STIs Impact on Fertility: PID, HPV, and Cervical Cancer

Sexually transmitted infections (STIs) can profoundly affect reproductive health, often in ways that remain hidden until complications arise. Many people tend to associate STIs with temporary symptoms or simple treatments, but the reality is more complex. The impact of STIs on fertility, particularly through conditions like pelvic inflammatory disease (PID), human papillomavirus (HPV), and cervical cancer, can be profound and long-lasting. Over the years, interacting with healthcare professionals and reviewing extensive research has revealed a consistent theme: the damage from these infections can be silent, with consequences surfacing much later. Understanding this chain reaction is crucial for improving outcomes and managing fertility challenges effectively. This article delves into the intricate relationships between STIs and fertility, unraveling how these infections interact with reproductive biology and exploring the pathways to preserving reproductive health.

The Intricate Dance of Fertility and STIs

Fertility hinges on a finely tuned system where eggs travel through fallopian tubes, sperm meet them at just the right moment, and the uterine environment must be conducive to implantation. However, STIs can disrupt this delicate balance at multiple points.

Cervix: The Gateway to the Reproductive Tract

The cervix acts as a barrier, protecting the upper reproductive tract from infections. However, diseases like chlamydia and gonorrhea often start here, causing inflammation that allows pathogens to spread upward. Persistent infections with high-risk HPV strains can lead to alterations in cervical cells over time, sometimes resulting in precancerous changes or cervical cancer.

Uterus and Endometrium: The Site of Implantation

Inflammation here can disrupt the uterine lining, affecting its ability to support a pregnancy. Even after infections are treated, residual inflammation can persist, influencing fertility.

Fallopian Tubes: A Critical Junction

The fallopian tubes are particularly vulnerable to infections. When pathogens ascend to the tubes, the body’s healing response can lead to scar tissue and adhesions, potentially blocking the passage of eggs or causing ectopic pregnancies.

Ovaries: Indirectly Affected

While direct infection of the ovaries is rare, they can be impacted by inflammation or abscesses in adjacent tissues, which may influence ovarian function.

Immune Environment: A Delicate Balance

Chronic inflammation and persistent viral infections can subtly affect implantation and early pregnancy. Although research in this area is ongoing, maintaining immune balance is undoubtedly crucial for fertility.

The Silent Threat

A surprising aspect of STIs is their often silent nature. For instance, up to 70–80% of chlamydia infections are asymptomatic, silently causing damage and scarring that can affect fertility.

Navigating the Reproductive Anatomy

Understanding how STIs impact fertility requires a basic knowledge of the reproductive anatomy and its functions.

Fallopian Tubes

These slender tubes are the pathways for eggs traveling from the ovaries to the uterus. Blockages here due to infections are a common cause of infertility.

Uterus

As the site of implantation and fetal growth, any inflammation or infection can compromise its ability to support a pregnancy.

Cervix

This structure acts as a protective barrier against infections and helps maintain a pregnancy during gestation.

Ovaries

Responsible for producing eggs and hormones like estrogen and progesterone, the ovaries can be indirectly affected by STIs, impacting their function.

Recognizing these structures’ roles highlights the importance of early detection and treatment of STIs to prevent long-term fertility issues.

Pelvic Inflammatory Disease (PID): Hidden Consequences

PID represents a spectrum of infection and inflammation in the upper reproductive tract, including the uterus, fallopian tubes, and ovaries. It often results from untreated or inadequately treated lower tract infections like chlamydia and gonorrhea, but other organisms can also contribute.

The Development of PID

• Cervical Colonization: Microbes initially colonize the cervix, leading to cervicitis.

• Ascending Infection: The infection travels to the uterus, causing endometritis.

• Spread to Fallopian Tubes: It reaches the fallopian tubes (salpingitis) and sometimes the ovaries (oophoritis), occasionally forming a tubo-ovarian abscess.

• Inflammatory Response: The body responds with inflammation, which can lead to scarring and adhesions that distort the tubes even after the infection resolves.

This inflammatory response is why a seemingly short-term infection can have long-term implications for fertility.

Statistical Insights

• Untreated Chlamydia: Approximately 10–15% of untreated chlamydia cases lead to PID.

• Infertility Post-PID: About 1 in 8 women with a history of PID report difficulties conceiving later.

• Risk with Repeated Episodes: Infertility risk increases to 8–12% after one PID episode, approximately 20% after two, and up to 40% after three, with a heightened risk of ectopic pregnancy.

Symptoms and Subclinical Challenges

Classic PID presents with lower abdominal pain, pain during intercourse, abnormal bleeding, unusual discharge, fever, and sometimes nausea. However, a significant portion of PID cases are subclinical, meaning they present minimal symptoms while still causing damage. This silent progression underscores the importance of screening programs for chlamydia and other STIs in reducing ectopic pregnancy and infertility rates.

Diagnosing and Treating PID

Diagnosis is often clinical, based on symptoms and pelvic exam findings, with tests for chlamydia and gonorrhea. Ultrasounds may be used to detect a tubo-ovarian abscess, and pregnancy is ruled out to differentiate from an ectopic pregnancy. Treatment typically involves antibiotics targeting chlamydia, gonorrhea, and anaerobes. In severe cases, hospitalization and intravenous therapy are necessary. While symptoms improve rapidly with treatment, structural damage like scarring is irreversible.

Fertility After PID

Even after clearing the infection, anatomical restoration isn’t guaranteed. Some individuals may have open tubes and conceive easily, while others experience blockages. Fertility evaluations after PID often include:

• Fallopian Tube Patency Testing: Dye-based X-rays (HSG) or contrast ultrasounds (HyCoSy) assess whether tubes are open.

• Hydrosalpinx Detection: Identifying fluid-filled, damaged tubes is crucial as they lower implantation odds and increase miscarriage risk with IVF. Removing or clipping a hydrosalpinx before IVF can significantly improve success rates.

• Laparoscopic Examination: Direct visualization and dye testing can confirm patency and allow for surgical intervention when necessary.

In assisted reproduction, tubal factor infertility is a common indication for IVF, with studies indicating that treating hydrosalpinx beforehand improves live birth rates. The extent of tubal damage, rather than the mere history of PID, most strongly influences fertility outcomes.

Beyond Chlamydia and Gonorrhea

Several other factors can influence the development of PID and its impact on fertility:

• Mycoplasma Genitalium: This organism is increasingly implicated in cervicitis and PID and often presents treatment challenges due to antibiotic resistance.

• BV-associated Bacteria: While bacterial vaginosis (BV) itself is not classified as an STI, its associated bacterial communities frequently accompany PID and contribute to inflammation.

• Intrauterine Devices (IUDs): Modern data indicate that the risk of PID with an IUD is primarily limited to the first three weeks post-insertion, usually related to pre-existing cervical infections. Long-term IUD use doesn’t consistently pose a sustained risk for PID.

HPV and Fertility: Disentangling the Myths

HPV encompasses over 200 virus strains, with more than a dozen classified as high-risk for cancer. Almost all sexually active individuals will encounter HPV at some point, but the body’s immune system typically clears the virus within 1–2 years.

HPV’s Direct Impact on Fertility

For most people, HPV doesn’t directly reduce fertility. The primary concerns arise from:

• Cervical Precancer Treatments: Procedures like LEEP (loop electrosurgical excision) or cold knife cone can affect cervical strength or mucous production.

• Psychosocial and Logistical Challenges: Managing abnormal results during reproductive years can be stressful.

• Sperm and Embryo Effects: Some studies suggest a slight negative impact of HPV on sperm motility or IVF outcomes, but findings are inconsistent and the overall effect appears minimal.

From a fertility perspective, HPV’s indirect effects through cervical health are more significant than the infection itself.

HPV Persistence and Cancer Risk

• Clearance Rates: Approximately 70% of HPV infections clear within a year, and 90% within two years.

• Cancer-Causing Types: High-risk HPV types 16 and 18 account for about 70% of cervical cancers globally.

• Persistence Factors: Immunosuppression, smoking, and chronic cervical inflammation can increase the likelihood of persistent infections.

Cervical Procedures and Pregnancy Outcomes

For mild abnormalities, clinicians often opt for monitoring with repeat testing, as many lesions regress. When high-grade lesions (CIN2 or CIN3) persist, excisional procedures are typically recommended.

• Fertility: Ovulation and conception ability generally remain unaffected. The cervix doesn’t obstruct sperm, and conception rates post-LEEP usually align with general population rates.

• Miscarriage: Early miscarriage rates don’t consistently rise after shallow excisions, though deeper or repeated excisions may slightly increase risk.

• Preterm Birth: Meta-analyses indicate a modest increase in preterm birth risk after LEEP, especially with deeper excisions. Monitoring cervical length during pregnancy is standard after significant excisions.

• Cervical Insufficiency: While rare, it can occur, particularly after extensive or repeated cones. Some patients may require a cerclage during pregnancy if cervical length is concerning.

The depth and volume of tissue removed correlate with obstetric risks. Decisions about excision often involve weighing lesion severity, likelihood of regression, and future pregnancy plans.

HPV Vaccination and Reproductive Health

Countries with high HPV vaccine uptake report remarkable reductions in high-grade cervical abnormalities and cervical cancers among vaccinated populations. For instance, in England, women vaccinated at ages 12–13 experienced an 87% reduction in cervical cancer compared to unvaccinated groups. Similar declines are observed in Australia and Scotland.

There’s no evidence that vaccination harms fertility. By preventing precancer and reducing the need for excisional procedures, vaccination indirectly supports better pregnancy outcomes. Some studies even suggest higher fecundability among vaccinated women with prior STI histories, likely due to fewer cervical procedures and reduced inflammation rather than any direct biological effect of the vaccine on fertility.

Cervical Cancer: From Persistent HPV to Fertility Loss

Cervical cancer doesn’t develop suddenly. The progression from persistent high-risk HPV to precancer (CIN) and then to invasive cancer is a slow process. Screening plays a crucial role in interrupting this progression by detecting abnormalities before they advance to cancer.

Screening and Diagnosis

Screening methods include Pap cytology, high-risk HPV testing, or co-testing, with approaches varying by country and age. Abnormal results lead to colposcopy, where the cervix is examined under magnification, and biopsies are taken.

• Precancerous Changes: Graded as CIN1–3, with CIN2/3 often prompting treatment, especially in older individuals or when changes persist.

• Cancer Diagnosis: Once a biopsy confirms invasive cancer, it is staged using clinical findings and imaging to guide treatment.

Fertility-Sparing Options for Early Cervical Cancer

Advancements in gynecologic oncology have enabled some women to retain fertility without compromising survival.

• Microinvasive Disease (Stage IA1 without Lymphovascular Invasion): Conization with clear margins can be curative, allowing patients to conceive and carry pregnancies with careful monitoring.

• Early-Stage Disease (IA2 to IB1, Especially Tumors ≤2 cm without Lymph Node Involvement): Radical trachelectomy removes the cervix and surrounding tissues while preserving the uterus, often with lymph node assessment. A permanent cerclage is typically placed at the uterine isthmus.

Oncologic and Reproductive Outcomes

• Recurrence Risks: Well-selected patients experience low recurrence risks, around 3–5%.

• Pregnancy Rates: Following trachelectomy, pregnancy rates vary (approximately 40–70% of those who try), with higher success rates when assisted reproduction is available. The risk of second-trimester loss and preterm birth is higher due to cervical shortening and surgical changes, with many births occurring preterm.

In cases where radiation is planned, ovarian transposition can sometimes preserve ovarian function by surgically moving the ovaries out of the radiation field.

When Treatment Threatens or Ends Fertility

• Chemoradiation: The standard care for many locally advanced cancers, pelvic radiation can cause ovarian failure and damage the uterus, even if ovarian function is preserved. Discussion of embryo or oocyte cryopreservation before treatment is common.

• Radical Hysterectomy: Necessary in many cases where fertility-sparing isn’t safe, shifting the focus to survivorship and sometimes third-party reproduction using previously frozen embryos or donor eggs.

Survival statistics highlight the importance of early detection, with localized cervical cancer having a five-year survival rate exceeding 90%, compared to much worse outcomes for late-stage disease. This gap underscores the fertility benefits of screening and vaccination, reducing the number of individuals reaching stages that require fertility-compromising treatments.

Global Disparities and the STI-Fertility Chain Reaction

Cervical cancer remains a leading cause of cancer deaths among women in many low- and middle-income countries. The World Health Organization (WHO) estimated around 604,000 new cases and 342,000 deaths worldwide in 2020, with about 90% occurring in regions with limited access to vaccination and screening. In these areas, fertility implications are compounded by restricted access to fertility-sparing surgery and assisted reproduction.

Fertility risks are not isolated events but the cumulative result of several factors:

• Silent Infections: Such as chlamydia and gonorrhea, which ascend and inflame the fallopian tubes.

• Repeated Inflammation: Increases scarring exponentially.

• Persistent High-Risk HPV Infections: Leading to precancer and excisional treatments, which can slightly increase preterm birth risk.

• Progression to Cervical Cancer: Where necessary treatments can remove or disable reproductive organs.

A history involving multiple risk factors, such as prior PID and a deep cervical excision, doesn’t guarantee fertility issues, but it does shift probabilities. Clinicians often view fertility as a spectrum of odds influenced by anatomy, ovarian reserve, partner factors, and the cervical environment.

Clinical Pathways: Navigating Care

Understanding standard clinical approaches to these conditions helps demystify the process and expectations.

Suspected PID

• Evaluation: Typically involves a pelvic exam, pregnancy test, and testing for chlamydia and gonorrhea, with additional tests for trichomonas or BV as needed. Inflammatory markers and ultrasound may be considered based on severity.

• Immediate Treatment: Begins promptly if clinical signs align, as delays can worsen outcomes.

• Follow-Up: Ensures symptom resolution. If symptoms don’t improve within 48–72 hours, the plan may escalate to imaging, broader antibiotics, or hospitalization.

• Partner Evaluation: Partners are assessed and treated to prevent reinfection, with expedited partner therapy used where available.

Fertility Assessment After PID

Infertility evaluation is generally stepwise and includes both partners. In the context of PID history, a clinician may:

• Order a Semen Analysis: Early, as male factors contribute to infertility in up to half of cases.

• Assess Ovulation and Ovarian Reserve: Based on age and menstrual patterns.

• Evaluate Tubal Patency: Using HSG or HyCoSy. If obstruction is suspected, or if imaging suggests hydrosalpinx, laparoscopy might be discussed.

• Consider Surgical Management: Of hydrosalpinx before assisted reproduction. Studies suggest salpingectomy or proximal tubal occlusion before IVF improves implantation and live birth rates.

Abnormal Pap or HPV Test

• Low-Grade Results: Often lead to repeat testing, as many regress, particularly in individuals under 25.

• Persistent High-Grade Lesions: Typically warrant treatment, with excision tailored to the lesion and reproductive plans.

• Pregnancy Care Post-Procedure: May involve second-trimester cervical length monitoring. Most pregnancies progress without interventions like cerclage, though these are available if needed.

Early Cervical Cancer with Fertility Goals

• Staging: Involves pelvic imaging and often sentinel or pelvic lymph node evaluation.

• Oncologic Evaluation: A gynecologic oncology team considers tumor factors (size, LVSI, margins) alongside reproductive plans to determine trachelectomy candidacy.

• Post-Trachelectomy Pregnancy: Achieved via timed intercourse or assisted methods, with heightened vigilance for infection, cervical shortening, and preterm labor.

Anchoring Expectations: Key Data Points

A few key statistics provide context for understanding risks and outcomes:

• Chlamydia and Gonorrhea: Remain prevalent, with over 1.6 million chlamydia cases and over 700,000 gonorrhea cases reported annually in the U.S., many of which are asymptomatic.

• Untreated Chlamydia: Leads to PID in about 10–15% of cases, with a single PID episode causing infertility in roughly 10%, and this risk increasing with recurrent episodes.

These insights underscore the importance of proactive STI management, early detection, and comprehensive care in protecting fertility and reproductive health.