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测试未刺激的体外成熟对卵母细胞成熟异常女性未成熟卵母细胞潜在发育的作用。

Testing the role of unstimulated in vitro maturation for potential development of immature oocytes in women with oocyte maturation abnormalities.

作者信息

Kalyoncu Şenol, Başbuğ Alper, Hatırnaz Ebru, Ellibeş Kaya Aşkı, Dokuzeylül Güngör Nur, Ürkmez Sebati Sinan, Civil Ürkmez Yeşim, Hatırnaz Şafak

机构信息

Department of Obstetrics and Gynecology, Hasan Kalyoncu University Faculty of Medicine, Gaziantep, Turkey

Department of Obstetrics and Gynecology, Düzce University Faculty of Medicine, Düzce, Turkey

出版信息

J Turk Ger Gynecol Assoc. 2024 Dec 10;25(4):219-223. doi: 10.4274/jtgga.galenos.2024.2023-10-9. Epub 2024 Jul 29.

DOI:10.4274/jtgga.galenos.2024.2023-10-9
PMID:39069733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11632636/
Abstract

OBJECTIVE

The aim of this study was to investigate the developmental potential of immature oocytes and evaluate whether unstimulated in vitro maturation (IVM) could serve as a treatment option for women with oocyte maturation abnormalities (OMAs).

MATERIAL AND METHODS

This cohort study was conducted between September 2019 and December 2022, and included women who underwent unstimulated, non-human chorionic gonadotropin (hCG) priming IVM. Oocytes were incubated with IVM medium for 26-48 hours and evaluated to compare their maturation profiles with the immature oocytes retrieved from the same patients in their previous in vitro fertilization cycles.

RESULTS

Among the twelve women in the study, eleven (91.6%) underwent whole exome sequencing analysis. Of these, 18 variants were identified in 10 individuals, excluding case 1, who had no previous mutation analysis. Of the mutations identified, 9 (50%) were located in , 5 (27.8%) in , 1 (5.6%) in , 1 (5.6%) in , 1 (5.6%) in , and 1 (5.6%) in . Apart from one woman with resistant ovary syndrome (ROS), none treated with unstimulated IVM had oocyte maturation. Remarkably, the only patient to achieve oocyte maturation in an unstimulated IVM cycle was case 11, who had ROS and a single variant.

CONCLUSION

Unstimulated, non-hCG primed IVM does not appear to be effective in the treatment of OMAs, perhaps with the exception of women with ROS. However, this study led our team to develop novel treatment options based on physiological mechanisms for some subtypes and supraphysiological approach for other subtypes of OMAs.

摘要

目的

本研究旨在探讨未成熟卵母细胞的发育潜能,并评估未刺激的体外成熟(IVM)是否可作为卵母细胞成熟异常(OMA)女性的一种治疗选择。

材料与方法

本队列研究于2019年9月至2022年12月进行,纳入接受未刺激、非人绒毛膜促性腺激素(hCG)预处理IVM的女性。卵母细胞与IVM培养基孵育26 - 48小时,并进行评估,以将其成熟情况与同一患者先前体外受精周期中获取的未成熟卵母细胞进行比较。

结果

研究中的12名女性中,11名(91.6%)接受了全外显子测序分析。其中,在10名个体中鉴定出18个变异,不包括病例1,其之前未进行突变分析。在鉴定出的突变中,9个(50%)位于 ,5个(27.8%)位于 ,1个(5.6%)位于 ,1个(5.6%)位于 ,1个(5.6%)位于 ,1个(5.6%)位于 。除一名患有抵抗性卵巢综合征(ROS)的女性外,接受未刺激IVM治疗的患者均未出现卵母细胞成熟。值得注意的是,在未刺激IVM周期中唯一实现卵母细胞成熟的患者是病例11,她患有ROS且有一个单一的 变异。

结论

未刺激、非hCG预处理的IVM似乎对OMA治疗无效,患有ROS的女性可能除外。然而,本研究促使我们的团队基于某些亚型的生理机制和其他亚型的超生理方法开发新的治疗选择。

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本文引用的文献

1
Unraveling the Puzzle: Oocyte Maturation Abnormalities (OMAS).解开谜团:卵母细胞成熟异常(OMAS)。
Diagnostics (Basel). 2022 Oct 15;12(10):2501. doi: 10.3390/diagnostics12102501.
2
Oocyte maturation abnormalities - A systematic review of the evidence and mechanisms in a rare but difficult to manage fertility pheneomina.卵母细胞成熟异常——对一种罕见但难以处理的生育现象的证据和机制的系统评价
Turk J Obstet Gynecol. 2022 Mar 28;19(1):60-80. doi: 10.4274/tjod.galenos.2022.76329.
3
Genetic factors as potential molecular markers of human oocyte and embryo quality.遗传因素作为人类卵子和胚胎质量的潜在分子标志物。
J Assist Reprod Genet. 2021 May;38(5):993-1002. doi: 10.1007/s10815-021-02196-z. Epub 2021 Apr 24.
4
Can in vitro maturation overcome cycles with repeated oocyte maturation arrest? A classification system for maturation arrest and a cohort study.体外成熟是否可以克服卵母细胞成熟阻滞的反复周期?成熟阻滞的分类系统和队列研究。
Int J Gynaecol Obstet. 2021 Jun;153(3):496-502. doi: 10.1002/ijgo.13490. Epub 2020 Dec 21.
5
In vitro maturation (IVM) of oocytes in patients with resistant ovary syndrome and in patients with repeated deficient oocyte maturation.卵母细胞在抵抗卵巢综合征患者和反复卵母细胞成熟不足患者中的体外成熟(IVM)。
J Assist Reprod Genet. 2018 Dec;35(12):2161-2171. doi: 10.1007/s10815-018-1317-z. Epub 2018 Sep 20.
6
Mutation analysis of the TUBB8 gene in primary infertile women with arrest in oocyte maturation.原发性卵母细胞成熟停滞的不孕女性中TUBB8基因的突变分析
Gynecol Endocrinol. 2018 Oct;34(10):900-904. doi: 10.1080/09513590.2018.1464138. Epub 2018 Apr 19.
7
Novel mutations in genes encoding subcortical maternal complex proteins may cause human embryonic developmental arrest.编码皮质下母质复合物蛋白的基因突变可能导致人类胚胎发育停滞。
Reprod Biomed Online. 2018 Jun;36(6):698-704. doi: 10.1016/j.rbmo.2018.03.009. Epub 2018 Mar 21.
8
Is elective single-embryo transfer a viable treatment policy in in vitro maturation cycles?在体外成熟周期中,选择性单胚胎移植是否是一种可行的治疗策略?
Fertil Steril. 2016 Dec;106(7):1691-1695. doi: 10.1016/j.fertnstert.2016.08.026. Epub 2016 Sep 24.
9
Clinical definition paper on in vitro maturation of human oocytes.关于人类卵母细胞体外成熟的临床定义文件。
Hum Reprod. 2016 Jul;31(7):1383-6. doi: 10.1093/humrep/dew109. Epub 2016 May 9.
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Mutations in TUBB8 and Human Oocyte Meiotic Arrest.TUBB8基因的突变与人类卵母细胞减数分裂阻滞
N Engl J Med. 2016 Jan 21;374(3):223-32. doi: 10.1056/NEJMoa1510791.