Meta-analysis of trigger timing in normal responders undergoing GnRH antagonist ovarian hyperstimulation protocol.

IMPORTANCE: The first meta-analysis focused only on gonadotropin-releasing hormone (GnRH) antagonists, which helped determine the effect of delay trigger on pregnancy outcomes. OBJECTIVE: To evaluate the impact of delay trigger compared with standard trigger in normal responders undergoing GnRH antagonist protocol in improving pregnancy outcomes. METHODS: Studies published before April 2023 in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and CBM databases were searched. Randomized controlled trials (RCTs) and cohort studies conducted in normal responders reporting the efficacy of delay trigger using GnRH antagonist protocol were included. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for categorical variables with their corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q test. RESULTS: Endpoints, including clinical pregnancy rate (CPR), live birth rate (LBR), the number of oocyte retrievals and embryos, and fertilization rate, were analyzed. Six (6) clinical studies (4 RCTs and 2 cohort studies) with 1,360 subjects were included. The pooled results showed that the number of oocyte retrievals (MD: 1.20, 95% CI: 1.10, 1.30, p < 0.01), fertilization rate (MD: 0.64, 95% CI: 0.29, 0.99, p < 0.01) and days of stimulation (MD: 0.95; 95% CI: 0.54, 1.37; p < 0.01) in the delay trigger group was significantly higher than that in the standard trigger group. However, there was no significant difference in the number of embryos (MD: 0.19, 95% CI: -0.29, 0.67, p = 0.44), CPR (OR: 1.12; 95% CI: 0.72, 1.75; p = 0.062), and LBR (OR: 1.23; 95% CI: 0.90, 1.66; p = 0.19) between the two trigger groups. CONCLUSION: Delaying trigger time in GnRH antagonist protocol increased the number of oocytes retrieved but not the number of embryos. Furthermore, delay trigger shot was not associated with a clinical benefit towards CPR and LBR in women who underwent fresh embryo transfer cycles. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews (PROSPERO), registration number: CRD42023413217.

Follicular fluid C3a-peptide promotes oocyte maturation through F-actin aggregation.

BACKGROUND: Immature cumulus-oocyte complexes are retrieved to obtain mature oocytes by in vitro maturation (IVM), a laboratory tool in reproductive medicine to obtain mature oocytes. Unfortunately, the efficiency of IVM is not satisfactory. To circumvent this problem, we therefore intended to commence with the composition of ovarian follicular fluid (FF), an important microenvironment influencing oocyte growth. It is well known that FF has a critical role in oocyte development and maturation. However, the components in human FF remain largely unknown, particularly with regard to small molecular peptides. RESULTS: In current study, the follicular fluid derived from human mature and immature follicles were harvested. The peptide profiles of FF were further investigated by using combined ultrafiltration and LC-MS/MS. The differential peptides were preliminary determined by performing differentially expressed analysis. Human and mouse oocyte culture were used to verify the influence of differential peptides on oocyte development. Constructing plasmids, cell transfecting, Co-IP, PLA etc. were used to reveal the detail molecular mechanism. The results from differentially expressed peptide as well as cultured human and mouse oocytes analyses showed that highly conserved C3a-peptide, a cleavage product of complement C3a, definitely affected oocytes development. Intriguingly, C3a-peptide possessed a novel function that promoted F-actin aggregation and spindle migration, raised the percentage of oocytes at the MII stage, without increasing the chromosome aneuploidy ratio, especially in poor-quality oocytes. These effects of C3a-peptide were attenuated by C3aR morpholino inhibition, suggesting that C3a-peptide affected oocytes development by collaborating with its classical receptor, C3aR. Specially, we found that C3aR co-localized to the spindle with ß-tubulin to recruit F-actin toward the spindle and subcortical region of the oocytes through specific binding to MYO10, a key regulator for actin organization, spindle morphogenesis and positioning in oocytes. CONCLUSIONS: Our results provide a new perspective for improving IVM culture systems by applying FF components and also provide molecular insights into the physiological function of C3a-peptide, its interaction with C3aR, and their roles in enabling meiotic division of oocytes.

Y chromosome AZFc microdeletion may have negative effect on embryo euploidy: a retrospective cohort study.

BACKGROUND: Embryo aneuploidy is a main of principal reason of pregnancy loss, in vitro fertilization (IVF) failure and birth defects in offspring. Previous researchs have demonstrated that Y chromosome AZFc microdeletion was associated with reproduction outcomes, however, the relationship between Y chromosome AZFc microdeletion and embryo aneuploidy remains unexplored. METHODS: This retrospective cohort study enrolled 513 patients with 603 cycles in the reproductive center of Nanjing Maternity and Child Health Care Hospital from January 1, 2016 to June 30, 2022. The study cohort was divided into two groups: the AZFc microdeletion group, comprising 53 patients and 58 cycles, and the control group, comprising 460 patients and 545 cycles. Statistical methods including restricted cubic spline and generalized estimating equation (GEE) were employed to evaluate the relationship between Y chromosome AZFc microdeletion and embryo euploidy. RESULTS: 294 and 2833 blastocysts were selected as AZFc microdeletion group and control group, respectively. Patients with Y chromosome AZFc microdeletion had significantly higher embryo aneuploid rate (33.0% vs. 27.3%, P < 0.05), lower rate of normal fertilization rate (81.5% vs. 90.3%, P < 0.05) and lower blastocysts formation rate (47.0% vs. 57.8%, P < 0.05) compared with the control group. However, no significant differences in pregnancy outcomes after euploid embryos transfer were observed between these two groups. CONCLUSIONS: Our study underscored the association between Y chromosome AZFc microdeletion and an elevated risk of embryo aneuploidy. Before the conventional intracytoplasmic sperm injection (ICSI) treatment, couples with Y chromosome AZFc microdeletion should be apprised of the heightened susceptibility to embryo aneuploidy. Preimplantation genetic testing for aneuploidy (PGT-A) should be introduced for selection.

Triclosan has a strong influence on the development of mouse preimplantation embryo via activating miR-134/Nanog axis.

Antimicrobial triclosan (TCS), one of the popular ingredients added to sanitizing products, has widespread use in personal care. However, it poses potential risks to reproduction and development. Unfortunately, the underlying mechanisms remain largely unclear. This study aimed to investigate effects of TCS on the development of preimplantation mouse embryo and explore related mechanisms Mouse zygotes were collected and cultured to blastocysts in KSOM medium supplemented with four different concentrations of TCS. The development rates, pluripotency or stem cells markers, and microRNA (miR)- 134 were compared between control and experimental groups across each specific developmental stage. Prolonged exposure to TCS remarkably impaired early embryo development in vitro by hampering morula and blastocyst formations (P < 0.05, P < 0.001). The arrest of embryo development was linked with decreased expressions of pluripotency or stem cells markers, especially Nanog and Notch1. Moreover, based on miRWalk database and in vitro luciferase assays, we confirmed that miR-134 induced by TCS was a negative regulator of Nanog. Crucially, impaired TCS-treated embryos could be rescued by inhibiting miR-134 or forced overexpressing Nanog mRNA. Altogether, our results highlight that pathologically relevant level of TCS compromises preimplantation mouse embryo development by inducing miR-134 and triggering miR-134/Nanog axis. Considering high conservative of miR-134 between human and mouse, it should be the most promising potential target to regulate development of preimplantation embryo.

Intramural pregnancy after in vitro fertilization and embryo transfer: A case report.

BACKGROUND: Intramural pregnancy is a rare type of ectopic pregnancy, which is diagnosed by transvaginal ultrasound and magnetic resonance imaging. Management strategies vary depending on the site of the pregnancy, the gestational age and the desire to maintain fertility. The incidence of intramural pregnancy in assisted reproductive technology is higher than that in natural pregnancy. CASE SUMMARY: We present a case of intramural pregnancy after in vitro fertilization and elective single embryo transfer following salpingectomy. The patient was completely asymptomatic and her serum ß-human chorionic gonadotropin level increased from 290 mIU/mL to 1759 mIU/mL. Three-dimensional transvaginal ultrasound indicated a heterogeneous echogenic mass arising from the uterine fundus which was surrounded by myometrium and a slender and extremely hypoechoic area stretching to the uterine cavity which was thought to be a fistulous tract. Therefore, we considered a diagnosis of intramural pregnancy and laparoscopic surgery was conducted at 7 wk gestation. CONCLUSION: Early diagnosis and treatment of intramural pregnancy is significant for maintaining fertility.