An interpretable artificial intelligence approach to differentiate between blastocysts with similar or same morphological grades.

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 with continuous scores, enabling finer differentiation between blastocysts with similar or same grades, with higher scores significantly correlating with higher live birth rates.

What Is Known Already: While the Gardner grading system is widely used by embryologists worldwide, blastocysts having similar or same ICM and TE grades cause challenges for embryologists in decision-making. Furthermore, human assessment is subjective and inconsistent in predicting which blastocysts have higher potential to result in live birth.

Effects of Alpinia oxyphylla fructus polysaccharide on the gelatinization, retrogradation, structural characteristics, antioxidant activity, and in vitro digestibility of corn starch.

Alpinia oxyphylla fructus polysaccharide (AOFP) exhibits diverse biological activities, but its influence on starch properties remains underexplored. This study elucidates the effects of AOFP on the gelatinization, retrogradation behavior, and functional characteristics of corn starch (CS). Iodine binding capacity, XRD, and FTIR analyses revealed that AOFP significantly inhibited amylose leaching, likely through hydrogen bonding interactions, thereby suppressing starch recrystallization and retrogradation.

A case report of a normal fertile woman with 46,XX/46,XY somatic chimerism reveals a critical role for germ cells in sex determination.

Individuals with 46,XX/XY chimerism can display a wide range of characteristics, varying from hermaphroditism to complete male or female, and can display sex chromosome chimerism in multiple tissues, including the gonads. The gonadal tissues of females contain both granulosa and germ cells. However, the specific sex chromosome composition of the granulosa and germ cells in 46,XX/XY chimeric female is currently unknown.

Oxygen concentration from days 1 to 3 after insemination affects the embryo culture quality, cumulative live birth rate, and perinatal outcomes.

Purpose: We aimed to compare embryo development, cumulative live birth rate (CLBR), and perinatal outcomes of embryos cultured in 20% and 5% oxygen from days 1 to 3 after insemination.

Methods: This retrospective study included patients who received in vitro fertilization (IVF) treatment between January 2015 and November 2019. Embryos of each patient were cultured at 20% or 5% oxygen from days 1-3 after insemination.

Reproductive risks and preimplantation genetic testing intervention for X-autosome translocation carriers.

Research Question: What is the genetic cause of multiple congenital disabilities in a girl with a maternal balanced X-autosome translocation [t(X-A)]? Is preimplantation genetic testing (PGT), to distinguish non-carrier from euploid/balanced embryos and prioritize transfer, an effective and applicable strategy for couples with t(X-A)?

Design: Karyotype analysis, whole-exome sequencing and X inactivation analysis were performed for a girl with congenital cardiac anomalies, language impairment and mild neurodevelopmental delay. PGT based on next-generation sequencing after microdissecting junction region (MicroSeq) to distinguish non-carrier and carrier embryos was used in three couples with a female t(X-A) carrier (cases 1-3).

Results: The girl carried a maternal balanced translocation 46,X,t(X;1)(q28;p31.

Clinical outcomes following preimplantation genetic testing and microdissecting junction region in couples with balanced chromosome rearrangement.

Purpose: The purpose of this study is to summarize the clinical outcomes of apparently balanced chromosome rearrangement (ABCR) carriers in preimplantation genetic testing (PGT) cycles by next-generation sequencing following microdissecting junction region (MicroSeq) to distinguish non-carrier embryos from balanced carriers.

Methods: A retrospective study of 762 ABCR carrier couples who requested PGT for structural rearrangements combined with MicroSeq at the Reproductive and Genetic Hospital of CITIC-Xiangya was conducted between October 2014 and October 2019.

Results: Trophectoderm biopsy was performed in 4122 blastocysts derived from 917 PGT-SR cycles and 3781 blastocysts were detected.

The genetic cause of intellectual deficiency and/or congenital malformations in two parental reciprocal translocation carriers and implications for assisted reproduction.

Purpose: To elucidate the genetic cause of intellectual deficiency and/or congenital malformations in two parental reciprocal translocation carriers and provide appropriate strategies of assisted reproductive therapy (ART).

Materials And Methods: Two similar couples having a child with global developmental delay/intellectual disability symptoms attended the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) in 2017 and 2019, respectively, in order to determine the cause(s) of the conditions affecting their child and to seek ART to have a healthy baby. Both of the healthy couples were not of consanguineous marriage, denied exposure to toxicants, and had no adverse life history.

The mitochondrial DNA copy number of cumulus granulosa cells may be related to the maturity of oocyte cytoplasm.

Study Question: Is the mitochondrial DNA (mtDNA) copy number of cumulus granulosa cells (CGCs) related to the maturation of oocyte cytoplasm?

Summary Answer: Compared with the mtDNA copy number of CGCs from germinal vesicles (GV), CGCs from Metaphase I (MI) oocytes appear to have a lower mtDNA copy number.

What Is Known Already: The growth and development of CGCs and oocyte are synchronised. The interaction between CGCs and the oocyte provides the appropriate balance of energy, which is necessary for mammalian oocyte development.

ZP1 mutations are associated with empty follicle syndrome: evidence for the existence of an intact oocyte and a zona pellucida in follicles up to the early antral stage. A case report.

Empty follicle syndrome (EFS) is the complete failure to retrieve oocytes after ovarian stimulation. Although LHCGR and ZP3 were identified as causative genes, it is still unclear what happens to these patients' oocytes, and the pathogenesis of EFS remains obscure. Here, we identified six novel ZP1 mutations associated with EFS and female infertility that was inherited recessively in five unrelated families.

Analysis of molecular cytogenetic features and PGT-SR for two infertile patients with small supernumerary marker chromosomes.

Research Question: Can preimplantation genetic testing for structural rearrangement (PGT-SR) with next-generation sequencing (NGS) be used to infertile patients carrying small supernumerary marker chromosomes (sSMCs)?

Design: In this study, two infertile patients carrying ring sSMCs were recruited. Different molecular cytogenetic techniques were performed to identify the features of the two sSMCs, followed by clinical PGT-SR cycles.

Results: The results of G-banding and FISH showed that patient 1's sSMC originated from the 8p23-p10 region, with a resulting karyotype of [ 47,XY, del(8)(p23p10), +r(8)(p23p10).

New biallelic mutations in PADI6 cause recurrent preimplantation embryonic arrest characterized by direct cleavage.

Purpose: To investigate the pathogenesis of the recurrent preimplantation embryonic arrest characterized by direct cleavage.

Methods: Two affected individuals underwent time-lapse imaging to observe the cleavage behaviors in their final ICSI attempts. In addition, both patients were subjected to whole-exome sequencing.

Novel homozygous variations in PLCZ1 lead to poor or failed fertilization characterized by abnormal localization patterns of PLCζ in sperm.

Total fertilization failure (TFF), which is the failure of fertilization in all oocytes, occurs in 1%-3% of intracytoplasmic sperm injection (ICSI) cycles. However, the sperm-related factors that cause fertilization failure in humans are still largely unknown. Here, we identified three novel homozygous variations in the PLCZ1 gene in a recessive inheritance pattern in three consanguineous families, which all located in a key catalytic domain, and predicted to modify its secondary structure and thus impair its hydrolytic activity.

New biallelic mutations in WEE2: expanding the spectrum of mutations that cause fertilization failure or poor fertilization.

Objective: To investigate the genetic cause of fertilization failure or poor fertilization.

Design: Genetic analysis.

Setting: University-affiliated center.

An integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos.

Human pre-implantation embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here, we report on LiCAT-seq, a technique that enables simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells, and map the chromatin accessibility and transcriptome landscapes for human pre-implantation embryos. We observed global difference in chromatin accessibility between sperm and all stages of embryos, finding that the accessible regions in sperm tend to occur in gene-poor genomic regions.

Clinical and neonatal outcomes of patients of different ages following transfer of thawed cleavage embryos and blastocysts cultured from thawed cleavage-stage embryos.

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.

Prevalence and authenticity of de-novo segmental aneuploidy (>16 Mb) in human blastocysts as detected by next-generation sequencing.

Research Question: What is the prevalence and authenticity of de-novo segmental aneuploidies (>16 Mb) detected by next-generation sequencing (NGS) in human preimplantation blastocysts?

Design: Between April 2013 and June 2016, 5735 blastocysts from 1854 couples (average age 33.11 ± 5.65 years) underwent preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) or for aneuploidy (PGT-A) using NGS on trophectoderm (TE) biopsy samples.

ZP2 pathogenic variants cause in vitro fertilization failure and female infertility.

Purpose: The oocyte-borne genetic causes leading to fertilization failure are largely unknown. We aimed to identify novel human pathogenic variants (PV) and genes causing fertilization failure.

Methods: We performed exome sequencing for a consanguineous family with a recessive inheritance pattern of female infertility characterized by oocytes with a thin zona pellucida (ZP) and fertilization failure in routine in vitro fertilization.

The clinical and neonatal outcomes after stimulation of immotile spermatozoa using SperMagic medium.

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 asthenozoospermia and these patients were assigned to control group. The immotile spermatozoa in 49 TESE patients and 34 absolute asthenozoospermia were stimulated with SperMagic medium.

Single embryo transfer by Day 3 time-lapse selection versus Day 5 conventional morphological selection: a randomized, open-label, non-inferiority trial.

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 model had a significantly lower OPR compared with Day 5 SET with CM selection.

What Is Known Already: Cleavage-stage SET is an alternative to blastocyst SET. Time-lapse imaging assists better embryo selection, based on studies of pregnancy outcomes when adding time-lapse imaging to CM selection at the cleavage or blastocyst stage.

Inner cell mass incarceration in 8-shaped blastocysts does not increase monozygotic twinning in preimplantation genetic diagnosis and screening patients.

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 undergoing preimplantation genetic diagnosis/screening (PGD/PGS), we compared the clinical and neonatal outcomes of human 8-shaped blastocysts hatching with ICM incarceration with partially or fully hatched blastocysts, and attempted to verify whether this phenomenon increases the incidence of MZT pregnancy or negatively impact newborns.

Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis.

A diploid genome is necessary for normal mammalian development, thus haploid parthenogenetic embryos undergo frequent self-diploidization during preimplantation development; however, the underlying mechanism is unclear. In this study, time-lapse recording revealed that human haploid parthenotes (HPs) undergo self-diploidization via failed cytokinesis (FC) and endomitosis (EM). The frequencies of FC/EM were significantly higher in HPs than in normal fertilized embryos (26.

Polar body transfer restores the developmental potential of oocytes to blastocyst stage in a case of repeated embryo fragmentation.

Purpose: We aimed to determine the developmental potential of human reconstructed oocytes after polar body genome transfer (PBT) and to report the case of a woman with multiple cycles of severe embryo fragmentation.

Methods: Fresh and cryopreserved first polar bodies (PB1s) were transferred to enucleated metaphase II oocytes (PB1T), while fresh PB2s were removed from fertilized oocytes and used instead of the female pronucleus in donor zygotes. Reconstructed oocytes underwent intracytoplasmic sperm injection (ICSI) and were cultured to blastocyst.

Reciprocal Translocation Carrier Diagnosis in Preimplantation Human Embryos.

Preimplantation genetic diagnosis (PGD) is widely applied in reciprocal translocation carriers to increase the chance for a successful live birth. However, reciprocal translocation carrier embryos were seldom discriminated from the normal ones mainly due to the technique restriction. Here we established a clinical applicable approach to identify precise breakpoint of reciprocal translocation and to further distinguish normal embryos in PGD.

The Relationship between Cell Number, Division Behavior and Developmental Potential of Cleavage Stage Human Embryos: A Time-Lapse Study.

Day 3 cleavage embryo transfer is routine in many assisted reproductive technology centers today. Embryos are usually selected according to cell number, cell symmetry and fragmentation for transfer. Many studies have showed the relationship between cell number and embryo developmental potential.

Obstetric and neonatal outcomes in blastocyst-stage biopsy with frozen embryo transfer and cleavage-stage biopsy with fresh embryo transfer after preimplantation genetic diagnosis/screening.

Objective: To study whether embryo biopsy for preimplantation genetic diagnosis/preimplantation genetic screening (PGD/PGS) can influence pregnancy complications and neonatal outcomes.

Design: Retrospective analysis.

Setting: University-affiliated center.