Reproductive and Oncofertility Science Academy: A review
The term “oncofertility”, first coined by Teresa Woodruff, refers to the emerging field of medicine that bridges the gap between oncology and reproductive medicine in order to expand fertility options for cancer survivors. With the increasing rate of cancer survival, concerns about fertility are becoming more and more prevalent. Therefore, in 2006, the National Institute of Health funded a grant aimed at addressing this unmet need. One component of this grant was the creation of an educational outreach program, ROSA, to encourage girls to pursue careers in science. The Reproductive and Oncofertility Science Academy (ROSA) at University of California, San Diego gave 13 girls, including myself, the opportunity to further their interest in reproductive science and research through a rigorous seven week program with intensive Saturday sessions, engaging field trips, and collaborative group meetings. Along with learning about various aspects of reproductive medicine, we were also tasked with putting together and presenting our own research posters.
During the Saturday sessions, we learned from world-renowned doctors and researchers and gained hand-on experience through labs and discussions about real-life applications of our newly gained knowledge. The first session focused on the foundation of academy, reproductive biology, and metabolism. In this session, we learned about the ovarian cycles and the anatomy of the male and female reproductive systems from Dr. R. Jeffrey Chang and Dr. Michael Hsieh. Comprehending these processes is important in oncofertility because they give an understanding of how cancer treatments can inhibit certain pathways which in turn lead to infertility. It also explains why and how cryoprotectants can decrease the viability of the sperm or ovary. For example, in order to preserve the fertility of a young male cancer patient who has not gone through puberty, the typical procedure is to remove and freeze testicular tissue using cryoprotectants. One important factor that can lead to the failure of this method is temperature. If testicular temperature increases, this can lead to an undescended testes and decreased fertility [3, 4]. To complement these riveting lectures, we retrieved the ovaries of a mouse through a dissection and observed them in a microscope. Before many fertility treatments reach the human trial stage, they are typically tested in animal trials, specifically mice. Mice are great specimen to study because their reproductive systems closely resemble the female reproductive systems, the only notable difference being that the mouse has two mullerian ducts instead of one like the typical human female. The knowledge we gained through this session led to better comprehension of how human reproductive systems work and how research is applied in animal trials.
The second session centered on the pathophysiology of Polycystic ovary syndrome (PCOS). PCOS is a multi-system reproductive metabolic disorder found in 5-10% of reproductive aged women. Common markers include hirsutism (androgen excess), chronic anovulation, and polycystic ovaries. Anovulation causes disruptions in Hypothalamic-Pituitary-Ovary interactions. The hypothalamus produces gonadotropin releasing hormone (GnRH) which stimulates the production of follicle secreting hormone (FSH) and luteinizing hormone (LH) in the pituitary. The FSH and LH trigger ovulation in the ovary. During ovulation, the ovary releases estrogen and progesterone. With PCOS, ovulation is interrupted, and progesterone is not produced as a by-product. The primary concern with PCOS are the following co-morbidities: uterine cancer, non-alcoholic fatty liver disease, type-2 diabetes, and metabolic syndrome [5, 6]. The best way to prevent the onset of these comorbidities is through diagnosis and treatment with birth control. Many women go undiagnosed and suffer through the comorbidities of this disorder. This session was important because if more people are informed about this disorder, then more people will be diagnosed and treated.
The third session was about an innovative approach to curing infertility: in vitro fertilization. For IVF, mature eggs are retrieved from the ovaries and fertilized by sperm in a laboratory setting. From there, the embryo is planted into the uterus . IVF has been a revolutionary tool in solving infertility for many patients. During this session, we visited the Scripps Oceanography Institute (SIO) and the UCSD Regional Fertility Center. At the SIO, we witnessed the fertilization of sea urchin eggs and learned about the role of marine species in the evolution of fertility techniques. IVF is performed in algal gel to increase the success rate of fertilization. At the fertility center, we learned more about the techniques used for IVF through a series of hands on experiences. Also, during this session, we explored the ethical implications of fertility treatments through a series of case studies. This session was extremely valuable because ethics, the moral principles that govern behavior, play a vital role in all science; it is important that science is done for the right reasons. Bioethics is when these ethical principles are applied to bioengineering and medicine. It involves all parts of human life from In Vitro Fertilization and abortion to euthanasia and palliative care.
The final session of the academy updated us on the current fertility preservation options for cancer patients and showed us new innovative techniques that may soon be introduced to the public . We learned that in vitro maturation of preantral follicles is the future of oncofertility. For this fertility technique, the preantral follicle is isolated from the ovary and grown through hydrogel encapsulation. This session was important because it really emphasized the purpose of this academy: to encourage women to pursue their careers in fields of science and find solutions to problems like the infertility of cancer patients.
In accordance with this purpose, each of the members of the academy created a research poster in which they presented a potential solution to a problem in reproductive medicine. My research focused on the viability of autotransplantation of the whole ovary for women who are at risk for premature ovarian failure. One fourth of women diagnosed with some form of cancer are of fertile age and may be receiving chemotherapy. The treatment greatly increases survival rates, but it also causes premature ovarian failure or the loss of ovarian function before the age of 40. One way to potentially lower the rate of POF in female cancer patients is autotransplantation of the ovary. This technique could prove beneficial because follicle atresia and ischemia are reduced, no ovarian stimulation is needed, and no delay in cancer treatment is necessary. In terms of viability, autotransplantation of the whole ovary has not yet occurred in humans; there has, however, been success with similar types of autotransplantation. There have been reports of 26 successful births through autotransplantation of ovarian tissue . Subsequently, there has been success in animal studies with the procedure. In a foreign study, 4 out of 9 sheep regained luteal function and one of the four sheep was able to conceive spontaneously after the procedure . In addition, there has been a successful case in which a monozygotic twin donated her ovary to her sister who was eventually able to reproduce . These cases show the viability and restorative potential of whole ovary autotransplantation.
While the ROSA program focused on reproductive medicine and oncofertility, it also empowered 13 young girls by furthering their interest in science. As we learned about the comorbidities of PCOS and the ethical consequences of medical decisions, we also learned about the importance of work ethic and how to communicate effectively to our mentors. Through intense study sessions and group discussion, we gained lifelong friendships with each other. All in all, this academy was a life changing opportunity that solidified my interest in medicine and taught me valuable life skills.
Imhof, M., Bergmeister, H., Lipovac, M., Rudas, M., Hofstetter, G., & Huber, J. (2006). Orthotopic microvascular reanastomosis of whole cryopreserved ovine ovaries resulting in pregnancy and live birth. Fertility and Sterility, 85, 1208-1215.
Macklon, K. T., Jensen, A. K., Loft, A., Ernst, E., & Andersen, C. Y. (2014). Treatment history and outcome of 24 deliveries worldwide after autotransplantation of cryopreserved ovarian tissue, including two new Danish deliveries years after autotransplantation. Journal of Assisted Reproduction and Genetics, 31(11), 1557-1564.
McLaren, J. F., & Bates, W. (2012). Fertility preservation in women of reproductive age with cancer. American Journal of Obstetrics and Gynecology, 207(6), 455-462.
Rosendahl, M., Wielenga, V. T., Nedergaard, L., Kristensen, S. G., Ernst, E., Rasmussen, P. E., . . . Andersen, C. Y. (2011). Cryopreservation of ovarian tissue for fertility preservation: no evidence of malignant cell contamination in ovarian tissue from patients with breast cancer. Fertility and Sterility, 95(6), 2158-2161.
Salama, M., & Woodruff, T. K. (2015). New advances in ovarian autotransplantation to restore fertility in cancer patients. Cancer and Metastasis Reviews, 34(4), 807-822.
Silber, S. J., Grudzinskas, G., & Gosden, R. G. (2008). Successful Pregnancy after Microsurgical Transplantation of an Intact Ovary. New England Journal of Medicine, 359(24), 2617-2618.
Reproductive and Oncofertility Science Academy: A review