scholarly journals International consensus: ovarian tissue cryopreservation in young Turner syndrome patients: outcomes of an ethical Delphi study including 55 experts from 16 different countries

2020 ◽  
Vol 35 (5) ◽  
pp. 1061-1072 ◽  
Author(s):  
M J Schleedoorn ◽  
B H Mulder ◽  
D D M Braat ◽  
C C M Beerendonk ◽  
R Peek ◽  
...  

Abstract STUDY QUESTION What is the standpoint of an international expert panel on ovarian tissue cryopreservation (OTC) in young females with Turner syndrome (TS)? SUMMARY ANSWER The expert panel states that OTC should be offered to young females with TS, but under strict conditions only. WHAT IS KNOWN ALREADY OTC is already an option for preserving the fertility of young females at risk of iatrogenic primary ovarian insufficiency (POI). Offering OTC to females with a genetic cause of POI could be the next step. One of the most common genetic disorders related to POI is TS. Due to an early depletion of the ovarian reserve, most females with TS are confronted with infertility before reaching adulthood. However, before offering OTC as an experimental fertility preservation option to young females with TS, medical and ethical concerns need to be addressed. STUDY DESIGN, SIZE, DURATION A three-round ethical Delphi study was conducted to systematically discuss whether the expected benefits exceed the expected negative consequences of OTC in young females with TS. The aim was to reach group consensus and form an international standpoint based on selected key statements. The study took place between February and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Anonymous panel selection was based on expertise in TS, fertility preservation or medical ethics. A mixed panel of 12 gynaecologists, 13 (paediatric) endocrinologists, 10 medical ethicists and 20 patient representatives from 16 different countries gave consent to participate in this international Delphi study. In the first two rounds, experts were asked to rate and rank 38 statements regarding OTC in females with TS. Participants were offered the possibility to adjust their opinions after repetitive feedback. The selection of key statements was based on strict inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE A total of 46 participants completed the first Delphi round (response rate 84%). Based on strict selection criteria, six key statements were selected, and 13 statements were discarded. The remaining 19 statements and two additional statements submitted by the expert panel were re-evaluated in the second round by 41 participants (response rate 75%). The analysis of the second survey resulted in the inclusion of two additional key statements. After the approval of these eight key statements, the majority of the expert panel (96%) believed that OTC should be offered to young females with TS, but in a safe and controlled research setting first, with proper counselling and informed consent procedures, before offering this procedure in routine care. The remaining participants (4%) did not object but did not respond despite several reminders. LIMITATIONS, REASONS FOR CAUTION The anonymous nature of this study may have led to lack of accountability. The selection of experts was based on their willingness to participate. The fact that not all panellists took part in all rounds may have resulted in selection bias. WIDER IMPLICATIONS OF THE FINDINGS This international standpoint is the first step in the global acceptance of OTC in females with TS. Future collaborative research with a focus on efficacy and safety and long-term follow-up is urgently needed. Furthermore, we recommend an international register for fertility preservation procedures in females with TS. STUDY FUNDING/COMPETING INTEREST(S) Unconditional funding (A16-1395) was received from Merck B.V., The Netherlands. The authors declare that they have no conflict of interest.

2019 ◽  
Vol 13 ◽  
pp. 117955811987338 ◽  
Author(s):  
Natalia C Llarena ◽  
Tommaso Falcone ◽  
Rebecca L Flyckt

Infertility affects 30% to 50% of women with endometriosis. Women with endometriosis are at risk of decreased ovarian reserve, both because of the pathophysiology of the disease and iatrogenic injury resulting from surgical intervention. Fertility preservation must occur at multiple levels, including careful selection of surgical candidates, avoidance of repeat procedures, and meticulous surgical technique. Fertility preservation with oocyte or ovarian tissue cryopreservation may be considered on an individual basis for women with endometriosis, particularly those at risk of bilateral ovarian injury, such as women with bilateral endometriomas.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xia Hao ◽  
Amandine Anastácio ◽  
Laia Viñals-Ribé ◽  
Ana Santamaria Lacuesta ◽  
Christina Diakaki ◽  
...  

Ovarian tissue cryopreservation is the only feasible method for fertility preservation in prepubertal girls that will undergo gonadotoxic chemotherapy. To date, the only clinical use of cryopreserved tissue is by a later tissue retransplantation to the patient. Clinical challenges in fertility preservation of very young patients with cancer include time constraints that do not allow to retrieve the tissue for cryopreservation before starting chemotherapy and the preclusion of future ovarian tissue transplantation due to the risk of reintroduction of malignant cells in patients with systemic diseases. To overcome these two challenges, we investigated using an experimental model the feasibility of retrieving secondary follicles from ovaries of prepubertal mice after cyclophosphamide (CPA) treatment in increasing doses of 50, 75, and 100 mg/kg. The follicles were thereafter cultured and matured in vitro. The main outcomes included the efficiency of the method in terms of obtained matured oocytes and the safety of these potentially fertility preservative procedures in terms of analyses of oocyte competence regarding normality of the spindle and chromosome configurations. Our findings demonstrated that it was feasible to isolate and culture secondary follicles and to obtain mature oocytes from prepubertal mice ovaries recently treated with CPA. The efficiency of this method was highly demonstrated in the 100 mg/kg CPA group, with near 90% follicle survival rate after 12 days’ culture, similarly to control. Around 80% of the follicles met the criteria to put into maturation, and more than 40% of them achieved metaphase II, with normal spindle and chromosome configurations observed. Suboptimal results were obtained in the 50 and 75 mg/kg CPA groups. These paradoxical findings towards CPA dose might probably reflect a more difficult selection of damaged growing follicles from ovaries recently treated with lower doses of CPA and a hampered ability to identify and discard those with reduced viability for the culture.


2018 ◽  
Author(s):  
Chantae S Sullivan-Pyke ◽  
Clarisa Gracia

Fertility preservation has becoming increasingly important for patients at risk for gonadal failure, including those needing treatment for cancer or autoimmune conditions, genetic conditions that predispose to gonadal insufficiency, and age-related fertility decline. Embryo cryopreservation and mature oocyte cryopreservation are the standards for fertility preservation in postpubertal women. Ovarian tissue cryopreservation and gonadotropin-releasing hormone agonist use for ovarian suppression are experimental methods that may be offered to patients for whom embryo and/or mature oocyte cryopreservation are not applicable. The cryopreservation of spermatozoa is the standard for fertility preservation in postpubertal males, but testicular tissue cryopreservation may be offered to prepubertal males.   This review contains 10 figures, 6 tables and 53 references Key words: controlled ovarian stimulation, embryo cryopreservation, gonadotropin-releasing hormone agonist, in vitro maturation, oocyte cryopreservation, ovarian tissue cryopreservation, sperm extraction, testicular tissue cryopreservation  


2018 ◽  
Vol 36 (2) ◽  
pp. 335-340 ◽  
Author(s):  
Daniel Lantsberg ◽  
Adel Farhi ◽  
Inna Zaslavsky-Paltiel ◽  
Barbara G. Silverman ◽  
Liat Lerner-Geva ◽  
...  

2018 ◽  
Vol 14 (4) ◽  
pp. 363-378 ◽  
Author(s):  
Austin G Armstrong ◽  
Bruce F Kimler ◽  
Brigid M Smith ◽  
Teresa K Woodruff ◽  
Mary Ellen Pavone ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S. Van der Coelen ◽  
M Schleedoorn ◽  
S Nadesapillai ◽  
R Peek ◽  
D Braat ◽  
...  

Abstract Study question What are the experiences with the decision-making process of girls with Turner syndrome (TS) considering ovarian tissue cryopreservation (OTC), their parents and healthcare providers? Summary answer Offering a new option to preserve fertility in TS caused unrealistic hope leading to challenges for healthcare providers to fulfil the ideal of informed consent. What is known already Due to premature ovarian insufficiency, girls with TS have only a small chance of genetic offspring. OTC might increase these odds. Healthcare providers and scientist are still cautious in offering OTC to girls with TS because of the many uncertainties regarding OTC in this patient group. Hence, OTC is now offered to girls with TS between 2 and 18 years old in a research setting: the TurnerFertility study. Study design, size, duration A retrospective qualitative study consisting of a survey and focus groups. Within a year after counselling, families (n = 132) received a survey with 30 questions regarding their experiences with the decision-making process and also an invitation for a focus group. The focus groups were conducted between January and October 2019 and lasted 51-84 minutes. The topic lists were based on literature research and survey results. Results were analysed following a thematic analysis approach. Participants/materials, setting, methods This is a sub-study of the prospective intervention study within an academical medical centre. Focus groups were composed through purposive sampling. Focus group 1 (FG1) consisted of five gynaecologists involved in counselling, FG2 with seven paediatricians who referred girls for counselling, FG3 with nine parents of girls with TS between 2 and 12 years old and FG4 with three parents of girls with TS between 13 and 17 years old. Main results and the role of chance 90% of survey respondents appreciated counselling regarding fertility options and considered it an enrichment of existing healthcare. The individual consultation was rated as most contributing by 66% of the survey respondents, followed by the information meeting (37%) and decision aid (3%). The focus groups revealed that many had not discussed options for future parenthood with a healthcare provider before. Girls with TS and their parents indicated that the option of OTC raised hope for future genetic offspring, and at once made them feel like they had no choice but to take this chance. The small chance of success did not influence the decision for families who opted for OTC. Some parents who had to decide for their young daughter accepted OTC to give their daughter the option to decide herself whether to make use of the cryopreserved tissue later in life. Gynaecologists found it challenging to truly make families grasp a realistic perspective of OTC in TS and the associated mental and physical risks. Gynaecologists and paediatricians struggled with conflicting moral principles of non-maleficence against respect for autonomy: healthcare providers recognized the scientific relevance for the TS population, while it felt inconsistent with the disproportionate burden for some individual patients. Limitations, reasons for caution Because there was no validated survey for this topic in TS, we developed a survey based on literature research and experiences of a dedicated TS team. Among the survey responders and focus group participants a greater proportion decided for OTC compared to the overall counselled group (75% vs 60%). Wider implications of the findings This study gives insight in the issues to consider when implementing new technologies regarding fertility, in which parents have to decide for their child, where it is expected that anticipated decision regret plays a major role, or where healthcare providers experience conflicting duties as scientist and physician. Trial registration number not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Yasmin ◽  
S Latif ◽  
C Dia. Garcia ◽  
S. Martin. D Silva

Abstract Study question What is the gap between guidance and practice of fertility preservation between countries and within countries with common clinical guidelines? Summary answer Substantial variation in provision of FP exists between countries and within individual countries with gaps between national and international guidelines and policies governing provision. What is known already A robust guideline on female FP was published by ESHRE in 2020, advising the application of FP in cancer and other conditions where treatment with cytotoxic agents or surgery will compromise reproductive function. Across Europe, in 13 countries (43.3%) FP is funded for all available FP procedures, in 13 countries (43.3%) no FP funding is available, and in 4 countries (13.3%) at least one FP option is funded. Variation in state provision of fertility care in different countries in Europe was highlighted in the ESHRE guidance. It did not specifically examine individual national policies or whether a national policy exists. Study design, size, duration Five clinicians performing FP in Europe were contacted to collect current FP provision data. Policies retrieved from the internet were not included as they could not be verified. Finally, FP funding policies for 135 Clinical Commissioning Groups (CCGs) in England, 14 Health Boards in Scotland, 7 Health Boards in Wales and 5 Trusts in Northern Ireland and 17 policies for regional heath services in Spain were included were included. Participants/materials, setting, methods Policies on FP for the UK and Spain were reviewed (n = 178), including policies from the 161 regions from the four nations of the UK and policies of 17 autonomous bodies in Spain. Information on funded procedures, type of conditions included for funding and duration of storage were extracted. The provision of FP was compared to the current European Society of Human Reproduction and Embryology (ESHRE) and National Institute for Health and Care Excellence (NICE) guidelines. Main results and the role of chance In England, 127/128 (99%) CCGs fund cryopreservation of oocytes, sperm and embryos. Cancer is the exclusive indication in 11%. Provision of FP for transgender individuals is specified in 28%, ovarian tissue cryopreservation is funded in 8% and storage funding varies from five to ten years. In Scotland, a national policy is applied. All 14 health boards equitably fund cryopreservation of oocytes, sperm, embryos and ovarian and testicular tissue. Funding is provided for cancer, medical conditions which may impair fertility and transgender individuals. Storage funding is based on a five yearly review until age 43 in women and 60 in men. In Wales and Northern Ireland, cryopreservation of oocytes, sperm and embryos is funded for people undergoing medical or surgical treatment that is likely to make them infertile, provision for transgender individuals is not specified and ovarian tissue cryopreservation is not funded. In Spain, all 17 Health Services fund cryopreservation of oocytes, sperm and embryos for patients whose fertility is at risk due to gonadotoxic treatments or other pathological processes. Ovarian tissue cryopreservation is funded in 94%, provision for transgender individuals is specified in 12%, and storage funding is available until the age of 50 in women and 55 in men. Limitations, reasons for caution Inability to retrieve fertility preservation policies for every country in Europe is a limitation, for which ongoing collaboration is sought. The variable nature of FP provision is likely to be multi-factorial; a lag in publication of guidelines and updated policies, ethical considerations and resource distribution may govern health policies. Wider implications of the findings: The study highlights that provision of FP not only varies between countries but is also inconsistent within the same country. It is clear that there is a gap between ideal, evidence-based practice and actual provision. Variation in policies limits uniform access to care for patients. Trial registration number Not applicable.


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