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Screening for Chlamydia trachomatis in the Lower Genital Tract of Infertile Women

การตรวจคัดกรองการติดเชื้อ Chlamydia trachomatis ในอวัยวะสืบพันธ์ส่วนล่างของสตรีที่มีบุตรยาก

Kanok Seejorn (กนก สีจร) 1, Chumnan Kietpeerkool (ชำนาญ เกียรติพีรกุล) 2, Pilaiwan Kleebkaow (พิไลวรรณ กลีบแก้ว) 3, Chamsai Pientong (แจ่มใส เพียรทอง) 4, Thawalwong Ratanasiri (ถวัลย์วงค์ รัตนสิริ) 5, Ratana Kumwilaisak (รัตนา คำวิลัยศักดิ์) 6, Tipaya Ekalaksananan (ทิพยา เอกลักษณานันท์) 7




วัตถุประสงค์: เพื่อหาอุบัติการของการติดเชื้อ Chlamydia trachomatis ในอวัยวะสืบพันธุ์ส่วนล่างของสตรีที่มีบุตรยาก และรวบรวมข้อมูลทางลักษณะประชากรและการเจริญพันธุ์ของสตรีที่มีบุตรยากในโรงพยาบาลศรีนครินทร์ มหาวิทยาลัยขอนแก่น
ชนิดของการวิจัย:  การวิจัยเชิงพรรณนา
สถานที่ที่ทำวิจัย: ห้องตรวจคู่สมรสมีบุตรยาก แผนกผู้ป่วยนอก โรงพยาบาลศรีนครินทร์ คณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่น
กลุ่มตัวอย่าง:  สตรีที่มารับบริการตรวจรักษาที่ห้องตรวจผู้มีบุตรยากในระหว่างวันที่ 1 มิถุนายน พ.ศ. 2544 ถึงวันที่ 1 มิถุนายน พ.ศ. 2545
วิธีดำเนินการวิจัย: รวบรวมข้อมูลจากสตรีที่เข้าร่วมโครงการจำนวน 70 ราย ทำการส่งตรวจหาเชื้อ Chlamydia trachomatis ในมูกบริเวณปากมดลูก ในการมารับการตรวจรักษาครั้งแรก ด้วยวิธี PCR และ GENPROBE และบันทึกข้อมูลทางด้านลักษณะประชากรและการเจริญพันธุ์ ในแบบบันทึกห้องตรวจผู้มีบุตรยาก
ตัววัดที่สำคัญ:  อุบัติการการติดเชื้อ Chlamydia trachomatis ในอวัยวะสืบพันธุ์ส่วนล่าง ของสตรีที่มีบุตรยากในโรงพยาบาลศรีนครินทร์
ผลการวิจัย:  อุบัติการการติดเชื้อ Chlamydia trachomatis ในอวัยวะสืบพันธุ์ส่วนล่างคิดเป็นร้อยละ 1.43 หรือพบ 1 รายในสตรีที่มีบุตรยากที่ทำการศึกษาทั้งหมด 70 ราย อายุเฉลี่ยของประชากรเท่ากับ 29.6 ปี ส่วนใหญ่เป็นสตรีที่มีบุตรยากชนิดปฐมภูมิร้อยละ 81.4 ระยะเวลาเฉลี่ยของการมีบุตรยาก 4.6 ปี มีสตรีที่มีบุตรยากร้อยละ 28.6 เคยคุมกำเนิดมาก่อน โดยวิธีที่ที่พบมากที่สุดคือการใช้ยาเม็ดคุมกำเนิดชนิดฮอร์โมนรวม คิดเป็นร้อยละ 85 ของประชากรที่มีการคุมกำเนิดมาก่อน
สรุปการวิจัย: สตรีที่มารับการตรวจรักษาภาวะที่มีบุตรยากที่โรงพยาบาลศรีนครินทร์ มีการติดเชื้อ Chlamydia trachomatis ในอวัยวะสืบพันธุ์ส่วนล่าง คิดเป็นร้อยละ 1.43
คำสำคัญ:  การติดเชื้อ Chlamydia trachomatis ในอวัยวะสืบพันธ์ส่วนล่างและสตรีที่มีบุตรยาก

Objective:  To determine the prevalence of chlamydial infection in the lower genital tract, patient demographics and reproductive health, among infertile women being treated at Srinagarind Hospital, Khon Kaen University, Thailand.
Design:  Descriptive study
Setting:  Infertility Clinic, Department of Obstetrics and Gynecology, Srinagarind Hospital, Khon Kaen University, Thailand.
Subjects:  Infertile women attending the Clinic between June 2000 and June 2001.
Methods:  Screening for Chlamydial trachomatis was initiated at Srinagarind Hospital's Infertility Clinic in June 2000.  Specimens were taken by endocervical swabs at the first visit from 70 consecutive patients for PCR and GENPROBE testing.
Demographic and reproductive health data were recorded.
Outcome measurement:  The prevalence of chlamydial infection in the lower genital tract in infertile women being treated at the Hospital.
Results:  The overall chlamydial infection rate was 1.43% (0.04-7.70 95% CI). The average of studied women was 29.6 years.  The proportion of primary and secondary infertility was 81.4 and 18.6 %, respectively.  The average length of infertility was 4.6 years.  Only 28.6% of the consecutive women had previously used contraception of which 85% was a combined contraceptive tablets.
Conclusion:  The prevalence of chlamydial infection in the lower genital tract of infertile women at Srinagarind Hospital was 1.43%. 

Keywords:  Chlamydial infection; Infertile women

Introduction
Chlamydia trachomatis infection of the genitalia is a sexually transmitted disease.  Complications such as pelvic inflammatory disease1-2, infertility due to abnormal fallopian tube abnormalities 3, 4 and ectopic pregnancy 5 are suggestive of chlamydial infection.  A British study documented that about ?50 million was spent in treating these complications of Chlamydia infection6 .

.
In 1996, the British Royal College of Obstetricians and Gynecologists advised that non-pregnant women under 35 planning to use intrauterine instruments should be pre-screened for chlamydial infection.  If such screenings were not available, the women should receive prophylactic antibiotics7 .
In 1998, a group of research doctors for chlamydial infection in Britain advised screening for couples under treatment for infertility8.
In 1999, a study showed that infertile women with antibodies for Chlamydia trachomatis (IgG) and being treated with gamete intrafallopian transfer (GIFT) had an increased risk of embryo implantation failure9.
The guidelines for the management of infertility indicate that women seeking infertility treatment need to be assessed for tubal and uterine factors by hysterosalpingography or hysteroscopy.  If there is a history of a previous chlamydial infection, there is an increased risk of spreading the organism to the upper genital tract with sequelae including abnormal pelvic anatomy and decreased fertility.
We devised our study to determine the prevalence of chlamydial infection in the lower genital tract, patient demographics and reproductive health, among infertile women being treated at Srinagarind Hospital, Khon Kaen University, Thailand.


Materials and method
 Screening for Chlamydia trachomatis was conducted at Srinagarind Hospital's Infertility Clinic between June 1, 2000 and June 2001.  The Ethics Committee of the Faculty of Medicine, Khon Kaen University, approved the study protocols and candidates consented before joining the study.  We excluded women with bloody contamination and/or previous antibiotic treatment not more than 4 weeks prior examination. 
Endocervical swabs were performed at the first visit of 70 consecutive women and these were tested using polymerase chain reaction (PCR) and GENPROBE.  The participants also received appropriate management of their infertility problem.  The demographic and reproductive health data were recorded and analyzed using STATA Version 6.
Results
The study included 70 consecutive infertile women, averaging 29.6 years of age.  Only one woman (1.43%; 95% CI, 0.04-7.70) tested positive (by PCR though negative by GENPROBE) for chlamydial infection (Table 1).

Table 1.  Age of infertile patients with the results of PCR and GENPROBE screening for chlamydial infection

Age (yr.)

GENPROBE

PCR

Number of positive test

Number of positive test

   20 – 25

0

0

> 25 – 30

0

0

> 30 – 35

0

1

> 35

0

0

       Most of our patients worked in agriculture or were employee (34.3%), had an income between 60,000 and 90,000 Baht per year per family (44.3%), and had a Bachelor degree (44.3%) (Table 2).

Table 2.  Demographics and reproductive health of infertile women

 Data

Number

Percent

Age

 

 

Between 20 and 25 years

15

21.4

Between 25 and 30 years

24

34.3

Between 30 and 35 years

24

34.3

> 35 year

7

10.0

   Summary

70

100.0

Career

 

 

Agriculture

24

34.3

Employee

24

34.3

Government officer

8

11.4

Trader

7

10.0

State enterprise officer

4

5.7

House wife

3

4.3

Summary

70

100.0

Income per year per family (Baht)

 

 

Between 10,000 and 30,000

10

14.3

Between 30,000 and 60,000

14

20.0

Between 60,000 and 90,000

31

44.3

> 90,000

15

21.4

   Summary

70

100.0

Home town

 

 

Northeast

66

94.3

Other region

4

5.7

Summary

70

100.0

Education level

 

 

Primary education or equivalent

7

10.0

Secondary education or equivalent

14

20.0

High school or equivalent

15

21.4

Bachelor degree

31

44.3

Higher than Bachelor degree

3

4.3

   Summary

70

100.0

 

The data collection regarding contraception indicated the absence of any method among 71.4% of respondents.  Those using contraception took oral combined contraceptive tablets for periods of 6 months or less (65%).  Primary infertility accounted for 88.6% of cases and had lasted between 4 and 6 years (Table 3).

Table 3.  Reproductive health data

Data

Number

Percent

Method of contraception

 

 

No previous contraception

50

71.4

Oral combined pill

17

24.4

Condom

2

2.4

DMPA

1

1.4

   Summary

70

100.0

Duration of contraception

 

 

Between 1 and 6 months

13

65.0

Between 6 and 12 months

5

25.0

> 12 months

2

10.0

   Summary

20

100.0

Type of infertility

 

 

Primary

62

88.6

Secondary

8

11.4

   Summary

70

100.0

Duration of infertility

 

 

Between 1 and 2 years

22

31.4

Between 2 and 3 years

17

24.3

Between 3 and 4 years

6

8.6

Between 4 and 5 years

1

1.4

> 5 years

24

34.3

   Summary

70

100.0

Discussion
The prevalence of chlamydial infections in the lower genital tract of infertile women in Europe, the United States10,11,12 ,13  and Asia14,15,16 (Table 4) are well documented.  In Europe and the United States, the prevalence of chlamydial infections stand between 1 and 5 while it is between 10 and 28 percent in China and Israel.  This disparity is possibly due the greater level of development, education and income in the former countries over the latter. 
Interestingly, the overall chlamydial infection in our study subjects was only 1.43%. However, many of the subjects were well educated with an above average income, so they could afford the cost for transportation and treatment at a tertiary (as opposed to a rural primary) hospital.  These factors seem to have limited the prevalence of chlamydial infection.

Table 4.  Literature review on the prevalence of Chlamydia trachomatis of the lower genitalia in infertile women

Reference

Year

Location

Cases

Age

Test

Prevalence

Gump et al.

1982

USA

203

20 – 39

culture

0

Moller et al.

1984

Denmark

116

20 – 39

culture

3.4

Anestad et al.

1987

Norway

105

24 – 41

culture

1.0

Samra et al.

1994

Israel

135

19 – 41

culture

10.4

Aspock et al.

1995

Germany

100

20 – 40

PCR

5.0

Lu et al.

1997

China

147

22 – 40

PCR

22.45

Yu et al.

1998

China

262

20 – 45

culture

28.64

We used two laboratory methods to assess each specimen:  1) PCR as performed in the Department of Microbiology, Faculty of Medicine, Khon Kaen University; and, 2) GENPROBE (for confirmation) at the Microbiology Lab, Venereal Disease Center, Khon Kaen.  The GENPROBE is the standard method of this center and the technicians are highly experienced.  The results demonstrated that the PCR method was more sensitive than the GENPROBE test17,18.
Our observations corroborate previous studies, wherein a decrease in infection by Chlamydia trachomatis was associated with better education on safe sex and sexually transmitted diseases.  This knowledge should be made more available to people of lower socioeconomic status who have the greater risk for chlamydial infection.  Should prevention be successful, the community's health would be improved and national resources be conserved.
The limitation to our study was the decreased prevalence compared with other studies of a similar sample size.  The results reveal a widening of the 95% confidence interval, thereby decreasing the reliability of the study.  Our study population had a higher education and income than the general Thai population.  A follow-on study should compare the characteristics of the population and the cost effectiveness of the screening procedure and develop appropriate standard methods.


Conclusion
Our study was prospective and all of the data collected and the method statistically appropriate.  The prevalence of chlamydial infection in the lower genital tract of infertile women being treated at Srinagarind Hospital was 1.43%. 
Acknowledgments
 The authors thank Mr. Bryan Roderick Hamman for assistance with the English-language presentation of the manuscript.

References
1. Cates JR, Wasserheit JN. Genital chlamydial infection: epidermiology and reproductive sequelae. Am J Obstet Gynecol 1991; 164: 1771-81.
2. Paavonen J. Genital Chlamydia trachomatis infections in the female. J Infert 1992; 25 : 35-45.
3. Svensson L, Mardh PA, Westrom L. Infertility after acute salpingitis with special reference to Chlamydia trachomatis. Fertil Steril 1983; 40: 322-9.
4. Shibahara H, Takamizawa S, Hirano Y, Ayustawati, Takei Y, Fujiwara H. et al. Relationships between Chlamydia trachomatis antibody titers and tubal pathology assessed using transvaginal hydrolaparoscopy in infertile women. Am J Reprod Immunol 2003 Jul; 50: 7-12.
5. Coste J, Lauman B, Bremond A. Sexually transmitted disease as major cause of ectopic pregnancy: results from a large case control study in France. Fertil Steril 1994; 62: 289-95.
6. Tayler-Robinson D. Chlamydia trachomatis and sexually transmitted disease. Br Med J 1996; 308: 150-1.
7. Templeton A. The Prevention of Pelvic infection. RCOG Press 1996, London, UK, 3-278.
8. Expert Advisory Group Chlamydia trachomatis - Summary and Conclusion of CMO's Expert Advisory Group 1998. Department of Health, London, UK, 1-22.
9. Sharara FI, Queenan JT. Elevated serum Chlamydia trachomatis IgG antibodies associated with decreased implantation rate in GIFT. J Reprod Med 1999; 44: 581-6.
10. Gump DW, Gibson M, Ashikara T. Evidence of prior pelvic inflammatory disease and its relationship to  Chlamydia trachomatis. Am J Steril 1983; 146: 153-9.
11. Moller BR, Allen J, Toft B. Pelvic inflammatory disease after hysterosalpingography associated with Chlamydia trachomatis. Br J Obstet Gynaecol 1984; 91: 1181-7.
12. Anestad G, Lunde O, Moen M. Infertility and Chlamydial infection. Fertil Steril 1987; 48: 787-90.
13. Aspock C, Bettelhiem D, Fischl F. Infection with Chlamydia trachomatis in patients of an ambulatory infertility clinic. Eur J Epidermiol 1995; 107: 423-6.
14. Samra Z, Soffer Y. Prevalence of genital Chlamydia infection in couples attending a male infertility clinic. Eur J Epidermiol 1994; 33: 487-92.
15. Lu J, Liang Z. The relationship between female infertility and genital inflammation of Chlamydia trachomatis. Hua Hsi I Ko Ta Hsueh Hsueh Pao 1997; 28: 297-9.
16. Yu P, Zhang L, Dai H. Research in the relationship between Chlamydia trachomatis and infertility. Hunan I Ko Ta Hsueh Hsueh Pao 1998; 23: 67-9 (Abstract).
17. Black CM. Current methods of laboratory diagnosis of Chlamydia trachomatis infection. Clin Microbiol Rev 1997; 10: 160-84.
18. Skulnick M, Chua R, Simor AE. Use of Polymerase Chain Reaction for the detection of Chlamydia trachomatis from endocervical and urine specimens in an asymptomatic low prevalence population of women. Diagn Microbiol Infert Dis 1994; 20: 195-201.

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