Application of Ex-Vivo In Vitro Maturation (IVM) to Fertility Preservation in Cancer Patients

Abstract

Background: Oocyte in vitro maturation (IVM) is a reproductive technology that generates mature oocytes from patients who have received minimal or no ovarian stimulation (OS). The minimal-stimulation feature of IVM makes it a valuable option for cancer patients requiring fertility preservation (FP), before chemo- or radiotherapy. When ovarian tissue is collected for cryopreservation (OTC), only the ovarian cortex is preserved whereas the ovarian medulla containing growing follicles is discarded. To maximise the future fertility prospects for cancer patients, OTC should be coupled with a modified form of IVM, termed ex-vivo IVM, in which immature cumulus-oocyte complexes (COCs) are collected from antral follicles. Aim: To examine the utility of emergency ex-vivo IVM for FP. Method: A 31-year-old woman diagnosed with locally invasive appendiceal cancer required urgent FP as there was no time for conventional OS egg freeze before surgery, and OTC was contra-indicated due to the possibility of later regrafting of cancer cells. She underwent peritonectomy with bilateral oophorectomy with no prior ovarian stimulation or cycle management. Visible antral follicles were aspirated ex-vivo, the ovaries were then manually dissected, antral follicles punctured and intact COCs collected. COCs were washed and matured for 30-46h in G-2 PLUS medium supplemented with 0.1IU/mL rec-FSH, 0.5IU/mL rec-hCG, and 10% (v/v) autologous heat-inactivated patient serum. Results: 40 COCs were collected and 18 (45%) reached metaphase II, 1 was cryopreserved and 17 were inseminated by ICSI. 13/17 oocytes fertilised (2PN; 76%) and 7/13 (54%) blastocysts were generated (D5: 1× HB-1-1, 3× B-1-1, 1× B-2-1. D6: 1× HB-1-2, 1× B-2-2). Seven blastocysts and one oocyte were vitrified for future use by the patient. Conclusion: Ex-vivo IVM is a viable FP option for patients diagnosed with cancer. It can readily be coupled with OTC and/or a regular IVM oocyte pickup to maximise a cancer patient’s future fertility prospects.