Human papillomavirus (HPV) has received recent attention concerning fertility. Many however don’t know of its fertility implications. Most people are aware that sexually transmitted infections such as gonorrhea and chlamydia. These cause pelvic inflammatory disease (PID), can result in infertility and ectopic pregnancies. The mechanism is related to damage to the fallopian tube that causes blockage or scar tissue that distorts the tube or prevents an egg from entering it to be fertilized.
HPV has been long recognized as the cause for genital warts and precancerous conditions of the cervix, even cervical cancer. Anal and penile cancer are also linked to HPV. The vast majority of people with HPV are asymptomatic. Eventually, the viral growth slows, or the immune system keeps it in check. Past and ongoing studies are now evaluating the role of HPV in the success of in-vitro-fertilization (IVF) and miscarriages.
Other viral STIs, such as human herpes virus (HSV), adeno-associated virus, human immune-deficiency virus (HIV), and human cytomegalovirus (HCMV) are associated with lower fertility rates but the mechanisms are not well-understood.
It is well known that inflammation or vaginal infections of any sort have adverse pregnancy implications. These are mostly fungal or bacterial infections. Inflammation or active infection at the time of conception can result in early pregnancy loss or premature births, primarily due to ruptured membranes before the due date.
Human papillomavirus (HPV) and Intrauterine Insemination
A recent article in Fertility and Sterility (in press) discusses how males with HPV contribute to infertility associated intrauterine insemination (IUI) due to semen quality. In this study, five hundred and seventy-three infertile couples underwent IUI. Each sperm sample was tested for 18 different HPV subtypes (6,11, 16, and 18) being the most common.
Overall, there was 12.5% of sperm samples infected with one or more strains of Human papillomavirus (HPV). Compared to HPV-negative IUIs, HPV-positive cycles were associated with lower clinical pregnancies (2.9% lower compared to 11.1%). This represented a four-fold decrease in pregnancies for HPV-positive partner.
HPV, In-Vitro Fertilization and Intracytoplasmic Sperm Injection
Another study by Gorilla et al. in Fertility and Sterility, evaluated spontaneous fertility to in-vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) among men with and without HPV. The rate of pregnancy was 38.4% in those not infected and 14.2% in HPV positive sperm. The miscarriage rate was also higher in HPV positive; 62.5% compared to 16.7% in uninfected couples.
Human papillomavirus (HPV), Semen, IVF, and Pregnancy Outcomes
A large retrospective review of prior research on HPV and fertility analyzed 55 articles grouped and settled on 21 articles covering three topics: Semen Quality, IVF Outcomes and Pregnancy Outcomes
- Semen Quality: HPV DNA induces DNA fragmentation in sperm cells which leads to cell death, but it depends on the subtype. Exposure to DNA from HPV 16 or 31 leads to cell death but, nothing occurs when these cells are exposed to DNA from HPV types 18, 33 or 6 /11.In the same studies, DNA from HPV 16 or HPV 6/11 reduced the degree of lateral head placement of the sperm compared to DNA from HPV types 18, 31 and 33. In addition, Lee et al. showed a significant decrease of sperm total motility in the presence of DNA from HPV 6/11, 16, 18, 31 or 33. Other studies failed to confirm this finding.Overall, there was reduced sperm viability, less motility, distortions in the head placement, decreased sperm counts, more abnormal shapes, and an increase in antibodies to sperm (antibodies attack the sperm) in the presence of HPV DNA.
- IVF: Similar to Italian studies, it was found in the USA a higher rate of IVF failure in HPV positive women (76.5% vs. 57%). It was believed the effect of HPV on IVF was due to the cervical abnormalities or to the health of the fetus. One study from the Netherlands demonstrated that precancerous conditions of the cervix were associated with two times the number of sub-fertile women compared to those without HPV but not confirmed in a study from China.
- Pregnancy Outcomes: Placental cell death was six times higher in HPV infected cells compared to normal cells. This cell death could explain placental dysfunction, the reduction in the ability of the embryo to implant in the uterine wall to gain a blood supply (miscarriage) or premature rupture of membranes (PROM). Two separate studies confirmed HPV was associated with miscarriages and PROM. HPV likely weakens the membranes or amniotic sac in pregnancy.
If you suspect HPV, consult your doctor…
If you suspect you have HPV or were exposed to it, consult your doctor for testing. Either men or women who are negative for HPV might consider the vaccine if eligible. Hopefully, there will be anti-viral therapies that may be able to slow or stop viral growth as they do for the herpes virus for those who are HPV positive with fertility issues.
- Depuydt, C.E., et al. (In Press). Infectious human papillomavirus virions in semen reduce clinical pregnancy rates in women undergoing intrauterine insemination. Fertility and Sterility, Volume 0, Issue 0. Retrieved from https://www.fertstert.org/action/showCitFormats?pii=S0015-0282%2819%2930080-9&doi=10.1016%2Fj.fertnstert.2019.02.002
- Garolla, A. et al. (2016 Jan). Spontaneous fertility and in vitro fertilization outcome: new evidence of human papillomavirus sperm infection. Fertility and Sterility. 105(1):65-72.e1. doi:10.1016/j.fertnstert.2015.09.018. Epub 2015 Oct 9. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26453270
- Souho, T., Benlemlih, M. and Bennani, B. (May 18, 2015). Human papillomavirus infection and fertility alteration: a systematic review. PLoS One. 2015;10(5):e0126936. doi:10.1371/journal.pone.0126936. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25992782