Trophectoderm grade as a predictor of beta human-chorionic gonadotropin rise in early pregnancy.

PURPOSE: To evaluate the association, if any, between the grade of the trophectoderm (TE) and the rate at which ß-human-chorionic gonadotropin (ß-HCG) rises in early pregnancy. METHODS: This is a retrospective cohort study including 1116 singleton clinical pregnancies resulting from in vitro fertilization with single day 5 blastocyst transfer at an academic fertility center. TE quality was assessed by trained embryologists employing standard criteria. Three groups were formed based on the TE grade: grade A (n = 358), grade B (n = 628), and grade C (n = 130). Main outcome measure was the rise (%) in serum levels of ß-HCG (days 12 to 14 post embryo transfer), using the following formula [(ß-HCG D14 - ß-HCG D12) * 100/ß-HCG D12]. RESULTS: Fresh embryo transfers accounted for 64.1% of the population. Overall, in adjusted models there were no significant differences in the ß-HCG% rise when comparing the TE grade C group to TE grade A [adjß (95%CI): 10.09 (- 0.05, 20.22)] or when comparing TE grade Β group to TE grade A [4.46 (- 2.97, 11.88)]. When the analysis was restricted to fresh embryo transfers, significant differences were observed in the % rise of ß-HCG when comparing the TE grade C group to TE grade A [adjß (95%CI): 21.71 (5.67, 37.74)], but not when comparing the TE grade B group to TE grade A [2.68 (- 5.59, 10.95)]. In frozen transfers, there were no significant differences. CONCLUSION: TE grade appears to impact early pregnancy serum ß-HCG levels in the setting of a fresh day 5 embryo transfer, even after adjusting for potential confounders.

Live birth outcomes following single-step blastocyst warming technique - optimizing efficiency without impacting live birth rates.

PURPOSE: To evaluate the impact of a single-step (SS) warming versus standard warming (SW) protocol on the survival/expansion of vitrified blastocysts and their clinical outcomes post-frozen embryo transfer (FET). METHODS: Retrospective analysis was performed on 200 vitrified/warmed research blastocysts equally divided amongst two thawing protocols utilizing the Fujifilm Warming NX kits (Fujifilm, CA). SW utilized the standard 14-minute manufacturer's guidelines. SS protocol required only a one-minute immersion in thaw solution (TS) before the embryos were transferred to culture media. A time-interrupted study was performed evaluating 752 FETs (SW: 376 FETs, SS 376 FETs) between April 2021-December 2022 at a single academic fertility clinic in Boston, Massachusetts. Embryologic, clinical pregnancy, and live birth outcomes were assessed using generalized estimated equation (GEE) models, which accounted for potential confounders. RESULTS: There was 100% survival for all blastocysts (n = 952 embryos) with no differences in blastocyst re-expansion regardless of PGT status. Adjusted analysis showed no differences in implantation, clinical pregnancy, spontaneous abortion, or biochemical pregnancy rate. A higher odds of multiple gestation [AdjOR(95%CI) 1.06 (1.01, 1.11), p = 0.019] were noted, even when adjusting for number of embryos transferred [AdjOR(95%CI) 1.05 (1.01, 1.10)]. Live birth outcomes showed no differences in live birth rates or birthweight at delivery. CONCLUSIONS: The study found equivalent outcomes for SS and SW in all parameters except for a slight rise in the rate of multiple gestations. The results suggest that SS warming is an efficient, viable alternative to SW, reducing thaw times without adverse effects on live birth rates or neonatal birth weights.

ANRIL rs4977574 Gene Polymorphism in Women with Recurrent Pregnancy Loss.

BACKGROUND: ANRIL rs4977574 gene polymorphism has been associated with arterial thrombosis and cardiovascular disease development. ANRIL rs4977574 gene polymorphism could also be associated with recurrent pregnancy loss (RPL) since there is increasing evidence in favor of a potential shared pathophysiological mechanism with cardiovascular disease, potentially through arterial thrombosis. This study's goal is to investigate the differences in ANRIL rs4977574 gene polymorphism between women with and without RPL, if any, as well as a potential association with the number of pregnancy losses. METHODS: DNA was isolated from peripheral blood samples, and the sequence containing the polymorphism of interest was amplified with PCR. Results were visualized under UV light following electrophoresis in 3% agarose gel with ethidium bromide. ANRIL rs4977574 (A>G) prevalence was compared between 56 women with and 69 without RPL. Results were adjusted for women's age and BMI, while a stratified analysis was performed according to number of pregnancy losses. RESULTS: Allele A was significantly more prevalent in the control group compared to RPL women [31 (44.9%) vs. 14 (25%), p = 0.021]. Although not reaching statistical significance, a gradually decreasing prevalence of allele A with an increasing number of pregnancy losses was observed [31 (44.9%) in control, eight (30.7%) with two, six (23.1%) with three, and 0 (0.0%) with four pregnancy losses, p = 0.078]. Results were also similar following adjustment. CONCLUSIONS: This is the first study that demonstrates an association between RPL presence and ANRIL rs4977574 gene polymorphism (lower prevalence of allele A), while a difference according to the number of pregnancy losses cannot be excluded.

The impact of cryopreserved sperm on intrauterine insemination outcomes: is frozen as good as fresh?

Introduction: Frozen sperm utilization might negatively impact cycle outcomes in animals, implicating cryopreservation-induced sperm damage. However, in vitro fertilization and intrauterine insemination (IUI) in human studies are inconclusive. Methods: This study is a retrospective review of 5,335 IUI [± ovarian stimulation (OS)] cycles from a large academic fertility center. Cycles were stratified based on the utilization of frozen (FROZEN, n = 1,871) instead of fresh ejaculated sperm (FRESH, n = 3,464). Main outcomes included human chorionic gonadotropin (HCG) positivity, clinical pregnancy (CP), and spontaneous abortion (SAB) rates. Secondary outcome was live birth (LB) rate. Odds ratios (OR) for all outcomes were calculated utilizing logistic regression and adjusted (adjOR) for maternal age, day-3 FSH, and OS regimen. Stratified analysis was performed based on OS subtype [gonadotropins; oral medications (OM): clomiphene citrate and letrozole; and unstimulated/natural]. Time to pregnancy and cumulative pregnancy rates were also calculated. Further subanalyses were performed limited to either the first cycle only or to the partner's sperm only, after excluding female factor infertility, and after stratification by female age (<30, 30-35, and >35 years old). Results: Overall, HCG positivity and CP were lower in the FROZEN compared to the FRESH group (12.2% vs. 15.6%, p < 0.001; 9.4% vs. 13.0%, p < 0.001, respectively), which persisted only among OM cycles after stratification (9.9% vs. 14.2% HCG positivity, p = 0.030; 8.1% vs. 11.8% CP, p = 0.041). Among all cycles, adjOR (95% CI) for HCG positivity and CP were 0.75 (0.56-1.02) and 0.77 (0.57-1.03), respectively, ref: FRESH. In OM cycles, adjOR (95% CI) for HCG positivity [0.55 (0.30-0.99)] and CP [0.49 (0.25-0.95), ref.: FRESH] favored the FRESH group but showed no differences among gonadotropin and natural cycles. SAB odds did not differ between groups among OM and natural cycles but were lower in the FROZEN group among gonadotropin cycles [adjOR (95% CI): 0.13 (0.02-0.98), ref.: FRESH]. There were no differences in CP and SAB in the performed subanalyses (limited to first cycles or partner's sperm only, after excluding female factors, or after stratification according to female age). Nevertheless, time to conception was slightly longer in the FROZEN compared to the FRESH group (3.84 vs. 2.58 cycles, p < 0.001). No significant differences were present in LB and cumulative pregnancy results, other than in the subgroup of natural cycles, where higher LB odds [adjOR (95% CI): 1.08 (1.05-1.12)] and higher cumulative pregnancy rate (34% vs. 15%, p = 0.002) were noted in the FROZEN compared to the FRESH group. Conclusion: Overall, clinical outcomes did not differ significantly between frozen and fresh sperm IUI cycles, although specific subgroups might benefit from fresh sperm utilization.

Artificial intelligence for sperm selection-a systematic review.

Despite the increasing number of assisted reproductive technologies based treatments being performed worldwide, there has been little improvement in fertilization and pregnancy outcomes. Male infertility is a major contributing factor, and sperm evaluation is a crucial step in diagnosis and treatment. However, embryologists face the daunting task of selecting a single sperm from millions in a sample based on various parameters, which can be time-consuming, subjective, and may even cause damage to the sperm, deeming them unusable for fertility treatments. Artificial intelligence algorithms have revolutionized the field of medicine, particularly in image processing, because of their discerning abilities, efficacy, and reproducibility. Artificial intelligence algorithms have the potential to address the challenges of sperm selection with their large-data processing capabilities and high objectivity. These algorithms could provide valuable assistance to embryologists in sperm analysis and selection. Furthermore, these algorithms could continue to improve over time as larger and more robust datasets become available for their training.

The impact of different sperm preparation methods on clinical pregnancy and live birth rates in intrauterine insemination cycles: a retrospective single-center cohort study.

OBJECTIVE: To assess the impact of 2 different sperm preparation methods, density gradient centrifugation and simple wash, on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles with and without ovulation induction. DESIGN: Retrospective single-center cohort study. SETTING: Academic fertility center. PATIENTS: In total, 1,503 women of all diagnoses sought IUI with fresh-ejaculated sperm. EXPOSURE: Cycles were divided into 2 groups on the basis of sperm preparation technique: density gradient centrifugation (n = 1,687, unexposed group) and simple wash (n = 1,691, exposed group). MAIN OUTCOME MEASURES: Primary outcome measures consisted of clinical pregnancy and live birth rates. Furthermore, adjusted odds ratios and 95% confidence intervals for each outcome were calculated and compared between the 2 sperm preparation groups. RESULTS: Odds ratios did not differ between density gradient centrifugation and simple wash groups for clinical pregnancy and live birth (1.10 [0.67-1.83] and 1.08 [0.85-1.37], respectively). Additionally, when cycles were stratified using ovulation induction rather than adjusted for, no differences in clinical pregnancy and live birth odds were noted between sperm preparation groups (gonadotropins: 0.93 [0.49-1.77] and 1.03 [0.75-1.41]; oral agents: 1.78 [0.68-4.61] and 1.05 [0.72-1.53]; unassisted: 0.08 [0.001-6.84] and 2.52 [0.63-10.00], respectively). Furthermore, no difference was seen in clinical pregnancy or live birth when cycles were stratified using sperm score or when the analysis was limited to first cycles only. CONCLUSION: Overall, no difference was noted in clinical pregnancy or live birth rates between patients who received simple wash vs. density gradient-prepared sperm, suggesting similar clinical efficacy between the 2 techniques for IUI. Because the simple wash technique is more time-efficient and cost-effective compared with the density gradient, adoption of this technique could lead to comparable clinical pregnancy and live birth rates for IUI cycles, although optimizing teamwork flow and coordination of care.

The use of voting ensembles to improve the accuracy of deep neural networks as a non-invasive method to predict embryo ploidy status.

PURPOSE: To determine if creating voting ensembles combining convolutional neural networks (CNN), support vector machine (SVM), and multi-layer neural networks (NN) alongside clinical parameters improves the accuracy of artificial intelligence (AI) as a non-invasive method for predicting aneuploidy. METHODS: A cohort of 699 day 5 PGT-A tested blastocysts was used to train, validate, and test a CNN to classify embryos as euploid/aneuploid. All embryos were analyzed using a modified FAST-SeqS next-generation sequencing method. Patient characteristics such as maternal age, AMH level, paternal sperm quality, and total number of normally fertilized (2PN) embryos were processed using SVM and NN. To improve model performance, we created voting ensembles using CNN, SVM, and NN to combine our imaging data with clinical parameter variations. Statistical significance was evaluated with a one-sample t-test with 2 degrees of freedom. RESULTS: When assessing blastocyst images alone, the CNN test accuracy was 61.2% (± 1.32% SEM, n = 3 models) in correctly classifying euploid/aneuploid embryos (n = 140 embryos). When the best CNN model was assessed as a voting ensemble, the test accuracy improved to 65.0% (AMH; p = 0.1), 66.4% (maternal age; p = 0.06), 65.7% (maternal age, AMH; p = 0.08), 66.4% (maternal age, AMH, number of 2PNs; p = 0.06), and 71.4% (maternal age, AMH, number of 2PNs, sperm quality; p = 0.02) (n = 140 embryos). CONCLUSIONS: By combining CNNs with patient characteristics, voting ensembles can be created to improve the accuracy of classifying embryos as euploid/aneuploid from CNN alone, allowing for AI to serve as a potential non-invasive method to aid in karyotype screening and selection of embryos.

Quality assurance (QA) for monitoring the performance of assisted reproductive technology (ART) staff using artificial intelligence (AI).

PURPOSE: Deep learning neural networks have been used to predict the developmental fate and implantation potential of embryos with high accuracy. Such networks have been used as an assistive quality assurance (QA) tool to identify perturbations in the embryo culture environment which may impact clinical outcomes. The present study aimed to evaluate the utility of an AI-QA tool to consistently monitor ART staff performance (MD and embryologist) in embryo transfer (ET), embryo vitrification (EV), embryo warming (EW), and trophectoderm biopsy (TBx). METHODS: Pregnancy outcomes from groups of 20 consecutive elective single day 5 blastocyst transfers were evaluated for the following procedures: MD performed ET (N = 160 transfers), embryologist performed ET (N = 160 transfers), embryologist performed EV (N = 160 vitrification procedures), embryologist performed EW (N = 160 warming procedures), and embryologist performed TBx (N = 120 biopsies). AI-generated implantation probabilities for the same embryo cohorts were estimated, as were mean AI-predicted and actual implantation rates for each provider and compared using Wilcoxon singed-rank test. RESULTS: Actual implantation rates following ET performed by one MD provider: "H" was significantly lower than AI-predicted (20% vs. 61%, p = 0.001). Similar results were observed for one embryologist, "H" (30% vs. 60%, p = 0.011). Embryos thawed by embryologist "H" had lower implantation rates compared to AI prediction (25% vs. 60%, p = 0.004). There were no significant differences between actual and AI-predicted implantation rates for EV, TBx, or for the rest of the clinical staff performing ET or EW. CONCLUSIONS: AI-based QA tools could provide accurate, reproducible, and efficient staff performance monitoring in an ART practice.

Economic analysis of open versus laparoscopic versus robotic hepatectomy: a systematic review and meta-analysis.

BACKGROUND: Following the publication of reports from landmark international consensuses (Louisville 2008 and Morioka 2014), minimally invasive hepatectomy became widely accepted as a legitimate alternative to open surgery. We aimed to compare the operative, hospitalization, and total economic costs of open (OLR) vs. laparoscopic (LLR) vs. robotic liver resection (RLR). METHODS: We performed a systematic literature review (end-of-search date: July 3, 2020) according to the PRISMA statement. Random-effects meta-analyses were conducted. Quality assessment was performed with the Cochrane Risk of Bias tool for randomized controlled trials, and the Newcastle-Ottawa Scale for non-randomized studies. RESULTS: Thirty-eight studies reporting on 3847 patients (1783 OLR; 1674 LLR; 390 RLR) were included. The operative costs of LLR were significantly higher than those of OLR, while subgroup analysis also showed higher operative costs in the LLR group for major hepatectomy, but no statistically significant difference for minor hepatectomy. Hospitalization costs were significantly lower in the LLR group, with subgroup analyses indicating lower costs for LLR in both major and minor hepatectomy series. No statistically significant difference was observed regarding total costs between LLR and OLR both overall and on subgroup analyses in either major or minor hepatectomy series. Meta-analyses showed higher operative, hospitalization, and total costs for RLR vs. LLR, but no statistically significant difference regarding total costs for RLR vs. OLR. CONCLUSION: LLR's higher operative costs are offset by lower hospitalization costs compared to OLR leading to no statistically significant difference in total costs, while RLR appears to be a more expensive alternative approach.