Influence of breast cancer prognostic factors on oocyte in vitro maturation outcomes performed for urgent fertility preservation
Authors: Raad Jade , Sonigo Charlotte , Benoit Alexandra , Cedrin-Durnerin Isabelle , Sifer Christophe , Sermondade Nathalie , Grynberg Michaël 
Published: May 2022

Abstract

STUDY QUESTION
Do breast cancer (BC) characteristics influence IVM of oocytes outcomes in patients undergoing fertility preservation (FP)?

SUMMARY ANSWER
Scarff-Bloom-Richardson (SBR) III grade, triple-negative BC and HER2 overexpression are independent predictors of fewer oocytes or poor IVM outcomes in young women seeking FP.

WHAT IS KNOWN ALREADY
SBR grade, triple-negative status and overexpression of HER2, as well as a high Ki67 proliferation index are all established prognostic factors for BC, influencing patients’ therapeutic management. Yet there are also concerns about the potential impact of cancer status on ovarian reserve and function. Previous studies analysing the results of ovarian stimulation in BC patients have shown conflicting findings. Nevertheless, there is no data on the potential impact of BC status and prognostic factors on IVM outcome in women undergoing urgent FP.

STUDY DESIGN, SIZE, DURATION
We studied 321 BC patients, 18 to 41 years of age, who were also candidates for oocyte cryopreservation following IVM. The number of oocytes recovered, maturation rate and total number of cryopreserved oocytes were assessed.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Ovarian reserve markers (antral follicle count [AFC] and serum anti-Müllerian hormone [AMH] levels) and IVM outcomes were compared according to BC characteristics (Ki67 proliferation index &gt;20%, progesterone and/or oestrogen receptors expression, HER2 status and SBR grade). Logistic regression analysis was then performed to determine the variables that could be independently associated with poor IVM outcomes, such as oocyte retrieval rate &lt;50%, oocyte maturation rate &lt;60% and total number of frozen oocytes &lt;5.

MAIN RESULTS AND THE ROLE OF CHANCE
Overall, the mean age of the population was 32.3 ± 4.1 years. Mean AFC and serum AMH levels were 22.8 ± 13.9 follicles and 3.8 ± 3.1 ng/ml, respectively. AMH levels were significantly lower in case of triple-negative BC when compared with ER/PR/HER2 status positive cancer (3.1 ± 2.6 ng/ml vs 4.0 ± 3.3 ng/ml, P = 0.02). The mean number of recovered oocytes was 10.2 ± 9.1. After a mean maturation rate of 58.0 ± 26.1%, 5.8 ± 5.3 mature oocytes were cryopreserved per cycle. The number of retrieved and cryopreserved oocytes after IVM were significantly lower in patients presenting with an SBR III tumour when compared with an SBR I or II tumour (9.6 ± 8.7 vs 11.7 ± 9.8, P = 0.02 and 5.4 ± 5.4 vs 6.6 ± 5.8, P = 0.02, respectively). Multivariate statistical analysis showed that HER2 positive status was associated with a mean maturation rate &lt;60% (odds ratio: 0.54; 95% CI (0.30–0.97)). Ki67 and hormonal status were not correlated with poor IVM outcomes.

LIMITATIONS, REASONS FOR CAUTION
A weakness is the retrospective nature of the study. Moreover, as with many studies focusing on FP in oncology patients, the lack of data after reutilization of IVM oocytes prevents drawing reliable conclusions on the fate of these frozen gametes.

WIDER IMPLICATIONS OF THE FINDINGS
BC prognostic factors might influence IVM outcomes. Moreover, HER2 is likely to be involved in the ovarian function and oocyte maturation process. Further investigations are needed to better understand the mechanisms at play and their possible impact on the competence of IVM oocytes.

STUDY FUNDING/COMPETING INTEREST(S)
No specific funding was used and there are no conflicts of interest.

TRIAL REGISTRATION NUMBER
N/A.