Mystery, Medicine & the Magnificent Mile
Many aspects of reproductive health continue to be a mystery. When couples struggle with infertility, they will likely be asked to undergo various types of tests to identity the causes for concern and determine treatments. Patients’ feelings may fluctuate between hopeful, frustrated, upbeat, sad and angry.
“What causes infertility?” is a question asked by nearly every patient at CARE Fertility.
CARE Fertility co-founder Kevin Doody, M.D., continues to conduct research to find answers for patients. Dr. Kevin recently presented at the 2019 Midwest Reproductive Symposium International (MRSi). Held in Chicago, the event was appropriately named, Mystery, Medicine & the Magnificent Mile.
One mystery is the Human Herpesvirus 6 (HHV-6) and how the virus impacts infertility in men and women. Dr. Kevin presented findings from the latest research on HHV-6A and HHV-6B.
First, some background. Herpes is a large family of viruses that cause infections and disease. Nine herpesvirus types are known to infect humans: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2,), varicella-zoster virus (VZV, which may also be called by its ICTV name, HHV-3), Epstein–Barr virus (EBV or HHV-4), human cytomegalovirus (HCMV or HHV-5), human herpesvirus 6A and 6B (HHV-6A and HHV-6B), human herpesvirus 7 (HHV-7), and Kaposi's sarcoma-associated herpesvirus (KSHV, also known as HHV-8). Herpesviruses are known for their ability to establish lifelong infections. One way this is possible is through immune evasion. Herpesviruses have many different ways of evading the immune system.
Here are highlights from Dr. Kevin’s presentation, “HHV-6 (Human Herpesvirus 6) and Reproductive Failure”:
- The two viruses, HHV-6A and HHV-6B, like all human herpesviruses, following primary infection the viruses establish a life-long infection in the host. The viruses are maintained usually in a “latent” or inactive state.
- However, periodic “reactivations” of the viruses from latency can result in a range of symptomatic illness.
- HHV-6A and HHV-6B have impacted reproduction:
- HHV6A has been implicated in Infertility
- Early miscarriage (HHV-6A/B)
- Fetal death (HHV-6A/B)
- 43% of unexplained infertile women tested positive for HHV-6A
- HHV-6A appears to:
- Alter micro-environment of uterine endometrium
- Cause a cascade of changes in the uterine micro environment,
- Without any obvious clinical signs and
- Without being detected in the blood.
- 40% of infertile women demonstrated HHV-6A in Endometrial Epithelial cells - per Caselli et al 2017
- Medical Hypothesis, May, 2017 by Eliassen, et al
- “HHV-6A has been implicated in cases of poor pregnancy outcomes. The ability to disrupt endothelial cell functioning may inhibit…an appropriate uterine environment for implantation and fetal development.”
- HHV-6A is “able to enter a latent state after primary infection…and can reactivate in response to stress, immunosuppression or drugs such as steroids and HDAC inhibitors.”
- Testing for HHV-6A in Unexplained Infertility
Traditional HHV-6 blood sample testing inappropriate
- HHV-6A was detected in uterine epithelial cells
- HHV-6A not detected in the blood
Immunohistochemistry for viral protein expression
- The most sensitive test for HHV-6 in tissue
- Has strong history over many years in other organs
- liver, lung, heart, brain, bone marrow and GI
- Distinguishes low-level latent virus from active replicating virus
- Diagnostic Testing
Immunohistochemistry is the preferred method for confirming active beta-herpesvirus infections in tissue
- Treatment considerations for HHV-6 Antivirals: acyclovir, valacyclovir
Safety profile in pregnancy
- First trimester use of acyclovir demonstrated no increase in major birth defects in 1804 exposed infants vs 19,920 infants not exposed to acyclovir (Pasternak B et al, JAMA;2010)
- Prophylactic high dose acyclovir associated with significantly lower incidence of HHV-6 in BMT recipients (Wang FZ et al, BLOOD; 1996)
Research continues to identify tests and treatments to minimize the impact of HHV-6 on infertility. Dr. Kevin acknowledges his collaborators, Konstance Knox and Coppe Labs. Dr. Knox is a virologist and microbiologist, who is an expert in HHV-6 and was the first to associate HHV-6 infection with disease in transplant recipients and MS. Coppe Labs has over 30 years of experience and research with HHV-6.
Dr. Kevin’s recent research on HHV-6 is just one example of CARE Fertility’s commitment to providing the latest in healthcare treatments and technology to patients.
Scroll down to get in touch, learn more and schedule a consultation.