4.4 Review

Advances in the study of genetic factors and clinical interventions for fertilization failure

Related references

Note: Only part of the references are listed.
Review Developmental Biology

Fertilization failure after human ICSI and the clinical potential of PLCZ1

A. Cardona Barberan et al.

Summary: It has been twenty years since the discovery of PLCZ1 as the sperm oocyte-activating factor, which is responsible for triggering calcium oscillations necessary for oocyte activation. Abnormal PLCZ1 can lead to fertilization failure in human spermatozoa. Assisted oocyte activation using Ca+2 ionophores has proven to be effective for sperm-related fertilization failure but not for female-related failure. Therefore, the development of diagnostic tests is crucial for improving clinical management in these cases.

REPRODUCTION (2022)

Article Reproductive Biology

Mutation analysis of the TUBB8 gene in primary infertile women with oocyte maturation arrest

Zhongyuan Yao et al.

Summary: This study identified novel mutations in the TUBB8 gene and their prevalence, which may interfere with human oocyte maturation and result in infertility.

JOURNAL OF OVARIAN RESEARCH (2022)

Article Genetics & Heredity

Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation

Hongxia Yuan et al.

Summary: Genetic screening is an important tool in reproductive center management for determining etiology and optimizing treatment protocols. In this study, a target-sequencing panel of 22 genes related to female infertility was designed, and 68 patients with primary infertility or recurrent pregnancy loss were sequenced. Multiple variants were detected, including two frequently mutated genes and a novel TUBB8 variant. This target-sequencing method offers an efficient and cost-effective approach for screening in IVF clinics and supports the discovery of new pathogenic variants.

FRONTIERS IN GENETICS (2022)

Article Genetics & Heredity

Mutations in OOEP and NLRP5 identified in infertile patients with early embryonic arrest

Xiaomei Tong et al.

Summary: This study found that compound heterozygous missense variants in the OOEP gene and novel NLRP5 variants are associated with recurrent preimplantation embryonic arrest. These mutations result in downregulated transcriptome and decreased protein levels in arrested embryos.

HUMAN MUTATION (2022)

Review Endocrinology & Metabolism

Gene mutations associated with fertilization failure after in vitro fertilization/intracytoplasmic sperm injection

Yamei Xue et al.

Summary: This review summarizes and discusses the mutations of nine important genes associated with fertilization failure in infertile patients. The review highlights their roles in the fertilization process and suggests these mutations as potential targets for precision treatments in reproductive medicine. Furthermore, the review provides helpful clues for genetic counseling and optimizing clinical treatments for human infertility by supplying timely information on the genetic causes of fertilization failure.

FRONTIERS IN ENDOCRINOLOGY (2022)

Article Medicine, Research & Experimental

IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect

Jing Dai et al.

Summary: This study used whole-exome sequencing to identify the genetic causes of total fertilization failure (TFF) in male infertility. Homozygous variants in the novel gene IQCN were found in two individuals with abnormal acrosome structures. Knockout mice lacking the Iqcn gene showed similar phenotypes to humans with TFF. The study also revealed the role of IQCN in regulating microtubule nucleation during manchette assembly, and provided a genetic marker and therapeutic option for male TFF.

EMBO MOLECULAR MEDICINE (2022)

Article Multidisciplinary Sciences

Mutations in CCIN cause teratozoospermia and male infertility

Yong Fan et al.

Summary: Teratozoospermia, a disorder with genetic heterogeneity, is associated with CCIN gene mutations. The study found that Calicin, encoded by CCIN, plays a crucial role in sperm head shaping and male fertility. Mouse models and human samples confirmed the impact of CCIN mutations on sperm morphology and function. Intracytoplasmic sperm injections (ICSI) were effective in achieving healthy offspring for couples with CCIN variants.

SCIENCE BULLETIN (2022)

Article Genetics & Heredity

Mutation analysis of tubulin beta 8 classVIIIin infertile females with oocyte or embryonic defects

Ping Yang et al.

Summary: This study revealed a large number of variants of the TUBB8 gene in infertile females with oocyte or embryonic defects, broadening the mutational and phenotypic spectra of TUBB8 variants. The results further confirmed the critical role of TUBB8 in oocyte maturation, fertilization, and early embryonic development.

CLINICAL GENETICS (2021)

Article Endocrinology & Metabolism

A newNLRP5mutation causes female infertility and total fertilization failure

Mingzhao Li et al.

Summary: A new NLRP5 mutation has been identified as causing female infertility and total fertilization failure. This study aims to uncover the genetic reasons for TFF, with only PLCZ1, TLE6, and WEE2 mutations known to result in human fertilization failure.

GYNECOLOGICAL ENDOCRINOLOGY (2021)

Article Obstetrics & Gynecology

Novel bi-allelic variants in ACTL7A are associated with male infertility and total fertilization failure

Jing Wang et al.

Summary: The study identified novel compound heterozygous variants in ACTL7A as a genetic factor for human TFF and successfully rescued TFF through AOA.

HUMAN REPRODUCTION (2021)

Article Genetics & Heredity

Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice

Jing Dai et al.

Summary: Genetic variations in the ACTL9 gene in male individuals have been found to cause total fertilization failure (TFF). These variations disrupt the perinuclear theca structure and affect the localization of PLCz in sperm, leading to abnormal calcium oscillations in oocytes and subsequent TFF. Overcoming TFF can be achieved through assisted oocyte activation with calcium ionophore exposure.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

Article Andrology

Altered mitochondrial function in spermatozoa from patients with repetitive fertilization failure after ICSI revealed by proteomics

Marc Torra-Massana et al.

Summary: This study conducted the first proteomic analysis of spermatozoa from patients who experienced fertilization failure after ICSI, revealing significant alterations in protein content in the FF group, mainly related to mitochondrial proteins. Novel stable-protein pair analysis indicated that specific mitochondrial proteins lost correlations in specific FF samples, highlighting mitochondrial deregulations in FF patients.

ANDROLOGY (2021)

Article Endocrinology & Metabolism

Clinical exome sequencing identifies novel compound heterozygous mutations of the WEE2 gene in primary infertile women with fertilization failure

Ancong Wang et al.

Summary: This study identified novel compound heterozygous mutations of the WEE2 gene in a female with fertilization failure through clinical exome sequencing, expanding the spectrum of WEE2 mutations and enhancing the prognostic value of testing for WEE2 mutations in infertile women with fertilization failure.

GYNECOLOGICAL ENDOCRINOLOGY (2021)

Review Genetics & Heredity

The comprehensive variant and phenotypic spectrum of TUBB8 in female infertility

Wei Zheng et al.

Summary: TUBB8 gene is frequently analyzed in the genetic diagnosis of female infertility, and 102 variants of this gene have been identified. Through whole exome sequencing, 29 TUBB8 variants were identified in this study, including 20 novel ones. The study also provides evidence that TUBB8 variants with large polar bodies had chromosome segregation errors, expanding the spectrum of TUBB8 variants, particularly for embryonic arrest.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2021)

Article Cell Biology

Identification of Novel Mutations in CDC20: Expanding the Mutational Spectrum for Female Infertility

Lin Zhao et al.

Summary: Mutations in the CDC20 gene play a crucial role in oocyte maturation and fertilization, leading to various infertility phenotypes. This study expands the spectrum of known mutations in CDC20 and provides new evidence for its involvement in female infertility characterized by oocyte maturation arrest and fertilization failure.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Article Genetics & Heredity

Novel WEE2 compound heterozygous mutations identified in patients with fertilization failure or poor fertilization

Jiamin Jin et al.

Summary: Three novel compound heterozygous WEE2 variants were identified in patients with pronucleus formation failure, leading to reduced levels of WEE2 protein in oocytes. In vitro experiments showed that mutant WEE2 gene caused decreased WEE2 protein levels or subcellular translocation in HeLa cells, resulting in decreased levels of phosphorylated Cdc2 protein.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2021)

Review Cell Biology

Oxidative stress in oocyte aging and female reproduction

Ling Wang et al.

Summary: Oxidative stress plays a significant role in oocyte aging, leading to a gradual decrease in oocyte quantity and quality, as well as various reproductive pathologies. Strategies to delay oocyte aging include targeting oxidative stress through autophagy antioxidant pathways and antioxidants, along with creating a hypoxic culture environment for oocytes in vitro.

JOURNAL OF CELLULAR PHYSIOLOGY (2021)

Article Multidisciplinary Sciences

Structure of a mammalian sperm cation channel complex

Shiyi Lin et al.

Summary: The CatSpermasome is a complex structure consisting of multiple components essential for sperm motility and fertility. The organization of this complex includes pore-forming proteins and auxiliary subunits, forming a pavilion-like structure that stabilizes the entire complex. The detailed assembly and organization of the CatSpermasome provide a foundation for the development of treatments related to male infertility and non-hormonal contraceptives.

NATURE (2021)

Review Endocrinology & Metabolism

Should rescue ICSI be re-evaluated considering the deferred transfer of cryopreserved embryos in in-vitro fertilization cycles? A systematic review and meta-analysis

Alessio Paffoni et al.

Summary: The success rates of fresh embryo transfers after late rescue ICSI are not satisfactory, but transferring cryopreserved rescue ICSI embryos seems to offer improved results. Combining rescue ICSI with frozen embryo transfer may overcome technical and biological issues associated with fresh transfer after late rescue ICSI, possibly representing an efficient procedure for couples experiencing fertilization failure.

REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY (2021)

Article Endocrinology & Metabolism

Calcium Ionophore (A23187) Rescues the Activation of Unfertilized Oocytes After Intracytoplasmic Sperm Injection and Chromosome Analysis of Blastocyst After Activation

Ziwen Xu et al.

Summary: The study found that using calcium ionophore (A23187) for rescue activation of unfertilized oocytes can obtain a certain proportion of high-quality blastocysts with normal karyotype, and it does not significantly affect the timing of embryo development. In clinical practice, direct activation with calcium ionophore (A23187) after ICSI is more effective than rescue activation the next day.

FRONTIERS IN ENDOCRINOLOGY (2021)

Article Cell Biology

A Novel Assisted Oocyte Activation Method Improves Fertilization in Patients With Recurrent Fertilization Failure

Meng Wang et al.

Summary: The study demonstrates that a new AOA method combining cycloheximide and ionomycin significantly increases fertilization rates for most TFF patients, potentially offering therapeutic benefits for couples experiencing severe fertilization deficiencies even after conventional AOA treatment.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Review Obstetrics & Gynecology

Molecular genetics of infertility: loss-of-function mutations in humans and corresponding knockout/mutated mice

Shi-Ya Jiao et al.

Summary: Infertility is a major issue affecting 15% of couples worldwide, with genetic causes accounting for approximately 50% of cases. Research on genetic causes of infertility focuses on identifying and understanding mutations related to infertility.

HUMAN REPRODUCTION UPDATE (2021)

Article Genetics & Heredity

Genetic analyses of a large cohort of infertile patients with globozoospermia, DPY19L2 still the main actor, GGN confirmed as a guest player

Tristan Celse et al.

Summary: Globozoospermia is a rare phenotype of primary male infertility, with anomalies of DPY19L2 accounting for the majority of cases. Genetic analyses revealed homozygous DPY19L2 deletions in some patients, while others had different DPY19L2 defects or mutations in other candidate genes. Patients with a higher rate of round-headed spermatozoa were more often diagnosed, and diagnosis efficiency increased for patients with > 50% globozoospermia.

HUMAN GENETICS (2021)

Article Obstetrics & Gynecology

Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia

M. S. Oud et al.

HUMAN REPRODUCTION (2020)

Article Genetics & Heredity

Novel homozygous mutations in PATL2 lead to female infertility with oocyte maturation arrest

Zhenxing Liu et al.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2020)

Article Genetics & Heredity

Expanding the genetic and phenotypic spectrum of female infertility caused by TLE6 mutations

Jing Lin et al.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2020)

Review Endocrinology & Metabolism

Frozen IVF Cycles to Circumvent the Hormonal Storm on Endometrium

Paola Vigano et al.

TRENDS IN ENDOCRINOLOGY AND METABOLISM (2020)

Article Genetics & Heredity

A genomics approach to females with infertility and recurrent pregnancy loss

Sateesh Maddirevula et al.

HUMAN GENETICS (2020)

Article Genetics & Heredity

Novel mutations in the PLCZ1 gene associated with human low or failed fertilization

Ping Yuan et al.

MOLECULAR GENETICS & GENOMIC MEDICINE (2020)

Article Obstetrics & Gynecology

Intracytoplasmic sperm injection (ICSI) for non-male factor indications: a committee opinion

Alan Penzias et al.

FERTILITY AND STERILITY (2020)

Article Genetics & Heredity

ZP2 pathogenic variants cause in vitro fertilization failure and female infertility

Can Dai et al.

GENETICS IN MEDICINE (2019)

Article Obstetrics & Gynecology

Novel WEE2 gene variants identified in patients with fertilization failure and female infertility

Shuai Zhao et al.

FERTILITY AND STERILITY (2019)

Article Genetics & Heredity

Homozygous missense mutation Arg207Cys in the WEE2 gene causes female infertility and fertilization failure

Xiaoyu Yang et al.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2019)

Article Genetics & Heredity

Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest

Jian Mu et al.

JOURNAL OF MEDICAL GENETICS (2019)

Article Obstetrics & Gynecology

Novel phospholipase C zeta 1 mutations associated with fertilization failures after ICSI

Marc Torra-Massana et al.

HUMAN REPRODUCTION (2019)

Article Genetics & Heredity

Novel compound heterozygous mutations in WEE2 causes female infertility and fertilization failure

Xiaopei Zhou et al.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2019)

Article Biochemistry & Molecular Biology

The comprehensive mutational and phenotypic spectrum of TUBB8 in female infertility

Biaobang Chen et al.

EUROPEAN JOURNAL OF HUMAN GENETICS (2019)

Article Andrology

Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility

Yong-Liang Shang et al.

ASIAN JOURNAL OF ANDROLOGY (2019)

Article Genetics & Heredity

Mutational analysis of IZUMO1R in women with fertilization failure and polyspermy after in vitro fertilization

Mengru Yu et al.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2018)

Article Genetics & Heredity

Homozygous Mutations in WEE2 Cause Fertilization Failure and Female Infertility

Qing Sang et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2018)

Article Medicine, Research & Experimental

PATL2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice

Marie Christou-Kent et al.

EMBO MOLECULAR MEDICINE (2018)

Article Obstetrics & Gynecology

Temporal Differences in Utilization of Intracytoplasmic Sperm Injection Among US Regions

Pavel Zagadailov et al.

OBSTETRICS AND GYNECOLOGY (2018)

Article Multidisciplinary Sciences

Sperm-borne phospholipase C zeta-1 ensures monospermic fertilization in mice

Kaori Nozawa et al.

SCIENTIFIC REPORTS (2018)

Article Genetics & Heredity

Dosage effects of ZP2 and ZP3 heterozygous mutations cause human infertility

Wenqiang Liu et al.

HUMAN GENETICS (2017)

Article Genetics & Heredity

Female Infertility Caused by Mutations in the Oocyte-Specific Translational Repressor PATL2

Sateesh Maddirevula et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2017)

Article Genetics & Heredity

Biallelic Mutations in PATL2 Cause Female Infertility Characterized by Oocyte Maturation Arrest

Biaobang Chen et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2017)

Article Genetics & Heredity

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility

Tailai Chen et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2017)

Article Medicine, Research & Experimental

SPINK2 deficiency causes infertility by inducing sperm defects in heterozygotes and azoospermia inhomozygotes

Zine-Eddine Kherraf et al.

EMBO MOLECULAR MEDICINE (2017)

Review Obstetrics & Gynecology

Oocyte activation deficiency: a role for an oocyte contribution?

Marc Yeste et al.

HUMAN REPRODUCTION UPDATE (2016)

Article Genetics & Heredity

A new mutation identified in SPATA16 in two globozoospermic patients

Elias ElInati et al.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2016)

Article Medicine, General & Internal

Mutations in TUBB8 and Human Oocyte Meiotic Arrest

Ruizhi Feng et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

Article Multidisciplinary Sciences

Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models

Felipe A. Navarrete et al.

SCIENTIFIC REPORTS (2016)

Article Biochemistry & Molecular Biology

Novel signalling mechanism and clinical applications of sperm-specific PLCζ

Michail Nomikos

BIOCHEMICAL SOCIETY TRANSACTIONS (2015)

Editorial Material Obstetrics & Gynecology

A plea for caution and more research in the 'experimental' use of ionophores in ICSI

Jonathan van Blerkom et al.

REPRODUCTIVE BIOMEDICINE ONLINE (2015)

Article Biotechnology & Applied Microbiology

TLE6 mutation causes the earliest known human embryonic lethality

Anas M. Alazami et al.

GENOME BIOLOGY (2015)

Review Obstetrics & Gynecology

Rescue intracytoplasmic sperm injection: a systematic review

Ronit Beck-Fruchter et al.

FERTILITY AND STERILITY (2014)

Review Obstetrics & Gynecology

Assisted oocyte activation following ICSI fertilization failure

Frauke Vanden Meerschaut et al.

REPRODUCTIVE BIOMEDICINE ONLINE (2014)

Review Obstetrics & Gynecology

Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature

B. C. J. M. Fauser et al.

REPRODUCTIVE BIOMEDICINE ONLINE (2014)

Article Genetics & Heredity

A HOMOZYGOUS DELETION OF THE DPY19L2 GENE IS A CAUSE OF GLOBOZOOSPERMIA IN MEN FROM THE REPUBLIC OF MACEDONIA

P. Noveski et al.

BALKAN JOURNAL OF MEDICAL GENETICS (2013)

Article Obstetrics & Gynecology

Phospholipase Cζ rescues failed oocyte activation in a prototype of male factor infertility

Michail Nomikos et al.

FERTILITY AND STERILITY (2013)

Article Obstetrics & Gynecology

MLPA and sequence analysis of DPY19L2 reveals point mutations causing globozoospermia

Charles Coutton et al.

HUMAN REPRODUCTION (2012)

Article Genetics & Heredity

A Recurrent Deletion of DPY19L2 Causes Infertility in Man by Blocking Sperm Head Elongation and Acrosome Formation

Radu Harbuz et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2011)

Article Genetics & Heredity

DPY19L2 Deletion as a Major Cause of Globozoospermia

Isabelle Koscinski et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2011)

Article Endocrinology & Metabolism

Clinical and economic analysis of rescue intracytoplasmic sperm injection cycles

Einat Shalom-Paz et al.

GYNECOLOGICAL ENDOCRINOLOGY (2011)

Article Multidisciplinary Sciences

Global quantification of mammalian gene expression control

Bjoern Schwanhaeusser et al.

NATURE (2011)

Article Andrology

A newly discovered mutation in PICK1 in a human with globozoospermia

Gang Liu et al.

ASIAN JOURNAL OF ANDROLOGY (2010)

Review Biochemistry & Molecular Biology

Genetic male infertility and mutation of CATSPER ion channels

Michael S. Hildebrand et al.

EUROPEAN JOURNAL OF HUMAN GENETICS (2010)

Article Obstetrics & Gynecology

Artificial oocyte activation and intracytoplasmic sperm injection

Mohammad Hossein Nasr-Esfahani et al.

FERTILITY AND STERILITY (2010)

Article Genetics & Heredity

Cdc20 Is Critical for Meiosis I and Fertility of Female Mice

Fang Jin et al.

PLOS GENETICS (2010)

Article Genetics & Heredity

Human Male Infertility Caused by Mutations in the CATSPER1 Channel Protein

Matthew R. Avenarius et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2009)

Article Obstetrics & Gynecology

Electrical activation of oocytes after intracytoplasmic sperm injection: a controlled randomized study

Ragaa Mansour et al.

FERTILITY AND STERILITY (2009)

Article Biochemistry & Molecular Biology

A combinatorial code for CPE-mediated translational control

Maria Pique et al.

Editorial Material Obstetrics & Gynecology

Ongoing twin pregnancy after rescue intracytoplasmic sperm injection of unfertilized abnormal oocytes

Navid Esfandiari et al.

FERTILITY AND STERILITY (2008)

Article Developmental Biology

Ion channels that control fertility in mammalian spermatozoa

Betsy Navarro et al.

INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY (2008)

Article Genetics & Heredity

Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia

Anika H. D. M. Dam et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2007)

Article Genetics & Heredity

Sensorineural deafness and male infertility: a contiguous gene deletion syndrome

Yuzhou Zhang et al.

JOURNAL OF MEDICAL GENETICS (2007)

Article Biochemistry & Molecular Biology

CATSPER2, a human autosomal nonsyndromic male infertility gene

N Avidan et al.

EUROPEAN JOURNAL OF HUMAN GENETICS (2003)

Article Obstetrics & Gynecology

Failed fertilization: is it predictable?

NG Mahutte et al.

CURRENT OPINION IN OBSTETRICS & GYNECOLOGY (2003)

Article Genetics & Heredity

Mater, a maternal effect gene required for early embryonic development in mice

ZB Tong et al.

NATURE GENETICS (2000)