Successful pregnancies after transplantation of ovarian tissue retrieved and cryopreserved at time of childhood acute lymphoblastic leukemia – A case report

Rodriguez‐Wallberg, Kenny A.; Milenković, Milan; Papaikonomou, Kiriaki; Keros, Victoria; Gustafsson, Britt; Sergouniotis, Fotios; Wikander, Ida; Perot, Ronak; Borgström, Birgit; Ljungman, Per; Barbany, Gisela

doi:10.3324/haematol.2021.278828

Cited by 35 publications

(25 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, clinical data from young female patients that have undergone ovarian tissue cryopreservation after several chemotherapy rounds and even after hematologic stem cells transplantation (HSCT) has demonstrated presence of primordial ovarian follicles in the cryopreserved tissue when the ovarian tissue was retrieved during childhood or adolescence (35). Moreover, ovarian tissue retrieved following HSCT conditioning at pubertal age has demonstrated full functionality after retransplantation, allowing two normal pregnancies, as recently reported (36).…”

Section: Discussionmentioning

confidence: 88%

Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 88%

Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our finding confirms the previous reports that ovarian leukemic contamination at the MRD level carries a risk of leukemia transmission and contaminated ovaries should not be used in clinical reimplantation [ 16 , 31 , 32 ], although potential leukemic contamination did not always lead to transmission of leukemia. There are recent publications on first pregnancies in leukemia survivors after transplantation of cryopreserved MRD negative ovarian tissue [ 33 , 34 ]. In line with the clinical observations, all 25 hosts in the present study that received MRD negative grafts remained healthy in the 22-week follow-up.…”

Section: Discussionmentioning

confidence: 99%

Effect of Previous Alkylating Agent Exposure on Follicle Numbers in Cryopreserved Prepubertal and Young Adult Ovarian Tissue after Long-Term Xenografting

Nurmio

Asadi-Azarbaijani

Hou

et al. 2022

Cancers

View full text Add to dashboard Cite

Purpose and methods: To elucidate whether previous cancer treatment affects graft recovery and follicle numbers, morphology, and development in grafts, cryopreserved ovarian biopsies obtained from 18 cancer patients aged 1–24 years with and without exposure to chemotherapy were xenografted as 1 mm3 fragments to immunodeficient mice for 22 weeks with exogenous stimulation. Results: Graft recovery showed no association with chemotherapy exposure, pubertal stage, or leukemia contamination. Total follicle number per recovered graft varied between 0 and 1031 in the chemotherapy-exposed and between 0 and 502 in the non-chemotherapy-exposed group. Atretic follicles formed the largest proportion of the follicle pool in chemotherapy-exposed grafts. Increased atresia correlated with exposure to alkylating agents (mean ± SD 8866.2 ± 9316.3 mg/m2) but not with anthracyclines, pubertal stage, or leukemia contamination. Conclusion: The observation confirms the harmful effects of alkylating agents on ovarian tissue. Therapy at the median cumulative dose of 8866 mg/m2 leads to the decreased quality of cryopreserved ovarian follicles in children and young adults.

show abstract

“…Inducing complete remission through several chemotherapy cycles prior to OTC in cases at high risk of ovarian contamination is reasonable, since it helps to reduce the risk of ovarian metastasis and does not interfere with reproductive outcomes after transplantation [36,37,40,77,78]. To the best of our knowledge, 4 live births have been reported to date in patients transplanted with ovarian tissue cryopreserved at the time of complete remission of their acute leukemia [79][80][81][82]. Nevertheless, excluding the presence of malignant cells by histological, immunohistochemical and molecular analysis was always performed and is highly recommended before contemplating reimplantation [79][80][81][82][83] (Figure 3).…”

Section: Ovarian Tissue Reimplantationmentioning

confidence: 99%

“…To the best of our knowledge, 4 live births have been reported to date in patients transplanted with ovarian tissue cryopreserved at the time of complete remission of their acute leukemia [79][80][81][82]. Nevertheless, excluding the presence of malignant cells by histological, immunohistochemical and molecular analysis was always performed and is highly recommended before contemplating reimplantation [79][80][81][82][83] (Figure 3).…”

Section: Ovarian Tissue Reimplantationmentioning

confidence: 99%

“…Due to a lack of longterm experience and the relatively recent development of the technique, there are still very few data on outcomes of ovarian transplants performed with ovarian tissue from children or adolescents. Table 3 summarizes data on autografts of ovarian cortex cryopreserved before the age of 18 years with the goal of restoring fertility [4,39,40,52,80,82,86,98,[104][105][106][107][108][109]. A total of 15 patients were involved.…”

Section: Autotransplantation Of Cryopreserved Ovarian Cortex From Patients Aged 18 and Undermentioning

confidence: 99%

See 1 more Smart Citation

Fertility Preservation: How to Preserve Ovarian Function in Children, Adolescents and Adults

Dolmans

Hossay

Nguyen

et al. 2021

JCM

View full text Add to dashboard Cite

Chemotherapy, pelvic radiotherapy and ovarian surgery have known gonadotoxic effects that can lead to endocrine dysfunction, cessation of ovarian endocrine activity and early depletion of the ovarian reserve, causing a risk for future fertility problems, even in children. Important determinants of this risk are the patient’s age and ovarian reserve, type of treatment and dose. When the risk of premature ovarian insufficiency is high, fertility preservation strategies must be offered to the patient. Furthermore, fertility preservation may sometimes be needed in conditions other than cancer, such as in non-malignant diseases or in patients seeking fertility preservation for personal reasons. Oocyte and/or embryo vitrification and ovarian tissue cryopreservation are the two methods currently endorsed by the American Society for Reproductive Medicine, yielding encouraging results in terms of pregnancy and live birth rates. The choice of one technique above the other depends mostly on the age and pubertal status of the patient, and personal and medical circumstances. This review focuses on the available fertility preservation techniques, their appropriateness according to patient age and their efficacy in terms of pregnancy and live birth rates.

show abstract

Successful pregnancies after transplantation of ovarian tissue retrieved and cryopreserved at time of childhood acute lymphoblastic leukemia – A case report

Abstract: Not available.

Cited by 35 publications

References 15 publications

Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation

Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation

Effect of Previous Alkylating Agent Exposure on Follicle Numbers in Cryopreserved Prepubertal and Young Adult Ovarian Tissue after Long-Term Xenografting

Fertility Preservation: How to Preserve Ovarian Function in Children, Adolescents and Adults

Contact Info

Product

Resources

About