Francesca Salvagno

Cancer and fertility preservation: International recommendations from an expert meeting

In the last years, thanks to the improvement in the prognosis of cancer patients, a growing attention has been given to the fertility issues. International guidelines on fertility preservation in cancer patients recommend that physicians discuss, as early as possible, with all patients of reproductive age their risk of infertility from the disease and/or treatment and their interest in having children after cancer, and help with informed fertility preservation decisions. As recommended by the American Society of Clinical Oncology and the European Society for Medical Oncology, sperm cryopreservation and embryo/oocyte cryopreservation are standard strategies for fertility preservations in male and female patients, respectively; other strategies (e.g. pharmacological protection of the gonads and gonadal tissue cryopreservation) are considered experimental techniques. However, since then, new data have become available, and several issues in this field are still controversial and should be addressed by both patients and their treating physicians.In April 2015, physicians with expertise in the field of fertility preservation in cancer patients from several European countries were invited in Genova (Italy) to participate in a workshop on the topic of “cancer and fertility preservation”. A total of ten controversial issues were discussed at the conference. Experts were asked to present an up-to-date review of the literature published on these topics and the presentation of own unpublished data was encouraged. On the basis of the data presented, as well as the expertise of the invited speakers, a total of ten recommendations were discussed and prepared with the aim to help physicians in counseling their young patients interested in fertility preservation.Although there is a great interest in this field, due to the lack of large prospective cohort studies and randomized trials on these topics, the level of evidence is not higher than 3 for most of the recommendations highlighting the need of further research efforts in many areas of this field. The participation to the ongoing registries and prospective studies is crucial to acquire more robust information in order to provide evidence-based recommendations.

Live birth after orthotopic grafting of autologous cryopreserved ovarian tissue and spontaneous conception in Italy

OBJECTIVE To describe a live birth obtained in Italy after autologous orthotopic transplantation of cryopreserved ovarian cortical tissue. DESIGN Case report. SETTING University department of gynecology and obstetrics, reproductive medicine and IVF unit. PATIENT(S) A 29-year-old patient affected by β-thalassemia (intermedia phenotype) who underwent chemotherapy and bone marrow transplantation at age 21 years, resulting in a complete precocious ovarian failure. INTERVENTION(S) Before being treated with chemotherapy (busulfan, cyclophosphamide, and cyclosporine) for bone marrow transplantation, the patient underwent laparoscopic sampling of ovarian cortical tissue that was frozen and cryopreserved in liquid nitrogen. Eight years later, the ovarian tissue was thawed and grafted during laparoscopy at an orthotopic site. MAIN OUTCOME MEASURE(S) Ultrasound and endocrine monitoring of the postgrafting restoration of ovarian function; conception, pregnancy, and live birth. RESULT(S) Three months after grafting, the decrease of circulating FSH levels and the parallel increase of E(2) levels demonstrated ovarian function restoration, which was confirmed by bidimensional ultrasound and color Doppler examinations. After some ovulatory cycles, the patient spontaneously conceived 16 months after transplantation. After 39 weeks of uneventful gestation, a healthy girl weighing 3,970 g was born. CONCLUSION(S) Autologous grafting of cryopreserved ovarian cortex at an orthotopic site may allow ovarian function restoration, spontaneous conception, and birth of a healthy baby.

Obesity and female malignancies

Obesity increases the risk of endometrial and ovarian cancer, and oestrogen receptor (ER)-progesterone receptor (PR)-positive postmenopausal breast cancer. A modest positive association between body mass index (BMI) and cervical cancer has also been found. By contrast, an inverse correlation between BMI and premenopausal breast cancer exists. Endogenous sex hormones, insulin resistance/hyperinsulinaemia, adipokines, cytokines and chronic inflammation, among other factors, may be involved in the promotion of cancer in obese patients. Obesity is also associated with an increased risk of cancer recurrence and mortality most likely due to suboptimal treatment and/or co-morbidities. It is recommended that chemotherapy doses be calculated on the actual body weight and that radical surgery be performed as in non-obese patients. The high risk of peri-operative complications may be reduced by optimizing preoperative clinical conditions. As part of cancer prevention, obese women should be encouraged to adopt healthy lifestyles leading to weight loss and to undergo regular cancer screening.

Oocyte Cryostorage to Preserve Fertility in Oncological Patients

Thanks to the progress in oncostatic treatments, young women affected by cancer have a fairly good chance of surviving the disease and leading a normal post-cancer life. Quite often, however, polychemiotherapy and/or radiotherapy can induce ovarian damage and significantly reduce the content of follicles and oocytes inside the ovary, thus predisposing the patient to menstrual disorders, infertility, and precocious menopause. Several techniques have been proposed to preserve fertility in these patients; among them oocyte collection and cryopreservation prior to the oncostatic treatment has been widely applied in the last decade. The proper indications, the permitting conditions, the available hormonal stimulation protocols, as well as the effectiveness and limits of this option will be discussed herein, with a comprehensive and up-to-date review of the two techniques commonly used to cryostore oocytes, the slow-freezing technique and the vitrification technique.

Fertility Preservation Methods in Breast Cancer

Thanks to the recent advances in reproductive medicine, more and more young women with breast cancer may be offered the possibility of preserving their fertility. Fertility can be endangered by chemotherapy, by treatment duration and by patient’s age at diagnosis. The currently available means to preserve a young woman’s fertility are pharmacological protection with gonadotrophin-releasing hormone analogues during chemotherapy, and ovarian tissue or oocyte/embryo freezing before treatment. New future venues, including in vitro maturation, will improve the feasibility and efficacy of the fertility preservation methods in breast cancer patients.

Fertility preservation program before ovarotoxic oncostatic treatments: role of the psychological support in managing emotional aspects.

Abstract Fertility preservation programs (FPPs) based on oocyte or ovarian tissue cryostorage may be offered to women facing oncostatic treatments at risk of precocious ovarian insufficiency. The way in which FPPs are presented to patients affects their decision to join them. We studied herein 48 young women to whom a FPP was proposed, aiming at clarifying the emotional aspects involved. A psychologist attended the consultations in which the FPP was offered to patients; at the end of the talk, a questionnaire was administered and a semi-structured interview was carried out. Finally, the STAI test was administered to measure trait (TAI) and state (SAI) anxiety, both immediately after consultation, and later on, when patients returned home. We observed that the possibility to join a FPP implied important emotional aspects, and that the presence of a psychologist was helpful to integrate technical information and emotions as well as to reduce trait and state anxiety levels. Our study suggests that the presence of a psychologist during the meeting in which a FPP is offered improves communication between doctors and patients, and helps these women to get a full awareness before choosing to join the FPP. Chinese abstract 生殖力保护项目(FPPs)是基于为面临制瘤治疗存在卵巢功能早衰风险的患者 提供卵母细胞或卵巢组织冻存。在此，我们对48位建议进行FPP的妇女进行研究，目的是明确情绪方面的关联性。一位心理学家参加了建议进行FPP的患者们的会诊咨询，在谈话最后，进行一个调查问卷和一个半结构的会谈。最后，STAI 测试测量显著性(TAI)及焦虑状态(SAI)，这2项都是会诊结束后立即进行，和后来患者返家后。我们观察到参加FPP的可能性隐含重要的情绪因素，心里学家的参与有助于技术信息与情绪的结合降低焦虑的显著性及程度水平。我们的研究提示在FPP会诊中，心理专家的参与可改善医患交流，帮助这些妇女在选择FPP前充分知情。

Come preservare la fertilità nel paziente oncologico

SommarioGrazie ai progressi compiuti dall’oncologia negli ultimi decenni, oggi le percentuali di guarigione dei bambini e dei giovani adulti affetti da tumore si attestano intorno all’80%. Tuttavia, anche con i moderni protocolli di terapia oltre il 50% dei giovani pazienti sviluppa nel tempo infertilità, nella maggior parte dei casi dovuta a danno gonadico diretto. La proposta di preservare la fertilità, in un momento così critico della vita, diviene quindi essenziale di fronte a trattamenti che possono ledere in modo irreversibile la capacità fecondante dell’individuo. Esistono per entrambi i sessi metodi consolidati e approcci ancora sperimentali per salvaguardare le potenzialità procreative cui si deve ricorrere nel contesto dell’inquadramento oncologico iniziale poiché, tuttora, non esistono parametri per poter prevedere con certezza l’entità dell’effetto gonadotossico dei vari trattamenti oncologici. I problemi attualmente emergenti sono relativi alla preservazione della fertilità nei prepuberi e su tale aspetto si sta soprattutto orientando la ricerca biomedica.

Fertility Preservation, ART, and Breast Cancer

Interest in fertility preservation for young women affected by breast cancer facing gonadotoxic therapies is increasing according to enhanced long-term survival rates of these patients. Prompt counseling about different fertility preservation options should be offered to all young girls and women at high risk of ovarian insufficiency and infertility because of chemotherapy.

A slowly reabsorbed, echogenic surgical thread provides a long-lasting ultrasound- detectable marker of grafted ovarian tissue

This communication reports a novel technical solution for the orthotopic transplant of cryostored-thawed ovarian tissue. The described technique was applied to three young women with iatrogenic ovarian failure. An echogenic thread that is reabsorbed after 6 months was used to fasten the thawed ovarian small fragments before grafting them onto the atrophic ovary. This technical solution made it possible to avoid the loss of small tissue pieces during laparoscopic grafting as well as to precisely localize the grafted tissue by transvaginal ultrasound during the following months. The precise localization of the grafted tissue was particularly helpful when its revascularization and functional recovery were followed up using, respectively, colour Doppler and transvaginal follicle growth examination. In conclusion, the use of a slowly reabsorbed, ultrasound-detectable surgical thread as an ultrasound-detectable marker able to improve the localization of the exact site at which ovarian tissue was grafted is proposed.

La crioconservazione del tessuto gonadico femminile

RiassuntoLa crioconservazione del tessuto ovarico è una tecnica innovativa per preservare la fertilità delle giovani pazienti a rischio di insufficienza ovarica a causa di trattamenti oncostatici gonadotossici oppure per cause benigne quali patologie genetiche, autoimmuni od ovariche. Il tessuto ovarico crioconservato, dopo scongelamento, può essere reimpiantato orto elo eterotopicamente oppure posto in coltura per ottenere la maturazione in vitro dei follicoli primordiali. Ad oggi nel mondo sono nati 17 bambini da ritrapianto ortotopico di tessuto ovarico. Il primo e unico caso di bambino nato con questa tecnica in Italia è stato recentemente ottenuto dalla nostra équipe.