Chlamydia infection, PID and infertility: additional evidence from a case-control study in China | BMC Women’s Health


Study population

This was a 1:2 matched case-control study to explore the effects of chlamydia infection and PID on infertility. Women between the ages of 18 and 44 were considered for the study if they sought health care between January 1, 2019 and October 30, 2019, in outpatient care settings, including clinics or health centers. auxiliary reproduction, in five cities (Guangzhou, Zhanjiang, Shenzhen, Dongguan, Yunfu) of Guangdong province, China [12].

Infertility was defined as the inability to conceive after 12 months or more of regular unprotected intercourse [1]. All cases involved in our study underwent professional diagnostic workup, and if patients self-reported infertility, they would receive laparoscopy and hysterosalpinography for further verification. And according to the American Society for Reproductive Medicine, we have further classified infertility into several subtypes, including tubal disorders, endocrine disorders, cervical/uterine/peritoneal factors, immune factors, sexual factors and other or unknown. [13]. Participants were excluded if they met any of the following conditions: (1) male factor-induced infertility and (2) had used antibiotics in the vagina within two weeks.

We performed a 1:2 matched case-control study with two control groups: pregnant controls and non-pregnant controls. For each case of infertility observed, two control women were matched by age (± 3 years). For pregnant controls, we included documented pregnant women in selected hospitals in the study cities. As non-pregnant controls, we selected those who sought health care other than infertility at obstetrics/gynecology clinics, family planning clinics, dermatology and STD department, or urology for the first time in the past year, and reported having had sex before and willing to be tested for chlamydia. The indications for exclusion were the same as those for the cases. Finally, we included 255 infertile women, 510 pregnant women (control 1) and 510 non-pregnant women (control 2) in this study. Information on baseline characteristics, including sociodemographic characteristics, reproductive history, smoking and alcohol consumption, disease history, and sexually transmitted infections (STIs), was collected through online questionnaires (Fig. 1).

Fig. 1

The study was approved by the Southern Medical University Dermatology Hospital Institutional Review Board. All participants gave their informed consent in writing.

Sample Collection and Nucleic Acid Amplification Testing

The first sample of urine samples was collected from all participants. At least an hour interval before the last urination was necessary. Self-cleaning of the voiding site was not allowed. After collection, transfer to cobas®PCR MEDIA tubes and mix upside down five times. Then store the sample at 2–8°C. Cobas® 4800 (Cobas® 48000 CT/NG Amplification/Detection Kit, Shanghai, China) was used to process urine specimens for the diagnosis of chlamydia trachomatis.

According to the Health Industry Standard of the People’s Republic of China (WS/T 513-2016), women with a positive NAAT result but without any associated symptoms such as odynuria, frequent and/or urgent urination, hypogastralgia , lumbago, abnormal vaginal bleeding, and/or discharge, would be diagnosed as asymptomatic chlamydia infection. And those with a positive NAAT result and associated symptoms would be considered symptomatic chlamydia.

Sample size calculation

In this 1:2 matched case-control study, we assumed that the prevalence of chlamydia infection in women was 4.7%. [14]the odds ratio of infertility to Chlamydia is 1.91 [15], α = 0.05, β = 0.2. Finally, a sample of 239 infertile cases was obtained, and the controls were supposed to be 478 per group.

For PID, approximately 4.4% of sexually active women have been diagnosed with PID in their lifetime [16]and self-reported PID was associated with a four times higher risk of infertility [6]. Then, a sample of 36 infertile cases with 72 matched non-infertile controls can reach a power of 81% under α = 0.05.

Overall, at least 239 infertile cases with 478 matched non-infertile controls were needed.

statistical analyzes

We used the chi-square test to assess baseline characteristics between non-pregnant/pregnant women and infertile women. Associations between chlamydia infection, including NAAT-verified infection and self-reported previous infection, and IDP with infertility in women were investigated by conditional logistic regression, calculating odds ratios (ORs) with their corresponding 95% confidence intervals (CI), adjusting for maternal age, BMI, monthly income, chronic diseases and other genital tract infections, which have been suggested as risk factors infertility potentials by published study [8]. Additionally, prior chlamydial infection was added to adjust for the association between PID and infertility.

We performed several sensitivity analyses. First, we compared different effects on primary infertility and secondary infertility. The former refers to women who have never been pregnant before, while the latter is referred to the inability to repeat conception after a previous pregnancy. [2]. Then, considering that some of the infertility subtypes should probably not be associated with chlamydia infection or PID, we retained only cases of infertility induced by tubal disorders and excluded those related to sexual factors. and/or cervical/uterine/vaginal.

Data analyzes were performed using Stata 14 software (StataCorp LLC, Texas). Statistical significance was considered twice P value


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