder is the main cause for discontinuation of DMPA. The underlying mechanism of irregular uterine bleeding with DMPA is still unclear. In this study, we observed that blood perfusion in uterine and spiral arteries was significantly increased in group of abnormal uterine bleeding as indicated by significant decrease in RI and PI of both arteries. These data are consistent with Rezk et al. [13], which is a 3-year prospective observational study that included 102 women using levonorgestrel intrauterine system (LNG-IUS) and 104 women using DMPA for contraception. Participants were followed at regular intervals over 3 years with performance of transvaginal ultrasound to measure uterine artery PI and RI before starting the method and at 6, 12 months, 2, and 3 years in which uterine artery RI and PI were significantly reduced in women having abnormal uterine bleeding and significantly elevated in women who experienced amenorrhea. In a study performed in Assiut University Hospitals, 40 users of DMPA were divided into two groups: group 1 included 20 users with amenorrhea and group 2 included 20 users with irregular uterine bleeding. Doppler blood flow in the cervical branch of uterine artery and in the spiral arteries was significantly higher in group 2 as indicated by the lower Doppler indices of both uterine and spiral arteries and decreased impedance to the flow, which is also consistent with our study [12]. Moreover, Jiménez et al. [14] conducted a clinical trial that included 27 patients who received the LNG-IUS compared with 25 patients who received the TCU 380 (Copper T 380) A intrauterine device (IUD). Uterine artery PI and RI were evaluated just before inserting the IUD in the midluteal phase and 3 months after. PI and RI variability (before and after) increased and endometrial thickness reduced in LNG-IUS users, which were statistically significant (PI, 2.47 ± 0.19 in LNG-IUS vs. 2.87 ± 0.21 in TCU 380 A IUD and RI, 0.83 ± 0.02 in LNG-IUS vs. 0.87 ± 0.02 in TCU 380 A IUD), which is consistent with our study. It is also consistent with a study by Bastianelli et al. [15], which evaluated if different bleeding patterns associated with the use of the LNG-IUS are associated with different uterine and endometrial vascularization patterns. All participants included in the study were retrospectively divided into three groups: normal cycling women (group I), amenorrheic women (group II), and women with prolonged bleedings (group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean PI and RI in the spiral arteries were significantly lower in group I and group III compared with group II. Cases with amenorrhea using DMPA showed increased PI and an increase in RI in both spiral and uterine artery levels in our study. This lies in accordance with Dane et al. [16], who observed the same hemodynamic changes in amenorrheic cases using DMPA or LNG-IUS. Zalel et al. [17] conducted a study evaluating the local effects of LNG-IUS compared with the copper IUD, where 47 women carrying LNG-IUS (group A) were compared with 35 women carrying copper IUD in a control group (group B). Endometrial thickness and Doppler flow of the cervical branch of the uterine artery and spiral artery were evaluated and compared between the two groups. Doppler flow in the cervical branch of the uterine artery did not reveal any changes between the groups (RI, 0.6 ± 0.01 in both groups). Endometrial width was significantly thinner in group A (4.1 ± 0.2 mm) compared with group B (7.3 ± 0.2 mm). Subendometrial flow in the spiral artery was significantly reduced in 35 (75%) women of group A and in none of group B. In our study, we compared between groups according to duration of use of DMPA less and more than 1 year, and the results did not show any statistical significance, which was not consistent with Haberal et al. [18], who conducted a study on 48 premenopausal women in which endometrial thickness and Doppler flow of the uterine artery (RI and PI) were evaluated before and 1 year after insertion of the LNG-IUS. There was an increase in mean RI 1 year after insertion, which statistically significant (0.86 ± 0.07 vs. 0.81 ± 0.08). This conflict may be because of the small sample size in our study in comparison with their study. These hemodynamic changes correlate well with the histopathological changes in the endometrium. Runic et al. [19] demonstrated that microscopic examination of endometrial biopsies obtained by camera-guided hysteroscopy during Norplant contraception revealed that significantly larger numbers of enlarged, distended vessels were present in bleeding sites, compared with nonbleeding sites. From data obtained in our study and previous studies, Doppler velocimetry presents an important diagnostic dimension in evaluating the pathophysiologic mechanism in cases with irregular uterine bleeding using progestogen-only method. However, it is still unclear why some women experiencing amenorrhea whereas others do not while using the same progestogenic method of contraception.


  Conclusion Top


Abnormal uterine bleeding with DMPA is associated with hemodynamic changes in transvaginal Doppler in the form of increased blood flow in subendometrial and uterine vessels, so that it increase probability of trial of using of antiangiogenic drugs in treatment of abnormal uterine bleeding with DMPA.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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