Viral Infection and Female Infertility

HIV-1 can be detected in both vaginal and cervical secretions as a cell-free viruses and also as a cell-associated viruses. Most HIV-1 in the female genital tract arises from the cervix. Blood plasma HIV-1 RNA concentration is the most important predictor for HIV-1 genital shedding, but the use of oral contraceptives, vitamin A deficiency, Candida albicans infection and gonorrhoea cervicitis are associated with increased vaginal or cervical shedding of HIV-1. Highly active antiretroviral therapy (HAART) results in decreased shedding of HIV-1 in the female genital tract. The risk of sexual and vertical transmission can be reduced by HAART but never eliminated. As a consequence, even during successful HAART, unprotected intercourse should be discouraged at all times.

Cohort studies have demonstrated a high prevalence of Sexually Transmitted Diseases (STD) in HIV-1-infected women. These women may therefore also be at risk for tubal. The Ovarian reserve of HIV-1-infected women is conflicting. Some describe a normal ovarian reserve, whereas others claim a higher incidence of severe ovarian dysfunction, that is premature ovarian failure. Case studies have suggested lower pregnancy rates in HIV-1-infected women when compared with women without HIV-1 infection, irrespective of past or current additional STD. The purpose of ART in case of HIV-1 infection varies from merely an HIV-1 transmission reduction strategy to treatment for co-existing subfertility or a combination of both. Which type of ART to use depends on whether the man is HIV-1 infected or the woman or both. In serodiscordant couples in which the male partner is HIV-1 infected, high-technology ART is necessary to prevent sexual transmission. This type of ART involves semen processing in such a way that an HIV-1-free spermatozoal fraction is obtained. This HIV-1-free spermatozoal fraction can then be used for intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmatic sperm injection (ICSI).

Several herpesviruses have been implicated in male infertility, and now human herpesvirus 6A (HHV-6A) has been found in endometrial cells of women with unexplained infertility. Endometrial epithelial cells from 13/30 (43%) infertile women were positive for HHV-6A DNA; this viral DNA was not detected in the endometrium of fertile women. When placed in culture, endometrial epithelial cells produced viral early and late proteins, suggesting the presence of an infectious virus. The presence of HHV-6A DNA in endometrial epithelial cells was also associated with an altered hormonal and immune environment. Estradiol levels were higher in infected versus uninfected infertile women. The authors suggest that higher levels of this hormone could be involved in allowing HHV-6A infection of the endometrium. The virus seems to activate immune cells called natural killer cells in the uterus, and lead those cells to produce chemicals called cytokines. Cytokines are tools the immune system uses to orchestrate an attack on a foreign invader, like a virus. However, the activated immune system cells and abnormal levels of certain cytokines may make it harder for a fertilized egg to lodge in the uterus, and grow into a baby.

Hepatitis does not have any effect on the normal functioning of the ovarian or uterine glands. However, this virus impacts spermatogenesis negatively in males. This causes a reduction in the sperm count, free testosterone levels, motility, viability, and morphology which further impacts overall fertility and ability to produce offspring in them. “Transmission risk from mother to baby increases by 80% to 90% in Hepatitis B cases and 11% in Hepatitis C positive cases, where there is high viral load. Some ways to reduce this risk include semen washing, administering the uninfected partner with hepatitis B vaccination, and treatment with Interferon and Ribavirin. Many couples would have doubts, fears, and misconceptions in their mind about this condition. Our results suggest HBV infection in either partner was associated with tubal infertility. HBV infection in either partner probably increases the risk of pelvic infection in the female partners through impaired immune response to sexually transmitted infections, with consequent tubal damage and infertility. For couples where one partner is HBsAg positive, the best option is HBV vaccination to prevent transmission. Since 95 % of patients will seroconvert after vaccination, physicians will rarely see a patient in which the patient and partner are at risk of transmission

Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by a successful HCV cure. Studies showed that the prevalence of HCV infection was lower in infertile patients than in the general population. In the presence of infection, semen viraemia was extremely low. HCV is found in the semen of HCV-positive patients in very low or of undetectable levels by the available methodology; however, these data must be interpreted with care, since semen is known for its ability to inhibit PCR. Moreover, the importance of HCV virus in semen can be related to virus concentration, since viral infections might contribute to male infertility by causing an inflammatory/immunologic reaction or by a direct toxic effect. We also found a positive association between HCV-positivity in males and risk for HCV-positivity in their female partners. Some investigators have demonstrated that sexual transmission is more probable in cases with co-infection by HIV, suggesting an association with the elevated HCV charge produced by immune suppression. Prisant et al. found clinical pregnancy rates for HCV infertile seropositive couples was not significantly different from those for seronegative controls. Pirwany et al. showed that HCV positive couples had lower implantation and pregnancy rates. HCV receptors are found not on the oocyte itself, but rather on granulosa cells surrounding the oocytes, and since HCV is an RNA virus, it cannot integrate into the host genome to potentially cause chromosomal instability like HBV. Some studies suggest HBV infection does not effect IVF outcomes. Additionally, for HCV, many studies have denied the possible risk of sperm/oocyte-HCV transmission during ART. Further supporting this point, spent culture media used after ovum pickup or embryo culture and in liquid nitrogen used for oocyte or embryo vitrification in HCV positive IVF patients could detect no HBV, HCV, or HIV-1 transcripts. The HCV RNA in those samples would likely be a result of blood contamination during the surgical procedure, like an ovarian puncture or testicular sperm extraction (TESE) and microsurgical epididymal sperm aspiration (MESA). Furthermore, it seems widely accepted that the washing protocol was effective for HCV risk reduction and concerns about the transmission of the virus to the newborn through gametes or embryos seemed unfounded. HCV causes abnormal liver function, which can induce improper hormone levels and altered metabolism, some studies noted these hormonal disturbances may lead to a poor ovarian response to stimulation and in turn hurt ART outcomes. Nevertheless, IVF patients with abnormal liver function are taking a risk in ovarian aspiration and pregnant procedures and should always be pre-treated with anti-viral therapy before IVF cycles. For cycles with oocyte retrieval, HCV-seropositive women required more GnRH units and a decreased ovarian response Testing for HBsAg and HCV should be offered to high-risk infertile couples seeking fertility therapy to reduce the potential risk of transmission to an uninfected partner, baby, staff members, and disease-free gametes and embryos in the same laboratory. Testing for HIV, HBsAg, and HCV status should be performed on the couple before cryopreservation of semen or embryos. With HCV, however, the risks are different, as no vaccine for HCV is currently available. Recent studies have shown that the presence of HIV, HBV, or HCV in semen impairs sperm parameters, DNA integrity and in particular reduces forward motility. In addition, treatment with antiviral and antiretroviral therapies may further affect sperm parameters. Ideally, semen and embryos from HCV and HBV patients should be stored in HCV- or HBVdesignated storage tanks. Methods suggested for reducing the potential risk of virus transmission among cryopreserved sperm and embryos include storage of sample in the nitrogen vapour state instead of the liquid state; use of sperm washing techniques to reduce viral load before freezing semen samples; and use of a double-sealing technique for cryo-containers.