Mosaic embryos contain two or more genetically distinct cell lines, which can be detected by pre-implantation genetic testing for aneuploidy. At present, it has been reported that mosaic embryo transfer can lead to healthy live births. In order to prevent severe adverse pregnancy outcomes, such as implantation failure, abortion, congenital malformation and neonatal death after implantation of mosaic embryos, it is critical to carry out genetic counseling, prenatal diagnosis and pregnancy supervision for mosaic embryo transfer. This article reviews the selection of mosaic embryos, the pregnancy outcomes of mosaic embryo transfer, and the safety of offspring, in order to provide references for the clinical practice of mosaic embryo transfer.
Pregnancy ; Female ; Infant, Newborn ; Humans ; Preimplantation Diagnosis ; Embryo Transfer ; Pregnancy Outcome ; Genetic Testing ; Embryo Implantation/genetics*

The transcription factor X-box binding protein-1 (XBP1) plays a key role in unfolded protein reaction. This study was aimed to investigate the expression pattern and regulation of XBP1 in the mouse uterus during early pregnancy. The methods of immunohistochemistry (IHC) and real time quantitative RT-PCR were used to test XBP1 expression in early pregnancy, artificial decidualization, oestrous cycle and hormone-regulated mouse models. The results showed that XBP1 was spatiotemporally expressed in mouse uterus during early pregnancy. The XBP1 protein was mainly detected in the luminal and glandular epithelia on days 1-4 of pregnancy, and was strongly detected in the decidual area on days 5-8 of pregnancy. Similarly, XBP1 expression was also mainly expressed in decidual cells following artificial decidualization. During the oestrous cycle, Xbp1, Xbp1u, and Xbp1s mRNA was predominantly present in proestrus. In the ovariectomized uterus, the expression of XBP1 in luminal and glandular epithelia was up-regulated after estrogen treatment. These results suggest that XBP1 is associated with embryo implantation and decidualization during early pregnancy in mice, and the expression of XBP1 in luminal and glandular epithelia may be regulated by estrogen.
Animals ; Decidua ; Embryo Implantation ; Estrogens ; Female ; Mice ; Pregnancy ; RNA, Messenger/genetics* ; Uterus

Endometrial receptivity has become the main cause of fertilization and pregnancy outcomes in infertile patients,bringing large psychological damage and economic loss to the patients and their family. In recent years,the role of non-coding RNA has increasingly been recognized. The relationship between non-coding RNA and endometrial receptivity is reviewed in this article.
Embryo Implantation ; Endometrium ; physiology ; Female ; Fertilization in Vitro ; Humans ; Pregnancy ; Pregnancy Outcome ; RNA, Untranslated ; genetics

BACKGROUNDAt present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis.

METHODSA total of 12 repeated implantation failure (RIF) patients and 10 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs.

RESULTSCompared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stem cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations of microRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result of microarray analysis.

CONCLUSIONSThere is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.

Adult ; Embryo Implantation ; genetics ; physiology ; Endometrium ; metabolism ; Female ; Humans ; Infertility, Female ; genetics ; MicroRNAs ; genetics ; Microarray Analysis ; Pregnancy ; Real-Time Polymerase Chain Reaction

This study investigated the molecular markers of DS-1-47, a component of an implantation- promoting traditional Chinese medicine consisting of Astragalus mongholicus, Atractylodes macrocephala, Scutellaria baicalensis and Dipsacales, in an attempt to clarify the molecular mechanism and action targets of DS-1-47. Controlled ovarian stimulation (COS) method was used to establish the implantation dysfunction models of mice. Animals were divided into normal pregnant group, COS model group and DS-1-47 group. Laser capture microdissection-double dimensional electrophoresis-mass spectrum (LCM-DE-MS) was used to analyze the uterine protein molecules that were possibly involved in the promotion of implantation. Twenty-three proteins in DS-1-47 group were significantly changed as compared to those in COS model group, with 7 proteins down-regulated and 16 proteins up-regulated. Except for some constituent proteins, the down-regulated proteins included collagen α-1 (VI) chain, keratin 7, keratin 14, myosin regulatory light chain 12B, myosin light polypeptide 9, heat shock protein β-7, and C-U-editing enzyme APOBEC-2; the up-regulated proteins included apolipoprotein A-I, calcium regulated protein-3, proliferating cell nuclear antigen, L-xylulose reductase, and calcium binding protein. These 23 proteins that were regulated by DS-1-47 represented a broad diversity of molecule functions. The down-regulated proteins were associated with stress and immune response, and those up-regulated proteins were related to proliferation. It was suggested that these proteins were important in regulating the uterine environment for the blastocyst implantation. By identification of DS-1-47 markers, proteomic analysis coupled with functional assays is demonstrated to be a promising approach to better understand the molecular mechanism of traditional Chinese medicine.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Embryo Implantation ; drug effects ; Female ; Mice ; Ovulation Induction ; Pregnancy ; Proteome ; genetics ; metabolism ; Uterus ; drug effects ; metabolism ; physiology

OBJECTIVETo investigate the effect of acupuncture on progesterone (P4) and prolactin (PRL) in rats of embryo implantation dysfunction (EID).

METHODSOn the first day of pregnancy, 72 female Wistar rats were randomly allocated into the normal group, the EID model group, the acupuncture group and the P4 group (18 in each group). The normal group was injected sesame oil, while the other three groups were given mifepristone to establish the EID model. The acupuncture group and the P4 group were given treatment of acupuncture and P4 injection, respectively. The serum of P4 and PRL were detected by radioimmunoassay, and the mRNA and protein expressions of P4 receptor (PR) and PRL receptor (PRLR) were detected using real-time polymerase chain reaction and immunohistochemical method, respectively.

RESULTSCompared with the normal group, the serum levels of P4 and PRL as well as the mRNA and protein expression levels of PR and PRLR in the EID model group were significantly lowered (P<0.01 or P<0.05). The above indices in the acupuncture group and the P4 group were significantly elevated compared with the EID model group (P<0.01 or P<0.05).

CONCLUSIONAcupuncture can promote embryo implantation effectively, which might be related to the effects of acupuncture on upregulating the P4 and PRL levels in serum and the PR and PRLR expression levels in rats.

Acupuncture Therapy ; Animals ; Embryo Implantation ; Endometrium ; metabolism ; Female ; Gene Expression Regulation ; Immunohistochemistry ; Male ; Pituitary Gland ; metabolism ; Pregnancy ; Progesterone ; blood ; Prolactin ; blood ; RNA, Messenger ; genetics ; metabolism ; Rats, Wistar ; Receptors, Progesterone ; genetics ; metabolism ; Receptors, Prolactin ; genetics ; metabolism

To observe the effect of acupuncture on CXCL8 receptors (CXCR1 and CXCR2) in rat endometrium experiencing embryo implantation failure, 72 pregnant rats were randomly divided into four groups: normal group (N), embryo implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). Then the rats in each group were equally randomized into a day-6 (D6) group, a day-8 (D8) group, and a day-10 (D10) group. The rats in group M, group A, and group W were treated with mifepristone-sesame oil solution on day 1, while the rats in group N were injected with the same amount of sesame oil. Meanwhile, "Housanli" and "Sanyinjiao" were selected for acupuncture. From day 1 to the time of death, the rats in group A were fastened up and then acupuncture was administered while the rats in group N and group M were only fixed, and the rats in group W were given progestin. The number of implanted embryos was calculated. The expression of CXCR1 and CXCR2 in rat endometrium was detected by immunohistochemistry, Western blotting and real-time PCR. Compared to group N, the average number of implanted embryos, the protein and mRNA expression of CXCR1 (D6, D8 and D10), and the protein and mRNA expression of CXCR2 (D8 and D10) in rat endometrium were significantly decreased in group M. Compared to group M, there was significant elevation in the average number of implanted embryos, the protein expression (D6, D8 and D10) and mRNA expression (D8) of CXCR1 in rat endometrium of group A, and the protein expression (D8 and D10) and mRNA expression (D8) of CXCR2 in rat endometrium of group W. These findings indicated that acupuncture can increase the number of implanted embryos in rats of embryo implantation failure, which may be relevant with up-regulation the expression of CXCR1 and CXCR2 at maternal-fetal interface of rats with embryo implantation failure.
Acupuncture Therapy ; methods ; Animals ; Blotting, Western ; Embryo Implantation ; drug effects ; genetics ; Endometrium ; drug effects ; metabolism ; Female ; Gene Expression Regulation, Developmental ; Hormone Antagonists ; pharmacology ; Immunohistochemistry ; Mifepristone ; pharmacology ; Pregnancy ; Progestins ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Interleukin-8A ; genetics ; metabolism ; Receptors, Interleukin-8B ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Treatment Outcome ; Up-Regulation ; drug effects

OBJECTIVETo observe the effect of Yiqixue Buganshen recipe(, YBR) on the expression of integrin ανβ3 in the endometrium of controlled ovarian hyperstimulation mice.

METHODSA total of 180 mice were divided into three groups: model group, treatment group and control group. The treatment and model groups were intraperitoneally injected with gonadotropin-releasing hormone analogue for 7 days; pregnant mare serum gonadotropin was also injected on the 7th day. After 48 h, human chorionic gonadotropin was injected. The control group was injected with an equal volume of saline at the same time. From the start of the experiment, the treatment group was intragastrically administered Jinghouzengzhi Recipe() and Cuhuangti Recipe(). The model group and the control group were intragastrically administered an equal volume of saline. Real-time reverse transcription polymerase chain reaction and Western blotting were used to detect the mRNA and protein expression of integrin ανβ3 in mouse endometrium.

RESULTSIntegrin ανβ3 was expressed in mouse endometrium in all groups. Integrin αββ3 expression increased gradually along with pregnancy, progressing from pregnant day (Pd) 1. Integrin ανβ3 expression significantly increased on Pd 4, then began to decrease on Pd 6. Integrin ανβ3 expression in the treatment group was higher than in the model group, and the difference was statistically significant (P <0.05). The difference between the treatment group and the control group was not statistically significant (P >0.05).

CONCLUSIONYBR improves endometrial receptivity, and may play an important role in embryonic implantation.

Animals ; Blotting, Western ; Drugs, Chinese Herbal ; pharmacology ; Embryo Implantation ; drug effects ; Endometrium ; drug effects ; metabolism ; Female ; Gene Expression Regulation ; drug effects ; Horses ; Humans ; Integrin alphaVbeta3 ; genetics ; metabolism ; Mice ; Ovulation Induction ; Pregnancy ; RNA, Messenger ; genetics ; metabolism

OBJECTIVETo study the correlation between sperm DNA fragmentation index (DFI), age of male, various parameters of sperm, rates of fertilization, high quality embryo and pregnancy and implantation rates.

METHODSOne hundred and eleven infertile couples were selected randomly, and DFI was tested by flow cytometry for the sperm used for IVF. The patients were divided into different groups according to the DFI scores. The results of each group were analyzed.

RESULTSThe IVF normal fertilization was significantly lower in couples with sperm DFI over 10% (60.5%) than that in couples with DFI below 10% (70.1%) (P<0.05). Significantly positive correlation was found between DFI and the age of male (r=0.624, P<0.05). DFI was also significantly negatively correlated with the percentage of linearly progressive sperm (r=-0.360, P<0.05). There was no significant correlation between the rates of high quality cleaved embryos, pregnancy and implantation rate and sperm DFI.

CONCLUSIONDFI scores are increased with male's age, and it can influence the sperm motility. DFI=10% can be considered as a critical point which can be used to estimate the clinical fertility rate of IVF. But it could not provide relative information about the rates of high quality embryos and pregnancy for infertile couples undergoing IVF procedure.

Adult ; Aging ; genetics ; physiology ; DNA Fragmentation ; Embryo Implantation ; genetics ; Female ; Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Regression Analysis ; Spermatozoa ; metabolism ; physiology

This study examined the effects of Bangdeyun on the expressions of nuclear factor-kappaB (NF-kappaB), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in the endometrium of mice with embryo implantation dysfunction (EID) during the implantation time (namely on pregnancy day 5, 6, 7 and 8) and explored the local immune regulatory effects of Bangdeyun. The gestational mice were randomly divided into normal group, model group and Bangdeyun-treated group. EID models of mice were established by using indomethacin. The endometrial expression of NF-kappaB was detected by immunohistochemistry and Western blotting. IFN-gamma and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in the normal group, NF-kappaB and IFN-gamma were weakly expressed and IL-10 was strongly expressed in the endometrium during the whole implantation period. In the model group, the expressions of NF-kappaB and IFN-gamma were increased on pregnancy day 5, 6 and 7, and IL-10 expression decreased during the whole implantation time when compared with those in the normal group (P<0.01 for all). In the Bangdeyun-treated group, little amount of NF-kappaB and IFN-gamma was expressed and IL-10 expression was strong, much the way they were expressed in the normal group (P>0.05). The expressions of NF-kappaB and IFN-gamma were much lower in the Bangdeyun-treated group than those in the model group on pregnancy day 5, 6 and 7 (P<0.01 for all), while the expression of IL-10 was much higher than in the model group during the whole implantation time (P<0.01). It was suggested Bangderun may favor a shift from Th1- to Th2-type immune response, therefore inhibiting the maternal immune rejection, inducing the immune tolerance and improving the fetal implantation.
Drugs, Chinese Herbal/*pharmacology ; Embryo Implantation, Delayed/*drug effects ; Embryo Implantation, Delayed/immunology ; Endometrium/*immunology ; Endometrium/metabolism ; Interferon-gamma/genetics ; Interferon-gamma/metabolism ; Interleukin-10/genetics ; Interleukin-10/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism