High-quality Embryos Research Articles

Human oocyte zona pellucida abnormalities: evaluation of clinical impact for different zona pellucida abnormalities and role of using assisted hatching.

Zona pellucida (ZP) plays an important role in oocyte development and fertilisation, as well as in early embryo development. However, there is currently no exploration of systematic categorising and clinical treatment measures for patients with abnormal ZP, especially the fast and easy method that can be used clinically. In this study, 185 patients with abnormal ZP (ZPA) and 222 patients with normal ZP (ZPN) were enrolled and analysed. Patients with ZPA exhibited altered hormone levels and lower laboratory outcomes in in vitro fertilisation (IVF), such as reduced MII rate, cleavage rate, high-quality embryo rate, and blastocyst formation rate compared to ZPN group. ZPA patients were sub-categorised into ZPA-A/B/C/D group according to the status of oocyte polar body and the width of perivitelline space (PVS). There are also differences in the degree of sperm binding to ZP derived from different ZPA patients and the elasticity of the oocyte membrane. ZPA subgroup analysis revealed further disparities in various IVF parameters and pregnancy outcomes. In addition, by performing different treatments on oocytes derived from ZPA patients, we found that ZP assisted hatching before the first oocyte cleavage on D1 of embryonic development in the ZPA-A/B groups and before blastocyst expansion on D4 of embryonic development in the ZPA-C/D groups were beneficial to improve embryonic development. The degree of the impact on clinical outcomes is correlated with the types of ZPA, and laser-assisted hatching of the ZP helps to improve embryonic development in patients with ZPA.

High-altitude hypoxia exposure alters follicular metabolome and oocyte developmental potential in women.

To explore the effects of high-altitude hypoxia on the microenvironment of oocyte development and fertilization potential, we compared the metabolomic patterns of follicular fluid from women living in different altitude areas and traced their oocyte maturation and subsequent development. A total of 315 clinical cases were collected and divided into three groups according to their residence altitudes: 138 cases in low-altitude (< 2300m) group, 100 cases in middle-altitude (2300-2800m) group and 77 cases in high-altitude (> 2800m) group. The clinical outcomes were statistically estimated, including hormonal level, oocyte maturation, in vitro fertilization, and embryo development. Meanwhile, a metabolomic analysis was performed on the follicular fluid of women from different groups using ultra-high-performance liquid chromatography and high-resolution mass spectrometry and differential metabolites were analyzed through the KEGG pathway. The clinical data indicated that the physical condition and reproductive hormone secretion were similar among different groups. Although personalized gonadotropin-releasing hormone strategies were applied, the numbers of antral follicles and obtained oocytes were not impacted by the residence altitude change. In in vitro culture, the maturing rate, fertility rate and cleavage rate of high-altitude group were compared with the other groups. However, the rates of high-quality embryo, formative blastocyst, and available blastocyst were gradually decreased with the rise of residence altitude. Metabolome analysis identified 1193 metabolites in female follicular fluid. Differential analysis indicated that metabolic components in follicular fluid were remarkably changed with the elevation of residence altitude. These differential metabolites were closely related with amino acid metabolism, protein digestion and absorption, oocyte meiosis and steroid biosynthesis. The residence altitude alters the microenvironment of follicular fluid, which could damage the oocyte developmental potential. This study provides diagnostic basis and therapeutic targets for research on female oocyte and embryo development.

High proportion of zygotes with multiple pronuclei increase the embryo multinucleation rate during conventional IVF

The incidence of multiple pronuclei (≥ 3PN) zygotes and blastomere multinucleation was found to be elevated in the presence of increased estradiol (E2) levels and a greater number of retrieved oocytes. This implies a potential link between the incidence of multinucleation at the two-cell stage (MN2) and a higher proportion of ≥ 3PN zygotes. We aimed to investigate the effect of high proportion of ≥ 3PN zygotes on MN2 incidence during conventional in vitro fertilization (C-IVF) by using time-lapse monitoring. This study included 1195 patients from January 2020 to December 2022. The patients were categorized into three groups: Group 1 comprised patients with no ≥ 3PN zygotes (n = 422), Group 2 included those with 0–25% ≥3PN zygotes (n = 617), and Group 3 consisted of patients with more than 25% ≥3PN zygotes (n = 156). The MN2 rate, types of MN2 and clinical outcomes were compared among the three groups. Our data indicated that the MN2 rate was significantly lower in groups 1 and 2 compared to group 3 (18.33 versus 25.62%; p < 0.001 and 19.45 versus 25.62%; p < 0.001). The MN2 embryos exhibited similar rates of high-quality embryos (42.27 versus 43.50 versus 40.67%; p = 0.401) and available embryos (84.96 versus 84.04 versus 83.21%; p = 0.460) rates among the three groups. There were no significant differences in the proportion of MN2 with different types among the three groups (p > 0.05). The embryos displaying binucleated at the two-cell stage in one blastomere (2BI1) and true multinucleated at the two-cell stage in one blastomere (2MULTI1) showed significantly higher blastocyst formation rates compared to embryos exhibiting true multinucleated at the two-cell stage in both blastomeres (2MULTI2) (59.50 versus 45.40%; p < 0.001 and 59.40 versus 45.40%; p < 0.001). In conclusion, the occurrence of MN2 events might be associated with high proportion of ≥ 3PN zygotes incidence. The types of MN2 had significant reference value when selecting embryos for transfer during the cleavage stage.

Predictions of live birth in IVF programs of patients with recurrent implantation failure

BackgroundWhen a high-quality embryo is implanted into the uterus, but the pregnancy is not established as shown by the ultrasound visualization of an intrauterine gestational sac, this is known as “implantation failure.” Cases when more than two times implantation failure occurred was defined as recurrent implantation failure (RIF). Additional testing is done at this stage of infertility treatment to avoid a repeat of the same result with a future in vitro fertilization (IVF) effort. Aim of the studyThe study aimed to evaluate predictive value of using embryo transfer personalization because of the implantation window study in combination with preimplantation genetic testing in patients with recurrent implantation attempts. MethodsBriefly describe the main methods or treatments applied: Ninety-three infertile women make up the sample for this prospective cohort study. In regard to treatment results, the study intends to assess the predictive importance of patient characteristics, screening indicators, and several features of IVF cycles, such as the quantity, quality, and developmental stage of the transferred embryos. Statistical methods employed include the calculation of the median (Me) and interquartile range (IQR) for continuous variables. The Mann-Whitney U test was used to discern differences between unrelated samples, while categorical variables were presented as absolute and percentage values. The Pearson’s Chi-squared test assessed differences between groups. Logistic regression, utilizing both enter and backward Wald methods, was applied to establish associations with binary outcomes. ResultsThe integration of individualized embryo transfer and preimplantation genetic testing (PGT) significantly enhanced the likelihood of live births by 3.4 times in patients experiencing recurrent implantation failure (RIF), with a statistical significance of p = 0.026. In contrast, employing PGT alone increased the probability of live births by 1.5 times; however, this result was not statistically significant (p = 0.439). The predictive model for live birth in patients with RIF, based on our study findings, is defined as follows: the probability of live birth = 1.936 + [1.014 if PGT-A embryos are utilized for transfer] + [1.742 if endometrial preparation is tailored according to the Wellbeing Index (WI)] − [1.860 in cases of secondary infertility] − [1.891 when a male factor is involved]. ConclusionsThe determination of the implantation window (IW) and PGT of the embryo are efficient methods of live birth achievement for patients with RIF.

Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial

BackgroundPoor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.MethodsIn this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.ResultsAfter the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.ConclusionAST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.Trial registrationClinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16.Graphical

Trace elements exposure affects the outcomes of in vitro fertilization embryo transfer, a cohort study in Northern China.

With urbanization and industrialization process accelerated, humans are exposed more and more trace elements. This study aimed to explore the potential associations of trace elements with the outcomes of in vitro fertilization embryo transfer (IVF-ET). Total 181 women who underwent IVF-ET were enrolled, among which 89 women underwent fresh ET after IVF. Trace elements were measured in the serum and follicular fluid (FF) samples by inductively coupled plasma-mass spectroscopy. The associations of the levels of different trace elements with IVF-ET outcomes, including normal fertilization, high-quality embryos, and clinical pregnancy (fresh ET) were analyzed. Twenty-five out of twenty-eight trace elements showed higher concentrations in the serum than those in the FF. Normal fertilization was positively associated with Cu and Mn in the FF. High-quality embryos was positively associated with Cu in the serum and FF, and Zn in the serum. Clinical pregnancy was positively associated with Ge in the serum, and inversely associated with Al, Ba, and Pb in the serum. Additionally, poor outcomes of IVF-ET should be noticed in women with FF level of Cu < 955.38ng/mL, FF level of Mn < 3.42ng/mL, serum level of Ge < 6.11ng/mL, serum level of Al > 28.44ng/mL, and serum level of Pb > 0.90ng/mL. IVF-ET outcomes were positively associated with Cu, Mn, Zn, and Ge, and inversely associated with Al and Pb. Properly controlling the exposure of relevant trace elements is necessary for patients with the need of IVF-ET.

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.

The effects of fresh embryo transfer and frozen-thawed embryo transfer on the perinatal outcomes of single fetuses from mothers with PCOS.

To investigate the effects of fresh embryo transfer and frozen-thawed embryo transfer on perinatal outcomes among patients with PCOS. Patients who underwent in vitro fertilization and embryo transfer at the reproductive medicine center of the Affiliated Hospital of Guangdong Medical University from February 2013 to March 2021 were retrospectively analyzed. Patients were divided into the fresh embryo transfer group and frozen-thawed embryo transfer group according to whether fresh embryo transfer was performed. According to their conditions, patients were further classified into the ET-PCOS group (group A, n = 104), ET-non-PCOS group (group B, n = 212), FET-PCOS group (group C, n = 102), or FET-non-PCOS group (group D, n = 148); the general data, laboratory indicators and pregnancy outcomes of the patients were statistically analyzed, and the perinatal outcomes and related factors between the groups were compared and analyzed. The level of E2 on the HCG test day in the ET group was lower than that in the FET group. The natural birth rate of group D was lower than that of group A and group B, and the cesarean section rate was higher than that of group A and group B; the clinical pregnancy rate of group A was higher than that of group B and group D, and the difference was statistically significant (P < 0.05). There was no significant difference in the total abortion rate, early abortion rate or late abortion rate between the groups (P > 0.05). There was no significant difference in gestational age, neonatal sex or neonatal weight between the groups (P > 0.05). The incidence of placenta previa in Group B was significantly lower than that in Group D, and the difference was significant (P < 0.05). The incidence of fetal distress in Group B was significantly lower than that in Groups C and D, and the incidence of neonatal jaundice in Group D was significantly higher than that in Groups A and B (P < 0.05). In the multivariate analysis, the number of high-quality embryos was independent factors affecting clinical pregnancy, and the embryo transfer method was an independent factor affecting fetal distress and neonatal jaundice. Young PCOS patients without risk of OHSS have a high clinical pregnancy rate with fresh transplant cycles. PCOS disease itself has no significant effect on the perinatal outcomes of the mother or singleton infant. Frozen-thawed embryo transfer may increase the incidence of low placenta, fetal distress and neonatal jaundice.

Interleukin-22 improves ovulation in polycystic ovary syndrome via STAT3 signaling.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease, which leads to serious impairment of reproductive health in women of child-bearing age. Anovulation or oligo-ovulation is a common clinical manifestation of PCOS patients. A disturbance of the ovarian immune microenvironment contributes to the disorders of follicle development and ovulation; however, the underlying mechanism remains unclear. Here we demonstrated the protective effect of immune factor interleukin-22 (IL-22) on PCOS follicle development and ovulation. Follicular IL-22 levels were significantly lower in PCOS patients than in the control group and were positively correlated with oocyte fertilization rate and high-quality embryo rate. Additionally, IL-22 evidently improved follicle development in vitro and promoted ovulation-related gene expression, which was disrupted by the depletion of interleukin-22 receptor 1 (IL-22R1) or inhibition of STAT3 in granulosa cells. This indicates that IL-22 acts through IL-22R1 and the STAT3 signaling pathway to promote follicle development and ovulation in PCOS. In summary, this study has elucidated the vital role of the ovarian immune microenvironment in follicle development and ovulation. Application of IL-22 may provide new insights into the treatment of PCOS patients.

Multi-omics approach to reveal follicular metabolic changes and their effects on oocyte competence in PCOS patients.

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder linked with endocrine and metabolic disturbances. The underlying mechanism of PCOS, especially its effect on oocyte competence, remains unclear. The study aimed to identify abnormal follicular metabolic changes using a multi-omics approach in follicular fluid from PCOS patients and to determine their effects on oocyte competence. A total of 36 women with PCOS and 35 women without PCOS who underwent in vitro fertilization and embryo transfer were included in the study. Cumulus cells and follicular fluid samples were collected. Follicular fluid samples underwent metabolomic analysis, while cumulus cell clusters from the same patients were assessed using transcriptomic analysis. Clinical information of patients and assisted reproductive technology (ART) results were recorded. Transcriptomics and metabolomics were integrated to identify disrupted pathways, and receiver operation characteristics (ROC) analysis was conducted to identify potential diagnostic biomarkers for PCOS. Pearson correlation analysis was conducted to assess the relationship between metabolites in follicular fluid and oocyte competence (fertilization and early embryo development potential). Through multi-omics analysis, we identified aberrantly expressed pathways at both transcriptional and metabolic levels, such as the citrate cycle (TCA cycle), oxidative phosphorylation, the cAMP signaling pathway, the mTOR signaling pathway, and steroid hormone biosynthesis. Ten candidate metabolites were identified based on metabolic profiling data from these altered pathways. Phytic acid, succinic acid, 2'-deoxyinosine triphosphate, and 4-trimethylammoniobutanoic acid in the follicular fluid exhibited high specificity and sensitivity in distinguishing PCOS. Among these metabolites, L-arginine showed a negative correlation with the 2PN fertilization rate and cleavage rate, while estrone sulfate showed a negative correlation with the high-quality embryo rate in the in-vitro fertilization (IVF) cycle. We have conducted a preliminary study of a novel metabolic signature in women with PCOS using a multi-omics approach. The alterations in key metabolic pathways may enhance our understanding of the pathogenesis of PCOS.

Pre- and Procedural Factors Influencing the Success of In Vitro Fertilization: Evaluating Embryo Quality and Clinical Pregnancy in Cases of Tubal Factor Infertility.

Introduction: While tubal occlusion is a prevalent cause of infertility, accounting for 11-35% of infertility cases among women, there remains a limited understanding of the factors influencing clinical pregnancy following in vitro fertilization (IVF). Methods: In our retrospective, cross-sectional cohort study conducted at a single tertiary center, medical records of women aged 19 to 43 years were analyzed. Logistic regression models were employed to identify the prognostic factors associated with clinical pregnancy after IVF in patients with tubal factor infertility, excluding cases with hydrosalpinx. Results: Data from 219 women diagnosed with tubal occlusion were compared to 1140 cases with non-tubal indication, covering a total of 1359 IVF cycles. A lower maternal age (adjusted odds ratio [AOR]: 0.89, p = 0.001) and a higher embryo quality (AOR: 1.26, p = 0.01) emerged as important factors in clinical pregnancy in the tubal infertility group. Moreover, a lower maternal (AOR:0.91, p < 0.01) and paternal age (p = 0.001), and favorable semen quality (AOR: 1.32, p = 0.03) were critical determinants in the non-tubal infertility group. BMI was generally higher in tubal infertility patients (p = 0.01). Furthermore, FSH level (AOR: 0.93, p = 0.004), AMH level (p < 0.04), number of embryos transferred (AOR: 2.04, p < 0.001), and embryo quality (AOR: 1.26, p < 0.001) came into prominence only in the non-tubal infertility group. The clinical pregnancy rate (34.2%) of women with tubal occlusion did not differ significantly from those in other forms of infertility undergoing IVF (35.4%). Conclusions: Although tubal infertility is typically anticipated to yield the highest clinical pregnancy rates following IVF, it is crucial to acknowledge that both maternal and paternal characteristics can also significantly impact the outcomes.

Successful Sperm Retrieval and Clinical Pregnancies Following Micro-TESE and ICSI Treatments in Patients with Nonobstructive Azoospermia Due to Various Etiologies.

(1) Background: Nonobstructive azoospermia (NOA) etiologies affect the sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) and the clinical outcomes following intracytoplasmic sperm injection (ICSI); (2) Methods: We investigated seven NOA etiologies. The SRR and clinical outcomes of 627 patients were analyzed between November 2017 and July 2022 in the Reproductive and Genetic Hospital of China International Trust and Investment Corporation-Xiangya (CITIC-Xiangya); (3) Results: The overall SRR was 39.4% (247/627). The SRR according to NOA etiologies were: Y chromosome azoospermia factor c microdeletions (26/46, 56.5%), Klinefelter syndrome (KS), 36/85, 42.4%), idiopathic (110/398, 27.6%), cryptorchidism (20/29, 69.0%), chromosome anomalies (7/13, 53.9%), orchitis (45/50, 90.0%), and cancer (3/6, 50.0%). The SRR were different for spermatogonia arrest (26/96, 27.1%), maturation arrest (76/177, 42.9%), and SCOS (30/80, 37.5%) according to histological examinations. The clinical pregnancy rate was similar among the NOA etiologies. The high-quality embryo rate differed between successful (54.7%) and unsuccessful (40.9%) pregnancies. Moreover, the successfully pregnant women (28.99 years) were younger than the unsuccessfully pregnant ones (30.92 years); (4) Conclusions: The SRR from patients with NOA was associated with the etiology and histological categories, while the clinical outcome was associated with the high-quality embryo rate and the female partner's age.

Agrobacterium-mediated Transformation of Tropical Maize Using Seedling Leaf Whorl Explants

Conventional maize transformation has largely relied on immature embryos as explants, and is thus often hampered by the limited access to high-quality immature embryos year-round. Here, we present a detailed protocol using seedling leaf whorls as alternative explants for tropical maize inbred transformation. This approach involves the use of a cassette that drives the expression of the morphogenic transcription factors (MTFs)Baby boom(Bbm) andWuschel2(Wus2), which have been shown to greatly enhance transformation efficiency. We outline here the steps required for the preparation of seedling leaf whorl explants and subsequentAgrobacteriuminfection, and describe the tissue culture regimen that results in transgenic plant regeneration. Because constitutive expression ofBbmandWus2prevents normal plant regeneration and the production of fertile plants, the cassette containing these genes must be excised. As such, we include the steps for theCre/loxP-mediated excision of the MTF gene cassette. The protocol outlines a year-round, more affordable, and efficient approach for carrying out maize transformation for crop improvement.

The TLI system can help day-3 single cleavage embryo transfer to obtain comparative clinical outcomes to day-4 or day-5.

The aim was to explore whether the time-lapse imaging system can help day-3 single cleavage embryo transfer to obtain comparative clinical outcomes to day-4 or 5. The data of 1237 patients who underwent single embryo transfer from January 1, 2018, to September 30, 2020, in our reproductive medicine centre were retrospectively analysed. They were divided into the day-3 single cleavage-stage embryo transfer (SCT) group (n = 357), day-4 single morula transfer (SMT) group (n = 129) and day-5 single blastocyst transfer (SBT) group (n = 751) according to the different embryo transfer stage. The clinical and perinatal outcomes of the three groups were analysed and compared. The clinical pregnancy rates of the patients in the day-3 SCT group, day-4 SMT group and day-5 SBT group were 68.07, 70.54 and 72.04%, respectively. The live birth rates were 56.86, 61.24 and 60.99%, respectively. The monozygotic twin (MZT) rate in the day-3 SCT group was significantly lower than that in the day-5 SBT group (P = 0.049). Regarding perinatal outcomes, only the secondary sex ratio had a significant difference (P < 0.05). After age stratification, no improvement was found in the pregnancy outcomes of patients >35 years of age receiving blastocyst transfer. Our findings suggest that for patients with multiple high-quality embryos on day-3, prolonging the culture time can improve the pregnancy outcome to some extent, but it will bring risks. For centres that have established morphodynamic models, day-3 SCT can also achieve an ideal pregnancy outcome and reduce the rate of monozygotic twins and sex ratio.

Analysis of assisted reproductive outcomes in patients with atypical endometrial hyperplasia and early-stage endometrial cancer after fertility-sparing treatment.

To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early-stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment. This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent invitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility-sparing treatment received: the oral medication group and the levonorgestrel-releasing intrauterine system (LNG-IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high-quality embryo rate. The LNG-IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG-IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant. For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG-IUS can achieve better assisted reproductive outcomes.

Exploring the benefits of astaxanthin as a functional food ingredient: Its effects on oxidative stress and reproductive outcomes in women with PCOS - A systematic review and single-arm meta-analysis of randomized clinical trials.

Polycystic ovary syndrome (PCOS) is a prevalent gynecological-endocrinological disorder characterized by hyperandrogenism, menstrual irregularities, and metabolic disturbances. Recent research has highlighted the role of oxidative stress and chronic inflammation in exacerbating PCOS symptoms and impeding reproductive outcomes. Astaxanthin, a potent antioxidant found in marine organisms, has been suggested as a potential therapeutic intervention due to its ability to reduce oxidative stress and inflammation. This meta-analysis systematically reviews randomized controlled trials assessing the impact of astaxanthin supplementation on oxidative stress and reproductive outcomes in women with PCOS. Data from four trials were analyzed, focusing on markers of oxidative stress and reproductive health metrics. The meta-analysis utilized fixed and random-effects models to synthesize results, with heterogeneity assessed using Chi-square and I2 statistics. The findings indicate that while astaxanthin significantly improves markers of total antioxidant capacity (TAC) in follicular fluid, it does not show a consistent effect on other oxidative stress biomarkers such as malondialdehyde (MDA), catalase (CAT), or superoxide dismutase (SOD). Reproductive outcomes, including oocyte quality and the number of high-quality embryos, showed moderate improvements, although effects on fertilization rates and pregnancy outcomes were insignificant. The analysis highlights variability in study designs and dosing, suggesting a need for further research with standardized protocols and larger sample sizes. Future studies should focus on determining optimal dosing, exploring mechanistic pathways, and investigating the combined effects of astaxanthin with other interventions. Longitudinal studies are needed to assess long-term benefits and safety, and personalized approaches could enhance treatment efficacy for individualswithPCOS.

High risk of low birth weight in couples with advanced paternal age in in vitro fertilization treatment.

With the development of socio-economic conditions and a shift in attitudes towards fertility, there has been a gradual increase in delayed childbearing since the 2000s. Ageplays a significant role in the decline of fertility. However, we know very little about the association of paternal age with reproductive outcomes. To investigate the correlation between advanced paternal age and semen quality, embryo quality, pregnancy, and neonatal outcomes in IVF cycles. In this study, after excluding female partners aged ≥35 years, we analyzed data from 761 infertile couples who underwent in vitro fertilization cycles at the First Affiliated Hospital of USTC between June 2020 and March 2023. Cases were classified into three groups according to the age of the male: <35 years (530 infertile couples), 35 years ≤ paternal age <40 years (125 infertile couples), and ≥40 years (106 infertile couples). Then, we compared the general clinical data arising from in vitro fertilization cycles between the three groups, including semen parameters, embryonic parameters, and pregnancy and neonatal birth outcomes. Data analysis showed that the duration of infertility and the incidence of secondary infertility were significantly higher in paternal age ≥35 years groups than those aged <35 years (all p<0.05). We also observed a significant difference between ≥40 years and <35 years groups in terms of the normal fertilization rate, high-quality embryo rate, clinical pregnancy rate, miscarriage rate, live birth rate, Apgar scores, and the low birth weight neonatal rate (all p<0.05). The group with paternal age ≥40 years showed statistically significant differences in terms of clinical pregnancy rate, miscarriage rate, live birth rate, and low birth weight on multivariable logistic regression (all p<0.05). The results of our study indicate that advanced paternal age (≥40 years) has a significant impact on the embryo quality, pregnancy outcome, and neonatal outcome. Paternal age over 40 years is a risk for in vitro fertilization success rate.

Nomogram for predicting live birth in ovulatory women undergoing frozen-thawed embryo transfer

BackgroundStudy objectives included the development of a practical nomogram for predicting live birth following frozen-thawed embryo transfers in ovulatory women.MethodsTotally, 2884 patients with regular menstrual cycles in our center were retrospectively enrolled. In an 8:2 ratio, we randomly assigned patients to training and validation cohorts. Then we identified risk factors by multivariate logistic regression and constructed nomogram. Finally, receiver operating characteristic curve analysis, calibration curve and decision curve analysis were performed to assess the calibration and discriminative ability of the nomogram.ResultsWe identified five variables which were related to live birth, including age, anti-Müllerian hormone (AMH), protocol of frozen-thawed embryo transfer (FET), stage of embryos and amount of high-quality embryos. We then constructed nomograms that predict the probabilities of live birth by using those five parameters. Receiver operating characteristic curve analysis (ROC) showed that the area under the curve (AUC) for live birth was 0.666 (95% CI: 0.644–0.688) in the training cohort. The AUC in the subsequent validation cohorts was 0.669 (95% CI, 0.625–0.713). The clinical practicability of this nomogram was demonstrated through calibration curve analysis and decision curve analysis.ConclusionsOur nomogram provides a visual and simple tool in predicting live birth in ovulatory women who received FET. It could also provide advice and guidance for physicians and patients on decision-making during the FET procedure.

Constructing a predictive model for live birth following fresh embryo transfer in antagonist protocol for polycystic ovary syndrome.

The present research aims to assess the factors that influence live birth outcomes following fresh embryo transfers using antagonist protocols in individuals diagnosed with polycystic ovary syndrome (PCOS). Furthermore, it seeks to develop a predictive nomogram model to facilitate clinical decision-making and provide personalized treatment strategies. This retrospective cohort research analyzed the clinical data of 1242 individuals having PCOS who went through fresh embryo transfers employing antagonist protocols and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at Fujian Provincial Maternal and Child Health Hospital between January 2018 and December 2022. Individuals were assigned randomly to a modeling group (869 cases) and a validation group (373 cases) in a 7:3 ratio. The Boruta algorithm and multivariable logistic regression were utilized to identify independent risk factors linked to live births after transfer. A predictive nomogram was subsequently developed. The discriminatory power of the model and its accuracy were monitored by utilizing receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. Multivariable logistic regression analysis identified several independent factors that influence live birth rates in fresh embryo transfer cycles for individuals having PCOS using antagonist protocols, including female age, body mass index (BMI), infertility duration, serum testosterone levels, progesterone levels at the time of human chorionic gonadotropin (hCG) injection, number of high-quality cleavage-stage embryos, type of embryo transferred, and the total number of embryos transferred. Based on these findings, a predictive nomogram was developed. The area under the ROC curve stood at 0.804 (95% confidence interval (CI), 0.775-0.833) for the modeling group and 0.807 (95% CI, 0.762-0.851) for the validation group. Calibration curves confirmed that the predictions of the nomogram closely matched the actual live birth outcomes. Decision curve analysis highlighted that the model provides significant net benefits for predicting live birth rates, with optimal performance across a probability range of 16.5 to 88.6%. Independent factors, including female age, infertility duration, BMI, serum testosterone levels, progesterone levels on the day of hCG injection, and the number and type of high-quality cleavage-stage embryos transferred are pivotal in influencing live birth outcomes in fresh embryo transfer cycles under antagonist protocols in individuals with PCOS undergoing IVF/ICSI treatments. The predictive nomogram developed from these factors offers substantial predictive accuracy and clinical utility, providing a reliable basis for clinical prognosis, targeted interventions, and the development of personalized treatment plans.

The effect of endocrine-disrupting chemicals in follicular fluid: The insights from oocyte to fertilization

Endocrine-disrupting chemicals (EDCs) exhibited the detriment in female reproductive health. Our objective was to investigate the individual and mixture effects of EDCs present in follicular fluid, the environment in which oocytes grow and develop, on early reproductive outcomes. We recruited 188 women seeking reproduction examination from the Study of Exposure and Reproductive Health (SEARCH) cohort between December 2020 and November 2021. We assessed the concentrations of 7 categories of 64 EDCs in follicular fluid, and measured early reproductive outcomes, including retrieved oocytes, mature oocytes, normal fertilized oocytes, and high-quality embryos. In this study Monomethyl phthalate (MMP) (2.17 ng/ml) were the compounds found in the highest median concentrations in follicular fluid. After adjusting for multiple testing, multivariate regression showed that multiple EDCs were significantly negatively associated with early assisted reproduction outcomes. For example, MMP showed a significant negative correlation with the number of high quality embryos (β: −0.1, 95 % CI: −0.15, −0.04). Specifically, eight types of EDCs were significantly negatively associated with four early assisted reproductive outcomes (β range: −0.2 ∼ -0.03). In the mixed exposure model, we found that mixtures of EDC were significantly negatively correlated with all four outcomes. In the quantile g-computation (QGCOMP) model, for each interquartile range increase in the concentration of EDC mixtures, the number of oocytes retrieved, mature oocytes, normally fertilized oocytes, and high-quality embryos decreased by 0.46, 0.52, 0.77, and 1.2, respectively. Moreover, we identified that phthalates (PAEs) predominantly contributed to the negative effects. Future research should validate our findings.