The United Nations AIDS Report [1] estimated that around 37 million people are infected with the human immunodeficiency virus (HIV) worldwide and around 17 million people undergo highly active antiretroviral treatment (HAART). The World Health Organization report [2] predicted that about 80 million people live with chronic hepatitis C (HCV). Furthermore, about 257 million people were estimated to be living with hepatitis B (HBV) in 2015 [3].

The advance of antiretroviral therapies has allowed seropositive people to live with higher expectancy and better quality of life, and adequate treatment allows infected couples to conceive without the risk of infecting the offspring [4] [5] [6]. Nowadays, almost no horizontal or vertical infection occurs in couples submitted to assisted reproductive technologies (ART) [6] [7] [8] [9]. An interesting study performed by Del Romero and collaborators [10] reported that in the absence of fertility problems, it is possible for serodiscordant couples to conceive naturally under controlled conditions in terms of safety and effective reproduction. The same authors showed that 66% of couples achieved at least one pregnancy [10]. However, most couples face issues other than the risk of infection and these include infertility which resulted from the infection, regardless of whether couples are serodiscordant or seroconcordant [11] [12] [13]. The data available so far are very disperse, but some studies state that couples infected with HIV present higher infertility rates and duration [13] [14]. Indeed, it was found that women infected with HIV presented lower number of retrieved oocytes [14]. Another case-control study reported that women infected with HCV presented a poorer ovarian response as they need more follicle-stimulating hormone (FSH) administration to obtain an equal number of oocytes [15]. Couples infected with HCV show a significant decrease of the pregnancy rate even after administration of higher doses of gonadotrophins, without changing the duration of stimulation [12]. Also, Terriou and collaborators [16] observed that equal pregnancy rates in HIV-positive women were achieved when a longer duration of stimulation was applied. An interesting finding by Coll and colleagues [17] showed that the rate of pregnancy was higher in HIV-positive women when oocytes were donated by healthy women. These HIV-positive women faced ovarian resistance to hyperstimulation because higher doses of gonadotrophins were needed to stimulate them adequately [17].

Overall, the above-mentioned data reported that the difficulties to conceive may reside in the aggravation of infertility, and adequate gonadotrophin stimulation as well as the duration of treatment should be taken into consideration.

In view of the evidence thus established, we aim at assessing the results of IVF cycles of our group infected with HBV, HCV and HIV-1 compared with a control group of uninfected couples.

In this study, we aimed at determining IVF cycle results from a Portuguese infected group which resorted to ART to conceive. We also sought to analyze HIV- and HCV-infected couples individually, two major subgroups of this infected group. The main findings of the present study reside in lower baby home and clinical pregnancy rates in total infected group. In particular, we verified that the clinical pregnancy rate was very low in the HCV subgroup, suggesting that HCV individuals within the infected group contributed the most to this reduction. However, the reduction in baby home rates was only statistically significant for the infected group and not for each subgroup. This could be explained by the high variability observed in both HIV and HCV subgroups when analyzed separately.

The development of HAART provides an increase in life expectancy and quality of life. Administration of specific HAART solutions makes it possible for infected couples to conceive [18] [19]. Furthermore, vertical transmission is almost inexistent when couples undergo ART [7] [8] [9], although they may face infertility-related issues caused by the diseases.

The data provided in the present work was obtained from the only Portuguese Public Health Hospital that provides free of charge fertility care to couples with viral infections.

Our findings revealed that the pregnancy rate was decreased in HCV subgroup. Pieces of evidence demonstrated that HCV serodiscordant couples face difficulties in conceiving [12] [15]. These impairments included poorer ovarian response to stimulation, which could be associated with low ovarian reserve, resulting in an increment of cancelled cycles [15]. Additionally, when there was a response to stimulation, low levels of E₂ and reduced number of antral follicles were observed [12]. Our numbers did not differ from control regarding stimulation duration, doses of gonadotrophins administered and E₂ levels. Also, we did not find any differences in the number of antral follicles, or in FSH and AMH levels. Most likely, the HCV group might have required an increased duration of stimulation to reach equivalent pregnancy rates to control. One study pointed out that HCV-infected women required more gonadotrophins doses to obtain similar peak levels of E₂, but lower numbers of embryos were obtained [15]. The present data suggest that tubal causes of infertility might be the reason behind low pregnancy rates. Another possible reason to explain low pregnancy rates could be the decreased pregnancy rate/transfer as implantation might not have occurred after embryo transfer. Hanafi and collaborators [12] found a decrease in implantation rates in women infected with HCV, but another study showed that HCV did not have any influence in this parameter [15]. We propose that the presence of the disease alongside other infertility outcomes may increase the difficulty of couples to conceive. In fact, male individuals carrying HIV, HCV or HBV present reduced semen volume, sperm count and motility, and increased abnormal sperm morphology [20] [21] [22] [23]. It has also been demonstrated that HIV and HBV can increase the prevalence of unilateral and bilateral tubal-related, and uterine infertilities [13] [16] [24]. Another parameter that could interfere with pregnancy rate is smoking habits as we observed a significant increase in tobacco use in HCV couples. In fact, women who smoke have a high prevalence of poorer ovarian reserves and lower pregnancy rates [25] and men have lower sperm count, motility, and viability [26]. These effects, in association with the disease, may aggravate the impairment to conceive.

We observed that the rate of clinical pregnancy did not significantly change in the HIV subgroup. Other studies corroborate ours, observing that HIV did not have any effect in the total dose of administered gonadotrophins, the duration of stimulation, E₂ levels, or in the number of mature follicles, oocytes, and embryos. The number of clinical pregnancies in HIV-positive women also did not change [13] [27]. In a similar line of study, another group did not find any differences in AMH levels and antral follicles count between HIV-1-positive and non-infected women [28]. These authors did not note any differences in ovarian stimulation, duration, total gonadotropins units administered, except for a difference in E₂ levels, but lower pregnancy rates were observed [28], in line with the results we obtained in this work. Except for AMH levels that were reduced in HIV subgroup, no other differences were observed for the number of antral follicles and the concentrations of FSH in relation to controls, which suggests that all groups possess similar ovarian reserve. Gonadotrophin’s administration and duration of stimulation did not differ in the HIV subgroup. However, the number of oocytes, the number of oocytes under metaphase II and the number of embryos were reduced in the infected group, but not specifically in the HIV subgroup. Once again, we propose that ovarian stimulation is not compromised by HIV-1.

Baby home rates were significantly lower in total infected group, but it did not differ across the subgroups. Vankerkem and colleagues [14] did not see any differences in delivery rates in serodiscordant (HIV-positive women or HIV-positive male partners) or in seroconcordant couples. Curiously, clinical pregnancy and baby home rates in the HIV subgroup matched those of the control group. In contrast, Ohl and collaborators [29] showed that the rate of newborns was reduced in HIV- and HBV-infected women, but no differences were observed in HCV-infected women. The number of individuals in the HCV group [29] was drastically smaller than that in subgroups HIV and HBV, and it did not offer a solid estimate of the number of newborns. In this study, we also present a low number of individuals within the HIV and HCV subgroups. In 2015, the rate of HIV and HCV in Portugal were 9.5 and 1.1 per 100,000 population, respectively [30] [31], so higher numbers of infected individuals undergoing ART should not be expected. Moreover, no evidence is available regarding the incidence of infected individuals who are assisted in private health centers that could help us to establish a comparison with our data. However, of the 10 HCV-positive women with negative male partners belonging to the HCV subgroup, only one woman had a clinical pregnancy that ended in a miscarriage in the first trimester. In fact, one study showed a substantial decrease of live-birth rates in HIV-infected women with age above 35 years [32].

The present work reveals that the group with viral infection presented a similar response to stimulation. Despite the HCV subgroup presenting lower clinical pregnancy rate (17.78% vs. 34.66% in the control group), the baby home rate was similar to the uninfected control group.

ART results from couples with viral infections (HBV, HCV, HIV or mixed) in a Portuguese public hospital. Despite low pregnancy rates, promising results on baby home rates were observed.

This study was supported by Gedeon Richter Portugal.

The authors declare no conflicts of interest regarding the publication of this paper.

Figueiredo, S., Correia, S., Pinto, G. and Simões, T. (2021) Fertility Care Provided by a Public Health Hospital to Viral-Infected Couples: A Case-Control Study. Open Journal of Obstetrics and Gynecology, 11, 1013-1025. https://doi.org/10.4236/ojog.2021.118095