Cross-Border Reproductive Care: Psychological Distress in A Sample of Women Undergoing In Vitro Fertilization Treatment with and without Oocyte Donation

Infertility is defined as the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse. The prevalence of infertility is between 17% and 28% in industrialized countries (1). Cross-border reproductive care (CBRC), also known as reproductive tourism, refers to a phenomenon in which infertile patients travel to other countries to obtain specific assisted reproduction treatments (ART), mainly intrauterine insemination, in vitro fertilization (IVF) and oocyte donation (2). Several clinical, social and legal issues can make the treatment more difficult in the patients’ country of origin, which leads patients to seek CBRC. In most cases, the treatment is forbidden by law in the country of origin for the following reasons: it is considered an unsafe technique (e.g., oocyte freezing); ethical considerations (e.g., gamete donation, preimplantation genetic diagnosis), or patient characteristics (e.g., postmenopausal or homosexual women). Likewise, excessively long waiting lists in one’s home country, lack of expertise (e.g., preimplantation genetic diagnosis) and high financial costs also block access to reproductive treatments (3). Consequently, there has been a progressive increase in migration to obtain ART. With regards to Europe, countries in which CBRC is most prevalent are France, Italy and Germany, 79% of those applicants are treated in Spain mostly due to the absence of legal restrictions in gamete donation. In 2016, the Spanish Fertility Society (SEF) Registry documented 12 939 ART cycles. The majority of these patients were from Italy and France. A total of 86% of cases had gamete donation, which was mostly from an oocyte source (53.3%) (4).

Infertility can have a negative impact on quality of life (5- 7), and the IVF treatment process is associated with stress (8), depression, anxiety and psychosomatic symptoms that interfere with fertility treatment (9). In terms of personality traits, some studies have found that 'sensation seeking' profiles are less prevalent in infertile women, who tend to engage in more experiential avoidance and self-judgment coping mechanisms (10). Evidence suggests that neuroticism, the relatively stable tendency to respond with negative emotions (hostility, sadness, anxiety, etc.) to threat, frustration, or loss (11) is related to the presence and maintenance of anxiety and depressive symptoms/disorders (12). It remains unclear, however, if the same holds true in infertile women and in women who seek CBRC.

In women who seek CBRC, it appears that multiple elements combine to increase vulnerability to psychopathological conditions. According to data from the SEF Registry, more than half of CBRC women in Spain seek oocyte donation. This, in turn, entails resorting to what may be considered as illegal fertility techniques in their respective countries (13). In addition, these women are usually older; have a longer duration of infertility; experience an increased conception failure rate; and have more difficulties in attaining healthy and normal births (14). In addition, further stress results from living in and adapting to unfamiliar environments, seeking justification for their work absence, the economic expense of treatment (15), and the travel costs involved.

Numerous studies carried out from a medical-legal perspective mainly considered the ethical aspects of this practice (16,17). However, only some studies have highlighted the fact that the adaptation to a different medical care context together with the associated psychological/ economic discomfort caused by displacement can interfere with the quality of life of these patients. Therefore, studies relating CBRC to psychopathological consequences are needed.

In order to improve treatment interventions for patients who receive CBRC, a better understanding of the mechanisms underpinning its associated psychiatric symptomatology is required. To our knowledge, no empirical study has yet explored the association between CBRC and psychopathology in women. As such, we aimed to determine if there were differences in emotional states and personality profiles of women who receive CBRC in comparison to local women. Our study aims were twofold: a) to compare anxiety and depression levels between the CBRC patient group and the local patient group and b) to explore the sociodemographic, clinical and personality profiles of both groups. We hypothesized that CBRC patients: 1. would show higher anxiety and depression levels derived from factors associated with displacement and 2. would show a distinct personality profile in comparison with local women.

This study analysed whether there were psychopathological differences between CBRC women and local women undergoing IVF. We explored CBRC issues and the clinical, sociodemographic and personality profiles of both groups.

In a similar way to another Spanish study (24), the majority of women in the CBRC group were from Italy where Spain's CBRC treatment approach is particularly well-perceived (13). The main cause of cross-border travel in the CBRC group was the illegality/difficulty of access to the practice in their home country, which explained why all of the participants originated from Italy, a country with some of the most highly restrictive laws in Europe in terms of medically assisted procreation (25).

Both clinical groups showed a similar profile with respect to sociodemographic and clinical features. The only difference was that the CBRC group had previously undergone more ART, specifically more IVF with their own oocytes. This was in line with the causes of CBRC described by these patients in our study, most of whom had had experienced failed treatments and came to Spain to receive infertility treatment that was illegal in Italy.

Regarding psychopathology, our study finds higher anxiety-state levels in CBRC oocyte recipient patients in comparison with the local group. These findings suggest that anxiety is simultaneously associated with the migratory process and the type of ART used. These findings cannot be compared with other results as there have been no similar previous investigations. In terms of depression, no significant differences were found between the groups, which was in line with other research where women who underwent CBRC IVF in Spain had low levels of depression (24). Therefore, the present data has supported the position that the migratory process, when an oocyte donation is needed, exacerbates anxiety symptomatology. Previous studies described high and moderate levels of anxiety in women requiring donor oocytes, assessed immediately prior to the IVF (26). Before treatment, many oocyte recipients expressed concern about the lack of a genetic tie to a child born after the donor procedure and doubts about whether or not to disclose the donation (27). These fears could increase anxiety levels; thus, a psychological consultation prior to treatment with gamete donation is recommended (28). In addition, Italian women who undergo treatment with oocyte donation endure a technique that was illegal in Italy until 2013 (13, 29). Currently, despite being legal, oocyte donation presents with greater difficulties in terms of access compared to other countries, which potentially increases patients’ anxiety levels. All of the above factors add to the anxiety generated by infertility itself and support the observation that anxiety-related symptoms of infertile women are more prominent than those of fertile females (30). Furthermore, repeated fertility treatments and the accumulation of unsuccessful IVF treatments generate a sensation of vulnerability-based anxiety (31). The CBRC women in our study had more previous infertility treatments with their own oocytes. The psychological burden of conceiving through the donation of oocytes is added to the process of undergoing the treatment outside their country of origin. CBRC poses new challenges and difficulties for patients, such as having to live away from home and to adapt to an unknown country with possible language barriers and little social support (32). In fact, a third of the women in the CBRC group endorsed significant psychological significant discomfort, and more than half reported significant and relevant difficulties in cross-border infertility treatment. As reported in other studies (33), the majority of psychological discomfort in our CBRC sample arose from economical costs, with absence from the participant's workplace listed as the second most relevant difficulty.

In light of these results, assisted reproduction centres that assist CBRC patients should be prepared to identify patients’ anxiety levels prior to treatment, especially with oocyte donation and, if necessary, facilitate patient access to psychological support. Previous CBRC research in Spain (24) showed that couples with a history of oocyte donation treatments were more likely to perceive psychosocial support as useful and to desire it. Psychosocial interventions for couples under treatment for infertility, particularly cognitive behaviour therapy, has proven to be effective, both in reducing psychological distress and in improving clinical pregnancy rates.

On the other hand, no significantly different personality profiles were obtained between both groups, other than the Activity characteristic. This means that the CBRC group, specifically when an oocyte donation was required, was characterized by a greater tendency for general activity, an inability to relax and do nothing when the opportunity arises, a preference for hard and challenging work, a busy life, and a high energy level (34). CBRC patients who need oocyte donations tend to face more difficulties accessing reproductive treatment, thus making this personality tendency coherent in this subgroup of CBRC women given that CBRC recipient women must develop a proactive attitude towards infertility. These women must overcome the barriers and regulations of their countries to be able to carry out the reproduction treatment necessary for them to become mothers.

Finally, regarding CBRC issues and in accordance with previous studies (35), the main cause of reproductive tourism in our sample was the legal prohibition in the country of origin. This finding stresses the importance of taking a rapidly changing legal environment into consideration and to promote the adequate regulation of ART (36).

The present study is not without its limitations. First, all data were collected only from women who sought ART treatment. Future studies should aim to assess their partners in in order to obtain a more comprehensive view of CBRC effects (24). Second, the CBRC patients were from Italy, which limited the external validity of our analysis and comparisons with other countries of origin. The existence of country-based differences in the mental health of couples who undergo CBRC has been reported in previous studies (24), which suggests that this kind of analysis could be of interest. Third, the evaluation was carried out only through questionnaires, without a complementary clinical interview. Fourth, the cross-sectional perspective of this study did not permit the detection of differences between both groups after clinical intervention. It would be of interest to determine if a relationship existed between anxiety levels prior to fertility treatment and during pregnancy or postpartum. Finally, despite having been identified in infertile women (10), we did not assess coping strategies, cognitive style, quality of life or other psychopathologies of interest, such as somatic disorders.

This study provides further information about the existence of increased anxiety in CBRC women, specifically those who receive oocyte donations. The findings suggest that screening systems and psychological support for anxiety in this population should be considered in order to improve the quality of care in CBRC.