Doxorubicin (DOX), one of the most commonly used anticancer medications, has been reported to affect fertility by damaging ovarian follicles; however, the dose-dependent toxicity of DOX on the dynamic follicle development and oocyte maturation has not been well-defined. Our objective is to determine the effects of human-relevant exposure levels of DOX on follicular functions across developmental time. In vitro cultured multilayered secondary mouse follicles were treated with DOX at 0, 2, 20, 100, and 200 nM for 24 h, and follicle development, hormone secretion, and oocyte maturation were analyzed. DOX caused dose-dependent toxicity on follicle growth, survival, and secretion of 17β-estradiol (E2). At 200 nM, DOX induced DNA damage and apoptosis in follicle somatic cells first and then in oocytes, which was correlated with the uptake of DOX first to the somatic cells followed by germ cells. Follicles treated with DOX at 0, 2, and 20 nM showed similar oocyte metaphase II (MII) percentages after in vitro oocyte maturation; however, 20 nM DOX significantly increased the number of MII oocytes with abnormal spindle morphology and chromosome misalignment. In an effort to harmonize the in vitro study to in vivo treatment, dose-dependent toxicity on oocyte meiotic maturation was found in 16-day-old CD-1 mice treated with DOX at 0, 0.4, 2, and 10 mg/kg, consistent with the in vitro oocyte maturation outcomes. Our study demonstrates that DOX has dose-dependent toxicity on ovarian follicle development, hormone secretion, and oocyte maturation, which are three key factors to support the female reproductive and endocrine functions.

Objectives: Our review aimed to consolidate the latest update on the application of in vitro maturation among immature oocyte harvest in combination with ovarian tissue cryopreservation known as ovarian tissue oocyte–in vitro maturation. Methods: A thorough search for relevant studies was conducted via PubMed, Google Scholar, EMBASE, and clinical.gov databases up to December 2020. The primary outcome was the oocyte maturation rate, which measured the number of immature oocytes (geminal vesicle stage) that progressed to mature oocytes (meiosis II stage) following in vitro maturation. The secondary outcomes were the fertilization rate following intracytoplasmic sperm injection/in vitro fertilization of these oocytes for the embryo cryopreservation cohort. Our review included pre-pubertal girls and women with cancer who underwent ovarian tissue oocyte–in vitro maturation as fertility preservation. Results: The primary search identified 207 studies. Twelve manuscripts were selected for inclusion in our review following duplication assessment, title and abstract screening, and full-text evaluation tailored to our inclusion criteria. All the population belonged to a cancer group and underwent concurrent ovarian tissue oocyte–in vitro maturation. A total of 5724 immature oocytes were obtained following ovarian tissue cryopreservation. Approximately 33.84% of the immature oocytes successfully matured via in vitro maturation, which were cryopreserved as oocytes or fertilized as embryos and subsequently stored for future use. Conclusion: Our review proposed the potential application of ovarian tissue oocyte–in vitro maturation in increasing the number of mature oocytes. The acceptable improvement in oocyte maturation rate following in vitro maturation indicates that improving oocyte outcomes is an excellent cost-effective strategy for fertility preservation among women with cancer.

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Purpose Closed vitrification poses a risk of adversely affecting embryo development, while it may minimize the risk of contamination. We assessed the effects of closed-system human embryo vitrification on fetal development after implantation, neonatal outcome, and clinical safety. Methods This was a retrospective cohort study conducted at a private fertility clinic. A total of 875 vitrified-warmed blastocysts that were single-transferred under hormone-replacement cycles between November 2011 and December 2013 were randomly divided into two groups (closed vitrification, n 313; open vitrification, n 562) after receiving the patients' consent forms. Developmental competence after implantation, including gestational age, birth weight, sex, Apgar score, and anomalies of newborns, after the transfer of blastocysts vitrified by closing vitrification was compared with that obtained in the case of open vitrification. Results There were no significant differences between the use of closed and open vitrification systems in embryo development after implantation, gestational age, birth weight, sex ratio, Apgar score, and congenital anomalies of newborns. Conclusion Human embryos can be vitrified using a closed vitrification system without impairment of neonatal development.

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