The association of Chlamydia trachomatis infection in infertile women with the occurence of tubal occlusion detected with HSG Hubungan antara Infeksi Chlamydia trachomatis dengan oklusi tuba yang dideteksi dengan HSG pada wanita infertil Reynanta, Binarwan Halim, M Fidel Ganis Siregar Deparment of Obstetrics and Gynecology Medical Faculty of North Sumatera University – Haji Adam Malik Central General Hospital / Halim Fertility Centre Medan
Abstract Objective: to assess the association between the C trachomatis infection with the tubal occlusion among the infertile woman and to investigate the proportion of Chlamaydia trachomatis with tubal occlusion in infertile women and the proportion of Chlamaydia trachomatis with normal tube. Material and methods: The comparation analytic study with cross sectional method was conducted during March 2010 until January 2011. Consecutive method was used tocollect the sample from any reproductive age of infertile woman who presented to the gynecology clinic at RSU H Adam Malik, RSU Putri Hijau, RSU Sundari and Halim Fertility centre Medan. Women of reproductive age refers to all women aged 15-49 years. Infertility is defined as ≥ 1 year of unprotected intercourse without pregnancy. The inclusion criteria : infertile women in reproductive age, no surgical history of ectopic tubal pregnacy, appendix, pelvic or tube. Exclusion criteria : The patient with uterin myoma , endometriosis cyst, abnormal uterus. This research had get approval from the Health Research Ethical Committee of North Sumatera. Tubal patency of the woman was determined with HSG. Patients were devided into two groups, normal tube and tubal occlusion. Laboratory test for serum IgG antibody to C trachomatis were done with ELISA method at Laboratory Thamrin Medan. Serum IgG positive(+) indicating chlamydia’s infection. Statistical analysis with Chi-Square test with CI 95% or (p<0.05) and OR evaluation. Results :Statistically, Chlamydia trachomatic antibody were significantly higher in the group of tubal occlusion than those women with normal tube. There was significant association statistically between the C trachomatis infection and tubal occlusion among the infertile women (p<0.05).The proportion of Chlamydia infections from patients with tubal occlusion were 11 of 29 (0.38) that more common than Chlamydia infection in the group of normal tube, 2 out of 29 (0.07).The infertile woman with positive serologic test IgG anti C trachomatis lead to the occurence of tubal occlusion, that were 11/13 cases (85%) while the infertile women with negative result of serologic test, most of them would not lead to the occurence of tubal occlusion, that were 27/45 cases (60%). The Odd Ratio (OR)value was 8.25. OR value > 1 indicated that C trachomatis infection can be used as a predictor for tubal abnormality. Conclusion: There was significant association statistically between the C trachomatis infection and tubal occlusion among the infertile women (p<0.05).The risk of 8.25 times for C trachomatis infection higher than those without infection.Chlamydia serology is an inexpensive and non invasive test, as a screening test before using HSG for the likelihood of tubal occlusion in infertile woman and may facilitate decisions on which women should proceed with further investigations without delay. Keywords: Infertile woman, HSG, tubal occlusion, IgG anti Chlamydia trachomatis.
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Abstrak Tujuan :Melihat apakah ada hubungan infeksi Chlamydia trachomatis pada wanita infertil dengan terjadinya oklusi tuba. Melihat proporsi chlamydia trachomatis pada wanita infertil dengan oklusi tuba dan proporsi chlamydia trachomatis pada wanita infertil dengan tuba normal. Bahan dan cara kerja :Penelitian studi analitik komparatif, potong lintangdilaksanakan sejak Maret 2010 sampai dengan Januari 2011. Pengambilan sampel secara konsekutif dengan subjek penelitian wanita usia reproduksi infertil, yang berobat ke RSUP H Adam Malik, RSU Haji, RSU Putri Hijau, RSU Sundari dan Klinik Halim Fertility Centre, Medan. Wanita usia reproduksi adalah wanita pada umur 15-49 tahun. Infertil adalah wanita yang dalam satu tahun atau lebih telah melakukan hubungan seksual tanpa alat pelindung namun tidak mendapat kehamilan. Kriteria inklusi: wanita infertil dalam masa usia reproduksi, tidak ada riwayat operasi kehamilan ekstra tuba, appendix, pelvis atau tuba. Kriteria eksklusi : Pasien dengan mioma uteri, kista endometriosis, kelainan uterus. Penelitian telah mendapat persetujuan dari Komite etik penelitian kesehatan Sumatera Utara.Pemeriksaan histerosalpingografi dilakukan untuk melihat keadaan tuba pada sampel penelitian dan dibagi atas kelompok tuba normal dan tidak normal.Pemeriksaan laboratorium dilakukan pada kedua kelompok dengan memeriksa antibodi dalam serum IgG anti Chlamydia trachomatis antibody secara ELISA, di laboratorium klinik Thamrin Medan.IgG(+) menunjukkan adanya infeksi C trachomatis. Analisa statistik memakai Chi-Square dengan tingkat kepercayaan 95% dan batas kemaknaan dengan p< 0,05 serta penentuan rasio Odds. Hasil :Secara statistik, antibodi chlamydia trachomatis lebih tinggi secara signifikan pada grup dengan oklusi tuba dibandingkan dengan tuba normal. Didapati hubungan bermakna antara infeksi Chlamydia trachomatis dengan terjadinya oklusi tuba (p<0,05).Proporsi infeksi Chlamydia trachomatis pada kelompok oklusi tuba adalah 11/29 (0,38) dibanding pada kelompok tuba normal 2/29 (0,07). Wanita infertil dengan serologi IgG positif umumnya mengalami oklusi tuba (85%), sebaliknya wanita infertil dengan serologi IgG negative sebagian besar tidak mengalami oklusi tuba (60%). OR= 8,25. Dengan nilai OR>1, maka infeksi C.Trachomatis dapat dijadikan sebagai predictor untuk menilai oklusi tuba. Kesimpulan :Didapati hubungan bermakna antara infeksi Chlamydia trachomatis dengan terjadinya oklusi tuba (p<0,05).Resiko seorang ibu yang menderita infeksi Chlamydia trachomatis untuk mengalami oklusi tuba adalah 8,25 kali lebih besar dibandingkan dengan ibu yang tidak terinfeksi Chlamydia trachomatis. Pemeriksaan serologi chlamydia trachomatis tidak mahal dan tes yang tidak invasif, sebagai tes skrining sebelum pemeriksaan HSG untuk melihat oklusi tuba pada wanita infertil untuk mendukung tindakan selanjutnya.
Kata kunci :wanita infertil, hsg, oklusi tuba, IgG anti chlamydia trachomatis,
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Introduction Infertility is a major problem, that influences 1 of 10 couples. Infertility affects about 10% to 15% of reproductiveage couples in the United States. Despite an increased awareness of available therapies, only 43% of infertile couples seek treatment, and only 24% seek specialized care.In the general population, conception is expected to occurin 84% of women within 12 months and in 92% within 24months (te velde et al. 2000).Data from population-basedstudies suggest that 10–15% of couples in the westernworld experience infertility (templeton et al. 1990; evers,2003). Half of them (8%) will subsequently conceive withoutthe need for specialist advice and treatment. Of theremaining 8% who require input from fertility clinics, half(4%) comprise couples with primary infertility (no historyof a previous pregnancy) while the other half have secondaryinfertility (difficulties in conceiving after an initialpregnancy). 1-3 Women of reproductive age refers to all women aged 15-49 years. Infertility is defined as 1 year of unprotected intercourse without pregnancy. This condition may be further classified as primary infertility, in which no previous pregnacies have occured, and secondary infertility, in which a prior pregnancy, although not necessarily a live birth has occured. The main causes of infertility include male factor, decreased ovarian reserve, ovulatory disorders, tubal injury , uterine factors, cervical and immunologic factors and unexplained factors. Chlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide, especially among young adults. Chlamydia infections remain often underdiagnosed, as they are asymptomatic in the majority of patients. Undiagnosed and untreated chlamydia infections can ascend to the upper genital tract, where they colonize the endometrial mucosa and the fallopian tubes, leading to pelvic inflammatory disease (PID). Chlamydial PID can cause tubal occlusion and subsequent infertility. However, most women who have tubal infertility have never been diagnosed with C.trachomatis PID because their infections have been asymptomatic or subclinical. The United States Centres for Disease Control and Prevention recommend annual screening of all sexually active women aged 25 or less, as is screening of older women with risk factors (for example, those who have a new sexual partner or multiple sex partners). 4-24 Chlamydia trachomatis is a small Gram-negative bacterium that is an obligate Intracellular parasite. Seroepidemiological studies have indicated that chlamydia infections account for a large proportion of asymptomatic genital tract infections by demonstrating a strong link between tubal abnormality and the presence of chlamydia antibodies. Thus, Chlamydia IgG antibodies are associated with the development of late sequelae and are markers for previous exposure or endogenous reactivation of a
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previous chlamydia infection. In chronically infected patients negative for endocervical c.trachomatis, a positive serological test may be the only indication of chlamydia involvement. 25-36 The assessment on the tubal occlusion to the infertile woman can be implemented by any method such
as
HSG,
Hysterosalpingocontrastsonography(HyCoSy)
or
laparoscopic
examination.
Laparoscopy with tubal patency testing remains the most accurate method of diagnosing tuboperitoneal pathology. Laparoscopy is an expensive method and invasive to the patient.HSG is used for screening purposes. Patients tend to experience this procedure as a painful and annoying test. Furthermore, HSG has an infection-risk of 1-3 %. The Chlamydia trachomatis antibody test (CAT), on the other hand, is a simple blood test,quick, suitable for screening, sensitivity is 91.1%, specificity 98.5%, minimum invasive and and causes little inconvenience for patients. We investigated the value of the C trachomatis test in screening for tubal factor infertility.37-52 In the study, we evaluated whether prior exposure to c.trachomatis, as determined by IgG chlamydia antibody, was associated with tubal infertility. This study aimed to assessed the association of c.trachomatis infection with tubal occlusion, and to assessed the proportion of Chlamydia trachomatis infection in infertile woman among tubal occlusion compared with infertile woman with normal tube.
Materials and methods This study is a comparison analytic study conducted at Adam Malik hospital, Haji hospital, Putri Hijau hospital, Sundari hospital and Halim fertility centre Medan during March 2010 until January 2011. This research had get approval from the Health Research Ethical Committee of North Sumatera. Consecutive method was used for collecting sample. This study is a comparison analytic study between infertile case with tubal occlusion and normal tube to the infection of Chlamaydia trachomatis, by the cross sectional study approach. In this study the infertile women’s age range from 20 to 49 years. The informed consent was performed as a protocol. The patient give a written permit.Patient with infertility problem who undertake the infertility treatment as a subject of this research.The inclusion criteria : reproductive age of infertile woman with menstrual cycle (not amenore) for one year that do sexual activity without having the protection of birth control method, no surgical history of ectopic tubal pregnacy, appendix, pelvic or tube. The patient with uterinfibroid, endometriosis cyst, abnormal uterus were not involved in this research. Tubal occlusion of the infertile woman were determined with HSG. Patients were devided into two groups, i.e. tubal occlusion and normal tube. After the examination of HSG, blood test were done. The venous blood sample, 3 ml wasobtained from the patient and sent to the laboratory service for assay. In the
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laboratory, the specific serum antibody was assessed to the Chlamydia trachomatis by Enzyme Linked Immunosorbent Assay (ELISA),and then the sample
is classified into 2 group, i.e.
seropositive group of Chalmydia trachomatis and group of seronegative Chlamydia trachomatis. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) software version 17.0 for Windows. Association between the C trachomatis infection with tubal occlusion among the infertile women were made by using the chi-square test. A p value of less than 0.05 was considered statistically significant.
Results Table 1. Baseline Characteristic Characteristic
Tubal occlusion Positive (%) Negative (%)
Total
Serology Ctrachomatis. IgG (+) (%) IgG (-) (%) Total
Age (years) 20 – 24
2 (6,89)
4 (13,79)
6
1(0,07)
5(0,11)
6
25 – 29
12 (41,37)
10 (34,48)
22
6(0,46)
16(0,35)
22
30 – 34
4 (13,79)
9 (31,03)
13
1(0,07)
12(0,27)
13
35 – 39
7 (24,13)
4 (13,79)
11
4(0,31)
7(0,16)
11
40 – 44
3 (10,34)
2 (6,89)
5
1(0,07)
4(0,09)
5
45 – 49
1 (3,44)
0 (0)
1
0(0)
1(0,02)
1
Total
29(100)
29(100)
58
13(100)
45(100)
58
Type of Infertility Primary
15 (51,72)
15 (51,72)
30
6(0,46)
24(0,53)
30
Secondary
14 (48,28)
14 (48,28)
28
7(0,54)
21(0,47)
28
Total
29(100)
29(100)
58
13(100)
45(100)
58
Duration of infertility (month) 12-36
12 (41,37)
14 (48,28)
26
6(0,46)
20(0,44)
26
37-60
8 (27,58)
7 (24,13)
15
4(0,31)
11(0,24)
15
61-72
1 (3,44)
4 (13,79)
5
1(0,07)
4(0,09)
5
73-84
0 (0)
1 (3,44)
1
0(0)
1(0,02)
1
85-96
2 (6,89)
0 (0)
2
0(0)
2 (0,04)
2
97-108
0 (0)
1 (3,44)
1
0(0)
1(0,02)
1
109-120
2 (6,89)
2 (6,89)
4
0(0)
4(0,09)
4
4 (13,79)
0 (0)
4
2(0,15)
2 (0,04)
4
29(100)
29(100)
58
13(100)
45(100)
58
≥ 121 Total
A total 58 infertile women who underwent HSG investigation for infertility were identified. The women’s age ranged from 20 to 49 years. The number of cases with tubal occlusion (positive) was found more common in the group of age 25 – 29 yearsold, that was 12of 29 and the number of cases with normal tube (negative) was more common in the group of age 25 – 29 years old that was 10 of
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29.The chlamydia antibody were more common found in women aged 25-29 years in this study. In the group of age 25 – 29 years, 4 of 12 tubal occlusion cases, were positive serologic test, mean while 2 of 10 cases with normal tube were positive serologic test. In the group of primary infertile women, 6 of 15 tubal occlusion were positive serologic test for C trachomatis, meanwhile there was no serologic positive from normal tube cases.
In the group of
secondary infertile women 5 of 14 tubal occlusion cases were positive serologic test, meanwhile 2 of 14 normal tube were positive serologic test. From the duration of infertility, the chlamydia antibody were more common found in 12 – 36 months in this study. In the group of 12 to 36 months 4 of 12 tubal occlusion were positive serologic test, meanwhile 2 of 14 normal tube were positive serologic test.
Table.2.The comparison of Chlamydia trachomatis infectionamong patients with tubal occlusion and normal tube. Research group Serologic test C. Trachomatis Total
IgG Positive Ig G Negative
Tubal occlusion Positive Negative N N 11 a 2 b 18 c 27 d 29 29
Total N 13 45 58
P 0.012 X2=8,031
Our study showed that the proportion of serologic test for Chlamydia trachomatis infection among the group of tubal occlusion were 11/29 (0.38) compared with the group of normal tube were 2/29 (0.07). The table showed the infertile woman with positive serologic test IgG anti C trachomatis lead to the occurence of tubal occlusion, that were 11/13 cases (85%) while the infertile women with negative result of serologic test, most of them would not lead to the occurence of tubal occlusion, that were 27/45 cases (60%). Statistically, Chlamydia trachomatic antibody were significantly higher in the group of tubal occlusion than those women with normal tube. There was significant association statistically between the C trachomatis infection and tubal occlusion among the infertile women (p<0.05). The Odd Ratio (OR)value was 8.25. It means that a risk for a woman withthe infection of Chlamydia trachomatis to the occurence of tubal occlusion was 8.25 times higher than women without the infection. OR value > 1 indicated that C trachomatis infection can be used as a predictor for tubal occlusion.
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Discussion The chlamydia antibody were more common found in women aged 25-29 years in this study. The studies was similar to studies performed in Women’s Hospital in Iran. No significant correlation was found between the participants’ age and the results of Chlamydia test in health care centers in Iran. The prevalence was slightly higher in patients within the age group 25-29 (17,68%) than in the age group 20-24 (15,24%). 53,54,55,56,57 In this study, the chlamydia antibody were more common found in those women who had conceived previously as compared with primary infertile women. Women with primary infertility had a statistically insignificant reduction in prevalence of antibody to chlamydia compared with women who had secondary infertility in the Reproductive Medicine Clinic in Bristol, UK, the infertility clinic in Iran, gynaecology clinic in Gambia. Secondary infertility may be a sequela of postpartum sepsis, which is commonly observed at hospitals and clinics in the Gambia and which, given the association between cervical chamydial infection and endometritis, may be due in part to chlamydiae.
53,58,61
From the duration of infertility, the chlamydia antibody were more common found in 12 – 36 months in this study. The studies was similar to studies performed in The Netherlands. There was not a significant relation between the Chlamydia antibody and duration of infertility in infertility clinic in Iran.53,60 The infection of Chlamydia trachomatic were significantly higher in the group of tubal occlusion than those women with normal tube in this study. The results indicate that infertil Gambian woman with tubal occlusion have a higher prevalence and higher levels of circulating IgG antibody against C. Trachomatis than controls and that these differences are statistically highly significant. Tubal occlusion was associated with chlamydia trachomatis antibody, which is in agreement with Tiitinen et al (2006) that C.trachomatis-specific IgG antibodies were found more frequently (43,2 versus 13,5%), and the antibody levels were higher in the tubal factor infertility cases than in the controls (p<0,001). The studies was similar to studies performed in Bristol, UK, clinic specialized in Brazil, infertility clinic in Cairo University and clinic in The Netherlands.58,59, 61,62, 63, 64 The limitation in this study concerns its inability to distinguish between various micro-organisms other than C.trachomatis, for example : N. gonore, haemophilusinfluenzae, grup A streptococci, poneumococci,all of which are causes of tubal infertility. Chlamydia serology is an inexpensive and non invasive test, as a screening test before using HSG for the likelihood of tubal occlusion in infertile woman and may facilitate decisions on which women should proceed with further investigations without delay.
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Pendahuluan Infertilitas merupakan suatu masalah umum, mempengaruhi sekitar 1 dari 10 pasangan. Infertilitas mempengaruhi sekitar 10% sampai 15% dari pasangan usia reproduktif di Amerika Serikat. Walaupun terdapat peningkatan pengetahuan mengenai infertilitas, hanya 43% pasangan infertil mencari terapi, dan hanya 24% yang mencari terapi spesialistik. te Velde et al. (2000)dari kepustakaan 3, mendapatkan, pada populasi umum, konsepsi diperkirakan terjadi pada 84% wanita dalam 12 bulan dan pada 92% dalam 24 bulan. Templeton et al. 1990; Evers (2003)
dari kepustakaan 3
mendapatkan data
dari studi berbasis-populasi menunjukkan bahwa 10-15% pasangan di Barat mengalami infertilitas. Setengah di antaranya (8%) selanjutnya akan mencapai konsepsi tanpa membutuhkan nasehat dan pengobatan spesialis. Dari 8% lainnya yang membutuhkan penanganan dari klinik fertilitas, setengahnya (4%) terdiri dari pasangan dengan infertilitas primer (tidak ada riwayat kehamilan sebelumnya) sementara setengah lainnya mengalami infertilitas sekunder (kesulitan dalam mencapai konsepsi setelah kehamilan awal).1-3 Wanita usia reproduktif mengacu pada semua wanita usia 15–49tahun. Infertilitas secara umum didefenisikan sebagai tidak terjadinya kehamilan dalam setahun hubungan seksual tanpa proteksi. Infertilitas diklasifikasikan menjadi infertilitas primer (tidak pernah hamil) dan infertilitas sekunder (pernah hamil, walau kehamilan tidak harus dengan kelahiran hidup).1, 21 Faktor penyebab infertilitas dapat digolongkan menjadi : Faktor pria, Penurunan cadangan ovari, gangguan ovulasi (faktor ovulasi), faktor tuba, Faktor servikal, Faktor uterus, Kondisi seperti
penyimpangan imunologis, Faktor yang tak dapat dijelaskan. Chlamydia trachomatis adalah bakteri transmisi seksual yang paling umum dijumpai diseluruh dunia, khususnya orang dewasa muda. Infeksi chlamydia sering tidak terdiagnosis, sebagaimana asimptomatik pada kebanyakan pasien. Sekali bakteri pathogen seperti chlamydia trachomatis memasuki serviks dan infeksi tidak ditangani, dapat menyebar ke uterus dan tuba fallopii dan akan menyebabkan penyakit radang panggul. PID Chlamydia dapat menyebabkan oklusi tuba dan menyebabkan infertilitas. Bagaimanapun, kebanyakan wanita yang mempunyai infertilitas tuba jarang terdiagnosa PID C.trachomatis karena infeksinya asimptomatik atau subclinical. Pusat Pengendalian dan Pencegahan Penyakit merekomendasikan screening gadis remaja yang aktif secara seksual pada pemeriksaan ginekologik tahunan rutin usia 25 atau lebih muda, atau yang lebih tua dengan faktor resiko (untuk contoh, yang mempunyai pasangan seksual baru atau banyak mitra seksual). 4-24 Chlamydia adalah mikroorganisma intrasel parasit yang mempunyai dinding sel yang serupa dengan dinding sel bakteri gram-negatip. Studi seroepidemiologi menunjukkan bahwa infeksi Chlamydia meliputi populasi yang besar dalam infeksi saluran kelamin asimptomatik dengan ditunjukkannya
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hubungan yang kuat antara tuba yang abnormal dan keberadaan antibodi Chlamydia. Oleh karena itu, antibodi Chlamydia IgG dihubungkan dengan sekuel dan marker untuk keterpaparan sebelumnya atau reaktivasi endogen dari infeksi Chlamydia sebelumnya. Pada pasien infeksi kronik yang negatif untuk c.trachomatis endocervik, test serologi positif boleh menjadi satu-satunya indikasi keterlibatan chlamydia. 25-36 Mengevaluasi patensi tuba pada wanita infertil diterapkan melalui metode pemeriksaan HSG, Hysterosalpingocontrastsonography(HyCoSy) dan laparoskopi. Laparoskopi dengan tes patensi tuba metode yang paling akurat untuk diagnosis patologi tuboperitoneal. Laparoskopi adalah metode yang invasif dan mahal untuk pasien. HSG digunakan untuk tujuan penyaringan. Pasien cenderung mengalami nyeri dan tidak mengenakkan pada prosedur tes ini. Lagipula, HSG mempunyai risiko infeksi 1-3%. Tes antibodi Chlamydia trachomatis, disisi lain, adalah sebuah tes darah sederhana, cepat, cocok untuk skrining, sensitivitas 91,1%, spesifisitas 98,5%, minimal invasif, dan menyebabkan sedikit tidak menyenangkan untuk pasien. Kita menyelidiki nilai tes chlamydia trachomatis dalam skrining untuk infertilitas faktor tuba. 37-52 Pada studi ini, kita mengevaluasi apakah keterpaparan Chlamydia trachomatis, sebagaimana ditentukan dengan antibodi IgG Chlamydia, dihubungkan dengan infertilitas tuba. Studi ini bertujuan untuk menilai hubungan infeksi C.trachomatis dengan tuba yang abnormal(oklusi), dan untuk menilai proporsi infeksi chlamydia trachomatis pada wanita infertil dengan tuba abnormal(oklusi) dibandingkan dengan wanita infertil tuba normal.
Bahan dan metode Studi ini merupakan studi analitik komparatif yang dilaksanakan pada RS Adam Malik, RS Haji, RS Putri Hijau, RS Sundari dan Halim Fertility Center Medan selama Maret 2010 sampai Januari 2011. Penelitian ini mendapatkan persetujuan dari Health Research Ethical Committee Sumatera Utara. Metode Consecutive digunakan dalam pengambilan sampel. Studi ini membandingkan wanita infertil antara kasus infertil dengan tuba abnormal(oklusi) dan tuba normal dihubungkan dengan infeksi Chlamydia trachomatis, dengan cara studi cross sectional. Pada studi ini usia wanita infertil 20-49 tahun. Inform konsen dilakukan sebagai protokol. Pasien menandatangani surat izin penelitian. Pasien dengan masalah infertil yang ingin berobat masalah infertil dimasukkan sebagai subjek penelitian. Kriteria inklusi : wanita usia reproduksi infertil yang tidak amenore untuk setahun hubungan seksual tanpa proteksi dari metode pembatasan kelahiran, tidak ada riwayat operasi kehamilan ektopik, apendik, pelvis atau tuba. Pasien dengan mioma uteri, kista endometriosis, uterus abnormal tidak dimasukkan dalam penelitian ini. Tuba yang oklusi dari wanita infertil diperiksa
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dengan HSG. Pasien dibagi menjadi dua grup; tuba oklusi dan tuba normal. Setelah pemeriksaan HSG, tes darah dilakukan. Sampel darah vena, 3 ml diperoleh dari pasien dan dikirim ke laboratorium untuk diperiksa. Serum antibodi spesifik Chlamydia trachomatis oleh Enzyme Linked Immunosorbent Assay (ELISA), dan kemudian sampel diklasifikasi dalam 2 grup, seropositif Chlamydia trachomatis dan seronegatif Chlamydia trachomatis. Analisa statistik menggunakan SPSS versi 17 Windows. Hubungan antara infeksi C.trachomatis dengan oklusi tuba pada wanita infertil dengan menggunakan tes chi-square. Nilai p < 0,05 dianggap signifikan secara statistik.
Hasil Tabel 1. Karakteristik Peserta Penelitian Oklusi tuba
Serologi Chlamydia trachomatis
Karakteristik Positif (%)
Negatif (%)
Total
IgG Positif (%)
IgG Negatif (%)
Total
Usia : 20 - 24 tahun
2 (6,89)
4 (13,79)
6
1(0,07)
5(0,11)
6
25 - 29 tahun
12 (41,37)
10 (34,48)
22
6(0,46)
16(0,35)
22
30 - 34 tahun
4 (13,79)
9 (31,03)
13
1(0,07)
12(0,27)
13
35-39 tahun
7 (24,13)
4 (13,79)
11
4(0,31)
7(0,16)
11
40-44 tahun
3 (10,34)
2 (6,89)
5
1(0,07)
4(0,09)
5
45-49 tahun
1 (3,44)
0 (0)
1
0(0)
1(0,02)
1
Total
29(100)
29(100)
58
13(100)
45(100)
58
Primer
15 (51,72)
15 (51,72)
30
6(0,46)
24(0,53)
30
Sekunder
14 (48,28)
14 (48,28)
28
7(0,54)
21(0,47)
28
29(100)
29(100)
58
13(100)
45(100)
58
12 – 36
12 (41,37)
14 (48,28)
26
6(0,46)
20(0,44)
26
37 – 60
8 (27,58)
7 (24,13)
15
4(0,31)
11(0,24)
15
61 – 72
1 (3,44)
4 (13,79)
5
1(0,07)
4(0,09)
5
73 – 84
0 (0)
1 (3,44)
1
0(0)
1(0,02)
1
85 – 96
2 (6,89)
0 (0)
2
0(0)
2 (0,04)
2
97 – 108
0 (0)
1 (3,44)
1
0(0)
1(0,02)
1
109 – 120
2 (6,89)
2 (6,89)
4
0(0)
4(0,09)
4
≥ 121
4 (13,79)
0 (0)
4
2(0,15)
2 (0,04)
4
Total
29(100)
29(100)
58
13(100)
45(100)
58
Tipe Infertilitas :
Total Lama Infertilitas (bulan) :
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58 wanita infertil yang dilakukan HSG untuk infertilitas diidentifikasi. Wanita berusia 20-49 tahun. Jumlah oklusi tuba lebih banyak ditemukan pada usia 25-29 tahun, dimana 12 dari 29 kasus dan jumlah tuba normal lebih banyak dijumpai pada usia 25-29 tahun, dimana 10 dari 29 kasus. Antibodi Chlamydia dijumpai lebih banyak pada wanita usia 25-29 tahun. Pada grup usia 25-29 tahun, 4 dari 12 kasus oklusi tuba, ditemukan positif tes serologi, sementara 2 dari 10 kasus dengan tuba normal ditemukan positif tes serologi. Pada grup infertil primer, 6 dari 15 oklusi tuba ditemukan positif tes Chlamydia trachomatis, sementara tidak ada serologi positif dari tuba normal. Pada grup dengan infertil sekunder, 5 dari 14 tuba yang oklusi ditemukan positif tes serologi, sementara 2 dari 14 tuba normal ditemukan positif tes serologi. Dari durasi infertil, antibodi chlamydia ditemukan lebih banyak pada lama infertil 12-36 bulan pada studi ini. Pada grup lama infertil 12-36 bulan, 4 dari 12 oklusi tuba ditemukan positif tes serologi, sementara 2 dari 14 tuba normal ditemukan positif tes serologi Chlamydia.
Tabel 2. Hubungan Infeksi Chlamydia trachomatis dengan Oklusi Tuba dan tuba normal Oklusi Tuba Total Positif Negatif P Kelompok Penelitian N N N Serologi Chlamydia trachomatis
Ig G Positif
11
a
2
b
13
Ig G Negatif
18
c
27
d
45
Total
29
29
58
0.012 X2= 8,031
Dari tabel diatas juga dapat dihitung bahwa proporsi infeksi Chlamydia trachomatis pada oklusi tuba dalam penelitian ini adalah 11/29 (38%) lebih tinggi dari proporsi infeksi Chlamydia trachomatis pada tuba normal yaitu 2/29 (7%). Dari tabel diatas dapat diketahui bahwa wanita infertil dengan serologi IgG positif umumnya mengalami oklusi tuba, dengan didapati 11/13 (85%), sebaliknya wanita infertil dengan serologi IgG negative sebagian besar tidak mengalami oklusi tuba, 27/45 (60%). Dari uji statistic, antibodi Chlamydia dengan signifikan lebih tinggi pada grup yang oklusi tuba dibandingkan dengan tuba normal. Adanya hubungan yang bermakna secara antara infeksi Chlamydia trachomatis dengan terjadinya oklusi tuba pada wanita infertil (p<0,05). Didapatkan nilai OR adalah 8,25. Hal ini berarti resiko seorang ibu yang menderita infeksi Chlamydia trachomatis untuk mengalami oklusi tuba adalah 8,25 kali lebih besar dibandingkan
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dengan ibu yang tidak terinfeksi Chlamydia trachomatis. Dengan nilai OR>1, maka infeksi C.Trachomatis dapat dijadikan sebagai predictor untuk menilai kelainan tuba.
Diskusi Antibodi Chlamydia ditemukan lebih banyak pada usia 25-29 tahun pada penelitian ini. Penelitian ini serupa dengan penelitian yang dilaksanakan di Women’s Hospital di Iran. Tidak ada hubungan signifikan ditemukan antara usia dan hasil tes Chlamydia pada Health Care Centers di Iran. Prevalensi
ditemukan
lebih
tinggi
pada
usia
25-29(17,68%)
daripada
grup
usia
20-
24(15,24%).53,54,55,56,57 Pada studi ini, antibodi chlamydia ditemukan lebih banyak pada wanita yang pernah hamil dibandingkan dengan wanita infertil primer. Wanita dengan infertil primer secara signifikan berkurang dalam prevalensi antibodi Chlamydia dibandingkan dengan wanita dengan infertil sekunder pada Reproductive Medicine Clinic in Bristol,UK, Klinik Infertilitas di Iran, Klinik Ginekologi di Gambia. Infertil sekunder boleh disebabkan sekuel sepsis post partum, yang mana umum dijumpai pada Rumah Sakit dan Klinik di Gambia dan yang mana, memberikan hubungan antara infeksi Chlamydia cervix dan endometritis, merupakan bagian dari Chlamydia. 53,58,61 Dari durasi infertil, antibodi Chlamydia ditemukan lebih banyak pada 12-36 bulan pada penelitian ini. Penelitian ini serupa dengan penelitian di Belanda. Tidak ada hubungan signifikan diantara antibodi Chlamydia dengan lamanya infertil pada Klinik Infertil di Iran. 53,60 Infeksi Chlamydia trachomatis ditemukan lebih tinggi pada grup dengan oklusi tuba dibandingkan wanita dengan tuba normal pada penelitian ini. Hasil menunjukkan bahwa wanita infertil di Gambia dengan oklusi tuba lebih tinggi prevalensinya dan level lebih tinggi sirkulasi antibodi IgG terhadap Chlamydia trachomatis dibandingkan dengan kontrol dan perbedaan ini lebih tinggi signifikan secara statistik. Hubungan tuba oklusi dengan antibodi Chlamydia trachomatis, sesuai dengan Tiitinen dkk(2006) bahwa antibodi IgG spesifik Chlamydia trachomatis lebih banyak ditemukan(43,2 versus 13,5%), dan level antibodi lebih tinggi pada oklusi tuba dibandingkan kontrol (p<0,001). Ini sesuai dengan studi yang dilaksanakan di Bristol, UK, klinik spesialis di Brazil, Klinik Infertil di Universitas Kairo dan klinik di Belanda. 58,59, 61,62, 63, 64 Keterbatasan dalam penelitian ini adalah tidak dilakukannya pemeriksaan kemungkinan infeksi lain selain infeksi chlamydia trachomatis untuk contoh : N.gonore Haemophilus influenzae, group A streptococci, and pneumococci dapat menyebabkan oklusi tuba.
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Tes Serologi Chlamydia tidak mahal dan tidak invasif, sebagai skrining sebelum menggunakan HSG untuk kemungkinan oklusi tuba pada wanita infertil dan bisa memudahkan keputusan untuk pemeriksaan selanjutnya pada wanita dengan segera.
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