Oncofertility Publications - Human Follicle Culture

Building off our work in the mouse and nonhuman primate models, we recently showed that we can grow human secondary follicles in the alginate hydrogel-based follicle culture system. Early secondary follicles, isolated from ovarian tissues from human cancer patients, grew to the antral stage after thirty days in culture. These follicles produced hormones, had intact somatic cell-oocyte architecture, and contained oocytes that appeared to have nuclear competence. This breakthrough highlights the huge potential of translating bench science into clinical practice for fertility preservation.

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Noninvasive Index of Cyrorecovery and Growth Potential for Human Follicles In Vitro

Abstract

Cryopreservation of oocytes and embryos is commonly used to preserve fertility. However, women undergoing cancer treatment may not have the time or may not be good candidates for these options. Ovarian cortical tissue cryopreservation and subsequent tissue transplant has been proven successful yet inefficient in preserving larger secondary follicles, and is not recommended as a fertility preservation option for women with certain cancers. We evaluated cryopreservation of individual follicles as an alternative option in rodents, nonhuman primates, and human primates. Under optimal conditions, cryopreserved mouse secondary follicles were able to reestablish granulosa cell-oocyte interactions, which are essential for subsequent follicle growth. Individual secondary follicles survived cryopreservation, were able to be cultured in a three-dimensional alginate hydrogel matrix to the antral stage, and the enclosed oocytes were competent for fertilization. Using a vital imaging technique (pol-scope) employed in many fertility centers, we were able to bioassay the thawed, cultured follicles for the presence of transzonal connections between the somatic and germ cells. Perturbations in these linkages were shown to be reversed when follicles were cryopreserved under optimal freezing conditions. We applied the optimized cryopreservation protocol to isolated rhesus monkey and human secondary follicles, and using the birefringent bioassay, we were able to show good correlation between early follicle growth and healthy somatic cell-oocyte connections. Our results suggest that ovarian follicles can be cryopreserved, thawed, and analyzed noninvasively, making follicle preservation an additional option for young cancer patients.

Susan L. Barrett, Lonnie D. Shea, Teresa K. Woodruff.  Biology of Reproduction, 2010.

 		Basic Science, Research Resources, Human Follicle Culture, Oncofertility-Related Publications
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In Vitro Grown Human Ovarian Follicles From Cancer Patients Support Oocyte Growth

Abstract

BACKGROUND: Young female adult and adolescent cancer patients facing life-preserving but fertility-threatening chemo- or radiation-therapy are increasingly seeking options to protect their reproductive potential. Ovarian tissue cryopreservation with transplantation is a promising technique to safeguard fertility in cancer patients. However, this method may risk re-introduction of the original cancer to the survivor of the disease. Thus, developing a method for in vitro growth of immature follicles may provide a method for fertility restoration in the future.

METHODS: Human secondary follicles were isolated from ovarian tissues obtained from cancer patients and grown in vitro within a bio-engineered culture system for 30 days.

RESULTS: Human ovarian follicles became steroidogenically active, and developed from the early secondary to antral stage in vitro. The follicles contained healthy, growing oocytes that were connected by transzonal projections between the somatic cells and oocyte.

CONCLUSIONS: Our data support the notion that human follicle development can be achieved in vitro in a bio-engineered culture system. More studies are required to investigate whether the fully sized oocytes obtained from in vitro grown follicle are competent to resume meiosis and be fertilized.

Min Xu, Susan L. Barrett, Erin West-Farrell, Laxmi A. Kondapalli,, Sarah E. Kiesewetter, Lonnie D. Shea, and Teresa K. Woodruff; Human Reproduction Vol.24, No.10 2531-40 Oct. 24, 2009

 		Basic Science, Research Resources, Human Follicle Culture, Oncofertility-Related Publications
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