1 Fédération de Gynécologie-Obstétrique et Médecine de la Reproduction, CHU La Grave, 31052 Toulouse, 2 Laboratoire de Virologie and 3 Service d'Hépato-Gastro-Entérologie, CHU Purpan, Toulouse, France
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Abstract |
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Key words: hepatitis C/in-vitro fertilization/virus
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Introduction |
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Case report |
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The second case was a 32 year old anti-HCV negative woman having an IVF attempt with donor spermatozoa for non-obstructive azoospermia associated with tubal infertility. The HCV infection was clinically occult and the contamination was detected through a systematic search for anti-HCV antibodies and confirmed by the presence of HCV RNA in serum. Since she was not pregnant, the patient was immediately treated by -interferon, 3x106 units twice a week for 6 months after which HCV RNA disappeared from her serum.
Since these two patients were negative for anti-HCV antibodies at the time of their attempts at assisted reproduction and did not present any risk factors (blood transfusion, endoscopy, piercing, etc.) we suspected a nosocomial transmission in the course of the various procedures carried out during assisted reproduction treatment. We investigated the patients' records and the procedures used during these attempts. We found that each of them was treated concomitantly, but at different periods (one in May 1997, the other in September 1997), at the same time as a patient known to be HCV infected. In both cases the contaminated patient had follicular puncture immediately after the infected one. The HCV genotypes from the three patients, characterized by the line probe assay (LIPA HCVII®; Innogenetics, Zwijndrecht, Belgium), were 1b. Two-strand direct sequencing was carried out on a nested polymerase chain reaction (PCR) product in the E2 gene encompassing the hypervariable region 1 of the HCV genome as previously described (Izopet et al., 1999). Phylogenetic analysis of E2 sequences from these 1b strains and a control panel consisting of 1b strains from the same geographical area plus 1b strains extracted from the EMBL (EMBLEuropean Bio-Informatics Institute) data bank indicated clustering of the two cases of de-novo infections with the already infected patient attending the IVF centre (Figure 1
). We screened all other patients treated in the same periods (sharing same days of puncture, ultrasonographic examinations and blood sampling) for anti-HCV antibodies and none of them appeared to be infected. Moreover, all the staff of the assisted reproduction treatment centre (physicians, biologists, nurses, etc.) were tested and found to be negative. Follicular puncture was therefore not suspected as the cause of contamination. Moreover, the contaminated patients and the suspected contaminating one underwent follicular puncture in different rooms, with different probes and single use materials, the follicular fluids were treated in different laminar hoods and oocytes placed in different incubators. These findings led us to postulate that the contamination occurred outside the direct practice of IVF, and possibly through procedures practised by ancillary staff.
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Discussion |
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Contamination during the follicle puncture itself seems also to be unlikely. Indeed, contaminating and contaminated patients were punctured in different rooms, with different probes and all other materials were disposable. This situation looks like the one reported in dialysis centres, where patients treated on different but adjacent machines were contaminated by the same viruses (Natov and Pereira, 1996; Pereira and Levey, 1997
; Ouzan, 1997
). Therefore a physical proximity during routine health care appears to be a risk of HCV transmission. This risk seems to be linked to percutaneous exposure during i.v. injection processes or to the use of multi-dose vials of drugs (MacDonald et al., 1996
; Pereira and Levey, 1997
; Couzigou, 1997
). Cross-infection between patients has been reported in a care unit where nurses did not change their gloves but disinfected them with alcohol-based products, inactive on HCV viruses (Schvarcz et al., 1996; Van der Poel and Ebeling, 1998
). The use of multi-dose vials of heparin has also been shown to be a route of contamination in dialysis patients (Pereira and Levey, 1997
).
Laboratory contamination by hepatitis B has been reported due to the use of serum containing culture medium (Quint et al., 1994). This cannot be the case in our team since protein-free media without any supplementation are used for IVF (Parinaud et al., 1998
, 1999
). Moreover, the laboratory instruments used for follicular fluid examination, IVF and embryo culture were different.
Contamination during embryo transfer is unlikely since it is not bloody, only disposable materials were used and no i.v. injection was done.
Patients with anti-HCV antibodies are now included in our programme only if HCV RNA is negative at the beginning of the IVF cycle. French law includes guidelines concerning assisted reproduction procedures, published in February 1999 (Ministère de l'Emploi et de la Solidarité, 1999). Assisted reproduction treatment in HCV positive patients (male or female partner) is possible only in the case of a clinical research protocol accepted by the governmental health ministry. However, these measures are mainly made to protect against partner to partner and mother to child contamination and not for nosocomial transmissions. Our experience leads us to recommend extreme prudence and to take all possible hygienic precautions when including such patients in an IVF programme. A way to minimize the risks could be to treat these patients before IVF in order to eradicate the virus.
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Notes |
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References |
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Submitted on December 13, 1999; accepted on February 10, 2000.