A Randomized Clinical Trial of Intrauterine Device MYCu
Chinese Journal of General Practitioners, November 2010, Vol. 9, No.11
A Randomized Clinical Trial of Intrauterine Device MYCu
LI Shu-zhi*, ZUO Wen-li, WU Shu-ying, WANG Yu, ZHANG Shu-lan, ZHAO Yan-hui, CUI Man-hua, LI Kai-bin, HU Jian-qiang. *Department of Obstetrics and Gynecology of Peking University First Hospital, Beijing 100034, China
Corresponding author: ZUO Wen-li, Email:wenlizuo@sina.com
[Abstract] Objective To observe safety and efficacy of intrauterine device MYCu IUD that releases indomethacin. Methods In total, 2000 women requiring IUD for contraception were chosen from domestic multiple clinical centers according to unified standard. MYCu IUD and TCu 380A IUD were randomly inserted for 1000 women each, respectively. All the women were regularly followed-up one, three, six and 12 months after insertion. Results All the women were followed-up for 11985.9 and 11753.6 person-months in MYCu IUD and TCu 380A IUD groups, respectively, with cumulative IUD application rates of 97.80% and 94.70%, and cumulative pregnancy rates with IUD of 0.10% and 0.31%, respectively. Cumulative expulsion (or partial expulsion) rate in MYCu IUD group was 0.10%, significantly lower than that in TCu 380A IUD one (1.73%), p<0.01, and cumulative removal rate due to medical reasons (bleeding or pain)was 1.51% and 2.94%, respectively, P<0.05. Rate of IUD-associated termination and overall rate of termination differed significantly between the two groups, p<0.01. Adverse reactions one, three, six and twelve months after IUD insertion included irregular bleeding, prolonged menstruation, increased menstrual blood volume and pain, less in indomethacin-containing MYCu IUD group than those in TCu 380A IUD without containing it, p<0.01. Conclusions MYCu IUD is a comparatively ideal IUD that should be promoted for extensive use, with extremely low expulsion rate, good contraceptive effect, convenience and safety in insertion and removal, and less adverse effects.
[Key words] Intrauterine devices, medicated; Intrauterine device, copper; Contrast clinical trial
Intrauterine device is a safe, effective, convenient, and reversible contraceptive device. It is the main contraceptive measure for women of child-bearing age in China [1]. V shape MCu functional IUD (MCu IUD and MCu II IUD) researched in China is designed according to the dynamic mechanism of uterus. Its support has temperature memory effect. Active substance copper on it is put in high place of uterine cavity. Clinical application shows that it has such characteristics as high contraceptive effect, low expulsion rate, low adverse effect, and high safety [2-3]. To further enhance the clinical effect and safety of MCu IUD, V shape IUD containing copper and indomethacin (MYCu IUD) researched on the basis of it has got patent and been launched into market. The result of clinical observation for 12 months is as follows.
DOI:10.3760/cma.j.issn. 1671-7368.2010.11.010
Authors’ work unit: 100034 Department of Obstetrics and Gynecology of Peking University First Hospital (Li Shuzhi, Zuo Wenli); Department of Obstetrics and Gynecology of Peking University Third Hospital (Wu Shuying); Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University (Wang Yu, Zhang Shulan); Department of Obstetrics and Gynecology of Jilin University Second Hospital (Zhao Yanhui, Cui Manhua); Department of Obstetrics and Gynecology of Sino-Japanese Friendship Hospital of Jilin University (Li Kaibin); Department of Obstetrics and Gynecology of Pudong New Area People’s Hospital (Hu Jianqiang).
Subjects and methods
I. Study subjects
All together 2000 women of child-bearing age aged from 20~40, healthy, with regular menstruation, without history of ectopic pregnancy and trophoblastic disease, live with husband, willing to use MYCuIUD or TCu380A IUD as the unique contraceptive method, followed-up in time, filled in uniformed consent form, and without contraindication in physical examination were observed from October 1 to December 31 of 2004 in different areas in China.
II. Method
Subjects were divided into 2 groups, each with 1000 cases, random sampling were carried out strictly according to random envelop. MYCu IUD was inserted in subjects of the test group. Produced by LIAONING AIMU MEDICAL SCIENCE & TECHNOLOGY CO., LTD., MYCu IUD has titanium nickel shaped memory alloy support, with copper surface area of 225m2, and containing 25 mg indomethacin. T shape IUD containing copper (TCu380A) produced by SIPING MEDICAL DEVICE FACTORY were inserted in subjects of the contrast group.
Each center accepted subjects by unified standard, filled in uniform observing table, and carried out operation by professional doctors. Followed up after 1, 3, 6, and 12 months, including side effects and its main symptoms after insertion, such as general reaction, change in menstruation and other changes. IUD’s position was confirmed by X ray, B ultra-sonic or tail observing method. Those pregnant in 2 months after 12 months and confirmed to imprenation in 12 months after insertion in analysis were recorded together.
Standard for the determination of clinical observation target and effect: mainly observe rates of pregnancy with IUD in situ, expulsion, removal due to adverse symptoms (for medical reasons) and side effects. Effect determination standard is in accordance with IUD optimal standard (apply for 1 year) of National Population and Family Planning Commission: rate of pregnancy with IUD in situ. <2/100 women, expulsion rate <4/100 women, removal rate due to adverse symptoms ≤4/100 women, total termination rate related to IUD application was ≤10/100 women[4]. Side effects occurrence rate is got by: follow-up visitors record whether subjects have chief complaint, if so, side effects was thought to happen, further understand symptoms of chief complaint, one person could have ≥2 symptoms, count by person-time of occurrence.
III Statistical method
All data were double logged in by two person employing Epidata 3.0 statistical software after inquiry and audit, and were confirmed to be without mistake after check and correction. Effect analysis adopted life table method, and statistical analysis of the result of life table employed WHO LTA 2.0 edition life table statistical software. Statistical description adopted SPSS 13.0 statistical software. Checking employed x2 or t. p<0.05 was used to indicate difference has statistical significance.
Results
I Equilibrium comparison between two groups of subjects
The difference between subjects of MYCu IUD group and TCu380A IUD group in age, history of gestation and birth, result of last pregnancy, lactation situation, menstruation parameter, with or without past medical history, gynecological history, height, weight, insertion time, uterus location, depth of uterine cavity and so on aspects had no statistical significance(p>0.05), see table 1and 2.
Table 1 General data comparison between subjects of MYCu IUD group and TCu 380A IUD group ( ±s)
Group |
case No. |
age (years) |
gravidity (times) |
parity (times) |
history of cesarean section |
height(cm) |
weight(kg) | |
|
|
|
|
|
case No. |
rate (%) |
|
|
MYCu IUD group |
1000 |
30±3 |
1.9±1.0 |
1.1±0.4 |
153 |
15.3 |
160±4 |
57±8 |
TCu380A IUD group |
1000 |
30±4 |
1.8±1.0 |
1.1±0.4 |
141 |
14.1 |
160±4 |
56±7 |
t or x2 value |
|
-0.788 |
0.796 |
1.101 |
0.574n |
|
0.683 |
1.822 |
p value |
|
0.431 |
0.426 |
0.271 |
0.449 |
|
0.494 |
0.069 |
note: MYCu IUD V shape intrauterine device containing copper and drugs; TCu380A IUD T shape intrauterine device containing copper; αx2 value
Table2 Last pregnancy result and insertion time comparison between subjects of MYCu IUD group and TCu380A IUD group
Group |
result of last pregnancy |
insertion time | ||||||||||||||
|
vaginal delivery |
cesarean section |
natural abortion |
induced abortion |
mens. interphase |
immediately after induced abortion |
suckling period |
other | ||||||||
|
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
MYCu IUD group |
504 |
50.4 |
145 |
14.5 |
6 |
0.6 |
345 |
34.5 |
835 |
83.5 |
84 |
8.4 |
68 |
6.8 |
13 |
1.3 |
TCu380A IUD group |
498 |
49.8 |
131 |
13.1 |
12 |
1.2 |
359 |
35.9 |
844 |
84.4 |
93 |
9.3 |
56 |
5.6 |
7 |
0.7 |
X2 value |
3.024 |
3.467 | ||||||||||||||
P value |
0.388 |
0.325 |
Note: MYCu IUD-V shape intrauterine device containing copper and drugs; TCu380A IUD-T shape intrauterine device releasing copper
II. Operation complication
No complication such as infection and perforation occurred in two groups of subjects at the time of IUD insertion.
III. Comparison of effect, side effects and safety between subjects in two groups after IUD insertion
1. Effect analysis between subjects in two groups inserted with IUD: full 12 months after insertion, the cumulative continuous application rates of subjects in MYCu IUD group and TCu380A IUD group were 97.80% and 94.70% respectively; cumulative rates of pregnancy with IUD in situ were 0.10% and 0.31% respectively. The difference in contraceptive effect in subjects of two groups had no statistical significance(p>0.05). All pregnant women undergone induced abortion after IUD removal. Cumulative expulsion (including partial expulsion) rates were 0.10% and 1.73% respectively. The difference between two groups had statistical significance (p<0.01). Cumulative removal rate for medical reasons [bleeding and (or) pain] of MYCu IUD group was lower than that of TCu380A IUD group, being 1.51% and 2.94% respectively. The difference had statistical significance (p<0.05). The difference in rates of termination and total termination related to IUD application between subjects in two groups had statistical significance(p<0.01). Other comparison difference had no statistical significance(p>0.05). See table 3.
Table 3 Application effect comparison between subjects in MYCu IUD and TCu380A IUD groups after inserted with IUD for 12 months
Reason for termination |
MYCu IUD group (1000 cases) |
TCu 380A IUD group (1000 cases) |
x2 value |
p value | ||||
|
case No. |
rate (%) |
SE |
case No. |
rate (%) |
SE |
|
|
pregnancy |
1 |
0.10 |
0.1011 |
3 |
0.31 |
0.1804 |
1.0449 |
〉0.05 |
pregnant with IUD in situ. |
1 |
0.10 |
0.1011 |
3 |
0.31 |
0.1804 |
1.0449 |
〉0.05 |
extopic pregnancy |
0 |
0.00 |
- |
0 |
0.00 |
- |
- |
- |
expulsion |
1 |
0.10 |
0.1005 |
17 |
1.73 |
0.4162 |
14.4663 |
﹤0.01 |
completely expulsion |
0 |
0.00 |
- |
0 |
0.00 |
- |
- |
- |
partial expulsion |
1 |
0.10 |
0.1005 |
17 |
1.73 |
0.4162 |
14.4663 |
﹤0.01 |
removal for medical reasons |
15 |
1.51 |
0.3864 |
29 |
2.94 |
0.5377 |
4.6937 |
0.030 |
uterus perforation |
0 |
0.00 |
- |
0 |
0.00 |
- |
- |
- |
bleeding and (or) pain |
15 |
1.51 |
0.3864 |
29 |
2.94 |
0.5377 |
4.6937 |
0.030 |
pain |
3 |
0.30 |
0.1742 |
6 |
0.61 |
0.2499 |
1.0452 |
〉0.05 |
bleeding |
7 |
0.71 |
0.2670 |
11 |
1.13 |
0.3382 |
0.9671 |
〉0.05 |
pain and bleeding |
5 |
0.50 |
0.2248 |
12 |
1.23 |
0.3515 |
2.9913 |
〉0.05 |
removal for pelvic inflammation |
0 |
0.00 |
- |
0 |
0.00 |
- |
- |
- |
termination related to IUD use |
17 |
1.71 |
0.4103 |
49 |
4.92 |
0.6850 |
16.0566 |
﹤0.01 |
expected pregnancy |
1 |
0.10 |
0.1014 |
0 |
0.00 |
- |
0.9797 |
〉0.05 |
lost to follow-up |
4 |
0.40 |
0.2002 |
4 |
0.40 |
0.2009 |
0.0001 |
〉0.05 |
total termination |
22 |
2.20 |
0.4639 |
53 |
5.30 |
0.7085 |
13.3125 |
﹤0.01 |
continuous application rate (%) |
|
97.80 |
|
|
94.70 |
| ||
application woman month(month) |
|
11985.9 |
|
|
11753.6 |
| ||
The number of people fulfilled interval (case) |
|
978 |
|
|
947 |
|
Note: MYCu IUD-V shape IUD containing copper and drugs; TCu380A IUD-T shape IUD containing copper; reasons for lost to follow-up are subjects can not be found; application woman month=number of woman×applied months; number of people completed interval stands for the number of people used IUD for more than a year;-no data
2. Side effects analysis between two groups of subjects after IUD insertion: side effects in subjects of MYCu IUD group and TCu380A IUD group after IUD insertion including: The occurrence rates of irregular bleeding, prolonged menstruation, increased menstrual blood volume, and pain and menorrhagia after1, 3, 6, and 12 months of MYCu IUD group were obviously lower than that of TCu380A IUD group. The difference had statistical significance (p<0.01). The leucorrhea increasing symptom of MYCu IUD group was lower than that of TCu380A IUD group in all 4 follow-ups. The difference in 1 and 3 months had no statistical significance(p>0.05), in 6 months had statistical significance(p<0.05), and in 12 months had marked statistical significance(p<0.01), see table 4.
3. Analysis of safety in 4 follow-up visits between two groups of subjects after IUD insertion: In MYCu IUD group, all together 18 IUDs were removed out. The metal friction sense between probe and IUD was clear during removal procedure. In TCu380A IUD group, all together 49 IUDs were removed out. All removals in two groups were successful. In 4 follow-up visits, there was no reported severe adverse event and recorded anemia in two groups of observing subjects.
Table 4 Side effects comparison between subjects in MYCu IUD group and TCu380A IUD group after IUD inserted for 1, 3, 6, and 12 months
Group |
follow-up time(month) |
followed-up cases |
no chief complaint |
chief complaint |
irregular uterus bleeding |
prolonged mens. and heavy mens. |
increasing leucorrhea volume |
pain or dysmenorrheal | ||||||
case No. |
rate(%) |
caseb No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) | |||
MYCu group |
1 |
994 |
685 |
68.9 |
309 |
31.1 |
42 |
4.2 |
202 |
20.3 |
102 |
10.3 |
77 |
7.7 |
TCu380Agroup |
1 |
993 |
546 |
55.0 |
447 |
45.0 |
133 |
13.4 |
326 |
32.8 |
126 |
12.7 |
172 |
17.3 |
X2value |
|
|
|
|
40.88 |
51.99 |
39.83 |
2.88 |
41.55 | |||||
P value |
|
|
|
|
0.000 |
0.000 |
0.000 |
0.090 |
0.000 |
Group |
follow-up time(month) |
followed-up cases |
no chief complaint |
chief complaint |
irregular uterus bleeding |
prolonged mens. and heavy mens. |
increasing leucorrhea volume |
pain or dysmenorrheal | ||||||
case No. |
rate(%) |
caseb No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) | |||
MYCu group |
3 |
991 |
849 |
85.7 |
142 |
14.3 |
17 |
1.7 |
124 |
12.5 |
44 |
4.4 |
30 |
3.0 |
TCu380Agroup |
3 |
983 |
660 |
67.1 |
323 |
32.9 |
85 |
8.6 |
281 |
28.6 |
63 |
6.4 |
128 |
13.0 |
X2value |
|
|
|
|
94.21 |
48.16 |
77.54 |
3.67 |
66.61 | |||||
P value |
|
|
|
|
0.000 |
0.000 |
0.000 |
0.055 |
0.000 |
Group |
follow-up time(month) |
followed-up cases |
no chief complaint |
chief complaint |
irregular uterus bleeding |
prolonged mens. and heavy mens. |
increasing leucorrhea volume |
pain or dysmenorrheal | ||||||
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) | |||
MYCu group |
6 |
982 |
911 |
92.8 |
71 |
7.2 |
9 |
0.9 |
43 |
4.4 |
23 |
2.3 |
22 |
2.2 |
TCu380Agroup |
6 |
956 |
713 |
74.6 |
243 |
25.4 |
52 |
5.4 |
169 |
17.7 |
39 |
4.1 |
92 |
9.6 |
X2value |
|
|
|
|
118.03 |
32.51 |
87.94 |
4.72 |
47.70 | |||||
P value |
|
|
|
|
0.000 |
0.000 |
0.000 |
0.030 |
0.000 |
Group |
follow-up time(month) |
followed-up cases |
no chief complaint |
chief complaint |
irregular uterus bleeding |
prolonged mens. and heavy mens. |
increasing leucorrhea volume |
pain or dysmenorrheal | ||||||
case No. |
rate(%) |
caseb No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) |
case No. |
rate(%) | |||
MYCu group |
12 |
978 |
947 |
96.8 |
31 |
3.2 |
5 |
0.5 |
15 |
1.5 |
17 |
1.7 |
12 |
1.2 |
TCu380Agroup |
12 |
947 |
877 |
92.6 |
70 |
7.4 |
37 |
3.9 |
42 |
4.4 |
45 |
4.8 |
56 |
5.9 |
X2value |
|
|
|
|
17.25 |
26.00 |
14.09 |
14.02 |
31.01 | |||||
P value |
|
|
|
|
0.000 |
0.000 |
0.000 |
0.000 |
0.000 | |||||
|
|
|
|
|
|
|
|
|
|
Note: MYCu IUD-V shape IUD containing copper and drugs; TCu 380A IUD-T shape IUD containing copper; followed-up cases=[1000-﹙lost to follow-up cases + terminated cases﹚]; the rates (%) of irregular bleeding, prolonged menstruation, menorrhagia, increased leucorrhea, pain and dysmenorrheal are the occurrence rates in all followed-up women. One people could have≥ 2 symptoms, count by person-time of occurrence.
Discussion
I MYCu IUD has good antifertility effect
MYCu IUD is copper-containing IUD. The antifertility effect of copper ions has been fully affirmed. However, “the function of copper relates to its position in uterine cavity and its exposure area. It is more effective when being inserted to a comparatively high position of uterine cavity. And the larger the surface area is, the more effective its contraceptive function will be. But increased surface area relates to high occurrence rate of side effects [5]. The copper surface area of MYCu IUD is increased to 225mm2. Copper grains are fixed and pressed to the end of the support arm, thus copper can be sent to the highest position in uterus, and a zone with high density of copper ions is formed in this area. Besides, for capillary copper sleeves are installed to its side arms, effective contraceptive substance copper can be sent to high, middle and low position of uterine cavity, thus antifertility function is better exerted. The observation shows, in random comparison between MYCu IUD with comparatively small copper surface area and TCu 380A IUD with comparatively large copper surface area and has internationally-recognized good contraceptive effect, cumulative pregnancy rates with IUD in situation are 0.10% and 0.31% respectively, the difference has no statistical significance, and contraceptive effects of both two groups are the same. The copper surface area of MYCu IUD is at comparatively low level in all IUDs containing copper, so it has slight stimulation to endometrium and slight side effects.
II. MYCu IUD has low expulsion rate
For several years, MCu IUD has good clinical effect, especially with low expulsion rate. Ni Fengxian [6] and so on people reported the expulsion rate observed in 550 cases with MCu IUD inserted for 48 months from 6 clinical units in 5 provinces was 0.42% when employing random, multi-center contrast prospective study method. Zhang Lei and so on people [7] made a systematic evaluation by evidence-based medicine method and considered the comprehensive clinical effect of MCu IUD is superior to that of TCu220C, and its expulsion rate was lower than that of TCu380A. MYCu IUD retains the basic design concept of MCu IUD. It is made by memory alloy according to the shape and dynamic mechanism of uterus, and assumes completely open V shape. Copper grains are fixed and pressed on the end of two arcuate arms. For memory alloy has memory function, it can keep the designed shape under human body temperature, contract and expand as the womb does, not easy to deform, shift, expulse, and has such characteristics as ultra-elasticity, anti-fatigue, corrosion-resistance, and good tissue compatibility. The cumulative expulsion rate of MYCu IUD at 1 year time is 0.10%.
III. MYCu IUD has low side effects occurrence rate
25g indomethacin is installed on side arms of MYCu IUD as carrier [8]. Since 1980s, people in China has researched IUD releasing indomethacin and proved that indomethacin can inhibit the synthesis of prostaglandin and decrease side effects caused by IUD [9-10]. This study observes that in follow-up visits at 1, 3, 6 and months after insertion, the occurrence rates of irregular bleeding, prolonged menstruation, increasing menstrual blood volume, pain and cumulative rate of removal for medical reasons (bleeding or pain) of MYCu IUD containing indomethacin are lower than that of TCu 380A IUD which doesn’t containing it, p<0.01 and p<0.05 respectively, the difference has statistical significance. These prove that MYCu IUD releasing indomethacin can obviously decrease normal side effects such as bleeding and pain during early insertion, and decrease cumulative rate of removal due to bleeding or pain. Besides, for MYCu IUD is without tail, it can prevent psychological displeasure caused by tail and discomfort during sexual life arousing from foreign body sensation.
IV. Indication of MYCu IUD
For MYCu IUD has good contraceptive effect and special “V” shape, it is broadly used in clinic application. It meets the needs of many women of child-bearing age who require inserting IUD for contraception. Those women who can not insert IUD for uterus bicornis, frequent expulsion with other type of IUDs, got pregnant for IUD displacement may try MYCu IUD. It is usually inserted during menstruation period. Insert immediately after induced abortion and during lactation period has the same good effect.
V. The insertion and removal of MYCu IUD
MYCu IUD is inserted by withdrawal method, which is easy, convenient, and safe. Removal hook which is easy to operate can be used at removal. But MYCu IUD is a kind of open IUD, must be operated according to instruction for use. Slowly expand the MYCu IUD of the right size and insert it to a position in uterine cavity which near uterus bottom. For subjects with overbending uterus, special care should be taken. Violent operation is prohibited. And to avoid embedment or displacement, IUD should not be inserted in the middle section of uterus.
This study observes for 1 year and finds MYCu IUD group has good clinical effect, but follow-up visit to subjects should be further strengthened to get long term application data. Comparison between MYCu IUD containing indomethacin and MCu IUD doesn’t containing it should be carried out to verify that MYCu IUD can decrease normal side effects of bleeding and pain during early insertion.
MYCu IUD group has low rate of pregnancy with IUD in situation, extremely low expulsion rate, and can obviously decrease side effects of bleeding and pain during early insertion. Moreover, it is safe and easy to insert and remove, so it is a comparatively ideal IUD deserving promotion.
Reference
[1] Le Jie. Obsterics and Gynecology, the 6th edition. Beijing: People's Medical Publishing House, 2004:387.
[2] Ni Fengxian, Tian Jing, Li Jun and so on people. “Clinical Report of Inserting 1050 New-type MCu Functional IUDs for 24 Months”. Journal of Practical Obstetrics and Gynecology, 2003, 19:343-344.
[3] Ni Fengxian, Wu Xiaofeng, Sun Chengcheng and so on people. “Clinical Effect Observation of AiMu New-type MCu II Functional IUD”. Chinese Journal of Family Planning, 2007, 15 Supplement: 27-28.
[4] National Population and Family Planning Commission. NPFPC issued 199821 Notify with regard to “Optimal Standard of IUD Containing Copper” and “Guideline for IUD Clinical Study”. Beijing: National Population and Family Planning Commission, 1998.
[5] Han Xiangyang. Journal of Practical Family Planning. Harbin: Heilongjiang Science and Technology Publishing House. 1999:371-378.
[6] Ni Fengxian, Lv Linlin, Wu Shaolian and so on. “Multi-center Comparative Study of MCu IUD and TCu380A IUD”. Chinese Journal of Family Planning, 2005, 13:609-611.
[7] Zhang Lei, He Yang, Mao Yanyan and so on people. “Systematic Evaluation of Comparison among MCu 110, TCu 220C and TCu380A IUD”. Chinese Journal of Family Planning, 2009, 17:262-266.
[8]Yang Bangyuan, Zhuang Liuqi, and Yuan Huiliang. “Comparative Study among r Shape IUDs Containing Indomethacin of Different Doses”. Reproduction & Contraception, 1995, 15:300-305.
[9] Zhuang Liuqi. “Study of IUD Containing Drugs”. Journal of Practical Obstetrics and Gynecology, 2003, 19:324-326.
[10] Liu Changguan, Li Shuxiang, Liu Xiaoai and so on people. “Study on the Major Pharmacological Effects of IUD Releasing Indomethacin”. Reproduction & Contraception, 2000, 20:165-171.
(Received date: 2010-02-21)