Ovarian stimulation and oocyte cryopreservation in females and transgender males aged 18 years or less: a systematic review

BackgroundFertility preservation is an important healthcare focus in the paediatric and adolescent population when gonadotoxic treatments are required. Ovarian stimulation (OS) resulting in oocyte cryopreservation is a well-established fertility preservation option in the adult population. It’s utility, however, is little known in young patients. The purpose of this review was to synthesise the available literature on OS in patients ≤18 years old, to identify gaps in current research and provide suggestions for future research directions.MethodsUsing PRISMA guidelines, a systematic review of the literature was performed for all relevant full-text articles published in English in Medline, Embase, the Cochrane Library and Google Scholar databases. The search strategy used a combination of subject headings and generic terms related to the study topic and population. Two reviewers independently screened studies for eligibility, extracted data and assessed the risk of bias. Characteristics of the studies, objectives and key findings were extracted and summarised in a narrative synthesis.ResultsDatabase search and manual review identified 922 studies, 899 were eliminated based on defined exclusion criteria. Twenty-three studies were included and comprised 468 participants aged ≤18 years who underwent OS (median 15.2, range 7-18 years old). Only three patients were premenarchal, and four patients were on treatment to suppress puberty. Patients had OS for a broad range of indications including oncology treatment, transgender care and Turner syndrome. A total of 488 cycles of OS were completed, with all but 18 of these cycles (96.3%) successfully resulting in cryopreserved mature oocytes (median 10 oocytes, range 0-35). Fifty-three cycles (9.8%) were cancelled. Complications were rare (<1%). One pregnancy was reported from a female who had OS aged 17 years old.ConclusionThis systematic review demonstrates that OS and oocyte cryopreservation is achievable in young females however there are only a few cases in the literature describing OS in premenarcheal children or those who have suppressed puberty. There is little proof that OS can lead to pregnancy in adolescents, and no proof that this can be achieved in premenarchal girls. Therefore it should be regarded as an innovative procedure for adolescents and experimental for premenarcheal girls.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=265705, identifier CRD42021265705

Recommendations for fertility preservation in patients with lymphoma, leukemia, and breast cancer

Fertility issues should be addressed to all patients in reproductive age before cancer treatment. In men, cryopreservation of sperm should be offered to all cancer patients in reproductive age regardless of the risk of gonadal failure. In women, the recommendation of fertility preservation should be individualized based on multiple factors such as the urgency of treatment, the age of the patient, the marital status, the regimen and dosage of cancer treatment

The impact of the law in helping or hindering fertility preservation for children with cancer facing gonadotoxic therapies

Children diagnosed with cancer who require treatment with chemotherapy and/or radiation therapy have ever-increasing survival rates. However, as a result of such treatment they face the added, and significant, burden of infertility into their futures. Options for fertility preservation and future reproduction for such children do exist, but some such options continue to be considered experimental. Collaborative multidisciplinary teams support children and their families to make decisions about such options in the treatment environment. When collection of gonadal tissue from children is consented to in such circumstances, it is subject to stringent institutional clinical and human research ethics review, often in both the pediatric oncology setting and the fertility setting in which it will be preserved, examined and, potentially, used. Laws and guidelines may support the collection and use of reproductive tissue from children for treatment and research, subject to the meeting consent requirements concerning the child and/or their parent(s). This article examines such laws across Australia. It also examines the legal complexities found in some jurisdictions that may hinder research and practice, consequently having a negative impact on the prospects for children with cancer, in relation to their fertility preservation and possibilities for future reproduction

The impact of the law in helping or hindering fertility preservation for children with cancer facing gonadotoxic therapies

Children diagnosed with cancer who require treatment with chemotherapy and/or radiation therapy have ever-increasing survival rates. However, as a result of such treatment they face the added, and significant, burden of infertility into their futures. Options for fertility preservation and future reproduction for such children do exist, but some such options continue to be considered experimental. Collaborative multidisciplinary teams support children and their families to make decisions about such options in the treatment environment. When collection of gonadal tissue from children is consented to in such circumstances, it is subject to stringent institutional clinical and human research ethics review, often in both the pediatric oncology setting and the fertility setting in which it will be preserved, examined and, potentially, used. Laws and guidelines may support the collection and use of reproductive tissue from children for treatment and research, subject to the meeting consent requirements concerning the child and/or their parent(s). This article examines such laws across Australia. It also examines the legal complexities found in some jurisdictions that may hinder research and practice, consequently having a negative impact on the prospects for children with cancer, in relation to their fertility preservation and possibilities for future reproduction

Skewed Segregation of the mtDNA nt 8993 (TrG) Mutation in Human Oocytes

SummaryRapid changes in mtDNA variants between generations have led to the bottleneck theory, which proposes a dramatic reduction in mtDNA numbers during early oo-genesis. We studied oocytes from a woman with hetero-plasmic expression of the mtDNA nt 8993 (TrG) mutation. Of seven oocytes analyzed, one showed no evidence of the mutation, and the remaining six had a mutant load ú95%. This skewed expression of the mutation in oocytes is not compatible with the conventional bottleneck theory. A possible explanation is that, during amplification of mtDNA in the developing oocyte, mtDNA from one mitochondrion is preferentially amplified. Thus, subsequent mature oocytes may contain predominantly wild-type or mutant mitochondrial genomes

Cryopreservation of reproductive material before cancer treatment: a qualitative study of health care professionals’ views about ways to enhance clinical care

Abstract Background Cancer treatment can diminish fertility in women and men. The need for fertility preservation is growing as increasing numbers of people survive cancer. Cryostorage of reproductive material to preserve potential for conception for cancer survivors has moved from being experimental to being a part of clinical management of women and men who are diagnosed with cancer in their reproductive years. There is little existing evidence about how fertility preservation services can be enhanced to meet the complex needs of patients who are diagnosed with cancer in their reproductive years. The aim of this research was to inform clinical practice development by drawing on the collective experience and knowledge of staff at well-established clinics that offer fertility preservation before cancer treatment. Methods A qualitative research model was adopted using semi-structured interviews with professionals involved in the care of people who freeze reproductive material before cancer treatment. In the state of Victoria, Australia, two large assisted reproductive technology (ART) centres have been providing fertility preservation services for more than two decades. An invitation to participate in a semi-structured interview about clinical care in the context of fertility preservation was emailed to past and current staff members. To capture diverse perspectives, informants were sought from all relevant professions: fertility specialists, andrologists, nurses, embryologists/scientists, counsellors, and administrative staff. Transcripts were analysed thematically. Results Thirteen key informants were interviewed from August 2013 to February 2014. The identified themes relating to enhancing clinical care in a fertility preservation service were communication between oncology and ART specialists; managing urgency; managing patients’ expectations; establishing and implementing protocols, systems, and data bases; and maintaining contact with patients. Conclusion The collective knowledge of this study’s informants, who represent multidisciplinary teams with more than two decades’ experience in fertility preservation, yields important insights into strategies that fertility preservation services can employ to promote the integration of oncology and fertility care, the psychosocial care of patients, data recording and monitoring, and reporting of outcomes