Prior exposure to chemotherapy does not reduce the in vitro maturation potential of oocytes obtained from ovarian cortex in cancer patients
Authors: Karavani Gilad , Vedder Koral , Gutman-Ido Einat , Gruda Sussman Raizl , Goldschmidt Neta , Mordechai-Daniel Talya , Ben-Meir Assaf , Imbar Tal 
Published: July 2023

Abstract

STUDY QUESTION
Does chemotherapy exposure affect IVM potential of immature oocytes retrieved from the ovarian cortex following ovarian tissue cryopreservation (OTC) for fertility preservation?

SUMMARY ANSWER
The IVM potential of oocyte retrieved from ovarian cortex following OTC is not affected by prior exposure to chemotherapy but primarily dependent on patient’s age, while successful retrieval of immature oocytes from the ovarian tissue is negatively affected by chemotherapy and its timing.

WHAT IS KNOWN ALREADY
The potential and feasibility of IVM in premenarche patients was previously demonstrated, in smaller studies. The scarce data that exist on the IVM potential of oocytes retrieved during OTC following chemotherapy support the feasibility of this process, however, this was not previously shown in the premenarche cancer patients population or in larger cohorts.

STUDY DESIGN, SIZE, DURATION
A retrospective cohort study evaluating 229 cancer patients aged 1–39 years with attempted retrieval of oocytes from the ovarian tissue and the medium following OTC in a university affiliated fertility preservation unit between 2002 and 2021.

PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 172 chemotherapy naïve and 57 chemotherapy exposed patients aged 1–39 years underwent OTC in university affiliated tertiary infertility and IVF center. OTC and IVM outcomes were compared between the chemotherapy naïve and exposed groups. The main outcome measure was mean IVM rate per patient in the chemotherapy naïve and exposed groups, with subgroup analysis of a 1:1 chemotherapy exposed group matched for age at OTC and type of malignancy. We additionally analyzed premenarche and postmenarche patients’ outcomes separately and investigated the effect of time from chemotherapy to IVM, malignancy type and chemotherapy regimen on oocyte number and IVM outcomes in the chemotherapy exposed group.

MAIN RESULTS AND THE ROLE OF CHANCE
While the number of retrieved oocytes and percentage of patients with at least one oocyte retrieved was higher in the chemotherapy naïve group (8.7 ± 7.9 versus 4.9 ± 5.6 oocytes and 87.2% versus 73.7%, P &lt; 0.001 and P = 0.016, respectively), IVM rate and number of mature oocytes were comparable between the groups (29.0 ± 25.0% versus 28. 9 ± 29.2% and 2.8 ± 3.1 versus 2.2 ± 2.8, P = 0.979 and P = 0.203, respectively). Similar findings were shown in subgroup analyses for premenarche and postmenarche groups. The only parameter found to be independently associated with IVM rate in a multivariable model was menarche status (F = 8.91, P = 0.004). Logistic regression models similarly showed that past chemotherapy exposure is negatively associated with successful retrieval of oocytes while older age and menarche are predictive of successful IVM. An age and the type of malignancy matched (1:1) chemotherapy naïve and exposed groups were created (25 patients in each group). This comparison demonstrated similar IVM rate (35.4 ± 30.1% versus 31.0 ± 25.2%, P = 0.533) and number of matured oocytes (2.7 ± 3.0. versus 3.0 ± 3.9 oocytes, P = 0.772). Type of malignancy and chemotherapy regimen including alkylating agents were not associated with IVM rate.

LIMITATIONS, REASONS FOR CAUTION
This study’s inherited retrospective design and the long study period carries the possible technological advancement and differences. The chemotherapy exposed group was relatively small and included different age groups. We could only evaluate the potential of the oocytes to reach metaphase II in vitro but not their fertilization potential or clinical outcomes.

WIDER IMPLICATIONS OF THE FINDINGS
IVM is feasible even after chemotherapy broadening the fertility preservation options of cancer patients. The use of IVM for fertility preservation, even after exposure to chemotherapy, should be further studied for optimal postchemotherapy timing safety and for the in vitro matured oocytes potential for fertilization.

STUDY FUNDING/COMPETING INTEREST(S)
No funding was received for this study by any of the authors. The authors report that no competing interests.

TRIAL REGISTRATION NUMBER
N/A.