scholarly journals Ovarian Tissue Transplantation: Experience From Germany and Worldwide Efficacy

2019 ◽  
Vol 13 ◽  
pp. 117955811986735 ◽  
Author(s):  
Laura Lotz ◽  
Ralf Dittrich ◽  
Inge Hoffmann ◽  
Matthias W Beckmann

Extraction of ovarian tissue prior to oncologic therapy and subsequent transplantation is being performed increasingly often to preserve fertility in women. The procedure can be performed at any time of the cycle and, therefore, generally does not lead to any delay in oncological therapy. Success rates with transplantation of cryopreserved ovarian tissue have reached promising levels. More than 130 live births have been reported worldwide with the aid of cryopreserved ovarian tissue and the estimated birth rate is currently approximately 30%. In Germany, Austria, and Switzerland, the FertiPROTEKT consortium has successfully achieved 21 pregnancies and 17 deliveries generated after 95 ovarian tissue transplantations by 2015, one of the largest case series worldwide confirming that ovarian tissue cryopreservation and transplantation are successful. Approximately, more than 400 ovarian tissue cryopreservation procedures are performed each year in the FertiPROTEKT consortium, and the request and operations for ovarian tissue transplantation have increased in recent years. Therefore, recommendations for managing transplantation of ovarian tissue to German-speaking reproductive medicine centers were developed. In this overview, these recommendations and our experience in ovarian tissue transplantation are presented and discussed with international procedures.

The Lancet ◽  
2012 ◽  
Vol 380 (9837) ◽  
pp. 107
Author(s):  
J Donnez ◽  
MM Dolmans ◽  
D Demylle ◽  
P Jadoul ◽  
C Pirard ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1114-1114
Author(s):  
Izhar Hardan ◽  
Dror Meirow ◽  
Avichai Shimoni ◽  
Jacob Levron ◽  
Noga Shemtov ◽  
...  

Abstract Loss of fertility is a major concern in young women undergoing high dose chemotherapy (HDT). Although it is generally accepted that therapy of the myeloabelative range is related with a high rate of fertility loss, we observed during the last years eight spontaneous pregnancies with normal deliveries in young women after bone marrow transplantation. Seven patients (pt’s) were with lymphoma and MM and were conditioned with BEAM regimen (n=6) and melphalan 200mg/sm (n=1) prior to an autologous SCT, while one patient had a secondary AML and underwent BEAM primed autologous SCT and Busulfex/FA primed allogeneic BMT. The median age at transplant of this group was 28y and median time from transplant to pregnancy was 25 months. More than 100 women of 18–40y.o were transplanted in our center during this period; however, obviously the fertility rate cannot be calculated as it is related with additional parameters including survival, post transplant complications and mainly patient’s preferences. Naturally we observed during the same period many young patients with ovarian failure post transplant, as well as one successful pregnancy from a cryopreserved embryo. Methods. We Therefore initiated in October 2000 a fertility preservation program in which all women of 18 – 40y.o were offered a pretransplant IVF with embryo preservation, and/or ovarian tissue cryopreservation (OTC), according to their clinical status. 651 pt’s were transplanted in our center in the last 44 months, of which 81 were women of 18–41y.o that were all enrolled in this program. Results. Seven pt’s of this group (8.6%) underwent IVF. The major causes of denying IVF were the need to delay BMT for more than clinically accepted, prolonged preexisting ovarian failure, lack of a suitable partner and patient’s preference. Seventeen pt’s (21%) underwent OTC. The major causes of denying OTC were patient’s preference (mainly due to no evidence of success with this method) and thrombocytopenia/neutropenia. During this period: One patient of this group was fertilized with her cryopreserved embryos 32 months after transplant and is at her 16 week of pregnancy. One patient underwent a successful transplantation of her cryopreserved ovarian tissue 2.5 years after HDC while in a documented ovarian failure, and gave birth to a healthy baby on June 2005. The OTC of this patient was performed after cis-platinum containing salvage therapy for relapsing NHL, prior to BEAM primed SCT, and immediately after a failure of hormonal stimulation for IVF. One patient underwent a cryopreserved ovarian tissue transplantation on July 2005 Conclusions: 1. Spontanous pregnancy after HDT, mainly at the younger age, is not a rare phenomenon. 2. Most young patients prior to HDT are not eligible for IVF. 3. Pretransplant ovarian tissue cryopreservation is a feasible tool in this set-up. The first success with this method is promising.


Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. F35-F44 ◽  
Author(s):  
Hadassa Roness ◽  
Dror Meirow

Ovarian tissue cryopreservation and transplantation (OTCP-TP) has progressed over the past decade from a revolutionary experimental procedure to a well-accepted treatment in many centers for young patients with a high risk of ovarian failure after cancer treatment. The procedure is remarkably successful, with studies reporting return of ovarian function in up to 95% of graft recipients and pregnancy rates of between 30 and 50%. The most significant limitation of OTCP-TP is the massive loss of follicles that occurs following transplantation, which is primarily attributed to ischemic damage and follicle activation. We review the current approaches to reducing follicle loss and maximizing graft lifespan via pharmacological agents which reduce ischemic damage and follicle activation. We further discuss the value and disadvantage of inducing follicle activation in the graft as a means of generating mature follicles in the immediate short term.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
T Y T Nguyen ◽  
L Cacciottola ◽  
A Camboni ◽  
M De Vos ◽  
I Demeestere ◽  
...  

Abstract Study question Is cryopreserved ovarian tissue transplantation safe in patients with central nervous system (CNS) tumors? Summary answer Cancer cell contamination was not detected in any ovarian samples from patients with CNS tumors by histological analysis, immunohistochemistry, molecular biology or long-term xenotransplantation. What is known already Frequently encountered CNS cancers in childhood include astrocytoma, medulloblastoma, ependymoma, glioblastoma and germinoma. CNS tumors have the capacity for extraneural metastases in 0.5-18% of cases. There are two publications reporting metastases to patients’ ovaries from medulloblastoma. Study design, size, duration Prospective experimental study conducted in an academic gynecology research laboratory using frozen-thawed ovarian tissue from 20 patients suffering from 6 types of CNS tumors, including the most common forms mentioned above and primitive neuroectodermal tumors (PNET). Five-month xenotransplantation was performed to severe combined immunodeficient (SCID) mice. Participants/materials, setting, methods Cryopreserved ovarian tissue from 20 patients with CNS cancers was thawed and analyzed for minimal disseminated disease and long-term xenografting to immunodeficient mice. The presence of malignant cells was assessed in both cryopreserved and xenografted ovarian tissue using histological analysis, immunohistochemistry for disease-­specific markers (neuron-specific enolase [NSE] and glial fibrillary acidic protein [GFAP]) and reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) for quantification of GFAP gene amplification. Main results and the role of chance No malignant cells were detected in frozen-thawed ovarian tissue from any of the patients by histology, immunolabeling for NSE and GFAP, RT-ddPCR for detection of GFAP gene amplification or xenotransplantation to SCID mice. One patient successfully underwent frozen-thawed ovarian tissue transplantation, resulting in the birth of 3 healthy children, but suffered a recurrence of her PNET 6 years after reimplantation and sadly died. Scrupulous analysis of her remaining frozen tissue showed no infiltration by malignant cells, neither after thawing nor long-term xenotransplantation. No relationship was ever established between the patient’s relapsed cancer and reintroduction of her cryopreserved ovarian tissue. The risk of reseeding cancer cells when transplanting ovarian tissue in patients with CNS cancers can therefore be considered low. Limitations, reasons for caution The risk of ovarian metastases cannot be completely ruled out for any type of tumor because we cannot analyze the actual fragments that will be reimplanted. Wider implications of the findings Our results indicate that the risk of disseminated disease in ovarian tissue from CNS patients is minimal. This is useful information for doctors when counseling women looking to undergo ovarian tissue transplantation. Trial registration number Not applicable


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.


2021 ◽  
Vol 10 (22) ◽  
pp. 5217
Author(s):  
Vinnie Hornshøj Greve ◽  
Margit Dueholm ◽  
Linn Salto Mamsen ◽  
Stine Gry Kristensen ◽  
Erik Ernst ◽  
...  

Ovarian tissue cryopreservation (OTC) and transplantation of frozen/thawed ovarian tissue (OTT) are used for fertility preservation in girls and women. Here, we evaluated the hormonal characteristics of women with or without postmenopausal levels of FSH at the time of OTT to study differences and conditions that best support the initiation of ovarian function. A total of 74 women undergoing OTT (n = 51 with menopausal levels of FSH; n = 23 with premenopausal levels) were followed by measurements of FSH, LH, AMH, and oestradiol. Concentrations of FSH and LH returned to premenopausal levels after 20 weeks on average, with a concomitant increase in oestradiol. Despite resumption of ovarian activity, AMH concentrations were in most instances below the detection limit in the menopausal group, suggesting a low ovarian reserve. Despite a higher age in the premenopausal group, they more often experienced an AMH increase than the menopausal group, suggesting that conditions in the premenopausal ovary better sustain follicle survival, perhaps due to the higher concentrations of oestradiol. Collectively, this study highlights the need for improving follicle survival after OTT. Age and the amount of tissue transplanted are important factors that influence the ability to regain ovarian activity and levels of FSH may need to be downregulated and oestradiol increased prior to OTT.


Author(s):  
Attila Vereczkey ◽  

Fertility Preservation, Cryopreservation, Ovarian Tissue Autotransplantation and Malignancies. Abstract: Autotransplantation of cryopreserved ovarian tissue is one of the most advanced methods for fertility preservation of patients suffering from malignant diseases. Even though the method itself is still experimental, nearly a hundred live births have been documented worldwide, and its efficacy is comparable with the efficacy of any other assisted reproductive technology. Our prospective, nonrandomized study was the first in Hungary that aimed to examine the safety and efficacy of fertility preservation based on ovarian tissue cryopreservation and autotransplantation. Patients were included only with stage I-III malignancy confirmed by histological diagnosis with a high risk for post-treatment infertility. 13 patients met the inclusion criteria and were enrolled in the study. After successful treatment and recovery, cryopreserved ovarian tissue was thawed and autotransplanted in three cases. The ultrathin slices of ovarian cortex were transplanted on the remaining ovaries with laparoscopic or minilaparotomic intervention. Patients were discharged home after an uneventful postoperative period and are followed up currently. In summary, cryopreservation and autotransplantation of ovarian tissue is a safe technology for fertility preservation, which should be considered to offer and perform prior to gonadotoxic treatment, after individual evaluation of patients


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