FOR MANY INDIVIDUALS, achieving complete cancer remission is an extremely positive event that allows them to enjoy the rest of their lives free of chemotherapy appointments or the fear of returning disease. But for some, the cost of remission is associated with significant consequences to major decisions later in life. One such consequence is infertility for female cancer patients; as such, scientists are currently working on developing an artificial ovary system that will allow these patients a chance at experiencing childbirth.
To begin, we must explore the current status of fertility preservation methods. Women are born with a fixed number of immature eggs that begin to mature after puberty. Current fertility preservation methods allow women to retain the ability to procreate later in life by freezing down these mature eggs. Some of these methods have been successfully carried out for more than 30 years. According to a study looking at 137 women who underwent fertility preservation, the cumulative live-birth rate is twice as high in women who were 35 years or younger compared to older women, suggesting that freezing down eggs at a younger age yields higher birth success rate. These methods have the highest success rate in women who delay childbirth for personal reasons rather than due to malignant diseases.
Females with prepubertal cancer represent individuals that require a very specific treatment regimen in order to not only prevent the spread of 
cancer, but also preserve fertility later into life. These individuals have only immature eggs within their ovaries which are prone to permanent damage from many cancer treatments, rendering them non-viable. Common fertility preservation methods of freezing down eggs for later use is not a viable option for these patients, as their immature eggs will not survive the freezing process. To further complicate things, the procedure requires ovary stimulation and egg removal over a period of 2 weeks, which is not an option for many patients whose chemotherapy cannot be delayed. As such, freezing down ovarian tissue (either by taking multiple biopsies or removing an entire organ) is on the rise as an alternative solution. This method has been quite successful, leading to more than 130 live births as of mid-2017. However, it is not without risks. The process of implanting preserved ovarian tissue puts the patient at risk of reintroducing cancerous cells back into their body. This is why scientists are currently researching new and improved methods of fertility preservation. One such method is to isolate immature eggs from ovarian tissue and grow them in a lab until they reach maturity so that can then be re-introduced to the patient. As such, scientists are looking into the creation of an artificial ovary: a physiological environment that can maintain the three-dimensional structure of ovarian follicles, which can be used to mature isolated eggs in vitro.
Growing immature eggs in a lab is undoubtedly challenging as maturation of eggs requires a well-controlled yet dynamic environment with regards to the availability of oxygen, hormones and proteins. Such manipulation of the environment has been done with mouse eggs as early as the 1990s, 
and lab-grown mouse eggs have even been used to create live mice offspring. This type of laboratory culture, however, could not support human eggs. Recently, there has been attention on using highly biocompatible and biodegradable substances such as fibrin formulations with fibrinogen and thrombin as part of the artificial ovary that could potentially support the survival and proliferation of immature human eggs.
The latest breakthrough research comes from a group in Edinburgh that devised a multi-step culture system (“artificial ovary”) for these immature eggs that allowed a portion of them to reach full maturity. However, this was a small proportion, and many of these mature eggs exhibited abnormalities; thus, more studies are needed to follow up on this initial report. Despite these caveats, this represents a milestone as the first case in which scientists were able to remove immature human eggs and grow them to full maturity in a lab. This work brings us one step closer to achieving the goal of allowing prepubertal cancer patients to have a chance at childbirth without the risk of re-introducing their cancer.
References:
1. Donnez, J.D. & Dolmans, M-M. (2017). Fertility Preservation in Women. N Engl J Med, 377(17): 1657-1665.
2. Diaz-Garcia, C. & Herraiz, S. (2014). The artificial ovary: any new step is a
step forward. Fertil Steril, 101(4):940.
3. Luyckx, V. et al. (2014). A new step toward the artificial ovary:
survival and proliferation of isolated murine follicles after autologous transplantation in a fibrin scaffold. Fertil Steril, 101(4):1149-1156.
4. McLaughlin, M. et al. (2018). Metaphase II oocytes from human unilaminar follicles grown in a multistep culture system. Mol Hum Reprod, 24(3):135-142.
5. Teifer, E.E. & Fauser, B.C. (2016). Important steps towards materializing the
dream of developing an artificial ovary. Reprod Biomed Online, 33(3):333-334.
Yoojin Choi
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