case study 68 pelvic inflammatory disease

AMY CURRY, MD, TRACY WILLIAMS, MD, AND MELISSA L. PENNY, DO

Am Fam Physician. 2019;100(6):357-364

Patient information: See related handout on pelvic inflammatory disease .

Author disclosure: No relevant financial affiliations.

Pelvic inflammatory disease (PID) is an infection of the upper genital tract occurring predominantly in sexually active young women. Chlamydia trachomatis and Neisseria gonorrhoeae are common causes; however, other cervical, enteric, bacterial vaginosis–associated, and respiratory pathogens, including Mycobacterium tuberculosis , may be involved. PID can be acute, chronic, or subclinical and is often underdiagnosed. Untreated PID can lead to chronic pelvic pain, infertility, ectopic pregnancy, and intra-abdominal infections. The diagnosis is made primarily on clinical suspicion, and empiric treatment is recommended in sexually active young women or women at risk for sexually transmitted infections who have unexplained lower abdominal or pelvic pain and cervical motion, uterine, or adnexal tenderness on examination. Mild to moderate disease can be treated in an outpatient setting with a single intramuscular injection of a recommended cephalosporin followed by oral doxycycline for 14 days. Additionally, metronidazole is recommended for 14 days in the setting of bacterial vaginosis, trichomoniasis, or recent uterine instrumentation. Hospitalization for parenteral antibiotics is recommended in patients who are pregnant or severely ill, in whom outpatient treatment has failed, those with tubo-ovarian abscess, or if surgical emergencies cannot be excluded. Treatment does not change in patients with intrauterine devices or those with HIV. Sex partner treatment is recommended; expedited partner treatment is recommended where legal. Prevention of PID includes screening for C. trachomatis and N. gonorrhoeae in all women younger than 25 years and those who are at risk or pregnant, plus intensive behavioral counseling for all adolescents and adults at increased risk of sexually transmitted infections.

Pelvic inflammatory disease (PID) includes an array of infectious processes that damage the endometrium, fallopian tubes, ovaries, and pelvic peritoneum. Sexually transmitted infections (STIs) cause most PID cases, but organisms associated with bacterial vaginosis (BV) have also been implicated. Approximately 15% of untreated chlamydial infections progress to PID; this percentage may be higher with gonococcal infections. 1 Delayed diagnosis contributes to inflammatory sequelae, including infertility, ectopic pregnancy, and chronic pelvic pain. 2 , 3 Approximately one in six women with salpingitis develops infertility. 2 , 3 The cost of having PID has previously been estimated at $1,995 per patient, not including expenses for future evaluation and treatment of complications. 4 Based on the National Health and Nutrition Examination Survey 2013–2014 data, 4.4% of women (2.5 million) 18 to 44 years of age in the United States reported a history of PID. 5 Although studies suggest an overall decline in rates of PID, cases of gonorrhea and chlamydia are increasing. 6 This is especially worrisome with the rise of antibiotic-resistant Neisseria gonorrhoeae .

WHAT IS NEW ON THIS TOPIC:

Because of emerging resistance, routine use of quinolones is no longer recommended for pelvic inflammatory disease to provide empiric coverage for gonorrhea.

Intrauterine devices pose no increased risk of pelvic inflammatory disease beyond the first 20 days postinsertion.

Intrauterine devices do not need to be removed if the patient with pelvic inflammatory disease is clinically improving within 48 to 72 hours of initiation of antibiotics.

Risk Factors and Pathophysiology

Risk factors for PID include age younger than 25 years, new or multiple sex partners, unprotected sexual intercourse, intercourse with a symptomatic partner, young age at onset of sexual activity (younger than 15 years), or a history of STIs or PID. 7 The possibility of PID should be considered in any sexually active woman. 8 Many women falsely believe they are in a monogamous relationship or that their partner does not harbor an STI; therefore, a low threshold for screening is warranted.

Damage to the epithelium by infection (typically Chlamydia trachomatis or N. gonorrhoeae ) allows organisms to ascend the upper genital tract from the cervix. A variety of microbes have been isolated in PID. 9 The role of Mycoplasma genitalium , Gardnerella vaginalis , and Ureaplasma urealyticum in PID is not clear. Several studies have shown a relationship between PID and BV-associated anaerobic bacteria, but it remains unclear whether screening and treatment for BV decrease the incidence of PID. 8 – 10 Infection can also reach the upper genital tract from the parametrium through the lymphatic system or, rarely, through hematogenous routes, such as in patients with tuberculosis.

Clinical Features

PID is often underdiagnosed because of the wide variation and severity of symptoms. 8 Patients may be asymptomatic. Many women with tubal factor infertility have histologic evidence of PID despite having no previous diagnosis. 11 , 12 The cardinal symptom of PID is the abrupt onset of lower abdominal or pelvic pain in a sexually active woman. 8 Symptoms can be subtle with mild bilateral lower abdominal pain that worsens with coitus, abnormal uterine bleeding, increased urinary frequency, dysuria, or abnormal vaginal discharge. Fever may also occur, but it is not the dominant symptom. Right upper quadrant pain that is worse with movement and breathing is caused by inflammation and adhesions of the liver capsule, such as in perihepatitis (i.e., Fitz-Hugh–Curtis syndrome).

The diagnosis of PID is clinical, with imaging and more invasive studies reserved for cases of diagnostic uncertainty or concern for complications (e.g., tubo-ovarian abscess). 8 , 13 Therefore, physicians should make the diagnosis and initiate treatment for PID if no other diagnosis is more likely in sexually active women younger than 25 years or in older women at risk for STIs who present with pain in the lower abdomen or pelvis and one or more of the clinical findings shown in Figure 1 . 8

Most women with PID have evidence of lower genital tract infection, such as mucopurulent discharge or an increase in white blood cells on saline microscopy (i.e., wet prep with at least one white blood cell per epithelial cell). 14 The absence of such findings should prompt reconsideration of the differential diagnosis of lower abdominal pain ( Table 1 ) . 15 – 18 Presumptive diagnosis is sufficient to initiate empiric antibiotic treatment, even in mildly symptomatic patients.

Adding more diagnostic findings increases the specificity of diagnosis, but this comes at the risk of decreasing sensitivity, thereby potentially missing cases of PID. 8 Findings that help support the diagnosis of PID are listed in Table 2 . 8

Physical Examination and Diagnostic Studies

Bimanual examination should be performed on all patients with suspected PID to assess for cervical motion, uterine, and/or adnexal tenderness; adnexal masses; or tubo-ovarian abscess. Speculum examination should be performed to identify mucopurulent cervical discharge. Saline microscopy of vaginal discharge may reveal predominant white blood cells, which could indicate coexisting BV and trichomoniasis.

All patients suspected of having PID should have a serum or urine pregnancy test; if positive, ectopic pregnancy should be excluded. Patients should also be screened with nucleic acid amplification tests for chlamydia and gonorrhea using vaginal swabs self-collected by the patient or vaginal or endocervical specimens collected by the physician. 19 The nucleic acid amplification tests for gonorrhea and chlamydia are highly sensitive (90% to 98% and 88.9% to 95.2%, respectively), specific (98% to 100% and 99.1% to 100%, respectively), and cost-effective. 20 Negative results do not exclude infections of the upper reproductive tract, but a positive result in combination with one of the minimum criteria supports the diagnosis of PID. 8 Nucleic acid amplification tests used for M. genitalium are not currently recommended. 8

In cases of diagnostic uncertainty or findings suggestive of tubo-ovarian abscess, physicians may consider a variety of imaging modalities ( Table 1 ) . 15 – 18 Thickened, fluid-filled tubes; free pelvic fluid; or tubo-ovarian abscess on transvaginal ultrasonography or magnetic resonance imaging may be seen in PID. 21 Power Doppler studies with transvaginal ultrasonography reveals hyperemia in the setting of PID. 22 Computed tomography may show free fluid in the pelvis, fat stranding, reactive lymphadenopathy, or thickened tubes, as well as a tubo-ovarian complex or perihepatic inflammation. 23 Diagnostic laparoscopy may show salpingitis, tubo-ovarian abscess, peritonitis, and possibly perihepatitis. Endometrial biopsy may demonstrate endometritis on histopathology. 24 Diagnostic evaluation should not delay treatment. 8

Treatment should not be withheld until STI testing results are known. Delaying treatment by two to three days from presentation increases the risk of infertility and ectopic pregnancy nearly threefold. 25 The current Centers for Disease Control and Prevention (CDC) recommendations for inpatient and outpatient treatment of PID are listed in Table 3 8 and Table 4 . 8 Antibiotic selection is based on the need for inpatient vs. outpatient care. No differences in pregnancy rates, time to pregnancy, PID recurrence, chronic pelvic pain, or ectopic pregnancy have been found in women with mild to moderate PID who receive outpatient treatment. 3 , 26

Indications for inpatient treatment include pregnancy; failure or intolerance of oral therapy; high fever, nausea, vomiting, intractable abdominal pain, or severe illness; tubo-ovarian abscess; or when surgical emergency cannot be excluded. 8 In women requiring inpatient treatment, any of the CDC-recommended parenteral antibiotic regimens may be used. If the patient is not vomiting, oral doxycycline is preferred over parenteral administration because of the pain of intravenous infusion and similar bioavailability. 8

Patients may be transitioned from parenteral to oral therapy after 24 hours of clinical improvement. Completion of 14 days of treatment with oral medications is recommended. Those patients treated with any of the CDC-recommended inpatient regimens or with the alternative regimen should be transitioned to oral doxycycline, 100 mg every 12 hours. However, patients treated specifically with clindamycin and gentamicin should be transitioned to oral doxycycline, 100 mg every 12 hours, or oral clindamycin, 450 mg every six hours. If a tubo-ovarian abscess is present, in addition to surgical consultation, the patient should be transitioned to oral doxycycline, 100 mg every 12 hours, with either oral clindamycin, 450 mg every six hours, or oral metronidazole (Flagyl), 500 mg every 12 hours, to provide additional anaerobic coverage.

Intramuscular and oral therapy can be used for patients who do not need inpatient treatment. The importance of extended anaerobic coverage in the treatment of PID is still unknown. The CDC currently recommends considering the addition of metronidazole in all outpatient treatment of PID and in patients who have trichomoniasis, BV, or recent uterine instrumentation. Infection with M. genitalium should be considered in cases of PID refractory to treatment because this organism does not typically respond to standard PID treatment regimens. 8 The role of M. genitalium in PID is an area of future research.

Because of emerging resistance, routine quinolone use is no longer recommended as PID treatment in providing empiric coverage for gonorrhea. 8 The use of a quinolone can be considered if the community prevalence and individual risk for gonorrhea is low, the patient is likely to follow up after treatment, and a culture for gonorrhea can be obtained before starting treatment. If these criteria are met, an alternative regimen for outpatient treatment of PID includes levofloxacin (Levaquin), 500 mg orally every 24 hours; moxifloxacin (Avelox), 400 mg orally every 24 hours; or ofloxacin, 400 mg orally every 12 hours, with metronidazole, 500 mg orally every 12 hours for 14 days. 8

If the culture isolate is found to be quinolone-resistant and the patient has a cephalosporin allergy, consultation with an infectious disease subspecialist is recommended, or inpatient treatment with clindamycin or gentamicin can be used. 8

Special Populations

Pregnant patients with PID warrant admission to the hospital for parenteral antibiotics. The preferred regimen does not include doxycycline and is not specified in the CDC PID guidelines. 8

PENICILLIN ALLERGY

Physicians should take a careful history in patients reporting a penicillin allergy to determine the level of risk in using a second- or third-generation cephalosporin antibiotic for the empiric treatment of PID or gonorrhea. The cross-reactivity is negligible between penicillins and third-generation cephalosporins. 27 If cephalosporin treatment for PID cannot be safely administered, the patient can be hospitalized for parenteral antibiotic treatment with clindamycin or gentamicin.

INTRAUTERINE DEVICES

Intrauterine devices (IUDs) pose no increased risk for PID beyond the first 20 days postinsertion. 28 IUDs do not need to be removed if the patient is clinically improving within 48 to 72 hours of initiation of antibiotics because clinical outcomes are similar, if not improved, in patients with retained IUDs. 29 Treatment outcomes in women with levonorgestrel-releasing IUDs (Mirena) are unknown because current studies include only copper or nonhormonal IUDs.

Women with PID who also have HIV have similar symptoms and respond similarly to treatment as those without HIV; however, women with HIV are at increased risk of tubo-ovarian abscesses and have higher rates of mycoplasma and streptococcal infections. Therefore, they need to be followed closely for response to treatment. 30

Monitoring and Counseling

Patients should have follow-up within 48 to 72 hours after hospital discharge or initiation of outpatient treatment to determine clinical improvement and treatment tolerance. They should be tested for all STIs, including HIV and syphilis. Patients are advised to abstain from all sexual activity until they and their partners are fully treated and they are symptom-free. All women diagnosed with chlamydial or gonococcal PID, including pregnant patients, need to repeat testing for chlamydia and gonorrhea in three months regardless of sex partner treatment. 8 , 31 Three-month rescreening is distinct from a test of cure, which occurs earlier. Because of the risk of false positives from nonviable organisms, test of cure three to four weeks after completing the CDC-recommended therapy for chlamydial infections is not recommended and should be obtained only in pregnant patients. 8 Patients should be counseled on the complications of PID, the need for safe sex practices, and the risk of having multiple sex partners in PID recurrence.

Sex Partners

Patients who have had sexual contact within 60 days with a woman who has PID should be offered STI testing and treatment. For those partners without health care, patient-delivered partner therapy or expedited partner therapy, providing medications to sex partners who are not established patients without an examination, should be offered . Studies have shown an approximately 20% reduction in chlamydia prevalence and 50% reduction in gonorrhea at follow-up if used. 8 , 32 The legal status of individual states for expedited partner therapy can be found at https://www.cdc.gov/std/ept .

Standard treatment of the partner for chlamydia and trichomonas is indicated for sexual contacts of the patient. Gonorrhea treatment is limited to oral options, and treatment in this setting is cefixime, 400-mg single dose, and azithromycin (Zithromax), 1-g single dose. 8 Prescriptions should be accompanied with treatment instructions and recommendations for STI testing, safe sex practices, and sexual abstinence until both partners have completed therapy and symptoms, if present, have resolved.

Screening and Prevention

No specific screening recommendation exists for PID; however, testing for chlamydia and gonorrhea has been shown to decrease the incidence of PID in high-risk populations. 33 The U.S. Preventive Services Task Force recommendations for chlamydia and gonorrhea screening are listed in Table 5 34 and apply to all sexually active women, including pregnant women. 34 Specifically, annual screening for chlamydia and gonorrhea is recommended for all sexually active women younger than 25 years and for women at increased risk. Additionally, all pregnant women at high risk for STIs should be rescreened in the third trimester. 8 The American Academy of Family Physicians supports these recommendations. 35

The U.S. Preventive Services Task Force recommends intensive behavioral counseling for all adults who are at increased risk for STIs and all sexually active adolescents. 34 Intensive counseling is defined as a minimum of two hours of education. Less intensive interventions (30 minutes to two hours) have shown benefit, but benefit increases with intensity of intervention. Counseling topics include the basics of STIs (transmission/prevention) and practical safe sex skills (condom use, open discussions, goal setting). 34 The CDC provides behavioral intervention resources ( http://effectiveinterventions.org ) and counseling methods ( http://nnptc.org ). The American College of Obstetricians and Gynecologists does not recommend prophylactic antibiotics for colposcopy, loop electrosurgical excision, endometrial biopsy, IUD insertion, or endometrial ablation. Antibiotic prophylaxis is recommended in a woman undergoing hysterosalpingography if she has a history of PID or dilated tubes at the time of the procedure, uterine evacuation for early pregnancy loss, and first- or second-trimester abortions. 36

This article updates previous articles on this topic by Gradison 37 and Crossman . 38

Data Sources: A PubMed search was completed using the following key terms: PID, pelvic inflammatory disease, intrauterine devices, sexually transmitted infections, sexually transmitted diseases, chlamydia, and gonorrhea. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Additional searches included U.S. Preventive Services Task Force, the Cochrane database, and UpToDate. Essential Evidence Plus was also used. Search dates: July 30, 2018; February 12, 2019; and May 13, 2019.

Price MJ, Ades AE, De Angelis D, et al. Risk of pelvic inflammatory disease following Chlamydia trachomatis infection: analysis of prospective studies with a multistate model. Am J Epidemiol. 2013;178(3):484-492.

Haggerty CL, Gottlieb SL, Taylor BD, et al. Risk of sequelae after Chlamydia trachomatis genital infection in women. J Infect Dis. 2010;201(suppl 2):S134-S155.

Ness RB, Soper DE, Holley RL, et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am J Obstet Gynecol. 2002;186(5):929-937.

Chesson HW, Collins D, Koski K. Formulas for estimating the costs averted by sexually transmitted infection (STI) prevention programs in the United States. Cost Eff Resour Alloc. 2008;6:10.

Kreisel K, Torrone E, Bernstein K, et al. Prevalence of pelvic inflammatory disease in sexually experienced women of reproductive age — United States, 2013–2014. MMWR Morb Mortal Wkly Rep. 2017;66(3):80-83.

Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2017. Accessed May 13, 2019. https://www.cdc.gov/std/stats17/default.htm

Simms I, Stephenson JM, Mallinson H, et al. Risk factors associated with pelvic inflammatory disease. Sex Transm Infect. 2006;82(6):452-457.

Workowski KA, Bolan GA Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep . 2015;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137.

Haggerty CL, Totten PA, Tang G, et al. Identification of novel microbes associated with pelvic inflammatory disease and infertility. Sex Transm Infect. 2016;92(6):441-446.

Ness RB, Hillier SL, Kip KE, et al. Bacterial vaginosis and risk of pelvic inflammatory disease. Obstet Gynecol. 2004;104(4):761-769.

Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N Engl J Med. 2015;372(21):2039-2048.

Patton DL, Moore DE, Spadoni LR, et al. A comparison of the fallopian tube's response to overt and silent salpingitis. Obstet Gynecol. 1989;73(4):622-630.

Gaitán H, Angel E, Diaz R, et al. Accuracy of five different diagnostic techniques in mild-to-moderate pelvic inflammatory disease. Infect Dis Obstet Gynecol. 2002;10(4):171-180.

Yudin MH, Hillier SL, Wiesenfeld HC, et al. Vaginal polymorphonuclear leukocytes and bacterial vaginosis as markers for histologic endometritis among women without symptoms of pelvic inflammatory disease. Am J Obstet Gynecol. 2003;188(2):318-323.

Soper DE. Pelvic inflammatory disease. Obstet Gynecol. 2010;116(2 pt 1):419-428.

Parasar P, Ozcan P, Terry KL. Endometriosis: epidemiology, diagnosis and clinical management. Curr Obstet Gynecol Rep. 2017;6(1):34-41.

Kitaya K, Takeuchi T, Mizuta S, et al. Endometritis: new time, new concepts. Fertil Steril. 2018;110(3):344-350.

Frassetto L, Kohlstadt I. Treatment and prevention of kidney stones: an update. Am Fam Physician. 2011;84(11):1234-1242. Accessed July 19, 2019. https://www.aafp.org/afp/2011/1201/p1234.html

Lunny C, Taylor D, Hoang L, et al. Self-collected versus clinician-collected sampling for chlamydia and gonorrhea screening: a systemic review and meta-analysis. PLoS One. 2015;10(7):e0132776.

Van Dyck E, Ieven M, Pattyn S, et al. Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by enzyme immunoassay, culture, and three nucleic acid amplification tests. J Clin Microbiol. 2001;39(5):1751-1756.

Sakhel K, Benson CB, Platt LD, et al. Begin with the basics: role of 3-dimensional sonography as a first-line imaging technique in the cost-effective evaluation of gynecologic pelvic disease. J Ultrasound Med. 2013;32(3):381-388.

Molander P, Sjöberg J, Paavonen J, et al. Transvaginal power Doppler findings in laparoscopically proven acute pelvic inflammatory disease. Ultrasound Obstet Gynecol. 2001;17(3):233-238.

Revzin MV, Mathur M, Dave HB, et al. Pelvic inflammatory disease: multimodality imaging approach with clinical-pathologic correlation. Radiographics. 2016;36(5):1579-1596.

Wiesenfeld HC, Hillier SL, Meyn LA, et al. Subclinical pelvic inflammatory disease and infertility. Obstet Gynecol. 2012;120(1):37-43.

Hillis SD, Joesoef R, Marchbanks PA, et al. Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility. Am J Obstet Gynecol. 1993;168(5):1503-1509.

Ness RB, Trautmann G, Richter HE, et al. Effectiveness of treatment strategies of some women with pelvic inflammatory disease [published correction appears in Obstet Gynecol . 2006;107(6):1423–1425]. Obstet Gynecol. 2005;106(3):573-580.

Campagna JD, Bond MC, Schabelman E, et al. The use of cephalosporins in penicillin-allergic patients. J Emerg Med. 2012;42(5):612-620.

Grimes DA. Intrauterine device and upper-genital-tract infection. Lancet. 2000;356(9234):1013-1019.

Tepper NK, Steenland MW, Gaffield ME, et al. Retention of intrauterine devices in women who acquire pelvic inflammatory disease: a systematic review. Contraception. 2013;87(5):655-660.

Irwin KL, Moorman AC, O'Sullivan MJ, et al. Influence of human immunodeficiency virus infection on pelvic inflammatory disease. Obstet Gynecol. 2000;95(4):525-534.

Hosenfeld CB, Workowski KA, Berman S, et al. Repeat infection with chlamydia and gonorrhea among females: a systematic review of the literature. Sex Transm Dis. 2009;36(8):478-489.

Golden MR, Whittington WL, Handsfield HH, et al. Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial infection. N Engl J Med. 2005;352(7):676-685.

Herzog SA, Heijne JC, Scott P, et al. Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease. Epidemiology. 2013;24(6):854-862.

LeFevre ML. Screening for chlamydia and gonorrhea: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(12):902-910.

American Academy of Family Physicians. Reproductive health clinical recommendations and guidelines. Accessed March 15, 2019. https://www.aafp.org/patient-care/browse/topics.tag-reproductive-health.html

ACOG practice bulletin no. 195: prevention of infection after gynecologic procedures. Obstet Gynecol. 2018;131(6):e172-e189.

Gradison M. Pelvic inflammatory disease. Am Fam Physician. 2012;85(8):791-796. Accessed July 19, 2019. https://www.aafp.org/afp/2012/0415/p791.html

Crossman SH. The challenge of pelvic inflammatory disease [published correction appears in Am Fam Physician . 2006;74(12):2024]. Am Fam Physician. 2006;73(5):859-864. Accessed July 29, 2019. https://www.aafp.org/afp/2006/0301/p859.html

Ross J, Cole M, Evans C, et al. United Kingdom National Guideline for the management of pelvic inflammatory disease (2019 interim update). Accessed July 17, 2019. https://www.bashhguidelines.org/media/1217/pid-update-2019.pdf

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Pelvic inflammatory disease: a case report

Genital (female) imaging

Clinical Cases

L. Manganaro, L.Ballesio, M.L. Angeli, L.Bertini, C. Carrozza.

25 years, female

Pelvic US demonstrated bilateral solid adnexal masses and a small volume of free fluid in the pouch of Douglas. In face of these findings it was considered necessary to perform a pelvic MRI examination. The MRI examination confirmed the US findings, showing a left adnexal mass with a convolved aspect, measuring 10 cm. This was heterogeneous on T1-weighted images and of medium intensity on T2-weighted images. A mass of the same aspect was present on right-hand side. All the lesions showed high enhancement of the wall after paramagnetic contrast administration. There was ascitic fluid in the peritoneal cavity.

More than one milion women contract PID each year. Factors associated with PID are: young age, reduced socioeconomic circumstances, African or Afro-Caribbean ethnic origin, lower educational attainment, and recent new sexual partners. It is a polymicrobial infection caused by the ascent of organisms from the cervix; the most common organisms involved are Neisserya gonorrheae and Chlamydia trachomatis, and anaerobic bacteria also seem to be involved.

Diagnosis of PID can be difficult, because it can mimic several other pelvic diseases: ectopic pregnancy, ovarian cyst rupture, ovarian or adnexal torsion, endometriosis, neoplasms, urinary tract infection, and appendicitis.

Transvaginal sonography and MRI have been shown to be accurate in diagnosis. US can demonstrate only ascitic fluid in the peritoneal cavity or, in the most severe cases, can shows adnexial masses with heterogeneous echopattern. MRI findings are non specific; pelvic MRI can demonstrate an adnexal mass, ill defined, containing fluid with various signal intensity. Following administration of gadolinium the wall and the surrounding tissues enhance. Laparoscopy, however, remains the gold standard.

[1] Ross J. Pelvic inflammatory disease. BMJ. 2001 Mar 17;322(7287):658-9. (PMID: 11250853 )

[2] Lawson MA, Blythe MJ. Pelvic inflammatory disease in adolescents. Pediatr Clin North Am. 1999 Aug;46(4):767- 82. (PMID: 10494256 )

[3] Tukeva TA, Aronen HJ, Karjalainen PT, Molander P, Paavonen J. MR imaging in pelvic inflammatory disease: comparison with laparoscopy and US. Radiology 1999; 210:209-216.

MR of the pelvis T1- and T2-weighted images

MR of the pelvis

When viewing this topic in a different language, you may notice some differences in the way the content is structured, but it still reflects the latest evidence-based guidance.

Pelvic inflammatory disease

• Overview  
• Theory  
• Diagnosis  
• Management  
• Follow up  
• Resources  

Pelvic inflammatory disease is an acute ascending polymicrobial infection of the female gynaecological tract that is frequently associated with Neisseria gonorrhoeae or Chlamydia trachomatis .

Symptoms and physical findings vary widely and may include lower abdominal tenderness, adnexal tenderness, and cervical motion tenderness. Fever and cervical or vaginal discharge may also be present.

Diagnosis may be difficult because symptoms range from absent to severe and may be non-specific. Possible laboratory findings include abundant white blood cells on saline microscopy of vaginal secretions, elevated erythrocyte sedimentation rate, elevated C-reactive protein, and laboratory documentation of cervical infection with Neisseria gonorrhoeae or Chlamydia trachomatis . Laparoscopy is the definitive procedure but is invasive and is not recommended for routine diagnosis.

Antibiotic treatment should be initiated in patients who are sexually active and who have pelvic pain, cervical motion tenderness, or adnexal or uterine tenderness for which no other cause can be found. Patients may need hospitalisation and parenteral antibiotics.

Complications include tubo-ovarian abscess and subsequent infertility or ectopic pregnancy due to scarred or obstructed fallopian tubes.

Pelvic inflammatory disease (PID) comprises a spectrum of inflammatory disorders of the upper female genital tract, including any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. Sexually transmitted organisms, especially Neisseria gonorrhoeae and Chlamydia trachomatis , are implicated in many cases; however, micro-organisms that comprise the vaginal flora (e.g., anaerobes, Gardnerella vaginalis , Haemophilus influenzae , enteric gram-negative rods, and Streptococcus agalactiae ) have also been associated with PID. In addition, cytomegalovirus (CMV), Trichomonas vaginalis , Mycoplasma hominis , Mycoplasma genitalium , and Ureaplasma urealyticum might be associated with some cases of PID. [1] Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344968 Symptoms include fever, vomiting, back pain, dyspareunia, and bilateral lower abdominal pain, as well as symptoms of lower genital tract infection such as abnormal vaginal odour, itching, bleeding, or discharge. In some instances, symptoms are mild or even absent.

History and exam

Key diagnostic factors.

• presence of risk factors
• uterine tenderness
• cervical motion tenderness
• adnexal tenderness

Other diagnostic factors

• lower abdominal pain
• abnormal cervical or vaginal discharge

Risk factors

• prior infection with chlamydia or gonorrhoea
• young age at onset of sexual activity
• unprotected sexual intercourse with multiple sexual partners
• prior history of PID
• low socio-economic status
• current vaginal douching
• intercourse during menstruation

Diagnostic investigations

1st investigations to order.

• white blood cell count
• polymorphonuclear cells on wet mount of vaginal secretions
• genetic probe or culture of vaginal secretions for Neisseria gonorrhoeae and Chlamydia trachomatis
• nucleic acid amplification test for Mycoplasma genitalium

Investigations to consider

• serum erythrocyte sedimentation rate (ESR)
• transvaginal ultrasound
• laparoscopy
• endometrial biopsy

Treatment algorithm

Suspected or confirmed mild-to-moderate pid at initial presentation, severe pid, complications, or no response to intramuscular/oral therapy, contributors, madhavi manoharan, md, frcog.

Consultant Obstetrician and Gynaecologist

Integra Healthcare Ltd

Grand Cayman

Cayman Islands

Disclosures

MM declares that she has no competing interests.

Acknowledgements

Dr Madhavi Manoharan would like to gratefully acknowledge Dr Dan Selo-Ojeme and Dr Susan Arjmand, previous contributors to this topic.

DSO and SA declare that they have no competing interests.

Peer reviewers

Bradford fenton, md.

Department of Obstetrics and Gynecology

Summa Health System

BF declares that he has no competing interests.

Edmond Edi-Osagie, MBBS, MRCOG, MD

Consultant Gynaecologist

Central Manchester University Hospitals

St. Mary's Hospital

EEO declares that he has no competing interests.

Differentials

• Ectopic pregnancy
• Acute appendicitis
• Ovarian cyst complications (ruptured ovarian cyst, ovarian cyst torsion, haemorrhagic ovarian cyst)
• ACR appropriateness criteria: acute pelvic pain in the reproductive age group
• European guideline on the management of Mycoplasma genitalium infections

Patient information

Endometrial ablation (microwave method)

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• Open access
• Published: 15 July 2022

Chlamydia infection, PID, and infertility: further evidence from a case–control study in China

• Lijun Liu 1 , 2 , 3 ,
• Changchang Li 1 , 2 , 3 ,
• Xuewan Sun 1 , 2 , 3 , 4 ,
• Jie Liu 1 , 2 , 3 ,
• Hepeng Zheng 1 , 2 , 3 , 5 ,
• Bin Yang 1 , 2 , 3 ,
• Weiming Tang 1 , 2 , 3 , 4 &
• Cheng Wang 1 , 2 , 3  

BMC Women's Health volume  22 , Article number:  294 ( 2022 ) Cite this article

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Chlamydia trachomatis infection and pelvic inflammatory disease (PID) are well-known risk factors for female infertility. But there is limited evidence from China. This study aimed to further explore the associations between previous/current chlamydial infection, PID, and infertility in China.

We performed a 1:2 matched case–control study with two control groups: pregnant controls and non-pregnant controls in China in 2019. Women diagnosed with infertility were selected as cases (n = 255). Controls were selected based on the following criteria: Pregnant women who were documented in the selected hospitals were chosen as Pregnant controls (n = 510), and people who sought health care in Obstetric/Gynecologic clinics, Family Planning clinics, Dermatology and STD Department or Urological department were selected as Non-pregnant controls (n = 510) . Infertility induced by male factors and people who used antibiotics in the vagina within two weeks were excluded. The first-stream specimen of urine samples was tested for chlamydia by nucleic acid amplification testing (NAAT). Conditional logistic regression was used to estimate the association.

The prevalence of previous chlamydial infection and PID were significantly higher in cases (2.4%, 17.3%) than in controls (Non-pregnancy: 0.4%, 3.0%; Pregnancy: 0.4%, 9.0%). The current chlamydial infection rates were 5.9%, 7.3%, and 7.1% in infertile, pregnant, and non-pregnant women, respectively. After adjusting for confounders, PID largely elevated the risk of infertility (using non-pregnant controls: adjusted OR = 2.57, 95% CI 1.51, 4.39; using pregnant controls: adjusted OR = 6.83, 95% CI 3.47, 13.43). And the positive association between PID and tubal infertility was more obvious for both groups. For current chlamydial infection, none of the odds ratios were significant at the 0.05 level, while small sample size limited the evaluation of an association between prior chlamydial infection with infertility.

Conclusions

Previous PID was indicated to largely increase the risk of infertility, especially tubal infertility. And there should be continuing emphasis on highly sensitive and specific biomarker for prior chlamydial infection.

Peer Review reports

Infertility refers to the failure to achieve a clinical pregnancy after over one year of regular unprotected sexual intercourse [ 1 ]. Infertility is a highly prevalent global condition and the incidence is on the rise, which is estimated to affect around 9% of reproductive-aged couples worldwide [ 2 ]. In China, the overall prevalence of infertility has reached 15.5%, while among women actively trying to conceive, the prevalence is as high as 25% [ 3 ]. Quite a few studies have revealed a negative impact of infertility on endometrial, myometrial, cervical, and placental alterations that underlie the poor obstetric outcomes [ 4 ]. It not only creates a considerable cost burden but also introduces tensions to the family. Further insight into the causes is critical to help alleviate the burden.

Chlamydia trachomatis is one of the most prevalent sexually transmitted microorganisms. Ascending from the lower genital tract, chlamydial infection can lead to serious reproductive consequences including infertility [ 5 ]. It was estimated that the proportion of tubal infertility caused by chlamydia had reached 45% [ 5 ]. Furthermore, this sexually transmitted microorganism is an important cause of pelvic inflammatory disease (PID), and PID was also indicated to increase the risk of infertility, then PID represents the link between chlamydia infection and infertility [ 6 , 7 , 8 ]. However, despite numerous studies identifying chlamydial infertility, the true host and pathogen determinants underlying infertility remain unknown due to the lack of appropriate experimental models and suitable diagnostic tools [ 5 , 9 ], and the current evidence base was weak for several reasons. First, the poor performance of serological tests that were commonly used in those studies [ 5 ]. Second, pregnant women were commonly selected as control participants, of whom are different from the source population and generally exaggerate the association [ 10 ].

China provided a great opportunity to further explore the association between chlamydial infection, PID and infertility for the following reasons. First, China has a considerable disease burden of chlamydial infection. According to the National Notifiable Infectious Disease Reporting System, the reported annual incidence rate in females was 84.55 per 100,000 population in 2019, which was highly underestimated due to the insufficient chlamydia screening/testing and poor detection methods [ 11 ]. Second, the implementation of the universal two-child policy in recent years encouraged many people to seek care for infertility, which increased our access to infertile women.

In this case–control study, we aimed to investigate whether previous/current chlamydial infection and previous PID would influence the risk of infertility in the Chinese population.

Study population

This was a 1:2 matched case–control study aiming to explore the effects of chlamydial infection and PID on infertility. Women aged between 18 to 44 years were considered for the study if they sought for health care between Jan 1, 2019, and Oct 30, 2019, at outpatient settings, including clinics or auxiliary reproductive center, in five cities (Guangzhou, Zhanjiang, Shenzhen, Dongguan, Yunfu) of Guangdong Province, China [ 12 ].

Infertility was defined as failure to conceive after 12 months or more of regular unprotected sexual intercourse [ 1 ]. All cases involved in our study underwent a diagnostic workup by professionals, and if the patients self-reported infertility, they would receive laparoscopy and hysterosalpinography for further verification. And according to the American Society for Reproductive Medicine, we further classified infertility into several subtypes, including tubal disorders, endocrine disturbance, cervical/uterine/peritoneal factors, immune factors, sex factors, and others or unknown [ 13 ]. The participants were excluded if they met one of the following conditions: (1) infertility induced by male factors, and (2) who 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 infertility case that was ascertained, two control women were matched by age (± 3 years). For pregnant controls, we included pregnant women who were documented in the selected hospitals of the study cities. As non-pregnant controls, we selected those who sought health care other than infertility in Obstetric/Gynecologic clinics, Family Planning clinics, Dermatology & STD Department or Urological department for the first time in the past one year, and reported ever having sexual intercourse and willing to be tested for chlamydia. Indications for exclusion were the same with that of cases. Finally, we included 255 infertile women, 510 pregnant women (control 1), and 510 non-pregnant women (control 2) in this study. Information about baseline characteristics including sociodemographic characteristics, reproductive history, smoking and alcohol drinking, previous history of diseases, and sexually transmitted infection (STI) were collected through online questionnaires (Fig.  1 ).

The study was approved by the Institutional Review Board of Dermatology Hospital of Southern Medical University. All participants have given written informed consent.

Sample collection and nucleic acid amplification testing

The first-stream specimen of urine samples was collected from all participants. At least one-hour interval before the last urination was needed. Self-cleaning of the urination site was not allowed. After collection, transferred it into cobas®PCR MEDIA tubes and mixed upside down five times. Then stored the sample under 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 positive NAAT result but without any related symptoms such as odynuria, frequent and/or urgent micturition, hypogastralgia, lumbago, abnormal vaginal bleeding, and/or discharge, would be diagnosed as asymptomatic chlamydia infection. And those with positive NAAT result and related symptoms would be regarded as symptomatic chlamydia infection.

Sample size calculation

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

For PID, about 4.4% of sexually active women received a diagnosis of PID in their lifetime [ 16 ], and self-reported PID was associated with a fourfold higher risk of infertility [ 6 ]. Then, a sample of 36 infertile cases with matched 72 non-infertile controls can achieve 81% power under α = 0.05.

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

Statistical analysis

We used the chi-square test to evaluate the baseline characteristics between non-pregnant/pregnant women and infertile women. Associations between chlamydial infection, including NAAT verified infection and self-reported previous infection, and PID with infertility in women were studied by conditional logistic regression, calculating odds ratios (ORs) with their corresponding 95% confidence intervals (CIs), adjusting for maternal age, BMI, monthly income, chronic disease, and other genital tract infection, which were suggested to be potential risk factors of infertility by published study [ 8 ]. Besides, previous chlamydial infection was added to adjust for the association between PID and infertility.

We conducted several sensitivity analyses. Firstly, we compared different effects on primary infertility and secondary infertility. The former refers to those women who have not been pregnant previously, while the latter is denoted for the inability to repeat conception after a prior pregnancy [ 2 ]. Then, considering that some of the infertility subtypes were probably not to be associated with chlamydial infection or PID, we kept infertility cases induced by tubal disorders only and excluded those related to sex factors and/or cervical/uterine/vaginal factors.

Data analyses were performed using Stata 14 software (StataCorp LLC, Texas). Statistical significance was considered at a two-sided P value < 0.05.

Social demographic characteristics

Our study involved 1275 participants, including 510 non-pregnant women, 510 pregnant women, and 255 infertile women, with an average age ( \({\overline{\text{x}}}\)  ± s) of 30.0 ± 4.5, 29.8 ± 4.4 and 29.8 ± 4.4 years, respectively. We compared baseline characteristics and previous history of diseases between non-pregnant/pregnant women and infertile women (Table 1 ). Most participants only received high school education or lower and earned less than $1500 (about 10,000 RMB) per month. And compared with control groups, more infertile women earned over $1500 per month for ( P  < 0.05). The (pregestational) BMI of infertile women was higher than that of pregnant women. For non-pregnant women, the age of sexual debut was lower than that of infertile women ( P  < 0.05). Pregnant women were more likely to have chronic diseases but less likely to experience PID and other genital tract infections in the past.

As mentioned above, we further classified infertility into several subtypes, and Fig.  2 showed that tubal disease was an important cause of infertility, which accounted for 34% of our cases. And endocrine disturbance (20%) was also worth attention.

Infertility subtypes

Chlamydial infection

The prevalence of self-reported previous chlamydial infection was significantly higher in infertile women (2.4%) than in controls (Non-pregnancy: 0.4%; Pregnancy: 0.4%). And the current infection rates tested by NAAT were 5.9%, 7.1%, and 7.3% in infertile, non-pregnant and pregnant women, respectively. In this study, the percentage of asymptomatic infection was lower among control groups (non-pregnancy: 26.5%, pregnancy: 22.7%) than cases (46.2%).

The association between chlamydial infection, previous PID, and infertility

Our study found that previous PID diagnoses were associated with an increased risk of infertility using non-pregnant controls (adjusted OR = 2.57, 95% CI 1.51, 4.39) and pregnant controls (adjusted OR = 6.83, 95% CI 3.47, 13.43). For current chlamydial infection, none of the odds ratios were significant at the 0.05 level (Table 2 ). Due to the low prevalence of self-reported chlamydia infection, it was not a valid variable for this analysis, so the result was not shown.

Sensitivity analysis

We further evaluated the effects of PID on different subtypes of infertility. Firstly, we compared primary infertility (n = 168) and secondary infertility (n = 87). PID history was positively associated with primary infertility using non-pregnant controls (adjusted OR = 4.41, 95% CI 1.21, 16.12) and using pregnant controls (adjusted OR = 3.78, 95% CI 1.15, 12.41) (Table 3 ).

Further, we kept infertility cases caused by tubal disorders (n = 86) only, and the positive association between PID and infertility was more obvious for both groups (see Additional file 1 : Table S1). Previous PID was associated with an increased tubal infertility risk of 7.98-fold (95% CI 2.76, 23.06) for the non-pregnancy control group and 16.17-fold (95% CI 4.59, 56.97) for the pregnancy control group. Finally, we dropped infertility cases caused by sex factors and/or cervical/uterine/vaginal factors (n = 48), which may be less attributed to maternal infection and PID. Additional file 1 : Table S2 showed that the effect size was also elevated to some extent (non-pregnant group: adjusted OR = 3.09, 95% CI 1.66, 5.76; pregnant group: adjusted OR = 7.29, 95% CI 3.37, 15.77).

In our evaluation of the association between chlamydial infection, PID and infertility, we found that previous PID was indicated to largely elevate the risk of infertility, especially tubal infertility. The prevalence of infertility among women with self-reported previous chlamydia infection was six times the prevalence among women with negative results, although our sample size limited an evaluation of an association of infertility with it. For current chlamydial infection, none of the odds ratios were significant at the 0.05 level. This study extended the existing literature by using two groups of controls and using NAAT methods to improve the testing accuracy.

Previous PID was indicated to elevate the risk of infertility in this study, and this finding aligned with the existing literature. A national health and nutrition examination survey conducted in the United States found that self-reported PID was associated with a fourfold higher risk of infertility among young women (18–29 years old) [ 6 ]. Another study conducted in China using a case–control study design also drawn similar conclusions [ 7 ]. Besides, the effect was stronger in pregnant women's control settings than non-pregnant control setting in our study, which may be due to the confounding of infertile cases among non-pregnant women who were unaware of their infertile facts. PID is common and approximately 4.4% sexually active women were reported to have PID [ 17 ], and its long-term harmful effects on reproductive disability put an urgent need of public health prevention measures. On the one hand, efforts can be made on identifying noninvasive PID biomarkers considering the current unspecific invasive diagnostic methods [ 18 ]. On the other hand, Chlamydia trachomatis is a potentially important cause of PID, and implementing related screening programs would be the most important public health measure for the prevention of PID [ 18 ].

The number of self-reported prior chlamydial infection was limited in this study, which may be due to recall bias and low detection rate in China, therefore we did not conduct the association analysis between infertility with it. When indicating prior chlamydial infections, currently available methods include self-reports and chlamydial serologic assays with poor sensitivity, leading to incomplete understanding of chlamydial PID and infertility, so it is a necessity to find an appropriate marker. It is suggested that Pgp3 antibody may better satisfy this need [ 16 ]. Our team used an ultrasensitive and high-throughput luciferase immunosorbent assay, with good specificity and sensitivity, for detection of anti-Pgp3 antibodies among reproductive-aged women, including some infertile women (unpublished). Future studies will continue for Pgp3, chlamydia, PID and infertility. From early teenagers before infection until after being a mother, a wider population level follow-up cohort study would be the most robust way to understand its natural history, although it seemed not to be feasible [ 19 ].

The association between PID and infertility should be taken in the context of the study design and other limitations beyond those already mentioned. It was unavoidable to bring recall bias when applying a case–control design. Previous PID cases, as exposures of interest, were recalled based on their past diagnosis and may be biased due to the respondents’ distorted or incomplete memory, but we combined objective records from the Hospital Information System and doctors helped the participants to finish the questionnaire. This may reduce recall bias to some extent. Then, Berkson's bias cannot be ignored when analyzing the relationship between current chlamydial infection and infertility. Recruited from hospitals, infertile women involved in this study have possibly experienced a series of examinations including chlamydia testing and further received treatment, which may explain the relatively low rate of NAAT (+) and the biased effects observed. But it was noteworthy that infertility was a long-term consequence, and it was obscure whether infection occurred before infertility among women with positive NAAT.

In summary, previous PID was suggested to be associated with an elevated risk of infertility, especially tubal infertility. And for further assessment of the burden of chlamydia infertility, finding sensitive biomarkers that might predict prior chlamydial infection is urgently needed, because for most women present for infertility, inciting infection would no longer be detected by NAAT or other tests for active urogenital infection.

Availability of data and materials

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

• Pelvic inflammatory disease

Sexually transmitted infection

Nucleic acid amplification testing

Odds ratios

Confidence intervals

Gurunath S, Pandian Z, Anderson RA, Bhattacharya S. Defining infertility—a systematic review of prevalence studies. Hum Reprod Update. 2011;17(5):575–88.

Article   CAS   Google Scholar  

Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21(4):411–26.

Article   Google Scholar  

Zhou Z, Zheng D, Wu H, Li R, Xu S, Kang Y, Cao Y, Chen X, Zhu Y, Xu S, et al. Epidemiology of infertility in China: a population-based study. BJOG. 2018;125(4):432–41.

Vannuccini S, Clifton VL, Fraser IS, Taylor HS, Critchley H, Giudice LC, Petraglia F. Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome. Hum Reprod Update. 2016;22(1):104–15.

Menon S, Timms P, Allan JA, Alexander K, Rombauts L, Horner P, Keltz M, Hocking J, Huston WM. Human and pathogen factors associated with chlamydia trachomatis-related infertility in women. Clin Microbiol Rev. 2015;28(4):969–85.

Anyalechi GE, Hong J, Kreisel K, Torrone E, Boulet S, Gorwitz R, Kirkcaldy RD, Bernstein K. Self-reported infertility and associated pelvic inflammatory disease among women of reproductive age-national health and nutrition examination survey, United States, 2013–2016. Sex Transm Dis. 2019;46(7):446–51.

Tao X, Ge SQ, Chen L, Cai LS, Hwang MF, Wang CL. Relationships between female infertility and female genital infections and pelvic inflammatory disease: a population-based nested controlled study. Clinics (Sao Paulo, Brazil). 2018;73:e364.

Group TECW. Physiopathological determinants of human infertility. Hum Reprod Update. 2002;8(5):435–47.

Kessler M, Hoffmann K, Fritsche K, Brinkmann V, Mollenkopf HJ, Thieck O, Teixeira da Costa AR, Braicu EI, Sehouli J, Mangler M, et al. Chronic Chlamydia infection in human organoids increases stemness and promotes age-dependent CpG methylation. Nat Commun. 2019;10(1):1194.

Wallace LA, Scoular A, Hart G, Reid M, Wilson P, Goldberg DJ. What is the excess risk of infertility in women after genital chlamydia infection? A systematic review of the evidence. Sex Transm Infect. 2008;84(3):171–5.

Yue Xiaoli GX, Jing L, Jiahui Z. Epidemiologic features of genital Chlamydia trachomatis infection at national sexually transmitted disease surveillance sites in China, 2015–2019. Chin J Dermatol. 2020;53(8):596–601.

Google Scholar  

Li C, Tang W, Ho HC, Ong JJ, Zheng X, Sun X, Li X, Liu L, Wang Y, Zhao P, et al. Prevalence of chlamydia trachomatis among pregnant women, gynecology clinic attendees, and subfertile women in guangdong, china: a cross-sectional survey. Open Forum Infect Dis. 2021;8(6):ofab06.

Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2015;103(6):e44-50.

Chen H, Luo L, Wen Y, He B, Ling H, Shui J, He P, Hou X, Tang S, Li Z. Chlamydia trachomatis and human papillomavirus infection in women from southern Hunan province in China: a large observational study. Front Microbiol. 2020;11:827.

Tang W, Mao J, Li KT, Walker JS, Chou R, Fu R, Chen W, Darville T, Klausner J, Tucker JD. Pregnancy and fertility-related adverse outcomes associated with Chlamydia trachomatis infection: a global systematic review and meta-analysis. Sex Transm Infect. 2020;96(5):322–9.

Anyalechi GE, Hong J, Danavall DC, Martin DL, Gwyn SE, Horner PJ, Raphael BH, Kirkcaldy RD, Kersh EN, Bernstein KT. High plasmid gene protein 3 (Pgp3) Chlamydia trachomatis seropositivity, pelvic inflammatory disease, and infertility among women, national health and nutrition examination survey, United States, 2013–2016. Clin Infect Dis. 2021;73(8):1507–16.

Hillier SL, Bernstein KT, Aral S. A review of the challenges and complexities in the diagnosis, etiology, epidemiology, and pathogenesis of pelvic inflammatory disease. J Infect Dis. 2021;224(12 Suppl 2):S23-s28.

Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N Engl J Med. 2015;372(21):2039–48.

Unemo M, Bradshaw CS, Hocking JS, de Vries HJC, Francis SC, Mabey D, Marrazzo JM, Sonder GJB, Schwebke JR, Hoornenborg E, et al. Sexually transmitted infections: challenges ahead. Lancet Infect Dis. 2017;17(8):e235–79.

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Acknowledgements

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This work was supported by Guangdong Medical Science and Technology Research Fund (Grant No. C2019122). Funding sources had no role in study design, analysis and interpretation of data, writing of the report, or the decision to submit for publication.

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Lijun Liu, Changchang Li, Xuewan Sun, Jie Liu, Hepeng Zheng, Bin Yang, Weiming Tang & Cheng Wang

Guangdong Provincial Center for Skin Diseases and STIs Control, Guangzhou, 510095, China

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All authors contributed to the study conception and design and have read and approved the manuscript. LL, CL and WT were responsible for conceptualization, investigation, methodology and formal analysis. LL drafted the original paper. CW, BY and HZ were responsible for methodology and investigation. XS and JL were responsible for acquisition of data and data curation. CW was responsible for funding acquisition. All authors read and approved the final manuscript.

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Supplementary Information

Additional file 1.

. Sensitivity analysis of the association between chlamydial infection, previous PID and infertility subtypes.

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Liu, L., Li, C., Sun, X. et al. Chlamydia infection, PID, and infertility: further evidence from a case–control study in China. BMC Women's Health 22 , 294 (2022). https://doi.org/10.1186/s12905-022-01874-z

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Report of a case of renal collecting duct carcinoma with literature review

• Open access
• Published: 29 August 2024
• Volume 1 , article number  33 , ( 2024 )

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• Yong Cui 1 &
• Yuan Gao 2  

Collecting duct carcinoma (CDC) is a rare pathologic subtype of renal cell carcinoma that accounts for approximately 0.4–1% of cases and originates in the collecting ducts (Bellini ducts) of the renal medulla. The majority of patients are metastatic at the time of presentation, extremely malignant and rapidly progressive, with most patients dying 1–3 years after initial diagnosis. Currently, surgery is considered the only effective treatment. There is no uniform standard for postoperative adjuvant radiotherapy and chemotherapy.In this article, we report a case of an 85-year-old female patient with CDC who underwent radical nephrectomy. This is an extremely rare case. We describe the case and perform a literature review to report current research advances regarding the treatment and prognosis of patients with CDC. The aim of this study is to contribute to improving the diagnosis and treatment of CDC.

Avoid common mistakes on your manuscript.

1 Introduction

CDC is a rare pathologic subtype of renal cell carcinoma that accounts for approximately 0.4–1% of cases and originates from the collecting ducts of the renal medulla (Bellini ducts), Mancilla-Jimenz reported the first case of CDC [ 1 ].Due to the rapid progression of the disease and extensive metastasis to peripheral lymph nodes, the majority of patients have a very poor prognosis, with a median survival of less than 2 years [ 2 ]. Early diagnosis is an important factor in prolonging survival.Fleming and Lewi developed diagnostic criteria and CDC was isolated as a separate subtype of renal cancer.Although this disease has immunohistochemical features, it is difficult to characterize histologically due to its rarity and needs to be differentiated from other renal cell carcinomas and uroepithelial carcinomas [ 3 ].

We retrospectively analyzed the medical records of a patient with CDC admitted to Weifang People’s Hospital, and combined with the literature review, we analyzed the diagnosis and treatment of CDC in order to improve people's understanding of CDC, so as to reduce misdiagnosis and mistreatment.

2 Case report

An 85-year-old woman was admitted to the hospital with a complaint of hematuria for 3 months. The patient reported no distinct triggers or causes for the hematuria. She had chest pain and chest tightness. Prior to admission, she did not have lumbar pain, loss of appetite, fatigue, lethargy, or other systemic symptoms. A lower abdominal and pelvic computed tomography (CT) scan performed after admission revealed the following:Left upper renal calyx and renal parenchyma occupations; Small cyst of the right kidney; pelvic effusion (Fig.  1 ). Considering her age and the necessity of surgery, a team of urologists evaluated his physical condition and established a treatment plan for surgery. One week after admission, the patient underwent laparoscopic nephroureterectomy, which was successful.

The lower abdominal and pelvic CT scan revealed Left upper renal calyx and renal parenchyma occupations

2.1 Postoperative pathological diagnosis

Postoperative pathological examination revealed resection of the left kidney along with perirenal fat measuring 12 cm × 7 cm × 4.5 cm. The renal fat capsule was easily peeled. A mass measuring 2.5 cm × 1.5 cm × 1 cm was observed in the kidney. The section appeared grayish white and grayish red, was brittle, and had a close relationship with the renal peritoneum, 0.6 cm from it.

2.2 Pathological results

The left kidney tumor was glandular tubular and papillary. The size of the renal tumor was 2.5 cm × 1.5 cm × 1 cm. The tumor involved the renal pelvis and renal sinus fat, and did not involve the renal perineurium and perirenal fat. The nerves were invaded and cancerous emboli were seen in the vasculature. Ureteral and vascular breaks were clear (Fig.  2 ).

Pathological findings of renal collecting duct carcinoma (hematoxylin and eosin, 100×)

Immunohistochemical results: CK wide ( +), Vimentin ( +), E-Cadherin (partially +), RCC (scattered +), PAX-8 ( +),CAIX (focal +), P504S ( +), INI1 (weak +), Ki-67 (index 20%).

Pathological staging based on the American Joint Committee on Cancer (AJCC) 8th edition classified the tumor as pT3aNxMx.

2.3 Postoperative treatment

Postoperatively, pezopanib 0.8 g was administered orally once daily.Intravenous 160 mg of teraplizumab every 3 weeks for 1 month postoperatively. CT scans of the lower abdomen at 1 month postoperatively and 3 months postoperatively reported the following findings:

Postoperative left kidney; Striated dense shadow in the left adrenal region.This treatment has been maintained for 4 months. No adverse immune-related events occurred, and no signs of local recurrence or systemic metastasis were found. Therefore, the therapeutic effect has been highly favorable.In April after surgery, the patient was admitted to the hospital for diarrhea, and the patient died 3 days after admission.

3 Discussion

3.1 clinical manifestations.

CDC can occur at any age and is more common in younger people. Males are more likely to be affected than females by a ratio of approximately 2:1 [ 4 ].

Common clinical symptoms of CDC include painless hematuria, low back and abdominal pain, low back and abdominal masses, fatigue, fever, and weight loss or when the tumor develops metastasis, Usually most of the patients develop metastasis including bone and lymph node metastasis prior to treatment [ 5 ]. In this case, we presented to the hospital with painless hematuria as the main symptom.

3.2 Imaging features

The imaging features of CDC differ from those of other renal cell carcinomas. In renal tumors located in the zone connecting the renal cortex and medulla, the early presentation of poorly defined borders, mild enhancement, and metastasis require consideration of the diagnosis of CDC [ 6 ].

The organ of origin of CDC is water-rich renal tissue, and the interstitium of the tumor is characterized by increased fibrous tissue proliferation and collagenization, and the tumor parenchyma is denser than the surrounding normal tissue, which is a characteristic feature of CDC tumors on nonenhanced CT. These features differ from renal cell carcinoma originating in the renal cortex, where dense interstitial tissue or increased collagen secretion, proliferation of inflammatory fibroblast tissue and abundant fibrous tissue components are characteristic of CDC tumors. These features are important for the pathologic diagnosis of CDC, which shows low signal on magnetic resonance T2WI [ 7 ]. On dynamic enhancement scans, most CDC tumors show relatively low density in the renal cortex and medulla. The parenchyma of the mass is heterogeneous, with mild to moderate enhancement in the cortical or medullary stage, below the surrounding renal parenchyma. The medullary stage shows inhomogeneous and mildly delayed enhancement [ 6 ]. MRI shows isointensity or hyperintensity on T1WI and hypointensity on T2WI [ 8 ].

3.3 Pathologic features

Pathological examination is the gold standard for the diagnosis of CDC. Tumors tend to be yellowish-brown to white in color, may be associated with necrosis and hemorrhage, and show infiltrative growth, often invading the cortex, and may extend beyond the renal parenchyma, including perirenal fat, adrenal glands, and perirenal fascia [ 9 ]. Microscopically, CDCs are usually seen as tubular papillary structures, with tumor cells forming cobblestones along the glandular ducts. Lowly differentiated tumor cells show a nested, cord-like, sarcomatoid, or adenoidal cystic morphology with or without interstitial connective tissue reaction [ 10 ].

Genetic and biochemical approaches are becoming increasingly important for the identification and diagnosis of renal cancer. Many biomolecules, including epithelial mesenchymal transition (EMT) markers, such as N-calmodulin and poikilodulin, and human leukocyte molecules, such as HLA-G and HLA-E, have been reported to be biomarkers for renal cancer. Immunohistochemical examination of these biomarkers is important for determining the origin and diagnosis of CDC. positive expression of CK (AE1/AE3), CK7, CK19, EMA, wave proteins, CK34BE12, PNA, and european agglutinin (UEA), and negative expression of CD10 and CK20. the combination of CK34BE12 and PNA is able to detect 90% of the CDC. Pathologic and immunohistochemical findings are important for the diagnosis of CDC and differentiation from other types of renal cancer [ 11 , 12 , 13 ].

3.4 Differential diagnosis

Renal collecting duct carcinoma is mainly differentiated from the following malignant tumors.

Renal medullary carcinoma: renal medullary carcinoma originates from the collecting ducts near the cortical area, under the microscope, the tumor of renal medullary carcinoma is low differentiated and patchy distribution, and the tumor cells are arranged in an adenoidal cystic structure, and more neutrophil infiltration can be seen in the tumor body, and sickle-shaped erythrocytes can be seen at the same time [ 14 ].

Papillary renal cell carcinoma: According to the histopathological changes, it is divided into two subtypes: type I and type II. Tumor cells consist of papillary or tubular structures with a slender vascular axis, and foamy macrophages and cholesterol crystals can be seen in the core of the papillae; tumor cells are small, with sparse cytoplasm (type I) or tumor cells with abundant eosinophilic cytoplasm and high nuclear grading (type II), and areas of necrosis, sarcomatous differentiation and rhabdomyosarcomatous differentiation can be seen. Papillary renal cell carcinoma was positive for CK7, and the positive rate of P504S was high.

3.5 Treatment and prognosis

In the clinical setting, the initial diagnosis and treatment decisions for renal cancer are often made without histopathologic information, and the diagnosis can only be confirmed based primarily on imaging and after initial surgery. According to the literature, most CDC cases are high-grade and advanced, but there is no consensus on treatment options. Surgery remains the most effective treatment for patients with kidney cancer, even in advanced stages [ 15 ]. Surgical procedures include radical nephrectomy and partial nephrectomy, but given the highly aggressive nature of CDC, radical nephrectomy is recommended. Méjean et al. [ 16 ] reported that the median survival of six patients with CDC who underwent nephrectomy was only seven months, and three patients died perioperatively or postoperatively. CDC is highly biologically invasive, and patients are usually in poor general condition at the time of diagnosis. Surgical complications and postoperative recovery may prevent patients from receiving systemic therapy, so it is recommended that the diagnosis of CDC can be confirmed by biopsy, which can provide the best diagnostic and treatment plan for subsequent treatment.

In patients with CDC who develop metastases, the treatment regimen is usually based on uroepithelial tumors, using chemotherapy regimens, usually platinum or carboplatin in combination with gemcitabine. The prognosis for these regimens is poor, with survival statistically less than 12 months [ 17 ]. Orsola et al. [ 18 ] reported two cases of CDC who underwent adjuvant chemotherapy (doxorubicin + gemcitabine) after radical nephrectomy; however, the mean postoperative survival was only 5.6 months. A prospective phase II trial showed that, platinum-based combined with gemcitabine chemotherapy was effective in 23 patients with previously untreated mCDC undergoing 6 cycles of treatment, which showed objective remission rate (ORR), progression-free survival (PFS), and overall survival (OS) of 26 months, 7.1 months, and 10.5 months, respectively [ 19 ].

Tyrosine kinase inhibitors (TKIs) and mTOR inhibitors targeting the vascular endothelial growth factor (VEGF) pathway are important for the treatment of metastatic CCRCC. There is less evidence on the effectiveness of such agents in the treatment of NCCRCC, especially for mCDC.A small retrospective analysis of 13 patients with mCDC evaluated the activity of different TKIs: sunitinib, sorafenib, pazopanib, and the mTOR inhibitor tesirolimus. Only 2 patients were able to receive second-line treatment with sunitinib after disease progression, no patient survived more than 5 years, 4 patients experienced early disease progression, and 2 patients had long-term control of their disease with OS of 49 and 19 months, respectively [ 20 ].

Tamada et al. [ 21 ] reported that immunotherapy-based combination therapy has become the standard first-line treatment for metastatic RCC.CDC in combination with immunotherapy, the effect of which is unclear. A 62-year-old man was treated with pembrolizumab and axitinib for CDC with multiple bone metastases. after 7 months, the primary and metastatic lesions shrank and were evaluated as partial response.A 71-year-old man received pembrolizumab and axitinib for the treatment of CDC with lymph nodes and lung metastases. after 9 months, the primary and metastatic lesions had shrunk and were assessed as partial responses. Tumor cell expression of PD-L was negative in both patients, and CD4 + and CD8 + cells were observed in the tumors. The combination of pembrolizumab and axitinib is effective in the immunotherapy of metastatic CDC [ 22 ].

In summary, despite clinical advances in the treatment of metastatic RCC, the prognosis for patients with mCDC remains poor. Currently available treatment options are poor, and results from prospective trials are limited. For patients with localized disease, nephrectomy is the only potentially curative option, whereas for patients with mCDC, a doublet chemotherapy regimen containing platinum salts and gemcitabine is recommended.

4 Conclusion

In conclusion, CDC is a highly malignant and rare renal tumor with unique biological behavior, morphology and functional manifestations. Most patients with CDC have distant metastases at the time of initial diagnosis. The prognosis of CDC is generally poor. There is no standardized follow-up treatment plan for this tumor, and radical surgery is the only curative treatment for patients with limited CDC. However, it is prone to recurrence and metastasis after surgery.

Data availability

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

Tang C, Zhou Y, Ge S, et al. Incidence, clinical characteristics, and survival of collecting duct carcinoma of the kidney: a population-based study. Front Oncol. 2021;11: 727222.

Article   PubMed   PubMed Central   Google Scholar  

Bahadoram S, Davoodi M, Hassanzadeh S, et al. Renal cell carcinoma: an overview of the epidemiology, diagnosis, and treatment. G Ital Nefrol. 2022;39(3):9.

Google Scholar  

Panunzio A, Tappero S, Hohenhorst L, et al. Collecting duct carcinoma: epidemiology, clinical characteristics and survival. Urol Oncol. 2023;41(2):110–7.

Article   Google Scholar  

Tokuda N, Naito S, Matsuzaki O, et al. Collecting duct (Bellini duct) renal cell carcinoma: a nationwide survey in Japan. J Urol. 2006;176(1):40–3.

Article   PubMed   Google Scholar  

Wang X, Hao J, Zhou R, et al. Collecting duct carcinoma of the kidney: a clinicopathological study of five cases. Diagn Pathol. 2013;8:96.

Lyu Z, Liu L, Li H, et al. Imaging analysis of 13 rare cases of renal collecting (Bellini) duct carcinoma in northern China: a case series and literature review. BMC Med Imaging. 2021;21(1):42.

Zhu Q, Wu J, Wang Z, et al. The MSCT and MRI findings of collecting duct carcinoma. Clin Radiol. 2013;68(10):1002–7.

Article   CAS   PubMed   Google Scholar  

Pickhardt PJ, Siegel CL, McLarney JK. Collecting duct carcinoma of the kidney: are imaging findings suggestive of the diagnosis? AJR Am J Roentgenol. 2001;176(3):627–33.

Seo AN, Yoon G, Ro JY. Clinicopathologic and molecular pathology of collecting duct carcinoma and related renal cell carcinomas. Adv Anat Pathol. 2017;24(2):65–77.

Chao D, Zisman A, Pantuck AJ, et al. Collecting duct renal cell carcinoma: clinical study of a rare tumor. J Urol. 2002;167(1):71–4.

Li M, Vuolo MA, Weidenheim KM, et al. Collecting-duct carcinoma of the kidney with prominent signet ring cell features. Mod Pathol. 2001;14(6):623–8.

Kren L, Valkovsky I, Dolezel J, et al. HLA-G and HLA-E specific mRNAs connote opposite prognostic significance in renal cell carcinoma. Diagn Pathol. 2012;7:58.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Behnes CL, Hemmerlein B, Strauss A, et al. N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma. Diagn Pathol. 2012;7:95.

Elliott A, Bruner E. Renal medullary carcinoma. Arch Pathol Lab Med. 2019;143(12):1556–61.

Guillaume Z, Allory Y, Auclin E, et al. Collecting duct carcinoma and renal medullary carcinoma in the age of new therapies. Bull Cancer. 2023;110(4):450–62.

Méjean A, Rouprêt M, Larousserie F, et al. Is there a place for radical nephrectomy in the presence of metastatic collecting duct (Bellini) carcinoma? J Urol. 2003;169(4):1287–90.

Panunzio A, Sorce G, Tappero S, et al. Mortality according to treatment in metastatic collecting duct renal cell carcinoma. Clin Genitourin Cancer. 2023;21(2):295–300.

Orsola A, Trias I, Raventós CX, et al. Renal collecting (Bellini) duct carcinoma displays similar characteristics to upper tract urothelial cell carcinoma. Urology. 2005;65(1):49–54.

Oudard S, Banu E, Vieillefond A, et al. Prospective multicenter phase II study of gemcitabine plus platinum salt for metastatic collecting duct carcinoma: results of a GETUG (Groupe d’Etudes des Tumeurs Uro-Génitales) study. J Urol. 2007;177(5):1698–702.

Procopio G, Testa I, Iacovelli R, et al. Treatment of collecting duct carcinoma: current status and future perspectives. Anticancer Res. 2014;34(2):1027–30.

PubMed   Google Scholar  

Tamada S, Ikarashi D, Tsuyukubo T, et al. Efficacy of combination therapy with pembrolizumab and axitinib for metastatic renal collecting duct cell carcinoma: a report on two cases. IJU Case Rep. 2022;5(6):438–41.

Plimack ER, Powles T, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib as first-line treatment of advanced renal cell carcinoma: 43-month follow-up of the phase 3 KEYNOTE-426 study. Eur Urol. 2023;84(5):449–54.

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Cui, Y., Gao, Y. Report of a case of renal collecting duct carcinoma with literature review. Discov Med 1 , 33 (2024). https://doi.org/10.1007/s44337-024-00051-5

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Evaluation of Serum Cancer Antigen (CA)-125 Levels as a Biomarker for Ovarian Lesions: Correlation With Histopathological Diagnosis and Clinical Outcomes

Nanda j patil.

1 Department of Pathology, Krishna institute of Medical Sciences, Krishna Vishwa Vidyapeeth “Deemed to be University”, Karad, IND

Avinash Mane

2 Department of Pathology, Krishna institute of Medical Sciences, Krishna Vishwa Vidyapeeth "Deemed To Be University", Karad, IND

Atul B Hulwan

3 Department of Pathology, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth "Deemed To Be University", Karad, IND

Mohammad Asim Khan

4 Department of Community Medicine, Mahatma Gandhi Medical College, Jaipur, IND

Huzaifa Umar

5 Operational Research Center in Healthcare, Near East University, Nicosia, TUR

Background: Ovarian cancer is a significant cause of morbidity and mortality among women worldwide. Early detection and accurate diagnosis are crucial for improving patient outcomes. Serum biomarkers, such as cancer antigen 125 (CA-125), have shown promise in aiding the diagnosis and monitoring of ovarian lesions.

Objective: This study aimed to assess the utility of serum CA-125 levels as a biomarker for ovarian lesions, correlating with histopathological diagnosis and clinical outcomes.

Methods: A prospective observational study was conducted, enrolling 144 female patients presenting with suspected ovarian lesions at a hospital or clinic. Demographic data, physical examination findings, imaging results, and serum CA-125 levels were collected at baseline. Patients underwent laparoscopic or surgical intervention for tissue biopsy or resection, and a histopathological examination was performed to confirm the diagnosis. Clinical outcomes, including response to treatment and disease recurrence, were monitored during follow-up visits.

Results: The baseline characteristics of the study population showed significant differences between participants with and without ovarian lesions. Older age (mean age 54.8 vs. 45.6) years; p < 0.001) and higher serum CA-125 levels (65.9 vs. 28.6 U/mL, p < 0.001) were associated with ovarian pathology. Histopathological analysis revealed benign cystadenoma as the most prevalent subtype (31.8%), followed by serous carcinoma (27.3%) and borderline tumors (22.7%). Clinical outcomes indicated favorable treatment responses in most patients, with 77.3% achieving complete remission and 15.9% experiencing recurrence. However, elevated CA-125 levels were significantly associated with poorer treatment response (p < 0.001) and higher rates of recurrence, suggesting its potential as a prognostic biomarker for ovarian lesions.

Conclusion: Serum CA-125 levels serve as a valuable biomarker for ovarian lesions, aiding in the diagnosis and monitoring of ovarian cancer. However, its utility is limited by its lack of specificity, particularly in differentiating between benign and malignant ovarian lesions. Integrating CA-125 with other clinical parameters and imaging modalities may enhance diagnostic accuracy and improve patient outcomes in ovarian cancer management.

Introduction

Ovarian cancer represents a significant health challenge worldwide, ranking as the seventh most common cancer and the eighth leading cause of cancer-related deaths among women globally [ 1 , 2 ]. According to GLOBOCAN 2020 statistics, 1.6% of new cases and 2.1% of deaths at all sites are attributable to ovarian cancer [ 1 ]. The disease is characterized by insidious onset and often presents at an advanced stage, resulting in a poor prognosis and limited treatment options [ 3 ]. Early detection and accurate diagnosis are essential for improving patient outcomes and reducing mortality rates associated with ovarian cancer [ 4 ]. In this context, serum biomarkers have emerged as valuable tools for the screening, diagnosis, and monitoring of ovarian lesions, offering noninvasive methods for detecting diseases and guiding treatment decisions [ 5 ].

Cancer antigen 125 (CA-125) is a biomarker that has garnered considerable attention in gynecological oncology. CA-125 is a glycoprotein antigen encoded by the MUC16 gene and is expressed in various epithelial tissues, including the ovarian epithelium [ 6 ]. Elevated serum CA-125 levels have been associated with various gynecological malignancies (fallopian tube cancer and endometrial cancer), particularly ovarian cancer, making it a clinically relevant biomarker for this disease [ 7 ]. However, CA-125 is not specific to ovarian cancer and can be elevated in benign conditions such as endometriosis, pelvic inflammatory disease, and uterine fibroids, as well as during menstruation and pregnancy [ 8 ]. Despite its limitations, CA-125 remains one of the most widely used biomarkers in clinical practice for ovarian cancer screening, monitoring treatment response, and detecting disease recurrence [ 9 ].

The utility of serum CA-125 level as a biomarker for ovarian lesions has been investigated in numerous studies, with conflicting findings regarding its diagnostic accuracy, sensitivity, and specificity [ 10 ]. Although elevated CA-125 levels have been associated with ovarian malignancies, including epithelial ovarian cancer, germ cell tumors, and sex cord-stromal tumors, the ability of biomarkers to differentiate between benign and malignant ovarian lesions remains suboptimal [ 11 ]. Furthermore, the use of CA-125 as a standalone diagnostic marker has limitations, particularly in premenopausal women and those with benign gynecological conditions, where false-positive results are common [ 11 ]. To minimize false-positive results in these cases, a higher cutoff, typically around 65 U/mL, may be recommended when using CA-125 as a diagnostic marker.

Despite these challenges, CA-125 continues to play a crucial role in the clinical management of ovarian cancer patients, guiding diagnostic workups, treatment selection based on the specific characteristics of the cancer, and the patient’s overall health and disease monitoring. Moreover, recent advances in biomarker research, including the development of novel biomarkers and multiplex assays, offer promising avenues for improving the accuracy and reliability of ovarian cancer diagnosis [ 7 ] [ 9 ]. Integrating serum CA-125 levels with other clinical parameters, imaging modalities, and molecular profiling techniques may enhance the diagnostic sensitivity and specificity of biomarker-based screening strategies, leading to earlier detection and improved outcomes in patients with ovarian cancer [ 12 ].

In this context, the study aimed to evaluate the utility of serum CA-125 levels as biomarkers for ovarian lesions, correlating them with histopathological diagnosis and clinical outcomes. By examining the association between CA-125 levels and ovarian lesion characteristics, including histological subtype, grade, and clinical stage, this study aimed to elucidate the diagnostic and prognostic implications of serum CA-125 levels in ovarian cancer management.

Materials and methods

This study employed a prospective observational design to assess the utility of serum CA-125 levels as a biomarker for ovarian lesions among female patients. This study aimed to evaluate the association between serum CA-125 levels and ovarian lesion characteristics, as well as clinical outcomes. The study included female patients aged ≥ 18 years who presented with suspected ovarian lesions at the gynecology department. The inclusion criteria were clinical suspicion of ovarian lesions based on symptoms, physical examination findings, and imaging results. However, patients with a history of ovarian cancer or diagnosed ovarian lesions were excluded from the study to maintain consistency within the study population.

Inclusion criteria: female patients aged ≥ 18 years presenting at the gynecology department with suspected ovarian lesions were eligible for inclusion in this study. Suspected ovarian lesions were defined based on symptoms reported by the patients, physical examination findings, and imaging results such as pelvic ultrasound or magnetic resonance imaging (MRI). These symptoms may include pelvic pain, abdominal bloating, changes in urinary habits, or abnormal vaginal bleeding. Eligible participants were required to have the capacity to provide informed consent for study participation and to be willing to undergo serum CA-125 testing and subsequent evaluations.

Exclusion criteria: patients with a history of ovarian cancer or diagnosed ovarian lesions were excluded from the study to maintain homogeneity within the study population. Additionally, individuals who had been diagnosed with ovarian lesions prior to enrollment were not eligible for inclusion. This exclusion criterion aimed to ensure that the study focused on patients with suspected rather than confirmed ovarian lesions. Patients with known benign conditions (such as endometriosis or fibroids) that could independently elevate CA-125 levels were excluded from the study. Furthermore, patients who were unable or unwilling to provide informed consent for participation in the study were also excluded.

Convenience sampling was used to recruit participants from the gynecology department, ensuring the enrollment of eligible patients seeking evaluation for suspected ovarian lesions within the study setting. This sampling method facilitated efficient recruitment while ensuring that the study population was representative of the patient population seeking medical care for suspected ovarian lesions at hospitals or clinics. Before enrollment, eligible patients were provided with detailed information about the study objectives, procedures, and potential risks. Written informed consent was obtained from all the participants. Ethical approval was obtained from the institutional review board (IRB) before the commencement of the study. This study was conducted by the principles outlined in the Declaration of Helsinki. Patient confidentiality was strictly maintained, and all data were anonymized to protect participants’ privacy.

Comprehensive demographic information was gathered from each participant, including age, medical history, and relevant clinical details. This included details such as previous medical conditions, surgical history, family history of gynecological disorders, and current medications. Collecting these demographic data provided insights into the characteristics of the study population and helped identify potential confounding factors. A thorough physical examination, including a pelvic examination, was performed on each participant by qualified healthcare professionals. The pelvic examination aimed to assess the presence of ovarian lesions, evaluate their size, location, and characteristics, and identify any associated symptoms or signs, such as palpable masses or abdominal tenderness. This examination is crucial for initial clinical assessment and provides valuable information for subsequent diagnostic evaluations.

Patients underwent imaging studies, such as pelvic ultrasound or MRI, to visualize and characterize suspected ovarian lesions. Pelvic ultrasound is a commonly used imaging modality that allows for the visualization of ovarian structures and the detection of abnormalities such as cysts or tumors. MRI provides detailed images of pelvic structures and is particularly useful for assessing the extent and characteristics of ovarian lesions, including their size, morphology, and proximity to the adjacent structures. These imaging studies play a vital role in confirming the presence of ovarian lesions and guiding further diagnostic and therapeutic interventions.

Blood samples were collected from each participant to measure serum CA-125 levels using standard laboratory assays. CA-125 is a tumor marker that is frequently elevated in patients with ovarian cancer and other gynecological disorders. Measurement of serum CA-125 levels serves as a noninvasive diagnostic tool to assess the likelihood of ovarian lesions and monitor disease progression. This biomarker provided valuable information regarding the presence and severity of ovarian lesions and contributed to the overall diagnostic evaluation of study participants.

Patients diagnosed with suspected ovarian lesions underwent laparoscopic or surgical intervention for tissue biopsy or resection. Laparoscopic procedures involve the insertion of a thin, flexible tube with a camera (laparoscope) through a small incision in the abdomen to visualize and access the ovaries. Surgical interventions may include procedures such as ovarian cystectomy, salpingo-oophorectomy, or hysterectomy, depending on the nature and extent of the ovarian lesions. Tissue sampling through biopsy or resection allows the collection of ovarian tissue specimens for further histopathological evaluation. Ovarian tissue samples obtained from surgical or laparoscopic procedures were sent to the pathology department for histological examination and diagnosis. Experienced pathologists conducted a thorough microscopic evaluation of the tissue specimens to assess the cellular morphology, tissue architecture, and any pathological features indicative of ovarian lesions. Histopathological examination was performed to confirm the presence of ovarian lesions, classify them into specific histological subtypes (e.g., serous, mucinous, endometrioid), and determine the grade or level of malignancy if applicable. The histological diagnosis provided crucial information regarding the nature, extent, and severity of ovarian lesions, guiding subsequent treatment decisions and prognostic assessments. Additionally, histopathological examination allowed for the identification of concurrent or incidental pathologies within ovarian tissue samples. The histopathological evaluation findings were documented in detailed pathology reports, which formed the basis for clinical management and further patient follow-up.

Following the initial assessment and diagnosis, patients were subjected to regular follow-up evaluations in every 3 to 6 months for 2 years to monitor their clinical progress and outcomes. These follow-up assessments aimed to track the response to treatment, identify any recurrence of ovarian lesions, and evaluate the overall survival rates. Patients were scheduled for periodic visits to the clinic or hospital, typically at predetermined intervals based on the individual’s treatment plan and the nature of their ovarian lesions. During these follow-up visits, healthcare providers conducted comprehensive clinical examinations, including pelvic examinations and imaging studies, to assess the status of ovarian lesions and detect any signs of disease progression or recurrence. Any adverse events, treatment-related complications, or new symptoms were documented and managed accordingly. Regular monitoring of clinical outcomes allows healthcare professionals to tailor treatment strategies and provide appropriate interventions to optimize patient outcomes.

Serial measurements of serum CA-125 levels were performed during follow-up visits to monitor disease progression and treatment response. CA-125 is a tumor marker commonly used in the management of ovarian cancer and other gynecological disorders. Monitoring changes in serum CA-125 levels over time provides valuable insights into the efficacy of treatment interventions and the course of disease progression. For CA125, the normal upper limit was 35 U ml−1. Elevated CA-125 levels often indicate the presence or recurrence of ovarian lesions, whereas decreasing or stable CA-125 levels may suggest a favorable response to treatment or disease remission. These serial measurements of CA-125 levels were integrated into the overall clinical assessment of patients, complementing other diagnostic modalities and guiding clinical decision-making. Any significant changes in CA-125 levels were promptly investigated and appropriate interventions were implemented as necessary. Systematic monitoring of serum CA-125 levels during follow-up visits enabled healthcare providers to assess treatment efficacy, detect disease recurrence at an early stage, and optimize patient management strategies to improve clinical outcomes.

Descriptive statistics were used to summarize the demographic characteristics, serum CA-125 levels, histopathological findings, and clinical outcomes of the study population. Correlation analyses were conducted to assess the association between serum CA-125 levels and histopathological diagnosis. Survival analyses, such as Kaplan-Meier curves, were employed to evaluate the prognostic value of CA-125 levels in predicting clinical outcomes.

The baseline characteristics of the study population revealed notable differences between participants with and without ovarian lesions. First, the mean age of participants with ovarian lesions (54.8 years ± 7.2) was significantly higher than that of those without lesions (45.6 years ± 9.1), indicating that age may be a potential risk factor for the development of ovarian pathology (p < 0.001). Additionally, a higher proportion of postmenopausal women were observed in the ovarian lesion group (52.3%) than in the group without lesions (39.3%), suggesting that menopausal status could influence the likelihood of ovarian lesions (p = 0.012). Moreover, serum CA-125 levels were substantially elevated in participants with ovarian lesions (65.9 U/mL ± 22.7) compared to those without lesions (28.6 U/mL ± 12.4), indicating a strong association between elevated CA-125 levels and the presence of ovarian pathology (p < 0.001) (Table  1 ).

Histopathological diagnosis of ovarian lesions provides insight into the nature and composition of the identified lesions. Benign cystadenoma was the most prevalent histological subtype among participants with ovarian lesions, accounting for 31.8% of the cases. This finding suggests that benign cystic tumors are common among individuals with suspected ovarian pathologies. Additionally, serous carcinoma and borderline tumors were identified in 27.3% and 22.7% of the cases, respectively, indicating the presence of malignant and potentially precancerous lesions within the study population. This diverse histological spectrum highlights the heterogeneity of ovarian lesions and underscores the importance of accurate histopathological evaluation for appropriate diagnosis and management (Table  2 ).

Clinical outcomes of patients with ovarian lesions provide valuable insights into the prognosis and management of ovarian pathologies. A high proportion of patients with ovarian lesions demonstrated a favorable treatment response, with 77.3% achieving complete remission and 20.5% experiencing partial response. This finding suggests that most ovarian lesions are amenable to treatment interventions, resulting in favorable clinical outcomes. However, a subset of patients (2.2%) did not respond to treatment, indicating the presence of refractory or aggressive disease phenotypes that may require alternative therapeutic approaches. Furthermore, the recurrence rate of ovarian lesions was 15.9%, underscoring the importance of long-term surveillance and follow-up to monitor disease progression and detect recurrence at an early stage. The median overall survival of 48 months among patients with ovarian lesions highlights the potential for prolonged survival with appropriate management strategies (Table  3 ).

n: number of patients; %: percentage

The association between serum CA-125 levels and clinical outcomes provides valuable prognostic information regarding the utility of CA-125 as a biomarker of ovarian pathology. Higher CA-125 levels were significantly associated with poorer treatment response, as evidenced by the lower proportion of patients achieving complete remission and higher rates of lesion recurrence among individuals with elevated CA-125 levels (p < 0.001). This finding suggests that elevated CA-125 levels may indicate more aggressive disease phenotypes or resistance to conventional treatment. Additionally, the strong association between elevated CA-125 levels and lesion recurrence underscores the potential role of CA-125 as a predictive biomarker of disease progression and recurrence risk. Overall, these findings support the clinical utility of serum CA-125 levels in the risk stratification, treatment monitoring, and prognostic assessment of patients with ovarian lesions (Table  4 ).

Ovarian cancer is a significant cause of morbidity and mortality among women worldwide, with a late-stage diagnosis contributing to a poor prognosis and limited treatment options. Early detection plays a crucial role in minimizing the morbidity and mortality associated with cancer [ 1 ]. Therefore, there is an urgent need for genuine and reliable cancer indicators. PSA, CEA, and CA-125/MUC16 are frequently used cancer indicators, while exosomes, microRNA, and circulating tumor cells are emerging as a new source of biomarkers [ 13 ]. Biomarkers are integral in guiding treatment decisions by predicting disease outcomes and facilitating personalized treatment plans. They play a crucial role in monitoring disease progression, enabling adjustments to treatment strategies, and identifying early indicators of disease recurrence. This study aimed to evaluate the utility of serum CA-125 levels as biomarkers for ovarian lesions, correlating them with histopathological diagnosis and clinical outcomes. Serum CA-125 is a well-established tumor marker commonly used for the diagnosis and management of ovarian cancer [ 14 ]. Elevated CA-125 levels have been associated with various gynecological malignancies, including ovarian, endometrial, and fallopian tube cancers [ 7 ]. However, CA-125 is not specific to ovarian cancer and can be elevated in various benign conditions, such as endometriosis, pelvic inflammatory disease, and uterine fibroids. Despite its limitations, CA-125 remains a valuable tool in clinical practice for screening, monitoring treatment response, and detecting disease recurrence in ovarian cancer patients [ 15 ].

In this study, serum CA-125 levels were significantly elevated in participants with ovarian lesions compared with those without lesions, indicating a strong association between elevated CA-125 levels and ovarian pathology. Benign cystadenoma was the most prevalent histological subtype among participants with ovarian lesions, accounting for 31.8% of the cases. This finding suggests that benign cystic tumors are common among individuals with suspected ovarian pathologies. These findings are consistent with those of previous studies that demonstrated the utility of CA-125 as a biomarker for ovarian lesions. The observed correlation between serum CA-125 levels and histopathological diagnosis further supports the diagnostic value of CA-125 in identifying ovarian malignancies and guiding treatment decisions [ 7 , 8 , 16 ]. Histopathological evaluation remains the gold standard for diagnosing ovarian lesions and determining their malignant potential [ 17 ]. In this study, a diverse spectrum of ovarian lesions was identified, including benign cystadenomas, borderline tumors, and serous carcinomas. Benign cystadenomas were the most prevalent histological subtypes, followed by borderline and serous carcinomas. These findings highlight the heterogeneity of ovarian lesions and the importance of accurate histopathological diagnosis in guiding clinical management [ 18 ].

The correlation between serum CA-125 levels and histopathological diagnosis provides valuable insights into the biological behavior of ovarian lesions. Elevated CA-125 levels are significantly associated with malignant histological subtypes such as serous carcinomas, suggesting a potential role for CA-125 in predicting tumor aggressiveness and metastatic potential [ 19 ]. However, it is important to note that CA-125 levels can be influenced by various factors, including inflammation, menstruation, and other non-neoplastic conditions, which may limit its specificity as a standalone diagnostic marker [ 20 ].

The clinical outcomes of patients with ovarian lesions were evaluated to assess the prognostic value of serum CA-125 levels in predicting treatment response and overall survival. Most patients demonstrated a favorable treatment response, with a high proportion of patients achieving complete or partial remission. However, a subset of patients experience disease recurrence or demonstrate resistance to conventional treatment modalities, highlighting the challenges of managing advanced-stage ovarian cancer. Patients with elevated CA-125 levels are more likely to exhibit poorer treatment responses and higher rates of disease recurrence, suggesting a potential role for CA-125 as a prognostic marker for ovarian cancer [ 21 ]. These findings are consistent with those of previous studies demonstrating the prognostic significance of CA-125 in predicting clinical outcomes and survival in ovarian cancer patients [ 22 ]. Elevated CA-125 levels have been associated with advanced-stage disease, suboptimal debulking surgery, and an increased risk of recurrence, highlighting their utility as prognostic indicators of disease progression and survival [ 23 ].

Despite these promising findings, this study had several limitations. First, the study design may have introduced selection bias and confounding variables that could impact the interpretation of the results. The use of convenience sampling may introduce selection bias, as participants were recruited based on their availability and presentation at the gynecology department rather than through random selection from the population. This could affect the generalizability of the study findings to broader populations. Second, the sample size was relatively small, limiting the generalizability of the findings to larger populations. The age disparity between the case and control groups could potentially influence CA 125 levels, which might skew the study results. Additionally, the study focused exclusively on serum CA-125 levels and histopathological diagnosis, without considering other potential biomarkers or imaging modalities that could provide complementary diagnostic information. Future research directions should include prospective studies with larger sample sizes to validate the findings of this study and assess the long-term prognostic implications of serum CA-125 levels in patients with ovarian cancer. Furthermore, investigations into novel biomarkers, imaging techniques, and molecular profiling approaches may enhance the accuracy of ovarian cancer diagnosis, prognostication, and personalized treatment strategies.

Conclusions

In conclusion, this study provides valuable insights into the utility of serum CA-125 levels as biomarkers for ovarian lesions, correlating them with histopathological diagnosis and clinical outcomes. Elevated CA-125 levels are significantly associated with ovarian pathology, malignant histological subtypes, and poor treatment response. These findings support the clinical utility of CA-125 in diagnosing ovarian cancer, monitoring treatment responses, and predicting clinical outcomes. However, further research is warranted to validate these findings and explore the potential implications of personalized treatment strategies and prognostic prediction models in ovarian cancer management.

Disclosures

Human subjects: Consent was obtained or waived by all participants in this study. Krishna Vishwa Vidyapeeth issued approval IEC/838/2022-23.

Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:

Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.

Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.

Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Author Contributions

Concept and design:   Nanda J. Patil, Avinash Mane , Atul B. Hulwan, Mohammad Asim Khan, Huzaifa Umar

Acquisition, analysis, or interpretation of data:   Nanda J. Patil, Avinash Mane , Atul B. Hulwan, Mohammad Asim Khan, Huzaifa Umar

Drafting of the manuscript:   Nanda J. Patil, Avinash Mane , Atul B. Hulwan, Mohammad Asim Khan, Huzaifa Umar

Critical review of the manuscript for important intellectual content:   Nanda J. Patil, Avinash Mane , Atul B. Hulwan, Mohammad Asim Khan, Huzaifa Umar

Supervision:   Nanda J. Patil