Vitro Fertilization Research Articles

AREG expression in cumulus cells as a prognostic marker of oocyte quality

Background. Assisted reproductive technologies (ART) represent the most promising and successful methods of infertility treatment. A personalized approach may enhance its efficacy. One such approach is the development of reliable methods for assessing the quality and selection of embryos for transfer. The quality of the embryo is largely contingent upon the quality of the gametes involved in fertilization; thus, the development of non-invasive methods to assess oocyte quality represents a crucial step in the advancement of personalized ART. It is proposed that molecular and biological characterization of cumulus cells can be utilized to assess oocyte quality and predict the success of implantation of transferred embryos. The aim of the study was to evaluate the expression levels of potential oocyte quality marker genes (AREG, STAR, PTGS2, HAS2 and SCD5) in cumulus cells from healthy donors and patients with primary and secondary infertility. Materials and Methods. Nine donors and 19 patients were enrolled in the study. RNA was isolated from cumulus cells obtained during oocyte preparation for fertilization, and cDNA was synthesized. The cDNA was used as a matrix for real-time PCR with primers for the above-mentioned genes of interest. Results. Significant difference in AREG gene expression was observed between patients with successful (i.e. ended with birth) outcome and with IVF failure. No difference was found for the STAR, HAS2, PTGS2 and SCD5 genes. Conclusion. The method of assessing the expression level of marker genes in cumulus cells by real-time PCR shows considerable promise for the assessment of oocyte quality. The AREG gene is a potential candidate for use as a marker of oocyte quality.

Human papillomavirus and male infertility correlation analysis following World Health Organization 2021 guidelines

Male infertility is a complex issue influenced by multiple environmental and pathological factors. In this context, the impact of Human papillomavirus (HPV) infection on male fertility remains controversial. The introduction of new WHO 2021 evaluation criteria, included in the 6th ed. of Laboratory Manual for the examination and processing of human semen, i.e. DNA fragmentation index (DFI), slow and rapid progressive motility, could provide additional information about this correlation. 121 semen samples of male partners of HPV-positive women attending In Vitro Fertilization (IVF) were evaluated following WHO 2021 and HPV-DNA test. Comparing HPV-negative and positive samples for rapid and slow progressive motility showed significantly different results (p = 0.0018, p = 0.0004), contrary to what was observed for total progressive motility. Regarding sperm DFI, only high-risk HPV infections affected DNA integrity. In addition, the correlation between the different semen parameters revealed a significant correlation between midpiece morphological defects and rapid progressive motility in the HPV-positive group (rho = 0.43, p = 0.0006). In conclusion, WHO 2021 provides additional information regarding HPV’s impact on seminal parameters. The correlation between HPV positivity, midpiece defects and a higher rapid progressive motility opens new research perspectives that may help unravel the issues surrounding the role of HPV in compromising sperm quality.

Melatonin supplementation attenuates cuproptosis and ferroptosis in aging cumulus and granulosa cells: potential for improving IVF outcomes in advanced maternal age

BackgroundAdvanced maternal age is associated with decreased oocyte quantity and quality and in vitro fertilization (IVF) success rates. This study aimed to investigate whether melatonin supplementation can improve IVF outcomes in women of advanced maternal age by modulating cuproptosis and ferroptosis.MethodsThis prospective cohort study included 161 women aged 35–45 years undergoing IVF-frozen embryo transfer cycles. Participants were assigned to either melatonin (n = 86, 2 mg daily for ≥ 8 weeks) or control (n = 75) groups. Cumulus cells were analyzed for cuproptosis and ferroptosis-related gene expression. Additional experiments were conducted on the HGL5 human granulosa cell line to assess mitochondrial function and metabolic reprogramming.ResultsMelatonin supplementation significantly improved IVF outcomes in women aged ≥ 38 years, increasing clinical pregnancy rates (46.0% vs. 20.3%, P < 0.01), ongoing pregnancy rates (36.5% vs. 15.3%, P < 0.01), and live birth rates (33.3% vs. 15.3%, P < 0.05). In cumulus cells from patients, gene expression analysis revealed that melatonin modulated cuproptosis and ferroptosis-related genes, including ATP7B and GPX4, with more pronounced effects in the ≥ 38 years group. This suggests melatonin enhances cellular resilience against oxidative stress and metal-induced toxicity in the ovarian microenvironment. In vitro studies using HGL5 cells showed melatonin reduced oxidative stress markers, improved mitochondrial function, restored expression of glycolysis and TCA cycle-related genes and modulated cuproptosis and ferroptosis-related gene expression. These findings provide mechanistic insight into melatonin’s protective effects against regulated cell death in ovarian cells, potentially explaining the improved IVF outcomes observed.ConclusionsMelatonin supplementation significantly improved IVF outcomes in women of advanced maternal age, particularly those ≥ 38 years old, likely by modulating cuproptosis and ferroptosis and enhancing mitochondrial function in cumulus and granulosa cells. These results suggest that melatonin could be a promising adjuvant therapy for improving IVF success rates in older women.

Support of the luteal phase in programs for transferring thawed embryos into the uterine cavity in patients with overweight and obesity

Introduction. Progesterone levels are a critical factor for embryo implantation in in vitro fertilization (IVF) programs, including thawed embryo transfer programs. Overweight/obese patients often have lower blood progesterone concentrations in the luteal phase during IVF cycles, which requires an individual approach to planning luteal support in this category of patients.Aim. To compare the pregnancy ratе and miscarriage rates up to 12 weeks of pregnancy in overweight/obese patients who underwent a program of transfer of thawed embryos into the uterine cavity, depending on the type and route of administration of gestagens.Materials and methods. The study included 76 overweight or obese patients. All patients were treated for infertility using a program for transferring a thawed embryo into the uterine cavity; luteal phase support was carried out either using micronized progesterone, identical to natural, – the drug Utrogestan in a daily dose of 800 mg intravaginally (40 patients), or combination therapy was prescribed – vaginal gel with progesterone 90 mg in combination with the synthetic progestin dydrogesterone in a daily dose of 30 mg, taken orally (36 patients).Results. The rates of pregnancy and miscarriage in the first trimester were comparable in both groups and did not depend on differences in luteal support.Conclusions. The formation of the luteal phase of the cycle in patients with overweight/obesity is equally effective using various forms of gestagens. The use of micronized progesterone may be preferable in patients with overweight/obesity in terms of the ability to monitor blood progesterone levels, a more favorable metabolic profile when used vaginally, and the possibility of switching to oral administration of the drug in the event of the development of adverse local events.

Comparative study on pregnancy complications: PGT-A vs. IVF-ET with gender-specific outcomes

The safety and clinical effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving pregnancy outcomes for sub-fertile patients remains controversial. Potential sex-based differences in the relationship between PGT-A and pregnancy complications have not been investigated, which could guide the appropriate clinical application of PGT-A. In this secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141), 940 women who achieved singleton live birth during the trial were included to estimate the between-group differences in pregnancy complications following PGT-A versus conventional in vitro fertilization (IVF) vary with fetal sex. Logistic regression analysis was used to adjust for possible confounders, and subgroup analysis was also performed. Among male fetuses, the risk of maternal preeclampsia was significantly lower after PGT-A compared to conventional IVF treatment (3.37% vs. 7.88%; adjusted OR, 0.40; 95% CI, 0.17-0.92; P = 0.032). However, this protective effect was not observed in pregnancies with female fetuses (3.63% vs. 3.38%; adjusted OR, 1.04; 95% CI, 0.36-3.00; P = 0.937). In addition, no significant sex-dependent differences in the risks of other pregnancy complications or neonatal outcomes were detected between PGT-A and conventional IVF groups (P &amp;gt; 0.05). In summary, PGT-A was associated with a decreased risk of maternal preeclampsia in singleton pregnancies with male fetuses, highlighting its potential utility in preeclampsia prevention in addition to spontaneous abortion rate reduction.

Molecular cloning of PRD-like homeobox genes expressed in bovine oocytes and early IVF embryos.

Embryonic genome activation (EGA) is a critical step in early embryonic development, as it marks the transition from relying on maternal factors to the initiation of transcription from embryo's own genome. The factors associated with EGA are not well understood and need further investigation. PRD-like (PRDL) homeodomain transcription factors (TFs) are considered to play crucial roles in this early event during development but these TFs have evolved differently, even within mammalian lineages. Different numbers of PRDL TFs have been predicted in bovine (Bos taurus); however, their divergent evolution requires species-specific confirmation and functional investigations. In this study, we conducted molecular cloning of mRNAs for the PRDL TFs ARGFX, DUXA, LEUTX, NOBOX, TPRX1, TPRX2, and TPRX3 in bovine oocytes or in vitro fertilized (IVF) preimplantation embryos. Our results confirmed the expression of PRDL TF genes in early bovine development at the cDNA level and uncovered their structures. For each investigated PRDL TF gene, we isolated at least one homeodomain-encoding cDNA fragment, indicative of DNA binding and thus potential role in transcriptional regulation in developing bovine embryos. Additionally, our cDNA cloning approach allowed us to reveal breed-related differences in bovine, as evidenced by the identification of a high number of single nucleotide variants (SNVs) across the PRDL class homeobox genes. Subsequently, we observed the prediction of the 9aa transactivation domain (9aaTAD) motif in the putative protein sequence of TPRX3 leading us to conduct functional analysis of this gene. We demonstrated that the TPRX3 overexpression in bovine fibroblast induces not only protein-coding genes but also short noncoding RNAs involved in splicing and RNA editing. We supported this finding by identifying a shared set of genes between our and published bovine early embryo development datasets. Providing full-length cDNA evidence for previously predicted homeobox genes that belong to PRDL class improves the annotation of the bovine genome. Updating the annotation with seven developmentally-important genes will enhance the accuracy of RNAseq analysis with datasets derived from bovine preimplantation embryos. In addition, the absence of TPRX3 in humans highlights the species-specific and TF-specific regulation of biological processes during early embryo development.

Catalyzing IVF outcome prediction: exploring advanced machine learning paradigms for enhanced success rate prognostication

This study addresses the research problem of enhancing In-Vitro Fertilization (IVF) success rate prediction by integrating advanced machine learning paradigms with gynecological expertise. The methodology involves the analysis of comprehensive datasets from 2017 to 2018 and 2010–2016. Machine learning models, including Logistic Regression, Gaussian NB, SVM, MLP, KNN, and ensemble models like Random Forest, AdaBoost, Logit Boost, RUS Boost, and RSM, were employed. Key findings reveal the significance of patient demographics, infertility factors, and treatment protocols in IVF success prediction. Notably, ensemble learning methods demonstrated high accuracy, with Logit Boost achieving an accuracy of 96.35%. The implications of this research span clinical decision support, patient counseling, and data preprocessing techniques, highlighting the potential for personalized IVF treatments and continuous monitoring. The study underscores the importance of collaboration between gynecologists and data scientists to optimize IVF outcomes. Prospective studies and external validation are suggested as future directions, promising to further revolutionize fertility treatments and offer hope to couples facing infertility challenges.

Use of Laughter Therapy for In Vitro Fertilization: A Systematic Review

Background/Objectives: In vitro fertilization (IVF) is an assisted reproductive technique for women and couples experiencing difficulties in achieving a spontaneous pregnancy, often due to stressors that negatively affect fertility. Humor can be beneficial in these stressful situations, helping to reduce symptoms of anxiety and depression. The primary aim was to analyze the effectiveness of laughter therapy in increasing pregnancy rates in women undergoing IVF. The secondary aims were to identify different types of laughter therapy interventions and evaluate their benefits. Methods: A systematic review was conducted using Medline, Web of Science, Scopus, Cinahl, ProQuest and Lilacs, with the search terms “laughter”, “laughter therapy”, “fertilization in vitro” and “fertilization”. Intervention studies published in English, Spanish, or Portuguese were included, with no limits on the date of publication. Studies with other designs, those conducted with animals and grey literature were excluded. The quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal tools. Results: In total, n = 3 studies (1 randomized clinical trial and 2 quasi-experimental) were included, evaluating pregnancy rates and symptoms of depression and anxiety. The interventions included clowns performing magic tricks and interpreting comic situations. Additionally, they incorporated hand clapping, breathing exercises, childlike playfulness, drinking milk, muscle relaxation exercises, candles, and music. Conclusions: This review does not provide clear evidence on the effectiveness of laughter therapy in increasing pregnancy success in IVF. Although it may have some positive effects in reducing symptoms of depression and anxiety, it is important to note that while the reduction of these symptoms may enhance the emotional well-being of patients, it has not been demonstrated to directly lead to an increase in pregnancy rates. Laughter therapy is an innovative, non-pharmacological intervention that is simple, non-invasive, easy to implement and cost-effective; however, the number of available studies is insufficient. More research is needed to provide better and higher-quality evidence using rigorous designs to evaluate this intervention in IVF clinical practice.

IVF with frozen-thawed sperm after prolonged capacitation yields comparable results to ICSI in horses: A morphokinetics study

Intracytoplasmic sperm injection (ICSI) is the current clinical practice for the in vitro production of equine embryos. The use of conventional fertilization methods such as in vitro fertilization (IVF), has historically been associated with poor success in horses. However, recent improvements have led to better outcomes with IVF, though only when using fresh semen, which limits its use in clinical practice. IVF remains in its infancy in equine reproduction, and several unknowns remain about the technique. One significant gap in knowledge concerns the morphokinetics of IVF embryos and how they differ from their ICSI counterparts. To address this, we performed IVF using frozen-thawed sperm from five different stallions following sperm selection and a prolonged capacitation period of 10 h, on a total of 109 oocytes. We then analyzed the cleavage rate (cleaved/initial oocytes), blastocyst rate (blastocyst/initial zygotes), and blastocyst development (blastocyst/cleaved zygotes) of the IVF cycles, and compared them with those of the clinical ICSI cycles during the same period. We also evaluated time-lapse images of the developed embryos to assess developmental time points such as time to morula compaction and blastocyst expansion, as well as morula and blastocyst sizes. Overall, developmental rates were not different between IVF and ICSI cycles (blastocyst rate 41.1 % IVF and 41.8 % ICSI, p > 0.05). However, development proceeded faster in IVF cycles (blastocyst expansion IVF 155.5 ± 18.5 h; ICSI 167.2 ± 19.6 h; p < 0.05) and IVF embryos were also larger (blastocyst area IVF 22608 ± 2857 μm2; ICSI 20806 ± 1505 μm2; p < 0.05). The faster development and larger size might suggest a more advanced developmental stage. The implications of these findings need to be further evaluated to assess their association with pregnancy potential. The successful developmental rates achieved in IVF cycles demonstrate the potential of this technique for clinical application, although the amount of frozen-thawed semen required is significantly higher in IVF than in ICSI, which is an important consideration for mare and stallion owners. Nonetheless, the use of frozen-thawed semen in equine IVF, coupled with comparable blastocyst rate, presents promising potential for broader clinical adoption of the IVF technique.

Long-term effects of IVF on offspring kidneys: observations from adolescence to adulthood

Research questionWhat is the effect of in-vitro fertilization (IVF) on long-term health of offspring kidney? DesignWe established an IVF mouse model and subsequently observed renal structure, function, and cortical oxidative stress from the age of 2 months to ascertain any disparities compared to natural conceived (NC) offspring. And this kind of process continued until the mice reached 5 months old. ResultsWe found no significant difference in the body weight of mice aged 2 to 5 months between IVF and NC offspring. However, the renal/weight ratio of IVF offspring was higher than that of NC offspring at 2 months and 3 months, but this difference disappeared in offspring aged 4 to 5 months. IVF offspring at 5 months of age had lower urine creatinine (Ucr) levels compared to NC offspring. Moreover, The expression of ACE2 was observed to decrease in the kidneys of 4 to 5-month-old IVF mice, and the expression of AGTR1A was higher in 5-month-old IVF mice compared to NC mice. The malondialdehyde (MDA) level in 5-month-old IVF offspring was higher than in NC offspring. ConclusionOur study indicated that microvascular thickness in the kidneys of IVF offspring remains unchanged, but minor alterations in kidney function, RAS gene expression, and renal cortical oxidative stress were evident by 5 months of age.

Sexual Function and Satisfaction among Women Undergoing In Vitro Fertilization (IVF) in the West of Iran: A Cross-Sectional Study

Background: We haven’t found any reported study that addressed sexual function and satisfaction in infertile women who are undergoing IVF treatment in the west of Iran. Objective: The present study was conducted to investigate sexual performance and satisfaction among women undergoing in vitro fertilization (IVF) in Western Iran. Methods: This cross-sectional study was conducted on 170 women from December 2022 to March 2023. The participants were selected by convenience sampling until the sample size was reached. The participants were included in the study as available sampling. Women completed the demographic questionnaire, FSFI (female sexual function index), and Linda Berg’s Sexual Satisfaction Questionnaire. For data analysis, we used the Stata version 14 (StataCorp, College Station, TX) and we considered the P-value less than 0.05 significant. Result: There was a significant relationship between husband occupations, economic status, marriage duration, period of infertility, cause of infertility, and intercourse times with sexual satisfaction (P&lt;0.05). The highest percentage of the obtained score was related to pain (51.6%) and the lowest was related to desire (38%). All of the patients with weak sexual function had weak sexual satisfaction and 60.19% of the patients with good sexual function had good sexual satisfaction (P&lt;0.001). Conclusion: Women with weak sexual function had weak sexual satisfaction. Policymakers should consider strategies, such as counseling and psychological support for women during the treatment process to help them cope with their problems, especially psychological problems.

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.

Effect of protein acetylation on capacitation of stallion sperm

Sperm capacitation is considered the main factor limiting conventional in vitro fertilization (IVF) in horses. A recent scientific breakthrough in sperm processing for IVF in horses has resulted in embryos and foals being produced; however, various aspects of the IVF process remain to be fully elucidated. Lysine acetylation has been shown to play a role in sperm capacitation in several species and the objective of this study was to detect and evaluate this process in the horse. Ejaculates of two stallions were collected and incubated in different conditions with deacetylase inhibitors to induce a hyperacetylation state. Although lysine acetylation was successfully detected in all experimental groups, sperm hyperacetylation could not be induced following incubation with deacetylase inhibitors. In addition, no hyperactivation was detected by kinematic sperm evaluation and tyrosine phosphorylation increased only in the positive control group. Treatments with high doses of deacetylase inhibitors increased acrosome reaction indicating a possible connection between induction of acrosome reaction and protein acetylation. Future studies investigating the effect of longer incubation periods with different doses of deacetylase inhibitors are warranted to elucidate the ability of protein acetylation to induce capacitation of stallion sperm.

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.

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

BackgroundPolycystic 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.MethodsPart 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.ResultsBased 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.ConclusionCFDT 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 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.

Quantitative Standardized Expansion Assay: An Artificial Intelligence-Powered Morphometric Description of Blastocyst Expansion and Zona Thinning Dynamics

Artificial intelligence applied to time-lapse microscopy may revolutionize embryo selection in IVF by automating data collection and standardizing the assessments. In this context, blastocyst expansion dynamics, although being associated with reproductive fitness, have been poorly studied. This retrospective study (N = 2184 blastocysts from 786 cycles) exploited both technologies to picture the association between embryo and inner-cell-mass (ICM) area in µm2, the ICM/Trophectoderm ratio, and the zona pellucida thickness in µm (zp-T) at sequential blastocyst expansion stages, with (i) euploidy and (ii) live-birth per transfer (N = 548 transfers). A quantitative-standardized-expansion-assay (qSEA) was also set-up; a novel approach involving automatic annotations of all expansion metrics every 30 min across 5 h following blastulation. Multivariate regressions and ROC curve analyses were conducted. Aneuploid blastocysts were slower, expanded less and showed thicker zp. The qSEA outlined faster and more consistent zp thinning processes among euploid blastocysts, being more or as effective as the embryologists in ranking euploid embryo as top-quality of their cohorts in 69% of the cases. The qSEA also outlined faster and more consistent blastocyst expansion and zp thinning dynamics among euploid implanted versus not implanted blastocysts, disagreeing with embryologists’ priority choice in about 50% of the cases. In conclusion, qSEA is a promising objective, quantitative, and user-friendly strategy to predict embryo competence that now deserves prospective validations.

Risk Factors for Prematurity and Congenital Malformations in Assisted Reproductive Technology Pregnancies—A Retrospective Study

Background: Assisted reproductive technology (ART) nowadays plays a major role in the treatment of infertility, with the most frequently used techniques being in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The objective of this study is to analyze pregnancies achieved using these ART techniques and their correlations with the prematurity and congenital malformations rates. Methods: This is an observational retrospective longitudinal study that includes 814 newborns conceived through an ART, namely IVF or ICSI. Results: Using a multivariate logistic regression analysis mode, there is a higher prematurity rate in twin pregnancies OR 16 (95% CI 10.7, 23.8), donor conception OR 1.8 (95% CI 1.1, 3.3) and PIH pregnancy OR 2.6 (95% CI 1.5, 4.5). The odds of malformations in these ART pregnancies are increased by the stage of the embryo (day 3) OR 2.6 (95% CI 1.3, 5.2), fresh embryo transfer OR 2 (95% CI 1.2, 3.4) and donor conception OR 2.3 (95% CI 1.2, 4.4). The ART used (IVF/ICSI) does not influence the prematurity or birth defects rate. Conclusions: Donor conception is found to increase the odds of both prematurity and congenital malformations. The ART used (IVF/ICSI) does not influence the prematurity or birth defects rate.

The effect of depression on the outcome of infertile females underwent the first In Vitro Fertilization procedure

Background: Infertility affects married adults, and In Vitro Fertilization (IVF) is an Assisted Reproductive Technology (ART) that can treat it. Women undergoing IVF are more likely to experience depression. There is a need to reduce depression by supporting and advising sufferers. The aim of this study is to evaluate the effect of depression on pregnancy rates among infertile females underwent IVF treatment. Materials and Methods: This observational study analyzed 149 patients attending the infertility center at Kamal Al-Samaraie hospital seeking a chance of a conception. The participants received a traditional hospital protocol. The study assessed depression status using the CES-D (Center for Epidemiologic Studies Depression) scale at the beginning of the IVF cycle. Results: Conclusion: Our findings show that the pregnancy rate was not related to baseline depression of women underwent the first IVF procedure. .

Non-genetic risk factors for preeclampsia: an updated umbrella review

Abstract Background Preeclampsia (PE) is a common pregnancy disorder with complex mechanisms, and multiple risk factors may contribute to its development. Our objective is to update our literature search from our previous umbrella review, summarizing recent evidence on non-genetic risk factors associated with PE and assessing their credibility to identify those supported by robust epidemiological evidence. Methods We searched PubMed, EMBASE, Scopus, and ISI Web of Science up to June 2023. For each meta-analysis, we computed summary effect estimates, 95% confidence intervals, 95% prediction intervals, and assessed heterogeneity using I², while also examining small-study effects and excess significance bias. Quality assessment was conducted using the AMSTAR-2 tool. Results 89 meta-analyses were identified, providing data on 219 associations. Of these, 151 (69%) showed statistically significant findings at P &amp;lt; 0.05, with 52 (24%) remaining significant at P &amp;lt; 10-6. Large or very large heterogeneity was observed in 121 (55%) associations. Evidence for small-study effects and excess significance bias was found in 27 (12%) and 29 (13%) associations, respectively. Only 16 (7%) presented convincing evidence: Polycystic Ovary Syndrome (PCOS), PCOS (adjusted), Obstructive Sleep Apnea (OSA), Obesity (adjusted), Chronic Kidney Disease (CKD), Pregnancy Intrahepatic Cholestasis, SARS-CoV-2 infection (adjusted), Oocyte donation (OD) vs. In vitro fertilization (IVF), Fresh embryo transfer vs. spontaneous conception (SC) (singleton), Frozen embryo transfer vs. SC, OD vs. SC (singleton), IVF-OD vs. IVF-AO, IVF-OD fresh ET vs. IVF-AO fresh ET, NC frozen embryo transfer vs. AC frozen embryo transfer, Fetal sex (term), and Smoking. Conclusions Maternal health conditions like PCOS, along with reproductive interventions such as OD and IVF, as well as lifestyle factors like obesity and smoking, showed convincing associations with PE. Key messages • Maternal health conditions, reproductive interventions, and lifestyle factors showed compelling evidence of association with preeclampsia. • Our findings emphasize the multifactorial nature of preeclampsia and suggest potential avenues for further research and clinical intervention.