scholarly journals Disruption in ACTL7A causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest

2020 ◽  
Vol 6 (35) ◽  
pp. eaaz4796
Author(s):  
Aijie Xin ◽  
Ronggui Qu ◽  
Guowu Chen ◽  
Ling Zhang ◽  
Junling Chen ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Semen Analysis ◽  
Oocyte Activation ◽  
Male Factor ◽  
Vitro Fertilization ◽  
Whole Exome ◽  
Embryonic Arrest ◽  
Future Practice ◽  
Human And Mouse

Early embryonic arrest is a challenge for in vitro fertilization (IVF). No genetic factors were previously revealed in the sperm-derived arrest of embryonic development. Here, we reported two infertile brothers presenting normal in conventional semen analysis, but both couples had no embryos for transfer after several IVF and intracytoplasmic sperm injection (ICSI). Whole-exome sequencing identified a homozygous missense mutation of ACTL7A in both brothers. This mutation is deleterious and causes sperm acrosomal ultrastructural defects. The Actl7a knock-in mouse model was generated, and male mutated mice showed sperm acrosomal defects, which were completely consistent with the observations in patients. Furthermore, the sperm from ACTL7A/Actl7a-mutated men and mice showed reduced expression and abnormal localization of PLCζ as a potential cause of embryonic arrest and failure of fertilization. Artificial oocyte activation could successfully overcome the Actl7a-mutated sperm-derived infertility, which is meaningful in the future practice of IVF/ICSI for the ACTL7A-associated male infertility.

scholarly journals Homozygous mutations in REC114 cause female infertility characterised by multiple pronuclei formation and early embryonic arrest

2019 ◽  
Vol 57 (3) ◽  
pp. 187-194 ◽  
Author(s):  
Wenjing Wang ◽  
Jie Dong ◽  
Biaobang Chen ◽  
Jing Du ◽  
Yanping Kuang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Splice Site ◽  
Genetic Factors ◽  
Splice Site Mutation ◽  
Female Infertility ◽  
Site Mutation ◽  
Whole Exome ◽  
Pronuclear Formation ◽  
Embryonic Arrest

BackgroundAbnormal pronuclear formation during fertilisation and subsequent early embryonic arrest results in female infertility. In recent years, with the prevalence of assisted reproductive technology, a few genes have been identified that are involved in female infertility caused by abnormalities in oocyte development, fertilisation and embryonic development. However, the genetic factors responsible for multiple pronuclei formation during fertilisation and early embryonic arrest remain largely unknown.ObjectiveWe aim to identify genetic factors responsible for multiple pronuclei formation during fertilisation or early embryonic arrest.MethodsWhole-exome sequencing was performed in a cohort of 580 patients with abnormal fertilisation and early embryonic arrest. Effects of mutations were investigated in HEK293T cells by western blotting and immunoprecipitation, as well as minigene assay.ResultsWe identified a novel homozygous missense mutation (c.397T>G, p.C133G) and a novel homozygous donor splice-site mutation (c.546+5G>A) in the meiotic gene REC114. REC114 is involved in the formation of double strand breaks (DSBs), which initiate homologous chromosome recombination. We demonstrated that the splice-site mutation affected the normal alternative splicing of REC114, while the missense mutation reduced the protein level of REC114 in vitro and resulted in the loss of its function to protect its partner protein MEI4 from degradation.ConclusionsOur study has identified mutations in REC114 responsible for human multiple pronuclei formation and early embryonic arrest, and these findings expand our knowledge of genetic factors that are responsible for normal human female meiosis and fertility.

scholarly journals Evaluation of comparison of clinical outcome treated oocyte with ionomycin and strontium chloride in infertile couple with previous failed in vitro fertilization

2019 ◽  
Author(s):  
Marziyeh Norozi-Hafshejani ◽  
Marziyeh Tavalaee ◽  
Mohammad Hossein Nasr- Esfahani
Keyword(s):  
Clinical Results ◽  
Fertilization Rate ◽  
Infertile Couple ◽  
Strontium Chloride ◽  
Oocyte Activation ◽  
Male Factor ◽  
Chi Square ◽  
Vitro Fertilization ◽  
Failed Fertilization

Introduction: Several factors are involved in failed fertilization following intracytoplasmic sperm injection (ICSI), which could be related to sperm, oocyte factors and/or both. Failure in oocyte activation is considered as the most important factor in failed fertilization after ICSI. To overcome this shortcoming, artificial oocyte activation (AOA) after ICSI has been suggested. Commonly, ionomycin and strontium chloride are used as the most efficient agents for oocyte activation in the clinic. In this study, for the first time, the clinical results of ionomycin and strontium chloride were compared on sister oocytes of couples who previously have had fertilization failure after ICSI. Methods: In this intervention study, 14 couples with male factor infertility and previous failed fertilization after ICSI were included in this study. Oocytes of their wives were divided into two groups. Half of the oocytes after ICSI were treated with ionomicin and other half were treated with strontium chloride. Then, fertilization rate, embryo quality and pregnancy status were compared through SPSS 18 software, Paired sample t-test and chi-square test. Results: Percentage of fertilization rate was significantly higher in oocytes that were activated using strontium chloride compared to those that were activated with ionomycin (p<0.0001). Although, the pregnancy rate was insignificantly higher in strontium chloride group than ionomycin group (p=0.387), but the quality of embryo was similar between the two groups (p=0.924). Conclusion: In infertile men with previous failed fertilization after ICSI, the use of strontium chloride can also be recommended for oocyte activation.

scholarly journals RGS12 as a Novel Maternal-Effect Gene Causes Arrest at the Pronuclear Stage of Human Zygote

2021 ◽  
Author(s):  
Tianzhong Ma ◽  
Chengpeng Zhang ◽  
Songxia Zhou ◽  
Xuezhen Xie ◽  
Jingyao Chen ◽  
...  
Keyword(s):  
Transcriptome Profiling ◽  
Missense Variant ◽  
Oocyte Activation ◽  
Vitro Fertilization ◽  
Cytostatic Factor ◽  
Pn Stage ◽  
Cell Transcriptome ◽  
Species Specific ◽  
Embryonic Arrest

Abstract Background: Early embryonic arrest is one of the major causes of female infertility after in vitro fertilization (IVF), but the causal gene of arrest at the pronuclear (PN) zygote stage is largely unknown. Results: To understand this process, we recruited a family characterized by recurrent PN arrest during IVF cycles and performed whole-exome sequencing. The missense variant c.C1630T (p.R544W) in RGS12 was responsible for a phenotype characterized by paternal transmission. RGS12 controls Ca2+ oscillation, which is required for oocyte activation after fertilization. Single-cell transcriptome profiling of PN-arrest zygotes revealed defective established translation, RNA processing and cell cycle, which explained the failure of complete oocyte activation. Furthermore, we identified proximal genes involved in Ca2+ oscillation–cytostatic factor–anaphase-promoting complex (Ca2+ oscillation–CSF–APC) signaling, including upregulated CaMKII, ORAI1, CDC20, and CDH1 and downregulated EMI1 and BUB3. The findings indicated abnormal spontaneous Ca2+ oscillations leading to oocytes with prolonged low CSF and high APC level, which resulted in defective nuclear envelope breakdown and DNA replication. The changes in levels of critical genes were confirmed by examining other independent PN-arrest zygotes. However, the PN-arrest zygote phenotype was not consistent with that of RGS12-deficient mice, thereby indicating species-specific functions between human and mouse. Conclusion: Our findings expand our knowledge of the genetic determinants of human early embryonic arrest at the PN stage and provide guidance for selecting clinically infertile individuals with PN-arrest zygotes for Ca2+ intervention.

scholarly journals Post-wash total motile sperm count a useful predictor in the decision to perform IVF/ICSI in patients with non-male factor infertility

2020 ◽  
Vol 3 (2) ◽  
pp. 99-106
Author(s):  
Sara Mahmood Qureshi ◽  
Salma Kafeel ◽  
Riffat Bibi ◽  
Jawad Mohmand
Keyword(s):  
Sperm Quality ◽  
Sperm Count ◽  
Adverse Outcomes ◽  
Male Factor Infertility ◽  
Motile Sperm ◽  
Operating Characteristics ◽  
Male Factor ◽  
Vitro Fertilization ◽  
Total Motile Sperm Count

Introduction: The unrestricted use of intracytoplasmic sperm injection (ICSI) for non-male factor infertility is associated with adverse outcomes. Post-wash total motile sperm count (PW-TMSC) offers prognostic value to assess sperm quality and aid in the decision to perform in vitro fertilization (IVF) or ICSI. Objectives: The aim of this study was to identify the effect of PW-TMSC on fertilization rates in patients undergoing IVF cycles exclusively with non-male factor infertility. It also aimed to identify whether unnecessary ICSI could be avoided in such cases, thus maximizing optimal outcomes. Materials & Methods: We retrospectively analyzed age, semen volume, prewash TMSC, and PW-TMSC in 68 conventional IVF cycles of infertile couples with non-male factor infertility. Clinical characteristics including female age, number of follicles, level of estradiol on trigger day, mature cumulus-oocyte complexes (COCs) collected, were also included. Results: Incidence of <30% fertilization was significantly higher in the 4-<10 Million group compared with the ≥20 Million post-wash TMSC group (P<0.001). Furthermore, Receiver operating characteristics (ROC) analysis revealed post-wash TMSC as a significant predictor (P<0.05) of total failed fertilization (TFF) and of ≥30% fertilization (P<0.05) with area under curve (AUC) of 0. 79 and 0.77, respectively, with a deemed cutoff of 10.89 Million. Conclusion: Post-wash TMSC is a good predictor of fertilization; it can help in avoiding potentially low or even total fertilization failure (TFF). A cut-off point of 10.89 Million or less should warrant the use of ICSI.

scholarly journals Poor ovarian reserve and male infertility in a rural in vitro fertilization setup: a case report

2021 ◽  
Vol 10 (10) ◽  
pp. 4020
Author(s):  
Neha V. Harne ◽  
Vaibhav K. Nadkarni ◽  
Purnima Nadkarni ◽  
Jigna Garasia
Keyword(s):  
Semen Analysis ◽  
Oocyte Quality ◽  
Reproductive Age ◽  
Vitro Fertilization ◽  
Advanced Reproductive Age ◽  
Sperm Chromosomes ◽  
Definition Of ◽  
Poor Ovarian Reserve ◽  
Strict Definition

Female fertility begins to decline many years prior to the onset of menopause despite continued regular ovulatory cycles. Although there is no strict definition of advanced reproductive age in women, infertility becomes more pronounced after the age of 35. In the female, the number of oocytes decreases with age until the menopause. Oocyte quality also diminishes, due in part to increased aneuploidy because of factors such as changes in spindle integrity. Although older male age affects the likelihood of conception, abnormalities in sperm chromosomes and in some components of the semen analysis are less important than the frequency of intercourse. Age is as accurate as any other predictor of conception with assisted reproductive technology.

scholarly journals Results and experiences after 1000 IVF cycles at the Clinic for gynecology and obstetrics in Novi Sad

2011 ◽  
Vol 64 (11-12) ◽  
pp. 565-569
Author(s):  
Vesna Kopitovic ◽  
Stevan Milatovic ◽  
Aleksandra Trninic-Pjevic ◽  
Artur Bjelica ◽  
Irena Bujas ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Intracytoplasmic Sperm Injection ◽  
Clinical Pregnancy ◽  
Reproductive Age ◽  
Male Factor ◽  
Fertilization Program ◽  
Vitro Fertilization ◽  
Gynecology And Obstetrics ◽  
Novi Sad

Introduction. Infertility affects 15-17% of reproductive age couples in our country, and 10-15% of couples worldwide. The aim of this paper was to present results and experience gained after the first 1000 cycles of the national In Vitro Fertilization (IVF) program, to offer professional standard of work in our country and to compare it with results obtained in Europe and worldwide. Material and methods. The study prospectively included 1000 women who had undergone national In Vitro Fertilization program from October 2006 until November 2009 at the Department of Gynecology and Obstetrics, Clinical Center of Vojvodina, Novi Sad. Results. The analysis included 1000 in vitro fertilization cycles. Male factor infertility was the leading cause (56.9%) followed by tubal factor (45.9%). The classic method of in vitro fertilization constituted 72.3% of all cycles, while intracytoplasmic sperm injection (ICSI) method was used in 27.7% of all cycles. The average number of embryos transferred was 2.67. The cycle cancellation rate was 14.10% and the aspiration rate was 94.40%. The clinical pregnancy and live birth rate were 33.41% and 26.78% per embryo transfer, respectively. Discussion and conclusion. The results in our study showed that in our setting there are far less intracytoplasmic sperm injection cycles compared with the European average of 66.5% of all fresh cycles, and that we transferred more embryos on average. Our success rates are comparable with those in other European countries where the clinical pregnancy rates per aspiration and per transfer for in vitro fertilization were 29 and 32.4%, respectively in the period of observation. For intracytoplasmic sperm injection, the corresponding rates were 29.9 and 33%.

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