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Objective: To investigate whether LHX1 gene mutations exist in Han Chinese patients with müllerian duct abnormalities (MDAs). Design: Mutation screening. Setting: University hospital. Patient(s): Ninety-six MDA patients and 105 control subjects from a Han Chinese population. The parents of the patients carrying the genetic variation were also screened. Intervention(s): Gene sequencing. Main Outcome Measure(s): Karyotype, LHX1 gene sequencing. Result(s): We found no significant mutation in coding regions of LHX1. However, there is a new rare polymorphism of LHX1 gene, c.1070–1081del, found in 1 out of 77 incomplete müllerian fusion patients and 1 out of 105 control individuals in the Han Chinese population (thus affecting ∼1% of Han Chinese). Conclusion(s): No causative perturbation was identified in the LHX1 gene. Mutations in the coding regions of LHX1 may not be a common genetic etiologic factor involved in Han Chinese MDA patients. [ABSTRACT FROM AUTHOR]

We screened growth differentiation factor 9 coding regions for mutations in a Chinese sample of 100 women with premature ovarian failure and discovered four novel single-nucleotide polymorphisms: c.436C>T (p.Arg146Cys), c.588A>C (silent), c.712A>G (p.Thr238Ala), and c.1283G>C (p.Ser428Thr). Nonsynonymous single-nucleotide polymorphisms c.436C>T and c.1283G>C were also detected in the control population. The c.712A>G perturbation results in a missense mutation (p.Thr238Ala) and was not present in any of 96 controls. Substitution of the hydrophobic amino acid residue alanine for hydrophilic threonine may disrupt growth differentiation factor 9 function. [Copyright &y& Elsevier]

NANOS3 encodes an RNA-binding protein and has a conserved function in germ cell development. Our objective was to investigate whether mutations in NANOS3 were present in Chinese and Caucasian women with premature ovarian failure. A known synonymous single-nucleotide polymorphism (rs 2016163) in exon 1 was identified through sequencing 80 Chinese and 88 Caucasian women with premature ovarian failure. No additional single-nucleotide polymorphisms or mutations were found in exons encoding for NANOS3. Our findings suggest that mutations in NANOS3 exons are rare in both Chinese and Caucasian women with premature ovarian failure. [Copyright &y& Elsevier]

Objective: To prospectively examine the association between sleep quality before embryo transfer with pregnancy outcomes in a population with infertility.Design: Prospective observational cohort study.Setting: Center for Reproductive Medicine, Shandong University.Patient(s): From 7,847 women who enrolled from July 2019 to July 2020, 3,183 were eligible.Intervention(s): Information about sleep, including sleep quality, sleep duration, and sleep chronology, were collected before embryo transfer using an integrated questionnaire. Sleep quality is quantified by the Pittsburgh Sleep Quality Index (PSQI) with a cut-point of 5 (PSQI >5 identifying poor sleep vs. PSQI ≤5 identifying good sleep). Average weekly sleep duration was calculated and divided into 5 groups (≤7, 7-8, 8-9, 9-10, and >10 h/d). In defining sleep chronotype, women with a sleep midpoint earlier than 2:30 AM were defined as morningness type, whereas those with a sleep midpoint later than 3:30 AM were defined as eveningness type, and the remainder were defined as an intermediate type.Main Outcome Measure(s): Rate of clinical pregnancy and live birth.Result(s): Compared with those reporting poor sleep quality, those reporting good sleep quality showed high clinical pregnancy (69.3% vs. 65.1%) and live birth rates (50.5% vs. 45.7%). After adjusting for confounding factors, women who self-reported good sleep had a higher probability of acquiring clinical pregnancy (RR, 1.07; 95% confidence interval, 1.01-1.13) and of live birth (RR, 1.12; 95% confidence interval, 1.02-1.23). Women with the morningness chronotype had the lowest rates of clinical pregnancy and live birth and had the highest rate of miscarriage. Sleep duration was found to have no significant association with any outcomes. In the stratified analyses, the positive associations of good sleep quality with clinical pregnancy and live birth existed only among women younger than 35 years old or who had undergone fresh embryo transfer.Conclusion(s): Good seep quality was positively associated with outcomes in in vitro fertilization embryo transfer (IVF-ET), particularly with clinical pregnancy and live birth. Poor sleep quality may be a risk factor for adverse IVF-ET outcomes for women <35 years old. Treating sleep disorders and providing sleep behavior guidance to patients receiving IVF-ET may improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective: To describe a case with repeated total fertilization failure due to oocyte defect. Design: Case report. Setting: University hospital. Patient(s): A patient with repeated total fertilization failure. Intervention(s): Assisted oocyte activation, intracytoplasmic sperm injection (ICSI) with calcium ionophore oocyte activation, donor semen, and donor oocytes. Main Outcome Measure(s): Fertilization, pregnancy, and live birth. Result(s): Five cycles of IVF/ICSI were performed. In the first IVF cycle, 19 oocytes failed to fertilize. In the second ICSI attempt, 12 oocytes were retrieved and were not fertilized. In the third and fourth natural cycles, donor semen was used for IVF and ICSI, respectively, yet the oocytes could not be fertilized even by assisted activation. Then donor oocytes were used in the fifth cycle by ICSI. All five donated oocytes fertilized normally, and three embryos were transferred on day 3. Clinical pregnancy was confirmed, and a healthy girl weighing 3,200 g was delivered at 39 weeks of gestation by cesarean section. Conclusion(s): In cases of repeated fertilization failure caused by oocyte defects, oocyte donation seems to be a good choice for patients who wish to become pregnant. [ABSTRACT FROM AUTHOR]

Objective: To identify the major causative gene(s) of genuine empty follicle syndrome (GEFS) characterized by oocyte degeneration.Design: Genetic and functional studies.Setting: University-based reproductive medicine center.Patient(s): Thirty-five unrelated women with GEFS and oocyte degeneration.Intervention(s): Whole-exome sequencing (WES) and targeted Sanger sequencing.Main Outcome Measure(s): Variants predicted by software and the functional effects of variants assessed via Western blot and immunofluorescence in Chinese hamster ovary (CHO) cells.Result(s): We identified zona pellucida (ZP) gene variants in 18 individuals, which included 20 variants in the ZP1 gene, two variants in the ZP2 gene, and one previously reported recurrent variant in the ZP3 gene. The women carrying ZP variants constituted 51.43% of the GEFS cohort. The ZP1 variants were inherited in an autosomal recessive pattern; the ZP2 and ZP3 variants were inherited in an autosomal dominant pattern. All variants were predicted to be deleterious. Studies in CHO cells suggested that most ZP1 variants led to increased intracytoplasmic protein and some variants influenced the intracellular transportation of other ZP proteins. Variant p.R642Q of ZP2 caused the secretion of ZP2 protein with an increased molecular weight, suggesting altered protein modification. Variant p.I619N of ZP2 resulted in increased ZP2 protein in cell lysate and decreased ZP2 protein in culture medium. These results showed that ZP variants might block the intracellular transportation and secretion of ZP proteins and disrupt the zona pellucida.Conclusion(s): We identified novel variants of ZP genes in more than half the cohort with GEFS and oocyte degeneration. Variants of ZP genes caused protein intracellular sequestration and failure to assemble the ZP filaments, resulting in EFS and female infertility. Our findings not only reveal the critical roles of ZP genes but also pave the way for the efficient genetic diagnosis of females with GEFS and oocyte degeneration. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of resveratrol on oocyte maturation in aged mice and humans.Design: Experimental laboratory study.Setting: University-based reproductive medicine center.Patient(s): A total of 64 women 38-45 years of age undergoing intracytoplasmic sperm injection (ICSI) and 48-52-week-old female C57BL/6J mice.Intervention(s): In vitro culture in the presence of three different concentrations of resveratrol (0.1, 1.0, and 10 μm) or dimethylsulfoxide.Main Outcome Measure(s): Parameters of oocyte nuclear maturation, fertilization, immunofluorescence intensity of mitochondria, and normal morphology of spindle and chromosome of oocytes undergoing in vitro maturation (IVM) in aged mice and humans; blastocyst formation and levels of SRIT1, CAT, SOD1, and GPX4 gene expressions in aged mice.Result(s): Resveratrol at 1.0 μm significantly increased first polar body emission rate in oocytes derived from aged mice and humans, and an increased percentage of fertilization and blastocyst formation was observed in aged mice. In addition, immunofluorescence intensity of mitochondria and normal morphology of spindle and chromosome of oocytes undergoing IVM were notably improved compared with control samples in aged mice and human. Furthermore, the use of resveratrol exhibited enhanced expression patterns of SRIT1, CAT, SOD1, and GPX4 in aged mice.Conclusion(s): Resveratrol induced oocyte maturation and blastocyst formation in aged mice, and improved oocyte maturation and quality was examined in aged humans. In conclusion, 1.0 μm resveratrol was the appropriate concentration in IVM medium. [ABSTRACT FROM AUTHOR]

Objective: To detect ZP (zona pellucida) gene (ZP1-ZP4) mutations in patients with oocyte anomalies.Design: Case-control genetic study.Setting: University-based reproductive medicine center.Patient(s): A total of 92 infertile patients with repeated cycles of oocyte maturation arrest (group I, n = 49) or oocyte morphologic defect (group II, n = 43) as well as 373 healthy controls.Intervention(s): Genomic DNA extracted from peripheral blood and coding regions of ZP genes amplified by polymerase chain reaction and sequenced by a DNA analyzer.Main Outcome Measure(s): Variant prediction of ZP genes with software.Result(s): In group I with oocyte maturation arrest, no novel variants were found. In group II with oocyte morphologic defects, four novel variants, two in the ZP1 gene [c.247T>C (p.W83R) and c.1413G>A (p.W471X)] and two in the ZP2 gene [c.1599G>T (p.R533S) and c.1696T>C (p.C566R)] were detected in 4 of 43 patients (approximately 9%) but were absent from the controls. Protein alignments showed that the four variants were highly conserved among different species, and all four variants were predicted to be deleterious by gene software predictions.Conclusion(s): ZP gene variants may account for patients with oocyte morphologic abnormalities but not for those with oocyte maturation arrest. [ABSTRACT FROM AUTHOR]