What are STIs and STDs?

Sexually transmitted infections (STIs) are caused by contagious bacteria, viruses, fungi, or parasites transmitted between individuals through sexual contact. This sexual contact may be vaginal, anal, oral, or via the use of shared sex toys. STIs were previously called sexually transmitted diseases (STDs). However, not all sexually transmitted infections will result in a disease, which is defined as a chronic medical condition.ⁱ

STIs are incredibly common. The Centers for Disease Control and Prevention (CDC) has estimated that, at any given time, 1 in 5 people in the United States has an STI.ⁱⁱ The incidence of STIs also appears to be on the rise, especially in adolescents (15 to 24 years of age), who account for approximately half of new STI cases in the U.S.ⁱⁱⁱ

Here are some examples of STIs:^iv,v

• Gonorrhea
• Chlamydia
• Syphilis
• Genital herpes
• Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS)
• Human papillomavirus (HPV)
• Mycoplasma genitalium
• Trichomoniasis
• Chancroid
• Granuloma inguinale
• Lymphogranuloma venereum  

How do STIs impact fertility?

STIs can have long-term effects on the reproductive organs, which increases the likelihood of infertility in both males and females. The longer an STI is left untreated, the higher the risk of fertility loss. Infertility may result from an infection that leads to a medical condition that impacts fertility. Infected individuals may also be unable to engage in frequent sexual intercourse due to the STI.

How STIs can impact female fertility

In individuals wishing to carry a pregnancy, certain STIs can lead to tubal or endometrial factor infertility due to a complication called pelvic inflammatory disease (PID). An STI will typically infect the lower female reproductive tract at first, including the vagina and outer cervix; this infection is known as cervicitis. If untreated, the STI can then ascend into the upper female reproductive tract and infect its organs, including the inner cervix (causing endocervicitis), uterus (causing endometritis), fallopian tubes (resulting in salpingitis), and ovaries (causing oophoritis). It can also infect a membrane known as the peritoneum, which results in peritonitis. This ascending infection is called pelvic inflammatory disease.^vi

Pelvic inflammatory disease is most likely to lead to infertility when salpingitis (an infection of the fallopian tubes) occurs. When one or both fallopian tubes become infected, they develop inflammation, which can result in scarring and dysfunction, or blockage of the tube(s). These side effects can lead to tubal factor infertility by physically blocking sperm from reaching an egg, by preventing fertilization, or by impeding the fertilized egg (embryo) from moving through the tube to the uterus, resulting in an ectopic (or tubal) pregnancy.^vii,viii

Evidence from a large study by Anyalechi et al (2019) that analyzed self-reported infertility in 2,626 females found that the overall prevalence was 13.8 percent. The infertility rate was significantly higher in people with a history of pelvic inflammatory disease (24.2 percent) versus those without (13.3 percent).^ix Furthermore, data from the PEACH Study, a randomized clinical trial researching different methods of treating pelvic inflammatory disease, included 831 females and found that 19.0 percent of these treated patients were infertile at a follow-up 84 months (about seven years) after treatment.^x

Some STIs are more likely to cause infertility through pelvic inflammatory disease (PID) than others. Here are some examples:

• ‍Chlamydia trachomatis: an estimated 128.5 million new cases globally per year^xi‍
  • Chlamydia is the most common bacterial STI, and the most common bacterial cause of tubal infertility.
  • A female’s risk of at least one chlamydia infection by the age of 44 is 42.9 percent.^xii This number is likely an underestimate as chlamydia is asymptomatic in many cases, which means it may go undiagnosed and unreported.^xiii‍
  • 10 to 15 percent of females with untreated chlamydia develop PID.^xiv
• ^‍Neisseria gonorrhea: an estimated 82.4 million new cases globally per year^xv‍
  • Gonorrhea is the second most common bacterial STI, and its incidence is increasing.^xvi One Canadian study showed that rates have increased by over 81 percent in the past 10 years.^xvii‍
  • Gonorrhea infection leads to PID in 10 to 20 percent of cases.^xviii
• ^‍Mycoplasma genitalium:
  • ‍Mycoplasma genitalium is a bacterial STI that may be asymptomatic, but in some cases is associated with cervical infection and PID.^xix‍
  • Patients diagnosed with mycoplasma genitalium have approximately double the risk of PID and infertility.

Other STIs that may affect fertility:

• ‍Human papillomavirus (HPV):
  • ‍HPV is extremely common: 98 percent of females are exposed to HPV, and approximately 30 percent of them become infected within 24 months (about two years) of their first exposure.^xx‍
  • HPV is not thought to cause infertility on its own.^xxi In a large study of 10,595 females, the rate of infertility was similar among people who were found to have a high-risk subtype of HPV and those who did not.^xxii  However, some studies indicate HPV may affect fertility treatment outcomes from intrauterine insemination (IUI) and in vitro fertilization (IVF).^{xxiii,xxiv,xxv,xxvi}‍
  • Small studies have identified an association between HPV infection and higher rates of spontaneous fetal loss while undergoing IVF, but this data is limited and requires further study.^xxvii‍
  • HPV infection is associated with an increased risk of cervical cancer, and cancer treatments can cause infertility.
• ‍Syphilis:
  • ‍Syphilis has a drastic impact on the fetus if conception does occur. Around 40 percent of pregnancies in which the mother is infected with syphilis will end in stillbirth, birth defects, and/or neonatal death.^xxviii,xxix‍

How STIs can impact male fertility

STIs can also lead to infertility in males if an infection ascends through the male reproductive tract and damages the testes, epididymis, vas deferens (also known as the ductus deferens), or ejaculatory ducts where sperm are produced, mature, and are ejaculated.^xxx Infection can lead to direct or indirect disruption of spermatogenesis (the process of sperm production) in the testes, leading to dysfunction in semen production and ejaculation. It can also cause inflammation-related obstruction of the male reproductive tract, which prevents the sperm from exiting.^xxxi,xxxii

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There are a variety of STIs that are known to affect male fertility:

• ‍Chlamydia trachomatis:
  • ‍Chlamydia is the most common bacterial STI in males.
  • The impact of chlamydia infection on male fertility is not as clear as its impact on female infertility.
  • Chlamydia may cause inflammation of the male reproductive tract and, along with gonorrhea, results in the majority of cases of epididymitis (infection of the epididymis, the tube that connects each testicle to its vas deferens) in males aged 14 to 35. Epididymitis can lead to direct sperm damage, impaired sperm maturation, or epididymal obstruction, preventing sperm from entering the semen for ejaculation.^xxxiii‍
  • The impact of asymptomatic chlamydia infection (an infection that does not cause inflammation of the urethra, testes, or epididymis) on male infertility is not clear.
  • Chlamydia infection may be more prevalent than realized due to asymptomatic cases. These undiagnosed cases may play a role in male factor infertility without the individual knowing. For example, in a study looking at a population of infertile males with no identified cause of infertility, testicular biopsies showed that 45.3 percent were positive for chlamydia despite being asymptomatic.^xxxiv It could be that more unexplained male factor infertility is due to chlamydia than previously thought.
  • In contrast, several older studies found no association between asymptomatic chlamydia infections and male infertility.^xxxv
• ^‍Neisseria gonorrhea:
  • ‍As in females, gonorrhea is the second most common STI in males in Canada and the U.S.^xxxvi,xxxvii‍
  • Urethritis, or infection of the urethra, is the most frequently reported presentation. However, gonorrhea is frequently asymptomatic. It can also cause epididymitis, prostatitis, or orchitis (infections of the epididymitis, prostate or testes, respectively).^xxxviii‍
  • The effect of gonorrheal epididymitis on male infertility is similar to that seen in epididymitis caused by chlamydia or other bacteria.
  • Reduced sperm health is seen in most patients with acute epididymitis caused by chlamydia or gonorrhea, but it resolves in most cases after three months. However, in up to 40 percent of cases, semen analysis abnormalities may not resolve or may resolve more slowly after the acute infection.^xxxix,xl
• ^‍Human papillomavirus (HPV):
  • ‍HPV has a prevalence of approximately 40 percent in the general population.^xli‍
  • More recently, HPV infection has been suggested as a possible cause of male factor infertility, while it was previously thought to be transient and clinically insignificant in males.
  • A systematic review of 31 studies including 5,194 males found that in infertile couples, the prevalence of HPV infection in sperm was 20.4 percent, compared to 11.4 percent in the general population. The authors found that HPV positivity was significantly associated with an increased risk of infertility. It is thought that the HPV virions (virus particles) bind to sperm, which decreases sperm quality and can impair fertility.^xlii
• ^‍Syphilis:
  • ‍Syphilis does not directly cause infertility in males. However, if it leads to epididymitis (an infection of the epididymis), then obstruction of the male reproductive tract or a disruption in sperm maturation could result.^xliii‍
  • Additionally, if the syphilis progresses to infect the nervous system (known as neurosyphilis), it can lead to erectile dysfunction, which can result in infertility.^xliv

Preventing STIs

STI prevention strategies, such as practicing safe sex and getting vaccinated against HPV and other STIs, are essential for minimizing risk of infection. Aside from abstinence, the following practices may help prevent STIs:

• ‍Barrier protection: The male condom offers 90 percent protection against Neisseria gonorrhea, and 50 to 90 percent protection against Chlamydia trachomatis when used correctly.^xlv The female condom may be even more effective than the male condom in preventing gonorrhea or chlamydial transmission.^xlvi
• ^‍HPV prevention: As HPV is a viral infection, it can be prevented by vaccination, which is known to be safe and highly effective. In Canada and the U.S., Gardasil and Cervarix are vaccines available for HPV prevention. Gardasil-9 protects against nine HPV subtypes, which are known to be oncogenic (cancer-causing) or to cause genital warts. Cervarix prevents HPV 16 and 18 only. Because Gardasil-9 has broader coverage in preventing HPV infection, it is the recommended HPV vaccine in the U.S. Canadian and American (CDC) immunization guidelines recommend vaccination for males and females aged 9 to 26, but the vaccine may also be given to individuals older than 26 years old.^xlvii,xlviii
• ^‍Pre-exposure prophylaxis (PrEP): PrEP describes the pre-emptive use of antiretroviral medications to prevent the acquisition of HIV. It is used when an individual plans to engage in sex with a partner who has HIV.^xlix If PrEP is used correctly, evidence has shown that it is approximately 95 percent effective for preventing transmission in heterosexual couples.^l

STI testing and fertility

STI testing is an important component of STI prevention and helps to safeguard fertility. However, it is rarely covered through a regularly scheduled screening program. Testing may be offered at family doctors' offices, sexual health clinics, and student health centers, but the ownness is often on the individual to request access to these tests.^li

For those at an average risk of acquiring an STI, chlamydia and gonorrhea screening is recommended annually for those who are younger than 30. More specifically, the Public Health Agency of Canada recommends annual STI screening for anyone who is sexually active and under 25 years old, or 25 years old or over and at higher risk (e.g., sex workers, those with prior STIs, pregnant females, etc.).^lii In the U.S., the CDC and American Academy of Family Physicians (AAFP) recommend testing for chlamydia and gonorrhea in females under 25 years old who are sexually active, older females at risk, males who have sex with males, and all HIV-positive individuals.^liii,liv They recommend testing for syphilis for anyone at higher risk, pregnant females, males who have sex with males, and HIV-positive individuals.^lv

Here is how STIs are generally tested:

• ‍Gonorrhea and chlamydia: Testing is completed through nucleic acid amplification testing (NAAT). A single test can be used to check for both organisms as they are often both present.^lvi NAAT tests can be used on samples from the vagina, cervix, urine, pharynx (back of mouth), and anus. A cervical swab is the preferred method of testing for most females, while a first-void urine sample is recommended for most males.^lvii
• ^‍HIV: It is typically diagnosed via a blood test, which identifies antibodies (proteins in the blood) against HIV. A viral load test can also be completed, which checks for viral RNA (genetic material). It is not typically used for diagnosis but rather to assess the progression of the disease once it has been diagnosed.^lviii In the U.S., the CDC recommends HIV testing at least once in all patients aged 13 to 64 and annual testing for those with risk factors.^lix
• ^‍Syphilis: It can be screened for (but not diagnosed) by blood tests known as nontreponemal tests. There are two options: a venereal disease research laboratory (VDRL) test or a rapid plasma reagin (RPR) test. It is definitively diagnosed by a treponemal test called a fluorescent treponemal antibody absorption assay (FTA-ABS).^lx
• ^‍HPV: Screening for females is completed by DNA testing on a cervical sample. This sample is typically collected during a Pap test. The collected cervical cells are then assessed under a microscope for precancerous or cancerous changes, which can be caused by HPV infection.^lxi
• ^‍Mycoplasma genitalium: Screening is completed by a NAAT test like those done for gonorrhea and chlamydia.^lxii

STI testing for sperm donors, egg donors, and intended parents

The American Society for Reproductive Medicine (ASRM) Practice Committee states that the following STI testing is necessary for all egg and sperm donors, as required by the U.S. Food and Drug Administration (FDA):^lxiii

• Chlamydia
• Gonorrhea
• Hepatitis B surface antigen, hepatitis B core antibody
• Hepatitis C antibody and NAAT
• HIV1 antibody and NAAT, HIV2 antibody and NAAT, HIV group O antibody

The following additional laboratory testing is required for sperm donors only:

• HTLV (human T-lymphotropic virus 1) types I and II
• CMV (cytomegalovirus) IgM and IgG

Although it is not required by the FDA, the ASRM recommends that egg/sperm/embryo recipients, and sexually intimate partner(s) of recipients, undergo infectious disease testing.^lxiv

Gestational carriers must also be tested for STIs to prevent transmission to the fetus. The ASRM recommends that gestational carriers and their partners undergo the following tests:^lxv

• HIV1 antibody and NAAT, HIV2 antibody and NAAT, HIV group O antibody
• Hepatitis C antibody and NAAT
• Hepatitis B surface antigen, hepatitis B core antibody (IgM and IgG)
• CMV (cytomegalovirus) IgM and IgG
• Blood testing for syphilis

Gestational carriers should also undergo a Pap test with HPV screening, as well as gonorrhea and chlamydia testing from the cervix, vagina, or urethral meatus (opening of the urethra). Males who are partners of gestational carriers should undergo HTLV (human T-lymphotropic virus 1) types I and II testing, CMV (cytomegalovirus) IgM and IgG testing, and gonorrhea and chlamydia testing from the urethra.

Treating STIs

If someone is diagnosed with an STI, treatment is a vital component of preserving their fertility. Depending on the STI type, treatment will vary. Bacterial STIs can typically be cured with antibiotics, whereas viral STIs may not be curable, or may require antiviral medications for management. Despite treatment of an underlying STI, there may still be complications from the infection, such as scarring, which may be managed separately through alternative approaches such as surgery or in vitro fertilization.

Treating bacterial STIs

• ‍Chlamydia: A patient will often take one dose of azithromycin (1 g by mouth) or doxycycline (100 mg by mouth twice a day) for seven days. Azithromycin is often preferred as only a single dose is required. To ensure that the antibiotics were effective, a chlamydia test of cure is recommended three weeks after treatment, followed by repeat screening three months later.^lxvi
• ^‍Gonorrhea (for an uncomplicated genital infection): One dose of ceftriaxone (250 mg by intramuscular injection), plus one dose of azithromycin (1 g by mouth) is typically recommended. A test of cure can be completed two or three weeks after treatment. Repeat screening is recommended six months after treatment.^lxvii
• ^‍Syphilis: Primary, secondary, and early latent syphilis is treated with benzathine penicillin — typically one dose of 2.4 million units by intramuscular injection. Latent or late syphilis is treated with benzathine penicillin (three doses (one per week) of 2.4 million units by intramuscular injection). Blood tests are used to ensure that the treatment was effective. The frequency of this testing depends on the severity of the disease but may be needed for up to two years.^lxviii
• ^‍Mycoplasma genitalium: Treatment usually involves azithromycin (500 mg taken by mouth) on day one, followed by 250 mg by mouth on days two through five. A test of cure should be completed three weeks after completion of treatment.^lxix

Treating viral STIs

• ‍Herpes (HSV): Genital herpes is not curable, but medications can improve symptoms. First-line medications include antivirals such as acyclovir, famciclovir, or valacyclovir.^lxx
• ^‍HIV: HIV is typically treated with a combination of medications known as antiretrovirals. People will often take two or three antiretrovirals at once. Some of these medications include tenofovir, emtricitabine, and dolutegravir. Treatment should be initiated as soon as HIV is diagnosed.^lxxi

Treating the damage from past STIs 

If a bacterial STI has not been treated and has resulted in pelvic inflammatory disease (PID), the PID should be treated as soon as it is diagnosed to prevent further inflammation and scarring of the reproductive tract. PID is typically treated with a combination of antibiotics, often administered intravenously rather than orally. An example treatment regimen would be cefotetan (2 g by IV every 12 hours) and doxycycline (100 mg by mouth or IV every 12 hours). However, there are alternate antibiotic regimens that may also be effective depending on the underlying bacterial infection.^lxxii

A tubo-ovarian abscess (TOA) is a complication of PID in which a complex infected mass forms in the fallopian tube or ovary. This mass can cause widespread bacterial infection (a.k.a. sepsis) and can potentially be life-threatening if the abscess ruptures. It is typically treated with IV antibiotics but may also require image-guided drainage through a small incision in the skin, or surgical drainage.^lxxiii

Epididymitis (inflammation of the epididymis) can be treated with antibiotics. If it is thought to be caused by an STI, the treatment regimen involves ceftriaxone (one dose of 250 mg by intramuscular injection) and doxycycline (100 mg twice daily for 10 days).^lxxiv

Tubal factor infertility following an STI may be treated surgically so that patients may then attempt to conceive without requiring IVF. Tubuloplasty is a microsurgical procedure of the fallopian tubes that might be an option if there is tubal scarring. This procedure involves opening the tube surgically and can lead to successful pregnancy rates of 27 to 60 percent depending on the type of tubal obstruction and the location. Different subtypes of tubuloplasty include adhesiolysis, fimbrioplasty, salpingostomy, tubotubal anastomosis, tubocornual anastomosis, and cornual implantation.^lxxv

A Cochrane review was conducted in 2017 to assess the effectiveness of tubal surgery for improving the chances of live birth compared to expectant management (a.k.a. consciously deferring treatment) or completing IVF. Unfortunately, there were no suitable randomized controlled trials eligible for inclusion, so future research is required in this area.^lxxvi Surgery is not recommended if there is extensive tubal scarring given the increased risk of failure.

Severe infection from an STI can lead to scarring of the male reproductive tract, leading to obstructive azoospermia (no sperm in the ejaculate) or oligospermia (reduced sperm in the ejaculate). In these patients, surgery to bypass the obstruction may be possible. A 2016 study evaluated 159 patients who underwent a surgical procedure known as microsurgical vasoepididymostomy, which relieves the obstruction by creating a new connection between the epididymis and the vas deferens, to treat azoospermia. They found that patency (a.k.a. unobstruction) was restored in 72 percent of patients, which led to a natural conception rate of 38.7 percent. These results indicate that this surgical procedure may be an effective treatment for males with infertility due to a prior STI.^lxxvii

In most cases of epididymal obstruction, surgical interventions to restore patency are not possible. Treatment alternatives where sperm is directly extracted from the testicle or epididymis through procedures such as testicular sperm extraction (TESE) or microsurgical epidydimal sperm aspiration (MESA) may be an option. This extracted sperm can then be used to fertilize oocytes (developing eggs) to create embryos for use in an IVF cycle.

STIs and IVF 

In vitro fertilization (IVF) is often used to help patients with STI-induced fertility issues, such as when fallopian tubes are blocked or damaged. In the case of infertility where STI-induced tubal factor infertility is suspected, a radiologic procedure called hysterosalpingography (HSG) is the first-line tool to diagnose fallopian tube obstruction.^lxxviii

Once tubal infertility has been identified, patients will often choose between tubal surgery and IVF. Tubal surgery directly addresses the problem leading to infertility, while IVF allows for the fallopian tubes to be bypassed altogether to lead to conception.

In 2017, data from the CDC National Assisted Reproductive Technology database revealed a 31.2 percent live birth rate per cycle in IVF patients with tubal factor infertility, compared to a rate of 34.1 percent overall. Therefore, IVF can be a highly effective treatment for infertility,^lxxix and has the added benefit of being less invasive than surgery. However, it is also more expensive than tubal surgery and has the risks of a multiple pregnancy (if more than one embryo is transferred) and potential ovarian hyperstimulation.^lxxx

Unfortunately, data for the success rate of surgical interventions for tubal infertility are lacking. The success of such procedures may depend on a surgeon’s expertise, the severity of the scarring, and the type of surgery performed. Some patients may opt for tubal surgery over IVF as the procedure is minimally invasive and often done just once. However, there are risks associated with any surgery, including infection, bleeding, and damage of surrounding structures. There is also an elevated risk of ectopic (tubal) pregnancy amongst patients conceiving after tubal surgery.^lxxxi

Conclusion

Since STIs can have a significant impact on fertility, individuals should heed STI prevention strategies, such as practicing safe sex, and getting vaccinated against HPV to minimize the risk of infection. STI testing also plays a critical role in maintaining fertility, as it allows individuals to detect STIs as early as possible and to begin appropriate treatment. Anyone who is struggling with infertility due to STIs may need to explore treatments such as IVF, depending on the STI involved.