Pseudo contrastive labeling for predicting IVF embryo developmental potential.

In vitro fertilization is typically associated with high failure rates per transfer, leading to an acute need for the identification of embryos with high developmental potential. Current methods are tailored to specific times after fertilization, often require expert inspection, and have low predictive power. Automatic methods are challenged by ambiguous labels, clinical heterogeneity, and the inability to utilize multiple developmental points. In this work, we propose a novel method that trains a classifier conditioned on the time since fertilization. This classifier is then integrated over time and its output is used to assign soft labels to pairs of samples. The classifier obtained by training on these soft labels presents a significant improvement in accuracy, even as early as 30 h post-fertilization. By integrating the classification scores, the predictive power is further improved. Our results are superior to previously reported methods, including the commercial KIDScore-D3 system, and a group of eight senior professionals, in classifying multiple groups of favorable embryos into groups defined as less favorable based on implantation outcomes, expert decisions based on developmental trajectories, and/or genetic tests.

Is the aging human ovary still ticking?: Expression of clock-genes in luteinized granulosa cells of young and older women.

BACKGROUND: It has been shown - mostly in animal models - that circadian clock genes are expressed in granulosa cells and in corpora luteum and might be essential for the ovulatory process and steroidogenesis. OBJECTIVE: We sought to investigate which circadian clock genes exist in human granulosa cells and whether their expression and activity decrease during aging of the ovary. STUDY DESIGN: Human luteinized granulosa cells were isolated from young (age 18-33) and older (age 39-45) patients who underwent in-vitro fertilization treatment. Levels of clock genes expression were measured in these cells 36 h after human chorionic gonadotropin stimulation. METHODS: Human luteinized granulosa cells were isolated from follicular fluid during oocyte retrieval. The mRNA expression levels of the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2 were analyzed by quantitative polymerase chain reaction. RESULTS: We found that the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2, are expressed in cultured human luteinized granulosa cells. Among these genes, there was a general trend of decreased expression in cells from older women but it reached statistical significance only for PER1 and CLOCK genes (fold change of 0.27 ± 0.14; p = 0.03 and 0.29 ± 0.16; p = 0.05, respectively). CONCLUSIONS: This preliminary report indicates that molecular circadian clock genes exist in human luteinized granulosa cells. There is a decreased expression of some of these genes in older women. This decline may partially explain the decreased fertility and steroidogenesis of reproductive aging.

Maternal morbidity following routine second trimester genetic amniocentesis.

Two cases of septic complications of routine second trimester amniocentesis are presented. The first case is a 37-year-old gravida suffering from ulcerative colitis who was admitted for amniocentesis in the 18th week of her third pregnancy. An uncomplicated transabdominal amniocentesis was performed using a sterile technique and ultrasound guidance. Twenty-eight hours later the patient had a septic abortion and sepsis. The second case is a 34-year-old gravida in the 24th week of her pregnancy who was admitted with amnionitis 10 h after an uncomplicated amniocentesis, and subsequently had a septic abortion. A high index of suspicion and rapid intervention were crucial in both cases.

Quality of life before and after laparoscopic Heller myotomy for achalasia.

BACKGROUND: Because the surgical treatment of achalasia is directed at the palliation of chronic symptoms, it is important to assess how surgery affects patients' health-related quality of life (HRQL). METHODS: We evaluated upper gastrointestinal symptoms, satisfaction, and HRQL in 19 patients with achalasia before and after undergoing a laparoscopic Heller myotomy and partial fundoplication. HRQL was assessed using the Medical Outcomes Study 36-item short form health survey (SF-36). RESULTS: The mean age of the patients was 40 years (range 16 to 74), and 58% were men. After a median follow-up of 21 months (range 2 to 35), 12 of 16 patients were satisfied with the results of their surgery. Liquid and solid dysphagia scores were improved after surgery, and the prevalence of heartburn symptoms did not change. Although all the health concepts measured by the SF-36 instrument showed some improvement, statistically significant increases (on a 0 to 100 scale) were detected in physical functioning (11.1, P = 0.02), role-physical (25.0, P = 0.05), bodily pain (12.2, P = 0.01), vitality (13.7, P = 0.02), and social functioning (18.4, P = 0.02). CONCLUSIONS: Most aspects of HRQL improve after a laparoscopic Heller myotomy and partial fundoplication for achalasia.

Tumor-preventive effects of the soluble p53 antigen on chemically-induced skin cancer in mice.

BACKGROUND: The tumor-suppressive effects of the rat soluble p53 antigen on chemically induced skin cancer in mice and the role of the spleen in the immune response to a carcinogen and vaccination were studied. METHODS: Skin cancer was induced by 9,10-dimethyl-1,2-benzanthracene (DMBA). Vaccination was initiated by injection of liposomes with the soluble p53 antigen (10-12 micrograms/mouse) while boosters were with the p53 mixed with Freund's incomplete adjuvant (two injections). Four months later, the spleen and tumors were removed and examined morphometrically (determination of areas of different spleen's zones) and immunohistochemically (determination of number of B lymphocytes and macrophages, apoptotic index). The following groups of mice were studied: A) control non treated mice; Bl) tumor-free mice treated with a carcinogen; B2) tumor-bearing mice; Cl) tumor-free vaccinated mice exposed to a carcinogen; C2) tumor-bearing vaccinated mice. RESULTS: Mice exposed to a carcinogen, which were tumor-free, displayed high proliferative activity of the spleenic lymphoid constitutes such as B lymphocytes and macrophages. This was reflected in the remarkable transformation of B lymphocytes in lymphoblasts (blast transformation) and an increase in the area of germinal centers, compared to untreated controls. In tumor-bearing non vaccinated mice, significantly more spleenic apoptotic cells were found than in their tumor-free counterparts. Shrinkage of the mantle layer and a decrease in cellular density of follicles were seen in all carcinogen-treated mice, reflecting the reduced total production of lymphoid cells, and thus the insufficiency of the immune reaction of animals to a carcinogen. A sharp decrease in the apoptotic index in the spleen of tumor-free mice may reflect an inhibition of apoptotic activity of the spleen by a carcinogen. Vaccination with the soluble p53 protein decreased the incidence of tumors and their size, significantly increased the apoptotic index within tumors, and reversed the splenic parameters of immune insufficiency. CONCLUSIONS: The immune system is active during tumorigenesis. Vaccination with the soluble p53 antigen had positive tumor-suppressive effects. The findings may facilitate the development of vaccines for the prevention of recurrent cancers in humans.