Spontaneous fertility and IVF outcome The new evidence of HPV sperm infection

Capsule:
This clinical study demonstrates a significant association between HPV sperm infection, reduced pregnancy rates, and higher miscarriage rates in couples undergoing assisted reproduction.

Authors:
Andrea Garolla, M.D., Bruno Engl, M.D., Damiano Pizzol, M.D., Marco Ghezzi, M.D., Alessandro Bertoldo, B.Sc., Aberto Bottacin, B.Sc., Marco Noventa, M.D., Carlo Foresta, M.D.

Volume 105, Issue 1, Pages 65-72

Abstract:

Objective:
To evaluate the reproductive outcome of infertile couples undergoing assisted reproduction techniques (ART) with or without human papillomavirus (HPV) semen infection.

Design:
Cross-sectional clinical study.

Setting:
Units of andrology, reproductive medicine, and gynecology.

Patient(s):
A total of 226 infertile couples.

Intervention(s):
Male partners were evaluated by means of fluorescence in situ hybridization (FISH) for HPV on semen. After a diagnostic period, female partners underwent intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI).

Main Outcome Measure(s):
Seminal parameters and FISH analysis for HPV in sperm head. Spontaneous or assisted pregnancies, live births, and miscarriages were recorded. Statistical analysis included unpaired Student t test and chi-square test.

Result(s):
Fifty-four male partners (23.9%) had HPV semen infection confined to sperm, confined to exfoliated cells, or in both cells. During the diagnostic period, noninfected couples showed spontaneous pregnancies. IUI and ICSI treatments were performed in, respectively, 60 and 98 noninfected and in 21 and 33 infected couples, with 38.4% and 14.2% cumulative pregnancy rates, respectively. The follow-up of pregnancies showed a higher miscarriage rate in infected couples (62.5% vs. 16.7%). Ongoing pregnancies of the latter group were characterized by HPV infection confined to exfoliated cells.

Conclusion(s):
A reduction in natural and assisted cumulative pregnancy rate and an increase in miscarriage rate are related to the presence of HPV at sperm level. Although the exact mechanism by which sperm infection is able to impair fertility remains unclear, this aspect is worthy of further investigations. If confirmed, these results could change the clinical and diagnostic approach to infertile couples.

  • 1 in 4 people are infected in the United States according to the CDC. I am surprised that we are not seeing more males seeking male infertility evaluations, given the negative impact of HPV on pregnancy rates and a miscarriage rate 4X higher (62.5%) as demonstrated in this study. I agree with Samplaski, maybe there is a very large role for HPV vaccinations, not only for the prevention of HPV related malignancies, but also for the fertility aspect. The next step in this study is to find out how we can treat couples that are already infected and have had difficulties conceiving.

    • Andrea Garolla

      Dear Dr. Ko,
      thank you for the valuable comment. I wonder to underline that male infertility due to HPV infection affects just males with HPV at sperm level while the largest part of infected people has the virus located only in the glans region. We already performed studies aimed to speed up the clearance of HPV from infected couples observing that both couple behavior and HPV vaccination are able to accelerate the clearance time. References of these studies are:
      1) Garolla A, Pizzol D, Vasoin F, Barzon L, Bertoldo A, Foresta C. Counseling reduces HPV persistence in coinfected couples. J Sex Med. 2014;11:127-35.
      2) Foresta C, Garolla A, Parisi S, Ghezzi M, Bertoldo A, Di Nisio A, De Toni L.
      HPV Prophylactic Vaccination in Males Improves the Clearance of Semen Infection. EBioMedicine. 2015;5:1487-1493.
      Thank you again and best regards,
      Andrea Garolla

  • msamplaski

    This is an interesting study, in an area with a paucity of data. Was serotyping of the HPV done? Was there any correlation between HPV presence and semen parameters? In addition, it would be interesting to know the incidence of HPV among fertile men. Nonetheless, this data is interesting and may eventually result in another role for HPV vaccinations.

    • Andrea Garolla

      Dear reader,
      HPV serotyping was performed and different HPV types were found. Bad IVF outcome was related to any HPV type. When HPV was present at sperm level, reduced progressive motility and higher percentage of antisperm antibodies were found. The prevalence of HPV in semen among fertile men was 2.2% as reported in “Clinical and prognostic significance of human papillomavirus DNA in the sperm or exfoliated cells of infertile patients and subjects with risk factors” by Foresta et al. Fertil Steril 2010;94:1723-1727.

  • Jason M. Franasiak

    An interesting cross-sectional study in which HPV+ findings in semen samples are associated with poor outcomes. It stated that pap smears for the female patients were negative. Was HPV DNA testing done for the female as well? Given high rates of co-infection it is likely positive results in the male represent positive results in the female. However, knowledge of HPV serotypes, either from the male or female, may be of interest.

    • Andrea Garolla

      HPV serotyping was performed only in males and different HPV types were found. Bad IVF outcome was related to any HPV type and no difference between high and low risk was observed.

      • Andrea Garolla

        Dear Dr. Franasiak,
        HPV serotyping was performed only in males and different HPV types were found. Bad IVF outcome was related to any HPV type and no difference between high and low risk was observed.

        • Jason M. Franasiak

          Thank you for your reply and interesting contribution Dr. Garolla!

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