Search

Oocyte vitrification is an important assisted reproductive technology (ART) that preserves the fertility of unmarried patients with malignant tumors, and promotes the development of the oocyte donation program. In recent years, the effects of ART, including the vitrification of oocytes and embryos on the health of offspring, have attracted much attention; however, it is difficult to conduct long-term follow-up and biochemical evaluation in humans. In this study, we detected the effect of oocyte vitrification on gene expression in the organs of adult mice offspring by RNA sequencing for the first time. Our results showed that only a small amount of gene expression was significantly affected. Seven genes (Tpm3, Hspe1-rs1, Ntrk2, Cyp4a31, Asic5, Cyp4a14, Retsat) were abnormally expressed in the liver, and ten genes (Lbp, Hspe1-rs1, Prxl2b, Pfn3, Gm9008, Bglap3, Col8a1, Hmgcr, Ero1lb, Ifi44l) were abnormal in the kidney. Several genes were related to metabolism and disease occurrence in the liver or kidney. Besides, we paid special attention to the expression of known imprinted genes and DNA methylation-related genes in adult organs, which are susceptible to oocyte cryopreservation in the preimplantation stage. As a result, some of these transcripts were detected in adult organs, but they were not affected by oocyte vitrification. In conclusion, we first report that oocyte vitrification did not significantly change the global gene expression in offspring organs; nonetheless, it can still influence the transcription of a few functional genes. The potential adverse effects caused by oocyte vitrification need attention and further study.

PURPOSE: This review aims to summarize the key findings of several miRNAs and their roles in polycystic ovary syndrome with insulin resistance, characterize the disease pathogenesis, and establish a new theoretical basis for diagnosing, treating, and preventing polycystic ovary syndrome. METHODS: Relevant scientific literature was covered from 1992 to 2020 by searching the PubMed database with search terms: insulin/insulin resistance, polycystic ovary syndrome, microRNAs, and metabolic diseases. References of relevant studies were cross-checked. RESULTS: The related miRNAs (including differentially expressed miRNAs) and their roles in pathogenesis, and possible therapeutic targets and pathways, are discussed, highlighting controversies and offering thoughts for future directions. CONCLUSION: We found abundant evidence on the role of differentially expressed miRNAs with its related phenotypes in PCOS. Considering the essential role of insulin resistance in the pathogenesis of PCOS, the alterations of associated miRNAs need more research attention. We speculate that race/ethnicity or PCOS phenotype and differences in methodological differences might lead to inconsistencies in research findings; thus, several miRNA profiles need to be investigated further to qualify for the potential therapeutic targets for PCOS-IR.

Diminished ovarian reserve (DOR) is associated with compromised fertility that affects approximately 10% of couples. Gene mutations are implicated in the pathogenesis of DOR. Here, we aimed to assess the clinical and genetic characteristics of two sisters with impaired fertility history. The two sisters showed DOR and suffered from recurrent pregnancy loss (RPL) in natural pregnancy and in vitro fertilization-embryo transfer (IVF-ET).Whole exome sequencing (WES) was performed for the proband and pathogenic variants detected were validated by Sanger sequencing in all available family members. Minigene assay was performed to evaluate the impact of sequence variants on splicing effect.Two novel heterozygous variants on the HFM1 gene, c.1978-2A C and c.2680 + 3_2680 + 4delAT, were observed in the two patients. The genotype of their parents was all heterozygous, while the unaffected sister and brother did not carry the variants. Both variants could produce alternative transcripts compared to wild-type counterparts, which might result in protein dysfunction.Our results demonstrated that the pathogenic splicing variants in HFM1 are associated with DOR in these two sisters. Mutations in HFM1 may contribute to RPL and poor IVF-ET outcomes because of descending quality and quantity of oocytes. The study enriched the genetic defect spectrum of DOR and understanding of the roles of HFM1 in female reproduction.

This study aimed to evaluate the cumulative live birth rate (CLBR) and surplus embryo rate of polycystic ovarian syndrome (PCOS) patients during in vitro fertilization and embryo transfer (IVF-ET) treatment. In this retrospective cohort study, we analyzed 1142 PCOS patients who underwent first IVF in our institution between January 2011 and December 2014. All patients were categorized into five groups according to the number of oocytes retrieved. Main outcomes include CLBR and surplus embryo rate. A strong correlation was observed between number of oocytes retrieved and CLBR as well as surplus embryo rate in PCOS patients. CLBR was elevated with the increasing number of oocytes and plateaued when oocyte number was up to ten, whereas the surplus embryo rate steadily increased in line with the increase of oocyte number. Patients transferred with frozen embryos showed higher CLBR and LBR during first ET than patients transferred with fresh embryos. For PCOS patients, retrieving more than ten oocytes leads to no significant benefit to CLBR but generates surplus embryos. Thus, moderate ovarian stimulation should be reconsidered during IVF treatment.

PURPOSE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-derived exosomes) can repair injured endometrial epithelial cells (EECs). METHODS: HucMSC-derived exosomes and mouse primary EECs were isolated and purified. EECs were exposed to oxygen and glucose deprivation for 2 h followed by reoxygenation to mimic injury. After oxygen and glucose deprivation/reoxygenation (OGD/R), hucMSC-derived exosomes were added to the EEC culture medium. After 24 h of co-treatment, cell viability and cell death were tested by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and lactate dehydrogenase (LDH) assay, respectively. The expression of proinflammatory cytokines was tested by real-time PCR, enzyme-linked immunosorbent assay (ELISA), and Western blot to investigate the potential mechanism. RESULTS: Compared with the control group, 5, 10, and 15 μg/mL of hucMSC-derived exosomes significantly attenuated cell viability decrease and inhibited LDH release of injured EECs, but 1 μg/mL of hucMSC-derived exosomes had no effect on either cell viability or LDH release. Real-time PCR and ELISA analysis revealed that 10 μg/mL of hucMSC-derived exosomes significantly inhibited the release of interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) and increased tumor necrosis factor alpha (TNFA) in injured EECs. In addition, 10 μg/mL of hucMSC-derived exosomes significantly inhibited toll-like receptor 4 (TLR4) and v-rel reticuloendotheliosis viral oncogene homolog A (RelA) expression in injured EECs. CONCLUSIONS: In OGD/R-induced injured EECs, hucMSC-derived exosomes efficiently improved the cell viability, reduced cell death, and exhibited anti-inflammatory properties against OGD/R.

PURPOSE: The objective of this study was to examine the effect of tauroursodeoxycholic acid (TUDCA) on intracytoplasmic sperm injection (ICSI) embryos by evaluating endoplasmic reticulum (ER) stress, apoptosis, and embryo developmental competence in vitro and in vivo. METHODS: ER stress–associated genes and apoptosis-associated genes were measured and apoptosis index was analyzed. Embryo developmental competence was assessed in vitro and in vivo via the inner cell mass (ICM)/trophectoderm (TE) index, pregnancy and implantation rates, and birth rate. RESULTS: The relative mRNA and protein expression of binding immunoglobulin protein (BIP) was significantly higher in the ICSI embryo group without TUDCA treatment (ICSI-C) than in the in vitro fertilization (IVF) group and in the ICSI embryo group with TUDCA treatment (200 μM) (ICSI-T), while TUDCA ameliorated ER stress in ICSI embryos. Embryos in the ICSI-C group showed a higher apoptosis index than those in the IVF group and ICSI-T group, and there was no significant difference between the IVF group and ICSI-T group. TUDCA can significantly improve ICSI embryo developmental competence in vitro and in vivo based on the ICM/TE index, pregnancy and implantation rates, and birth rate. CONCLUSION: ICSI embryos manifested high ER stress and high apoptosis, while TUDCA ameliorated ER stress and reduced apoptosis in ICSI embryos. TUDCA can significantly improve the developmental competence of ICSI embryos in vitro and in vivo. This study provides a new idea for improving the efficiency of ICSI, and it will also have a positive effect on the development of assisted reproduction technologies for humans and other animals.

The original article unfortunately contained a mistake. The 3rd author's name should be Cuilian Zhang. In addition, the 4th affiliation should be updated to "Reproductive Medicine Center, Henan Provincial People's Hospital; People's Hospital of Zhengzhou University; Henan Provincial People's Hospital, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China".

This study aimed to investigate the relationship between the number of oocytes retrieved and clinical outcomes in young women with normal ovarian reserve who were undergoing their first in vitro fertilization and embryo transfer (IVF-ET) cycle. The transfer strategy based on yielded oocytes was also discussed in this article.A total of 1567 patients who underwent first long protocol of IVF treatment in our reproductive medical center between January 2010 and June 2014 were categorized into five groups based on the retrieved oocyte number, namely, 4∼6, 7∼9, 10∼12, 13∼15, and ≥16. Baseline parameters were similar among the groups. Primary outcome was defined as the cumulative live birth rate (CLBR), and secondary outcomes included the rate of patients with high risks for ovarian hyperstimulation syndrome (OHSS).It was found that the CLBR increased with the number of oocytes, as well as the rate for high risks of OHSS. In fresh cycles, 10∼12 oocyte group demonstrated the highest implantation rate (53.32 %), clinical pregnancy rate (CPR) (73.13 %), and live birth rate (LBR) (61.14 %), with no significant differences. Moreover, both cumulative CPR (CCPR) and CLBR became significantly higher in the 10∼12 oocyte group, compared with 4∼6 and 7∼9 groups. However, when the retrieved oocytes increased to 13∼15 or ≥16, the cumulative results did not have a significant increase. Also, the high risk rate of OHSS was much lower in the 10∼12 group (11.53 %) than that in the 13∼15 group (29.97 %) and ≥16 group (77.30 %). Unconditional multivariate logistic regression analysis showed that when ≥10 oocytes were retrieved, the CLBR increased significantly (P 0.01). When oocyte number exceeded 16, the CPR of frozen embryo transfer cycle was much higher than that of fresh cycle (P 0.05).For young women with normal ovarian reserve, retrieving 10∼12 oocytes might result in optimized pregnancy outcomes in a fresh cycle with low OHSS risk and would not compromise cumulative outcomes. When ≥16 oocytes were retrieved, a "freeze-all" embryo strategy might be preferable.

Studies in bovine and porcine have indicated that melatonin (MT) could induce meiotic maturation of immature oocytes in vitro. The object of the current study was to investigate if MT could ameliorate human oocytes maturation during rescue in vitro maturation (IVM).Two hundred seventy eight germinal vesicle (GV) oocytes and 451 (MI) metaphase I oocytes were vitrified, thawed and then matured in vitro. All the oocytes were randomly allocated into six groups in which the oocytes were cultured in medium supplemented with different concentrations of MT (0, 10(-2), 1, 10(2), 10(4), 10(6) nM) and nuclear maturation was evaluated at 6 h, 12 h, 18 h, 24 h and 48 h of culture.The optimal MT concentration for both GV and MI oocytes was 1 nM. At 24 h of culture, nuclear maturation rate of MI oocytes cultured in 1 nM MT medium was significantly higher than other groups (P 0.05); Nuclear maturation rate of GV oocytes cultured in 1 nM MT medium was also significantly higher than the control group (P 0.05). On the other hand, decreased nuclear maturation rate was observed in the high MT concentration group (10(6) nM).The current study demonstrated that low concentration of exogenous MT could ameliorate nuclear maturation of human oocyte during rescue IVM, while high concentration of MT presented negative effects.