Cancer and reproductive health
Oncofertility
Teresa Woodroof, Post-Science
Over the past 40 years, research in the field of cancer diagnosis and treatment has been moving forward intensively. Scientists have presented to the world drugs that treat oncological diseases of different types. Survival statistics are becoming more optimistic than in the 1970s, especially when it comes to children: 85% of young patients are successfully cured of cancerous tumors. In light of this, a new problem field is opening up in oncology: more and more researchers are shifting their attention from diagnosis and treatment issues and working to improve the quality of life of people who have had cancer.
Anti-cancer therapy aggressively affects the body and has side effects. One of them is reproductive dysfunction. To solve this problem, scientists are integrating research in the field of oncology and reproductive health. Oncofertility appears at the crossroads of disciplines – a new field of medical research in which specialists deal with issues of reproductive dysfunction and hormonal imbalance in patients cured of cancer.
Mechanisms of action of anticancer therapy
Any patient, regardless of the type of cancer, faces reproductive dysfunction. The problem lies in the damaging effect of anti-cancer therapy. The purpose of cancer care is to destroy cancer cells and stop their rapid reproduction. To achieve this effect, drugs affect not only the organ affected by cancer, but also all the others. Alkylating agents used in cervical cancer and various types of leukemia, radiation therapy and chemotherapy destroy cancer cells. At the same time, they cause many side effects: toxicity from the cardiovascular system and liver, hair loss and damage to cells of reproductive tissues.
The greatest damage to the reproductive system is caused by those types of treatment in which the pelvic area is irradiated with radiation. Experts especially single out bone marrow transplantation as one of the sterilizing procedures. For successful transplantation, the patient's entire body is irradiated with radiation: this is necessary to get rid of the old bone marrow. Of course, in the course of this, other organs also receive radiation, which negatively affects their functions.
Risks for men and women
The male body produces sperm from stem cells that regenerate during life. Therefore, men rarely turn out to be completely infertile: most often by the end of treatment they have at least a few stem cells that produce sperm after 5-10 years.
For the female body, everything is not so simple. A woman is born with a million primordial (most immature) follicles in the ovaries. They are of paramount importance for the reproductive system: primary follicles develop until the oocytes inside them grow into eggs ready for ovulation and possible fertilization.
Throughout life, from birth to menopause, the body does not produce new ovarian follicles. Therefore, for women's reproductive health, the early loss of follicles caused by anti-cancer therapy often turns out to be fatal: patients can lose so many follicles that by the age of 27 they will not remain at all. Then they will begin menopause, which means they will not be able to get pregnant.
For very young patients who did not go through puberty by the beginning of treatment, the situation becomes even more complicated. In their case, the loss of ovarian follicles not only entails problems with childbirth, but also disrupts the normal hormonal cycle. Because of this, young patients risk not reaching puberty. That is why, when assessing the risks associated with the reproductive system, doctors always take into account the patient's age along with the type of cancer and the types of treatment he receives.
Ways to preserve fertility
Now special procedures are needed to preserve reproductive functions: the collection of reproductive cells before the start of anti-cancer therapy and their subsequent storage. Men are offered to preserve their sperm, women are offered to deposit eggs and embryos. Specialists have achieved significant results in cryopreservation of ovarian tissues. To do this, they take an ovarian biopsy and freeze this piece of tissue for later use. These methods are useful not only for restoring childbearing functions in patients – they are also basic techniques that are used in research.
Current research oncofertility
Specialists Woodruff Lab and the Oncofertility Consortium at Northwestern University in Chicago are looking for new approaches to the problem of oncofertility. First of all, they develop techniques for growing individual follicles. Inside each follicle there are oocytes and cells that surround and support it. The structure of their connections is difficult to maintain in artificial conditions. For this purpose, researchers have created a cubic follicle growth system, in which it turns out to reproduce the natural connections between the oocyte and the cells around it. They expect that this technology will be able to be used to grow immature follicles from cryopreserved ovarian tissues. In this case, doctors could, for example, take ovarian tissue from three-year-old patients and grow follicles based on it, which will allow them to have children in the future.
Another approach is ovarian bioprosthesis, which allows to preserve both reproductive functions and hormonal balance. Specialists Woodruff Lab prints frame structures on a 3D printer, inside which individual follicles can be placed, thus transplanting them back. Bioprostheses are printed from hydrogel "ink" – gelatin. This collagen derivative is characterized by flexibility and the fact that it is non-toxic to the cells of the body. With the help of ovarian bioprosthesis, scientists are already observing childbirth in mice. Now they are working to adapt this strategy for people.
The optimal approach to the problems of oncofertility is leveling the negative effect of anticancer therapy on the ovaries. If patients could take a pill that protected their ovaries from radiation and chemotherapy, that would be ideal. Therefore, we are now working on the creation of neoadjuvants that will protect fertility. Their action is based on the anti-muller hormone (AMH) – reproductive hormone that limits the excessive growth of reproductive tissues and regulates the activity of follicles. Studies show that elevated levels of AMH can temporarily block the activity of ovarian follicles, stop it at the rudimentary stage. This correlation can be used to develop drugs that will provide hormonal protection to the natural supply of primordial follicles.
The future of oncofertility
The most optimistic prospect is the complete elimination of oncofertility as a problem field. Pharmaceutical companies continue to develop anti-cancer drugs, the effect of these drugs is becoming more targeted. If they finally manage to invent drugs that will act only on cancer cells and will not affect healthy organs, the risks to the reproductive and hormonal systems of patients will disappear. In this case, oncofertility will turn out to be the area of medicine that will have the shortest life span. The technologies that we are developing to solve the problems of oncofertility can be widely used for other medical purposes. Ovarian bioprosthesis can be used in surgical sex correction and for the treatment of diseases of the uterus, fallopian tubes and other dysfunctions of the female reproductive system. With neoadjuvants blocking the activity of follicles, the development of a new generation of female hormonal contraceptives can begin.
About the author:
Teresa K. Woodruff – PhD, Dean and Associate Provost for Graduate Education in The Graduate School at Northwestern University, the Thomas J. Watkins Professor of Obstetrics & Gynecology, the Vice Chair for Research and the Chief of the Division of Reproductive Science in Medicine in the Department of Obstetrics and Gynecology, Feinberg School of Medicine.
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