Two missense gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome.

Background: Peutz-Jeghers syndrome (PJS) is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11 (/) gene mutations. Preimplantation genetic testing can protect a patient's offspring from mutated genes; however, some variations in this gene have been interpreted as variants of uncertain significance (VUS), which complicate reproductive decision-making in genetic counseling.

Aim: To identify the pathogenicity of two missense variants and provide clinical guidance.

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.

A hemizygous loss-of-function variant in BCORL1 is associated with male infertility and oligoasthenoteratozoospermia.

Oligoasthenoteratozoospermia (OAT) is a common type of male infertility; however, its genetic causes remain largely unknown. Some of the genetic determinants of OAT are gene defects affecting spermatogenesis. BCORL1 (BCL6 corepressor like 1) is a transcriptional corepressor that exhibits the OAT phenotype in a knockout mouse model.

Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF: not just ICSI failure.

Phospholipase C zeta (PLCζ) is a key sperm-borne oocyte-activating factor that triggers Ca 2+ oscillations and the subsequent block to polyspermy following gamete fusion. Mutations in PLCZ1 , the gene encoding PLCζ, cause male infertility and intracytoplasmic sperm injection (ICSI) fertilization failure; and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate (FR). However, in conventional in vitro fertilization (cIVF), whether and how sperm PLCζ affects fertilization remain unclear.

Mosaic variegated aneuploidy syndrome with tetraploid, and predisposition to male infertility triggered by mutant CEP192.

In this study, we report on mosaic variegated aneuploidy (MVA) syndrome with tetraploidy and predisposition to infertility in a family. Sequencing analysis identified that the CEP192 biallelic variants (c.1912C>T, p.

Immune profiling and RNA-seq uncover the cause of partial unexplained recurrent implantation failure.

Background: Detailed knowledge of the changes in endometrial immune cells during the window of implantation in unexplained recurrent implantation failure (RIF) patients, the functions performed by immune cells, and the interactions between them is largely lacking. This study aimed to classify RIF patients and explore the mechanism through endometrial immune profiling and RNA-seq analysis.

Methods: This study enrolled a total of 172 patients, comprising 144 women with unexplained RIF and 28 fertile women.

Biallelic variants in IQCN cause sperm flagellar assembly defects and male infertility.

Study Question: What is the effect of defects in the manchette protein IQ motif-containing N (IQCN) on sperm flagellar assembly?

Summary Answer: Deficiency in IQCN causes sperm flagellar assembly defects and male infertility.

What Is Known Already: The manchette is a transient structure that is involved in the shaping of the human spermatid nucleus and protein transport within flagella. Our group recently reported that the manchette protein IQCN is essential for fertilization.

Histological endometrial dating: a reliable tool for personalized frozen-thawed embryo transfer in patients with repeated implantation failure in natural cycles.

Objective: To evaluate the clinical availability and stability of histological endometrial dating as a tool for personalized frozen-thawed embryo transfer (pFET) in patients with repeated implantation failure (RIF) in natural cycles.

Methods: A total of 1245 RIF patients were recruited to the present study. All of the patients received an endometrial dating evaluation on day 7 post-ovulation (PO + 7) to guide their first pFET.

A DMD case caused by X chromosome rearrangement.

Duchenne/Becker muscular dystrophy (DMD/BMD) is one of the most common progressive muscular dystrophy diseases with X-linked recessive inheritance. It is mainly caused by the deletion, duplication and point mutation of gene. In rare cases, it is also caused by the destruction of gene by chromosomal structural rearrangement.

Pregnancy Outcomes of Different Endometrial Preparation in Patients With a History of Cesarean Section.

Objective: To investigate the efficacies of three cycle regimens in women receiving frozen embryo transfer with a history of cesarean section: natural cycle treatment, hormone replacement therapy and treatment with gonadotropin-releasing hormone agonist.

Design: Retrospective cohort study.

Methods: patients (N = 6,159) with a history of caesarean section who fulfilled the inclusion criteria were enrolled in the study from January 2014 to December 2019 at the CITIC-Xiangya Hospital of Reproduction and Genetics.

Biallelic variants in MOS cause large polar body in oocyte and human female infertility.

Study Question: What is the genetic basis of female infertility involving abnormal oocyte morphology with the production of a large first polar body (PB1)?

Summary Answer: The homozygous missense variant (c.791C>G) and compound missense variants (c.596A>T and c.

Biallelic variants cause male infertility in humans and mice with severe oligoasthenoteratozoospermia.

Background: The genetic causes for most male infertility due to severe oligoasthenoteratozoospermia (OAT) remain unclear.

Objective: To identify the genetic cause of male infertility characterised by OAT.

Methods: Variant screening was performed by whole-exome sequencing from 325 infertile patients with OAT and 392 fertile individuals.

Trophectoderm Biopsy Differentially Influences the Level of Serum β-Human Chorionic Gonadotropin With Different Embryonic Trophectoderm Scores in Early Pregnancy From 7847 Single-Blastocyst Transfer Cycles.

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, including 2657 preimplantation genetic testing (PGT) cycles and 5190 fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. All cycles were classified into biopsy and control groups, and further stratified based on the TE morphological scores into three subgroups: grades A, B, and C for TE scores, respectively.

RNA splicing analysis contributes to reclassifying variants of uncertain significance and improves the diagnosis of monogenic disorders.

Background: Numerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable.

Objective: To assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning.

Sperm flagellar 2 (SPEF2) is essential for sperm flagellar assembly in humans.

Spermiogenesis is a complex and tightly regulated process, consisting of acrosomal biogenesis, condensation of chromatin, flagellar assembly, and disposal of extra cytoplasm. Previous studies have reported that sperm flagellar 2 (SPEF2) deficiency causes severe asthenoteratozoospermia owing to spermiogenesis failure, but the underlying molecular mechanism in humans remains unclear. Here, we performed proteomic analysis on spermatozoa from three SPEF2 mutant patients to study the functional role of SPEF2 during sperm tail development.

CD19 and intraglandular CD163-positivity as prognostic indicators of pregnancy outcome in CD138-negative women with a previous fresh-embryo-transfer failure.

Many factors impede embryonic implantation, and excluding obvious known factors such as chronic endometritis, the immune status of the endometrium may be related to pregnancy. Although an abundantly large number of immune cells infiltrate the endometrium during the secretory phase, whether these immune cells can be used as a predictor of prognosis in ART has not yet been clarified. In the present study we therefore retrospectively analyzed 97 CD138-negative women with a previous fresh-embryo-transfer failure.

Next-generation sequence-based preimplantation genetic testing for monogenic disease resulting from maternal mosaicism.

Background: Mosaicism poses challenges for genetic counseling and preimplantation genetic testing for monogenic disorders (PGT-M). NGS-based PGT-M has been extensively used to prevent the transmission of monogenic defects, but it has not been evaluated in the application of PGT-M resulting from mosaicism.

Methods: Four women suspected of mosaicism were confirmed by ultra-deep sequencing.

Novel homozygous truncating variants in ZMYND15 causing severe oligozoospermia and their implications for male infertility.

Sequence variants of ZMYND15 cause azoospermia in humans, but they have not yet been reported in infertile men with severe oligozoospermia (SO). We performed whole-exome and Sanger sequencing to identify suspected causative variants in 414 idiopathic participating infertile men with SO or azoospermia. Three novel homozygous truncating variants in ZMYND15 were identified in three of the 219 (1.

Homozygous variants in cause premature ovarian insufficiency.

Background: The genetic causes of the majority of cases of female infertility caused by premature ovarian insufficiency (POI) are unknown.

Objective: To identify the genetic causes of POI in 110 patients.

Methods: Whole-exome sequencing was performed on 110 patients with POI, and putative disease-causative variants were validated by Sanger sequencing.

Novel loss-of-function mutation in MCM8 causes premature ovarian insufficiency.

Background: Premature ovarian insufficiency (POI) is one major cause of female infertility, minichromosome maintenance complex component 8 (MCM8) has been reported to be responsible for POI.

Methods: Whole-exome sequencing was performed to identify the genetic variants of women with POI. Sanger sequencing was used to validate the variants in all the family members.

Endometrial CD138 count appears to be a negative prognostic indicator for patients who have experienced previous embryo transfer failure.

Objective: To explore the predictive value of endometrial CD138 expression in the natural cycle preceding frozen embryo transfer in patients with normal endometrial dating and histopathologic features, who previously failed the transfer of two high-quality fresh embryos.

Design: Retrospective analysis.

Setting: University-affiliated hospital.