Estudio exploratorio de las motivaciones para la criopreservación de ovocitos en forma electiva / An exploratory study of motivations for elective oocyte cryopreservation

Introducción La vitrificación de óvulos es un avance científico que ha cambiado la perspectiva reproductiva de la sociedad humana. Este procedimiento se ha ofrecido como alternativa a la postergación voluntaria del embarazo, confiriéndole a la mujer una nueva perspectiva en su autonomía reproductiva. El número de mujeres que consultan y luego optan por congelar ovocitos ha aumentado en forma casi exponencial en Chile y en todo el mundo. En nuestro país, hay poco conocimiento acerca de la motivación, experiencia y resultados de la criopreservación electiva de ovocitos en Chile. El objetivo fue conocer la motivación, experiencia y el deseo reproductivo futuro de este grupo de mujeres sometidas a esta técnica. Métodos Estudio descriptivo transversal, basado en un cuestionario enviado por correo electrónico en el que participaron mujeres que se habían sometido previamente a criopreservación electiva de ovocitos entre enero de 2011 y diciembre de 2019 en Clínica Alemana, Santiago de Chile. Resultados De 342 mujeres que habían completado un ciclo de criopreservación electiva de ovocitos, 193 aceptaron participar y de estas, 98 (51%) de las mujeres contestaron la encuesta en forma satisfactoria. Se establecieron criterios de exclusión a aquellas mujeres que se habían sometido a este procedimiento por indicación médica como la endometriosis, el cáncer y la baja reserva ovárica. El motivo más frecuente para realizarse el procedimiento fue la edad (44%). En relación al procedimiento; el 94% no se arrepiente de haberlo realizado y 74% de las mujeres cree que utilizará sus ovocitos en algún momento de su vida. Por último, desde que se realizaron la criopreservación de ovocitos a la fecha, el 11% de las mujeres encuestadas ha usado sus ovocitos vitrificados y 27% ha logrado embarazarse con estos. Conclusión Las mujeres que se someten a criopreservación electiva de ovocitos por razones sociales, son principalmente mujeres sin pareja que tiene como motivación principal su edad reproductiva y la gran mayoría de ellas no se arrepienten de haberlo realizado.

Introduction Oocyte vitrification is a scientific advance that has changed the reproductive perspective of human society. This procedure has been offered as an alternative to the voluntary postponement of pregnancy, giving women a new perspective on their reproductive autonomy. The number of women who consult and then choose to freeze oocytes has increased almost exponentially in Chile and throughout the world. There is little knowledge about the motivation, experience, and results of elective oocyte cryopreservation in Chile. The objective was to know the motivation, experience, and future reproductive desire of the women who underwent this technique. Methods Cross-sectional descriptive study based on a questionnaire sent by e-mail in which females who had previously undergone elective oocyte cryopreservation between January 2011 and December 2019 at Clínica Alemana, Santiago, Chile, participated. Results Of 342 women who had completed a cycle of elective oocyte cryopreservation, 193 agreed to participate, and of these, 98 (51%) answered the survey satisfactorily. Women who underwent this procedure for medical indication, including endometriosis, cancer, and low ovarian reserve, were excluded. The most frequent reason for the procedure was age (44%). Concerning the procedure: 94% do not regret having it done, and 74% of the women believe that they will use their oocytes at some point in their lives. Finally, from the time of oocyte cryopreservation to date, 11% of the surveyed women have used their vitrified oocytes, and 27% have become pregnant. Conclusions Women who undergo elective oocyte cryopreservation for social reasons are mainly women without a partner whose main motivation is their reproductive age. The vast majority do not regret doing so.

Advances in gonadal damage in children induced by hematopoietic stem cell transplantation / 国际儿科学杂志

Hematopoietic stem cell transplantation(HSCT), as a technique to reconstruct normal hematopoietic and immune function, has become a treatment option for a variety of malignant and non-malignant diseases in children.With the development of medical technology, the long-term survival rate of children after HSCT is significantly improved.At the same time, there is more concern and awareness about the late effects of HSCT.As one of the endocrine complications with the highest incidence in children after HSCT, gonadal damage leads to sex hormone secretion disorder, adolescent dysplasia, and infertility in adulthood, which has a serious influence on children′s mental health and quality of life.Therefore, it is helpful to reduce the psychological and economic burden on children and their families by understanding its potential mechanism, evaluating risk factors, screening early warning and recovery markers of gonadal function as well as taking corresponding preventive and protective measures.

Ligadura temporal laparoscópica de arterias uterinas en un caso de vasculatura miometrial aumentada relacionada con el embarazo / Laparoscopic temporary uterine artery ligation in a case of pregnancy-related increased myometrial vasculature

Resumen ANTECEDENTES: La vasculatura miometrial aumentada es una afección poco común, con alto riesgo de hemorragia masiva. Su fisiopatología se relaciona con una remodelación inadecuada del endometrio y miometrio, posterior a un evento obstétrico. El tratamiento convencional, en caso de sangrado masivo, es la histerectomía. En la actualidad, los tratamientos con enfoque conservador que permiten el embarazo espontáneo, ofrecen una opción segura para estas pacientes. CASO CLÍNICO: Paciente de 20 años, primigesta, con deseo gestacional a futuro, llevada a la sala de urgencias debido a una hemorragia uterina profusa, con datos clínicos de bajo gasto, antecedente de aborto completo de 10 semanas de gestación un mes antes. En el ultrasonido Doppler se observó una imagen anecoica irregular en el fondo uterino que interrumpía la interfase endometrio-miometrial asociada con flujo sistólico alto. Para el control vascular se indicó cirugía conservadora de útero, con ligadura temporal laparoscópica de las arterias uterinas; además aspiración uterina. Estos procedimientos trascurrieron sin complicaciones. El reporte histopatológico del material aspirado fue de tejido trofoblástico asociado con ectasia vascular. CONCLUSIÓN: La ligadura temporal laparoscópica de las arterias uterinas es un procedimiento eficaz, en casos seleccionados, de control vascular durante la extracción del tejido trofoblástico remanente, en casos de vasculatura miometrial aumentada, relacionada con el embarazo, con recuperación completa de la irrigación uterina y preservación del útero.

Abstract BACKGROUND: Enlarged myometrial vasculature is a rare condition with a high risk of massive haemorrhage. Its pathophysiology is related to inadequate remodelling of the endometrium and myometrium following an obstetric event. The conventional treatment for massive haemorrhage is hysterectomy. Currently, conservative management approaches that allow spontaneous pregnancy offer a safe option for these patients. CLINICAL CASE: 20-year-old primigravida with future pregnancy aspirations, presented to the emergency department with heavy uterine bleeding, clinical data of low output, history of complete abortion at 10 weeks' gestation one month earlier. Doppler ultrasound showed an irregular anechoic image in the uterine fundus interrupting the endometrial-myometrial interface associated with high systolic flow. For vascular control, uterine-sparing surgery with laparoscopic temporary ligation of the uterine arteries and uterine aspiration was indicated. These procedures were performed without complications. The histopathological report of the aspirated tissue was trophoblastic tissue associated with vascular ectasia. CONCLUSION: Temporary laparoscopic ligation of the uterine arteries is an effective procedure in selected cases for vascular control during removal of the remaining trophoblastic tissue, in cases of pregnancy-related increased myometrial vasculature, with complete recovery of uterine irrigation and preservation of the uterus.

Ethical Considerations on Social Egg Freezing for Single Women / 中国医学伦理学

Since the occurrence of the first case of "egg freezing for single women" in China, it has aroused different discussions and thoughts from all walks of life. Through the ethical analysis of the four principles of bioethics, this paper found a reasonable ethical basis for single women’s egg freezing. From the perspective of favorable principle, egg freezing could temporarily preserve women’s fertility, which is conducive to women’s better realization of their own personal value and social values. From the perspective of no harm principle, no harm is relative, and the harm brought by egg freezing technology is within the acceptable and permissible range. From the perspective of justice principle, whether there is gender discriminatory in that men could freeze their sperm but women have many restrictions on egg freezing. From the principle of respect for autonomy, whether to choose egg freezing is a manifestation of women’s autonomy rights, which should be respected. This paper tried to propose corresponding solutions to the ethical and legal issues caused by the permission of egg freezing from the legal perspective, the medical ethics committee’s responsibilities, and the ethical level.

Research progresses in the radiotherapy effect on ovarian function and its protection / 中华放射医学与防护杂志

The survival rate of cancer patients was improved due to the development of cancer treatment techniques, and thus the fertility protection for young female cancer patients has attracted increasing attention. Radiotherapy, as one of the comprehensive cancer treatment, could cause ovarian damage in adolescent and child-bearing women, which leads to fertility decline and a series of side effects. Radiation can cause ovarian damage not only by acting on biological macromolecules directly, but also by increasing oxidative stress between oocytes and ovarian granulosa cells indirectly. At present, the fertility preservation of female cancer patients undergoing radiotherapy mainly includes physical protection, drug protection and biological protection. Recently, the development of new technologies for the preservation of fertility in female cancer patients has also brought new hope, including factors such as protective effects, patient age, and the selection of specific cancer treatment measures, which are the main considerations in the selection process of fertility preservation measures. This article reviews the research progress on radiation-induced ovarian damage, with a focus on the introduction of the fertility preservation measures and new technologies for young female tumor patients receiving radiotherapy.

Las TRHA como nexo entre el deseo y la biología / ART as a Link Between Desire and Biology

En la actualidad nos encontramos en un escenario social y económico totalmente diferente que hace 30 o 40 años, el acceso de las mujeres a la educación universitaria, su inserción en los diferentes ámbitos profesionales, e incluso el ritmo de vida que llevan hace que cada vez más mujeres decidan postergar sus proyectos parentales. Lo problemático aparece cuando deciden abordar el deseo de ser madres y aparecen cuestiones ligadas a lo biológico que no van a la par de los tiempos del deseo. Ante esta perspectiva, ¿con qué herramientas cuentan las mujeres para evitar de algún modo la hiancia que aparece entre deseo y biología? ¿Podemos pensar en las TRHA como nexo entre el deseo de hijo y las limitaciones biológicas del cuerpo? ¿Hay modo de evitar los emergentes psicológicos negativos que surgen ante los diagnósticos de infertilidad? En el siguiente trabajo se tomará el caso de la Doctora Helen Sharpe, personaje ficticio perteneciente a la serie New Amsterdam, con el fin de poder abordar los interrogantes planteados, y pensar como las TRHA funcionan no solo como nexo del deseo y la biología sino como un agente salutogénico, evitando o reduciendo los emergentes psicológicos negativos ante diagnósticos de infertilidad

Nowadays we find ourselves in a totally different social and economic scenario than 30 or 40 years ago, the access of women to university education, their insertion in different professional fields, and even the rhythm of life they lead makes more and more women decide to postpone their parental projects. The problem arises when they decide to address the desire to become mothers and issues related to the biological aspect appear that do not go hand in hand with the times of desire. In this perspective, what tools do women have to avoid the gap that appears between desire and biology? Can we think of ART as a link between the desire for a child and the biological limitations of the body? Is there a way to avoid the negative psychological emergents that arise in the face of infertility diagnoses? In the following paper we will take the case of Dr. Helen Sharpe, a fictional character from the series "New Amsterdam", in order to address the questions raised and to think about how the ART works not only as a link between desire and biology but also as a salutogenic agent, avoiding or reducing the negative psychological emergents in the face of infertility diagnoses

Ovarian Tissue Culture to Preserve Fertility in Transgender Male Patients after Hormonal Treatment / Cultura de tecido ovariano para preservação da fertilidade em pacientes transexuais masculinos após tratamento hormonal

Abstract Objective To evaluate the reproductive and histological characteristics of fresh cultured ovarian tissue from transgender male patients. Methods An in vitro pilot study in which samples were collected during sex reassignment surgery for transgender male patients. The ovarian cortex was cut into fragments of 2 mm, 3mm, and 4 mm, and placed in a 96-well plate suitable for cultivation at days 0, 2, 4, 6, and 8, when the histology was analyzed. Results Stromal hyperplasia was observed in all samples, and it was not associated with the obtainment of primordial or primary follicles. Peripheral reduction in cell count was also a recurrent finding. Primordial and primary follicles were identified with a heterogeneous pattern in fragments from the same patient and from different patients, and follicles in more advanced stages of development (secondary and antral) were not found. There was an association between the diameter of the ovarian fragments and the identification of primary follicles (p=0.036). The number of days in culture was associated with histological signs of tissue damaging in the fragments (p=0.002). The total number of follicles identified in the samples with 2mm in diameter was significantly lower than in those that measured 4mm in diameter (p=0.031). Conclusion A diameter of 4mm is suitable for ovarian tissue culture with the benefit of ease of handling. Even after prolonged exposure to testosterone, the ovarian fragments presented primordial and primary follicles, maintaining viability throughout the days they were exposed to the culture. Freezing the ovarian cortex of transgender patients who will undergo surgery for gender reassignment would be an interesting option, in the future, for the preservation of fertility.

Resumo Objetivo Avaliar as características reprodutivas e histológicas de tecido ovariano cultivado a fresco de pacientes transexuais masculinos. Métodos Estudo experimental in vitro e piloto, no qual amostras foram coletadas durante a cirurgia de redesignação de sexo para pacientes transexuais masculinos. O córtex ovariano foi cortado em fragmentos de 2mm, 3mm, e 4mm, e colocado em placa de 96 poços própria para cultivo nos dias 0, 2, 4, 6 e 8, quando a histologia foi analisada. Resultados Hiperplasia estromal foi observada em todas as amostras, e não esteve associada à obtenção de folículos primordiais ou primários. A redução periférica no número de células também foi um achado recorrente. Folículos primordiais e primários foramidentificados com padrão heterogêneo emfragmentos domesmo paciente e em fragmentos de pacientes diferentes, não sendo encontrados folículos em estágios mais avançados de desenvolvimento (secundários e antrais). Houve associação entre o diâmetro dos fragmentos ovarianos e a identificação dos folículos primários (p=0,036). O número de dias de cultura esteve associado a sinais histológicos de lesão tecidual nos fragmentos (p=0,002). O número total de folículos identificados nas amostras de 2mm de diâmetro foi significativamente menor do que nas de 4mm de diâmetro (p=0,031). Conclusão O diâmetro de 4mm parece ser mais adequado para a cultura de tecido ovariano com a vantagem de fácil manejo. Mesmo após exposição prolongada à testosterona, os fragmentos ovarianos apresentavam folículos primordiais e primários, e manteve a viabilidade ao longo dos dias de exposição à cultura. No futuro, o congelamento da cortical do ovário de pacientes transgêneros que se submeterão à cirurgia de redesignação sexual poderia ser uma opção interessante para a preservação da fertilidade.

Analyze of obesity indicators and effect of fertility preservation treatment in patients with endometrial atypical hyperplasia and early endometrial cancer / 中华妇产科杂志

Objective:To investigate the clinical features of obesity indicators in patients with endometrial atypical hyperplasia (EAH) and early endometrial cancer (EC) and analyze the relationship between these indexes and effect of fertility preservation therapy.Methods:The clinical data of patients with EAH, EC and endometrial benign lesions treated in Peking University People′s Hospital from January 1, 2018 to June 30, 2021 who required fertility-sparing treatment were collected, and obesity indicators were calculated and analyzed retrospectively.Results:(1) Obesity indicators: the obesity [body mass index (BMI) ≥28 kg/m 2] rate of patients with fertility preservation treatment was 40% (32/80), and abdominal obesity [waist circumference (WC) ≥80 cm] rate was 79% (63/80), and obesity indicators [BMI, WC, waist-hip ratio (WHR), weight height ratio (WHTR), body roundness index (BRI), lipid accumulation index (LAP), visceral adiposity index (VAI)] were higher than those with endometrial benign lesions (all P<0.001). (2) Related factors affecting the efficacy of fertility preservation treatment and their predictive value: EC, higher BMI, WC, WHR, WHTR and BRI were risk factors for lower complete remission rate after nine months′ treatment (all P<0.05). The predictive values of BRI and WHTR combined with pathological type were superior to other indicators [area under the curve (AUC)=0.716; AUC=0.714]. (3) Relation of obesity indicators and glucolipid indicators:BMI, WC, WHR, WHTR, BRI, LAP and VAI were positively correlated with homeostasis model assessment-insulin resistance index, glycosylated hemoglobin, and triacylglycerol (all P<0.05); while VAI was negatively correlated with high density lipoprotein cholesterol ( P<0.001). Conclusions:For patients with EAH and EC treated with fertility preservation therapy, abnormal obesity indexes affect the treatment effect. BRI and WHTR combined pathology have good predictive value for effect of fertility preservation treatment. In clinical practice, appropriate indicators could be selected to evaluate body shape, glucolipid metabolism and predict efficacy.

Significance of molecular classification in fertility-sparing treatment of endometrial carcinoma and atypical endometrial hyperplasia / 中华妇产科杂志

Objective:To investigate the molecular classification of endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) treated with fertility-sparing therapy, and to analyze its relationship with clinicopathological factors and treatment efficacy.Methods:A total of 46 EC and AEH patients who received fertility-sparing therapy and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2021, were retrospectively collected. The relationships between molecular classification and clinicopathological factors and treatment outcomes were analyzed.Results:(1) Of the 46 patients, including 40 EC and 6 AEH patients, 32 cases (71%, 32/45) had complete response (CR) after treatment, with median CR time of 8 months, 6 cases (13%, 6/45) had partial response, and 8 cases (25%, 8/32) had recurrence. (2) The cases were distributed as no specific molecular profile (NSMP) 34 cases (74%, 34/46) subtype mainly, high microsatellite instability (MSI-H) 7 cases (15%, 7/46), POLE ultra-mutated 3 cases (7%, 3/46), and copy number high (CNH) 2 cases (4%, 2/46). Patients with CNH had the hightest serum cancer antigen 125 (CA 125) level [(34.3±35.2) kU/L]. MSI-H subtype had more family history of tumors (6/7), more with loss of mismatch repair (MMR) protein expression by immunohistochemical (7/7), and higher nuclear antigen associated with cell proliferation (Ki-67) expression level (3/3). (3) Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6; P=0.019), and survival analysis showed that they were less likely to achieve CR than those with NSMP subtype ( P=0.022). Subgroup analysis of patients with NSMP showed that age ≥30 years related with longer treatment time to CR ( P=0.010). In addition, CR was obtained after treatment in 2/3 POLE ultra-mutated cases and 2/2 CNH, respectively. Conclusions:Molecular classification relates with the treatment response in patients with EC and AEH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy, and patients with NSMP need to be further studied and predict treatment benefit. However, there are few cases in POLE ultra-mutated and CNH subtypes, which need further clinical research.

Visualization analysis of research literature oncology nurses at home and abroad based on CiteSpace / 中国实用护理杂志

Objective:To understand the research hotspots and development trends of oncology nurses at home and abroad from 2011 to 2020, so as to provide reference for related research.Methods:The articles related to oncology nurses at home and abroad from 2011 to 2020 were retrieved through China National Knowledge Infrastructure database, Web of Science database and PUBMED database, and the included literatures′ published journals, institutions and keywords were analyzed by using the online analysis of Statistical Analysis Toolkit for Informetrics3.2 and the software CiteSpace5.7.R1.Results:A total of 588 domestic and 738 foreign articles were included. Keywords analysis showed that domestic oncology nurse related research hotspots were occupational evaluation, hospice care, psychology and occupational protection. Oncology nurse at home and abroad research hotspots had both similarities and differences, different in fertility preservation, communication and so on.Conclusions:The domestic core journal forums of oncology nurse research are still too scattered, and there is a certain gap in the number of articles published between our country and other countries. China still needs to increase the research efforts in this field.

Value of fertility-sparing surgery for young females with epithelial ovarian cancer: a comparative study / Valor de la cirugía de preservación de la fertilidad en mujeres jóvenes con cáncer de ovario epitelial: un estudio comparativo

Resumen OBJETIVO: Comparar la cirugía radical con la cirugía conservadora de la fertilidad en mujeres con cáncer de ovario epitelial en estadio 1A-C con respecto a la tasa de recurrencia y las tasas de supervivencia. Además, evaluar los desenlaces reproductivos y obstétricos para las mujeres con cáncer de ovario epitelial en estadio I tratadas con una conducta conservadora de la fertilidad. PACIENTES Y MÉTODOS: Estudio prospectivo efectuado en pacientes con cáncer de ovario epitelial, estadio I, con edad ≤ 40 años. A las pacientes del grupo de preservación de la fertilidad se les practicó salpingooforectomía del lado del ovario afectado y una biopsia por incisión o escisión en cuña del ovario contralateral. A las pacientes del grupo de cirugía radical se les practicó la histerectomía total y salpingooforectomía bilateral. Para evaluar los desenlaces reproductivos y oncológicos se dio seguimiento a todas las pacientes durante cinco años. RESULTADOS: Se estudiaron 60 pacientes; las del grupo de cirugía de preservación de la fertilidad eran significativamente más jóvenes (30 ± 4 en comparación con 35 ± 5) (p < 0.001), el tamaño de sus tumores era más pequeño 3.4 ± 1.3 en comparación con 6.0 ± 2,6 (p < 0.001), de menor grado (p < 0.001). = 0.011), estadio más precoz (p < 0.001) y con más histología mucinosa que las pacientes del grupo de cirugía radical. No hubo diferencias estadísticamente significativas entre ambos grupos en cuanto a la recurrencia tumoral o las tasas de supervivencia. De 25 pacientes operadas para preservación de la fertilidad 18 de 25 intentaron quedar embarazadas. Se registraron 15 de 18 embarazos, incluidos 13 nacidos vivos, 1 aborto espontáneo y 1 muerte fetal intrauterina. CONCLUSIÓN: La cirugía conservadora de la fertilidad podría ser una alternativa adecuada a la cirugía radical para mujeres jóvenes con cáncer epitelial de ovario en estadio I.

Abstract OBJECTIVE: In the current study, we aimed to compare between radical surgery and fertility saving surgery in females with stage 1A-C EOC regarding recurrence rate and patients survival rates in addition to evaluating reproductive and obstetric outcomes for stage I EOC females who were managed by fertility saving surgery. PATIENTS AND METHODS: We prospectively identified 60 patients diagnosed with stage I EOC aged ≤ 40 years. Patients in the fertility-preservation group underwent salpingo-oophorectomy on the side of the affected ovary in addition to incisional biopsy or wedge excision of the ovary on the other side. Patients in the radical surgery group underwent total hysterectomy and bilateral salpingo-oophorectomy. We followed up all patients for 5 years to assess their reproductive and oncological outcomes. RESULTS: Patients in the fertility preservation surgery group were significantly younger (30 ± 4 versus 35 ± 5) (p < 0.001), their tumor sizes were smaller 3.4 ± 1.3 versus 6.0 ± 2.6 (p < 0.001), of lower grade (p = 0.011), earlier stage (p < 0.001) and has more mucinous histology than patients in the radical surgery group. There were no statistically significant differences between both groups regarding tumor recurrence or survival rates. Of 25 patients underwent fertility preservation surgery, 18/25 (72%) tried to get pregnant. 15/18 (83%) pregnancies were recorded, including 13 live births, 1 miscarriage, and 1 intrauterine fetal death. CONCLUSION: Fertility sparing surgery could be adequate alternative to radical surgery for young females with stage I EOC.

Gene expression profile in experimental frozen-thawed ovarian grafts treated with scaffold-base delivery of adipose tissue-derived stem cells

Abstract Purpose: Gelfoam scaffold is a feasible and safe non-invasive technique for Adipose tissue-derived Stem Cell (ASC)-delivery in the treatment of frozen-thawed ovarian autografts. This study seeks to analyze the genes expression profile of rat frozen-thawed ovarian autografts treated with scaffold-based delivery of adipose tissue-derived stem cells. Methods: Eighteen adult Wistar rats were distributed into three groups: Control (frozen-thawed only); Group 1 (Gl) and Group 2 (G2) (frozen-thawed ovaries treated with culture medium or ASC, respectively). Both treatments were performed immediately after autologous retroperitoneal transplant with scaffold-based delivery. The ovarian grafts were retrieved 30 days after transplantation. Quantitative gene expression (qPCR) for apoptosis, angiogenesis, and inflammatory cytokines (84 genes in each pathway) were evaluated by RT-PCR. Graft morphology (HE), apoptosis (cleaved-caspase-3), neoangiogenesis (VEGF), and cellular proliferation (Ki-67) were assessed. Results: In grafts treated with ASC, the apoptosis pathway showed the highest number of genes over-regulated — 49 genes — compared to inflammation cytokines and angiogenesis pathway — 36 and 23 genes respectively, compared to grafts treated with culture medium. Serpinb5 family was highlighted in the angiogenesis pathway and Cxcl6 in the inflammation cytokines pathway. In the apoptosis pathway, the most over-regulated gene was Cap-sasel4. ASC treatment promoted the reduction of cleaved caspase-3 in the theca internal layer and increased cell proliferation by Ki-67 in the granulosa layer without altering VEGF. A mild inflammatory infiltrate was observed in both groups. Conclusion: ASC therapy in rat frozen-thawed ovarian autografts promoted an abundance of genes involved with apoptosis and inflammatory cytokines without compromising the ovary graft morphology and viability for short time. Further studies are necessary to evaluate the repercussion of apoptosis and inflammation on the graft in the long term. HIGHLIGHTS The scaffold-based delivery therapy with adipose tissue-derived stem cells in the rat ovarian autografts seems to be the best option when compared to direct injection or systemic route. Ovarian grafts treated with adipose tissue-derived stem cells showed the highest number of genes over-regulated in the apoptosis pathway, compared to inflammation cytokines and angiogenesis pathway. Capsase14 was the most over-regulated gene in the apoptosis pathway. The treatment with adipose tissue-derived stem cells in ovarian grafts treated didn't compromise the ovary graft morphology and viability for short time.

Tumor limítrofe del ovario: revisión de un viejo conocido con nuevas propuestas terapéuticas / Ovarian borderline tumor: Review of an old acquaintance with new therapeutic proposals

Resumen ANTECEDENTES: Las pacientes con un tumor limítrofe del ovario pueden tratarse conservadoramente en etapas tempranas y con ello conseguir una supervivencia considerable. Las etapas avanzadas tienen un periodo libre de enfermedad prolongado, algunas con crecimiento de implantes peritoneales y recaída posterior a 10 años del tratamiento. OBJETIVO: Conocer cuál es el pronóstico de las pacientes con un tumor limítrofe del ovario, y su tratamiento en México y otros países. MÉTODOLOGÍA: Revisión sistemática de ensayos clínicos recientes registrados en las bases de datos de PubMed, Embase y Cochrane de artículos publicados en inglés y en español entre los años 2006 y 2021. Además, una revisión analítica de la experiencia acumulada en 10 años en la atención de pacientes con tumor limítrofe del ovario atendidas en la Unidad Médica de Alta Especialidad de Oncología del Centro Médico Nacional siglo XXI del Instituto Mexicano del Seguro Social, en la Ciudad de México y otros centros médicos de la República Mexicana. RESULTADOS: Se encontraron 62 artículos relacionados con los términos de búsqueda; de éstos, se descartaron 11 porque no eran artículos originales solo de tumores limítrofes del ovario y 4 porque el texto completo estaba escrito en idiomas diferentes al inglés y español. Uno más se eliminó porque sus conclusiones diferían del objetivo planteado y su sustento se consideró endeble. Al final se analizaron 41 artículos. CONCLUSIONES: Las posibilidades de atención quirúrgica de pacientes con tumor limítrofe del ovario, con preservación de la fertilidad, son altas pues su recurrencia es baja. Los tumores microinvasores mucinosos, con permeación vascular y linfática, tendrán mayor posibilidad de recaída a largo plazo. En general, su pronóstico de supervivencia, en cada etapa, es alto. La linfadenectomía retroperitoneal no está indicada en etapas tempranas de la enfermedad.

Abstract BACKGROUND: Patients with borderline ovarian tumor can be treated conservatively in early stages and thereby achieve considerable survival. Advanced stages have a prolonged disease-free period, some with peritoneal implant growth and relapse after 10 years of treatment. OBJECTIVE: To know the prognosis of patients with borderline ovarian tumor and its treatment in Mexico and other countries. METHODOLOGY: Systematic review of recent clinical trials registered in PubMed, Embase and Cochrane databases of articles published in English and Spanish between 2006 and 2021. In addition, an analytical review of the experience accumulated in 10 years in the care of patients with borderline ovarian tumor attended at the Oncology High Specialty Medical Unit of the XXI Century National Medical Center of the Mexican Social Security Institute, in Mexico City and other medical centers in the Mexican Republic. RESULTS: We found 62 articles related to the search terms; of these, 11 were discarded because they were not original articles only on ovarian borderline tumors and 4 because the full text was written in languages other than English and Spanish. One more was eliminated because its conclusions differed from the stated objective and its support was considered weak. In the end, 41 articles were analyzed. CONCLUSIONS: The chances of surgical care of patients with ovarian borderline tumor, with fertility preservation, are high because its recurrence is low. Mucinous microinvasive tumors, with vascular and lymphatic permeation, will have a higher chance of long-term relapse. In general, their prognosis for survival, at each stage, is high. Retroperitoneal lymphadenectomy is not indicated in early stages of the disease.

Aconselhamento em preservação da fertilidade de mulheres em idade reprodutiva com diagnóstico de câncer: revisão integrativa / Fertility preservation counseling for women of reproductive age diagnosed with cancer: an integrative review

Introdução: as terapêuticas oncológicas oferecem riscos de infertilidade, por isso a mulher com câncer em idade reprodutiva requer cuidados abrangentes sobre a oncofertilidade, já que, de 3% a 10% dos diagnósticos de câncer em todo o mundo ocorrem neste grupo. Com o aconselhamento pretende-se auxiliar essas mulheres quanto à fertilidade futura, e na tomada de decisão sobre preservar ou não a fertilidade. Objetivo: analisar as evidências científicas sobre o aconselhamento em preservação da fertilidade de mulheres em idade reprodutiva com diagnóstico de câncer, realizado antes de um tratamento oncológico. Método: revisão integrativa da literatura, com buscas realizadas nas bases de dados PubMed/ Medline, Cinahl, Lilacs, Embase, Scopus e Web of Science, no dia 12 de abril de 2022, sem restrição de tempo. Para a seleção dos estudos foi utilizada a plataforma Rayyan. Foram seguidas as etapas: definição do tema e da questão de pesquisa, amostragem, categorização, avaliação, interpretação e síntese do conhecimento científico. Resultados: foram identificados 897 documentos, 230 eram duplicados, 667 estudos foram analisados por meio da leitura de título e resumo e 29 artigos selecionados para a leitura na íntegra. Após essa leitura, foram incluídos seis artigos e um outro foi incluído a partir da identificação da lista de referências, compondo a amostra final de sete estudos. Os estudos confirmaram a importância do esclarecimento a respeito dos riscos de infertilidade advindos do tratamento oncológico e dos aspectos que envolvem as técnicas de preservação da fertilidade; como taxa de sucesso, taxa de gestação, custos, opções disponíveis e riscos associados. Pode-se observar que, para muitas mulheres após o diagnóstico, importa a possibilidade da maternidade, não necessariamente por gerar filhos, mas recorrendo a outras estratégias, como adoção e útero de substituição. Os estudos foram classificados como baixo risco de viés e seis estudos eram nível VI de evidência, e um de nível II. Conclusões: o aconselhamento em preservação da fertilidade é fundamental para esclarecer as consequências dos tratamentos oncológicos considerados gonadotóxicos, na perspectiva do cuidado centrado na pessoa. Atribui-se ao profissional de saúde o papel de esclarecer as nuances das técnicas de preservação da fertilidade disponíveis e apoiar as mulheres no processo de tomada de decisão. Além disso, o uso de materiais educativos e auxiliares de decisão contribuem na transmissão das informações e minimizam o conflito de decisão sobre preservar ou não a fertilidade

Introduction: Oncological therapies offer risks of infertility, so women with cancer at reproductive age require comprehensive care about oncofertility, since 3% to 10% of cancer diagnoses worldwide occur in this group. With counseling we intend to help these women regarding future fertility, and in making a decision about preserving or not fertility. Objective: analyze the scientific evidence on fertility preservation counseling for women of reproductive age diagnosed with cancer, performed prior to oncologic treatment. Method: integrative literature review, with searches conducted in the PubMed/ Medline, Cinahl, Lilacs, Embase, Scopus and Web of Science databases on April 12, 2022, without time restriction. The Rayyan platform was used to select the studies. The steps were followed: definition of the theme and research question, sampling, categorization, evaluation, interpretation and synthesis of scientific knowledge. Results: a total of 897 documents were identified, 230 were duplicates, 667 studies were analyzed by reading the title and abstract, and 29 articles were selected for reading in full. After this reading, six articles were included and another one was included from the identification of the reference list, composing the final sample of seven studies. The studies confirmed the importance of clarifying the infertility risks arising from cancer treatment and the aspects involving fertility preservation techniques, such as success rate, pregnancy rate, costs, available options and associated risks. It can be observed that, for many women after the diagnosis, the possibility of motherhood matters, not necessarily by generating children, but by resorting to other strategies, such as adoption and surrogate uterus. The studies were classified as low risk of bias and six studies were level VI evidence, and one was level II. Conclusions: fertility preservation counseling is essential to clarify the consequences of oncologic treatments considered gonadotoxic, from the perspective of person-centered care. The healthcare professional was assigned the role of clarifying the nuances of available fertility preservation techniques and supporting women in the decision-making process. In addition, the use of educational materials and decision aids contribute to the transmission of information and minimize the conflict of decision about whether or not to preserve fertility

Pasado presente y futuro de la estimulación ovárica en el tratamiento de la infertilidad / Past, present and future of ovarian stimulation in infertility treatment

La mejor comprensión de la fisiología reproductiva y la disponibilidad de más y mejores recursos diagnóstico/terapéuticos permiten individualizar la estimulación ovárica y hacerla más efectiva (mejores resultados), eficiente (en menos tiempo y con dosis más bajas), segura (con menos y más leves complicaciones), cómoda (menos molestias y autonomía) y accesible (para más personas, a menores costos). Con tecnología de ADN recombinante se dispone ahora de todas las gonadotrofinas e incluso algunas con formas moleculares modificadas para aumentar la duración de acción y disminuir el número de inyecciones. El esquema más utilizado es el de FSH recombinante junto con antagonistas de GnRH. Hay indicaciones específicas para agregar LH o coadyuvantes como hGH o andrógenos transdérmicos. La estimulación ovárica, además de infertilidad, se usa para la preservación de la fertilidad. Cada vez se implementan más estrategias como acumulación de óvulos, esquemas no convencionales (random start, DuoStim y otros) junto a vitrificación ovular, estudio genético preimplantatorio, transferencias embrionarias diferidas y la investigación continúa. Se pronostican mejoras en un futuro próximo, entre otras antagonistas por vía oral y estudio genético de pacientes para diagnosticar mutaciones o polimorfismos de gonadotrofinas y sus receptores. Aunque ya es factible individualizar la estimulación y volverla más efectiva, segura y amigable, así como ofrecer otras opciones a pacientes de mal pronóstico.

Due to an increased understanding of reproductive physiology and to the availability of more and better diagnostic/therapeutic agents, ovarian stimulation through individualization, has become more effective (improved results), efficient (shorter span and lower doses), safe (less and milder complications), comfortable (less discomfort and dependance) and affordable (for more people at lower cost). All gonadotrophins are now available by recombinant DNA technology, including some modified compounds for specific purposes such as longer action and fewer injections. The most popular ovarian regime uses recombinant FSH and GnRH antagonist. There are precise indications for adding LH or adjuncts like hGH or transdermal androgens. Besides infertility, ovarian stimulation is also indicated for fertility preservation. Strategies like oocyte accumulation, non-conventional stimulation protocols (random start, DuoStim and others), oocyte vitrification, preimplantation genetic testing, freeze-all, deferred embryo transfer for particular cases are becoming popular, and the research still goes on. Future advances like oral GnRH antagonists, and the study of mutations and polymorphisms for gonadotropins and its receptors are foreseen. Today through individualization, ovarian stimulation is safe, effective and friendly, also we can offer good options to bad prognosis patients

Ex vivo retrieval of mature oocytes for fertility preservation in a patient with bilateral borderline ovarian tumor / Recuperação ex vivo de oócitos maduros para preservação da fertilidade em paciente com tumor ovariano borderline bilateral

Abstract We report a case of ultrasound-guided ex vivo oocyte retrieval for fertility preservation in a woman with bilateral borderline ovarian tumor, for whom conventional transvaginal oocyte retrieval was deemed unsafe because of the increased risk of malignant cell spillage. Ovarian stimulation with gonadotropins was performed. Surgery was scheduled according to the ovarian response to exogenous gonadotropic stimulation; oophorectomized specimens were obtained by laparoscopy, and oocyte retrieval was performed ~ 37 hours after the ovulatory trigger. The sum of 20 ovarian follicles were aspirated, and 16 oocytes were obtained.We performed vitrification of 12 metaphase II oocytes and 3 oocytes matured in vitro. Our result emphasizes the viability of ex vivo mature oocyte retrieval after controlled ovarian stimulation for those with high risk of malignant dissemination by conventional approach.

Resumo Relatamos um caso de obtenção ex vivo de óvulos, guiada por ultrassonografia, para preservação da fertilidade em uma mulher com tumor ovariano borderline bilateral, para quem a recuperação transvaginal convencional foi considerada insegura, devido ao aumento do risco de disseminação de célulasmalignas. Foi realizada estimulação ovariana com gonadotrofinas. A cirurgia foi agendada de acordo com a resposta ovariana à estimulação gonadotrófica exógena; após ooforectomia por laparoscopia, ~ 37 horas após a maturação folicular, procedeu-se à recuperação extracorpórea de oócitos. Umtotal de 20 folículos ovarianos foi aspirado e 16 complexos cumulus foramobtidos, resultando na vitrificação de 12 oócitos maduros e de 3 oócitos imaturos amadurecidos in vitro. Nosso resultado enfatiza a viabilidade da recuperação ex vivo de oócitos maduros após estimulação ovariana controlada para mulheres com alto risco de disseminação maligna pela captação oocitária realizada convencionalmente pela via transvaginal.

Conocimientos y prácticas actuales sobre cáncer de mama, preservación de la fertilidad y embarazo. Encuesta a los miembros de la Sociedad Argentina de Mastología / Knowledge and current practices on breast cancer, fertility preservation and pregnancy. Survey to the members of the Argentine Society of Mastology

Introducción: debido al retraso de la maternidad, es probable que las mujeres jóvenes con diagnóstico de cáncer de mama (CM) no hayan completado su proyecto de maternidad al momento del diagnóstico y estén interesadas en su fertilidad futura y podrían enfrentarse también a un cáncer de mama asociado al embarazo. El objetivo del trabajo fue analizar la práctica actual, de los miembros de la Sociedad Argentina de Mastología (SAM), sobre preservación de la fertilidad y embarazo. Material y método: se realizó una encuesta por correo electrónico. Respondieron 213 miembros. Resultados: la frecuencia con la que abordan el impacto del tratamiento oncológico en la fertilidad de las pacientes jóvenes y las derivan, fue "siempre" y "casi siempre" en 84,4% y 74,5% respectivamente. El 73,6% afirmó que el embarazo luego del CM no empeora el pronóstico. El 70,1% consideró seguro el uso de radiocoloides para identificar el ganglio centinela durante el embarazo. Encontramos una diferencia significativa en las respuestas de los profesionales pertenecientes a una UM. Conclusiones: el nivel de conocimiento es similar al de otras encuestas. La pertenencia a una unidad de mastología se asoció a un mejor nivel de actualización. Es necesario seguir trabajando en la capacitación de los profesionales.

Introduction: due to delayed motherhood, Young women diagnosed with breast cancer (BC) are likely to have not competed their maternity Project at the time of diagnosis, are interested in future fertility and may also face pregnancy-associated breast cancer. The aim of this study was to analyze the current practice of the Argentine Society of Mastology (SAM) members, on fertility preservation and pregnancy. Material and method: an email survery was conducted 231 members responded. Results: the frequency with which respondentes discuss the impact of cancer treatment of fertility among Young patients and referral was "always" and "almost always", 84.4% and 74.5% respectively. 73.6% considered pregnancy after BC does not worsen the prognosis. 70.1% used radiocoloids to identify sentinel node during pregnancy. We found a significant difference in the responses of professionals belonging to a Breast Unit. Conclusions: the level of knowledge is similar to that of other surverys. Working within a Breast Unit was associated with a better level of knowledge. Further work is needed in the training of professionals.

Fertility preservation in breast cancer with oral progestin: is it an option? A pilot study / Preservação da fertilidade com progestágeno oral em pacientes com câncer de mama: é uma opção? Estudo-piloto

ABSTRACT Objective To compare the effectiveness of oral progestins and injectable gonadotropin-releasing hormone antagonist medication in cancer fertility preservation in patients with breast cancer. Methods A cross-sectional study with 40 breast cancer patients submitted to cancer fertility preservation, who were divided into two groups according to histochemical analysis of progesterone receptors to define luteinizing hormone block: if positive, use of gonadotropin-releasing hormone antagonist, if negative, use of oral progestins. The mean age, medication days, antral follicle count, number of oocytes in metaphase II and the occurrence of ovarian hyperstimulation syndrome were compared. Results A total of 20 patients both in the group using gonadotropin-releasing hormone antagonist, and in the group with oral progestins, respectively, had a mean age of 33.9 (32-35.8) and 33.8 (32-35.6) years; days of medications of 11 (9.7-12.3) and 12.8 (11.6-13.9), p=0.037; antral follicle count of 9 (7.11-12) and 8.5 (6-11.9), p=0.370; metaphase II oocyte number of 4 (2.1-9.8) and 7.5 (3.1-10), p=0.348; and ovarian hyperstimulation syndrome of 2 (10%) and 5 (25%) cases, p=0.212. Conclusion The use of oral progestins, in spite of requiring longer treatment time, is effective in relation to the protocol with gonadotropin-releasing hormone antagonist, and offers greater comfort at a lower cost in breast cancer patients with negative progesterone receptors, submitted to cancer fertility preservation.

RESUMO Objetivo Comparar a efetividade dos progestágenos orais em relação à medicação injetável antagonista de hormônio liberador de gonadotrofina na preservação da fertilidade oncológica de pacientes com câncer de mama. Métodos Estudo transversal com 40 pacientes com câncer de mama submetidas à preservação da fertilidade oncológica, que foram divididas em dois grupos, conforme análise histoquímica dos receptores de progesterona, para definir o bloqueio de hormônio luteinizante: se positivos, uso de antagonista de hormônio liberador de gonadotrofina; se negativos, uso de progestágenos orais. Comparou-se média de idade, dias de medicações, contagem de folículos antrais, número de oócitos em metáfase II e ocorrência de síndrome do hiperestímulo ovariano. Resultados Vinte pacientes, tanto no grupo com uso de antagonista de hormônio liberador de gonadotrofina, quanto no grupo com progestágenos orais, respectivamente, apresentaram média de idade de 33,9 (32-35,8) e 33,8 (32-35,6) anos; 11 (9,7-12,3) e 12,8 (11,6-13,9) de dias de medicações com p=0,037; contagem de folículos antrais de 9 (7,11-12) e 8,5 (6-11,9), com p=0,370; número de oócitos metáfase II de 4 (2,1-9,8) e 7,5 (3,1-10), com p=0,348, e síndrome do hiperestímulo ovariano de 2 casos (10%) e 5 casos (25%), com p=0,212. Conclusão O uso de progestágenos orais, apesar de necessitar de maior tempo de tratamento, é efetivo em relação ao protocolo com antagonista de hormônio liberador de gonadotrofina e oferece maior conforto com menor custo em pacientes com câncer de mama com receptores de progesterona negativos, submetidas à preservação da fertilidade oncológica.

GnRH-a combined fertility-sparing re-treatment in women with endometrial carcinoma or atypical endomertial hyperplasia who failed to oral progestin therapy / 中华妇产科杂志

Objective:To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy.Methods:Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly.Results:(1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m 2 (range: 18.9-39.5 kg/m 2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions:GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.

Practical recommendations for the management of benign adnexal masses / Recomendações práticas para o tratamento de massas anexiais benignas

Abstract Objective To performa comprehensive review to provide practical recommendations regarding the diagnosis and treatment of benign adnexal masses, as well as information for appropriate consent, regarding possible loss of the ovarian reserve. Methods A comprehensive review of the literature was performed to identify the most relevant data about this subject. Results In total, 48 studies addressed the necessary aspects of the review, and we described their epidemiology, diagnoses, treatment options with detailed techniques, and perspectives regarding future fertility. Conclusions Adnexal masses are extremely common. The application of diagnosis algorithms is mandatory to exclude malignancy. A great number of cases can bemanaged with surveillance. Surgery, when necessary, should be performed with adequate techniques. However, even in the hands of experienced surgeons, there is a significant decrease in ovarian reserves, especially in cases of endometriomas. There is an evident necessity of studies that focus on the long-term impact on fertility.

Resumo Objetivo Realizar uma revisão abrangente para fornecer recomendações práticas sobre o diagnóstico e tratamento demassas anexiais benignas, bemcomo informações para um consentimento adequado com relação à possível perda da reserva ovariana. Métodos Uma revisão abrangente da literatura foi realizada para identificar os dados mais relevantes sobre o assunto. Resultados No total, 48 estudos abordaram os aspectos necessários da revisão, e descrevemos sua epidemiologia, diagnósticos, opções de tratamento com técnicas detalhadas, e perspectivas sobre fertilidade futura. Conclusões As massas anexiais são extremamente comuns. A aplicação de algoritmos de diagnóstico é obrigatória para excluiramalignidade. A maioria dos casos pode ser manejada conservadoramente. A cirurgia, quando necessária, deve ser realizada com técnicas adequadas. No entanto, mesmo nas mãos de cirurgiões experientes, há diminuição significativa da reserva ovariana, principalmente nos casos de endometriomas. Há uma evidente necessidade de estudos que enfoquemo impacto das massas anexiais benignas na fertilidade em longo prazo.