Human-assisted reproductive technologies (ART) are a widely accepted treatment for infertile couples. At the same time, many studies have suggested the correlation between ART and increased ...incidences of normally rare imprinting disorders such as Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Silver-Russell syndrome (SRS). Major methylation dynamics take place during cell development and the preimplantation stages of embryonic development. ART may prevent the proper erasure, establishment, and maintenance of DNA methylation. However, the causes and ART risk factors for these disorders are not well understood.
A nationwide epidemiological study in Japan in 2015 in which 2777 pediatrics departments were contacted and a total of 931 patients with imprinting disorders including 117 BWS, 227 AS, 520 PWS, and 67 SRS patients, were recruited. We found 4.46- and 8.91-fold increased frequencies of BWS and SRS associated with ART, respectively. Most of these patients were conceived via in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and showed aberrant imprinted DNA methylation. We also found that ART-conceived SRS (ART-SRS) patients had incomplete and more widespread DNA methylation variations than spontaneously conceived SRS patients, especially in sperm-specific methylated regions using reduced representation bisulfite sequencing to compare DNA methylomes. In addition, we found that the ART patients with one of three imprinting disorders, PWS, AS, and SRS, displayed additional minor phenotypes and lack of the phenotypes. The frequency of ART-conceived Prader-Willi syndrome (ART-PWS) was 3.44-fold higher than anticipated. When maternal age was 37 years or less, the rate of DNA methylation errors in ART-PWS patients was significantly increased compared with spontaneously conceived PWS patients.
We reconfirmed the association between ART and imprinting disorders. In addition, we found unique methylation patterns in ART-SRS patients, therefore, concluded that the imprinting disorders related to ART might tend to take place just after fertilization at a time when the epigenome is most vulnerable and might be affected by the techniques of manipulation used for IVF or ICSI and the culture medium of the fertilized egg.
Background and Aims: Excess lactate in culture medium accumulates may adversely affect the embryo as metabolic stress. The purpose of this study is to investigate whether culture media with a ...low-lactate concentration have an effect on embryonic development in IVF. Method: A split sibling study was performed on 8313 oocytes from 1,312 ICSI cycles from which at least two matured oocytes were retrieved from January 2020 through August 2022. Sperm-injected oocytes were allocated to Continuous Single Culture-NX (NX, N=4352) which contains a low concentration of lactate (1mM) and Global Ⓡ total Ⓡ LP (GL, N=3961), which contains 5mM concentration of lactate. Patients were classified into subgroups of <40 years (854 cycles) and Formula: see text40 years (458 cycles). Single frozen embryo transfers were performed in 859 cycles (NX; N = 500, GL; N = 359). Embryo development up to Day 6, clinical pregnancy and miscarriage rates were compared. Usable blastocysts were defined as any blastocyst cryopreserved on day 5 or day 6. P<0.05 was considered statistically significant. Results: The mean patient age was 37.1 ± 4.4 years. Overall fertilization rates and the blastocyst development rate were significantly higher in NX than GL (80.7% vs. 78.9% and 62.3% vs. 59.8% respectively). There was no significant difference in blastocyst utilization rate on day 5 with all ages considered (36.2% NX vs. 34.2% GL). There was no significant difference in blastocyst development rate for patients Formula: see text40 years, but for patients Formula: see text40 years, blastocyst development rate and day 5 usable blastocyst rate were significantly increased in NX (51.2% vs. 46.4% and 26.2% vs. 22.4% respectively). There were no significant differences in the clinical pregnancy or miscarriage rates (48.8% vs. 49.9% and 22.1% vs. 21.8% respectively). Conclusion: Our results suggest that the lower concentration of lactate in culture medium is effective for late embryonic development in advanced maternal age patients.
Frozen-thawed embryo transfer (FET) is increasingly available for the improvement of the success rate of assisted reproductive technologies other than fresh embryo transfer (ET). There have been ...numerous findings that FET provides better obstetric and perinatal outcomes. However, the birth weight of infants conceived using FET is heavier than that of those conceived via ET. In addition, some reports have suggested that FET is associated with perinatal diseases such as placenta accreta and pregnancy-induced hypertension (PIH).
In this study, we compared the microRNA (miRNA) expression profiles in term placentae derived from FET, ET, and spontaneous pregnancy (SP). We identified four miRNAs, miR-130a-3p, miR-149-5p, miR-423-5p, and miR-487b-3p, that were significantly downregulated in FET placentae compared with those from SP and ET. We found that DNA methylation of
-DMR, not but IG-DMR, was associated with miRNA expression of the
imprinted domain in the human placenta. In functional analyses, GO terms and signaling pathways related to positive regulation of gene expression, growth, development, cell migration, and type II diabetes mellitus (T2DM) were enriched.
This study supports the hypothesis that the process of FET may increase exposure of epigenome to external influences.
Background: It is important to select blastocysts based on their likelihood of leading to pregnancy. The purpose of this study was to focus on expansion time and blastocyst diameter as simple factors ...to assess blastocysts relative to clinical outcomes. Methods: This study is based on 1,514 cycles in women Formula: see text years who underwent frozen-thawed blastocyst transfer (FBT) between November 2017 and February 2021. Blastocysts were classified according to the time they reached Formula: see textm inner diameter (116, 120, and 140Formula: see texth). Furthermore, blastocyst diameter at freezing was classified into three groups: groups S (under 167Formula: see textFormula: see textm), M (167–181Formula: see textFormula: see textm), and L (over 181Formula: see textFormula: see textm), based on tertile values. We compared the clinical outcomes (including the clinical pregnancy rate CPR) of FBT. Results: CPR was significantly higher in groups M and L than in group S at 116Formula: see texth (Formula: see text). At 120Formula: see texth, CPR in group L was significantly higher than in group S (Formula: see text). However, at 140Formula: see texth, there were no significant differences among the three groups. There were no significant differences in miscarriage rates at 116, 120, and 140Formula: see texth. When only good quality embryos were compared, group L resulted in a significantly higher CPR than group S at 116Formula: see texth (Formula: see text). At 120Formula: see texth, both groups M and L had significantly higher CPR than group S (Formula: see text). There were no significant differences at 140Formula: see texth. Conclusion: These results suggest that when multiple embryos are frozen at the same time on day 5 of culture, a higher pregnancy rate can be obtained by selecting embryos with larger blastocyst diameters. In addition, it is important to confirm sufficient blastocyst expansion before cryopreservation.
Purpose
To investigate whether progestin‐primed ovarian stimulation (PPOS) with chlormadinone acetate (CMA) adversely affects clinical results and neonatal outcomes, or causes congenital deformities.
...Methods
This retrospective study was conducted at private IVF clinic from November 2018 to November 2021. Women underwent oocyte retrieval using gonadotropin‐releasing hormone (GnRH) antagonist protocol (n = 835) or PPOS protocol (n = 57) were included. Eligible patients were normal ovarian responders (aged <40, AMH ≧1.0 ng/mL) with freeze‐all cycle. Embryo developments, clinical results, or neonatal outcomes of singletons derived from transfer of frozen single blastocysts were compared within each group.
Results
Patient characteristics were similar in both groups. The median LH level (mIU/mL) at trigger in the GnRH antagonist group 2.0 (1.2–3.7) was significantly higher than in the PPOS group 0.9 (0.3–1.7). There was no cycle with premature LH surge in the PPOS group. Fertilization and blastocyst formation rates did not differ significantly between groups. Furthermore, clinical outcomes were also similar in the two groups. Congenital abnormality rates did not differ significantly 0.9% (3/329), 0.0% (0/17).
Conclusions
CMA using ovarian stimulation did not negatively affect clinical results. Our data suggest that PPOS with CMA is an appropriate ovarian stimulation method for normal ovarian responders.
This study analyzes the value conflict of a paper on fan fiction writing that used online fan fiction novels as a source to extract and filter sexual expressions from text. The boundaries of public ...and private information are ambiguous because users are not always aware of or have agreed to the fact that their content is to be used openly. The case was complicated by the fact that the use of these data by researchers violated an unconsciously infringed upon right of a vulnerable community with a weak legal position. This paper describes the debate on this topic among researchers from engineering and humanities fields on whether the purpose of the research was ethically acceptable; how the systems can be embedded in ethical values; and what ethical, legal, social, and educational lessons are appropriate for governance of artificial intelligence (AI). Our analysis aimed not only to clarify the abstract concept of privacy but also to make changes to the submission guidelines for authors. We hope that our analysis contributes to the governance of ethical AIs and AI ethics on handling sensitive aspects of online activities.
Some studies have suggested that blastocyst transfer is associated with i) imbalance in the secondary sex ratio (SSR) (which favors male offspring), ii) increased incidence of monozygotic twins ...(MZT). In contrast, others have not found these changes. In this study, we evaluated the association between blastocyst transfer and SSR and MZT, considering potential parental confounders.
The Japan Environment and Children's Study is a large, nationwide longitudinal birth cohort study funded by the Ministry of the Environment of Japan. We used this large dataset, including 103,099 pregnancies, to further investigate the association between blastocyst transfer, SSR and MZT, using spontaneously conceived pregnancies, non-assisted reproductive technology (non-ART) treatment (intrauterine insemination and ovulation induction with timed intercourse) and cleavage stage embryo transfer for comparison. We evaluated the association with each group, the SSR, and the frequency of MZT, calculating the adjusted odds ratio (AOR) using multivariable logistic regression analyses, adjusting for potential parental confounders such as basic health and socioeconomic status.
For each group (spontaneous conception vs. non-ART treatment vs. cleavage stage embryo transfer vs. blastocyst transfer), the percentages of males were 51.3% vs 50.7% vs 48.9% vs 53.4% and the monozygotic twinning rates per pregnancy were 0.27% vs 0.11% vs 0.27% vs 0.99% respectively. Multivariate logistic regression analyses indicated that blastocyst transfer was significantly associated with a higher SSR and higher incidence of MZT than the other three groups (SSR: AOR 1.095, 95% CI1.001-1.198; MZT: AOR 4.229, 95% CI 2.614-6.684).
There are significant relationships between blastocyst transfer and SSR imbalance and a higher occurrence of MZT.
Aim
To evaluate the association between use of assisted reproductive technology (ART) and mother‐to‐infant bonding.
Methods
Using nationwide birth cohort study with periodical follow‐ups for mothers ...and children during pregnancy and at 1 year after delivery, mothers were classified following three groups; infertility group with ART: 2792 mothers; infertility group with non‐ART treatment (ovulation induction and intrauterine insemination): 3835 mothers and unaided pregnancy group: 78 726 mothers. Data on maternal and child health as well as basic characteristics were collected via medical records and self‐administered questionnaires. The Japanese version of Mother‐to‐Infant Bonding Scale was used to evaluate maternal bonding style. To evaluate the association between ART and maternal bonding toward babies, multivariate analysis was used with adjustment for potential confounders such as babies' sex, socio‐economic status and history of maternal mental disorders.
Results
Multivariate logistic regression analysis indicated that ART was slightly but significantly associated with an increased risk of maternal lack of affection toward their newborn (adjusted odds ratio 1.10, 95% confidence interval 1.02–1.20), while non‐ART was significantly associated with both maternal lack of affection and anger/rejection toward the newborn. No substantial association was observed between ART and overall Mother‐to‐Infant Bonding Scale score (adjusted odds ratio 1.03, 95% confidence interval 0.94–1.12). Very slight negative correlations were observed between poor mother‐to‐infant bonding and good infant mental and physical development at both 6 months and 1 year.
Conclusion
ART may exert a negative influence on maternal emotion after delivery, but this does not have strong correlation with child development evaluated by mothers.
In this article, we present roadmaps and research issues pertaining to multiagent social simulation to illustrate the directions of technological achievements in that domain. Compared with physical ...simulation, social simulation is still in the phase of establishing simulation models. We focus on four issues, namely “undetermined model”, “awareness effects”, “obscure boundary”, and “incomplete data”, and consider ways to overcome these issues using the massive computational power of high-performance computing. We select three applications, namely evacuation, road traffic, and market, and estimate the required computational cost of real applications. Moreover, we investigate research issues on the application side and categorize possible future works on multiagent social simulations.
Background: To evaluate obstetrical and neonatal outcomes of singletons conceived after advanced assisted reproductive technology (ART) techniques: conventional IVF pregnancies (C-IVF), ejaculated ...sperm intracytoplasmic sperm injection (ICSI), assisted oocyte activation (AOA), in vitro maturation (IVM), and testicular sperm extraction (TESE). Methods: The subjects were 3,028 singletons who were born after fresh or frozen embryo transfer. The subjects were separated into five groups: C-IVF (Formula: see text), ICSI (Formula: see text), AOA (Formula: see text), IVM (Formula: see text), and TESE (Formula: see text). We evaluated obstetrical and neonatal outcomes calculating the adjusted odds ratio (AOR) using multivariable logistic regression analyses for fresh and frozen embryos and for cleavage and blastocyst transfer. The C-IVF group was used as a background control for the ICSI group. Moreover, the TESE, AOA, and IVM groups were compared to the ICSI group to evaluate the effects of the ICSI procedure itself. Results: The incidence of perinatal complications was significantly lower in the ICSI-fresh group (Formula: see text, 95% CI: 0.10–0.83, Formula: see text). Regarding sex ratio, the IVM was significantly associated with sex ratio imbalance toward female in both fresh and frozen groups (Formula: see text, 95% CI: 0.10–0.96, Formula: see text, 95% CI: 0.07–0.98, Formula: see text). On the other hand, there were no significant differences in preterm birth rate, low birth weight rate and congenital abnormalities rate between conventional IVF, ICSI, and the other groups. Conclusions: There were no negative effects on obstetrical and neonatal outcomes between conventional IVF and ICSI. Although this was a limited sample size study, advanced ART technologies such as AOA, IVM, and TESE also seem to have a low risk of adverse impact on obstetrical and neonatal outcomes but may have a slight impact on sex ratio.
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