What are STIs and STDs? 

Sexually transmitted infections (STIs) are caused by contagious bacteria, viruses, fungi, or parasites that are transmitted between individuals through sexual contact. The sexual contact may be vaginal, anal, oral, or through use of shared sex toys. STIs were previously known as sexually transmitted diseases (STDs) and are commonly referred to as such. However, not all sexually transmitted infections will result in a disease (chronic medical condition).ⁱ

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STIs are very common. The CDC has estimated that at any given time, 1 in 5 people in the United States has an STI.ⁱⁱ Furthermore, incidence of STIs appears to be increasing, especially in adolescents (15–24 years of age), which account for approximately half of new STI cases in the US.ⁱⁱⁱ

Examples of STIs include the following:^iv,v

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

How do STIs impact fertility?  

STIs can have long-term effects on the reproductive organs that can increase the likelihood of infertility in both males and females. This is particularly true if the STIs are not identified and are left untreated for a period of time. Infertility can result from: the infection leading to a specific disease that impacts fertility, the inability of infected individuals to engage in frequent sexual intercourse when trying to conceive (due to the STI), and other effects as discussed below.  

In women wishing to carry a pregnancy, certain STIs can lead to tubal or endometrial factor infertility due to a complication called pelvic inflammatory disease (PID). Similarly, in men intending to use their sperm for conception, STIs may ascend through the reproductive tract and cause scarring or blockage in the testes or epididymis, which can prevent sperm production or ejaculation.  These are discussed below, looking first at the impact of STIs on female fertility, and then male fertility.

How STIs can impact female fertility 

As suggested above, STIs can cause female infertility through PID. A STI typically infects the lower female reproductive tract initially, including the vagina and outer cervix; this is known as cervicitis. If untreated, the STI can then ascend to infect the upper female reproductive tract, including the inner cervix (endocerviticitis), uterus (endometritis), fallopian tubes (salpingitis), ovaries (oophoritis), and peritoneum (peritonitis). This ascending infection is referred to as pelvic inflammatory disease. .^vi

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

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

The STIs most likely to cause infertility through PID include:

Chlamydia trachomatis: 131 million new cases per year.  

• Chlamydia is the most common bacterial STI, and the most common bacterial cause of tubal infertility.  
• A woman’s risk of at least one chlamydia infection by the age of 44 is 42.9 percent.^xi This is likely an underestimate as chlamydia can be asymptomatic in many cases and therefore may not be diagnosed and reported.^xii
• 10-15 percent of women with untreated chlamydia develop PID^xiii

Neisseria gonorrhea: 78 million new cases per year.

• Gonorrhea is the second most common bacterial STI, and its incidence is increasing.^xiv For example, in one Canadian study, the rates have increased by over 81 percent in the past 10 years.^xv
• Gonorrhea infection leads to PID in 10-20 percent of cases.^xvi

Mycoplasma genitalium:  

• Mycoplasma genitalium is a bacterial STI that may be asymptomatic, but in some cases is associated with cervical infection and PID.^xvii
• Patients diagnosed with mycoplasma genitalium have an approximately twofold increased risk of PID and infertility.

Other STIs:

Human papillomavirus (HPV):

• HPV is extremely common: 98 percent of women are exposed to HPV, and approximately 30 percent of women become infected within 24 months of their first exposure to HPV.^xviii
• HPV is not thought to be an independent cause of infertility.^xix In a large study of 10 595 women, the rate of infertility was similar between women who were found to have a high-risk subtype of HPV and those who did not.^xx Thus, there was no association between high-risk HPV and infertility.  In contrast, there are some studies that indicate HPV may affect outcomes in fertility treatment such as IUI and IVF.  ^{xxi, xxii, xxiii, xxiv}
• Small studies have identified an association between HPV infection and higher rates of spontaneous fetal loss while undergoing IVF; however, this data is limited and requires further study.^xxv
• 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 end in stillbirth, birth defects, and/or or neonatal demise.^{xxvi, xxvii}

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, or ejaculatory ducts where sperm are produced, mature, and are ejaculated.^xxviii Infection can lead to direct or indirect disruption of spermatogenesis in the testes, leading to dysfunction in semen production and ejaculation, and/or inflammation-related obstruction of the male reproductive tract, which prevents the sperm from exiting the male tract.^xxix,xxx

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

Chlamydia trachomatis:

• Chlamydia is the most common bacterial STI in men.  
• The impact of chlamydia infection on male fertility is not as clear as the impact of PID on female infertility.
• Chlamydia is a cause of inflammation of the male reproductive tract, and along with gonorrhea, causes the majority of cases of epididymitis (infection of the epididymis) in men aged 14-35. Epididymitis can potentially lead to direct sperm damage, impaired sperm maturation, or epididymal obstruction, preventing sperm from entering the semen for ejaculation.^xxxi
• The impact of asymptomatic chlamydia infection (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 known due to asymptomatic cases. These cases may play a role in male factor infertility, without the individual knowing, since the cases are symptom-free. For example, in a study looking at a population of infertile men with no identified cause of infertility, testicular biopsies showed that 45.3 percent were positive for chlamydia despite being asymptomatic. ^xxxii Therefore, it could be that more unexplained male factor infertility is due to chlamydia than previously thought.
• In contrast, several older studies show no association between asymptomatic chlamydia infection and male infertility.^xxxiii  

Neisseria gonorrhea:

• As in women, gonorrhea is the second most common STI in men in Canada and the United States.^xxxiv,xxxv  
• 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 in men.^xxxvi
• The effect of gonorrheal epididymitis on male infertility is like that seen in epididymitis caused by chlamydia or other bacteria.  
• Reduced sperm parameters are seen in most patients with acute epididymitis caused by chlamydia or gonorrhea, but this 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.^{xxxvii,xxxviii}

Human papilloma virus (HPV):

• HPV has a prevalence of approximately 40 percent in the general population.^xxxix
• HPV infection is being 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 male 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 bind to sperm, which decreases sperm quality and can impair fertility.^xl

Syphilis:

• Syphilis does not directly cause infertility in males. However, if it leads to epididymitis, this can cause infertility by obstruction of the male reproductive tract or leading to disruption in sperm maturation.^xli
• Additionally, if the syphilis progresses to infect the nervous system (neurosyphilis), it can lead to erectile dysfunction which can result in infertility.^xlii

Preventing STIs 

STI prevention strategies, such as practicing safe sex and getting vaccinated against HPV and other STIs, are essential to minimize 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 50-90 percent protection against Chlamydia trachomatis when used correctly.^xliii The female condom may be even more effective than the male condom in preventing gonorrhea or chlamydial transmission.^xliv
• 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 United States, 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 United States. Canadian and American (CDC) immunization guidelines suggest that vaccination is recommended for males and females aged 9-26 but may also be given to individuals older than 26 years old.^xlv,xlvi
• Pre-exposure prophylaxis (PrEP): PrEP describes pre-emptive use of antiretroviral medications to prevent the acquisition of HIV, when an individual plans to engage in sex with a partner who has HIV.^xlvii If used correctly, evidence has shown that PrEP is approximately 95% effective for preventing transmission in heterosexual couples^xlviii

STI testing and fertility 

STI testing is an important component of STI prevention and helps to safeguard fertility. Screening for STIs is often completed opportunistically, rather than through a scheduled screening program occurring regularly. Testing may be offered in primary care settings such as family doctors' offices, sexual health clinics, and student health centers.^xlix For those at an average risk of acquiring an STI, chlamydia and gonorrhea screening is recommended annually for those who are younger than 30. The Public Health Agency of Canada recommends annual STI screening for those who are 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 women, etc.).^lIn the United States, the CDC and American Academy of Family Physicians (AAFP) recommends testing for chlamydia and gonorrhea in women under 25 years old who are sexually active, older women at risk, men who have sex with men, and all HIV-positive individuals. ^li,^lii They recommend testing for syphilis for anyone at higher risk, pregnant women, men who have sex with men, or HIV-positive individuals.^liii  

Testing is completed through nucleic acid amplification testing (NAAT) for gonorrhea and chlamydia. A single test can be used to check for both organisms as they are often both present.^liv 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.^lv

HIV is typically diagnosed via a blood test, which identifies antibodies (a protein in the blood) against HIV. A viral load test can also be completed which assesses 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.^lvi In the United States, the CDC recommends HIV testing at least once in all patients aged 13-64 and annual testing for those with risk factors.^lvii  

Syphilis can be screened for (not diagnosed) by blood tests known as nontreponemal tests. This can be through a venereal disease research laboratory test (VDRL test) or a rapid plasma reagin test (RPR test). It is definitively diagnosed by a treponemal test, known as fluorescent treponemal antibody absorption assay (FTA-ABS).^lviii

HPV screening for women is completed by DNA testing on a cervical sample. This is done at the same time as a Pap smear. This test involves looking at cervical cells under a microscope, to assess for precancerous cells often caused by HPV infection.^lix

Screening for Mycoplasma genitalium is completed by a NAAT test like those for gonorrhea and chlamydia.^lx

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

The ASRM Practice Committee states that the following STI testing is necessary for all egg and sperm donors, as required by the FDA:^lxi

• 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-lymphotrophic virus 1) types I and II  
• CMV (cytomegalovirus) IgM and IgG

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

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

• 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

Women who are 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). Men who are partners of gestational carriers should undergo HTLV (human T-lymphotrophic virus 1) types I and II testing, CMV (cytomegalovirus) IgM and IgG testing, and gonorrhea and chlamydia testing from the urethra.  

Treating STIs 

The treatment of STIs is a vital component of preserving and protecting fertility if one is diagnosed with an STI. The treatment of an STI depends on the STI type. 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, that may be managed separately through alternative approaches (e.g., surgery or in vitro fertilization).  

Treating current STIs 

A typical antibiotic treatment course for bacterial STIs includes the following:  

• Chlamydia: Azithromycin 1 gram PO x 1 dose, or doxycycline 100 milligrams PO BID x 7 days. Azithromycin is often preferred as only a single dose is required. To ensure that the antibiotics were effective, a test of cure is recommended three weeks after treatment. Repeat screening is recommended three months later.^lxiv  

• Gonorrhea (for an uncomplicated genital infection): Ceftriaxone 250 milligrams intramuscular x 1 dose, plus azithromycin 1 gram PO x 1 dose is typically recommended. Test of cure can be completed 2-3 weeks after treatment. Repeat screening is recommended six months after treatment.^lxv

• Syphilis: Primary, secondary, and early latent syphilis is treated with benzathine penicillin 2.4 million units intramuscularly x 1 dose. Latent or late syphilis is treated with benzathine penicillin 2.4 million units intramuscularly x 3 doses (1 dose/week). 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.^lxvi

• Mycoplasma genitalum: Azithromycin 500 milligrams PO is used on day one, followed by 250 milligrams PO on days two through five. Test of cure should be completed three weeks after completion of treatment.^lxvii

Treatment of 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.^lxviii
• HIV: HIV is typically treated with a combination of medications known as antiretrovirals. People will often take 2-3 antiretrovirals at once. Some of these medications include tenofavir, emtricitabine, and dolutegravir. Treatment should be initiated as soon as HIV is diagnosed.^lxix

Treating the damage from past STIs 

If a bacterial STI has been untreated and thus has resulted in 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 grams IV every 12 hours + doxycycline 100 milligrams PO or IV every 12 hours. However, there are alternate antibiotic regimens that may also be effective depending on the underlying bacterial infection.^lxx

A tubo-ovarian abscess (TOA) is a complication of PID, in which a complex infected mass forms in the fallopian tube or ovary. This can cause widespread bacterial infection (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.^lxxi

Epididymitis (inflammation of the epididymis) can be treated with antibiotics. If it is thought to be due to a STI, the treatment regimen involves ceftriaxone 250 mg IM x 1 dose + doxycycline 100 mg twice daily x 10 days.^lxxii

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 considered if there is tubal scarring. This procedure involves opening the tube surgically and can lead to successful pregnancy rates of 27-60 percent depending on the type of tubal obstruction and the location. Different subtypes of tubuloplasty include adhesiolysis, fibrioplasty, salpingostomy, tubotubal anastomosis, tubocornual anastomosis, and cornual implantation.^lxxiii A Cochrane review was conducted in 2017 to assess the effectiveness of tubal surgery relative to expectant management or IVF, but unfortunately, there were no suitable randomized controlled trials eligible for inclusion. Therefore, future research is required in this area.^lxxiv 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 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 was restored in 72 percent of patients, which led to a natural conception rate of 38.7 percent, thus indicating that this surgical procedure may be an effective treatment for males with infertility due to a prior STI.^lxxv In most cases of epididymal obstruction, surgical interventions to restore patency is not possible. In these cases, sperm can often be directly extracted from the testicle or epididymis through procedures such as testicular sperm extraction (TESE) or microsurgical epidydimal sperm aspiration (MESA). This extracted sperm can then be used to fertilize oocytes (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 and suspicion of STI-induced tubal factor infertility, hysterosalpingography (HSG) is the first-line tool to diagnose fallopian tube obstruction.^lxxvi Once tubal infertility has been identified, either tubal surgery or IVF may be options for treatment, and patients will often decide between one of these two options. While tubal surgery directly addresses the problem leading to the infertility, IVF allows for the fallopian tubes to be bypassed altogether to lead to conception.  

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

Unfortunately, data for the success rate of surgical interventions for tubal infertility are lacking. The success rate of such procedures can 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 this procedure can be a one-time, minimally invasive surgery. However, there are risks associated with any surgery, including infection, bleeding, and damage of surrounding structures. Additionally, there is an elevated risk of ectopic pregnancy amongst patients conceiving after tubal surgery.^lxxix

Conclusion

STIs can have a significant impact on an individual's fertility. STI testing plays a critical role in maintaining fertility, as it allows individuals to detect STIs as early as possible and to begin appropriate treatment. Individuals should heed STI prevention strategies, such as practicing safe sex and getting vaccinated against HPV to minimize risk of infection. Those who are struggling with infertility due to STIs may need to explore treatments such as IVF, depending on the STI involved. Overall, STIs should be taken seriously, as they could lead to infertility if those affected do not take the necessary steps to manage infections promptly.

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