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.

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 prospective and randomized trial comparing 225IU and 300 IU follitropin-α in a fixed-dose regimen for controlled ovarian stimulation / Estudo prospectivo e randomizado comparativo de 225 UI e 300 UI defolitropina-α em regime de dose fixa para estimulação ovariana controlada

Purpose: To compare the outcomes of 225 IU and 300 IU follitropin-α in a fi xed-dose regimen for controlled ovarian stimulation in women ≥35 years old. Material and methods: We studied 120 normo-ovulatory women ≥35 years old, undergoing IVF or ICSI cycles. After pituitary suppression, patients were randomly divided into two groups: G225 and G300. In G225 (n=60), ovarian stimulation was performed with a fixed daily dose of 225 IU of follitropin-α and in G300 (n=60), with a fixed daily dose of 300 IU, until hCG administration. The main outcomes were: the number of metaphase II oocytes retrieved, the percentage of MII oocytes, the cancellation rates, the number of days of stimulation and the fertilization rates. Data were analyzed statistically by the χ2 and Mann-Whitney tests, as p<0.05 was considered significant. Results: In G225, six cycles were cancelled (10%) and in G300, five cycles were cancelled(8.3%). The cancellation rates did not present statistical differences between groups (p>0.05). In G225, 301 oocytes were retrieved (5.02±1.32 per cycle); 261 were at MII stage. In G300, 338 o ocytes were collected (mean: 5.63±1.68 per cycle); 300 were at MII stage (p<0.05). The percentage of MII oocytes (86.7% in G225 versus 88.7% in G300), fertilization rate (69.7% in G225 versus 72.7% in G300), and the mean number of days of stimulation (9.7±0.6 in G225 versus 9.7±0.7 in G300) were not statistically different in both groups (p>0.05). Conclusions: We conclude that the dose of 225 IU r-FSH, rather than 300 IU, may be the dose of choice for ovarian stimulation in a fixed-dose regimen in this group of patients.

Objetivo: Comparar os resultados do uso de 250 UI e 300 UI de folitropina-α em regime de dose fixa em pacientes ≥35 anos de idade. Material e métodos: Foram estudadas 120 pacientes normo-ovulatórias submetidas a ciclos de fertilização in vitro ou injeção intracitoplasmática de espermatozoide. Apósa supressão hipofisária, as pacientes foram randomizadas nos grupos G225 e G300. No G225 (n=60), a estimulação ovariana foi realizada com 225 UI defolitropina-α e no G300 (n=60) com 300 UI, em regime de dose fixa até o dia do exame de hCG. Os resultados observados foram o número e porcentagem de oócitos em metáfase II coletados, taxa de cancelamento, número de dias de estímulo e taxa de fertilização. A análise estatística foi feita pelos testes χ2 e Mann-Whitney, considerando-se significante p<0,05. Resultados: No G225, houve seis ciclos cancelados (10%) e no G300 cinco (8,3%) (p>0.05). No G225, foram coletados 301 oócitos (5,02±1,32 por ciclo); 261 eram MII. No G300, foram coletados 338 oócitos (5,63±1,68 por ciclo), sendo 300 MII. A recuperação de oócitos MII (86,7% no G225 versus 88,7% no G300), as taxas de fertilização (69,7 versus 72,7%) e o número médio de dias de estimulação(9,7±0,6 versus 9,7±0,7) não foram estatisticamente diferentes entre os grupos (p>0,05). Conclusões: Concluímos que a dose de 225 UI de r-FSH podeser a dose de escolha para estimulação ovariana em regime de dose fixa nesse grupo de pacientes.

O papel do hormônio anti-Mulleriano na determinação da reserva ovariana / The role of anti-Mullerian hormone in the assessment of ovarian reserve

Os autores reafirmam a importância da determinação da reserva ovariana previamente aos procedimentos de reprodução assistida. São feitas referências a um novo método de avaliação da reserva ovariana, que é a determinação do hormônio anti-Mulleriano (AMH), ressaltando-se que a má resposta à estimulação ovariana em ciclos de TRA associa-se a concentrações diminuídas de AMH. Embora a determinação do AMH, em nosso meio, ainda não esteja incluída na rotina da avaliação da reserva ovariana, o método parece promissor e pode ter, em futuro próximo, papel relevante na investigação da função gonadal feminina, podendo ser empregado para predizer a má resposta ovariana e os resultados das técnicas de reprodução assistida

Associação de FSH e LH recombinantes na estimulação ovariana / Association of recombinant FSH and LH in ovarian stimulation

Os autores revisam a fisiologia do ciclo ovulatório e o papel das gonadotropinas na indução da ovulação, em pacientes com distúrbios ovulatórios e no desenvolvimento folicular múltiplo para técnicas de reprodução assistida. O emprego de gonadotropinas com atividade de LH e o uso do LH recombinante associado ao FSH são discutidos. Os autores reafirmam que a administração de gonadotropinas com atividade de LH é essencial na ovulação por hipogonadismo hipogonadotrópico. O uso do LH recombinante associado ao FSH pode ser particularmente benéfico nos regimes de estimulação ovariana com antagonistas do GnRH, prevenindo a queda nos níveis de estradiol e diminuindo as necessidades de FSH