A standardized approach for case selection and genomic data analysis of maternal exomes for the diagnosis of oocyte maturation and early embryonic developmental arrest in IVF

ABSTRACTOBJECTIVETo develop a methodology for case selection and whole-exome sequencing (WES) analysis in infertile women due to recurrent oocyte maturation defects(OOMD) and/or preimplantation embryo lethality (PREMBL).DESIGNRetrospective cohort study.SETTINGIVF patients attending the Istanbul Memorial Hospital (2015-2021). WES and bioinformatics were performed at Igenomix and National Research Council, Italy.PATIENTSA statistical methodology for identification of infertile endophenotypes (recurrent low oocyte maturation rate, LMR, low fertilization rate, LFR, and preimplantation developmental arrest, PDA, was developed using a large IVF dataset (11,221 couples). 28 OOMD/PREMBL infertile women were subsequently enrolled for WES.INTERVENTION30X-WES was performed on women’s gDNA. Pathogenic variants were prioritized using a custom-made bioinformatic pipeline set to minimize false positive discoveries through resampling in control cohorts (i.e., HGDP and 1,343 WES from oocyte donors). Individual scRNAseq data from 18 human MII oocytes and antral granulosa cells(AGC) was used for genome-wide validation.MAIN OUTCOME MEASUREIdentification of High-impact variants causative of OOMD/PREMBL endophenotypes.RESULTSVariant prioritization analysis identified 265 unique variants in 248 genes (average per sample 22.4). 87.8% of genes harbouring high-impact variants are expressed by MII oocytes and/or AGC, significantly higher compared to a random sample of controls. Seven of the 28 women (25%) are homozygous carriers of missense pathogenic variants in known candidate genes for OOMD/PREMBL, including PATL2, NLRP5 (N=2), TLE6,PADI6, TUBB8 and TRIP13. Furthermore, novel gene-disease associations were identified. One LMR woman was a homozygous carrier of high impact variants in ELSA, an essential gene for phopase I meiotic transition in mice, whereas three women carried biallelic pathogenic variants in CEP128 gene, participating in the formation of the spindle in mitosis and ciliogenesis.CONCLUSIONSThis analytical framework revealed known and new genes associated with isolated recurrent OOMD/PREMBL, providing essential indications for scaling this strategy to larger studies.

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O-115 Parental whole-exome sequencing allows the discovery of genetic causes of extreme IVF phenotypes such as oocyte/embryo developmental arrest and recurrent low fertilization

Human Reproduction ◽

10.1093/humrep/deab126.024 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

A Capalbo ◽

S Buonaiuto ◽

G Damaggio ◽

M Cetinkaya ◽

B Yuksel ◽

...

Keyword(s):

Exome Sequencing ◽

Candidate Genes ◽

Whole Exome Sequencing ◽

False Positive ◽

High Impact ◽

Unexplained Infertility ◽

Developmental Arrest ◽

New Genes ◽

Fold Enrichment ◽

Whole Exome

Abstract Study question Do whole-exome sequencing (WES) data from infertile women provide valuable information for the discovery of genes/pathways involved in extreme IVF phenotypes, i.e. oocyte/embryo developmental arrest? Summary answer The development of a specific bioinformatic WES pipeline revealed known and new candidate genes/pathways for isolated oocyte/embryo developmental failure,providing the foundation to scale up research. What is known already The use of IVF has made it possible to identify extreme and isolated infertility phenotypes such as recurrent low oocytes maturity (LMR), recurrent low fertilization rate (LFR), or preimplantation developmental arrest (PDA) that would remain concealed in natural conception attempts. Recent applications of WES in families with such extreme adverse IVF phenotypes have led to the discovery of new genes and pathways affecting unique functions of gametes and exclusive mechanisms necessary for early embryo development. Here, we apply a tailored bioinformatic approach to WES from women displaying extreme IVF phenotypes to discover new causative genes/pathways involved in unexplained infertility. Study design, size, duration Twenty-two infertile consanguineous women(December 2018-September 2020) suffering from long-term unexplained infertility. Eight cases were classified as PDA (<20% normally developed embryos in > 2 IVF cycles), 8 as LMR (<20% mature oocytes in > 2 IVF cycles), 4 as LFR (<20% of normally fertilized oocytes in > 2 IVF cycles). Two women with recurrent IVF failure (>10 IVF cycles) were also included. A control set of 1660 WES from oocyte donors was used to control for false-positive discoveries. Participants/materials, setting, methods WES at 30X was performed on enrolled women’s gDNA using Illumina short-reads technology. Following annotation, variants were filtered to prioritize putative detrimental variants in genes relevant for oocyte/embryonic development using a previously developed and validated pipeline that minimizes false-positive discoveries. Runs of homozygosity (ROH) within each sample were identified using Refined IBD software. Individual-level single-cell RNAseq (scRNAseq) dataset from 18 human oocytes was used to verify the expression of the identified target genes. Main results and the role of chance The variant prioritization pipeline employed identified 1,160 unique variants in 1,017 genes (average per sample 59.9 sd 8.5). 453 variants were private to this study compared to the 1000 Genomes and gnomAD databases, 3% affecting splicing and/or the gene product length. Significant 5-fold enrichment of 41 genes involved in DNA-damage and repair pathways commonly associated with ovarian function/oocyte quality was observed (p < 0.001). TP53/AKT pathway also showed significant 5-fold enrichment for 45 genes (p < 0.001). This finding is consistent with the known relationship between infertility and cell-cycle/cancer genes. Overall, 66.4% (675/1,017; 95%CI:63.4-69.3) of the targeted genes were expressed in MII human oocytes. Two women (9%) were homozygous carriers of missense pathogenic variants in known candidate genes previously associated to oocyte/embryo developmental arrest (TRIP13, chr5_901344_C/T, CADD percentile 0.999; PADI6, chr1_17394384_C/G, CADD percentile 0.999). Remarkably, four additional women were carriers of high-impact variants in JAKMIP1, a member of a recently characterized family of proteins involved in various cellular processes, including cytoskeleton rearrangement, cell polarization, and intracellular transport. High-impact JAKMP1 variants were never observed in the oocyte donor control dataset. JAKMIP1 mRNA was detected in each individual biological replicate of scRNAseq analysis of MII oocytes with a mean of 6 transcripts per million. Limitations, reasons for caution Functional analysis is ongoing to validate the newly identified genes, data need to be verified in different ethnicities. Nevertheless, this study demonstrates the establishment of a specific and scalable analytical framework that can be employed for the identification of genetic causes in unexplained infertility cases characterized by defective developmental patterns. Wider implications of the findings Scaling up this investigative approach would provide an effective strategy for discovering new genes/pathways in what is considered idiopathic infertility, further defining precision reproductive medicine interventions. Importantly, this study revealed lesions in genetic patterns involved in chronic diseases providing a molecular footprint of the well-established link between infertility and comorbidities. Trial registration number none

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Investigation of monogenic causes of familial breast cancer: data from the BEACCON case-control study

npj Breast Cancer ◽

10.1038/s41523-021-00279-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Na Li ◽

Belle W. X. Lim ◽

Ella R. Thompson ◽

Simone McInerny ◽

Magnus Zethoven ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Candidate Genes ◽

Familial Aggregation ◽

Loss Of Function ◽

Cancer Data ◽

Pathogenic Variants ◽

New Genes ◽

Predisposing Genes ◽

Predisposition Genes

AbstractBreast cancer (BC) has a significant heritable component but the genetic contribution remains unresolved in the majority of high-risk BC families. This study aims to investigate the monogenic causes underlying the familial aggregation of BC beyond BRCA1 and BRCA2, including the identification of new predisposing genes. A total of 11,511 non-BRCA familial BC cases and population-matched cancer-free female controls in the BEACCON study were investigated in two sequencing phases: 1303 candidate genes in up to 3892 cases and controls, followed by validation of 145 shortlisted genes in an additional 7619 subjects. The coding regions and exon–intron boundaries of all candidate genes and 14 previously proposed BC genes were sequenced using custom designed sequencing panels. Pedigree and pathology data were analysed to identify genotype-specific associations. The contribution of ATM, PALB2 and CHEK2 to BC predisposition was confirmed, but not RAD50 and NBN. An overall excess of loss-of-function (LoF) (OR 1.27, p = 9.05 × 10−9) and missense (OR 1.27, p = 3.96 × 10−73) variants was observed in the cases for the 145 candidate genes. Leading candidates harbored LoF variants with observed ORs of 2–4 and individually accounted for no more than 0.79% of the cases. New genes proposed by this study include NTHL1, WRN, PARP2, CTH and CDK9. The new candidate BC predisposition genes identified in BEACCON indicate that much of the remaining genetic causes of high-risk BC families are due to genes in which pathogenic variants are both very rare and convey only low to moderate risk.

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Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel

Frontiers in Endocrinology ◽

10.3389/fendo.2020.605237 ◽

2021 ◽

Vol 11 ◽

Author(s):

Vincenza Precone ◽

Rossella Cannarella ◽

Stefano Paolacci ◽

Gian Maria Busetto ◽

Tommaso Beccari ◽

...

Keyword(s):

Next Generation Sequencing ◽

Male Infertility ◽

Next Generation ◽

Male Population ◽

Pathogenic Variants ◽

Custom Made ◽

Number Of Genes ◽

General Male Population ◽

Generation Sequencing ◽

Spermatogenic Failure

BackgroundInfertility affects about 7% of the general male population. The underlying cause of male infertility is undefined in about 50% of cases (idiopathic infertility). The number of genes involved in human spermatogenesis is over two thousand. Therefore, it is essential to analyze a large number of genes that may be involved in male infertility. This study aimed to test idiopathic male infertile patients negative for a validated panel of “diagnostic” genes, for a wide panel of genes that we have defined as “pre-diagnostic.”MethodsWe developed a next-generation sequencing (NGS) gene panel including 65 pre-diagnostic genes that were used in 12 patients who were negative to a diagnostic genetic test for male infertility disorders, including primary spermatogenic failure and central hypogonadism, consisting of 110 genes.ResultsAfter NGS sequencing, variants in pre-diagnostic genes were identified in 10/12 patients who were negative to a diagnostic test for primary spermatogenic failure (n = 9) or central hypogonadism (n = 1) due to mutations of single genes. Two pathogenic variants of DNAH5 and CFTR genes and three uncertain significance variants of DNAI1, DNAH11, and CCDC40 genes were found. Moreover, three variants with high impact were found in AMELY, CATSPER 2, and ADCY10 genes.ConclusionThis study suggests that searching for pre-diagnostic genes may be of relevance to find the cause of infertility in patients with apparently idiopathic primary spermatogenic failure due to mutations of single genes and central hypogonadism.

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P–442 Cancer does not adversely affect oocyte maturation in vitro with the exception of breast cancer

Human Reproduction ◽

10.1093/humrep/deab130.441 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

I Viran. . Klun ◽

J Bedenk ◽

N Jancar

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Oocyte Maturation ◽

In Vitro Maturation ◽

Hormonal Stimulation ◽

Infertile Women ◽

Maturation In Vitro ◽

Infertile Patients

Abstract Study question Do different types of cancer affect the success of oocyte maturation in vitro compared to infertile women included in the in vitro fertilization (IVF) program? Summary answer Cancer does not adversely affect oocyte maturation in vitro, with the exception of breast cancer, compared to infertile women in the in vitro fertilization program. What is known already Vitrification and storage of oocytes in liquid nitrogen is one of the real options for maintaining reproductive function in cancer patients. Despite careful hormonal stimulation of the ovaries, however, the proportion of oocytes is immature and lost to the patient. In vitro maturation of oocytes can play an important role in resolving immature oocytes and increasing the chances of conception in cancer patients. Moreover, it can mean a safe way to store oocytes when ovarian hormonal stimulation could worsen the disease. Therefore, the aim of this study was to determine whether different types of cancer affect oocyte in vitro maturation. Study design, size, duration After ovarian stimulation in 18 cancer patients, the number and maturity of oocytes were compared to 21 infertile patients in the IVF program over a three-year period. In both groups, 119 germinal vesicle-GV oocytes were matured in vitro to compare the maturation rate. After IVF in a subset of 17 infertile patients, the fertilization of in vitro and in vivo matured oocytes was compared in the same cycles. The procedure was considered in cancer patients. Participants/materials, setting, methods In this prospective study, forty-five GV oocytes in cancer patients and 74 GV oocytes in infertile patients underwent in vitro maturation procedure. Each oocyte was matured in vitro in the MediCult IVM System by conditioning in LAG medium and maturation for up to 28 hours in IVM medium with added hormones FSH and hCG, in coculture with cumulus cells from mature oocytes in the same patients. Oocytes were fertilized by intracytoplasmic sperm injection (ICSI). Main results and the role of chance After controlled ovarian hormonal stimulation, 198 oocytes were retrieved in cancer patients and 259 oocytes in infertile women and there were no significant differences in the number of retrieved oocytes, proportion of degenerated oocytes and proportion of GV oocytes. In cancer patients, the proportion of oocytes that matured in vitro was lower than in infertile patients (66.0 vs. 80.0%), but the difference was not significant. Among cancer patients, the oocyte maturation rate tended to be lower in patients with breast cancer than in patients with other cancers (54.5% vs. 81.2%; difference not significant). However, in patients with breast cancer, significantly fewer oocytes matured in vitro than in infertile patients (54.5% vs. 80.0%; P < 0.05, Chi-Square test) even though they tended to be younger (29.3 ± 7.4 vs. 33.4 ± 5.0 years; non-significant difference). After in vitro maturation, there was a 13% increase in mature oocyte yield in cancer patients and a 20.1% increase in infertile women with no significant difference observed. After ICSI in a subset of infertile women, there was approximately the same fertilization rate between oocytes matured in vitro and in vivo (55.1% vs. 57.0%) in the same cycles. Limitations, reasons for caution For ICSI in oocytes matured in vitro, we had to use semen collected the day before, while oocytes matured in vivo were fertilized with fresh semen in the same cycle. Therefore, we could not compare the development of embryos in both groups. Wider implications of the findings: In vitro maturation of oocytes in connection with their vitrification or vitrification of embryos after their fertilization appears to be a valuable way to maintain the fertility of young cancer patients, but a worse outcome is expected in breast cancer patients. Trial registration number National Medical Ethical Committee Approval, No. 0120–222/2016–2; KME 115/04/16.

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High-impact rare genetic variants in severe schizophrenia

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2112560118 ◽

2021 ◽

Vol 118 (51) ◽

pp. e2112560118

Author(s):

Anthony W. Zoghbi ◽

Ryan S. Dhindsa ◽

Terry E. Goldberg ◽

Aydan Mehralizade ◽

Joshua E. Motelow ◽

...

Keyword(s):

Genetic Variants ◽

Odds Ratio ◽

High Impact ◽

Psychiatric Genetics ◽

Loss Of Function ◽

Treatment Resistant ◽

Complex Disorders ◽

Extreme Phenotype ◽

Case Selection ◽

Rare Genetic Variants

Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia. We sequenced 112 individuals with severe, extremely treatment-resistant schizophrenia, 218 individuals with typical schizophrenia, and 4,929 controls. We compared the burden of rare, damaging missense and loss-of-function variants between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls across mutation intolerant genes. Individuals with severe, extremely treatment-resistant schizophrenia had a high burden of rare loss-of-function (odds ratio, 1.91; 95% CI, 1.39 to 2.63; P = 7.8 × 10−5) and damaging missense variants in intolerant genes (odds ratio, 2.90; 95% CI, 2.02 to 4.15; P = 3.2 × 10−9). A total of 48.2% of individuals with severe, extremely treatment-resistant schizophrenia carried at least one rare, damaging missense or loss-of-function variant in intolerant genes compared to 29.8% of typical schizophrenia individuals (odds ratio, 2.18; 95% CI, 1.33 to 3.60; P = 1.6 × 10−3) and 25.4% of controls (odds ratio, 2.74; 95% CI, 1.85 to 4.06; P = 2.9 × 10−7). Restricting to genes previously associated with schizophrenia risk strengthened the enrichment with 8.9% of individuals with severe, extremely treatment-resistant schizophrenia carrying a damaging missense or loss-of-function variant compared to 2.3% of typical schizophrenia (odds ratio, 5.48; 95% CI, 1.52 to 19.74; P = 0.02) and 1.6% of controls (odds ratio, 5.82; 95% CI, 3.00 to 11.28; P = 2.6 × 10−8). These results demonstrate the power of extreme phenotype case selection in psychiatric genetics and an approach to augment schizophrenia gene discovery efforts.

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Host Gene Regulation by Transposable Elements: The New, the Old and the Ugly

Viruses ◽

10.3390/v12101089 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1089 ◽

Cited By ~ 2

Author(s):

Rocio Enriquez-Gasca ◽

Poppy A. Gould ◽

Helen M. Rowe

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Transposable Elements ◽

Essential Gene ◽

Expression Patterns ◽

Genetic Material ◽

Endogenous Retroviruses ◽

Host Gene ◽

New Genes ◽

Host Genes

The human genome has been under selective pressure to evolve in response to emerging pathogens and other environmental challenges. Genome evolution includes the acquisition of new genes or new isoforms of genes and changes to gene expression patterns. One source of genome innovation is from transposable elements (TEs), which carry their own promoters, enhancers and open reading frames and can act as ‘controlling elements’ for our own genes. TEs include LINE-1 elements, which can retrotranspose intracellularly and endogenous retroviruses (ERVs) that represent remnants of past retroviral germline infections. Although once pathogens, ERVs also represent an enticing source of incoming genetic material that the host can then repurpose. ERVs and other TEs have coevolved with host genes for millions of years, which has allowed them to become embedded within essential gene expression programmes. Intriguingly, these host genes are often subject to the same epigenetic control mechanisms that evolved to combat the TEs that now regulate them. Here, we illustrate the breadth of host gene regulation through TEs by focusing on examples of young (The New), ancient (The Old), and disease-causing (The Ugly) TE integrants.

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Definitive demonstration by synthesis of genome annotation completeness

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1905990116 ◽

2019 ◽

Vol 116 (48) ◽

pp. 24206-24213 ◽

Cited By ~ 7

Author(s):

Paul R. Jaschke ◽

Gabrielle A. Dotson ◽

Kay S. Hung ◽

Diane Liu ◽

Drew Endy

Keyword(s):

Essential Gene ◽

Single Point ◽

Viable Cell ◽

Essential Genes ◽

Single Point Mutation ◽

Evolutionary Adaptation ◽

Wild Type ◽

Bioinformatic Tools ◽

Design And Synthesis ◽

New Genes

We develop a method for completing the genetics of natural living systems by which the absence of expected future discoveries can be established. We demonstrate the method using bacteriophage øX174, the first DNA genome to be sequenced. Like many well-studied natural organisms, closely related genome sequences are available—23 Bullavirinae genomes related to øX174. Using bioinformatic tools, we first identified 315 potential open reading frames (ORFs) within the genome, including the 11 established essential genes and 82 highly conserved ORFs that have no known gene products or assigned functions. Using genome-scale design and synthesis, we made a mutant genome in which all 11 essential genes are simultaneously disrupted, leaving intact only the 82 conserved but cryptic ORFs. The resulting genome is not viable. Cell-free gene expression followed by mass spectrometry revealed only a single peptide expressed from both the cryptic ORF and wild-type genomes, suggesting a potential new gene. A second synthetic genome in which 71 conserved cryptic ORFs were simultaneously disrupted is viable but with ∼50% reduced fitness relative to the wild type. However, rather than finding any new genes, repeated evolutionary adaptation revealed a single point mutation that modulates expression of gene H, a known essential gene, and fully suppresses the fitness defect. Taken together, we conclude that the annotation of currently functional ORFs for the øX174 genome is formally complete. More broadly, we show that sequencing and bioinformatics followed by synthesis-enabled reverse genomics, proteomics, and evolutionary adaptation can definitely establish the sufficiency and completeness of natural genome annotations.

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A Survey of Essential Gene Function in the Yeast Cell Division Cycle

Molecular Biology of the Cell ◽

10.1091/mbc.e06-04-0368 ◽

2006 ◽

Vol 17 (11) ◽

pp. 4736-4747 ◽

Cited By ~ 67

Author(s):

Lisa Yu ◽

Lourdes Peña Castillo ◽

Sanie Mnaimneh ◽

Timothy R. Hughes ◽

Grant W. Brown

Keyword(s):

Cell Cycle ◽

Dna Replication ◽

Yeast Cell ◽

Dna Content ◽

Cell Cycle Progression ◽

Essential Gene ◽

Nucleotide Metabolism ◽

Cycle Progression ◽

New Genes ◽

Yeast Genes

Mutations impacting specific stages of cell growth and division have provided a foundation for dissecting mechanisms that underlie cell cycle progression. We have undertaken an objective examination of the yeast cell cycle through flow cytometric analysis of DNA content in TetO7promoter mutant strains representing 75% of all essential yeast genes. More than 65% of the strains displayed specific alterations in DNA content, suggesting that reduced function of an essential gene in most cases impairs progression through a specific stage of the cell cycle. Because of the large number of essential genes required for protein biosynthesis, G1 accumulation was the most common phenotype observed in our analysis. In contrast, relatively few mutants displayed S-phase delay, and most of these were defective in genes required for DNA replication or nucleotide metabolism. G2 accumulation appeared to arise from a variety of defects. In addition to providing a global view of the diversity of essential cellular processes that influence cell cycle progression, these data also provided predictions regarding the functions of individual genes: we identified four new genes involved in protein trafficking (NUS1, PHS1, PGA2, PGA3), and we found that CSE1 and SMC4 are important for DNA replication.

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New genes involved in Angelman syndrome-like: expanding the genetic spectrum

10.1101/2020.07.16.206052 ◽

2020 ◽

Author(s):

Cinthia Aguilera ◽

Elisabeth Gabau ◽

Ariadna Ramirez-Mallafré ◽

Carme Brun-Gasca ◽

Jana Dominguez-Carral ◽

...

Keyword(s):

Differential Diagnosis ◽

Genetic Heterogeneity ◽

Angelman Syndrome ◽

De Novo ◽

System Development ◽

Neuron System ◽

Pathogenic Variants ◽

New Genes ◽

Whole Exome ◽

Eeg Abnormalities

AbstractAngelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with absence of speech, happy disposition, frequent laughter, hyperactivity, stereotypies, ataxia and seizures with specific EEG abnormalities. There is a 10-15% of patients with an AS phenotype whose genetic cause remains unknown (Angelman-like syndrome, AS-like). Whole-exome sequencing (WES) was performed on a cohort of 14 patients with clinical features of AS and no molecular diagnosis. As a result, we identified 10 de novo and 1 X-linked pathogenic/likely pathogenic variants in 10 neurodevelopmental genes (SYNGAP1, VAMP2, TBL1XR1, ASXL3, SATB2, SMARCE1, SPTAN1, KCNQ3, SLC6A1 and LAS1L) and one deleterious de novo variant in a candidate gene (HSF2). Our results highlight the wide genetic heterogeneity in AS-like patients and expands the differential diagnosis. New AS-like genes do not interact directly with UBE3A gene product but are involved in synapsis and neuron system development.

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Outcome of GnRH antagonist ICSI cycles triggered by GnRH agonist plus Recombinant hCG versus triggered with Recombinant hCG alone in fresh autologous ICSI cycle

Iraqi Journal of Embryos and Infertility Researches ◽

10.28969/ijeir.v10.i1.r8 ◽

2020 ◽

Vol 10 (1) ◽

pp. 119-131

Author(s):

Wafaa Mohammed Abed ◽

Mohammed Oda Selman

Keyword(s):

Pregnancy Rate ◽

Oocyte Maturation ◽

Standard Dose ◽

Statistical Significance ◽

Control Group ◽

Infertile Women ◽

Final Oocyte Maturation ◽

Reproductive Techniques ◽

The Mean ◽

The Difference

To explore whether dual triggering for final oocyte maturation using a low dose of recombinant human chorionic gonadotropin (hCG) plus gonadotropin-releasing hormone agonist (GnRH-a) is as effective as the standard dose of recombinant hCG triggering alone in term of a total number of retrieved oocytes, fertilization and pregnancy rate in fresh autologous antagonist intracytoplasmic sperm injection (ICSI) cycles. 80 infertile women undergoing ICSI, aged ˂ 40 years, 18˂ Body mass index ˂30 Kg/m2 included in fresh autologous antagonist ICSI cycles. 40 women received a Standard dose of recombinant hCG (500 µg) alone and 40 women received GnRH-a (0.2 mg triptorelin plus 250 µg recombinant hCG) were used for final oocytes maturation. This study was conducted at the High Institute for Infertility Diagnosis and Assisted Reproductive Techniques, Al Nahrain University. The mean total number of retrieved oocytes, fertilization, and pregnancy rate were measured. The mean total oocyte number being statistically higher in the dual trigger group. The mean number of fertilized oocytes and clinical pregnancy rates was higher in the dual trigger group than in the control group, but the difference showed borderline statistical significance. Furthermore, fertilization rates show no statistical difference between the control group and the dual trigger group. Results of the study confirm that dual triggers show favorable improvement in fresh autologous antagonist ICSI cycles with the use of GnRH agonists plus hCG compared with hCG alone for triggering of final oocyte maturation.

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