Oncofertility for gynecologic and non-gynecologic cancers: Fertility sparing in young women of reproductive age

About ten percent of all female cancer survivors is younger than 40 years of age. For these young women the primary goal is to ensure the highest possibility of cure and to maintain the reproductive functions as well. Oncofertility is a new concept including both oncology and reproductive medicine. By this recently defined concept young women will have maximal chance to make an optimal decision without any significant impact and delay in oncologic outcome. Oncofertility concept could be applied for genital cancer as well as non-genital cancer of reproductive age. Currently sperm and embryo banking are the standard methods used for young patients with cancer whose future fertility is under risk. In contrary oocyte banking, ovarian tissue cryopreservation are all controversial procedures and still accepted as experimental by many authors although American Society of Reproductive Medicine (ASRM) consideres oocyte cryopreservation “no longer experimental”. For genital cancers procedures for oncofertility depends on the type of the cancer and the treatment of choice. In this review the current data and concepts regarding oncofertility concept including the gynecologic oncologic perspective is reviewed.     

Turner Syndrome and Fertility

Turner syndrome (TS) is tightly associated with hypergonadotropic hypogonadism and ovarian dysgenesis, typically resulting in infertility in the great majority of patients. Therefore females with TS are usually treated with female sex steroids from 11–12 years of age until the normal age of natural menopause of around 53–54 years of age. Infertility is rated among females with TS as a distressing concern and a detractor from a good quality of life. Options for motherhood for females with TS has expanded during recent years. Originally, only adoption was an option, unless of course for the small minority of TS females that still has ovarian function and are capable of achieving pregnancy through normal means. Oocyte donation has become the mainstream option in many countries and seems to work well, especially if patients have been treated with optimal estrogen and gestagen for a prolonged time before the intervention. It comes with an increased risk of cardiovascular complications and TS oocyte donation pregnancies are viewed as high risk pregnancies necessitating increased vigilance. Oocyte cryopreservation of own oocytes is also becoming an option in a select group of TS and has special challenges. Ovarian tissue cryopreservation is a promising new techniques that has been applied successfully in children with cancer. Currently, several trials are running around the world evaluating this techniques in TS. The genetics and genomics behind the ovarian dysgenesis seen in TS is not understood, but new studies have elucidated global changes in DNA methylation and RNA expression in blood from persons with TS and it is likely that similar changes are present in the ovaries. We still, however, need more thorough research to fully uncover the genetic background of ovarian failure in TS. Gene expression studies and methylation analysis from ovarian TS tissues still needs to be performed.     

Testicular function and fertility preservation in male cancer patients

The testis has been shown to be highly susceptible to the toxic effects of cancer therapy at all stages of life. Young cancer survivors are approximately half as likely as their siblings to sire a pregnancy. Radiation therapy to the testes and high cumulative dose of alkylating agents are the major factors decreasing the probability of fertility. This review aims to present an overview of the current state of knowledge in mechanisms how human spermatogonia proliferate and differentiate and how cancer therapy affects germ cells, what are the options for fertility preservation and what are the clinical risks and limitations related to such procedures. This area of research is discussed in the context of the potential future options that may become available for preserving fertility in male cancer patients.     

Fertility preservation for prepubertal boys: are we ready for autologous grafting of cryopreserved immature testicular tissue?

Fertility preservation in prepubertal boys is a matter that has been gaining ground fast during the past 20 years. As the life expectancy for childhood cancer survivors continues to increase (5-year survival rate > 80%), and as the risk of permanent infertility in adulthood is still high with current treatment options, offering a testicular biopsy to cryopreserve immature testicular tissue (ITT) containing spermatogonial stem cells is now recommended as an experimental option for fertility preservation.Transplantation of cryopreserved testicular prepubertal tissue fragments back to the cured patient appears to be one of the most feasible and promising techniques for fertility restoration. In 2019, the birth of a healthy female baby rhesus monkey after intracytoplasmic sperm injection using spermatozoa recovered from frozen-thawed ITT autografts fueled the hopes of translating the technique to humans.While gonadal tissue autotransplantation has already been successfully achieved in clinical practice for females, it has never been attempted in males to date.In this work, we review acquired knowledge on ITT transplantation in animal models and share our vision on the remaining challenges to autograft currently banked human ITT within pilot clinical trials in the near future.     

Cancer Survivorship,a Unique and Growing Cohort in Medical Practice: Radiology Perspective

The unique medical and psychologic burdens of cancer survivorship have only recently been recognized. This rapidly expanding cohort of patients will be seen increasingly by non-oncology physicians who must consider medical issues related to their cancer or its therapy for any presenting symptoms. Appropriate use of clinical imaging is essential for diagnosing treatment-related complications, recurrent tumor, or emergence of second primaries. This article will review clinical imaging in common medical problems uniquely found in cancer survivors.     

Insights into sperm cell motility signaling through sNHE and the CatSpers

Successful natural reproduction normally requires vigorously motile spermatozoa. Using a signal peptide trapping strategy, we identified two new genes, a putative sperm Na⁺/H⁺ exchanger (sNHE) and the putative cation channel CatSper2, with unique and essential roles in sperm motility. Disruption of the sNHE or CatSper2 genes in mice caused male infertility due to immotile spermatozoa or failed motility hyperactivation, respectively, without other apparent abnormalities. The immotility phenotype of the sNHE null spermatozoa appears to result from an intimate association of sNHE and the atypical adenylyl cyclase (sAC), while a failure of calcium entry requiring an apparent CatSper1 and -2 heteromeric ion channel correlates with a hyperactivation defect in these null animals. The specific expression of sNHE and the CatSpers in spermatozoa and their required function in cell motility make them excellent potential targets for the development of novel male contraceptives.     

Inflammatory bowel diseases and human reproduction: A comprehensive evidence-based review

To evaluate the effects of inflammatory bowel diseases (IBDs) on human reproduction, we reviewed the current literature using a systematic search for published studies (articles and/or abstracts) without limits for English language. We searched on Medline (through PubMed), the Institute for Scientific Information, the Web of Science and the websites for the registration of controlled trials (http://controlled-trials.com/). Bibliographies of retrieved articles, books, expert opinion review articles and reviewed bibliographies from subject experts were manually searched. Titles and abstracts were screened initially, and potential relevant articles were identified and reviewed. Whenever possible, data were analyzed by comparing IBD patients vs healthy controls, and patients with active IBDs vs those with disease in remission. The effects of IBDs on female fertility, fertility in infertile couples, pregnancy and male infertility were examined separately. Patients with IBDs in remission have normal fertility. At the moment, there is no established guideline for the preservation of fertility in women with IBD undergoing surgery. Further data are needed regarding guidelines for the management of these patients. Data regarding IBDs and infertility are currently completely lacking. Considering the prevalence of intestinal pathology in young adults of childbearing age, this field is of great scientific and clinical interest, opening up important future perspectives. Another important and as yet unexplored point is the response to treatments for infertility in patients with IBDs. In particular, the question is whether the reproductive outcomes (clinical and biological) can be influenced by the IBD of one of the partners. The goals for successful reproductive outcomes in IBD population are correct counseling and disease remission. IBDs significantly affect several reproductive aspects of human (female, male, couple) reproduction. Further data are needed to develop guidelines for the clinical management of subjects of reproductive age with IBDs.     

Pancreatic Disease in Children and Adolescents

Many childhood pancreatic disorders are rare, although they can represent significant and potentially severe disease. The spectrum of disease is very broad, ranging from the complex and bizarre congenital anomalies to the more typical acquired causes (eg, drug-induced pancreatitis or trauma injury). Genetics appears to play a major role in many childhood pancreas diseases, unlike adults where alcohol is a major factor. Nevertheless, there are similarities, and most of the disorders discussed here can be found in both the pediatric and adult age groups. Some of these disorders may be evolving and may be seen in both young and older patients. Newer imaging modalities and therapeutic endoscopy continue to be studied, although their ultimate role and utility in children has yet to be fully elucidated.