Abstract
Objective:Patients submitted to oncological fertility preservation with letrozole and gonadotropins seem to present a higher rate of immature oocytes and lower fertilization rates in comparison to infertile patients submitted to IVF cycles with gonadotropins. The aim of this study was to evaluate the influence of letrozole on oocyte morphology in patients with breast cancer submitted to fertility preservation.Methods:Retrospective analysis performed at a public tertiary hospital in São Paulo, Brazil. The oocytes were retrieved from patients with breast cancer undergoing fertility preservation (n=69), and from infertile women undergoing in vitro fertilization (n=92). We evaluated 750 oocytes obtained from breast cancer patients submitted to ovarian stimulation with letrozole and gonadotropins, and 699 oocytes from patients without breast cancer submitted to ovarian stimulation for in vitro fertilization with gonadotropins only due to male factor infertility. The mature oocytes retrieved were analyzed for the presence of refractile bodies, ooplasm color and regularity, central granulation degree, cortical granules, zona pellucida staining and regularity, perivitelline space, presence of vacuoles or abnormal smooth-surfaced endoplasmic reticle and oocyte retraction.Results:There was a higher incidence of alterations in oocyte morphology in the letrozole group when compared to the control group: increased perivitelline space (p=0.007), irregular zona pellucida (p<0.001), refractile bodies (p<0.001), dark ooplasm (p<0.001), granular ooplasm (p<0.001), irregular ooplasm (p<0.001) and dense central granulation (p<0.001).Conclusion:Letrozole is a risk factor for worse oocyte morphology. However, the clinical impact of ovarian stimulation protocol with combined use of gonadotropins and letrozole for fertility preservation remains unclear in this setting. These data underline the importance of establishing the predictive potential of morphological dimorphisms of human oocytes in IVF outcomes.
Highlights
Breast cancer is the leading worldwide cause of death by cancer in women, accounting for 30% of malignancies in the United States
The purpose of this study was to determine if co-administration of letrozole in conventional ovarian stimulation protocol is associated with oocyte morphological parameter changes in the setting of breast cancer patients undergoing fertility preservation
Patients submitted to controlled ovarian stimulation for in vitro fertilization due to infertility related to male factors and not affected by cancer were defined as controls, and the selection of patients was performed through age pairing (n=92), in order to obtain a similar proportion of 699 oocytes
Summary
Breast cancer is the leading worldwide cause of death by cancer in women, accounting for 30% of malignancies in the United States. Among all women diagnosed with breast cancer in the United States in 2017, about 4% were under 40 years of age (American Cancer Society, 2017). The high incidence and survival rate of breast cancer in women of childbearing age has led to a considerable concern about fertility preservation treatments. Ovarian failure is not always defined after chemotherapy treatment, many young women evolve to subfertility or infertility (Sonmezer & Oktay, 2006). In this context, the importance of fertility programs is a rising priority in order to improve the quality of life of these patients. Cryopreservation of oocytes or embryos are currently the first choice techniques to preserve fertility of patients with breast cancer who will undergo chemotherapy, and the protocol with letrozole is usually applied in patients with hormone-dependent tumors (Kasum et al, 2015)
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