Impact of Female Obesity on Cumulative Live Birth Rates in the First Complete Ovarian Stimulation Cycle.

Background: Female overweight/obesity has been reported to be associated with compromised pregnancy outcomes in fresh embryo transfer cycles. It is unclear whether the cumulative live birth rate (CLBR) is adversely affected after all viable embryos are transferred from the first ovarian stimulation cycle. Objectives: To investigate whether the CLBR was compromised in obese women. Method: A total of 9,772 young women underwent their first IVF/ICSI cycles from January 2012 to October 2017. Pregnancy outcomes were compared according to female BMI. Results: Among 1,671 women with polycystic ovary syndrome (PCOS), those with a BMI ≥ 28 kg/m2 had a lower cumulative clinical pregnancy rate (CCPR) and CLBR during the first complete ovarian stimulation cycle. Additionally, the pregnancy loss rate was increased in this group, although the difference was not significant. Among the 8,101 women without PCOS, the CCPR and CLBR of obese patients was also significantly decreased, and this group also showed increased pregnancy loss rates. Moreover, overweight women also had a decreased CLBR. Conclusions: Female obesity adversely affected the CLBR after utilizing the viable embryos from first oocytes retrieval.

The role of AMH and its receptor SNP in the pathogenesis of PCOS.

The etiology of polycystic ovaries syndrome (PCOS) is unknown. Studies probing the role of genetic variants of anti-Mullerian hormone (AMH) and its type II receptor (AMHR2) in the pathogenesis of PCOS have yielded inconsistent results. Thus, we performed a systematic review and meta-analysis to determine the role of genetic variants of AMH/AMHR2 in the pathogenesis of PCOS. A systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3). Pooled Odds Ratios (OR) (95% confidence intervals) were determined to assess the association between genetic variants of AMH/AMHR2 and PCOS. Five studies, involving a total of 2042 PCOS cases and 1071 controls, were included in the meta-analysis. Single nucleotide polymorphisms of AMH and AMHR2 did not appear to confer a heightened risk for PCOS (OR: 0.954, 95% CI: 0.848-1.073; P = 0.435; and OR: 1.074, 95% CI: 0.875-1.318; P = 0.494, respectively). In this study, genetic variants of AMH or AMHR2 were not found to be associated with a higher risk for PCOS.

Differential genes in adipocytes induced from polycystic and non-polycystic ovary syndrome-derived human embryonic stem cells.

We explored the molecular mechanisms of obesity and insulin resistance in patients with polycystic ovary syndrome (PCOS) using a human embryonic stem cell model (hESCs). Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total RNA was extracted. The differentially expressed PCOS-derived and non-PCOS-derived adipocytes genes were identified using the Boao Biological human V 2.0 whole genome oligonucleotide microarray. Signals of interest were then validated by real-time PCR. A total of 153 differential genes were expressed of which 91 genes were up-regulated and 62 down-regulated. Nuclear receptor subfamily 0, group B, member 2 (NR0B2) was an up-regulated gene, and the GeneChip CapitalBio® Molecule Annotation System V4.0 indicated that it was associated with obesity and diabetes (Ratio ≥ 2.0X). Multiple genes are involved in PCOS. Nuclear receptor subfamily 0, group B, member 2 may play a role in obesity and insulin resistance in patients with PCOS.

Analysis of blastocyst culture of discarded embryos and its significance for establishing human embryonic stem cell lines.

In recent years, applications of stem cells have already involved in all domains of life science and biomedicine. People try to establish human embryonic stem cell lines (hESCs) in order to carry out hESC-related studies. In this study, we explored what embryos are conducive to the establishment of hESCs. The discarded embryos from in vitro fertilization-embryo transfer (IVF-ET) cycles were sequentially incubated into blastocysts, and then the inner cell mass (ICM) was isolated and incubated in the mixed feeder layer. The cell lines which underwent serial passage were identified. After a total of 1,725 discarded embryos from 754 patients were incubated, 448 blastocysts were formed with 123 high-quality blastocysts. The blastulation rate was significantly higher in the discarded embryos with non-pronucleus (0PN) or 1PN than in the discarded embryos with 2PN or ≥3PN. The blastulation rate of the D3 embryos with 7-9 blastomeres was higher. Among the originally incubated 389 ICMs, 22 hESCs with normal karyotype were established, and identified to be ESCs. Therefore, in establishing hESCs with discarded embryos, D(3) 0PN or 1PN embryos with 7-9 blastomeres should be first selected, because they can improve high-quality blastulation rate which can increase the efficiency of hESC establishment.

Chromosome dynamic changes in two cultured Chinese human embryonic stem cell lines: single nucleotide polymorphism, copy number variation and loss of heterozygosity.

The quality and safety of human embryonic stem cells (hESCs) in clinical application depend on gene stability. Two Chinese hESC lines, Zh1 and Zh21, were incubated over a long period. We observed and compared the gene stability in the passage numbers 20, 17 for Zh1 cell line and passage numbers 27, 60, 68 for Zh21 cell line. Single nucleotide polymorphisis analysis indicated that hESCs in early passages had relative gene stability; and with the increase in passage number, gene instability became strong. We also found that there were copy number variations (CNVs) in both Zh21 and Zh1. We analyzed the CNVs of Chinese Han Beijing man (CHB; normal Chinese people) and found that the all CNV forms were the loss in Zh21, Zh1, and CHB. We also analyzed and compared the related pathways of the mutant genes. We propose three steps to ensure hESC safety. Firstly, besides the conventional methods such as pluripotent genes, chromosome G-banding and teratoma, high-resolution DNA chip analysis should also be adopted; secondly, chromosomal properties are monitored every 10 passages in less than passage 50 and every 5 passages in more than passage 50; thirdly, the related pathways of mutant genes should be observed because only the mutant genes with variations of their related pathways may affected cell functions.

Differentiation of polycystic ovary syndrome-derived human embryonic stem cells into adipocytes and their glucose consumption.

BACKGROUND: Polycystic ovary syndrome (PCOS) is related to genetic factors. Adipose tissue and insulin resistance (IR) may play an important role in the pathogenesis and progression of PCOS. We investigate glucose consumption and insulin response abilities in the adipocytes differentiated from PCOS-derived human embryonic stem cells (hESCs) in vitro in order to provide a new idea for exploring PCOS pathogenesis. METHODS: hESC lines were established with the discarded embryos of non-PCOS or PCOS-women, and then were differentiated into adipocytes. The glucose consumption ability and insulin response ability for these adipocytes were detected. RESULTS: There was no significant difference in glucose consumption ability between non-PCOS and PCOS-derived adipocytes at the absence of insulin. Insulin could significantly increase glucose consumption abilities of both non-PCOS and PCOS-derived adipocytes, but there was no significant difference in the increased glucose consumption ability between the two types of adipocytes. CONCLUSION: The glucose consumption ability and insulin response ability in the PCOS-derived adipocytes are similar to that in non-PCOS-derived adipocytes.

Establishment of polycystic ovary syndrome-derived human embryonic stem cell lines.

BACKGROUND: Recently, human embryonic stem cells (hESCs) of some genetic diseases have been established, but little research has been done on polycystic ovary syndrome (PCOS)-derived hESCs. The establishment of PCOS-derived hESCs provides a biological basis for exploring the pathogenesis, gene mapping and gene therapy of PCOS. METHODS: Discarded fresh embryos were collected and cultured until the blastocyst stage, and then inner cell masses (ICM) were isolated by mechanical methods and incubated in the mixed feeder layer containing human stem cell medium. hESCs were identified whether to maintain normal karyotype and pluripotency by alkaline phosphates (AKP), stage-specific embryonic antigen-4 (SSEA-4), NANOG, SOX2 and TRA-1-60, octamer binding protein 4(OCT-4), and in vivo and in vitro differentiation. RESULTS: Of the 11 passaged ICM, nine showed adherent growths within 48 h with an adherence rate of 81.8% (9/11). Five PCOS-derived hESCs were established and all of them have the characteristics of pluripotent differentiation. One was from 2PN embryo which was retarded in the cleavage stage, one was from 1PN embryo and others were from 0PN embryo. They were named p-hES-1, p-hES-2, p-hES-3, p-hES-4, p-hES-5, respectively. CONCLUSION: We provide biological models for studying the pathogenesiss of PCOS.

[Analysis of 1540 neonates with birth defects related to different assisted reproductive technique].

OBJECTIVE: To investigate the incidence of and clinical factors influencing neonatal birth defects from different assisted reproductive technology. METHODS: Between October 1998 and December 2006, 1271 newborns from mothers treated by in vitro fertilization techniques [including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and thaw embryo transfer (Thaw-ET)] matched with 269 newborns from mothers treated by artificial insemination were enrolled in Reproductive Medicine Center in First Hospital Affiliated to Zhengzhou University. Their medical information was analyzed retrospectively to compared neonatal characteristics, the incidence of birth defect and anomalous organs involved between in vitro fertilization group and artificial insemination group. RESULTS: In group of in vitro fertilization, those newborns with low birth weight from IVF, ICSI and Thaw-ET were 20.0% (134/671), 22.4% (92/410), 18.9% (36/190) respectively, which were more than 11.5% (31/269) cases in group of artifical semination with statistical significance (P < 0.05). The rates of multiple pregnancy of 23.8% (160/671), 25.4% (104/410), 21.1% (40/190) in subgroup of IVF, ICSI and Thaw-ET were significantly higher than 10.0% (27/269) in group of artifical insemination (P < 0.05). The rate of macrosomia in group of in vitro fertilization was significantly lower than that of artificial insemination group (3.9% vs 8.2%, P < 0.05). However, the incidence of birth defect involved in various organs did not show significant difference between two groups (P > 0.05). CONCLUSIONS: The incidence of multiple pregnancy demonstrated obviously increasing trends born with various In Vitro Fertilization techniques, which pave the way to high risk pregnancy. However, the incidence of newborn birth defect was not increased significantly. Thus, to lower occurrence of multiple pregnancy was the key approach to obtain neonates health.