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Effect of Previous Chemotherapy on the Quality of Cryopreserved Human Ovarian Tissue In Vitro.

Asadi Azarbaijani B, Sheikhi M, Oskam IC, Nurmio M, Laine T, Tinkanen H, Mäkinen S, Tanbo TG, Hovatta O, Jahnukainen K - PLoS ONE (2015)

Bottom Line: Increasing dose of alkylating agents was identified by multivariate linear regression analysis as an independent predictor of a higher density of atretic follicles, whereas increasing age of the patient predicted a better outcome with less follicle atresia and a higher density of maturing follicles.The results indicate that fertility preservation should be carried out, if possible, before initiation of alkylating agents in order to guarantee better in vitro survival of ovarian follicles.In addition, ovarian samples from younger girls show lower viability and fewer developing follicles in culture.

View Article: PubMed Central - PubMed

Affiliation: Women and Children's Division, Oslo University Hospital, Rikshospitalet, Oslo, Norway; University of Oslo, Oslo, Norway.

ABSTRACT

Background: Cryopreservation of ovarian tissue has been widely accepted as an option for fertility preservation among cancer patients. Some patients are exposed to chemotherapy prior to ovarian tissue cryopreservation. Consequently, assessment of the developmental capacity of human ovarian tissue after chemotherapy is of primary importance.

Materials: In order to study the impact of previous chemotherapy on in vitro development and viability of ovarian follicles, quality control samples from 34 female cancer patients at median age of 15 years (range 1‒35), cryopreserved for fertility preservation before (n = 14) or after (n = 20) initiation of chemotherapy, were thawed and cultured for 7 days. The morphology and developmental stages of ovarian follicles were studied by light microscopy before and after culture. Possible associations between follicular densities, age and exposure to alkylating agents, expressed as cyclophosphamide equivalent dose (CED) were tested.

Results: Exposure to chemotherapy significantly impaired the survival and development of ovarian follicles in culture. After seven days, significantly higher densities of intermediary, primary and secondary follicles and lower densities of atretic follicles was detected in the samples collected before chemotherapy. Increasing dose of alkylating agents was identified by multivariate linear regression analysis as an independent predictor of a higher density of atretic follicles, whereas increasing age of the patient predicted a better outcome with less follicle atresia and a higher density of maturing follicles.

Conclusion: This study provides quantitative in vitro evidence of the impact of chemotherapy on developmental capacity of cryopreserved human ovarian tissue. The results indicate that fertility preservation should be carried out, if possible, before initiation of alkylating agents in order to guarantee better in vitro survival of ovarian follicles. In addition, ovarian samples from younger girls show lower viability and fewer developing follicles in culture.

No MeSH data available.


Related in: MedlinePlus

Relationship between follicle density and age before and after seven days of culture in controls (circles) and cancer patients with (triangles) and without (squares) chemotherapy.
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pone.0133985.g002: Relationship between follicle density and age before and after seven days of culture in controls (circles) and cancer patients with (triangles) and without (squares) chemotherapy.

Mentions: Patients who had not received chemotherapy before ovarian biopsy were significantly older than those who had received chemotherapy (Tables 1 and 2, Fig 2). Exposure to alkylating agents, expressed as CED, varied significantly between the patients (Tables 1 and 2). Spearman’s rank correlation analysis was performed to identify if age or CED correlated to follicle densities using 33 samples before and 34 samples after seven days of culture (Table 3). Increasing age correlated significantly with an increasing density of developing follicles and with a lower density of total and atretic follicles both before and after seven days of culture (Table 3). Increasing exposure to CED correlated with an increased density and proportion of atretic follicles before and after culture (Table 3). Increased CED also correlated with a decreased density of developing follicles after culture (Table 3).


Effect of Previous Chemotherapy on the Quality of Cryopreserved Human Ovarian Tissue In Vitro.

Asadi Azarbaijani B, Sheikhi M, Oskam IC, Nurmio M, Laine T, Tinkanen H, Mäkinen S, Tanbo TG, Hovatta O, Jahnukainen K - PLoS ONE (2015)

Relationship between follicle density and age before and after seven days of culture in controls (circles) and cancer patients with (triangles) and without (squares) chemotherapy.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520548&req=5

pone.0133985.g002: Relationship between follicle density and age before and after seven days of culture in controls (circles) and cancer patients with (triangles) and without (squares) chemotherapy.
Mentions: Patients who had not received chemotherapy before ovarian biopsy were significantly older than those who had received chemotherapy (Tables 1 and 2, Fig 2). Exposure to alkylating agents, expressed as CED, varied significantly between the patients (Tables 1 and 2). Spearman’s rank correlation analysis was performed to identify if age or CED correlated to follicle densities using 33 samples before and 34 samples after seven days of culture (Table 3). Increasing age correlated significantly with an increasing density of developing follicles and with a lower density of total and atretic follicles both before and after seven days of culture (Table 3). Increasing exposure to CED correlated with an increased density and proportion of atretic follicles before and after culture (Table 3). Increased CED also correlated with a decreased density of developing follicles after culture (Table 3).

Bottom Line: Increasing dose of alkylating agents was identified by multivariate linear regression analysis as an independent predictor of a higher density of atretic follicles, whereas increasing age of the patient predicted a better outcome with less follicle atresia and a higher density of maturing follicles.The results indicate that fertility preservation should be carried out, if possible, before initiation of alkylating agents in order to guarantee better in vitro survival of ovarian follicles.In addition, ovarian samples from younger girls show lower viability and fewer developing follicles in culture.

View Article: PubMed Central - PubMed

Affiliation: Women and Children's Division, Oslo University Hospital, Rikshospitalet, Oslo, Norway; University of Oslo, Oslo, Norway.

ABSTRACT

Background: Cryopreservation of ovarian tissue has been widely accepted as an option for fertility preservation among cancer patients. Some patients are exposed to chemotherapy prior to ovarian tissue cryopreservation. Consequently, assessment of the developmental capacity of human ovarian tissue after chemotherapy is of primary importance.

Materials: In order to study the impact of previous chemotherapy on in vitro development and viability of ovarian follicles, quality control samples from 34 female cancer patients at median age of 15 years (range 1‒35), cryopreserved for fertility preservation before (n = 14) or after (n = 20) initiation of chemotherapy, were thawed and cultured for 7 days. The morphology and developmental stages of ovarian follicles were studied by light microscopy before and after culture. Possible associations between follicular densities, age and exposure to alkylating agents, expressed as cyclophosphamide equivalent dose (CED) were tested.

Results: Exposure to chemotherapy significantly impaired the survival and development of ovarian follicles in culture. After seven days, significantly higher densities of intermediary, primary and secondary follicles and lower densities of atretic follicles was detected in the samples collected before chemotherapy. Increasing dose of alkylating agents was identified by multivariate linear regression analysis as an independent predictor of a higher density of atretic follicles, whereas increasing age of the patient predicted a better outcome with less follicle atresia and a higher density of maturing follicles.

Conclusion: This study provides quantitative in vitro evidence of the impact of chemotherapy on developmental capacity of cryopreserved human ovarian tissue. The results indicate that fertility preservation should be carried out, if possible, before initiation of alkylating agents in order to guarantee better in vitro survival of ovarian follicles. In addition, ovarian samples from younger girls show lower viability and fewer developing follicles in culture.

No MeSH data available.


Related in: MedlinePlus