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

Angiotensin-converting enzyme functions in the male reproductive system, but the extent of its function in reproduction is not fully understood. The primary objective of this work was to investigate the relationship between the testicular isoform of angiotensin-converting enzyme present in human spermatozoa and semen parameters, human embryo quality, and assisted reproduction success. A total of 81 semen samples and 635 embryos from couples undergoing oocyte donation cycles at the IVI Bilbao Clinic were analyzed. Semen parameters, embryos quality, and blastocyst development were examined according to the World Health Organization standards and the Spanish Association of Reproduction Biology Studies criteria. The percentage of testicular angiotensin-converting enzyme-positive spermatozoa and the number of molecules per spermatozoon were analyzed by flow cytometry. Both parameters were inversely correlated with human sperm motility. Higher percentages of testicular angiotensin-converting enzyme-positive spermatozoa together with fewer enzyme molecules per spermatozoon were positively correlated with better embryo quality and development. Our results suggest that embryos with a higher implantation potential come from semen samples with higher percentages of testicular angiotensin-converting enzyme-positive cells and fewer enzyme molecules per spermatozoon. Based on these findings, we propose that testicular angiotensin-converting enzyme could be used to aid embryologists in selecting better semen samples for obtaining high-quality blastocysts during in vitro fertilization procedures.
Adult ; Embryo Implantation/physiology* ; Embryo Transfer ; Embryonic Development/physiology* ; Fertility/physiology* ; Fertilization in Vitro ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/metabolism* ; Sperm Motility/physiology* ; Spermatozoa/enzymology* ; Testis/enzymology*

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

OBJECTIVETo evaluate the impact of sperm midpiece morphology observed under high-power microscope on embryo development following intracytoplasmic morphologically selected sperm injection.

METHODSMorphologically normal sperms from 57 patients undergoing intracytoplasmic sperm injection (ICSI) for male-factor infertility were selected microscopically (magnification of ×200 or 400) and subjected to motile sperm organellar morphology examination (MSOME) at high magnification of ×6000. According to the morphology of sperm medpiece, the sperms were divided into 3 groups, namely group A with a/b of 1-1.2, group B with a/b≥1.5, and group C with irregular morphology. The sperms in the 3 groups were intracytoplasmically injected in oocytes and the outcomes of the embryos were compared.

RESULTSGroups A, B, and C showed significant differences in the rate of ET-D3 top quality embryo (79.7% vs 55.6 % vs 33.3%) and implantation rate (43.2% vs 11.1% vs 0%), but not in the fertilization rate (73.3% vs 80.4% vs 63.5%), blastocyst formation rate (23.2% vs 22.2% vs 9.09%), cryopreservation rate (29.2% vs 25.0 % vs 13.0%), or D3 top quality embryo rate (35.3% vs 37.8% vs 18.8%).

CONCLUSIONSIn ICSI cycle, selecting morphologically normal sperms for intracytoplasic injection can increase the normal fertilization rate and top quality embryo rate on the transfer day and improve the implantation rate of the embryo.

Cryopreservation ; Embryo Implantation ; Embryonic Development ; Female ; Fertilization ; Humans ; Infertility, Male ; Male ; Oocytes ; Semen Analysis ; Sperm Injections, Intracytoplasmic ; Sperm Midpiece ; physiology

OBJECTIVETo investigate the role of endometrial macrophages in embryo implantation and in regulating the expression of vascular endothelial growth factor A (VEGFA) in mouse endometrium during the peri-implantation period.

METHODAt D3.5 (D0.5 defined as the morning when a vaginal plug was observed), pregnant mice were divided randomly into experimental group, control group and blank group. In the experimental group, the mice were subjected to intrauterine injection of clodronate liposomes on the left side of uterus to eliminate the macrophages, and PBS liposomes on the right side. PBS liposomes and PBS were administered in the control and blank groups, respectively. The uterine tissues were collected on D5.5 and stained with trypan blue to show the implantation sites. Flow cytometry was performed to examine the percentage of F4/80(+) CD11b(+) macrophages macrophages in the uterus. F4/80(+) macrophage population within the endometrium and ovary and changes in VEGFA expression at the implantation and non-implantation sites were examined using immunohistochemistry.

RESULTSEndometrial F4/80(+) CD11b(+) macrophages macrophages were significantly reduced by 74% following intrauterine injection of clodronate liposomes (P<0.05). The number of macrophages in the ovaries showed no significant difference among the 3 groups. In the experimental group, the left side of the uterine showed imcomplete cavity closure with a lower number of implantation site than the right side (2.20∓1.81 vs 5.10∓1.91, P<0.05). VEGFA expression at the implantation site were significantly decreased in the endometrium on the left side with macrophage suppression as compared with that on the right side (P<0.05).

CONCLUSIONEndometrial macrophages appear to modulate uterine receptivity by regulating the expression of VEGFA to affect embryo implantation, suggesting the important role of macrophages in embryo implantation.

Animals ; Embryo Implantation ; Endometrium ; physiology ; Female ; Immunohistochemistry ; Macrophages ; cytology ; Mice ; Ovary ; cytology ; Pregnancy ; Random Allocation ; Uterus ; cytology ; Vascular Endothelial Growth Factor A ; physiology

OBJECTIVETo investigate the influence of the rate of morphologically normal sperm (MNS) on the clinical outcomes of conventional in vitro fertilization (IVF) in patients with one retrieved oocyte.

METHODSFrom January 2013 to January 2015, a total of 256 couples with one retrieved oocyte underwent conventional IVF in our center. According to the rate of MNS, the patients were divided into two groups: MNS < 4% (134 cycles) and MNS ≥ 4% (122 cycles). We compared the rates of no transferrable embryo cycles, fertilization, cleavage, normal fertilization, abnormal fertilization, high-quality embryo and transferrable embryo between the two groups. A total of 75 fresh embryo transfer cycles were performed, 43 in the MNS < 4% group and the other 32 in the MNS ≥ 4% group. We also compared the rates of implantation, clinical pregnancy and abortion between the two groups.

RESULTSThere were no statistically significant differences between the two groups in the rates of no transferrable embryo cycles, fertilization, cleavage, normal fertilization, abnormal fertilization, high-quality embryo and transferrable embryo (P > 0.05). The rates of implantation, clinical pregnancy and abortion exhibited no remarkable differences either in the fresh embryo transfer cycles between the two groups (P > 0.05).

CONCLUSIONThe rate of MNS does not affect the clinical outcomes of conventional IVF in patients with one retrieved oocyte.

Abortion, Spontaneous ; Cleavage Stage, Ovum ; Embryo Implantation ; Female ; Fertilization ; Fertilization in Vitro ; methods ; statistics & numerical data ; Humans ; Male ; Oocyte Retrieval ; Pregnancy ; Pregnancy Rate ; Single Embryo Transfer ; statistics & numerical data ; Sperm Count ; Spermatozoa ; physiology

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

BACKGROUNDReduced endometrial receptivity in hyperstimulated cycles may lead to a lower implantation rate and a lower clinical pregnancy rate, but it is unclear if it is also associated with an increase in pregnancy loss rate. The aim of this study was to compare the implantation, miscarriage, and pregnancy rates between fresh and frozen thawed transfer of one or two day-3 embryos, with a view to understanding whether or not reduced endometrial receptivity encountered in hyperstimulated cycles is associated with an increase in miscarriage rate.

METHODSThis study involved a consecutive series of 1 551 single day-3 embryo transfer cycles and consecutive 5 919 double day-3 embryo transfer cycles in the Assisted Reproductive Unit of the Sir Run Run Shaw Hospital, Hangzhou, China, between January 2010 and December 2012.

RESULTSThe implantation and clinical pregnancy rates (single embryo 30.7% and double embryos 33.4% and 51.4%) using fresh cycle were both significantly lower than that of frozen-thawed cycles (single embryo 35.8% and double embryos 38.1% and 57.8%). There was no difference in biochemical loss or clinical miscarriage rates between the two groups.

CONCLUSIONSImpairment of endometrial receptivity associated with ovarian hyperstimulation leads to implantation failure at a very early stage, resulting in an increased number of non-pregnancy. It does not lead to increase in biochemical or clinical losses. The significantly reduced ongoing pregnancy rates in both fresh single and double embryo transfer are therefore due to failure to achieve a pregnancy, rather than pregnancy loss after conception.

Adult ; Cryopreservation ; Embryo Implantation ; physiology ; Embryo Transfer ; methods ; statistics & numerical data ; Female ; Fertilization in Vitro ; methods ; statistics & numerical data ; Humans ; Male ; Pregnancy ; Pregnancy Rate ; Retrospective Studies

The aim of this study was to investigate the effect of Bu-Shen-An-Tai recipe (BSATR) and its two components (Bushen recipe, and Huoxue recipe) on endometrial morphology during peri-implantation in superovulated mice. Mice were randomly divided into five groups, including the normal (N), model (M), Bushen (BS), Huoxue (HX) and Bu-Shen-An-Tai (BH) groups. The uteri were collected on day 4 of pregnancy, and the endometrium thickness, microvessel density (MVD) and number of pinopodes observed. Compared with the M group, the endometrial thickness in the BS, HX and BH groups was significantly increased and there was a significant difference in endometrial thickness between the BS and the BH groups. The mean MVD was significantly lower in the M group than in the N group, and there was a significant increase in MVD in the BS, HX and BH groups as compared with the M group. Compared with the M group, the pinopode scores in the endometrium were significantly increased in the HX and BH groups; and the BS group had significantly higher pinipode scores than the HX and BH groups. In conclusion, the results of the present study demonstrated that the recipes (Bushen, Huoxue and BSATR) could improve the endometrial environment by regulating the endometrial thickness, MVD and the number of pinopodes at the window of implantation. Moreover, the Huoxue recipe and the BSATR were more efficient than the Bushen recipe, with the BSATR tending to have the most beneficial effects.
Animals ; Antigens, CD34 ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Embryo Implantation ; physiology ; Endometrium ; drug effects ; physiology ; ultrastructure ; Female ; Immunohistochemistry ; Mice ; Microscopy, Electron, Scanning ; Microvessels ; metabolism ; physiology ; Ovulation ; physiology ; Pregnancy ; Random Allocation ; Time Factors

Asoprisnil, a member of the selective progesterone receptor modulators, exerts high progesterone receptor selectivity, endometrial targeted advantages and significant anti-implantation effect in rats. The purpose of this study was to confirm the anti-implantation effect of asoprisil, investigate the ultrastructural changes of the peri-implantation endometrium in mice and explore the effect of asoprisnil on endometrial receptivity and its targeted contraceptive proficiency. Post-coitus mice were administered with different dosages (0.2, 0.1, 0.05 mg·g(-1)·day(-1)) of asoprisnil from day 1 of pregnancy to day 3. Then 3 animals in each group were killed on day 5 of pregnancy, and uteri were collected to examine the ultrastructural changes of endometria under a transmission electron microscope (TEM). A total of 80 animals were sacrificed on day 8 of pregnancy, and the uterine horns were examined for the presence or absence of nidation sites and the number of implantation embryos. The results showed that the implantation rate and the average number of implantation embryos in asoprisnil groups were statistically significantly decreased as compared with the vehicle control group (P<0.05). The TEM results revealed that, in vehicle control group, the tight junction between the luminal epithelia cells was short and straight, the gap was wide; the luminal epithelia cells were covered with plenty of short, clavate and neatly arranged microvilli; the endometril stromal cells were large with plenty of cytoplasm, and showed significant decidual change; there was more than one nucleus in stromal cells, and the karyotheca was integrity. In low dosage and high dosage asoprisnil groups, the tight junction was longer and more curve than in the vehicle control group; microvilli were uneven and asymmetrically distributed in luminal epithelia; the stromal cells were small and the decidual change was not significant; there were karyopyknosis and karyolysis in stromal cells; there were abnormal thick-wall vessels in the endometrium. It was suggested that asoprisnil changed the ultrastructure of the endometrium in implantation window, disturbed the endometrial receptivity and finally resulted in embryo implantation failure.
Animals ; Contraception, Postcoital ; methods ; Embryo Implantation, Delayed ; drug effects ; physiology ; Endometrium ; drug effects ; physiology ; ultrastructure ; Estrenes ; administration & dosage ; Female ; Mice ; Oximes ; administration & dosage ; Oxytocics ; administration & dosage ; Pregnancy ; Pregnancy, Animal ; Treatment Outcome