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

ABSTRACT: 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.

A specific controlled ovarian stimulation (COS) protocol for fertility preservation in women with breast cancer undergoing neoadjuvant chemotherapy.

AIM OF THE STUDY: The authors present a novel and specific controlled ovarian stimulation protocol for fertility preservation in women with estrogen-positive receptor breast cancer undergoing neoadjuvant chemotherapy. The protocol foresees random start ovarian stimulation and the use of letrozole associated to tamoxifen. MATERIAL AND METHODS: Forty breast cancer patients were included in the study. COS was performed either with recombinant FSH or hMG. Concomitantly with COS, letrozole in a dose of 5 mg and tamoxifen in a dose of 20 mg were given orally on a daily basis. The trigger was performed with 0.2 mg of triptorelin, in the presence of follicles ≥ 19 mm. Oocyte retrieval was scheduled 35-36 hours after triptorelin injection. Our main outcome measures were the number of oocytes collected and number of oocytes vitrified, the length of ovarian stimulation, total dose of gonadotropins administered, and levels of estradiol on the day of the trigger. RESULTS: The mean age of patients was 30.43 ±4.25 years. Nineteen women commenced COS in the luteal phase, eleven in the early follicular phase and ten in the late follicular phase. The mean number of collected oocytes was 11.78 ±9.12 and the mean number of vitrified oocytes was 9.72 ±7.36. The mean duration of COS was 10.03 ±1.33 days. The mean estradiol concentrations on the triggering day was 623.10 ±441.27, and the mean dose of gonadotropins administered was 2540 ±713.10. CONCLUSIONS: The authors suggest that the protocol is efficient and may be a safe option for oocyte vitrification in these patients.

Hísterossonografia tridimensional em infertilidade: estudo preliminar / Three-dimensional hysterosonography in infertility: preliminary study

OBJETIVO: comparar as informações obtidas pela ultra-sonografia pélvica e transvaginal (USG), histerossalpingografia (HSG), histeroscopia diagnóstica (HSC), ressonância nuclear magnética pélvica (RNMP) e hísterossonografia tridimensional (HSSNG 3D) para melhorar a acurácia e simplificar a investigação do fator uterino cervical e corporal em infertilidade conjugal. MÉTODOS: no período de janeiro a julho de 2003, cinquenta mulheres com queixa de infertilidade de, no mínimo, dois anos foram submetidas a USG, HSG, HSC, RNMP e HSSNG 3D como exames de rastreamento para o diagnóstico do fator uterino. Foram analisados o canal endocervical, endométrio, miométrio e presença de malformações uterinas. Os resultados de cada exame foram analisados e comparados. RESULTADOS: das 50 mulheres incluídas, 12 (24 por cento) apresentaram alteração em pelo menos um dos exames realizados. Quando se comparou a HSSNG 3D com a USG, a HSSNG 3D forneceu informações adicionais em 7 casos (58,3 por cento); comparada com a HSG, forneceu informações adicionais em 7 casos (58,3 por cento); com a HSC, em 4 casos (32,1 por cento), e comparada à RNPM, em 6 casos (50 por cento). Somente em dois casos a HSG detectou alterações do canal endocervical que não foram visualizadas na HSSNG 3D; em todos os outros casos a HSSNG 3D forneceu o mesmo diagnóstico ou deu informações adicionais em relação aos outros exames. A análise pelo teste kappa mostrou que existe concordância entre os diagnósticos obtidos com o uso da HSSNG 3D e a USG, HSG e RNMP. No entanto, quando se associaram os resultados da HSG e da HSSNG 3D observamos que todas as condições clínicas poderiam ter sido diagnosticadas, de forma precisa, somente com esses exames. CONCLUSAO: a associação da HSG com a HSSNG 3D pode ser suficiente para o diagnóstico do fator uterino cervical e corporal em infertilidade, reduzindo o número de exames realizados por cada paciente, os custos totais finais, a ansiedade e o retardo para o início do tratamento.