Sexually-Transmitted Diseases (STD's) and Infertility

William M. Buckett, MB, ChB, MD, FRCOG

Fall 2008

Sexually-transmitted diseases (STDs) are one of the commonest reasons worldwide for seeing a doctor. A recent estimate is that 1.5% of people under the age of 25 years are treated for chlamydia infection each year¹. Overall, it is estimated that over 15 million new cases of STDs are diagnosed each year in the United States, resulting in a huge potential burden to any type of health care system. Particular problems stemming from lesser STDs include facilitation of HIV infection, later development of some anal and cervical cancers, complications during and after pregnancy, and male and female infertility.

 

Despite this high incidence of detected infection, many STDs can be carried without symptoms for months or years and some viral infections may persist for life. This underlines the importance of easy access to testing for STDs (particularly in settings where there are many young people, for example university clinics) as well as effective treatment of the affected individual and his or her partners. Although routine STD screening – unlike cervical cancer screening – is not considered cost effective at present, it would be prudent to have a low threshold to offer this for young men and women.  

 

Thankfully the stigma attached to STDs is finally disappearing, albeit some 40 years after the sexual revolution of the 1960s. STDs are not related to ethnic background, social class, education, income or personal hygiene.

 

The most common STDs in Canada today are genital warts, genital herpes, gonorrhea and chlamydia. Less frequently seen STDs include pubic lice, syphilis, hepatitis, HIV and ulcerative diseases. This review will outline the symptoms, treatment, and any effect these STDs have on fertility and pregnancy outcome.

 

Genital warts (condylomata) are the most common STD in Canada. They are caused by the human papilloma virus (HPV), and the presence of HPV can be found in 20-40% of the sexually active couples in Canada who do not have any genital warts². There are at least one hundred HPV virus subtypes, of which some - most particularly HPV 16 and HPV 18 - are associated with cervical cancer. Therefore, all women who have ever been sexually active should have regular cervical screening (usually performed as routine Pap tests).

 

Genital warts themselves are usually caused by HPV 6 and HPV 11. The warts can vary in appearance, but are usually raised growths or bumps on the skin surface. In women they usually appear around the vulva and perineum and in men on the glans penis or behind the foreskin.

 

Most warts will disappear or regress spontaneously. Where treatment is needed it is usually by local destructive agents, such as podophyllotoxin or trichlorpacetic acid. Sometimes boosting the local immune response with imiquimod cream helps. In persistent cases, removal by freezing (cryotherpay), burning (diathermy), laser or surgery is appropriate.

 

Despite their high incidence, genital warts have little effect on fertility and pregnancy outcome³. During pregnancy, genital warts can occasionally grow very large and cause problems with delivery, although this is rare. Similarly, transmission of the wart virus at delivery to the baby can occur, but it is also rare. Nevertheless, anyone with genital warts is at increased risk of having other STDs, which may have more profound effects on fertility, and therefore should be tested for all STDs.

 

In Canada, genital herpes is the commonest cause of genital ulcers. The ulcers are red, raw, and very painful areas or sores breaking the skin - typically affecting the perineum, vulva, vagina, and cervix in women and the glans penis and penile shaft in men. The ulcers are caused by the herpes simplex virus (which also causes oral 'cold sores') – usually by the HSV-2 virus, although HSV-1 infections are not uncommon.

 

The presence of the virus is usually life-long. Outbreaks of herpes ulcers can occur in repeated episodes, although the first or primary infection is usually the worst. Transmission occurs through sexual contact with a person who is 'shedding' or excreting the virus - usually when they have symptoms or an outbreak of the infection (although they may have no symptoms). The incubation period is 2-14 days and a first infection is usually accompanied by pelvic or groin pain and pain on urination. Recurrent episodes occur in about 50% of cases, and may be precipitated by various factors including stress, emotional or relationship difficulties, dietary factors, menstruation, sunlight or trauma during sexual intercourse.

 

It is impossible to completely eradicate the virus. Treatment should aim to control the symptoms. This usually involves local pain relief, antibiotics and saline baths to prevent secondary infection with bacteria, and acyclovir or other anti-viral medication. The possible benefits of imiquimod for immune modulation and therapeutic vaccines are also under investigation. Just as for genital warts, testing for other STDs and treatment of partners -- even if they have no symptoms -- is essential.

 

The most important complication of genital herpes is the transmission of the virus to a baby during labor and delivery, which can result in a severe herpes infection for the newborn with life-threatening complications. This is more usual with a primary infection, although the risk of transmission is still 1-4% with recurrent 'flare-ups.' Anyone with a previous history of genital herpes should be examined carefully during their ante-natal care and when presenting in labor. Antiviral treatment is indicated and caesarean section may be needed to reduce the risk of transmission.

 

There is no evidence that genital herpes directly causes infertility in the female. However, pain during recurrent episodes can make sexual intercourse difficult or impossible.

 

More recently, some studies have demonstrated an increased incidence of herpes simplex virus, the virus that causes genital herpes, in the semen of men with male factor infertility⁴ who have no other symptoms. The presence of this, or other viruses, may impair the ability of the sperm to spontaneously fertilize the egg. As noted earlier, no treatment has been found to eradicate the virus.

 

Gonorrhea is a bacterial infection which primarily affects the vagina, cervix, uterus, and fallopian tubes in women and affects the urethra, epididymis, and testes in men. Typical symptoms are pelvic pain and vaginal or penile discharge. Occasionally gonorrhea is associated with liver infection, tonsil infection, arthritis and septicaemia (blood infection). However, as is the case with many STDs, in over 50% of cases there will be no symptoms at all.

 

Worldwide, gonorrhea is the most common serious STD, particularly in the developing world. Some estimates show 1-2% of men and women in sub-saharan Africa are affected¹. In Canada, there was a peak in the rate of infection after the second world war, and although rates have been declining since the 1970s, more recently there has been a slight increase in the incidence of gonorrhea - possibly related to penicillin-resistant strains of the bacteria.

 

Treatment with an appropriate antibiotic – usually cephalosporin or ciprofloxacillin – is effective. However, all sexual contacts should also be treated and cultures taken to identify any resistant strains of bacteria -- particularly if infection has been acquired from overseas, especially in the Asia-Pacific region. These cases may require different antibiotics such as spectinomycin. Many doctors also recommend concomitant treatment for chlamydia infection as well⁵.

 

The major long-term effect of gonorrhea infection is the development of tubal disease and damage. Although tubal surgery may help affected women achieve pregnancies, most will need IVF. Tubal disease occurs in about 15% of infected women. Untreated or recurrent infection is associated with higher rates of later infertility. Unfortunately, since many cases present with no symptoms, routine testing for gonorrhea when other STDs are present is essential. It is also vital to have a low threshold to commence treatment in symptomatic women or men. The 'hidden' nature of gonorrhea (and chlamydia as well) highlights the importance of tracing and treating all sexual contacts of any infected person.

 

In pregnancy, gonorrhea is associated with miscarriage, low birth weight babies, premature delivery, and opthalmic (eye) infection of the baby, which, if untreated, can result in blindness. Appropriate screening and treatment is essential.

 

Untreated gonorrhea in men can result in infection of the testis and surrounding tissues (epididymitis or orchitis). Occasionally this can result in post-infective obstruction of the transport of sperm, and therefore male factor infertility⁶. The probability of male factor infertility following a gonorrhea infection in Canada is unknown, but a Nigerian study suggested that male factor infertility rates may be as high as 50% following untreated gonorrhea infection⁷.

 

Gonorhea and chlamydia infect the same tissues and cause a similar spectrum of disease. In fact, up to 50% of women with gonorrhea also have chlamydia infection¹. In developed countries, like Canada, chlamydia infection is the most common bacterial STD.

 

In women, most early chlamydia infections are 'silent' -- without symptoms -- and may remain so for months or years. Most women or men are diagnosed as a result of routine testing or sexual contact tracing. In addition to many cases being silent, the currently available tests for the detection of chlamydia are not 100% sensitive. This is why chlamydia infection has often been described as the 'silent epidemic.' When symptoms occur, women may present with lower pelvic pain, slight vaginal discharge, urinary discomfort or frequency, and very occasionally vaginal bleeding. Men are also usually asymptomatic, but may present with groin or testicular pain, penile discharge, or urinary symptoms.

 

Because of the increasing prevalence and silent nature of chlamyida infection, there should be a low threshold to treat possible infection. Treatment with antibiotics such as doxycycline or azithromycin is effective, and erythromycin is used during pregnancy. Treatment failure occurs in about 2% cases and can usually be attributed to incomplete treatment of the patient or sexual partners. Resistant strains have been reported, although these are not widespread.

 

Most men and women who have had a chlamydia infection treated are unlikely to develop later problems. But untreated chlamydia can result in chronic pelvic pain, pelvic inflammatory disease, and tubal infertility. Like gonorrhea, the probability of developing tubal disease after a chlamydia infection is estimated at 10-30%. However, this is probably an over-estimate, as so many cases of chlamydia are unrecognized. Nevertheless, due to the high incidence of chlamydia infection, it is the most important cause of tubal factor infertility in Canada.

 

In men, chlamydia epididymitis and orchitis can be associated with disruption of sperm transport, although this is rare⁸. More recently, the presence of current or ongoing (albeit asymptomatic) chlamydia infection has been shown to impair sperm function and is related to male factor infertility⁹.

 

During pregnancy, chlamydia infection is associated with premature delivery and transmission to the baby. This leads to opthalmic infection and pneumonia in the newborn. Treatment during pregnancy and of the newborn is appropriate.

 

Pubic lice and scabies are caused by insects which lay eggs. Symptoms include itching in scratching in the pubic area. Treatment is with topical preparations, such as benzene hexachloride. All contacts should be treated. Although there is a risk of infection with other STDs at the same time - and these should be looked for and treated - pubic lice and scabies infestations alone are not associated with infertility or problems during pregnancy.

 

Syphilis is a rare STD in Canada today. Ulcers can present around the groin and vulva in a primary infection, although they may be unseen. Treatment is with penicillin based antibiotics. Later manifestations in untreated cases include fever, headache, bone and joint pain, and generalized itchy rashes, particularly on the palms and soles of feet. The later cardiac and neurological complications encountered in previous centuries are thankfully very rare. The most significant reproductive risks of syphilis are late miscarriage, stillbirth and transmission of infection to the newborn. Therefore, all pregnant women should be screened for syphilis during their ante-natal care.

 

Tropical genital ulcer disease, lymphogranuloma venerum, chancroid and garnuloma inguinale (donovanosis) are all rare causes of genital ulcers. They are mostly found in the developing world and treatment is with appropriate antibiotics. Effects on fertility and reproduction are unknown.

 

Hepatitis can be caused by several viruses which may be sexually transmitted. These include hepatitis B, hepatitis C, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Although chronic health problems may ensue, their effect on fertility is limited. Acute CMV infection may rarely cause problems during pregnancy.

 

Bacterial vaginosis is a sexually associated infection, rather than an STD per se. It has not been linked with fertility problems, but hasbeen associated with adverse pregnancy outcomes, including chorioamnionitis,premature rupture of membranes, premature birth, and postpartumendometritis. Although no national surveillance data areavailable, bacterial vaginosis is probably the most prevalentinfectious cause of abnormal vaginal discharge. The principalgoal of therapy has been to relieve vaginal symptoms, whichcan be accomplished with oral metronidazole, clindamycin cream,or metronidazole gel. Several studies suggest thattreatment of bacterial vaginosis in pregnant women with a historyof preterm birth may reduce subsequent risk for prematurity^10,11. However, no studies have shown a reduction in adverseoutcomes of pregnancy among asymptomatic women without a historyof preterm birth, so current evidence does not support universalscreening for bacterial vaginosis in pregnancy.

 

Human immunodeficiency virus (HIV) infection is predominantly sexually acquired. A review of HIV is beyond the scope of this article, except that other STDs increase susceptibility to HIV, and therefore HIV should also be tested for in all cases of suspected STD infection. Testing will allow early treatment to prevent disease progression. Similarly - there is a risk of transmission of the virus to the baby during and after delivery. Screening prior to attempting pregnancy or during pregnancy will allow for treatment to be provided where necessary, which will decrease the likelihood of transmission to the newborn.

 

STDs are common. They often occur together and many may be completely symptom free. Because of this and the later effects, particularly of gonorrhea and chlamydia, on fertility, there should be effective targeted education -- most cases occur in women and men under 25 years old -- concerning the risks of unprotected sexual intercourse. There should be easy access to testing for STDs, especially for younger people. There should be a low threshold to treat STDs, particularly as treatment will prevent the later fertility and pregnancy related complications. Finally, there should effective and non-stigmatized contact tracing, testing, and treatment. These measures, with continued vigilance and a lack of complacency, will reduce the burden of STD infection on individuals and society. The development of vaccines, particularly against HPV virus (genital warts), HSV virus (genital herpes), gonorrhea, and chlamydia, will further help to conquer these diseases.

 

1.      Richardson H, Franco E, Pintos J, Bergeron J, Arella M, Tellier P. Determinants of low and high risk cervical human papilloma virus infections in Montreal University students. Sex Transm Dis 2000; 27: 79-86.

2.      Lundqvist M, Westin C, Lundkvist O, Simberg N, Strand A, Andersson S, Wilander E. Cytologic screening and human papilloma virus test in women undergoing artificial fertilization. Acta Obstet Gynecol Scand. 2002; 81: 949-53.

3.      Donovan B. Sexually transmible infections other than HIV. Lancet 2004; 9408: 545-556.

4.      .Osegbe DN. Testicular function after unilateral bacterial epididymo-orchitis. Eur Urol 1991; 19: 204-208.

5.      Veznik Z, Pospisil L, Svecova D, Zajicova A, Unzeitig V. Chlamydiae in the ejaculate: their influence on the quality and morphology of sperm. Acta Obstet Gynecol Scand. 2004; 83: 656-60.

6.      Hauth JC, Goldenberg RL, Andrews WW, DuBard MB, Copper RL. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis N Engl J Med. 1995; 333: 1732-1736.

7.      Morales WJ, Schorr S, Albritton J. Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am J Obstet Gynecol. 1994; 171: 345-347.

8.      Westrom LV. Chlamydia and its effect on reproduction. J Br Fer Soc 1996; 1: 23-30.

9.Veznik Z, Pospisil L, Svecova D, Zajicova A, Unzeitig V. Chlamydiae in the ejaculate: their influence on the quality and morphology of sperm. Acta Obstet Gynecol Scand. 2004; 83: 656-60.

10.Hauth JC, Goldenberg RL, Andrews WW, DuBard MB, Copper RL. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis N Engl J Med. 1995; 333: 1732-1736.

11.Morales WJ, Schorr S, Albritton J. Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am J Obstet Gynecol. 1994; 171: 345-347.