Chlamydia trachomatis seroprevalence was observed in 22.0% of patients seeking infertility treatment possibly indicating the contribution of C. trachomatis to the growing burden of infertility in the United Arab Emirates.
Abstract
Purpose
This study was designed to investigate the seroepidemiology of and identify factors associated with exposure to Chlamydia trachomatis (C. trachomatis) in fertility treatment–seeking patients in Abu Dhabi Emirate, United Arab Emirates.
Methods
A total of 308 fertility treatment–seeking patients were surveyed. Seroprevalence of past (IgG positive), current/acute (IgM positive), and active infection (IgA positive) with C. trachomatis was quantified. Factors associated with exposure to C. trachomatis were identified.
Results
Overall, 19.0%, 5.2%, and 1.6% found to have past, acute/recent, and ongoing active infection with C. trachomatis, respectively. Overall, 22.0% of the patients were seropositive to any of the 3 to C. trachomatis antibodies. Male compared with female patients (45.7% vs. 18.9%, P < 0.001) and current/ex-smokers compared with nonsmokers (44.4% vs. 17.8%) had higher seropositivity. Patients with a history of pregnancy loss had higher seropositivity compared with other patients (27.0% vs. 16.8%), particularly recurrent pregnancy losses (33.3%). Current smoking (adjusted odds ratio [aOR], 3.8; 95% confidence interval, 1.32–11.04) and history of pregnancy loss (adjusted odds ratio [aOR], 3.0; 95% confidence interval, 1.5–5.8) were significantly associated with higher odds of exposure to C. trachomatis.
Conclusions
The observed high seroprevalence of C. trachomatis, particularly in patients with a history of pregnancy loss, possibly indicates the contribution of C. trachomatis to the growing burden of infertility in the United Arab Emirates.
Sexually transmitted infections (STIs) are a major global public health concern. Worldwide, more than 1 million STIs are acquired on a daily basis.1 Beside the infection itself, STIs may cause long-term reproductive and pregnancy-related complications including infertility,1 in addition to the psychological distress such as stigma and depression.2,3 Chlamydia trachomatis is the most prevalent curable STI.1 Globally, in the 30-year period from 1990 to 2019, chlamydia cases increased by 53.3%, reaching an age-standardized incident rate of 2884 per 100,000 population in 2019.4 In 2020, around 129 million cases were reported worldwide.1 Chlamydia affects both male and female individuals and is higher in some ethnicity groups than other.5 Infection can spread during any type of sexual interaction or genital contact.5 Perinatal transmission from pregnant female individuals to her child is also possible.6
The silent nature of chlamydia has a critical impact on both the prevalence and the reproductive health. Although chlamydia infection is curable,7 because of the absence of symptoms, the bacteria can persist for several weeks leading to unintentional spread of the infection causing severe complications in both sexes. In female patients, C. trachomatis can cause acute cervicitis and salpingitis.6 Infection with C. trachomatis also triggers preterm labor, low birth weight,8 ectopic pregnancy, and infertility.9 In male patients, C. trachomatis can cause nongonococcal urethritis, epididymitis, and proctitis.6
In the United Arab Emirates (UAE), the infertility rate is among the highest in the world.10 According to experts, approximately 100,446 male and female patients face infertility-related problems in the UAE.10 However, the burden of exposure to chlamydia infection among fertility treatment–seeking populations remains poorly understood. In a recent meta-analysis11 that investigated the epidemiology of C. trachomatis in different populations, including fertility clinic attendees, in the Middle East and North Africa (MENA) region, only one study from the UAE reporting C. trachomatis prevalence in female patients attending primary and secondary care was identified.12 Given this apparent dearth of evidence, studies investigating exposure to C. trachomatis in different populations are needed. This study measures the seroprevalence of past, current/acute, and active infection with C. trachomatis and identifies factors associated with seropositivity to C. trachomatis in infertility treatment–seeking patients in the Abu Dhabi Emirate, UAE.
METHODS
Study Design, Setting, and Study Population
During the period from April to May 2021, a cross-sectional survey was carried out in one of the major fertility clinics in the Abu Dhabi Emirate, UAE. Fertility treatment–seeking patients 18 years and older were consecutively invited to complete a self-administered questionnaire and to provide blood samples for serological investigation. Patients younger than 18 years, spontaneously pregnant female individuals without a clear history of infertility, and patients seeking treatments other than infertility were excluded from the study.
Data Collection
Eligible fertility treatment–seeking patients presented at the clinic were introduced to the study objectives and procedure by trained interviewers. Patients answered a validated self-administered questionnaire via Qualtrix XM online survey tool (Qualtrics, Provo, UT). The questionnaire gathered data on sociodemographic and lifestyle characteristics including age, sex, nationality, education level, marriage duration, and smoking habit. Self-reported medical history including comorbidities, history of genital infections and symptoms, and pregnancy complications were also collected. Information on height and weight, the cause of infertility, and semen analysis were retrieved from patients' medical records.
Laboratory Screening for C. trachomatis Immunoglobulins
For serological investigation, each consented participant provided 10 mL of blood collected by certified phlebotomist. Collected blood samples were centrifuged under appropriate conditions, and yielded sera were separated into coded plain tubes and stored at −20°C. Sera were screened for the detection of 3 C. trachomatis immunoglobulin (IgG, IgM, and IgA) using enzyme-linked immunosorbent assay (ELISA) kits. The ELISA kits used to detect the anti–C. trachomatis IgG and IgM are based on the detection of species-specific and sensitive immunoglobulins against a purified C. trachomatis–specific major outer-membrane protein (Euroimmune, Lübeck, Germany, catalog number EI 2191-9601 G/M, and DRG International, Springfield, NJ, for IgA). IgG antibodies are generally considered as markers for any contact with the pathogen irrespective of disease stage. Sensitivity and specificity of the ELISA kit used to screen for C. trachomatis antibodies were 100% and 97.6% for IgG and 100% and 100% for IgM, respectively. The kits have a zero cross-reactivity with a set of different pathogens such as Chlamydia pneumoniae, Mycoplasma pneumoniae, adenovirus, influenza A and B viruses, rubella, and Toxoplasma.13,14 Sensitivity and specificity of the ELISA kit used to screen for C. trachomatis IgA antibodies were 96.0% and 98.2%, respectively.15 IgM antibodies are characteristic for acute current infection, and IgA antibodies indicate ongoing active infection.16,17 Enzyme-linked immunosorbent assay tests were performed according to the manufacturer's instructions. To ensure the reliability of the results, kits were chosen for their high sensitivity and specificity with no cross-reactivity features. Positive control, negative control, and calibrators were used in every testing run. In addition, 15% of the sera samples were tested in duplicate in the same testing round.
Data Management
At the time of the survey, age was collected as a continuous variable and then categorized into 3 classes (19–30, 31–40, and 41–54 years). Similarly, body mass index (BMI) was calculated as a continuous variable using the height and weight information retrieved from medical records then rearranged into 4 categories (underweight, <18.5 kg/m2; normal, 18.5–24.9 kg/m2; overweight, 25.0–29.9 kg/m2; and obese, ≥30.0 kg/m2). All other data were recorded as categorical variables. Information on semen analysis was retrieved from medical records. Data collected from the survey and medical records were linked to the serological investigation output by unique codes. Serological tests outputs were interpreted according to the cutoff points provided by the manufacturer. The overall seroprevalence of C. trachomatis was considered as being positive to any of the 3 screened immunoglobulins (IgG, IgM, or IgA). Patients who were not tested for all 3 immunoglobulins and had no positive results in any of the tested immunoglobulins were considered not counted in estimating the overall seroprevalence of C. trachomatis.
Sample Size Calculation
Conforming to the formula “n = Z2P(1 − P)/e2” and referring to the 21.5% seroprevalence of C. trachomatis IgG antibodies reported in infertility clinic attendees in the MENA region,11 the required sample size was foreseen at 264 participants based on the Epitools online calculator. Adjusting the sample size for an anticipated 15% refusal rate, the required sample size was increased to 300 participants.
Statistical Analysis
Categorical variables were reported as frequencies and valid percentages. Continuous variables were described as means and SD. χ2 Test or Fisher exact test was used to assess the difference in the measured characteristics by seropositivity to C. trachomatis IgG, IgM, or IgA and overall seropositivity to any of these 3 immunoglobulins. Binary logistic regression analysis was used to quantify the crude association, reported odds ratio (OR), between the measured characteristics and overall seropositivity to C. trachomatis. The multivariable binary logistic regression analysis was used to correct the crude association for the variation in age, sex, nationality, smoking status, and infertility causes.
The IBM SPSS Statistics version 26.0 was used for all statistical analyses. Two-tailed P values ≤0.05 was used to define statistically significant results.
RESULTS
Description of Study Participants
Three hundred eight fertility treatment–seeking patients were surveyed (Table 1). The patients had a mean ± SD age of 36.1 ± 6.8 years and a mean BMI of 28.1 ± 5.6 kg/m2, most were female (87.7%), and 91.4% were from a Middle Eastern country. History of pregnancy loss or ectopic pregnancy was reported by 35.6% and 9.7% of the patients, respectively. Nearly two-thirds (63.2%) of the patients were classified as with secondary infertility (ever-been pregnant before).
TABLE 1.
Sociodemographic Characteristics of Fertility Treatment–Seeking Patients and Seroprevalence of the 3 (IgG, IgM, and IgA) Measured C. trachomatis (Anti-CT) Antibodies by the Measured Characteristics
| Total N = 308, n (Valid %) | Anti-CT IgG (Tested = 306), Lifetime Infection | Anti-CT IgM (Tested = 308), Acute Recent Infection | Anti-CT IgA (Tested = 304), Ongoing Active Infection | Positive to at Least 1 Antibody (Tested = 305)* |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Positive, n = 58 (19.0%) | Negative, n = 248 (81.0%) | P | Positive, n = 16 (5.2%) | Negative, n = 292 (94.8%) | P | Positive, n = 5 (1.6%) | Negative, n = 299 (98.4%) | P | Positive, n = 67 (22.0%) | Negative, n = 238 (78.0%) | P | ||
| n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | ||||||
| Age, mean ± SD, y | 36.1 ± 6.8 | 36.8 ± 7.5 | 35.9 ± 67.5 | 0.290 | 34.6 ± 7.4 | 36.1 ± 6.8 | 0.402 | 31.6 ± 4.7 | 36.1 ± 6.8 | 0.135 | 36.1 ± 7.5 | 36.0 ± 6.7 | 0.838 |
| 19–30 | 68 (22.1) | 12 (17.6) | 56 (82.4) | 0.387 | 4 (5.9) | 64 (94.1) | 0.942 | 2 (2.9) | 66 (97.1) | 0.298 | 15 (22.1) | 53 (77.9) | 0.723 |
| 31–40 | 146 (47.6) | 24 (16.7) | 120 (83.3) | 7 (4.8) | 139 (95.2) | 3 (2.1) | 140 (97.9) | 29 (20.3) | 114 (79.7) | ||||
| 41–54 | 93 (30.3) | 22 (23.7) | 71 (76.3) | 5 (5.4) | 88 (94.6) | 0 | 92 (100.0) | 23 (24.7) | 70 (75.3) | ||||
| Missing | 1 | ||||||||||||
| Sex | <0.001 | 0.123 | 0.528 | <0.001 | |||||||||
| Male | 38 (12.3) | 16 (44.4) | 20 (55.6) | 0 | 38 (100.0) | 1 (2.9) | 33 (97.1) | 16 (45.7) | 19 (54.3) | ||||
| Female | 270 (87.7) | 42 (15.6) | 228 (84.4) | 16 (5.9) | 254 (94.1) | 4 (1.5) | 266 (98.5) | 51 (18.9) | 219 (81.1) | ||||
| Nationality | 0.273 | 0.735 | 0.487 | 0.075 | |||||||||
| Middle East | 278 (91.4) | 50 (18.1) | 226 (81.9) | 15 (5.4) | 263 (94.6) | 5 (1.8) | 269 (98.2) | 58 (21.1) | 217 (78.9) | ||||
| Others | 26 (8.6) | 7 (26.9) | 19 (73.1) | 1 (3.8) | 25 (96.2) | 0 | 26 (100.0) | 8 (30.8) | 18 (69.2) | 0.075 | |||
| Africa | 7 (2.3) | 4 (57.1) | 3 (42.9) | 0.031 | 0 | 7 (100.0) | 0.819 | 0 | 7 (100.0) | 0.786 | 4 (57.1) | 3 (42.9) | |
| America, Asia, and Europe | 19 | 3 (15.8) | 16 (84.2) | 1 (5.3) | 18 (94.7) | 0 | 19 (100.0) | 4 (21.1) | 15 (78.9) | ||||
| Missing | 4 | ||||||||||||
| Education | 0.415 | 0.298 | 0.498 | 0.205 | |||||||||
| Secondary and below† | 78 (26.4) | 17 (21.8) | 61 (78.2) | 6 (7.7) | 72 (92.3) | 2 (2.6) | 76 (97.4) | 21 (26.9) | 57 (73.1) | ||||
| College level and higher | 218 (73.6) | 38 (17.6) | 178 (82.4) | 10 (4.6) | 208 (95.4) | 3 (1.4) | 211 (98.6) | 43 (20.0) | 172 (80.0) | ||||
| Missing | 12 | ||||||||||||
| BMI, mean ± SD, kg/m2 | 28.1 ± 5.6 | 28.5 ± 5.5 | 28.0 ± 5.7 | 0.404 | 28.5 ± 5.9 | 28.1 ± 5.6 | 0.639 | 31.2 ± 4.2 | 28.1 ± 5.6 | 0.139 | 28.3 ± 5.4 | 28.1 ± 5.7 | 0.546 |
| Normal | 98 (32.8) | 16 (16.3) | 82 (83.7) | 0.610 | 4 (4.1) | 94 (95.9) | 0.167 | 0 | 97 (100.0) | 0.412 | 18 (18.6) | 79 (81.4) | 0.738 |
| Overweight | 99 (33.1) | 19 (19.2) | 80 (80.8) | 5 (5.1) | 94 (94.9) | 3 (3.0) | 96 (97.0) | 23 (23.2) | 76 (76.8) | ||||
| Obese | 99 (33.1) | 22 (22.2) | 77 (77.8) | 6 (6.1) | 93 (93.9) | 2 (2.0) | 96 (98.0) | 24 (24.2) | 75 (75.8) | ||||
| Underweight | 3 (1.0) | 0 | 3 (100.0) | 1 (33.3) | 2 (66.7) | 0 | 3 | 1 (33.3) | 2 (66.7) | ||||
| Missing | 9 | ||||||||||||
| Marriage duration | 0.571 | 0.253 | 0.788 | 0.544 | |||||||||
| <1 y | 20 (6.6) | 5 (25.0) | 15 (75.0) | 2 (10.0) | 18 (90.0) | 0 | 20 (100.0) | 5 (25.0) | 15 (75.0) | ||||
| 1–5 y | 94 (30.9) | 20 (21.5) | 73 (78.5) | 7 (7.4) | 87 (92.6) | 2 (2.2) | 91 (97.8) | 24 (25.8) | 69 (74.2) | ||||
| >5 y | 190 (62.5) | 33 (17.5) | 156 (82.5) | 7 (3.7) | 183 (96.3) | 3 (1.6) | 184 (98.4) | 38 (20.2) | 150 (79.8) | ||||
| Missing | 4 | ||||||||||||
| Smoking | <0.001 | 0.518 | 0.374 | <0.001 | |||||||||
| Nonsmoker | 262 (85.3) | 39 (15.0) | 221 (85.0) | 15 (5.7) | 247 (94.3) | 4 (1.5) | 255 (98.5) | 46 (17.8) | 213 (82.2) | ||||
| Current smoker | 25 (8.1) | 11 (44.0) | 14 (56.0) | 1 (4.0) | 24 (96.0) | 0 | 25 (100.0) | 12 (48.0) | 13 (52.0) | ||||
| Ex-smoker | 20 (6.5) | 7 (35.0) | 13 (65.0) | 0 | 20 (100.0) | 1 (5.3) | 18 (94.7) | 8 (40.0) | 12 (60.0) | ||||
| Missing | 1 | ||||||||||||
*All samples screened for all the 3 types of the antibodies. Samples screened only for 1 or 2 types of the antibodies were excluded.
†Five were with no schooling.
Seroprevalence of C. trachomatis Antibodies
All participants (n = 308) were tested for IgM, 306 participants were tested for IgG, and 304 participants were tested for IgA. The calculated seroprevalence of IgG, IgM, and IgA immunoglobulins were 19.0% (past exposure), 5.2% (with acute recent infection), and 1.6% (with active ongoing infection), respectively. Sixty-seven of the 305 fertility treatment–seeking patients had experienced infection with C. trachomatis, specified by being positive to at least 1 of the 3 immunoglobulins, yielding an overall 22.0% prevalence of infection with C. trachomatis (Table 2).
TABLE 2.
Seroprevalence of the 3 (IgG, IgM, and IgA) Measured C. trachomatis Antibodies in the Screened Fertility Treatment–Seeking Patients
| Seropositive, % | |
|---|---|
| Positive to IgG (tested = 306), mean titer ± SD | 58 (19.0), 15.9 ± 26.5 RU/mL |
| Positive to IgM (tested = 308), mean titer ± SD | 16 (5.2), 0.49 ± 0.46 RU/mL |
| Positive to IgA (tested = 304), mean titer ± SD | 5 (1.6), 4.1 ± 2.2 DU/mL |
| Positive to IgG and IgM (tested = 308) | 8 (2.6) |
| Positive to IgG and IgA (tested = 306) | 4 (1.3) |
| Positive to IgM and IgA (tested = 308) | 0 |
| Positive to either IgG, IgA, or IgM (tested = 305) | 67 (22.0) |
Characteristics of the Seropositive Patients
There was no statistically significant difference in the mean age of seropositive and seronegative patients to any of the 3 screened immunoglobulins. Compared with female patients, male patients exhibited remarkably higher seropositivity to IgG (44.4% vs. 15.6%, P < 0.001), and all were seronegative to IgA (100% vs. 94.1%, P = 0.123). Overall, 45.7% of male patients compared with 18.9% of female patients had evidence of infection with C. trachomatis (P < 0.001). Duration of marriage was not different across seropositivity status of the screened immunoglobulins. Overall, seropositivity was significantly more frequent in current and ex-smokers compared with nonsmokers (44.4% vs. 17.8%, P < 0.001), particularly seropositivity to IgG (40.0% vs. 15.0%; Table 2).
Of the medical and fertility-related characteristics, only history of pregnancy loss and original cause of infertility had a significant difference in distribution across the seropositive groups. There was a significantly higher proportion of seropositive patients who reported a history of pregnancy loss (36.7%) compared with patients never experienced pregnancy loss (16.8%), particularly IgG-seropositive patients (22.6% vs. 14.7%, respectively). Less than half (48.3%) of the patients diagnosed with male-caused infertility were seropositive to C. trachomatis compared with 19.0% of the patients diagnosed with female-caused infertility (P < 0.001; Table 3).
TABLE 3.
Medical and Fertility Characteristics of the Fertility Treatment–Seeking Patients and Seroprevalence of the 3 C. trachomatis (Anti-CT) IgG, IgM, and IgA Antibodies by the Measured Characteristics
| Total = 308, n(Valid %) | Anti-CT IgG (Tested = 306), Lifetime Infection | Anti-CT IgM (Tested = 308), Acute Recent Infection | Anti-CT IgA (Tested = 304), Ongoing Active Infection | Positive to at Least 1 Antibody (Tested = 305)* |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Positive, n = 58 (19.0%) | Negative, n = 248 (81.0%) | P | Positive, n = 16 (5.2%) | Negative, n = 292 (94.8%) | P | Positive, n = 5 (1.6%) | Negative, n = 299 (98.4%) | P | Positive, n = 67 (22.0%) | Negative, n = 238 (78.0%) | P | ||
| n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | n(Valid %) | ||||||
| Chronic comorbidity | 0.625 | 0.230 | 0.431 | 0.174 | |||||||||
| No | 208 (75.1) | 40 (19.3) | 167 (80.7) | 10 (4.8) | 198 (95.2) | 3 (1.5) | 202 (98.5) | 44 (21.4) | 162 (78.6) | ||||
| At least one | 69 (24.9) | 15 (22.1) | 53 (77.9) | 6 (8.7) | 63 (91.3) | 2 (2.9) | 66 (97.1) | 20 (29.4) | 48 (70.6) | ||||
| Ever had genital infection | 0.248 | 0.556 | 0.271 | 0.411 | |||||||||
| No | 246 (80.7) | 43 (17.6) | 202 (82.4) | 12 (4.9) | 234 (95.1) | 5 (2.1) | 238 (97.9) | 51 (20.9) | 193 (79.1) | ||||
| Yes | 59 (19.3) | 14 (24.1) | 44 (75.9) | 4 (6.8) | 55 (93.2) | 0 | 58 (100.0) | 15 (25.9) | 43 (74.1) | ||||
| Missing | 3 | ||||||||||||
| Frequency of genital infection | 0.340 | 0.823 | NA | 0.562 | |||||||||
| Once | 31 (55.4) | 8 (26.7) | 22 (73.3) | 2 (6.5) | 29 (93.5) | 0 | 30 (100.0) | 8 (26.7) | 22 (73.3) | ||||
| More than once | 25 (44.6) | 4 (16.0) | 21 (84.0) | 2 (8.0) | 23 (92.0) | 0 | 25 (100.0) | 5 (20.0) | 20 (80.0) | ||||
| Missing | 3 | ||||||||||||
| Genital infection symptoms occurrence† | 0.870 | 0.447 | 0.062 | 0.851 | |||||||||
| No | 160 (59.7) | 27 (17.0) | 132 (83.0) | 7 (4.4) | 153 (95.6) | 5 (3.2) | 152 (96.8) | 31 (19.6) | 127 (80.4) | ||||
| At least one | 108 (40.3) | 19 (17.8) | 88 (82.2) | 7 (6.5) | 101 (93.5) | 0 | 107 (100.0) | 22 (20.6) | 85 (79.4) | ||||
| Missing | 40 | ||||||||||||
| History of pregnancy loss | 0.029 | 0.090 | 0.382 | 0.048 | |||||||||
| No | 192 (64.4) | 28 (14.7) | 162 (85.3) | 7 (3.6) | 185 (96.4) | 2 (1.1) | 188 (98.9) | 32 (16.8) | 158 (83.2) | ||||
| Yes, once | 53 (17.8) | 16 (30.2) | 37 (69.8) | 3 (5.7) | 50 (94.3) | 2 (3.8) | 50 (96.2) | 17 (32.1) | 36 (67.9) | ||||
| Yes, recurrent loss | 53 (17.8) | 8 (15.1) | 45 (84.9) | 6 (11.3) | 47 (88.7) | 1 (1.9) | 51 (98.1) | 12 (23.1) | 40 (76.9) | ||||
| Missing | 10 | ||||||||||||
| History of ectopic pregnancy | 0.766 | 0.080 | 0.757 | 0.637 | |||||||||
| No | 269 (90.3) | 47 (17.6) | 220 (82.4) | 13 (4.8) | 256 (95.2) | 5 (1.9) | 260 (98.1) | 54 (20.3) | 212 (79.7) | ||||
| Yes, once | 26 (8.7) | 5 (19.2) | 21 (80.8) | 2 (7.7) | 24 (92.3) | 0 | 26 (100.0) | 7 (26.9) | 19 (73.1) | ||||
| Yes, recurrent | 3 (1.0) | 1 (33.3) | 2 (66.7) | 1 (33.3) | 2 (66.7) | 0 | 3 (100.0) | 1 (33.3) | 2 (66.7) | ||||
| Missing | 10 | ||||||||||||
| Type of infertility | 0.344 | 0.259 | 0.885 | 0.098 | |||||||||
| Primary | 111 (36.8) | 24 (21.8) | 86 (78.2) | 8 (7.2) | 103 (95.8) | 2 (1.8) | 108 (98.2) | 30 (27.3) | 80 (72.7) | ||||
| Secondary | 191 (63.2) | 33 (17.4) | 157 (82.6) | 8 (4.2) | 183 (95.8) | 3 (1.6) | 185 (98.4) | 36 (19.0) | 153 (81.0) | ||||
| Missing | 6 | 1 | 5 | 0 | 6 | 0 | 6 | ||||||
| Infertility duration | 0.541 | 0.040 | 0.565 | 0.409 | |||||||||
| <3 mo | 51 (17.1) | 10 (19.6) | 41 (80.4) | 6 (11.8) | 45 (88.2) | 0 | 51 (100.0) | 12 (23.5) | 39 (76.5) | ||||
| 3–6 mo | 44 (14.8) | 11 (25.6) | 32 (74.4) | 4 (9.1) | 40 (90.9) | 1 (2.4) | 41 (97.6) | 13 (30.2) | 30 (69.8) | ||||
| 6–12 mo | 34 (11.4) | 6 (17.6) | 28 (82.4) | 0 | 34 (100.0) | 0 | 33 (100.0) | 6 (18.2) | 27 (81.8) | ||||
| >12 mo | 169 (56.7) | 27 (16.1) | 141 (84.9) | 6 (3.6) | 163 (96.4) | 4 (2.4) | 164 (97.6) | 32 (19.0) | 136 (81.0) | ||||
| ≥6 mo | 203 (68.1) | 33 (16.3) | 169 (83.7) | 0.348 | 6 (3.0) | 197 (97.0) | 0.022 | 4 (2.0) | 197 (98.0) | 0.577 | 38 (18.9) | 163 (81.1) | 0.237 |
| Missing | 10 | ||||||||||||
| Infertility causes‡ | <0.001 | 0.175 | 0.322 | <0.001 | |||||||||
| Male infertility | 31 (11.1) | 14 (48.3) | 15 (51.7) | 0 | 31 (100.0) | 1 (3.6) | 27 (96.4) | 14 (48.3) | 15 (51.7) | ||||
| Female infertility | 248 (88.9) | 38 (15.3) | 210 (84.7) | 14 (5.6) | 234 (94.4) | 3 (1.2) | 245 (98.8) | 47 (19.0) | 201 (81.0) | ||||
| Missing | 29 | ||||||||||||
| Semen analysis§ | 0.092 | NA | 0.229 | 0.152 | |||||||||
| Normal | 14 (32.6) | 3 (21.4) | 11 (78.6) | 0 | 1 (100.0) | 0 | 13 (100.0) | 4 (28.6) | 10 (71.4) | ||||
| Abnormal | 29 (67.4) | 14 (48.3) | 15 (51.7) | 0 | 9 (100.0) | 3 (7.1) | 26 (89.7) | 15 (51.7) | 14 (48.3) | ||||
*Three patients were not tested for IgA with negative or missing results for the tested IgG and IgM.
†Symptoms in the past 3 months.
‡According to International Classification of Diseases codes.
§Reported in medical records.
Factors Associated With Seropositivity to C. trachomatis
The univariate binary logistic regression models identified number of the measured characteristics that were associated with a higher likelihood of seropositivity to C. trachomatis. Male patients had 3.6 times higher odds to be seropositive to C. trachomatis compared with female patients (OR, 3.6; 95% confidence interval [CI], 1.74–7.51; P < 0.001). Patients of African nationality also exhibited a significant association with being seropositive to C. trachomatis compared with patients of Middle Eastern nationalities (OR, 5.0; 95% CI, 1.09–22.92; P = 0.039). Current (OR, 4.3; 95% CI, 1.8–9.97; P < 0.001) and ex-smoker (OR, 3.1, 95% CI 1.19–7.98; P = 0.020) patients were at higher odds to be seropositive to C. trachomatis compared with nonsmokers. Patients with history of pregnancy loss had 2.3 times higher odds of being seropositive to C. trachomatis compared with other patients (OR, 2.3; 95% CI, 1.17–4.65; P = 0.016). In patients with male-caused infertility compared with patients with female-caused infertility, the odds of testing seropositive to C. trachomatis was significantly 4 times higher (OR, 4.0; 95% CI, 1.80–8.84; P < 0.001). Controlling for the potential confounders in the multivariate binary logistic regression model, statistically significant higher odds of testing seropositive to C. trachomatis retained only for patients of African nationality (adjusted OR [aOR], 13.6; 95% CI, 1.35–137.93), current smokers (aOR, 3.8; 95% CI, 1.32–11.04), and patients with history of pregnancy loss (aOR, 3.2; 95% CI, 1.46–7.15; Table 4).
TABLE 4.
Crude and Adjusted Association Between the Measured Characteristics of Fertility Treatment–Seeking Patients With Being Seropositive to Either of the 3 (IgG, IgM, and IgA) C. trachomatis Immunoglobins
| Positive to at Least 1 Antibody (n = 305) | ||||
|---|---|---|---|---|
| OR | P | aOR | P | |
| Age, continuous, y | 1.0 (0.96–1.04) | 0.873 | 0.99 (0.95–1.04) | 0.784 |
| 19–30 | 1.00 | — | 1.00 | — |
| 31–40 | 0.9 (0.44–1.81) | 0.766 | 0.9 (0.41–2.05) | 0.825 |
| 41–54 | 1.2 (0.55–2.44) | 0.693 | 1.1 (0.47–2.49) | 0.845 |
| Sex | ||||
| Female | 1.00 | — | 1.00 | — |
| Male | 3.6 (1.74–7.51) | <0.001 | 2.10 (0.80–5.52) | 0.130 |
| Nationality | ||||
| Middle East | 1.00 | — | 1.00 | — |
| Others | 1.7 (0.69–4.02) | 0.258 | 1.9 (0.68–5.45) | 0.217 |
| Africa | 5.0 (1.09–22.92) | 0.039 | 13.6 (1.35–137.93) | 0.027 |
| America, Asia, and Europe | 1.0 (0.32–3.12) | 0.997 | 1.0 (0.27–3.66) | 0.993 |
| Education | ||||
| Secondary and below* | 1.00 | — | 1.00 | — |
| College level and higher | 0.7 (0.37–1.23) | 0.207 | 0.7 (0.37–1.42) | 0.340 |
| BMI, continuous | 1.0 (0.96–1.06) | 0.796 | 1.0 (0.95–1.06) | 0.850 |
| Normal | 1.00 | — | 1.00 | |
| Overweight | 1.2 (0.6–2.5) | 0.422 | 1.1 (0.49–2.48) | 0.819 |
| Obese | 1.5 (0.7–3.0) | 0.333 | 1.4 (0.64–3.11) | 0.388 |
| Underweight | 2.2 (0.19–25.54) | 0.530 | 2.9 (0.25–34.87) | 0.396 |
| Overweight and obese | 1.4 (0.74–2.51) | 0.314 | 1.3 (0.62–2.53) | 0.529 |
| Marriage duration | ||||
| <1 y | 1.00 | — | 1.00 | — |
| 1–5 y | 1.0 (0.34–3.18) | 0.940 | 0.6 (0.18–2.39) | 0.513 |
| >5 y | 0.8 (0.26–2.22) | 0.616 | 0.6 (0.18–2.16) | 0.452 |
| Smoking | ||||
| Nonsmoker | 1.00 | 1.00 | — | |
| Current smoker | 4.3 (1.8–9.97) | <0.001 | 3.8 (1.32–11.04) | 0.013 |
| Ex-smoker | 3.1 (1.19–7.98) | 0.020 | 2.6 (0.83–8.18) | 0.100 |
| Chronic comorbidity | ||||
| No | 1.00 | — | 1.00 | — |
| At least 1 | 1.5 (0.83–2.85) | 0.175 | 1.9 (0.96–3.84) | 0.063 |
| Ever had genital infection | ||||
| No | 1.00 | — | 1.00 | — |
| Yes | 1.32 (0.68–2.56) | 0.412 | 1.4 (0.67–3.00) | 0.359 |
| Frequency of genital infection | ||||
| Once | 1.00 | — | 1.00 | — |
| More than once | 0.5 (0.1–2.0) | 0.345 | 1.0 (0.20–4.58) | 0.960 |
| Genital infection symptoms occurrence† | ||||
| No | 1.00 | — | 1.00 | — |
| At least 1 | 0.69 (0.19–2.45) | 0.563 | 1.4 (0.70–2.83) | 0.342 |
| History of pregnancy loss | ||||
| No | 1.00 | — | 1.00 | — |
| Yes | 1.9 (1.1–3.3) | 0.030 | 3.0 (1.5–5.8) | 0.002 |
| Yes, once | 2.3 (1.17–4.65) | 0.016 | 3.2 (1.46–7.15) | 0.004 |
| Yes, recurrent loss | 1.5 (0.70–3.13) | 0.304 | 2.7 (1.13–6.27) | 0.025 |
| History of ectopic pregnancy | ||||
| No | 1.00 | — | 1.00 | — |
| Yes | 1.5 (0.6–3.7) | 0.363 | 1.4 (0.5–3.7) | 0.520 |
| Yes, once | 1.4 (0.58–3.62) | 0.430 | 1.4 (0.48–3.94) | 0.553 |
| Yes, recurrent | 2.0 (0.18–22.05) | 0.585 | 1.5 (0.10–21.29) | 0.781 |
| Type of infertility | ||||
| Primary | 1.00 | — | 1.00 | |
| Secondary | 0.6 (0.36–1.09) | 0.100 | 0.6 (0.29–1.11) | 0.096 |
| Infertility duration | ||||
| <3 mo | 1.00 | — | 1.00 | — |
| 3–6 mo | 1.4 (0.56–3.53) | 0.465 | 1.5 (0.54–4.44) | 0.416 |
| 6–12 mo | 0.7 (0.24–2.16) | 0.561 | 0.6 (0.16–2.16) | 0.422 |
| >12 mo | 0.8 (0.36–1.62) | 0.485 | 0.7 (0.29–1.74) | 0.456 |
| ≥6 mo | 0.8 (0.36–1.58) | 0.461 | 0.7 (0.29–1.64) | 0.396 |
| Infertility causes‡ | ||||
| Female infertility/other or unspecified | 1.00 | — | 1.00 | — |
| Male infertility of other or unspecified origin | 4.0 (1.80–8.84) | <0.001 | 2.1 (0.80–5.52) | 0.130 |
| Semen analysis§ | ||||
| Normal | 1.00 | — | 1.00 | — |
| Abnormal | 2.68 (0.68–10.53) | 0.158 | 1.8 (0.29–11.60) | 0.525 |
*Five were with no schooling.
†Currently or during the past 3 months.
‡According to International Classification of Diseases codes.
§Reported in medical records.
aOR indicates adjusted odds ratio for age (continuous), sex, nationality, smoking, and infertility causes.
DISCUSSION
This study investigated the burden of infection with C. trachomatis using serological assays and identified characteristics of patients who exhibited higher odds of infection with C. trachomatis among fertility treatment–seeking patients. The findings show that 1 in every 5 fertility treatment–seeking patients exhibited evidence of exposure to C. trachomatis. In the present study, the prevalence of C. trachomatis IgG (19.0%) and IgM (5.2%) antibodies is 2.8 and 2.9 times higher than the weighted prevalence estimated in general populations in the MENA region in studies that used serological assays (6.9% [95% CI, 4.3–9.4] and 1.8 [95% CI, 0.3–3.9], respectively).11 The prevalence of C. trachomatis IgG (19.0%) is comparable to that estimated in infertility clinic attendees (21.5%; 95% CI, 16.3–27.2) in the MENA region.11 Compared with antigen-based C. trachomatis prevalence, the observed 22.0% seroprevalence is 9 times higher than that reported in female patients attending primary and secondary care in UAE.12 Compared with the nucleic acid amplification test–based prevalence, the overall C. trachomatis seroprevalence (22.0%) in this study is 4.9, 5.8, and 27.5 times higher than that estimated in general populations in the region of America (4.5%), in the region of Africa (3.8%), and in the region of Southeast Asia (0.8%), respectively.18 This noticeable high burden of C. trachomatis suggests a substantial infection in this vulnerable population and adds to the totality of evidence on the potential impact of C. trachomatis on fertility.19 To improve reproductive health and avoid further transmission to general populations, risk of exposure to C. trachomatis needs to be tackled through tailored routine screening and genital infection–specific awareness programs.
In female patients, the pathological process of chlamydia-induced infertility is typically attributed to pelvic inflammatory disease.20 The literature extensively discussed the upsurged cases of tubal factor infertility after pelvic inflammatory disease caused by C. trachomatis infection.21,22 The inflammatory response causes partial or complete fallopian obstruction and possible irreversible damage, consequentially leading to ectopic pregnancy and even infertility.23 In male patients, chlamydia induces infertility through damaging sperms DNA and altering sperm quality.24 Hence, the observed elevated level of exposure to C. trachomatis in both male and female infertility patients could be an indicator for one of the preventable causes of infertility in the UAE. In the present study, infertile male patients carried 2.8 times higher burden of history of exposure to C. trachomatis than their female counterparts. This observed higher burden in infertile males is also 3.9-time higher than that reported in general population in the region of MENA.11 Furthermore, a significant 3.8 times higher odds of exposure to C. trachomatis was observed among current smokers, suggesting an increased risk of infection. It was previously concluded that active smokers and those exposed to second-hand smoke are at increased risk of bacterial infection including chlamydia and other genitally transmitted infections25 that was derived from the downgrade effect of smoking on cytokine inflammatory response.26 Smoking was linked to a more risk-taking behavior engagement and significantly increased the odds of having chlamydia among male27 and female individuals.28 Smoking is a preventable risk factor associated with increased susceptibility to infections. In a country where the infertility rate is growing and 42% of male and 9% of female individuals are smokers,29 strengthening tobacco control programs and raising public awareness about the associated risk of infertility with smoking are warranted.
In our screened fertility treatment–seeking patients with a history of pregnancy loss, the observed prevalence of C. trachomatis IgG is 80% higher than the pooled prevalence reported in female patients with miscarriage in the MENA region (12.4%).11 This variation is influenced by the fact that the pooled prevalence was based on pooling prevalence estimates extracted from different studies that implemented different serological assays with varied sensitivities and specificities to screen for IgG antibodies. Irrespective of this variation, female patients with a history of pregnancy loss carried a noticeable high burden of exposure to C. trachomatis. Although C. trachomatis was reported to be associated with miscarriage and abortion,31s there is still a contradicting evidence in the literature on the role of C. trachomatis in miscarriage.32s,33s Taking into consideration the potential risk of other associated health outcomes, acquiring other genital infections, or transmitting the infection to healthy partners, raising public awareness of the possible reproductive health risks associated with C. trachomatis infection would be of paramount consideration.
Interpreting findings from this study should be exercised in light of potentially unavoidable limitations. The cross-sectional nature of this study hinders establishing a causality pathway between examined factors and seropositivity to C. trachomatis. A single-center study limits the generalizability of the findings to the whole country, and the small sample size for some patient groups (e.g., nationality and male sex) limits the generalizability of findings to the wider specific-population groups in the country. The study also did not explore the sexual risk behavior of the patients given the sensitivity of the research topic in a country with culturally and religiously conservative norms. Self-reported information is also subjected to recall and reporting bias. However, to minimize the level of this potential bias, study population was properly introduced to the research objectives and methodology and was assured on the confidentiality of their self-reported, medical record–extracted, and serologically obtained data. The serologic assays for C. trachomatis have the potential to be limited by issues such as cross-reactivity with other Chlamydia species, as well as sensitivity and specificity concerns.34s However, these potential limitations were mitigated by using highly sensitive and specific serological assays that manufacturers claim do not cross-react with other pathogens including C. pneumoniae and M. pneumoniae.13–15 Despite these limitations, this study is the first to seroepidemiologically investigate the burden of exposure to C. trachomatis in a population group having difficulty to conceive. The study followed an established and well-implemented research methodology to provide empirical evidence using validated serological assays. The comprehensive screening for 3 C. trachomatis immunoglobulins provides estimates on the burden of chronic (IgG positive), recent acute (IgM positive), and ongoing (IgA positive) infection with C. trachomatis. In addition, the high sensitivity and specificity of the used serological assays with no reported cross-reactivity support the obtained epidemiological estimates. In a culturally diverse society with a growing rate of infertility, this study furnishes the way for more descriptive and inferential research investigating the burden of more genital pathogens in different population groups including infertile populations, as well as investigating the link between infection with genital pathogen and risk of infertility using more rigorous research methodologies. Moreover, this study provides evidence-based findings to inform public health response against C. trachomatis and its associated sequelae through designing and implementing culturally appropriate prevention strategies.
In conclusion, 1 in 5 and 1 in 20 of the fertility treatment–seeking patients exhibited evidence of infection at one time point in life and evidence of acute recent infection with C. trachomatis, respectively. This observed high prevalence in infertile patients at general and in infertile patients with pregnancy loss in particular supports the possible link between infection with C. trachomatis and unfavorable reproductive outcomes in the UAE. In the light of very limited research on genital infections leading to a neglected and poorly recognized infection and disease burden in different population groups in UAE, our findings call for more research in this context. Designing evidence-based, tailored, and culturally oriented prevention programs to tackle the risk of infection with genital pathogens and its unfavorable consequences is essential to improve reproductive health and to achieve health development goals on improving sexual and reproductive health.
Supplementary Material
Appendix
For further references, please see “Supplemental References,” http://links.lww.com/OLQ/A961.
Footnotes
Acknowledgments: The authors greatly appreciate the patients who have participated, and fertility clinics participated in this study.
Conflict of Interest and Sources of Funding: The authors report no conflicts of interest. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study was funded by the Zayed Center for Health Sciences, College of Medicine and Health Sciences, United Arab Emirates University (grant no. 31R181).
Ethics Statement: The study is ethically approved by the Abu Dhabi Health Research and Technology Committee Institutional Review Board (reference: DOH/CVDC/2020/1191) and the Fertility Clinic Research Ethics Committee (REC/2020/P13). Informed consent was obtained from all participants in this study. This study was carried out in accordance with the Declaration of Helsinki–The Code of Ethics of the World Medical Association.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (http://www.stdjournal.com).
Contributor Information
Noor Motea Abdo, Email: 201890106@uaeu.ac.ae.
Irfan Aslam, Email: irfan.aslam@hplus.ae.
Shazia Irfan, Email: shazia.irfan@hplus.ae.
Junu A. George, Email: junugeorge@uaeu.ac.ae.
Ahmed R. Alsuwaidi, Email: alsuwaidia@uaeu.ac.ae.
Luai A. Ahmed, Email: luai.ahmed@uaeu.ac.ae.
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