Study About Patients Using Copper Intrauterine Device
Study About Patients Using Copper Intrauterine Device
THE AIM OF THE this study is to assess the hemodynamic changes of uterine artery in patients
 with CIUD induced bleeding by using transvaginal color Doppler indices (uterine artery
 resistance index and pulsatility index) to prove the relationship between these changes and
 bleeding in these patient .
Intrauterine contraceptive device (IUD) is one of the most frequently used methods of birth
 control around the world. IUD induced irregular uterine bleeding is one of the main problems
 for many women using this method. In the first year of insertion of the IUDs, between 5 to
 15% of women will have their IUDs removed because of bleeding. The use of IUD has been
 unfortunately associated with functional failure on one hand, and medical complications on
 the other hand. Despite the increasing use of intrauterine device, their further
 dissemination has been limited by high expulsion rates and the withdrawal of their use for
 medical reasons, mainly bleeding and pain.

 Following insertion of modern copper IUD, menstrual blood loss increases by about 55%, and
 this level of bleeding continues for the duration of IUD use. These changes occur more
 rapidly, and iron supplementation is recommended.

 There are several possible mechanisms that explain the cause of excessive bleeding in
 patients using IUD. Several studies reported that IUD insertion increase the production of
 prostaglandins in the endometrium which cause increased vascularity, vascular permeability,
 and inhibit platelet activity and therefore increase menstrual bleeding.

 Recent studies have reported that IUD causes cyclo-oxygenase-2 (COX-2) up expression, the
 subsequent elevated prostanoid biosynthesis and signaling can promote the expression of
 pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) , basic fibroblast
 growth factor (bFGF), platelet derived growth factor (PDGF), angioprotein-1 (Ang-1) and
 angioprotein-2 (Ang-2) or down-regulate the expression of anti-angiogenic genes such as
 cathepsin-D.

 There are several mechanisms explaining the association of the pulsatility index (PI) and
 resistance index (RI) of uterine artery with menstrual blood loss. It has been suggested that
 menorrhagia, may be caused by an increased uterine secretion of prostanoids leading to
 impaired haemostasis.

 Temporary post-insertion rise in prostaglandin concentrations coincided with the phase of
 increased bleeding and pain. There is over expression of mRNA and protein of COX-2 enzyme
 leading to overproduction of prostaglandins in the endometrium after the insertion of copper
 intrauterine device (CIUD).

 Other vasoactive substances may also be involved, including nitric oxide (NO) which is a
 potent vasodilator produced the vascular endothelium. NO is present in the human endometrium
 and myometrium.

 There is evidence that NO may play a part in acute and chronic inflammation. The introduction
 of intrauterine device into the uterine cavity induces a foreign body reaction in the
 surrounding endometrium. NO is present in the foreign body inflammatory reaction around
 loosened joint replacement implants. Thus, it is possible that IUD also induces NO synthesis
 in the surrounding tissue. There is also a connection between NO synthesis and prostaglandin
 synthesis. NO directly interacts with COX, which is responsible for prostaglandin synthesis
 and causes an increase in enzymatic activity.

 There are also other possible mechanisms explaining the association of the PI of uterine
 artery with menstrual blood loss. Women with menorrhagia show a significant increase in
 endothelial cell proliferation, reflecting disturbed angiogenesis.

 It is possible that there are also other vascular abnormalities resulting from disturbed
 angiogenesis. In abnormal vessels, poor contractibility and dysfunction of the haemostatic
 system may cause menorrhagia and decreased impedance. The expression of VEGF and its
 receptor, kinase insert domain-containing receptor (KDR) and microvessel density (MVD) were
 increased in endometrium after using CIUD.

 Based on these findings, uterine artery Doppler indices RI, PI were widely investigated in
 order to identify the uterine hemodynamic changes in patients with IUD induced bleeding.

 The protocol for this study will be approved by the local ethics committee, and informed
 consent will be obtained from the patients.

 Every woman will be subjected to the following:

 -  Complete history taking including age, parity, duration of CIUD use, timing of insertion
 of CIUD, history of other contraception method before insertion of CIUD, menstrual
 history before and after CIUD insertion including duration and amount of menstrual flow,
 regularity and length of the cycle, history of any drug intake, blood disease and any
 medical disorders were considered.

 -  Clinical examination including general, abdominal, and pelvic examination.

 -  Ultrasound examination will be done .After instructing the patients to empty their
 bladders, transvaginal ultrasound will done with the woman in the supine position with
 her legs semi-flexed and abducted to allow for easy manipulation of the vaginal probe at
 different angles with the application of the push-pull technique. A coupling gel will
 applied to the vaginal probe which was then introduced into a rubber glove and another
 layer of coupling gel was applied to the glove. The probe will then introduced into the
 vagina for systematic scanning.

 Ultrasound examination will done on cycle days 2-5 unless there was continual bleeding, using
 a 7.5 MHz transvaginal transducer with color Doppler facilities . All the ultrasound
 measurements were measured between 9:00 and 11:00 am to eliminate diurnal variation.

 The uterus and the ovaries will first visualized using conventional B-mode ultrasound to
 check the uterine size, the dimensions of its walls, presence of uterine masses and the
 accurate placement of the device inside the uterus.

 Blood flow indices of the uterine artery will then calculated to obtain the pulsatility index
 (PI) and the resistance index (RI) according to the following equations: PI = (A - B)/mean,
 and RI = (A - B)/A, where A is the peak systolic, B is the end-diastolic Doppler shift, and
 the mean is the maximum Doppler shift frequency taken over the cardiac cycle. The mean PI and
 RI will calculated by combining three waveforms of the left and right uterine artery and were
 used for subsequent statistical analysis.
Inclusion Criteria:

 1. Regularly menstruating women before CIUD insertion.

 2. Age between 18 and 35 years.

 3. Hormonal treatment has not been taken at least two months before the study.

 4. Non steroidal anti-inflammatory drugs has not been taken 24 hours before the
 examination.

 Exclusion Criteria:

 1. Pregnancy.

 2. The presence of pelvic pathology as ovarian cysts, pelvic endometriosis, endometrial
 polyps or fibrosis.

 3. Present or past history of pelvic inflammatory disease.

 4. Patients on hormonal treatment in the last two months before the study.

 5. Patients on non steroidal anti-inflammatory drugs last 24 hours before the
 examination.