Fertility Preservation In Children Research Articles

Clinicopathological pattern and outcome of pediatric malignant ovarian germ cell tumors: South Egypt Cancer Institute experience.

Malignant ovarian germ cell tumors (MOGCTs) are rare and represent 1-1.5% of all cancers in children and adolescents. The aim of this study is to analyze the clinicopathological pattern at presentation and management and outcome of MOGCTs in children and adolescents. Retrospective study included all girls diagnosed with MOGCTs between January 2005 and January 2015 in Pediatric and Surgical Oncology Departments at South Egypt Cancer Institute, Assiut University. Data were collected from patients' records including initial presentation, diagnosis (tumor markers and imaging), surgical staging and pathologic types. Management (surgical and chemotherapy details) and outcomes were also analyzed. Forty girls aged between 4 to 17years (mean age of 9.5years) with diagnosis of MOGCTs during study period were included. The most common presenting symptoms and signs were abdominal swelling, abdominal pain, and pelvic mass. Precocious puberty was noted in two patients. Surgical interventions in most patients were unilateral salpingo-oophorectomy (n=20). Early stages I and II were reported in 15 and 12 patients respectively, while 10 patients had stage-III disease and 3 patients had stage IV. Yolk sac tumors were reported in 27.5% of patients. All patients were treated with platinum based chemotherapy. The 7-year overall survival was higher for patients with early stages (I and II) compared with advanced stages (III and IV) (100% versus 30.8% respectively. Early presentation with appropriate management using fertility sparing surgery and platinum-based chemotherapy provides excellent survival with fertility preservation in children and adolescents. Based on the lower survival of patients with advanced disease, efforts should focus on increasing the awareness in the community of the importance of early diagnosis of ovarian tumors. II (retrospective study).

State-of-the-art fertility preservation in children and adolescents undergoing haematopoietic stem cell transplantation: a report on the expert meeting of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) in Baden, Austria, 29-30 September 2015.

Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant diseases. Decrease in short-term complications has substantially contributed to increased survival. Therefore long-term sequelae are reaching the focus of patient care. One of the most important risks of stem cell transplant survivors is infertility. As well as in the field of allo-HSCT also the field of reproductive medicine has achieved substantial advances to offer potential options for fertility preservation in both boys and girls. Access to these procedures as well as their financing differs significantly throughout Europe. As all European children and adolescents should have the same possibility, the Paediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation organised an expert meeting in September 2015. This manuscript describes the recommendations for the diagnosis and pre-emptive procedures that should be offered to all children and adolescents in Europe who have to undergo an allo-HSCT.

Klinefelter syndrome and fertility: sperm preservation should not be offered to children with Klinefelter syndrome.

Should fertility preservation be offered to children with Klinefelter syndrome (KS)? Current evidence shows that fertility preservation should not be offered to adolescents with KS younger than 16 years because of lower retrieval rates for germ cells by testicular sperm extraction (TESE) compared with retrieval rates for adolescents and adults between 16 and 30 years. KS, the most common chromosomal disorder in men leading to non-obstructive azoospermia, is caused by the presence of at least one additional X chromosome. The onset of puberty in adolescents with KS leads to progressive degeneration of the testicular environment. The impact of the subsequent tissue degeneration on fertility potential of patients with KS is unknown, but in previous literature it has been suggested that fertility preservation should be started in adolescents as early as possible. However spermatozoa can be found by TESE in about 50% of adults with KS despite severe testicular degeneration. This review discusses the current evidence for fertility preservation in children and adolescents and possible prognostic markers for fertility treatment in KS. An extensive literature search was conducted, searching Pubmed, Embase, Cinahl and Web of Science from origin until April 2016 for 'Klinefelter syndrome' and 'fertility' and various synonyms. Titles and abstracts have been scanned manually by the authors for eligibility. In total 76 studies were found to be eligible for inclusion in this review. Information from the papers was extracted separately by two authors. Various studies have shown that pre-pubertal children with KS already have a reduced number of germ cells despite a normal hormonal profile during childhood. The presence of spermatozoa in the ejaculate of adolescents with KS is extremely rare. Using TESE, the retrieval rates of spermatozoa for adolescents younger than 16 years old are much lower (0-20%) compared with those for adolescents and young adults between 16 and 30 years old (40-70%). Although spermatogonia can be found by TESE in about half of the peri-pubertal adolescents, there are currently no clinically functional techniques for their future use. Children and adolescents need to be informed that early fertility preservation before the age of 16 cannot guarantee fertility later in life and may even reduce the chances for offspring by removing functional immature germ cells which may possibly develop into spermatozoa after puberty. Furthermore, except for the age of patients with KS, there are no identified factors that can reliably be used as a predictive marker for fertility preservation. Most of the evidence presented in this review is based on studies including a small number of adolescents with KS. Therefore, the studies may have been underpowered to detect clinically significant differences for their various outcomes, especially for potential predictive factors for fertility preservation, such as hormone levels. Furthermore, the population of patients with KS diagnosed during childhood might be different from the adult population with KS where the diagnosis is based on infertility. Results based on comparisons between the two groups must be interpreted with caution. Despite the limitations, this review summarizes the current evidence for managing fertility preservation in patients with KS to provide optimal health care. There was no funding for this study. S.F., Y.H., K.D., W.L.M.N., D.S., H.L.C.-v.d.G. and L.R. declare to have no conflicts of interests. D.D.M.B. reports grants from Merck Serono, grants from Ferring and grants from MSD, outside the submitted work. K.F. reports personal fees from MSD (commercial sponsor), personal fees from Ferring (commercial sponsor), grants from Merck-Serono (commercial sponsor), grants from Ferring (commercial sponsor) and grants from MSD (commercial sponsor), outside the submitted work.

Fertility preservation in children, adolescents, and young adults with cancer: Quality of clinical practice guidelines and variations in recommendations.

Fertility preservation care for children, adolescents, and young adults (CAYAs) with cancer is not uniform among practitioners. To ensure high-quality care, evidence-based clinical practice guidelines (CPGs) are essential. The authors identified existing CPGs for fertility preservation in CAYAs with cancer, evaluated their quality, and explored differences in recommendations. A systematic search in PubMed (January 2000-October 2014); guideline databases; and Web sites of oncology, pediatric, and fertility organizations was performed. Two reviewers evaluated the quality of the identified CPGs using the Appraisal of Guidelines for Research and Evaluation II Instrument (AGREE II). From high-quality CPGs, the authors evaluated concordant and discordant areas among the recommendations. A total of 25 CPGs regarding fertility preservation were identified. The average AGREE II domain scores (scale of 0%-100%) varied from 15% on applicability to 100% on clarity of presentation. The authors considered 8 CPGs (32%) to be of high quality, which was defined as scores ≥60% in any 4 domains. Large variations in the recommendations of the high-quality CPGs were observed, with 87.2% and 88.6%, respectively, of discordant guideline areas among the fertility preservation recommendations for female and male patients with cancer. Only approximately one-third of the identified CPGs were found to be of sufficient quality. Of these CPGs, the fertility preservation recommendations varied substantially, which can be a reflection of inadequate evidence for specific recommendations, thereby hindering the ability of providers to deliver high-quality care. CPGs including a transparent decision process for fertility preservation can help health care providers to deliver optimal and uniform care, thus improving the quality of life of CAYAs with cancer and cancer survivors. Cancer 2016;122:2216-23. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Fertility Preservation in Children and Adolescents With Cancer

Advancements in oncologic therapy have increased long-term survival rates for children with childhood cancers. As survival has increased, the secondary effects of treatment have come into focus for patients and family. Infertility preservation in prepubertal children is a particularly difficult task as options are limited compared to adult counterparts with mature gametes. A systematic review of the published literature was conducted using keywords relevant to fertility preservation in the pediatric population undergoing oncologic treatment. We review the impact of cancer therapy upon gonadal function and identify the risk factors for future infertility in the prepubertal population. Treatment modifications that could modify the degree of potential damage to reproductive organs yet maintain oncologic principles were highlighted. Pubertal males and females have the opportunity to donate mature sperm or oocytes as do their adult counterparts; however, for the prepubertal child this is not the case. The options for these patients are considered investigational at this point and center on testicular tissue cryopreservation in males and oophorectomy vs ovarian cortical tissue cryopreservation in females. Infertility is an unfortunate side effect of oncologic treatment. Options are limited in the prepubertal population but tissue preservation and potential fertility should be discussed with all at-risk patients and their parents.

Fertility Preservation Counseling for Pediatric and Adolescent Cancer Patients.

Fertility preservation for children and young adults with cancer is an important part of comprehensive patient care. In 2013, the American Society of Clinical Oncology (ASCO) released updated clinical practice guidelines addressing fertility preservation. This study aimed to evaluate if pediatric oncologists were performing fertility preservation counseling, if the new guidelines were being adopted, and how reproductive endocrinologists can educate this patient population and their providers. A cross-sectional study was performed from May 26, 2014, to August 26, 2014. An online survey addressing fertility preservation practice patterns was created and provided to the members of the Children's Oncology Group (COG). Thirty-five percent of the 234 respondents reported reading the new 2013 ASCO guidelines. Ninety-five percent of providers reported mentioning fertility preservation options prior to treatment, most commonly including referral to a reproductive endocrinologist (28%), and sperm banking (57%). The most commonly reported barrier to fertility preservation counseling was the cost of treatment. Fertility preservation counseling is being performed by pediatric oncology providers. Familiarity of the ASCO guidelines is limited, revealing that the established methods for fertility preservation in women--embryo and oocyte cryopreservation--may be offered less than experimental methods in this younger patient population. Such differences in apparent practice patterns highlight the need for more education for providers.

Unique ethical and legal implications of fertility preservation research in the pediatric population

Research in fertility preservation for children and adolescents receiving gonadotoxic chemotherapy has brought forth ethical and legal concerns that require special consideration. This article will discuss many of these issues and possible methods to safeguard the rights of these children.

Cancer and ovarian tissue cryopreservation

Although ovarian tissue cryopreservation is still accepted as an experimental procedure, it has recently become an increasingly resorted technique in highly specialized in vitro fertilization (IVF) clinics. Its indications include many childhood cancers, breast cancer, some autoimmune diseases, hematopoietic stem cell transplantation, and pelvic radiation therapy due to solid tumors. The chemotherapeutics and radiation therapy may diminish ovarian reserve and cause premature ovarian failure. It currently seems as the only option for fertility preservation in children where ovulation induction is ethically not acceptable, and for those when cytotoxic therapy is urgent. There are 2 main methods for transplantation of frozen-thawed ovarian tissues: orthotopic and heterotopic transplantation. Together with its advantages, this method also has some risks, such as reimplantation of the primary tumor, malignant transformation, and loss of follicles. Therefore, a thorough counseling should be provided before going forward with the procedure. Although it is still an experimental method, there are 7 reports of live births after ovarian tissue cryopreservation. In this review, technical details of ovarian tissue cryopreservation, related indications, and methods of ovarian tissue transplantation are discussed and an algorithmic approach to fertility preservation is presented.

Advances in fertility preservation for children and adolescents with cancer

Advances in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of young women with cancer, but have resulted in a growing population of adolescent and adult long-term survivors of childhood malignancies who may experience premature ovarian failure (POF) and infertility as a result of aggressive chemotherapy and radiotherapy treatments (indicated for both cancer and bone marrow transplantation (BMT)). Ovaries are very sensitive to cytotoxic treatment, especially to radiation and alkylating agents, which are classified as high risk for gonadal dysfunction. The type and dose of chemotherapeutic agent are known to influence the progression to ovarian failure, with alkylating agents increasing the risk of POF by a factor of nine. Cyclophosphamide is the agent most commonly implicated in causing damage to oocytes and granulosa cells in a dose-dependent manner. This follicular destruction generally results in the loss of both endocrine and reproductive functions, depending on the dose and the age of the patient. Indeed, Larsen and colleagues reported a four-fold increased risk of POF in teenagers treated for cancer, rising to 27-fold in women between 21 and 25 years of age. Several options are currently available to preserve fertility in cancer patients and allow them to conceive when they have overcome their disease: embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. The choice of the most suitable strategy depends on different parameters: the type and timing of chemotherapy, the type of cancer, the patient’s age and partner status. The only established method of fertility preservation is embryo cryopreservation, according to the Ethics Committee of the American Society for Reproductive Medicine, but this option requires the patient to be of pubertal age, have a partner or use donor sperm, and be able to undergo a cycle of ovarian stimulation, which is not possible when chemotherapy has to be initiated immediately or when stimulation is contraindicated according to the type of cancer. Cryopreservation of oocytes can be performed in single women who are able to undergo a stimulation cycle, although the effectiveness of this technique is still low, with pregnancy and delivery rates ranging from 1 to 5% per frozen oocyte. Cryopreservation of ovarian tissue is the only option available for prepubertal girls, and for women who cannot delay the start of chemotherapy. Ovarian tissue can theoretically be frozen using three different approaches: as fragments of ovarian cortex, as an entire ovary with its vascular pedicle or as isolated follicles. The indications for cryopreservation of ovarian tissue in case of malignant and non-malignant disease are summarised in a recent review [1]. For patients who need immediate chemotherapy, ovarian tissue cryopreservation is the only possible alternative. The main aim of this strategy is to reimplant ovarian cortical tissue into the pelvic cavity (orthotopic site) or a heterotopic site like the forearm or abdominal wall once treatment is completed and the patient is diseasefree. To date, we have performed 11 reimplantations of cryopreserved ovarian cortex. All of them have recovered their ovarian function.

Fertility preservation in children newly diagnosed with cancer: existing standards of practice in Australia and New Zealand

To establish the extent to which sperm, oocyte and gonadal tissue collection and storage is offered to children newly diagnosed with cancer. A cross-sectional survey of all paediatric oncology services in Australia and New Zealand (ANZ) in December 2005. Sperm, oocyte and gonadal tissue collection and storage practices at paediatric oncology services; comparisons with recently published North American practices and with current recommendations for best practice. 12 of the 13 centres (92%) completed the survey. All centres offered sperm preservation, but only 10 (83%) offered oocyte/ovarian tissue preservation. Two centres were using gonadotrophin-releasing hormone analogues for fertility protection in postpubertal females. Five (42%) had offered fertility preservation to patients before the completion of their sexual development. All centres were more likely to offer sperm preservation than oocyte preservation for any given disease. The most common diseases for which conservation was offered were lymphomas and sarcomas. The anticipated cumulative dose at which centres elected to offer fertility preservation varied widely, both for the alkylator cyclophosphamide (any to 10 g/m(2)) and for abdominal/pelvic irradiation (any to 12 Gy) and spinal irradiation (any to 18 Gy). Fertility counselling was offered in a variety of settings by nine (75%) of the centres. Despite 11 centres (92%) agreeing that fertility preservation guidelines would be helpful, only two (17%) had guidelines in place. There are inconsistencies in the indications for and methods of gamete conservation in paediatric oncology centres throughout ANZ. Variations in practice on a background of unresolved medical, legal and ethical issues suggest the development of guidelines would be helpful.

Fertility preservation in children newly diagnosed with cancer: Existing standards of practice in Australia and New Zealand

9047 Background: Over the past two decades, rapid advances have occurred in both the successful treatment of childhood cancers and reproductive medicine. We sought to establish the current level of clinical practice for sperm, oocyte and gonadal tissue collection and storage in children newly diagnosed with cancer in Australia and New Zealand (ANZ). Methods: A cross-sectional survey of all pediatric oncology services in ANZ was performed. Comparisons to recently published North American practices and to current recommendations for best practice were also made. Results: Of the 13 centers invited to participate, 12 (92%) completed the survey. All centers had offered sperm conservation, but only ten (83%) had offered oocyte/ovarian tissue conservation. Available methods of gamete collection and storage were not consistent. Two centers were using GnRH agonists as fertility protection in post-pubertal females. Forty-two per cent had offered fertility conservation to males and females prior to completion of sexual development. All centers were more likely to offer sperm conservation than oocyte conservation for any given disease. The most common diseases for which conservation was offered were lymphomas and sarcomas. The anticipated cumulative dose at which centers elected to offer fertility preservation varied widely, both for the alkylator cyclophosphamide (1g/m2 to 10g/m2) and for abdominal/pelvic irradiation (any to 12 Gy) and spinal irradiation (any to 18Gy). Fertility counseling was offered in a variety of settings by 82% of centers. Despite 92% of centers agreeing that fertility preservation guidelines would be helpful, only two (17%) had any in place. Overall, there was greater uptake and consistency of utilization of fertility services in ANZ when compared with published North American data. Conclusions: There are inconsistencies regarding the indications for and methods of gamete conservation in pediatric oncology centers throughout ANZ. Unresolved medical, legal and ethical issues suggest the development of guidelines and a voluntary code of practice would be helpful. No significant financial relationships to disclose.

Clinical Potential and Putative Risks of Fertility Preservation in Children Utilizing Gonadal Tissue or Germline Stem Cells

Rapid progress in the development of novel experimental strategies to generate fertile gametes from cryo-preserved ovarian and testicular tissue motivates oncologists to investigate ways in which gonadal tissue might be preserved. Childhood cancer patients remain the major pediatric group which can benefit from these techniques. Other potential candidates include patients with systemic diseases, which require gonadotoxic chemotherapy, patients undergoing gonadectomy, patients with Turner or Kleinefelter's syndrome, and boys with cryptorchid testes. This review aims to present an overview of the current state of knowledge in experimental germ stem cell transplantation in higher primates including humans, and the clinical risks and limitations related to such procedures in children. This area of research is discussed in the context of the potential future options that may become available for preserving fertility in boys and girls.

Conference consensus statement: Ethical and research dilemmas for fertility preservation in children treated for cancer

Conference consensus statement: Ethical and research dilemmas for fertility preservation in children treated for cancer

Possibilities of fertility preservation in children and young adults undergoing treatment for malignancy

Acta Obstetricia et Gynecologica ScandinavicaVolume 79, Issue 4 p. 240-243 Free Access Possibilities of fertility preservation in children and young adults undergoing treatment for malignancy PER OLOF JANSON MD, PhD, Chief Editor, PER OLOF JANSON MD, PhD, Chief Editor From the Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Göteborg, SwedenSearch for more papers by this author PER OLOF JANSON MD, PhD, Chief Editor, PER OLOF JANSON MD, PhD, Chief Editor From the Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Göteborg, SwedenSearch for more papers by this author First published: 24 December 2001 https://doi.org/10.1034/j.1600-0412.2000.079004240.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume79, Issue4April 2000Pages 240-243 RelatedInformation

Possibilities of fertility preservation in children and young adults undergoing treatment for malignancy

Possibilities of fertility preservation in children and young adults undergoing treatment for malignancy