Yi-Fan Gu

• Researcher at Central South University

STUDY QUESTION Can a quantitative method be developed to differentiate between blastocysts with similar or same inner cell mass (ICM) and trophectoderm (TE) grades, while also reflecting their potential for live birth? SUMMARY ANSWER We developed BlastScoringNet, an interpretable deep-learning model that quantifies blastocyst ICM and TE morphology...

This study aimed to find the most effective PGT-M strategy for Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD), and to reduce misdiagnosis caused by embryo recombination in DMD. A retrospective study was performed by analyzing 158 PGT-M cycles for DMD/BMD in Reproductive and Genetic Hospital of CITIC-Xiangya between 2009 and 2023. P...

Several reports have presented that balanced chromosomal rearrangements (BCRs) carriers with normal phenotypes may be carriers of complex rearrangements. However, the incidence and PGT clinical outcomes of cryptic complex chromosome rearrangements (CCCRs) in individuals with BCRs is remain unknown. We recruited a cohort of 1,264 individuals with BC...

Background Recurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a limited number of cases. Variants of the β-tubulin subunit gene, TUBB8, cause oocyte mei...

Purpose To explore whether spermatozoa from AZFc microdeletion patients affect their outcomes of intracytoplasmic sperm injection (ICSI). Methods Eighty‐five patients with AZFc microdeletion were recruited. A control group of one hundred and forty patients with severe oligozoospermia but without AZF microdeletion was selected using propensity scor...

Aneuploidy is frequently detected in early human embryos as a major cause of early pregnancy failure. However, how aneuploidy affects cellular function remains elusive. Here, we profiled the transcriptomes of 14,908 single cells from 203 human euploid and aneuploid blastocysts involving autosomal and sex chromosomes. Nearly all of the blastocysts c...

Background Deep learning has been increasingly investigated for assisting clinical in vitro fertilization (IVF). The first technical step in many tasks is to visually detect and locate sperm, oocytes, and embryos in images. For clinical deployment of such deep learning models, different clinics use different image acquisition hardware and different...

In vitro fertilization (IVF) has revolutionized infertility treatment, benefiting millions of couples worldwide. However, current clinical practices for embryo selection rely heavily on visual inspection of morphology, which is highly variable and experience dependent. Here, we propose a comprehensive artificial intelligence (AI) system that can in...

Background Deep learning has been increasingly investigated for assisting clinical in vitro fertilization (IVF). The first technical step in many tasks is to visually detect and locate sperm, oocytes, and embryos in images. For clinical deployment of such deep learning models, different clinics use different image acquisition hardware and different...

Background: In infertility treatment, blastocyst morphological grading is commonly used in clinical practice for blastocyst evaluation and selection, but has shown limited predictive power on live birth outcomes of blastocysts. To improve live birth prediction, a number of artificial intelligence (AI) models have been established. Most existing AI...

Background Very low-coverage (0.1 to 1×) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for genome-wide association study (GWAS). To support genetic screening using preimplantation genetic testing (PGT) in a large population, the sequencing coverage goes below 0.1× to a...

Total fertilization failure (TFF) is an important cause of infertility; however, the genetic basis of TFF caused by male factors remains to be clarified. In this study, whole-exome sequencing was firstly used to screen for genetic causes of TFF after intracytoplasmic sperm injection (ICSI), and homozygous variants in the novel gene IQ motif-contain...

Objective To explore whether the associations of 3 blastocyst morphological parameters, namely, degree of blastocyst expansion (expansion), appearance of trophectoderm (TE) and inner cell mass, with live birth and singleton birth weight are influenced by blastocyst freezing and biopsy. Design A retrospective study. Setting An assisted reproductiv...

Background In infertility treatment, blastocyst morphological grading is commonly used in clinical practice for blastocyst evaluation and selection, but has shown limited predictive power on live birth outcomes of blastocysts. To improve live birth prediction, a number of artificial intelligence (AI) models have been established. Most existing AI m...

Study question Is vacuolization in embryos on Days 3 and 4 associated with parent-related factors, stimulation protocols, embryo development, embryo ploidy, pregnancy and neonatal outcomes? Study design, size, duration This is a retrospective cohort study that comprised 5,703 embryos from 611 patients who underwent preimplantation genetic testing...

Background Very low coverage (0.1 to 1x) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for Genome-Wide Association Study (GWAS). To support genetic screening using Preimplantation Genetic Testing (PGT) in a large population, the sequencing coverage goes below 0.1x to a...

Objective To evaluate whether trophectoderm (TE) biopsy differentially influence the level of serum β-human chorionic gonadotropin (β-hCG) with different TE-scored blastocysts transferred in early pregnancy. Methods This retrospective cohort study contained 7847 single-blastocyst transfer cycles executed between January 2019 and June 2020, includi...

Purpose: This study aimed to establish a non-invasive predicting model via Raman spectroscopy for evaluating the blastocyst development potential of day 3 high-quality cleavage stage embryos. Methods: Raman spectroscopy was used to detect the metabolic spectrum of spent day 3 (D3) embryo culture medium, and a classification model based on deep lear...

Early embryonic arrest and fragmentation (EEAF) is a common phenomenon leading to female infertility, but the genetic determinants remain largely unknown. The Moloney sarcoma oncogene (MOS) encodes a serine/threonine kinase that activates the ERK signaling cascade during oocyte maturation in vertebrates. Here, we identified four rare variants of MO...

Background Recurrent preimplantation embryo developmental arrest (RPEA) is the most common cause of assisted reproductive technology treatment failure associated with identified genetic abnormalities. Variants in known maternal genes can only account for 20%–30% of these cases. The underlying genetic causes for the other affected individuals remain...

Study question What are the other male factors that cause total fertilization failure (TFF) excepting for variants in PLCZ1? Summary answer Homozygous variants in ACTL9 (actin like 9) cause abnormal localization of PLCζ in a loosened perinuclear theca (PT) structure and leads to TFF. What is known already In previous studies, investigators have r...

Total fertilization failure (TFF) can occur during in vitro fertilization (IVF) treatments, even following intracytoplasmic sperm injection (ICSI). Various male or female factors could contribute to TFF. Increasing evidence suggested that genetic variations in PLCZ1, which encodes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 (PL...

The subcortical maternal complex (SCMC) is an oocyte‐to‐embryo‐specific maternal functional module. Some variants of SCMC genes that contribute to preimplantation embryonic arrest have been identified. However, more novel variants should be identified to broaden the genetic and phenotypic spectrum of SCMC genes and establish their roles in embryoni...

Background Frozen-thawed embryo transfer (FET) has become a routine procedure in assisted reproductive technology (ART). In FET, although blastocysts cultured from thawed cleavage-stage embryos are associated with better perinatal outcomes. it may increase cycle cancellation due to no suitable embryo to transfer. The overall clinical outcomes follo...

PLOSOne_Clinical_Studies_Checklist. (DOCX)

STROBE_checklist_v4_combined_PlosMedicine. (DOCX)

Objective: To select normal fertilized diploid blastocysts in patients who had only monopronucleated (1PN) embryos for transfer. Design: Experimental study. Setting: University-affiliated center. Patient(s): Couples who were undergoing intracytoplasmic sperm injection treatment and had 1PN blastocysts. Intervention(s): In a preliminary tes...

To evaluate the efficiency and safety of SperMagic medium on stimulating the immotile spermatozoa in testicular sperm extraction (TESE) and absolute asthenozoospermia, 96 patients with TESE and 106 patients with absolute asthenozoospermia were enrolled in this study. The motile spermatozoa were detected in 47 TESE patients and 68 absolute asthenozo...

Study question: Does single cleavage-stage (Day 3) embryo transfer using a time-lapse (TL) hierarchical classification model achieve comparable ongoing pregnancy rates (OPR) to single blastocyst (Day 5) transfer by conventional morphological (CM) selection? Summary answer: Day 3 single embryo transfer (SET) with a hierarchical classification mod...

Background The use of assisted reproductive technology (ART) has been reported to increase the incidence of monozygotic twinning (MZT) compared with the incidence following natural conception. It has been hypothesized that splitting of the inner cell mass (ICM) through a small zona hole may result in MZT. In this study, using a cohort of patients u...

Type II blastocysts. Partially hatched blastocysts without ICM incarceration in which ICMs were inside (A, B and C) or outside (D, E and F) of the ZP opening, or the blastocysts hatched with a U-shape (zona hole expanded >30 μm) (G, H and I); Bar = 30 μm. (TIFF)

Type III blastocysts. Fully hatched blastocysts in which all TE and ICM cells were hatched out of zone; Bar = 30 μm. (TIFF)

Type I blastocysts. Figure 8-shaped blastocysts with ICM incarceration in which a part of TE cells were hatched out, but ICMs were trapped in the ZP opening (zona hole ≤ 30 μm); Bar = 30 μm. (TIFF)

Chromosomal abnormalities are common in human embryos. Previous studies have suggested links between centrosome number and chromosome abnormalities, but information regarding abnormalities in centrosome number in human embryos is limited. We analyzed abnormalities in centrosome number in human embryos and embryonic stem cells (hESCs). Following nor...

Objective: To evaluate whether the developmental potential of the blastocyst is affected by the number of trophectoderm (TE) cells biopsied in preimplantation genetic diagnosis (PGD) cycles. Design: Retrospective study. Setting: University-affiliated center. Patient(s): Women underwent PGD cycles of blastocyst biopsy and fluorescence in situ...

The cell division cycle associated 8 (CDCA8) gene plays an important role in mitosis. Overexpression of CDCA8 was reported in some of human cancers and required for cancer growth and progression. We found its expression was also high in human ES cells (hESCs), upon differentiation which dropped significantly. However, the regulation of CDCA8 expres...

Time-lapse technique provides opportunities to observe the dynamic process of human early development. Previous studies have suggested several abnormal division patterns were associated with decreased developmental potential, but no systematic results are currently available. In this study, seven abnormal division patterns were observed during earl...

Next generation sequencing (NGS) is now being used for detecting chromosomal abnormalities in blastocyst trophectoderm (TE) cells from in vitro fertilized embryos. However, few data are available regarding the clinical outcome, which provides vital reference for further application of the methodology. Here, we present a clinical evaluation of NGS-b...

To evaluate the clinical value of re-examining the test-failure blastocysts in preimplantation genetic diagnosis/screening cycles. Retrospective study. University-affiliated center. Women with test-failure blastocysts cryopreserved in preimplantation genetic diagnosis/screening cycles. Cryopreserved test-failure blastocysts were warmed and underwen...

By comparing the chromosomal constitution among the arrested cleavage-stage embryos, blastocysts and human embryonic stem cells (hESCs) which are all derived from monopronuclear (1PN) zygotes, it is aimed to determine whether chromosomally normal embryos can be reliably selected by blastocyst culture. After 1PN zygotes are sequentially cultured for...

Tripronuclear zygotes (3PN) occur in about 5% of cases in human IVF programmes. Human 3PN zygotes derived from a conventional IVF programme may contain not only the extra male pronucleus but also a supplementary centriole. Researchers have tried to restore diploidy by removing the extra male pronucleus of the tripronuclear zygote. However, it is st...

The cryopreservation of human embryos is thought to induce alteration in the glycoprotein matrix and lead to zona change. However, this assumption has been full of controversies till now. The objective of this study was to evaluate the effect of cryopreservation on zona pellucida of human embryos. Fresh (n=106, from 40 patients) and frozen-thawed e...

Maintaining undifferentiated state and self-renewal ability of embryonic stem cells is a process that many genes and factors participate in. Using bioinformatics analyses and suppression subtractive hybridization we cloned a novel human gene related to the proliferation of human embryonic stem (hES) cells and its mouse homologue and identified them...

Homozygous human embryonic stem cells (hESCs) are thought to be better cell sources for hESC banking because their human leukocyte antigen (HLA) haplotype would strongly increase the degree of matching for certain populations with relatively smaller cohorts of cell lines. Homozygous hESCs can be generated from parthenogenetic embryos, but only hete...