Efficacy and safety of controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: A multicenter retrospective study.

INTRODUCTION: Fertility preservation (FP) is recommended in young breast cancer (BC) patients before (neo)adjuvant treatment. Letrozole-associated controlled ovarian hyperstimulation (LetCOH) is used worldwide to collect mature oocytes for FP, but its efficacy and safety compared to conventional protocols (cCOH) are still debated. AIMS: To compare efficacy and safety of FP procedure using LetCOH or cCOH in BC patients in terms of oocyte maturation rate and disease-free survival rates after at least two years of follow-up. METHODS: This multicenter retrospective study compared outcomes of 107 cycles in 97 non-metastatic BC patients aged ≤40 years who underwent cCOH (n = 56) or LetCOH (n = 41) for FP in CHU-Lille and Erasme Hospital, respectively, between December 2012 and January 2017. RESULTS: Patients and oncological characteristics were similar except for tumor size and HER2 status which were less favorable in the LetCOH group. Patients underwent adjuvant chemotherapy in 96.4% and 48.8% of the cases in cCOH and LetCOH groups, respectively. Hence, 51.2% of LetCOH patients underwent neoadjuvant chemotherapy (p < 0.001). Estradiol peak at ovulation trigger was lower in LetCOH compared to cCOH group while oocyte maturation rates were significantly higher (p < 0.001), without impacting the final number of mature oocytes collected. Seven and four patients relapsed in LetCOH and cCOH groups, respectively, and one patient died in each group after a median follow-up of four years. CONCLUSION: LetCOH is as effective as cCOH for FP. At this time point, there were no safety concerns regarding cCOH in the adjuvant setting but a longer follow-up is warranted.

Is ovarian recovery after chemotherapy in young patients with early breast cancer influenced by controlled ovarian hyperstimulation for fertility preservation or tumor characteristics? Results of a prospective study in 126 patients.

Young individuals, aged <40 years, represent 7% of all patients with early breast cancer (EBC), most of whom receive chemotherapy. Preserving future fertility in these patients has become a major concern. This prospective study assessed ovarian function during and after chemotherapy according to patient and tumor characteristics and evaluated the outcome of controlled ovarian hyperstimulation (COH). Ovarian reserve was evaluated in terms of amenorrhea duration and by longitudinal serum anti-Müllerian hormone (AMH) level variations measured at study entry, during treatment and until 24 months thereafter. COH has been proposed for patients receiving adjuvant chemotherapy. We studied the association between clinical factors and ovarian function using Cox models and logistic regression. In this young population (age < 38 years, median = 32), 85 of 90 evaluable patients (94%) experienced chemo-induced amenorrhea, including six persistent amenorrhea and one chemotherapy-induced definitive ovarian failure. Overall, 33% of patients still had undetectable AMH values 12 months after the end of chemotherapy, although most had recovered spontaneous and regular menstrual function. No specific factor was associated with clinical or biological late ovarian dysfunction, except for age and baseline AMH value. Overall, 58 patients underwent COH. The mean number of total retrieved oocytes and metaphase II oocytes were of 11.7 and 6.9, respectively. Thus, our study confirms the importance of fertility preservation in young patients with EBC. Our findings indicate that sequential chemotherapy is associated with a higher risk of persistent amenorrhea. There was no significant association between tumor characteristics, fertility preservation or recovery of ovarian reserve.

Different patterns of ovarian recovery after cancer treatment suggest various individual ovarian susceptibilities to chemotherapy.

The relationship between early recovery of menstrual activity and blood anti-Müllerian hormone (AMH) concentrations were investigated within the first year post-chemotherapy in 32 young patients with breast cancer. All were treated by surgery and the same chemotherapy protocol (three cycles of FEC100 plus three cycles of taxanes). Menstrual activity, blood AMH (using picoAMH ELISA) and FSH concentrations were measured longitudinally before, during and up to 12 months after the end of chemotherapy (six samples per patient). Among the cohort, 17 patients recovered spontaneous cycles at +6 months (fast recovery) whereas the remaining 15 patients were still amenorrheic at that time (slow recovery). Blood AMH differed between these two subgroups at each time of the recovery phase starting at 3 months post-chemotherapy. The AMH patterns were also different: rapid and large increase in the fast recovery versus slow and partial increase in the slow recovery subgroup. No difference in ovarian recovery was observed between patients with a hormone positive or negative tumour. In conclusion, studying the post-chemotherapy patterns of menstrual activity and AMH, two paces of early ovarian recovery are distinguishable in young breast cancer patients who received the same chemotherapy protocol. This suggests different individual ovarian susceptibilities to chemotherapy.