The impact of letrozole administration on oocyte morphology in breast cancer patients undergoing fertility preservation

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.

Evaluation of the relationship between vitamin D levels with oocyte quality in breast cancer women: a cross-sectional study

“…This can be caused by other factors that affect the morphology of oocytes in BC women. For example, Bercaire LMN et al reported that letrozole is a risk factor for worse oocyte morphology 29 . Also, the study of Hossein Rashidi et al showed that in the letrozole group estradiol level was significantly lower and testosterone significantly higher than in the control group.…”

“…On the day of oocyte retrieval, the oocytes in each woman were evaluated by an embryologist for (a) the number of oocytes retrieved, (b) the number of Metaphase II (MII) oocytes, (c) oocyte maturity (number of MII oocytes/total number of oocytes × 100), and (d) quality of MII oocytes. Oocyte dysmorphisms were divided into cytoplasmic anomalies (e.g., presence of vacuoles, refractile bodies, increased granularity, and smooth endoplasmic reticulum aggregations) and extracytoplasmic anomalies (e.g., irregular shape or thickness of the zona pellucida, abnormal morphology of the first polar body, and perivitelline space) 29 . In the Royan Institute, the quality of MII oocytes is classified into four categories based on morphological criteria: Morph, Slightly dysmorph, Dysmorph and Highly dysmorph 36 .…”

Effect of aromatase inhibitors on ovulation stimulation cycles in a female fertility cryopreservation program

“…Además, Bercarie et al (22) observaron un incremento en los dimorfismos ovocitarios tras el tratamiento con letrozole en ciclos de estimulación desencadenados con agonistas de la GnRH. Estas discrepancias podrían estar relacionadas con diferencias en los protocolos usados, ya que el desencadenamiento de la ovulación con hCG o antagonistas de GnRH en ciclos con letrozole conlleva diferencias en marcadores bioquímicos, foliculares y expresión de genes en células de la granulosa (23).…”