Embryo Transfer Research Articles

Complications in equine transvaginal ultrasound‒guided follicular aspiration

Transvaginal ultrasound-guided follicular aspiration has revolutionised equine assisted reproduction, particularly in in vitro embryo production. This literature review examines the complications associated with transvaginal ultrasound-guided follicular aspiration in mares and its potential impact on future fertility. While transvaginal ultrasound-guided follicular aspiration is generally safe, it has inherent risks, ranging from mild rectal bleeding to severe complications such as peritonitis and acute haemorrhage. Factors influencing complication rates include veterinarian experience, mare anatomy and procedural technique. Despite concerns, studies suggest that repeated transvaginal ultrasound-guided follicular aspiration does not significantly impair future fertility, with normal pregnancy rates observed in mares undergoing artificial insemination or embryo transfer after transvaginal ultrasound-guided follicular aspiration. However, further research is needed to fully understand the long-term effects on ovarian function and oocyte quality. Veterinary practitioners must prioritise appropriate training and procedural precautions to minimise the risk of complications and safeguard mare welfare and fertility in the expanding field of equine assisted reproduction.

Production of second-generation sheep clones via somatic cell nuclear transfer using amniotic cells as nuclear donors

Somatic Cell Nuclear Transfer (SCNT) has transformed animal genetic improvement, gene-editing in model production, xenotransplantation, and conservation efforts for endangered species. However, SCNT-derived embryos occasionally display developmental abnormalities, and following embryo transfer, the miscarriage rate is high. Gene-edited fetuses may experience birth defects, resulting in decreased survival rates. Correct selection of nuclear donor cells is essential for the success of somatic cell cloning. Fibroblasts are the most commonly used cells, but their rapid proliferation increases the risk of genetic mutation, impairing embryo development and production. Conversely, amniotic cells have slower proliferation rates, decreasing the mutation risk during cultivation. Amniotic cells are thus better SCNT candidates than fibroblasts because they offer genomic stability, low tumorigenic and teratogenic risks, reduced immunogenicity, high differentiation potential, ease of accessibility, and fewer ethical concerns. Cells derived from first-generation gene-edited animals exhibit stable genetic structures, reduced susceptibility to genetic alterations and artificial modifications, closely resembling natural cells, and enhanced compatibility with SCNT procedures. Amniotic cells derived from gene-edited sheep fetuses used as nuclear donor cells for SCNT successfully recloned three healthy second-generation gene-edited sheep. Using amniotic cells as nuclear donor cells for SCNT did not significantly alter embryo cleavage rates, blastocyst formation, or fetal birth compared to edited fibroblasts (p > 0.05). However, fetal survival rates were significantly higher than edited fibroblasts (p < 0.05). The results support the potential of amniotic cells as SCNT alternatives, suggesting a promising strategy to improve gene-edited fetus survival rates using first-generation gene-edited sheep-derived amniotic cells.

Characterization of conception rate after embryo transfer in comparison with that after artificial insemination in dairy cattle

Artificial insemination (AI) and embryo transfer (ET) are important in the reproduction of dairy cows. The conception rate after AI or ET is an essential indicator when selecting appropriate breeding methods. However, information on the environmental factors affecting ET conception rate when compared with AI is limited. We aimed to investigate environmental factors affecting ET conception rate and characterize the differences in environmental factors between AI and ET. Records of the first AI (n = 1,870,143) and ET (n = 29,922) from Holstein nulliparous, primiparous, and multiparous cows in Hokkaido, Japan, were analyzed using separate multivariable logistic regression models. For each breeding method, we grouped primiparous and multiparous cows according to milk yield at peak lactation (PY; < 25, 25-30, 30-35, ≥ 35 kg in primiparous, < 40, 40-45, 45-50, ≥ 50 kg in multiparous) and the interval from calving to first AI or ET (CFI/CFT; < 60, 60-79, 80-99, ≥ 100 d) to evaluate the effects of PY and CFI/CFT on conception rate. AI conception rate decreased with increasing PY in primiparous and multiparous cows, whereas ET conception rate did not decrease significantly. Additionally, the ET conception rate did not decrease even in primiparous and multiparous cows slightly earlier than 60 d in CFI/CFT when compared with those in CFI/CFT after 60 d, which differed from the AI conception rate. Collectively, breeding by ET leads to the avoidance of negative effects of high milk yield and calving on the conception rate, indicating that cows are fertile by ET within 60 d after calving.

The impact of prior levonorgestrel intrauterine device use at the time of embryo transfer.

To investigate whether infertile women with a history of levonorgestrel intrauterine device (LNG IUD) use have impaired pre-transfer endometrial thickness and pregnancy rates after embryo transfer. Retrospective cohort study at a single academic medical center of infertile women ages 18-44 with a history of LNG IUD use undergoing their first embryo transfer cycle between January 2019 and January 2021 compared to controls with a history of no prior birth control use (NONE) or only prior oral contraceptive use (OCP). The primary outcome is endometrial thickness prior to embryo transfer. Secondary outcomes include embryo transfer results. We analyzed data from a total of 616 patients (197 NONE, 357 OCP, 62 LNG IUD). Women with a history of LNG IUD use had thinner endometrial stripes than women with a history of no prior birth control use (LNG IUD 8.93mm, NONE 10.32mm [aRR 0.88, 95% CI 0.80-0.97]), but not when compared to women with a history of OCP use (OCP 9.61mm [aRR 0.92, 95% CI 0.84-1.01]). Women with a history of LNG IUD use had slightly higher implantation rates than those with no birth control use history (LNG IUD 43.37%, NONE 24.17% [RR 1.79, 95% CI 1.21-2.45]), though not when compared to prior OCP users (OCP 38.72% [RR 1.12, 95% CI 0.86-1.47]). The remainder of the embryo transfer outcomes were similar between the three groups. Prior LNG IUD users have reduced endometrial thickness at the time of embryo transfer but do not have worse pregnancy outcomes.

One fresh cleavage-stage single embryo transfer (SET) plus one frozen-thawed blastocyst-stage SET or one fresh cleavage-stage double embryo transfer? A retrospective matched cohort study.

Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle? In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle. The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies. Evidence regarding the outcomes of transferring two cleavage-stage embryos in a single fresh cycle versus transferring one cleavage-stage embryo in one fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle is scarce. This study is a retrospective matched cohort study, where data were gathered from the clinical database of women who underwent IVF treatment at the Reproductive Center of Peking University Third Hospital between January 2011 and December 2019, with follow-up extending until December 2021. The study group included cycles with a fresh cleavage-stage SET and a subsequent frozen-thawed blastocyst-stage SET (2xSET, N = 976). Fresh cleavage-stage DET was the control group (DET, N = 976). Included cycles were divided into subgroups based on age (≥38 years vs <38 years) and total number of utilizable (transferred or cryopreserved) embryos (=2 vs >2). The duration of infertility, prevalence of unexplained infertility, and controlled ovarian stimulation regimes differed significantly between the two groups and were adjusted for in the further analysis. We observed a significant increase in clinical pregnancies (55.5% vs 42%, adjusted odds ratio (OR) 1.87 [1.55-2.26]) and live births (44.8% vs 34.5%, adjusted OR 1.63 [1.35-1.97]) in favor of the 2xSET group. The preterm birth rate was lower in the study group (adjusted OR 0.64 [0.42-0.96]). Neonatal birth weight of singletons was similar between the two groups (adjusted B 4.94 g [-84.5 to 94.4]). The beneficial effect on the live birth rate disappeared in cases where aged 38 years and older or when only two embryos were utilizable. This study is limited by differences in baseline characteristics of the two groups. Analyzing two consecutive SETs at the cleavage stage was not feasible. Additionally, the homogeneous population limits generalizability to other ethnic groups, which should be considered when interpreting the results broadly. We recommend a combination strategy for women under 38 years old and with more than two embryos available: transfer one cleavage-stage embryo in the fresh cycle, followed by one blastocyst-stage embryo in the subsequent frozen-thawed cycle. This strategy reduces the risk of blastocyst culture failure while maintaining a high success rate. It offers hope to families seeking additional children and avoids unnecessary embryo disposal. B.W.M. had received grants from NHMRC, Ferring, Merck, and Guerbet, consulting fees and stock options from ObsEva, is on the advisory board of ObsEva, and reports consultancy for Guerbet, none of which are in relation to the present manuscript. All other authors have no conflict of interest to declare. N/A.

Maternal and Neonatal Perinatal Outcomes of Singleton Pregnancies in Advanced-Age Women Undergoing IVF/ICSI-ET Compared with Spontaneous Conception: A Retrospective Propensity Score Matched Cohort Study.

To assess the safety and efficiency of in vitro fertilization/ intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) on maternal and neonatal perinatal outcomes in women (≥40y) with singleton pregnancies. This multi-center retrospective cohort study, carried out from January 2018 to June 2023, enrolled 1762 women (≥40y) with singleton pregnancies of at least 28weeks. Participants were divided into two groups: the IVF/ICSI-ET group (204 cases) and the spontaneous conception (SC) group (1558 cases). After 1:2 propensity score matching (PSM), the two groups were compared for maternal and neonatal outcomes. The SC group (1558 cases) was further divided by age into the <43 years group (1195 cases) and the ≥43 years group (363 cases) for subgroup analysis. Adverse maternal and neonatal outcomes were comparable between the IVF/ICSI-ET group and the SC group, with a higher cesarean section rate (78% vs 67.5%, P =0.013), an increased maternal ICU admissions rate (5.5% vs 1.3%, P =0.008), and a lower birth defects rate (1.1% vs 4.6%, P =0.037) in the IVF/ICSI-ET group. Subgroup analysis showed that women aged ≥43 years had higher incidences of gestational diabetes, gestational hypertension, cesarean section, and neonatal asphyxia compared to women aged <43 years. This study indicated IVF/ICSI-ET is relatively safe for women ≥40 years with singleton pregnancies. However, advanced maternal age deteriorated maternal and neonatal outcomes, and IVF/ICSI-ET further heightened the risk of cesarean section and maternal ICU admissions. Therefore, enhanced care and vigilance are crucial for women over 40 undergoing IVF/ICSI-ET.

Recipients' age, fresh embryo and blastocyst-stage embryo transfer as favorable factors in a transnational oocyte donation program.

In Italy, egg donation is being allowed again following the ruling by the Constitutional Court N. 162/2014. Nevertheless, the number of voluntary donors is insignificant, probably because no reimbursement is provided. Therefore, the great majority of egg donation cycles are performed by using imported cryopreserved oocytes from foreign countries. However, recent evidence has questioned the overall efficacy of this strategy in comparison with the shipment of frozen sperm and vitrified embryos. Retrospective cohort study, conducted at ANDROS Day Surgery Clinic Palermo, Italy in the period 2016-2022, with the objective of evaluating the efficiency of each batch of vitrified oocytes, in terms of completed cycles. The cryopreserved donated oocytes came from a single Spanish clinic (Next Fertility, Valencia, Spain). The primary outcome was the cumulative live birth rate (CLBR). The secondary outcomes were the cumulative ongoing pregnancy rate (COPR), the cumulative clinical pregnancy rate (CCPR) and the miscarriage rate. The CLBR totaled 35.1%, the COPR 36.8%, the CCPR 49.2% and the miscarriage rate 24.7%. In the multivariate analysis, the probability of success was significantly higher in younger recipients, in fresh embryo transfer and in blastocyst-stage embryo transfer. Our "transnational" donation program with vitrified oocytes has good success rates. The main focus of our analysis is the negative effect of advancing recipient age on success rates, outlining a possible, important role of age-related uterine factor on implantation mechanisms. This aspect should be emphasized during the counselling with couples much more than is routinely done.

Comparative Analysis of Pregnancy Outcomes in Preimplantation Genetic Testing for Aneuploidy and Conventional In Vitro Fertilization and Embryo Transfer: A Stratified Examination on the Basis of the Quantity of Oocytes and Blastocysts From a Multicenter Randomized Controlled Trial

Comparative Analysis of Pregnancy Outcomes in Preimplantation Genetic Testing for Aneuploidy and Conventional In Vitro Fertilization and Embryo Transfer: A Stratified Examination on the Basis of the Quantity of Oocytes and Blastocysts From a Multicenter Randomized Controlled Trial

Application of disposable digital hysteroscope for outpatient hysteroscopy in women undergoing artificial assisted reproductive procedures: a clinical research

BackgroundHysteroscopy is the preferred method for the diagnosis and treatment of uterine diseases. With the increasing demand for outpatient hysteroscopy, disposable digital hysteroscopy has emerged, which can meet the requirements of diagnosis and treatment integration, and greatly reduce the labour and storage costs.MethodsA total of 108 outpatients who underwent hysteroscopy using disposable digital hysteroscope were divided into two groups: the non-porous group (group A, n=49) and the married with child group (group B, n=59). The patients’ general information and clinical data were recorded and statistical analysis was performed.ResultsNo differences were found between the age, weight, body mass index, menopausal status and indication for hysteroscopy of the two groups. The most common indication was embryo transfer failure. The surgical success rate of 108 patients was 100%, the concordance rate between hysteroscopic diagnosis of chronic endometritis and pathological diagnosis was 94.44% (68/72), while the false positive rate stood at 38.89% (14/36). Additionally, incidental findings rate for endometrial polyps was 92.00% (23/25) with a low false positive rate of only 6% (5/83). The mean visual analogue scale score of group A was 2.285±0.180, which was not significantly different from group B (p=0.483, 95% CI(−0.60-0.44)). The pregnancy rate among patients who received assisted reproductive technology and were followed up for 1 year after surgery was 66.67% (40/60), while the abortion rate stood at 5.00% (3/60).ConclusionsThe disposable digital hysteroscope is a valuable and effective tool for outpatient hysteroscopy.

Comparison of Fresh vs Frozen Embryo Transfer in Terms of successful Pregnancy Outcome in Pakistan

Comparison of Fresh vs Frozen Embryo Transfer in Terms of successful Pregnancy Outcome in Pakistan

Aneuploidy rates and clinical pregnancy outcomes after preimplantation genetic testing for aneuploidy using the progestin-primed ovarian stimulation protocol or the gonadotropin-releasing hormone antagonist protocol.

To investigate the chromosome abnormality rates and clinical pregnancy outcomes after preimplantation genetic testing for aneuploidy (PGT-A) using either the progestin-primed ovarian stimulation (PPOS) protocol or the gonadotropin-releasing hormone (GnRH) antagonist protocol. The study included 431 PGT-A cycles in which controlled ovarian stimulation was performed using the PPOS protocol (n = 320 cycles) or GnRH antagonist protocol (n = 111 cycles) between January 2018 and December 2021. Frozen embryo transplantation was subsequently performed in 309 cycles with transplantable blastocysts. The number of retrieved oocytes, embryo development, next-generation sequencing results, and clinical pregnancy outcomes were compared between the two protocols. The primary outcome measure was the aneuploidy rate. Secondary outcome measures were clinical pregnancy per first frozen-thawed embryo transfer cycle and cumulative live birth rates per PGT-A cycle. There were no statistically significant between-group differences in the number of retrieved oocytes, available blastocysts, and high-quality blastocyst rate. The aneuploidy rates were similar between the two groups. There was no significant difference in clinical pregnancy outcomes, including the clinical pregnancy, implantation, miscarriage, live birth, or cumulative live birth rates, after frozen-thawed embryo transfer cycles (P>0.05). The study found no significant difference in the aneuploidy rate, clinical pregnancy rate and cumulative live birth rate after PGT-A cycles between those using the PPOS protocol and those using the GnRH antagonist protocol.

Genomic regions associated with embryonic loss in primiparous Holstein cows

IntroductionReproductive efficiency in dairy cattle bred by artificial insemination (AI) or via embryo transfer (ET) is important as a means of facilitating the rate of genetic improvement by utilizing superior genetics from sires and donor dams. Fertility is especially challenging in primiparous cows as they have recently calved, are still growing, and are lactating. Fertility, measured by the conception rate from the first service (CCR1), is the number of cows that become pregnant as a result of the first AI or ET compared to all cows serviced, whereas times bred (TBRD) is the number of inseminations cows bred by AI needed to achieve a successful pregnancy.MethodsThis study aimed to identify the loci associated with and gene sets enriched for the CCR1 in primiparous cows that were bred by AI (n = 882) or were ET recipients (n = 353), and to identify the loci associated with the TBRD (n= 1,851) in primiparous cows. A genome-wide association analysis and gene set enrichment analysis were performed using single-nucleotide polymorphism (SNP) data for the CCR1 and TBRD in primiparous cows. In cows bred by AI, two loci containing five positional candidate genes were associated with the CCR1 (p &amp;lt; 1 × 10−5) and one gene set with 18 leading-edge genes was enriched (NES ≥3) for the CCR1.Results and discussionIn cows that were ET recipients, five loci were associated with the CCR1, but no gene sets were enriched for the CCR1. For the second phenotype, five loci with nine positional candidate genes were associated with the TBRD and two gene sets with eight leading-edge genes were enriched for the TBRD. Identifying the loci associated with or gene sets enriched for the CCR1 and TBRD provides an opportunity to better understand embryonic loss in AI-bred and ET-recipient cows and to use this information to select for higher reproductive efficiency.

IMPACT OF BLASTOCYST GRADES TO IMPLANTATION AND LIVE-BIRTH RATES IN WOMEN LESS THAN 30 YEARS WITH SINGLE EMBRYO TRANSFERS

Background:Morphological evaluation of blastocysts focusing on key factors such as expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality have been most widely used for embryo selection. The study emphasizes the importance of detailed blastocyst evaluation, highlighting that morphological variations can have substantial implications for ART outcomes. Methods:A total of 115women aged less than 30 years undergoing SET from from January 2023 to June 2023 were included in this study.The patients were divided into three groups based on their morphologic grading before embryo transfer: good-quality (n = 53), average-quality (n = 52) and poor-quality blastocysts (n = 10). The three morphologic groups pregnancy outcomes were examined, and the implantation rate was logistically regressed. Results:Good-quality blastocysts yielded a statistically significantly higher implantation rate (77%) than average / poor-quality blastocysts (44% and 20% respectively). Average-quality blastocysts still yielded in higher implantation rates (44%) compared to poor-quality blastocysts (20%). The baseline characteristics were analysed for significance using the Pearsons Chi-squared test. A P-value &lt; 0.05 was considered statistically significant. All the statistical analyses were performed using the social science statistics website with SPSS software. Conclusions:Higher blastocyst morphologic grading was associated with increased implantation rate for single embryo transfers. These findings suggest that evaluating blastocyst morphology is critical when selecting the best blastocyst.

Comparative analysis of pregnancy outcomes after embryo transfer in a stimulated in vitro fertilisation cycle depending on the progestogen type used for post-transfer support

Comparative analysis of pregnancy outcomes after embryo transfer in a stimulated in vitro fertilisation cycle depending on the progestogen type used for post-transfer support

The transfer of double cleavage embryos developed from two four-cell embryos may not represent an optimal treatment strategy in cycles with a greater number of four-cell embryos on Day 2.

This study examined the impact of the number of Day 2 four-cell (D2-4C) embryos on double embryo transfer and blastocyst culture therapy in the first invitro fertilization (IVF) cycle. A retrospective review was performed on 1039 blastocyst culture cycles to compare outcomes between available and unavailable blastocyst cycles, emphasizing the relationship between the number of D2-4C embryos and blastocyst availability. Furthermore, the correlation between four-cell embryo counts and live births was analyzed in 986 transfer cycles. The analysis revealed that the number of D2-4C embryos independently influenced the availability of blastocysts (odds ratio [OR] 1.693, 95% confidence interval [CI] 1.306-2.195, P < 0.001). Receiver operating characteristic (ROC) analysis indicated that D2-4C embryos displayed the highest predictive value for available blastocysts, with an area under the curve (AUC) of 0.861 (95% CI 0.826-0.896). The cut-off point was determined to be 4.5, particularly for individuals younger than 25 years, where the AUC reached 0.927. This suggests that the number of D2-4C embryos has significant predictive value for available blastocysts. The live birth rate (LBR) of fresh embryo transfers significantly increased with the number of D2-4C embryos (P = 0.004). LBRs for zero, one, and two four-cell embryos in double cleavage embryo transfer were 20.24%, 34.97%, and 38.08%, respectively (P = 0.005). In the twin group, the percentages for zero, one, and two four-cell embryos were 1.21%, 9.75%, and 89.02%, respectively (P < 0.001). Single blastocyst transfer achieved an LBR comparable to that of two four-cell embryos (34.8% vs 39.0%, P = 0.415), while the twin rate significantly decreased with single blastocyst transfer (25.17% vs 1.40%, P < 0.001). The number of D2-4C embryos exhibits significant predictive value for available blastocysts, particularly among young women. Furthermore, most twins resulted from the transfer of double cleavage embryos derived from two four-cell embryos. Consequently, when the D2-4C count exceeds four in a cycle, blastocyst culture therapy is preferred over double cleavage-stage embryo transfer.

Determining Factors Influencing The Successful Embryo Transfer and Pregnancy during The Frozen Cycle of In Vitro Fertilization: A Retrospective Cohort Study.

Frozen embryo transfer (FET) has been increasingly used due to advancements in cryopreservation techniques and the safety advantages. This study aims to determine various factors influencing the successful FET. Retrospective cohort analysis included 1112 women who underwent programmed FET between January 2012 and October 2022, at King Chulalongkorn Memorial Hospital, Thailand. Patient characteristics, embryo characteristics, endometrial preparation protocol, endometrial characteristics (thickness, pattern), embryo transfer procedure (tip and flow during transfer, embryo placement location, the difficulty of the procedure, presence of blood and mucous at catheter), and operator factor were analyzed. Multiple logistic regression analysis was used to assess the relationship between collected variables and successful embryo transfer which is defined by clinical pregnancy. The overall clinical pregnancy rate was 34.2%. Women aged 35-40 years and >40 years were less likely to have a clinical pregnancy compared to those aged <35 years [adjusted odds ratio (aOR): 0.523; 95% confidence intervals (CI): 0.360-0.757, P<0.001 and aOR: 0.260; 95% CI: 0.152-0.434, P<0.001, respectively]. Obese women with body mass index (BMI) ≥25 kg/m2 were significantly associated with decreased clinical pregnancy (aOR: 0.632; 95% CI: 0.403-0.978, P=0.042) compared to those with normal BMI. Day-3 and day-4 embryo transfer showed a significant decrease in clinical pregnancy compared to blastocyst transfer (aOR: 0.294; 95% CI: 0.173-0.485, P<0.001 and aOR: 0.497; 95% CI: 0.265-0.900, P=0.024). Double embryo transfer (DET) was 1.78 times more likely to have a clinical pregnancy than women with single embryo transfer (SET) (aOR: 1.779; 95% CI: 1.293-2.458, P<0.001). The cycles with endometrial thickness <8 mm were associated with a decrease in clinical pregnancy compared with those with a thickness ≥8 mm (aOR: 0.443; 95% CI: 0.225-0.823, P=0.013). Older age, obesity, non-blastocyst transfer, single embryo transfer, and endometrial thickness of <8 mm were significantly associated with a decreased clinical pregnancy in programmed FET.

Combining single-cell RNA sequencing and network pharmacology to explore the target of cangfu daotan decoction in the treatment of obese polycystic ovary syndrome from an immune perspective.

Polycystic ovary syndrome (PCOS) is a heterogeneous gynecological endocrine disorder linked to immunity. Cangfu Daotan Decoction (CFDT), a classic Chinese medicine prescription, is particularly effective in treating PCOS, specifically in patients with obesity; however, its specific mechanism remains unclear. Part 1: Peripheral blood mononuclear cells were collected on egg retrieval day from obese and normal-weight patients with PCOS and healthy women undergoing in vitro fertilization (IVF)-embryo transfer. Next, scRNA-seq was performed to screen the key genes of bese patients with PCOS. Part 2: Active ingredients of CFDT and obesity-related PCOS targets were identified based on public databases, and the binding ability between the active ingredients and targets was analyzed. Part 3: This part was a monocentric, randomized controlled trial. The obese women with PCOS were randomized to CFDT (6 packets/day) or placebo, and the healthy women were included in the blank control group (43 cases per group). The clinical manifestations and laboratory outcomes among the three groups were compared. Based on the scRNA-seq data from Part 1, CYLD, ARPC3, CXCR4, RORA, JUN, FGL2, ZEB2, GNLY, FTL, SMAD3, IL7R, KIR2DL1, CTSD, BTG2, CCL5, HLA, RETN, CTSZ, and NCF2 were potential key genes associated with obese PCOS were identified. The proportions of T, B, and natural killer cells were higher in patients with PCOS compared to healthy women, with even higher proportions observed in obese patients with PCOS. Gene ontology and the Kyoto encyclopedia of genes and genomes analysis depicted that the differentially expressed genes were related to immune regulation pathways. Network pharmacology analysis identified that the key active components in CFDT were quercetin, carvacrol, β-sitosterol, cholesterol, and nobiletin, and TP53, AKT1, STAT3, JUN, SRC, etc. were the core targets. The core targets and their enrichment pathways overlapped with those in Part 1. Clinical trials in Part 3 found that CFDT reduced the dosage of gonadotropins use in patients with PCOS, increased the number of high-quality embryos, and improved the ongoing pregnancy rate. CFDT can improve the immune microenvironment of patients to some extent, reduce their economic burden, and enhance IVF outcomes. The improvement in the immune microenvironment in obese patients with PCOS may be linked to targets such as JUN and AKT.

Outcomes of female fertility preservation with cryopreservation of oocytes or embryos in the Netherlands: a population-based study.

What are the reproductive outcomes of patients who cryopreserved oocytes or embryos in the context of fertility preservation in the Netherlands? This study shows that after a 10-year follow-up period, the utilization rate to attempt pregnancy using cryopreserved oocytes or embryos was 25.5% and the cumulative live birth rate after embryo transfer was 34.6% per patient. Fertility preservation by freezing oocytes or embryos is an established treatment for women with a risk of premature ovarian failure (caused by a benign or oncological disease) or physiological age-related fertility decline. Little is known about the success of cryopreservation, the utilization rate of oocytes or embryos, or the live birth rates. A retrospective observational study was performed in the Netherlands. Data were collected between 2017 and 2019 from 1112 women who cryopreserved oocytes or embryos more than 2 years ago in the context of fertility preservation in 10 IVF centers in the Netherlands. A total of 1112 women were included in this study. Medical files and patient databases were used to extract data. Women were categorized based on indication of fertility preservation: oncological, benign, or non-medical. To indicate statistical differences the t-test or Mann-Whitney U test was used. Kaplan-Meier analyses were used for time endpoints, and log-rank analyses were used to assess statistical differences. The study protocol was approved by the medical ethics committee. Fertility preservation cycles have been performed increasingly over the years in the Netherlands. In the first years, less than 10 cycles per year were performed, increasing to more than 300 cycles per year 10 years later. Initially, embryos were frozen in the context of fertility preservation. In later years, cryopreservation of oocytes became the standard approach. Cryopreservation of oocytes versus embryos resulted in comparable numbers of used embryos (median of 2) for transfer and comparable live birth rates (33.9% and 34.6%, respectively). The 5-year utilization rate was 12.3% and the 10-year utilization rate was 25.5%. The cumulative clinical pregnancy rate was 35.6% and the cumulative live birth rate was 34.6% per patient. Those who had fertility preservation due to benign diseases returned earlier to use their cryopreserved embryos or oocytes. The follow-up period after the fertility preservation procedure varied between patients in this study and not all frozen oocytes or embryos had been used at the end of this study. This might have led to underestimated outcomes reported in this study. Furthermore, intention to treat cannot be fully determined since women who started the fertility preservation procedure without success (cancellation due to low response) were not included in this study. This study provides data on the reproductive outcomes after various indications of fertility preservation. This knowledge can be informative for professionals and future patients to improve counseling and informed decision making regarding ovarian stimulation in the context of fertility preservation. No funding was obtained for this study. The authors have no conflicts of interest to declare related to this study. V.T.H. received grants paid to the institute for studies outside the present work from AstraZeneca, Gilead, Novartis, Eli Lily, Pfizer, and Daiichi Sankyo. V.T.H. received consulting fees from Eli Lily outside the present work. M.G. received grants paid to the institute for studies outside the present work from Guerbet and Ferring. E.M.E.B. received a grant from The Dutch Network of Fertility Preservation for a study outside the present work. N/A.

Global research trends in endometrial receptivity from 2000 to 2024: bibliometric analysis.

In recent years, extensive research has been conducted on endometrial receptivity (ER), with rapidly evolving research hotspots and trends. Our study aimed to explore the development of ER research from 2000 to the present and provide insights for future endeavors. Relevant research publications on ER from 2000 to 2024 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace, VOSviewer and Excel tools were employed to conduct the bibliometric analysis. A total of 3,354 articles were analyzed, revealing an overall upward trend in annual publication numbers, signifying the increasing attractiveness and research value of this field. Globally, China led with a notable advantage of 1,030 publications, followed by the United States (650) and Spain (251), constituting the first tier of international research. Valencia University topped the list of institutions with 108 publications, closely followed by Shanghai Jiao Tong University with 87. Fertility and Sterility (IF6.6, Q1) is the one with the largest number of publications, accounting for 7.96% of the total publications. The three most co-cited journals were Fertility and Sterility, Biology of Reproduction, and Human Reproduction. A co-citation reference analysis revealed that ER research can be categorized into ten major subfields, including embryo implantation, frozen embryo transfer, integrins, recurrent implantation failure, intrauterine adhesions, etc. Since 2020, the keywords with the strongest citation bursts include repeated implantation failure and frozen. This study employs bibliometric analysis to offer researchers in the field of ER a comprehensive perspective. Since 2000, there has been a remarkable surge in the number of publications in the ER research field. These studies primarily concentrate on delving into the pathophysiological mechanisms of ER, with the primary objective of enhancing clinical pregnancy rates and live birth rates, benefiting more infertile patients. Currently, addressing the ER issues in patients with recurrent implantation failure represents the forefront of research. The primary treatment approaches currently in use involve optimizing embryo transfer timing and employing innovative strategies such as immunotherapy. These cutting-edge analyses not only provide new insights into the treatment of ER but also offer researchers fresh research directions, and staying abreast of the latest trends and advancements in the field.

A Combination of Artificial Intelligence with Genetic Algorithms on Static Time-Lapse Images Improves Consistency in Blastocyst Assessment, An Interpretable Tool to Automate Human Embryo Evaluation: A Retrospective Cohort Study.

In recent times, various algorithms have been developed to assist in the selection of embryos for transfer based on artificial intelligence (AI). Nevertheless, the majority of AI models employed in this context were characterized by a lack of transparency. To address these concerns, we aim to design an interpretable tool to automate human embryo evaluation by combining artificial neural networks (ANNs) and genetic algorithms (GA). This retrospective cohort study included 223 human blastocyst time-lapse (TL) images taken at 110 hours post-injection. All the images were evaluated by five embryologists from different clinics in terms of blastocyst expansion (BE), quality of the inner cell mass (ICM), and trophectoderm (TE). The embryo database was used to develop an AI system (70% training, 15% validation, and 15% test) for automate blastocyst assessment. The entire set of images underwent a standardization process, followed by processing and segmentation using Matlab software. The resulting quantified variables were utilized in AI techniques (ANN and GA). Finally, the accuracy and performance of the automation tool was assessed with the area under the receiver operating characteristic (ROC) curve (AUC). Then, the level of agreement among embryologists and between embryologists and the AI system was compared with Kappa Index. The overall agreement among embryologists was low (Kappa: 0.4 for BE; and 0.3 for TE and ICM). The AI tool achieved higher consistency (Kappa 0.7 for BE and ICM; and 0.4 for TE). The AI exhibited high accuracy in classifying BE (test 81.5%), ICM (test 78.8%), and TE (test 78.3%) and better performance for BE (AUC 0.888-0.956) than for ICM (AUC 0.605-0.854) and TE (AUC 0.726-0.769) assessment. Our AI tool highlighted the superior consistency of AI compared to human operators in grading blastocyst morphology. This research represents an important step towards fully automating objective embryo evaluation.