Unexplained total abnormal fertilization of donor oocytes in ICSI with using spermatozoa from different patients

Fertilization is a fundamental process of development, and the blocking mechanisms act at the zona pellucida (ZP) and plasma membrane of the egg to prevent any additional sperm from binding, permeating, and fusing after fertilization. In clinical practice, some couples undergoing recurrent IVF failures that mature oocytes had abnormal fertilization for unknown reason. Ovastacin encoded by ASTL cleave the ZP protein ZP2 and play a key role in preventing polyspermy. Here, we identified bi-allelic variants in ASTL that are mainly characterized by fertilization problems in humans. All four independent affected individuals had bi-allelic frameshift variants or predicted damaging missense variants, which follow a Mendelian recessive inheritance pattern. The frameshift variants significantly decreased the quantity of ASTL protein in vitro. And all missense variants affected the enzymatic activity that cleaves ZP2 in mouse egg in vitro. Three knock-in female mice (corresponding to three missense variants in patients) all show subfertility due to low embryo developmental potential. This work presents strong evidence that pathogenic variants in ASTL cause female infertility and provides a new genetic marker for the diagnosis of fertilization problems.

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Bi-allelic variants in ASTL cause abnormal fertilization or oocyte maturation defects

Zeng

Chen

Sun

et al. 2023

Human Molecular Genetics

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Effect of the time interval between oocyte retrieval and ICSI on embryo development and reproductive outcomes: a systematic review

Xiao

Sun

Zhen

et al. 2021

Reprod Biol Endocrinol

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Background Intra-cytoplasmic sperm injection (ICSI) is used in assisted reproductive technology (ART) laboratories. However, there is no consensus regarding the precise time intervals within ICSI cycles [oocyte pick up (OPU), oocyte denudation (DN), and ICSI], and results are inconsistent and contradictory. Thus, we aim to evaluate whether there is a concordance regarding the time intervals used in different laboratories and a concrete time that gives better laboratory and reproductive results. Methods A systematic review of the literature until July 25, 2020, was performed with the keywords “Oocyte Denudation/Denudation/Oocyte,” “Intra-cytoplasmic Sperm Injection/ICSI,” “Oocyte/Oocyte maturation/ cumulus,” and “Cumulus removal/ removal.” Articles and abstracts in English and involving human subjects referring to the effects of oocyte DN time on embryo development and clinical outcomes were included. Results Of the 294 evaluated articles, 24 (including 20 full articles and 4 abstracts) were included in this review. Eighteen studies analysed the effect of OPU-DN time on embryo development and clinical outcomes. Most of these studies concluded that OPU-DN time did not influence ICSI outcomes, but some suggested that oocytes should be incubated for a short time before DN to improve oocyte maturity and enhance ICSI outcomes. In addition to reports on positive or negligible effects, adverse effects were reported in 12 studies on DN-ICSI timing. Neither OPU-DN nor DN-ICSI time could improve live birth rate. Conclusions Oocytes should be pre-incubated for a short duration (preferably < 4 h) before DN according to the ART laboratory schedule. More randomised controlled trials are warranted to clarify the effect of DN-ICSI timing on ICSI outcomes.

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Oocyte Spontaneous Activation: An Overlooked Cellular Event That Impairs Female Fertility in Mammals

Cui

2021

Front. Cell Dev. Biol.

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In mammals, including humans, mature oocytes are ovulated into the oviduct for fertilization. Normally, these oocytes are arrested at metaphase of the second meiosis (MII), and this arrest can be maintained for a certain period, which is essential for fertilization in vivo and oocyte manipulations in vitro, such as assisted reproduction in clinics and nuclear/spindle transfer in laboratories. However, in some species and under certain circumstances, exit from MII occurs spontaneously without any obvious stimulation or morphological signs, which is so-called oocyte spontaneous activation (OSA). This mini-review summarizes two types of OSA. In the first type (e.g., most rat strains), oocytes can maintain MII arrest in vivo, but once removed out, oocytes undergo OSA with sister chromatids separated and eventually scattered in the cytoplasm. Because the stimulation is minimal (oocyte collection itself), this OSA is incomplete and cannot force oocytes into interphase. Notably, once re-activated by sperm or chemicals, those scattered chromatids will form multiple pronuclei (MPN), which may recapitulate certain MPN and aneuploidy cases observed in fertility clinics. The second type of OSA occurs in ovarian oocytes (e.g., certain mouse strains and dromedary camel). Without ovulation or fertilization, these OSA-oocytes can initiate intrafollicular development, but these parthenotes cannot develop to term due to aberrant genomic imprinting. Instead, they either degrade or give rise to ovarian teratomas, which have also been reported in female patients. Last but not the least, genetic models displaying OSA phenotypes and the lessons we can learn from animal OSA for human reproduction are also discussed.

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Unexplained total abnormal fertilization of donor oocytes in ICSI with using spermatozoa from different patients

Cited by 4 publications

References 15 publications

Bi-allelic variants in ASTL cause abnormal fertilization or oocyte maturation defects

Bi-allelic variants in ASTL cause abnormal fertilization or oocyte maturation defects

Effect of the time interval between oocyte retrieval and ICSI on embryo development and reproductive outcomes: a systematic review

Oocyte Spontaneous Activation: An Overlooked Cellular Event That Impairs Female Fertility in Mammals

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