HPV λοίμωξη & Υπογονιμότητα. Γεώργιος Λ. Αντωνάκης Αναπληρωτής Καθηγητής Μαιευτικής-Γυναικολογίας Πανεπιστημίου Πατρών

Transcript

1 HPV λοίμωξη & Υπογονιμότητα Γεώργιος Λ. Αντωνάκης Αναπληρωτής Καθηγητής Μαιευτικής-Γυναικολογίας Πανεπιστημίου Πατρών

2 Δεν υπάρχει οποιαδήποτε σύγκρουση συμφερόντων. 2

3 ΓΥΝΑΙΚΕΣ & ΥΠΟΒΟΗΘΟΥΜΕΝΗ ΑΝΑΠΑΡΑΓΩΓΗ 3

4 Μπορεί η πρόκληση πολλαπλής ωοθυλακικής ωρίμανσης με γοναδοτροπίνες να επηρεάσει την ανίχνευση του HPV? Gene expression in HPVs 16 and 18 is induced directly by steroid hormones through hormone response elements in the regulatory region of the viral genome and HPV 16 transcription is enhanced by estrogen in vitro. Gloss B, et al. The upstream regulatory region of the HPV-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones. EMBO J 1987 Mittal R, et al. HPV type 16 expression in cervical keratinocytes: role of progesterone and glucocorticoid hormones. Obstet Gynecol Michelin D, et al. Regulation of HPV type 18 in vivo: effects of estrogen and progesterone in transgenic mice. Gynecol Oncol 1997 Long-term use of OCs increases the relative risk of condylomata acuminata up to a factor of 9.8. A positive interaction between HPV infection and the use of OCs has been shown for the risk of cervical cancer. Franceschi S, et al. Br J Cancer Daling JR, et al. Sex Transm Dis

5 5

6 6

7 7

8 Κυτταρολογικά ευρήματα και HPV-DNA test σε γυναίκες που υποβάλλονται σε Υποβοηθούμενη Αναπαραγωγή 8

9 9

10 10

11 11

12 12

13 RESULTS: The cases (n = 669) showed significantly more abnormal cervical smears compared to the controls (77 055) (6.1 and 3.9%, respectively, P < 0.02). CONCLUSIONS: The probability that subfertile women eligible for IVF are diagnosed with a high-grade cervical lesion is almost twice as high compared to women in the general population. We therefore suggest to take a cervical smear from all women referred for fertility problems. 13

14 Επηρεάζει η ύπαρξη του HPV την έκβαση της Υποβοηθούμενης Αναπαραγωγής; 14

15 15

16 16

17 17

18 18

19 19

20 20

21 21

22 22

23 23

24 24

25 ΜΗΧΑΝΙΣΜΟΣ 25

26 26

27 27

28 Ασφάλεια 28

29 29

30 30

31 31

32 32

33 33

34 34

35 35

36 ΑΝΔΡΕΣ 36

37 Η ΟΜΑΔΑ ΤΗΣ PADOVA ΚΑΙ ΟΙ «ΑΛΛΟΙ» 37

38 ΑΝΙΧΝΕΥΣΗ ΤΟΥ HPV ΣΤΟ ΓΕΝΝΗΤΙΚΟ ΣΥΣΤΗΜΑ ΤΟΥ ΑΝΔΡΑ ΚΑΙ ΟΙ ΣΥΝΕΠΕΙΕΣ 38

39 39

40 40

41 41

42 Conclusion(s): These results suggest that HPV can be found in human sperm cells and that certain HPV-specific genes are actively transcribed. Sperm motility parameters seem to be affected by the presence of HPV in the sperm cells, and also the incidence of asthenozoospermia may be associated with HPV infection. 42

43 43

44 44

45 45

46 46

47 Result(s): HPV infection was present in sperm cells of 10 subjects among those 100 young adults who already had unprotected intercourse and its presence was associated with reduced sperm motility. Furthermore, infected samples showed that about 25% of sperm had an HPV DNA positivity at the head site, but it is unclear whether it was integrated in the nucleus or not. 47

48 48

49 49

50 Result(s): The prevalence of HPV semen infection found in all groups was as follows: patients with genital warts, 53.8%; infected partners, 40.9%; infertile patients, 10.2%, fertile controls, 2.2%. Infertile patients had a higher HPV DNA prevalence in sperm cells than the other groups. The results of HPV investigation were compared with sperm parameters and the results of FISH analysis. Sperm motility was more frequently reduced in infected samples and in particular when the infection was 50

51 HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm exposed to HPV L1 capsid protein are capable to penetrate the oocyte and transfer the virus into oocytes, in which viral genes are then activated and transcribed. Sperm might function as vectors for HPV transfer into the oocytes, and open new perspectives on the role of HPV infection in males and are particularly intriguing in relation to assisted reproduction techniques. 51

52 52

53 53

54 Result(s): Infertile patients with HPV semen infection showed high percentages of ASAs. In these patients HPV sperm infection was associated with lower sperm motility, which was worse in subjects with ASAs. No alterations of sperm chromosomes were observed. To obtain a significant clearance of both HPV sperm infection and ASAs at least 24 months of follow-up were needed. Conclusion(s): HPV has been recently suggested to have an important role in male infertility. This study demonstrated that HPV sperm infection can be long lasting and frequently associated with ASAs that may further reduce male fertility. Infertile patients with positive sperm Mar test results should be considered for investigation for HPV, especially if they are candidates for assisted reproduction. 54

55 55

56 56

57 57

58 58

59 59

60 60

61 ΑΝΤΙΛΟΓΟΣ 61

62 62

63 Result(s): Results of HPV investigation were compared with sperm parameters and ISH analysis. Twenty-four out of 308 semen samples (7.8%) were HPV DNA positive, but HPV infection did not seem to affect semen quality. Moreover, ISH revealed a clear HPV localization at the equatorial region of sperm head in infected samples. Conclusion(s): Oncogenic HPV genotypes were detected on spermatozoa from asymptomatic 63

64 64

65 65

66 «Preliminary studies show not only that HPV is present in semen, but that it might reduce sperm motility probably causing reduced fertility in males. Moreover, the virus might interfere with the development of the embryo in animal models according to some studies. HPV might be a cause of infertility, even so, further studies are needed in order to clarify its relationship with fertility.» 66

67 67

68 Results. In all, 39% of parents were worried about VAI. Parents worried about VAI had similar knowledge of HPV compared with other parents. Parents worried about VAI had twice the odds of agreeing the vaccine may cause side effects and agreeing they did not have enough information compared to their counterparts. Parents worried about VAI less often intended to vaccinate sons than other parents. Conclusions. These findings suggest many 68

69 Συμπεράσματα Ο HPV είναι παρών με αρκετά μεγάλη συχνότητα στο σπέρμα ανδρών, τόσο με προδιαθεσικούς παράγοντες HPV λοίμωξης, όσο και σε ασυμπτωματικούς υπογόνιμους άνδρες. Η παρουσία του HPV στο σπέρμα συσχετίζεται με ελαττωμένη κινητικότητα. Τα προσβεβλημένα σπερματοζωάρια μπορούν να γονιμοποιήσουν το ωάριο, να μεταφέρουν το HPV γονιδίωμα στο ωάριο και τα γονίδια του HPV να μεταγραφούν από το γονιμοποιημένο ωάριο. Υπάρχει αυξημένος κίνδυνος αυτομάτου εκτρώσεως όταν ο άνδρας είναι HPV DNA (+). 69

70 Οι συνήθως εφαρμοζόμενες τεχνικές προετοιμασίας του σπέρματος πριν την Υποβοηθούμενη Αναπαραγωγή δεν δύνανται να απομακρύνουν τα προσβεβλημένα από τον HPV σπερματοζωάρια. 70

71 Ευχαριστώ για την προσοχή Σας! 71