Can day 3 embryo morphology serve as an independent criterion for optimal single blastocyst selection?
This retrospective, single-centre cohort study included 1517 single vitrified-warmed blastocyst transfer (SVBT) cycles conducted between October 2019 and July 2022. The live birth rate (LBR) and other clinical outcomes of SVBT cycles were evaluated, considering both good-quality and non-good-quality day 3 embryos. The associations of day 3 morphological characteristics, encompassing number of blastomeres and embryo grade, were assessed. Multivariable analyses were undertaken using multiple models adjusted for day of blastocyst development and blastocyst grade.
Blastocysts from good-quality day 3 embryos had significantly higher LBR compared with those from non-good-quality embryos for both day 5 (51.5% versus 42.9%; P = 0.013) and day 6 (25.1% versus 17.6%; P = 0.018) blastocysts. LBR did not differ significantly with number of blastomeres on day 3, regardless of day of blastocyst development (day 5/6) or blastocyst grade. LBR varied significantly by day 3 embryo grade for both day 5 (48.0%, 51.5%, 46.6% and 32.7% for grades I, II, III and IV–V; P = 0.005) and day 6 (41.5%, 23.6%, 15.9% and 16.1% for grades I, II, III and IV–V; P = 0.001) blastocysts. Multivariable logistic regression revealed that non-good-quality embryos and lower morphological grade (IV–V) on day 3 were significantly and negatively correlated with LBR, while the number of blastomeres on day 3 was not an independent factor.
When selecting blastocysts of equal quality for SVBT cycles, those with higher day 3 morphological scores are preferred. Day 3 morphological evaluation is a valuable supplement to conventional selection methods.
As Sjögren's syndrome is an autoimmune disease and an essential factor in recurrent pregnancy loss (RPL), are there gene-related relationships between the pathogenesis of Sjögren's syndrome and RPL?
The gene datasets for Sjögren's syndrome and RPL were obtained from the Gene Expression Omnibus database, and the co-expression modules and shared differentially expressed genes were identified through weighted gene co-expression network analysis (WGCNA) and limma analysis based on sample size. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses were applied to reveal the hidden biological pathways. Additionally, shared hub gene identification, gene set enrichment analysis, association of the hub gene with ferroptosis and immunity, drug sensitivity analysis, single-cell RNA sequencing analysis, and construction of the competing endogenous RNA (ceRNA) network were conducted.
By intersecting the genes from WGCNA and limma analysis, one shared hub gene (KCNN3) was derived, exhibiting up-regulation in Sjögren's syndrome and RPL. There was a positive relationship between KCNN3 and the immune-related gene TLR2. The ceRNA network revealed that XIST was the most shared long non-coding RNA, which may bind competitively with eight microRNA to regulate the expression of KCNN3. Forty-eight drugs were found to be strongly associated with KCNN3 expression, including estramustine and cyclosporine. Moreover, KCNN3 exhibited high expression in RPL endothelial cells of villous tissue.
This is one of the first studies to reveal that Sjögren's syndrome shares common biological pathways with RPL. KCNN3 was identified as the hub gene associated with Sjögren's syndrome and RPL, and may be a new target for mechanistic studies on Sjögren's syndrome and RPL.
The countercurrent opinion given in this paper is that the optimal management of frozen embryo transfers (FET) is not a one-size-fits-all matter, but rather one that should be decided after considering all the various parameters and options. This choice should notably encompass patients’ individual characteristics – including variable risks of obstetric complications – and weigh out the respective advantages of each FET option in each case. While there may be real advantages for natural-cycle FET in many cases, these need to be balanced against both practical and clinical issues. Contrary to several prevailing, sometimes loudly expressed suggestions, there is not a one single effective approach when it comes to choosing a mode of scheduling FET.
Are authors aware when they have cited a retracted paper in their manuscripts in the medically assisted reproduction (MAR) field?
A cross-sectional study based on an online survey was conducted to acquire information on the citation pattern from corresponding authors who had cited a retracted article. A dataset of retracted articles in the MAR field was collected from PubMed and Retraction Watch. A complete list of published articles that cited each retracted article was retrieved. The survey was distributed via e-mail to corresponding authors who had cited a retracted paper in their study.
The survey revealed a significant lack of awareness among authors, with 78.7% unaware that they had cited retracted articles. This lack of awareness was attributed to insufficient notification mechanisms within research databases and journals, alongside a reliance on previously stored copies of manuscripts. A notable finding was that reference checks were typically performed by a single author, with no instances of retraction concerns raised during the peer-review process. Only a small fraction (17.8%) of respondents reported verifying retraction notices on both journal websites and scientific databases.
Correcting publications that contain references which are subsequently retracted is significant for systematic reviews, meta-analyses and guidelines. Citations of retracted articles perpetuate erroneous scientific data, but assessing the accuracy of citations requires considerable effort. Proper notification of retraction status and cross-checking of citations can help to prevent errors.
What were the utilization, effectiveness and safety of assisted reproductive technology (ART) in Africa during 2020?
Cross-sectional, cycle-based and retrospective summary data were collected from voluntarily participating ART centres.
During 2020, 37,063 ART procedures were reported by 67 centres in 15 countries. Autologous fresh transfers were predominant at 65.0%, whereas autologous frozen embryo transfers (FET) represented 26.2% and oocyte donation cycles remained less than 10%. Women undergoing autologous fresh embryo transfer had a mean age of 34.9 years and received a mean number of 2.4 embryos per transfer. The clinical pregnancy rate (CPR) per embryo transfer was 37.3% after fresh embryo transfer and 37.8% after frozen embryo transfer. The cumulative CPR per aspiration was 41.9% in autologous cycles.
Most ART procedures resulted in a multiple delivery rate above 20%. After autologous ART, multiples were predominantly born preterm (twin and triplet deliveries 59.5% versus singleton 21.9% born before 37 weeks), with a substantially increased perinatal mortality compared with ART singletons (59.0‰ versus 22.2‰). Cycle-based data documented that elective single embryo transfer (eSET) provides the optimal balance of effectiveness (eSET CPR per embryo transfer 36.7%) and safety.
This fourth report of the African Network and Registry for ART provides real-world evidence of ART utilization, practices and outcomes in Africa, which is relevant to many stakeholders. It critically informs and represents regional ART development based on national, regional and global cooperation.
What is the impact of maternal and paternal alcohol consumption in the periconception period on embryonic and fetal development assessed using three-dimensional ultrasound and virtual reality techniques?
This prospective observational study was embedded in the Rotterdam periconception cohort (Predict study). Participating women received longitudinal three-dimensional transvaginal ultrasound examinations from week 7 to week 12 of gestation to measure crown–rump length and embryonic volume. Mid-pregnancy fetal size parameters and birth weight were retrieved from medical files. Participants completed a periconception exposure questionnaire and a validated food frequency questionnaire. Linear mixed models were used to analyse the association between parental alcohol consumption, and embryonic and fetal developmental parameters.
In total, 1141 female and 987 male participants were included in the analyses. Moderate maternal alcohol consumption in the periconception period resulted in a smaller head circumference (β = -1.85, SE = 0.84, P = 0.03), abdominal circumference (β = -2.65, SE = 0.93, P = 0.004), femur length (β = -0.56, SE = 0.22, P = 0.01) and estimated fetal weight (β = -9.36, SE = 4.35, P = 0.03) at 20 weeks of gestation. Paternal alcohol consumption showed significant positive associations, mainly with fetal size parameters (abdominal circumference: β = 0.033, SE = 0.01, P = 0.008; estimated fetal weight: β = 0.131, SE = 0.06, P = 0.03).
Moderate maternal alcohol consumption is negatively associated with fetal growth parameters. Moreover, alcohol is proven to be a strong teratogen, and its consumption before and during pregnancy should be discouraged in both women and men as it affects several parameters of embryonic and fetal development.
What influence does an intramural myoma have on the endometrium, and how is this mediated?
Endometrium was collected from 13 patients with non-cavity-distorting intramural myomas (diameter ≤4 cm; International Federation of Gynecology and Obstetrics type 4) and 13 patients without myomas undergoing hysterectomy for benign cervical diseases with a similar clinical baseline. Endometrial organoids were established in vitro and induced to reach the secretory phase by oestrogen and progesterone. Transcriptome sequencing was conducted on endometrial organoids in both untreated and secretory stages from three individuals with myomas and three control participants. Immunofluorescence and real-time quantitative PCR (RT-qPCR) were performed on endometrial organoids from another 10 myoma patients and 10 control patients for validation.
The data revealed abnormally increased hormone receptor (PGR) levels in the untreated endometrial organoids with myomas, resulting in potentially abnormal glandular and vascular development. The aberrant responses to oestrogen and progestogen prompted further investigation into the secretory phase. The secretory endometrial organoids with myomas exhibited greater changes in acetyl-α-tubulin, ODF2 and TPPP, demonstrating likely decreased cilia, and COL6A1, used as a marker for increased extracellular matrix (ECM) modelling. Both untreated and secretory endometrial organoids with myoma showed an up-regulation of genes and pathways related to ECM mechanotransduction. The expression pattern of receptivity-related genes was disturbed in endometrial organoids with myoma.
This study is the first to reveal that intramural myomas create an abnormal hormonal and mechanical environment in the untreated and secretory endometrial organoids. The intramural myomas negatively impacted gene expression relating to endometrial glands, blood vessels, cilia and ECM, indicating that intramural myomas impair endometrial decidualization and receptivity.