J Breast Cancer.  2008 Mar;11(1):10-17. 10.4048/jbc.2008.11.1.10.

Restoration of Reproductive Potential after Autotransplantation of Frozen Ovaries in Mice Pretreated with Cyclophosphamide

• Lee DH
• Kim JO
• Yoo YK
• Lee KJ
• Kim JS
• Ahn CJ

• KMID: 2175042
• DOI: http://doi.org/10.4048/jbc.2008.11.1.10

Abstract

PURPOSE: Infertility due to ovarian failure that is caused by antineoplastic chemotherapeutic agents is one of the primary problems of female cancer atients who are in their reproductive years. It has become important to preserve the reproductive potential of female cancer patients. This study was conducted to determine whether autotransplantation of frozen ovaries can restore reproductive potential.
METHODS
This study included 30 female mice that had normal reproductive potential. The mice were divided into 4 groups: the positive control, the negative control, the comparison group, and the experimental group. The positive control group received right total oophorectomy, and the negative control group received bilateral total oophorectomy. Greater than or equal to 90% of the left ovary was removed in the mice of the comparison group, and then cyclophosphamide was administered. In the experimental group, the right ovary taken out by right total oophorectomy, and this was crypreserved using the vitrification method. And then cyclophosphamide was administered. The cryopreserved ovary was autotransplanted to the left gonadal fat pad after greater than or equal to 90% of the left ovary was removed. The reproductive performance in each group was analyzed according to the pregnancy rate after mating.
RESULTS
In the positive control group, all five mice became pregnant, and the number of fetuses was 4 to 5 (mean=4.60+/-0.55). In the comparison group, the pregnancy rate was 50%, and the mean number of fetuses was 1.40+/-0.55. In the experimental group, 7 of 10 (70%) mice became pregnant, and the mean number of fetuses was 4.71+/-2.56. There was no significant difference in the number of fetuses between the positive control and the experimental group (p=0.093), but there was a significant difference in the number of fetuses between the comparison group and the experimental group (p=0.019).
CONCLUSION
The results of this study suggest that autotransplantation of frozen ovaries using the vitrification method may restore the impaired ovarian function induced by antineoplastic chemotherapeutic agents.

Keyword

Antineoplastic chemotherapeutic agent; Ovarian failure; Cryopreserved ovary; Vitrification method; Autotransplantation

MeSH Terms

Adipose Tissue
Animals
Cyclophosphamide
Female
Fetus
Gonads
Humans
Infertility
Mice
Ovariectomy
Ovary
Pregnancy Rate
Vitrification
Cyclophosphamide

Figure

• 

  Fig 1. Gross findings in the auto-transplanted ovary in the experimental group. (A) There are several fetuses in the left uterus after successful autotransplantation of cryopreserved ovary, (B) Even after successful autotransplantation of the cryopreserved ovary, no fetus is in the left uterus, (C) After autotransplantation of the cryopreserved ovary, there is no feus in the left uterus due to atrophic change of the autotransplanted ovary.

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  Fig 2. A primary follicle in the the positive control group (A) and the experimental group (B) after transplantation (H&E stain, original magnification ×200). A primary follicle of the experimental group is alive and there is no significant difference in the structural components between the two groups.

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  Fig 3. H&E-stained ovaries. (A) An ovary in the positive control group has about 13 living oocytes, (B) an autografted ovary (right ovary) in the experimental group has about 5 living oocytes, (C) an atrophied ovary treated with cychlophosphamide (left ovary) in the experimental group has no oocytes (original magnification ×40).

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