Controlled ovarian hyperstimulation applied before unilateral oophorectomy improves fertility preservation in cancer patients

Abstract Study question Can ovarian tissue cryopreservation (OTC) be performed after controlled ovarian hyperstimulation (COH)? Summary answer Unilateral oophorectomy after transvaginal oocyte retrieval is feasible on stimulated ovaries during one surgical step. What is known already In the fertility preservation (FP) field, the timeframe between patient referral and start of curative treatment is limited. Combining oocyte pick-up with ovarian tissue (OT) extraction has been reported to improve FP but COH applied before OT extraction is not currently recommended. Study design, size, duration This retrospective cohort-controlled study involved 58 patients who underwent oocyte cryopreservation immediately followed by OTC between September 2009 and November 2021. The exclusion criteria were a delay between oocyte retrieval and OTC of greater than 24 hours (n = 5) and in vitro maturation (IVM) of oocytes obtained ex-vivo in the ovarian cortex (n = 2). This FP strategy was performed either after COH (stimulated group, n = 18) or after IVM (unstimulated group, n = 33). Participants/materials, setting, methods Oocyte retrieval followed by OT extraction on the same day was performed either without previous stimulation or after COH. Adverse effects of surgery and ovarian stimulation, mature oocyte yield and pathology findings of fresh OT were retrospectively analysed. Thawed OTs were analysed prospectively, for vascularisation and apoptosis using immunohistochemistry, when patient consent was obtained. Main results and the role of chance No surgical complication occurred after OTC surgery in either group. In particular, no severe bleeding was associated with COH. The number of mature oocytes obtained increased after COH (8.5 [5.3–12.0] MII oocytes) compared to the unstimulated group (2.0 [1.0–5.3] MII oocytes, p < 0.001). Neither ovarian follicle density nor cell integrity was affected by COH. Fresh OT analysis showed congestion in half of the stimulated OT which was higher than in the unstimulated OT (3.1%, p < 0.001). COH also increased haemorrhagic suffusion (COH+OTC: 66.7%; IVM+OTC: 18.8%, p=0.002) and oedema (COH+OTC: 55.6%; IVM+OTC: 9.4%, p < 0.001). After thawing, the pathological findings were similar between both groups. No statistical difference in the number of blood vessels was observed between the groups. The oocyte apoptotic rate in thawed OT was not statistically different between the groups (ratio of positive cleaved caspase-3 staining oocytes/total number of oocytes equal to median 0.50 [0.33-0.85] and 0.45 [0.23-0.58] in unstimulated and stimulated groups respectively, p = 0.720). Limitations, reasons for caution The study reports FP from a small number of women following OTC. Follicle density and other pathology findings are an estimate only. Wider implications of the findings This approach could be proposed to post pubertal patients when the number of mature oocytes expected is low or when the risk of residual pathology is high. The reduction of surgical steps for cancer patients also has positive implications for introducing this approach into clinical practice. Trial registration number not applicable