Advancements in the cancer treatments have fortunately increased the number of survivors, but the side-effects of malignancy and its treatments i.e. chemo- and radiotherapy, bag along. The gonadotoxic effects of the therapy set off substantial disturbances in the endocrine and reproductive functions of the surviving women, rendering them incapable of conceiving.



What damage does cancer treatment cause?



In healthy women, the ovum is released in the fallopian tube when one of the follicles inside the ovary matures and bursts open. This ovum can then be fertilised by a sperm to form a zygote. Follicles are also responsible for reproductive hormonal secretion. These follicles get damaged during the course of cancer treatment affecting not only the fertility but also the hormone dependant pubertal changes. Thus no eggs, no hormones à no pregnancy.

Is there a solution?



The answer is Cryobanking. To preserve fertility, such women are offered cryopreservation of their ovarian tissue to be transplanted back after the cancer treatment has been completed. This restores ovarian function in up to 95% cases with a live birth rate between 23 and 77%. Nevertheless, it has a grave concern of reimplanting malignant cells along with the ovarian tissue, forcing researchers to work around this limitation, thus, an invention of the artificial 3D printed ovary.

CRYOPRESERVATION

http://www.futurefertilitytrustuk.org/home/ovarian-tissue-cryopreservation/

Artificial 3D printed ovaries



Many organs have been printed in the lab using 3D printing technology, giving females hopes for fertility after fighting cancer, with the bioengineered ovaries.

For the construction of a successful transplantable artificial ovary, first, intact preantral follicles are isolated from the ovaries and then the follicles are washed to eliminate the risk of contamination with malignant cells. Since follicles require vascularization in the artificial environment, this is obtained by isolated endothelial cells. The most critical and challenging step is to provide a 3D matrix for encapsulation of the follicles, that resembles the natural ovarian environment, with optimal porosity and rigidity to hold the follicles and to let them survive.

Image credit: Nature Communications

Don’t these isolated follicles carry the malignant cells along?



This question is legit! Since we talked about this drawback with cryopreservation, it most certainly rings a bell here. Basement membrane encloses follicles thus a barrier to any direct interaction with the vessels, blood cells or nerve processes. Moreover, the isolation process is followed by washing, completely eliminating the risk, if any at all.

Has this research shown positive results?



Experimental trials on mice have shown promising results. The natural ovary was replaced with the bioengineered one along with the isolated follicles embedded within it. After mating, successful implantation and birth of ‘pups’ were reported. Not only this, but female mice were able to nurse their babies too, proving the restoration of hormonal functions and also a proof of the establishment of vascular connections with the artificial ovary which enables hormones to circulate throughout the body, triggering milk production.

This has not yet been put into action for humans but studies have shown its feasibility with humans too.



Due to differences in the ovarian architecture of mice and humans, the creation of an artificial transplantable human ovary will need a distinct approach, this, along with the ethical concerns suggest that there is still a long road ahead.

https://link.springer.com/chapter/10.1007/978-4-431-55963-4_12

References

Amorim, M.-M. D. (2019, November). FERTILITY PRESERVATION: Construction and use of artificial ovaries. Reproduction, F15–F25. DOI:https://doi.org/10.1530/REP-18-0536

Laronda MM, R. A. (2017, May). A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nature communications, PMCID: PMC5440811. DOI:10.1038/ncomms15261

Piazza, G. (2017, May 23rd). Making artificial ovaries. Retrieved from National Institute of Health: https://www.nih.gov/news-events/nih-research-matters/making-artificial-ovaries