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      Pregnancy and fertilization potential of immature oocytes retrieved in intracytoplasmic sperm injection cycles

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          Abstract

          Objective

          The goal of this study was to evaluate the pregnancy potential of immature (metaphase I or germinal vesicle stage) oocytes retrieved in intracytoplasmic sperm injection (ICSI) cycles.

          Methods

          A total of 1,871 couples with infertility underwent 2,984 ICSI cycles. Cycles in which three or fewer oocytes were retrieved were included in this study in order to evaluate the pregnancy potential of immature oocytes. Cycles were divided into five groups (group I-V), according to the maturation status of the oocytes at the time of cumulus cell removal and ICSI. The fertilization and pregnancy rates after ICSI were analyzed and compared among the study groups based on the maturation status of the retrieved oocytes.

          Results

          The retrieval of only immature oocytes was associated with a significant decrease in the fertilization rate (76.1%±37.3% vs. 49.0%±49.1%, 66.7%±48.7%; group I vs. group II, group III, respectively) and the average number of transferred embryos (1.5±0.7 vs. 1.1±0.4, 1.1±0.6). The cycle cancellation rate was significantly higher when only immature oocytes were retrieved. The clinical pregnancy rate decreased significantly when the transferred embryos had originated from immature oocytes (16.9% vs. 10.3%, 1.2%).

          Conclusion

          In ICSI cycles, the fertilization potential and pregnancy potential of the immature oocytes retrieved in ICSI cycles were inferior to those of mature oocytes. Therefore, increasing the number of injectable oocytes and transferrable embryos by using immature oocytes after their spontaneous in vitro maturation does not necessarily improve pregnancy outcomes.

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          Most cited references28

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          Maturation in vitro of immature human oocytes for clinical use.

          Human oocyte maturation is considered as the reinitiation and completion of the first meiotic division from the germinal vesicle stage (prophase I) to metaphase II, and the accompanying cytoplasmic maturation for fertilization and early embryonic development. Immature human oocytes obtained from patients undergoing gynaecological surgery, or ovulation induction or having polycystic ovary syndrome (PCOS) can be matured and fertilized in vitro. To date, 80% of immature oocytes matured to metaphase II when cultured in maturation medium supplemented with gonadotrophins and 85% of matured oocytes fertilized and cleaved in vitro. Following transfer of these embryos, pregnancies and live births have been achieved. However, the capacity for oocyte maturation was different when the immature oocytes were retrieved from PCOS patients and when the oocytes were cryopreserved at germinal vesicle stage.
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            Assessment of nuclear and cytoplasmic maturation in in-vitro matured human oocytes.

            With improved prospects for the use of human oocyte in-vitro maturation in assisted reproductive technologies, the need to define more clearly the coordination of nuclear and cytoplasmic maturation has arisen. Immunofluorescence and confocal microscopy were used to evaluate cell cycle-dependent modifications in chromatin and microtubules in human germinal vesicle oocytes (n = 455) undergoing in-vitro maturation. Four distinct classes of germinal vesicle stage oocytes were identified based on the expression of G2/interphase characteristics, but, of these, only one class of oocytes was competent to complete meiotic progression to metaphase-II in vitro. The majority of germinal vesicle stage oocytes resumed meiosis within 6 h (88.9%) of culture and exhibited an accelerated pace of progression to metaphase-II (66.7%) over 24 h, but in general were unable to maintain meiotic arrest and defaulted into interphase within 24 h of polar body emission. Characterization of microtubule dynamics and chromatin phosphorylation demonstrates specific cell cycle deficiencies in in-vitro matured human oocytes. This work forms a basis for future studies aimed at optimizing nuclear and cytoplasmic maturation during in-vitro maturation.
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              Maturation of human oocytes in vitro and their developmental competence.

              Complete maturation of oocytes is essential for the developmental competence of embryos. Any interventions in the growth phase of the oocyte and the follicle in the ovary will affect oocyte maturation, fertilization and subsequent embryo development. Oocyte size is associated with maturation and embryo development in most species examined and this may indicate that a certain size is necessary to initiate the molecular cascade of normal nuclear and cytoplasmic maturation. The minimum size of follicle required for developmental competence in humans is 5-7 mm in diameter. Maturation in vitro can be accomplished in humans, but is associated with a loss of developmental competence unless the oocyte is near completion of its preovulatory growth phase. This loss of developmental competence is associated with the absence of specific proteins in oocytes cultured to metaphase II in vitro. The composition of culture medium used successfully for maturation of human oocytes is surprisingly similar to that originally developed for maturation of oocytes in follicle culture in vitro. The presence of follicle support cells in culture is necessary for the gonadotrophin-mediated response required to mature oocytes in vitro. Gonadotrophin concentration and the sequence of FSH and FSH-LH exposure may be important for human oocytes, particularly those not exposed to the gonadotrophin surge in vivo. More research is needed to describe the molecular and cellular events, the presence of checkpoints and the role of gene expression, translation and protein uptake on completing oocyte maturation in vitro and in vivo. In the meantime, there are very clear applications for maturing oocytes in human reproductive medicine and the success rates achieved in some of these special applications are clinically valuable.
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                Author and article information

                Journal
                Clin Exp Reprod Med
                Clin Exp Reprod Med
                CERM
                Clinical and Experimental Reproductive Medicine
                The Korean Society for Reproductive Medicine
                2233-8233
                2233-8241
                September 2015
                30 September 2015
                : 42
                : 3
                : 118-125
                Affiliations
                [1 ]Laboratory of Reproductive Medicine, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea.
                [2 ]Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea.
                Author notes
                Corresponding author: Chun Kyu Lim. Laboratory of Reproductive Medicine, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, 17 Seoae-ro 1-gil, Jung-gu, Seoul 04619, Korea. Tel: +82-2-2000-7592, Fax: +82-2-2265-5621, seungzzang@ 123456paran.com
                Article
                10.5653/cerm.2015.42.3.118
                4604295
                83101b57-6e89-4749-878d-b711e6534e46
                Copyright © 2015. The Korean Society for Reproductive Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 July 2015
                : 05 August 2015
                : 03 September 2015
                Categories
                Original Article

                Obstetrics & Gynecology
                fertilization,in vitro maturation,intracytoplasmic sperm injection,mature oocyte,pregnancy

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