Using Unlabeled Information of Embryo Siblings from the Same Cohort Cycle to Enhance In Vitro Fertilization Implantation Prediction.

High-content time-lapse embryo imaging assessed by machine learning is revolutionizing the field of in vitro fertilization (IVF). However, the vast majority of IVF embryos are not transferred to the uterus, and these masses of embryos with unknown implantation outcomes are ignored in current efforts that aim to predict implantation. Here, whether, and to what extent the information encoded within "sibling" embryos from the same IVF cohort contributes to the performance of machine learning-based implantation prediction is explored. First, it is shown that the implantation outcome is correlated with attributes derived from the cohort siblings. Second, it is demonstrated that this unlabeled data boosts implantation prediction performance. Third, the cohort properties driving embryo prediction, especially those that rescued erroneous predictions, are characterized. The results suggest that predictive models for embryo implantation can benefit from the overlooked, widely available unlabeled data of sibling embryos by reducing the inherent noise of the individual transferred embryo.

Assuring quality in assisted reproduction laboratories: assessing the performance of ART Compass - a digital art staff management platform.

PURPOSE: Staff management is the most cited ART/IVF laboratory inspection deficiency. Small ART/IVF clinics may be challenged to perform these activities by low staff volume; similarly, large ART/IVF networks may be challenged by high staff volume and large datasets. Here, we sought to investigate the performance of an automated, digital platform solution to manage this necessary task. METHODS: The ART Compass (ARTC) digital staff management platform was used to assess the clinical decision-making of ART laboratory staff. The survey modules presented standardized instructions to technologists and measured inter- and intra-technologist variability for subjective "clinical decision-making" type questions. Internal and external comparisons were achieved by providing technologists two answers: (1) a comparison to their own lab director and (2) to the most popular response collectively provided by all lab director level accounts. The platform is hosted on HIPAA compliant Amazon web servers, accessible via web browser and mobile applications for iOS (Apple) and Android mobile devices. RESULTS: Here, we investigated the performance of a digital staff management platform for single embryologist IVF practices and for three IVF lab networks (sites A, B, C) from 2020 to 2022. Embryology dish preparation survey results show variance among respondents in the following: PPE use, media volume, timing of oil overlay, and timing of moving prepared dishes to incubators. Surveying the perceived Gardner score and terms in use for early blastocysts reveals a lack of standardization of terminology and fair to poor agreement. We observed moderate inter-technologist agreement for ICM and TE grade (0.47 and 0.52, respectively). Lastly, the clinical decision of choice to freeze or discard an embryo revealed that agreement to freeze was highest for the top-quality embryos, and that some embryos can be highly contested, evenly split between choice to freeze or discard. CONCLUSIONS: We conclude that a digital platform is a novel and effective tool to automate, routinely monitor, and assure quality for staff-related parameters in ART and IVF laboratories. Use of a digital platform can increase regulatory compliance and provide actionable insight for quality assurance in both single embryologist practices and for large networks. Furthermore, clinical decision-making can be augmented with artificial intelligence integration.

Why do women choose to undergo oocyte aspiration without sedation or analgesia?

OBJECTIVE: Oocyte pick-up (OPU) is a painful but essential part of in-vitro fertilization (IVF) that is usually performed under sedation and analgesia (SaA). Our aim was to study that why some women decide to undergo OPU without SaA? METHODS: This was a prospective study using patient questionnaires and the standardized 7-item generalized anxiety disorder (GAD-7) score. The patients were asked to assess the pain experienced during OPU using a visual analog scale (VAS). The study sample was a convenience sample of 100 healthy women undergoing OPU at our unit with or without SaA. RESULTS: Women who chose to undergo OPU without SaA were significantly more likely to express the fear of anesthesia. A high pain score (VAS ≥ 6) was reported by significantly more patients who underwent OPU without SaA than with SaA. Yet, 98% of the patients who underwent OPU without SaA stated that in future IVF cycles, they would still choose to undergo OPU without SaA. More patients had high anxiety scores among those who underwent OPU with than without SaA. CONCLUSIONS: Women who chose to undergo OPU without SaA reported more often fear of anesthesia. Although these women experienced significantly more pain during OPU, almost all of them suggested that they would still choose to undergo OPU without SaA. Increased anxiety, as expressed by higher GAD-7 scores, was not associated with a tendency to choose SaA during OPU. The option of OPU without SaA seems to be an acceptable option for selected women. LAY SUMMARY: Egg retrieval from the ovaries is a painful part of in vitro fertilization (IVF). It is, therefore, usually performed under sedation and pain relief (analgesia). The aim of this study was to investigate: Why some women decide to undergo egg retrieval without sedation? We prospectively studied 100 women using patient questionnaires and standardized scores in order to measure patient's pain and anxiety levels. We found that women who chose to undergo egg retrieval without sedation were significantly more likely to express fear of anesthesia. As expected, women who decided to forgo sedation experienced more pain during egg retrieval, yet, 98% of them decided that in future IVF cycles, they would still choose to undergo egg retrieval without sedation. Surprisingly, women who had high anxiety scores were not more likely to ask for sedation during egg retrieval. The option to undergo egg retrieval without sedation during IVF seems to be acceptable for some women.

Expression of Concern to: Fetal Safety of Dydrogesterone Exposure in the First Trimester of Pregnancy.

The Editor-in-Chief of Clinical Drug Investigation has become aware that the original article contains a number of errors and inconsistencies.

Assisted reproductive technology and the risk of pediatric cancer: A population based study and a systematic review and meta analysis.

BACKGROUND: There is controversy whether exposure to assisted reproductive technology (ART) is associated with increased risk of pediatric cancer. We aimed at calculating the overall risk of pediatric cancers after ART in a large cohort of exposed women; and to conduct a systematic review and meta- analysis of cohort studies examining overall risk of pediatric cancers after ART. METHODS: All children born in Israel who were members of Maccabi Health Services (MHS) between 1999 and 2016 after ART, were linked to the Israeli Registry of Childhood Cancer (IGS) to identify those with cancer diagnosed before 16 years of age. In parallel we conducted a systematic review and meta-analysis of observational cohort studies with more than 5000 ART- exposed cases that measured pediatric cancer after ART. RESULTS: In the cohort study, the risk ratio for pediatric cancer after ART in general was 0.95 (95% CI, 0.76-1.19). The RR was 1.09 (95% CI, 0.79-1.48) for IVF treatments. Meta- analysis of 13 cohort studies with a total of 750,138 women exposed to ART (with 1152 pediatric cancers) and 214,008,000 unexposed controls (with 30,458 pediatric cancers) did not reveal increased risk for pediatric cancers (RR 0.99; 95% CI, 0.85-1.15). CONCLUSIONS: Based on very large numbers, ART in general, and IVF in particular, are not associated with overall increased risk of pediatric cancer.

Significant increase in serum hCG levels following methotrexate therapy is associated with lower treatment success rates in ectopic pregnancy patients.

OBJECTIVE: To determine the association between early increase in the serum hCG levels (days 0-4) and treatment success rates following methotrexate therapy in ectopic pregnancy patients. STUDY DESIGN: A level II-2 case-control study of involving 140 patients treated with methotrexate for ectopic pregnancy at the gynecology department in a tertiary care hospital. RESULTS: A logistic regression model for the "failure of treatment" was fitted with serum hCG levels change between day 0 and day 4, patient age, pregnancy age at day-0, and day-0 ß-hCG level as predictors. The logistic regression analysis indicated that having more than 50% increase in the ß-hCG levels between days 0 and 4 significantly (P = 0.011) increases the risk of MTX treatment failure. CONCLUSION: The results of this study indicate that >50% increase in ß-hCG levels between days 0 and 4 significantly increases the risk of methotrexate treatment failure. This novel information could assist patients and physicians in making decisions regarding ectopic pregnancy treatment.

HPV16 E6 augments Wnt signaling in an E6AP-dependent manner.

In this study we investigated the effect of HPV16 E6 on the Wnt/beta-catenin oncogenic signaling pathway. Luciferase reporter assays indicated that ectopically expressed E6 significantly augmented the Wnt/beta-catenin/TCF-dependent signaling response in a dose-dependent manner. This activity was independent of the ability of E6 to target p53 for degradation or bind to the PDZ-containing E6 targets. Epistasis experiments suggested that the stimulatory effect is independent of GSK3beta or APC. Coexpression, half-life determination, cell fractionation and immunofluorescence analyses indicated that E6 did not alter the expression levels, stability or cellular distribution of beta-catenin. Further experiments using E6 mutants defective for E6AP binding and E6AP knockdown cells indicated the absolute requirement of the ubiquitin ligase E6AP for enhancement of the Wnt signal by E6. Thus, this study suggests a role for the E6/E6AP complex in augmentation of the Wnt signaling pathway which may contribute to HPV induced carcinogenesis.