Ovarian tissue cryopreservation can be combined simultaneously with oocyte retrieval after controlled ovarian hyperstimulation
Authors: Puy Vincent , Dupeux Margot , Mayeur Anne , Grynberg Michael , Benoit Alexandra , Bendayan Marion , Zhegari Fayçal , Hesters Laetitia , Gallot Vanessa , Prevot Sophie , Frydman Nelly , Sonigo Charlotte 
Published: March 2023

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 &gt;24 h (n = 5) and 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 vascularization 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 (median = 8.5 (25% = 5.3–75% = 12.0)) compared to the unstimulated group (2.0 (1.0–5.3), P &lt; 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 &lt; 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 &lt; 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
Unilateral oophorectomy can be successfully performed after COH with limited bleeding risk and an absence of impact on thawed OT. 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.

STUDY FUNDING/COMPETING INTEREST(S)
This work was made possible through the support of the reproductive department of Antoine-Béclère Hospital and of the pathological department of Bicêtre Hospital (Assistance Publique Hôpitaux de Paris, France). The authors have no conflict of interest to disclose in this study.

TRIAL REGISTRATION NUMBER
N/A.