The Safe Use of a PTEN Inhibitor for the Activation of Dormant Mouse Primordial Follicles and Generation of Fertilizable Eggs

Primordial ovarian follicles, which are often present in the ovaries of premature ovarian failure (POF) patients or are cryopreserved from the ovaries of young cancer patients who are undergoing gonadotoxic anticancer therapies, cannot be used to generate mature oocytes for in vitro fertilization (IVF). There has been very little success in triggering growth of primordial follicles to obtain fertilizable oocytes due to the poor understanding of the biology of primordial follicle activation.We have recently reported that PTEN (phosphatase and tensin homolog deleted on chromosome ten) prevents primordial follicle activation in mice, and deletion of Pten from the oocytes of primordial follicles leads to follicular activation. Consequently, the PTEN inhibitor has been successfully used in vitro to activate primordial follicles in both mouse and human ovaries. These results suggest that PTEN inhibitors could be used in ovarian culture medium to trigger the activation of primordial follicle. To study the safety and efficacy of the use of such inhibitors, we activated primordial follicles from neonatal mouse ovaries by transient treatment with a PTEN inhibitor bpV(HOpic). These ovaries were then transplanted under the kidney capsules of recipient mice to generate mature oocytes. The mature oocytes were fertilized in vitro and progeny mice were obtained after embryo transfer.Long-term monitoring up to the second generation of progeny mice showed that the mice were reproductively active and were free from any overt signs or symptoms of chronic illnesses. Our results indicate that the use of PTEN inhibitors could be a safe and effective way of generating mature human oocytes for use in novel IVF techniques

Diagnosis and treatment of cervical cancer during pregnancy

CONTEXT AND OBJECTIVE: One third of all cervical carcinomas occur during the reproductive period. Cervical carcinoma is the second greatest cause of death due to cancer during this phase. The estimated frequency of cervical cancer during pregnancy is one case for every 1,000 to 5,000 pregnancies. The aim here was to provide information about the difficulties in diagnosing and managing cervical neoplasia during pregnancy. MATERIALS: A systematic review of the literature was undertaken through the PubMed, Cochrane, Excerpta Medica (Embase), Literatura Latino Americana e do Caribe em Ciências da Saúde (Lilacs) and Scientific Electronic Library Online (SciELO) databases, using the following words: pregnancy, cervical cancer, diagnosis and management. RESULTS: There was a consensus in the literature regarding diagnosis of cervical carcinoma and management of preneoplastic lesions during pregnancy. However, for management of invasive carcinoma, there was great divergence regarding the gestational age taken as the limit for observation rather than immediate treatment. CONCLUSION: All patients with cytological abnormalities should undergo colposcopy, which will indicate and guide biopsy. Conization is reserved for patients with suspected invasion. High-grade lesions should be monitored during pregnancy and reevaluated after delivery. In cases of invasive carcinoma detected up to the 12th week of pregnancy, patient treatment is prioritized. Regarding diagnoses made during the second trimester, fetal pulmonary maturity can be awaited, and the use of chemotherapy to stabilize the disease until the time of delivery appears to be viable.CONTEXTO E OBJETIVO: Um terço dos carcinomas de colo ocorrem no período reprodutivo, sendo que esta é a segunda causa de morte por câncer nessa fase. A freqüência estimada do carcinoma de colo uterino na gravidez é de um caso para cada 1.000 a 5.000 gestações. O objetivo foi informar sobre as dificuldades frente ao diagnóstico e manejo da neoplasia cervical durante a gravidez. MATERIAIS E MÉTODOS: Revisão sistemática da literatura foi realizada no PubMed, Cochrane, Excerpta Medica (Embase), Literatura Latino Americana e do Caribe em Ciências da Saúde (Lilacs) and Scientific Electronic Library Online (SciELO), usando as seguintes palavras: gestação, câncer cervical, diagnóstico e manejo. RESULTADOS: A literatura apresenta consenso quanto ao diagnóstico do carcinoma cervical e a conduta das lesões pré-neoplásicas durante a gestação. No manejo do carcinoma invasor há grande divergência quanto à idade gestacional considerada como limite para a adoção da observação em vez do tratamento imediato. CONCLUSÃO: Toda paciente com citologia alterada deve realizar colposcopia, a qual indicará e a biópsia. A conização é reservada para pacientes com suspeita de invasão. As lesões de alto grau devem ser acompanhadas durante a gestação e reavaliadas após o parto. Em casos de carcinoma invasor em gestantes com até 12 semanas o tratamento da paciente é priorizado. Nos diagnósticos ocorridos no segundo trimestre, pode-se aguardar a maturidade pulmonar fetal e o uso da quimioterapia para estabilizar a doença até o momento do parto parece ser viável