OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).
Pregnancy ; Humans ; Female ; Fertilization in Vitro/methods* ; Single-Blind Method ; Embryo Transfer ; Pregnancy Rate ; Acupuncture Therapy ; Endometrium/blood supply*

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC₅₀) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.
Animals ; Zebrafish/metabolism* ; Embryo, Nonmammalian/metabolism* ; Transcriptome ; Oxidative Stress ; Water Pollutants, Chemical/metabolism*

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*

BACKGROUND: Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups. METHODS: A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software ( http://www.R-project.org/ ) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio. RESULTS: The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) ( P  = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely ( P  = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) ( P  = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) ( P  = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes. CONCLUSIONS In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines show significant effects.
Pregnancy ; Humans ; Female ; Male ; Retrospective Studies ; COVID-19/prevention & control* ; Embryo Transfer ; Fertilization in Vitro ; Pregnancy Rate ; Vaccination

OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).
Infant, Newborn ; Pregnancy ; Female ; Humans ; Fertilization in Vitro/methods* ; Ovarian Reserve ; Prospective Studies ; Premature Birth ; Embryo Transfer/methods* ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone/therapeutic use*

Pregnancy ; Female ; Humans ; Placenta ; Nuclear Transfer Techniques ; Embryo, Mammalian ; Cell Nucleus

OBJECTIVES: To evaluate the report quality, methodological quality and evidence quality of the systematic reviews and meta-analyses (SRs/MAs) of acupuncture for in vitro fertilization-embryo transfer (IVF-ET). METHODS: The SRs/MAs of acupuncture for IVF-ET were searched electronically from databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, from inception of each database to September 27th, 2022. Two reviewers independently screened the literature and extracted the data. Using PRISMA statement, the AMSTAR 2 scale and the GRADE system, the report quality, methodological quality and evidence quality of the included SRs/MAs were assessed. RESULTS: A total of 28 SRs/MAs were included, with PRISMA scores ranging from 8.5 points to 27 points. The problems of report quality focused on protocol and registration, retrieval, risk of bias in studies, additional analysis, limitations and funding. The methodological quality of included studies was generally low, reflecting on items 2, 3, 7, 10, 12 and 16. A total of 85 outcome indexes were included in the GRADE system for evidence grade evaluation. Most of the evidences were low or very low in quality. The reasons for the downgrade were related to study limitations, inconsistency, imprecision and publication bias. CONCLUSIONS Acupuncture therapy improves the outcomes of IVF-ET, but the methodological quality and evidence quality of related SRs/MAs are low. It is recommended to conduct more high-quality studies in the future to provide more reliable evidences.
Acupuncture Therapy/methods* ; Databases, Factual ; Embryo Transfer ; Fertilization in Vitro ; Publication Bias ; Systematic Reviews as Topic

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.
Humans ; Pluripotent Stem Cells/metabolism* ; Embryo, Mammalian/metabolism* ; Cell Differentiation ; Blastocyst ; Cell Lineage ; Embryonic Development

OBJECTIVE: To observe the effect of conventional ovulation induction protocol and acupuncture combined with conventional ovulation induction protocol on pregnancy outcomes of frozen embryo transfer (FET) in patients with anovulatory infertility. METHODS: A total of 60 patients with anovulatory infertility were randomized into an observation group and a control group, 30 cases in each group. In the control group, conventional ovulation induction protocol was applied to prepare endometrium. On the basis of the control group, acupuncture was started on the 2nd day of menstrual cycle in the observation group，Baihui (GV 20), Mingmen (GV 4), Geshu (BL 17), Guanyuan (CV 4), Qihai (CV 6), etc. were selected, once every other day, until 1 day before transplantation. The clinical pregnancy rate, embryo implantation rate, endometrial morphology on HCG trigger day, ovulation rate and cycle cancellation rate were compared in the two groups. The endometrial thickness before treatment and on HCG trigger day, TCM symptom score before and after treatment were observed in the two groups. RESULTS: In the observation group, the embryo implantation rate and clinical pregnancy rate were higher than the control group (P<0.05), endometrial thickness and endometrial morphology on HCG trigger day were superior to the control group (P<0.05). After treatment, the TCM symptom score in the observation group was decreased compared with before treatment (P<0.05), and the variation was greater than the control group (P<0.01). CONCLUSION On the basis of the conventional ovulation induction protocol, acupuncture could enhance the embryo implantation rate and clinical pregnancy rate of FET, improve the endometrial receptivity of patients with anovulatory infertility.
Acupuncture Therapy ; Embryo Transfer ; Female ; Humans ; Infertility, Female/therapy* ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate