Abstract
The second World Congress on Fertility Preservation was held on 10–12 December 2009, in Brussels. The congress was organized by the Serono Symposia International Foundation and the International Society for Fertility Preservation (ISFP), and it was presided over by professor Jacques Donnez, first president of the ISFP. Approximately 350 participants attended the congress, which included 33 lectures by faculty members, 28 oral communications and 34 poster presentations. The program encompassed all aspects of fertility preservation, ranging from the specific challenges in so-called oncofertility to cryopreservation of oocytes, ovarian tissue and testicular tissue, ovary transplantation, in vitro maturation and the (dis)advantages of vitrification versus slow freezing.
The introductory theme of the congress was cancer therapy and fertility preservation, which – unsurprisingly – focused mainly on female cancer patients. In the opening lecture, Hamish Wallace (Royal Hospital for Sick Children, Edinburgh, UK) discussed the effect of radiotherapy on both the ovaries and the uterus, highlighting an increased risk of miscarriage, mid-trimester pregnancy loss, preterm birth and low birthweight. Several lectures followed on the effect of chemotherapy on ovarian function. Dror Meirow (Sheba Medical Center, Tel Hashomer, Israel) highlighted the importance of identifying the mechanisms by which primordial follicles are lost during chemotherapy, and presented results illustrating the protective effects of AS101 on both primordial and growing follicles. Mikkel Rosendahl (Copenhagen University Hospital, Copenhagen, Denmark) highlighted that although the age of the patient and the type and dose of chemotherapy are the most important factors influencing chemotherapy-induced amenorrhea, individual factors such as the level of anti-Müllerian hormone before starting treatment and (for younger patients) the degree of chemotherapy-induced bone marrow suppression are also indicative of the effect of chemotherapy on ovarian reserve. Yvon Englert (Université Libre de Bruxelles, Brussels, Belgium) discussed previous retrospective studies and an ongoing prospective randomized study on the presumed protective effect of gonadotropin-releasing hormone (GnRH) agonists against chemotherapy-induced gonadal damage. As the results are not conclusive, it was suggested that GnRH agonists be offered to patients as long as they are part of randomized controlled trials. Jehoshua Dor (Sheba Medical Center, Ramat Gan, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel) discussed fertility preservation options for breast cancer patients, recommending fertility preservation for patients over 35 years as they may be too old to conceive naturally after observing the waiting period following chemotherapy treatment. Finally, the risks of conservative surgery in women with borderline and malignant ovarian tumors was discussed by Philippe Morice (Institut Gustave Roussy, Villejuif, France). The important observation was made that although conservative treatment increases the risk of relapse, it does not alter the survival rates of patients. Whether or not conservative treatment should be offered depends largely on the stage of the cancer, and careful follow-up is necessary. Herman Tournaye (Universitair Ziekenhuis Brussel, Brussels, Belgium) was the only speaker to address the effect of cytotoxic therapies in men. Besides the risks of radio- and chemotherapy in terms of gonadal failure, there is also a risk of chromosomal damage in the surviving germ cells, which may lead to genetic diseases when passed on to the next generation. For adult men, the cryopreservation of sperm is thus recommended, especially when alkylating agents are used. For prepubertal boys, fertility preservation is less straightforward: the risk of damage is higher and fertility preservation options are more invasive, as they have to rely on the preservation of spermatogonial stem cells.
The second session focused on cryopreservation and transplantation of ovarian tissue. Samuel Kim (University of Kansas, Kansas City, MO, USA) and Jacques Donnez (Catholic University of Louvain, Brussels, Belgium) discussed heterotopic and orthotopic transplantation of ovarian tissue, respectively. Positive results were reported for both treatment options as far as the (temporary) restoration of ovarian function is concerned. For the restoration of fertility, orthotopic transplantation appears to be the preferred treatment option at present. Although heterotopic transplantation is the least invasive option, heterotopic sites may not offer a suitable environment for optimal follicle development. Moreover, heterotopic transplantation requires IVF and no live births have been reported thus far (although biochemical pregnancies were reported by Kirsten Tryde Schmidt [University Hospital of Copenhagen, Copenhagen, Denmark] in an oral communication after heterotopic transplantation to the abdomen). By contrast, 11 live births have been reported after orthotopic transplantation (six natural births and five after IVF). Claus Yding Andersen (University of Copenhagen, Copenhagen, Denmark) explained how in two of these cases, the ovarian tissue was extracted at a local hospital and transported on ice for 4–5 h prior to cryopreservation and storage. In oral communications, the experience of two different centers regarding the cryopreservation of ovarian cortex in young girls was discussed, and both recommended that cryopreservation should be offered to girls at risk for premature ovarian failure, as few other options for fertility preservation are available for them.
The risks of transplanting ovarian tissue in breast cancer and leukemia were discussed by Antonio Pellicer (Valencia University, Valencia, Spain) and Meirow, respectively. Although neither reported cases of cancer recurrence after transplantation, there appeared to be widespread agreement in the oral communications and discussions that followed that screening methods should be optimized to ensure the safety of this procedure. In the case of leukemia, Mikkel Rosendahl highlighted that while histology and immunochemistry might not show any malignant cells in the biopsied tissue, PCR often finds malignant cells in those same tissues; therefore, his research group does not recommend reimplantation of tissue to leukemia patients for the time being. This stance was confirmed in research presented on the next day by Marie-Madeleine Dolmans (Catholic University of Louvain, Brussels, Belgium). Caution was also advised by Koichi Kyono (Kyono ART Clinic, Sendai, Miyagi, Japan) and colleagues with regards to patients with both Hodgkin’s and non-Hodgkin’s lymphoma.
The second day of the congress started off with a session on ovarian cortex and whole-ovary preservation and transplantation. Regarding whole-ovary transplantation, all three invited speakers – Bruno Salle (University Claude Bernard Lyon I, Lyon, France), Pasquale Patrizio (Yale University, New Haven, CT, USA) and Sherman Silber (St Luke’s Hospital, Saint Louis, MO, USA) – confirmed that the main difficulty is the revascularization of the graft. In this same regard, Stéphanie Ploteau (Laboratoire d’Anatomie, Nantes, France) advised in the oral communications session that the gonadic pedicle is harvested with a minimal length of 5 cm from the ovary to ensure a safe microsurgical whole-ovary transplantation.
Christine Wyns (Catholic University of Louvain, Brussels, Belgium) presented a very interesting review of testicular tissue preservation options. Young boys who do not yet produce spermatozoa can cryopreserve immature testicular tissue in an effort to preserve their fertility. Although all these options are still experimental, possible strategies include spermatogonial stem cell transplantation, in vitro maturation of germ cells and autografting of either testicular cells, testicular tissue pieces or whole testes. Oral communications in this session discussed research into spermatogonial stem cell transplantation, slow freezing versus vitrification of testicular tissue, and the damage to sperm by the combination of the cancer drugs doxorubicin and amifostine.
In the afternoon, the focus shifted to fertility preservation in female patients again, with a number of invited speakers talking about isolated follicles transplantation and in vitro maturation of oocytes. Among the topics discussed were the potential of using alginate matrix for the culturing of primordial follicles (presented by Johan Smitz [Universitair Ziekenhuis Brussel, Brussels, Belgium], Christiani Andrade Amorim [Catholic University of Louvain, Brussels, Belgium] and Teresa Woodruff [Northwestern University, Chicago, IL, USA]) and more generally the reintroduction of isolated follicles embedded in a scaffold, to prevent malignant cells from being reintroduced (presented by Dolmans and Amorim).
David Albertini (University of Kansas, Kansas City, MO, USA), Evelyn E Telfer (University of Edinburgh, Edinburgh, UK) and Outi Hovatta (Karolinska University, Stockholm, Sweden) talked about the culture conditions for optimal in vitro maturation. Debra Gook (Royal Women’s Hospital, East Melbourne, Victoria, Australia) presented research on the impact of cryopreservation and grafting on folliculogenesis and identified ischemia as the main obstacle to be overcome in order to increase the longevity of folliculogenesis in autografted tissue. Seang Lin Tan (McGill University, Montreal, QC, Canada) presented encouraging data from the McGill Reproductive Center (Montreal, QC, Canada) on oocyte vitrification and in vitro maturation for cancer patients.
The final lecture of the day was the keynote lecture by Roger G Gosden (Cornell University, New York, NY, USA), offering a fascinating overview of the different research papers that have studied the controversial question of follicular renewal in adult ovaries. Although the debate remains ongoing, the currently available data suggest that it is plausible to assume that some germline stem cells persist in postnatal ovaries, but that their potential to restore fertility might not be physiologically significant. Nevertheless, success in generating fertile offspring from murine-induced pluripotent stem cells offers a reason for optimism regarding the role that stem cells might play in the treatment of female and male sterility. After his lecture, Gosden was presented with an award for his outstanding work as a pioneer in the area of fertility preservation.
The third and final day of the congress started with a number of oral communications on cryopreservation and transplantation, followed by lectures and debates on the pros and cons of vitrification versus slow freezing for oocytes, embryos and ovarian tissue. For oocytes, Andrea Borini (Centre for Reproductive Health, Tecnobios Procreazione, Bologna, Italy) and Anna Veiga (Institut Universitari Dexeus, Barcelona, Spain) judged both slow freezing and vitrification to be safe and effective methods. For embryos, Etienne Van den Abbeel (Vrije Universiteit Brussel, Brussels, Belgium) noted that, particularly for blastocyst-stage embryos, better results are obtained with vitrification than with slow freezing. For ovarian tissue, Outi Hovatta mentioned that all 11 live births after ovarian tissue transplantation were obtained after slow freezing, while none used vitrification. Nevertheless, vitrification offers excellent survival of ovarian stroma and blood vessels. Disadvantages include the need for training in order to obtain good results, as toxic influences on the tissue are possible if personnel are not well trained. This makes vitrification more attractive for larger centers than for smaller ones. Two main disadvantages of vitrification (for oocytes, embryos and ovarian tissue alike) were discussed both by the invited speakers and in the discussions that followed after. First, vitrification is an open system, which, according to a European directive, is not acceptable for clinical applications. Second, and of specific importance for applications in fertility preservation, when tissue is stored for a long period of time, spontaneous devitrification may occur.
The final lecture by Guido Pennings (Ghent University, Ghent, Belgium) dealt with the ethics of ovarian tissue and oocyte cryopreservation for social reasons. Both in professional circles and in the popular media the idea of storing oocytes or ovarian tissue of healthy women for possible future use has met with a lot of opposition. Pennings pointed out, however, that it is very difficult to make a clear distinction between fertility preservation for ‘medical’ reasons and fertility preservation for ‘non-medical’ reasons, and that there are few relevant differences between a decline in ovarian reserve due to medical treatment as opposed to aging. Moreover, the decline in fertility due to aging is a ‘condition’ that is routinely being treated in reproductive medicine. There appear to be no good arguments why ‘older’ women can be treated with donor oocytes but not with their own – previously frozen – oocytes. The latter actually offers some important advantages over the former. Also, the argument of responsibility was criticized, not only because women do not choose to find the right partner later in life but also because many other medical conditions that are self-inflicted (e.g., due to excessive alcohol intake or smoking) are being treated by medical interventions.
Overall, the second World Congress on Fertility Preservation was very successful both in terms of the number of participants and in terms of the outstanding expertise of the different speakers.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.