scholarly journals Fertility Preservation: Current and Future Perspectives for Oncologic Patients at Risk for Iatrogenic Premature Ovarian Insufficiency

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Sara Pinelli ◽  
Stefano Basile
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Tissue Cryopreservation ◽  
Adult Women ◽  
Childbearing Age ◽  
Ovarian Insufficiency ◽  
Require Time ◽  
Early Diagnosis Of Cancer ◽  
Oncologic Patients

Progress in recent years in the efficacy of oncologic treatment and early diagnosis of cancer has determined an increase in life expectance in cancer patients. About 10% of all cancer cases affect women younger than 45 years; therefore nowadays approximately 5-6% of the population in childbearing age consists in cancer survivors. A crucial issue is the high risk of premature ovarian insufficiency due to possible gonadotoxic effects of oncologic treatments. Considering combined chemotherapy, radiation therapy, and bone marrow transplantation, this risk can reach 92-100%, depending on the age and ovarian reserve of the patient, as well as the schedule and type of therapy. International guidelines recommend addressing all the patients diagnosed with a neoplasia treatable with potentially gonadotoxic therapies to fertility preservation. Moreover, fertility preservation also seems to reserve fascinating implications for women who want to delay childbearing for social reasons or women affected with endometriosis, who could receive unexpected opportunities. At present, the most widespread techniques to preserve fertility in adult women are embryo or oocyte cryopreservation, depending on the presence of a partner or according to legislative issues, but these procedures require time for ovarian stimulation. In prepubertal patients or when there is no possibility of delaying chemotherapy, ovarian tissue cryopreservation and subsequent transplantation represent the main strategy.

scholarly journals FERTILITY PRESERVATION: Freezing of ovarian tissue and clinical opportunities

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. F27-F34 ◽  
Author(s):  
C Yding Andersen ◽  
L S Mamsen ◽  
S G Kristensen
Keyword(s):  
Fertility Preservation ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Genetic Diseases ◽  
Endocrine Function ◽  
Ovarian Tissue Cryopreservation ◽  
Ovarian Insufficiency ◽  
Technical Aspects ◽  
Increased Risk ◽  
Tissue Cryopreservation

Ovarian tissue cryopreservation (OTC) is mainly used for fertility preservation in girls and women facing a gonadotoxic treatment. If the woman subsequently becomes menopausal, the ovarian tissue may be transplanted to regain ovarian function, including fertility. The method was developed more than two decades ago and today thousands of women worldwide have undergone OTC. Fewer than 500 patients have had tissue transplanted and close to 100% of those regain ovarian function. Several technical aspects of OTC are now becoming more established, including high quantitative follicle survival, defining the size of the tissue resulting in optimal tissue revascularisation and follicle loss resulting from transport of ovarian tissue prior to freezing. We have used OTC to safeguard fertility in patients with genetic diseases, which for some diagnoses is purely experimental, as no transplantations is yet been performed. Usage of OTC beyond fertility is now also being considered; here, the endocrine function of follicles is the focus. It has been suggested that ovarian tissue stored in the reproductive years may be used to avoid premature ovarian insufficiency (POI) when there is a familial disposition or to postpone menopause in patients with an increased risk of osteoporosis or cardiovascular diseases. The benefit of OTC beyond fertility requires, however, actual clinical studies. The current review includes several recent technical aspects with contributions from Denmark building on some of the early work by Roger Gosden.

P–431 Human oocytes in-vitro maturation efficacy from infancy to adulthood – is there an optimal age?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Karavani ◽  
P Wasserzug-Pash ◽  
T Mordechai-Daniel ◽  
M Klutstein ◽  
T Imbar
Keyword(s):  
Fertility Preservation ◽  
In Vitro Maturation ◽  
Ovarian Tissue ◽  
Age Groups ◽  
Ovarian Tissue Cryopreservation ◽  
Success Rates ◽  
Human Oocytes ◽  
Tertiary Center ◽  
Significant Difference

Abstract Study question Does human oocytes in-vitro maturation (IVM) effectiveness change throughout childhood, adolescence and adulthood in girls and women undergoing fertility preservation via ovarian tissue cryopreservation (OTC) prior to chemo-radiotherapy exposure? Summary answer The optimal age for IVM is from menarche to 25 years, while pre-menarche girls and women older than 30 years have extremely low maturation rates. What is known already In vitro maturation of oocytes from antral follicles seen during tissue harvesting is a fertility preservation technique with potential advantages over OTC, as mature frozen and later thawed oocyte used for fertilization poses decreased risk of malignant cells re-seeding, as compared to ovarian tissue implantation. We previously demonstrated that IVM performed following OTC in fertility preservation patients, even in pre-menarche girls, yields a fair amount of oocytes available for IVM and freezing for future use. Study design, size, duration A retrospective cohort study, evaluating IVM outcomes in chemotherapy naïve patients referred for fertility preservation by OTC that had oocyte collected from the medium with attempted IVM between 2003 and 2020 in a university affiliated tertiary center. Participants/materials, setting, methods A total of 133 chemotherapy naïve patients aged 1–35 years with attempted IVM were included in the study. The primary outcome was IVM rate in the different age groups – pre-menarche (1–5 years and ≥6 years), post-menarche (menarche–17 years), young adults (18–24 years) and adults (25–29 and 30–35 years). Comparison between paired groups for significant difference in the IVM rate parameter was done using the Tukey’s Studentized Range (HSD) Test. Main results and the role of chance A gradual increase in mean IVM rate was demonstrated in the age groups over 1 to 25 years (4.6% (1–5 years), 23.8% (6 years to menarche) and 28.4% (menarche to 17 years), with a peak of 38.3% in the 18–24 years group, followed by a decrease in the 25–29 years group (19.3%), down to a very low IVM rate (8.9%) in the 30–35 years group. A significant difference in IVM rates was noted between the age extremes – the very young (1–5 years) and the oldest (30–35 years) groups, as compared with the 18–24-year group (p < 0.001). Number of oocytes matured, percent of patients with matured oocytes and overall maturation rate differed significantly (p < 0.001). Limitations, reasons for caution Data regarding ovarian reserve evaluation was not available for most of the patients, due to our pre-op OTC procedures protocol. None of our patients have used their frozen in-vitro matured oocytes, as such further implications of age on in-vitro matured oocytes quality and implantation potential has yet to be evaluated. Wider implications of the findings: Our finding of extremely low success rates in those very young (under 6 years) and older (≥30 years) patients suggest that IVM of oocyte retrieved during OTC prior to chemotherapy should not be attempted in these age group. Trial registration number N/A

Fertility Preservation

2018 ◽  
Author(s):  
Chantae S Sullivan-Pyke ◽  
Clarisa Gracia
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Testicular Tissue ◽  
Mature Oocyte ◽  
Gonadotropin Releasing Hormone ◽  
Oocyte Cryopreservation ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Cryopreservation ◽  
Gonadotropin Releasing Hormone Agonist ◽  
Tissue Cryopreservation

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  

scholarly journals Deliveries following fertility preservation by ovarian tissue cryopreservation without autotransplantation—what should be expected?

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

P–466 Fertility preservation for medical reasons: International and intra-national variation in provision and the gap between guideline and practice

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Yasmin ◽  
S Latif ◽  
C Dia. Garcia ◽  
S. Martin. D Silva
Keyword(s):  
Northern Ireland ◽  
Fertility Preservation ◽  
Ovarian Tissue ◽  
National Policy ◽  
Cytotoxic Agents ◽  
Ovarian Tissue Cryopreservation ◽  
The Uk ◽  
And Storage ◽  
Tissue Cryopreservation ◽  
Health Boards

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.

P–449 Evaluation of ovarian reserve in female children and adolescents with non-iatrogenic primary ovarian insufficiency to establish criteria for ovarian tissue cryopreservation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Volodarsky-Perel ◽  
M Zajicek ◽  
D Shai ◽  
H Raanani ◽  
N Gruber ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Reserve ◽  
Predictive Value ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Antral Follicle ◽  
Ovarian Tissue Cryopreservation ◽  
Positive Parameter ◽  
Primordial Follicles

Abstract Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH > 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable

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