[Ovarian tissue cryopreservation and transplantation in patients with cancer or benign diseases to fertility preservation]

Paz Valiñas L, Maceira Rozas MC, Casal Acción B, Mejuto Martí T.
Record ID 32018004445
Original Title: Criopreservación y autotrasplante de tejido ovárico para la preservación de la fertilidad en pacientes con procesos oncológicos o no oncológicos
Authors' objectives: To evaluate the effectiveness and clinical safety of OTC and ovarian tissue autotransplantation (OTT) in adult women and pre-and postpubertal girls who require FP in oncological and non-oncological processes associated with diminished ovarian reserve
Authors' results and conclusions: For the preparation of this report, a total of 19 publications that met the inclusion criteria were included: the clinical practice guideline (CPG) Female Fertility Preservation prepared by the European Society of Human Reproduction and Embryology (ESHRE) in 2020, which was updated with 14 case series, 1 SR in prepubertal girls, 2 cost-effectiveness studies, and 1 SR on the patient perspective. Owing to the characteristics of the procedure, the evidence is based on case series, with its inherent risk of bias and low methodological quality. • The safety of this technique was evaluated by means of the following result variables: – Complications and adverse effects directly related to the surgical intervention. Both in pre- and postpubertal populations, few major or serious complications related to tissue extraction and subsequent autotransplantation has been reported, with scarce bleeding, although there are references to pain in the incision area following laparoscopy. – Reintroduction of malignant cells. There seems to be no risk of reintroduction of malignant cells in the OTT process, although the risks depend, to a large extent, on the type of cancer and its stage. Therefore, this risk should be assessed using appropriate techniques in all cancer survivors before ovarian tissue transplantation. – Live births with birth defects and offspring risk. No additional risk of birth defects or genetic disorders following OTT has been reported, with a rate of approximately 1.2%, which is comparable to the rate of major malformations occurring in the general population. – Interrupted pregnancies/miscarriages following OTC and OTT. The rate of miscarriages varied greatly, with averages between 27% and 33% with ranges between 4% and 60%. Only one study reported abortions, with a percentage of 9%. The only comparative study between OTC and oocyte vitrification found a miscarriage rate of 28.6% and 20%, respectively. • The effectiveness of this technique was evaluated by means of the following result variables – Live birth rate. The live birth rate reported by the studies is satisfactory, with rates between 26% and 38%, but with very wide percentages ranging between 0% and 67%, which may be due to the high heterogeneity of the published studies in terms of patient screening criteria (conditions with a worse prognosis in the development of premature ovarian insufficiency and others), patient age, exposure to gonadotoxic treatment before OTC, ovarian reserve, or whether or not assisted reproductive therapies (ARTs) are used. – Restoration of ovarian function and pubertal induction. High rates of restoration of ovarian function were seen, with values in excess of 68%, which may reach 94-100% of success according to some of the studies, including the prepubertal population. • Cost-effectiveness. OTC is more effective versus the alternative of not performing the procedure, but with a high cost per live birth, with an incremental costeffectiveness ratio (ICER) of €887,254 and €95,919 for rates of 5% and 60%, respectively. Compared to oocyte cryopreservation (OC), the estimated cost for OC was $16,588, and $10,032 for OTC, with 1.56% of live births following OC, and 1.0% following OTC. OC was more expensive but more effective than OTC, with an ICER of $1,163,954 per live birth. In both cases, the ICER will decrease as the procedure utilisation rate increases. • Organisational level. The sites performing the procedure should be accredited for this purpose and have the necessary facilities, staff and standardised processes as well as quality programmes. Also, they should participate in both regional and national registries in order to monitor their activities and results. The studies stress the high relevance of the experience curve of the site performing the transplant. The surgeon should acquire the necessary skills, and the laboratory requires a specific competence that is not readily available in ART laboratories, including equipment and specific standard procedures (handling, cryopreservation, transport, etc.). • Patient perspective. The women who have undergone this procedure have described their experiences as emotional, requiring urgent decision-making. In many cases, they feel uninformed in relation to the options they may have to preserve their fertility; consequently, it is important to implement protocols intended to provide counsel, both to help to make decisions on the fertility treatment and to support patients with emotional distress associated with a potential loss of fertility both at the time of cancer diagnosis and in the long term. Conclusions • OTC and OTT are the only option to preserve fertility in prepubertal girls. • This technique is performed mainly by laparoscopy and the slow-freezing protocol is well established and is considered the standard procedure. • The results on the safety and effectiveness of the procedure of cryopreservation and subsequent ovarian tissue autotransplantation in prepubertal and postpubertal populations with oncological or non-malignant conditions stem from case series that involve a methodological design with a moderate to high risk of bias and low to very low quality of evidence. • Safety of the procedure – Postpubertal and adult populations › The procedure could be considered safe, without major complications. However, it is a surgical intervention with its inherent adverse events, such as postoperative infections or potential complications of anaesthesia. GRADE quality of evidence: low. › The evidence suggests that the risk of reintroduction of malignant cells is low, but it depends on the type of cancer. GRADE quality of evidence: low. › The evidence suggests that there is no greater risk of birth defects for children born after this procedure. GRADE quality of evidence: low. › The evidence is highly uncertain in the case of patients with hormonesensitive tumours. Pregnancy and ovarian tissue transplantation are not considered to be contraindicated. GRADE quality of evidence: very low. › The procedure could result in a miscarriage rate between 4% and 60%. GRADE quality of evidence: low. – Prepubertal population The scarce evidence focused exclusively on prepubertal girls suggest that the technique is not associated with any complications or adverse events. GRADE quality of evidence: low. › In prepubertal patients, no information is available regarding cancer processes related to the reintroduction of malignant cells, live births with birth defects, cancer processes in hormone-sensitive diseases that are altered during pregnancy, or miscarriages, or in populations more susceptible to adverse events following OTC and OTT. • Effectiveness of the procedure – Postpubertal and adult populations › The evidence suggests a live birth rate per postpubertal or adult patient between 0% and 57% that might depend on the existence of associated fertility factors, use of different assisted reproductive techniques and patient age. GRADE quality of evidence: low. › The restoration of ovarian function could be between 68% and 100%, with a significant impact of age, with the threshold being 36 years of age. GRADE quality of evidence: low. › There is no available evidence on the quality of life of postpubertal and adult patients who receive ovarian tissue cryopreservation or transplantation. – Prepubertal population › Based on scarce and very uncertain evidence, the live birth rate is very wide, between 0% and 57%. GRADE quality of evidence: very low. › Scarce and very uncertain evidence indicates that the procedure could be successful in ovarian restoration. GRADE quality of evidence: very low. › Scarce and very uncertain evidence indicates that the procedure could be successful in pubertal induction in girls and adolescents. GRADE quality of evidence: very low. › There is no available information on the quality of life of prepubertal patients who receive ovarian tissue cryopreservation and ovarian tissue transplantation. Although OTC and OTT are currently a procedure used in a higher number of patients and countries, their results should be taken with caution. • Cost-effectiveness – The ICER was high for the live birth rate for OTC both versus the non-performance of any other procedures and versus OC. In both scenarios, the ICER of the procedure improves as usage rates increase. Organisational aspects – The procedure should be carried out in specialised centres, with specially trained and qualified professionals in a well-constituted multidisciplinary context, with established committees and agreed protocols, in a hospital setting, with a minimum number of annual cases and long-term follow-up that should be the responsibility of the site performing ovarian tissue cryopreservation. – It would be necessary to establish a national registry and a research database to generate evidence-based information on the return of reproductive function after the transplantation of cryopreserved ovarian tissue. – Patient perspective/counsel – There is no available information on the perspective of prepubertal girls. – The young and adult women who have undergone ovarian tissue cryopreservation have described their experiences as emotional and requiring urgent decision-making. – Healthcare professionals should take patients’ emotional wellbeing into account and have the necessary time and knowledge to give clear information on this technique to assist in making an informed decision. – Fertility counselling has a supportive role for patients with emotional distress associated with a potential loss of fertility at the time of cancer diagnosis. – Patients should be counselled individually on the indications and risks by a multidisciplinary team of professionals who can provide the necessary information, adapted to an adolescent or adult population.
Authors' methods: A systematic review (SR) was conducted by means of a literature search in May 2022 (updated in December 2022) in the main biomedical databases (Medline, Embase) and databases specialised in SRs and health technology assessment reports, such as the INAHTA database or the Cochrane Library.
Project Status: Completed
Year Published: 2023
URL for published report: http://hdl.handle.net/20.500.11940/18181
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Spain
MeSH Terms
  • Fertility Preservation
  • Cryopreservation
  • Neoplasms
  • Tissue Transplantation
  • Ovary
  • Cryopreservation
  • Oocytes
  • Neoplasms
Organisation Name: Scientific Advice Unit, avalia-t; The Galician Health Knowledge Agency (ACIS)
Contact Address: Conselleria de Sanidade, Xunta de Galicia, San Lazaro s/n 15781 Santiago de Compostela, Spain. Tel: 34 981 541831; Fax: 34 981 542854;
Contact Name: avalia-t@sergas.es
Contact Email: avalia-t@sergas.es
Copyright: <p>Galician Agency for Health Technology Assessment (AVALIA-T)</p>
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.