No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception? SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study. WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions. STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia). PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders. MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer. LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables. WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation. STUDY FUNDING/COMPETING INTEREST(S): The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare. TRIAL REGISTRATION NUMBER: N/A.

Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index.

BACKGROUND: Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). METHODS: Women with PCOS (n = 30) and controls (n = 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case-control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Asberg Depression Rating Scale (MADRS-S). RESULTS: Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1-24 versus 5.0, 0-28, P < 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0-5 versus 0, 0-2, P < 0.001), worry (1.5, 0-4 versus 0, 0-6, P = 0.004), phobias (1, 0-4 versus 0, 0-3, P < 0.001), and pain (1, 0-3 versus 0, 0-2, P < 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0-27 versus 5.5, 0-24, P = 0.053). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls. CONCLUSIONS: Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group.

Gelatinases and their tissue inhibitors during human ovulation: increased expression of tissue inhibitor of matrix metalloproteinase-1.

Remodelling of the extracellular matrix (ECM) of the follicular wall by matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) has been suggested to be crucial in ovulation. To investigate the expression of the gelatinases, MMP-2 and MMP-9, together with their inhibitors, TIMP-2 and TIMP-1, in the perifollicular ovarian stroma from women just before and during ovulation, we obtained biopsies of the stroma adjacent to the leading follicle. Laparoscopic surgery was performed either before the LH peak or at any of three intervals after ovulation triggering by hCG. Immunoblotting, immunohistochemistry and quantitative RT-PCR were performed. All four proteins were expressed by immunoblots, with no detectable changes in the expression of MMP-2, MMP-9 and TIMP-2. Scattered immunostaining for MMP-9 and TIMP-2 was seen, and MMP-2 was demonstrated in a concentric layer. A significant increase in TIMP-1 protein and mRNA was seen during the three ovulatory phases, and a strong and patchy immunostaining for TIMP-1 was shown. This is the first study that has demonstrated an ovulation-associated expression of these ECM-remodelling enzymes around the human follicle at ovulation. The increased expression of TIMP-1 may reflect a specific temporal inhibition of collagenolysis and thereby a time-dependent regulation of ECM breakdown in areas surrounding the apex of the follicle.

Collagens in the human ovary and their changes in the perifollicular stroma during ovulation.

BACKGROUND: Remodeling of the collagens around the follicle is a major event in ovulation. The aim of the present study was to investigate the distribution of collagen I, III, and IV in the human ovary. METHODS: Biopsies of the perifollicular stroma were obtained at sterilization during the preovulatory phase (follicle size >14 mm) or at any of three intervals (12-18 h after human chorionic gonadotrophin: early ovulatory phase; >18-24 h: late ovulatory phase; 44-77 h: postovulatory phase) after human chorionic gonadotrophin. Excised dominant follicles and whole ovarian sections were also obtained. Immunohistochemistry using antibodies against collagen I, III, IV, vimentin, and CD 45 was performed. RESULTS AND CONCLUSIONS: Collagens I and III were distributed in concentric layers in the capsular stroma with bundles of collagens connecting these layers to form a mesh. Collagen I was present in larger quantities in the outer layers and collagen III showed the inverse distribution. In the theca, collagen I was present in the externa and collagen III in the entire layer. The staining intensity of collagens I and III in the perifollicular stroma decreased from the preovulatory stage. Collagen IV was present in the basal lamina separating granulosa and theca cells. This study shows that collagen I and III are abundant in and around the ovulating human follicle with typical patterns of distribution. Collagen IV is present in the basal membrane that separates the granulosa from the theca cells. Taking into account the abundance of collagens in the follicular wall and their specific localization, major site-directed degradation of collagens seems to be necessary for follicular rupture to occur.

Increased urinary polyamine excretion in unselected cancer patients related to host factors.

Unselected patients with solid malignant tumours were investigated in order to determine whether they displayed elevated urinary excretion of polyamines; and if so, whether polyamine excretion in such patients predicts disease progression, or is secondary to host and systemic factors. Thirty-eight male and female patients with generalized solid, mainly gastrointestinal, malignant tumours were investigated. Ten male patients operated on for infrarenal aortic aneurysms and 15 otherwise healthy male and female patients hospitalized for minor surgical procedures served as reference patients, representing individuals with and without metabolic stress. Urine samples were collected from all patients during 24 h for measurement of both total and individual excretion of polyamines during three consecutive days. Polyamine excretion was not significantly increased in cancer patients when compared by analysis of variance among the three patient groups. However, polyamine excretion was significantly elevated in both cancer and stressed, non-cancer patients compared with patients without stress (p < 0.05). A multivariate analysis indicated that plasma protein and albumin concentrations, abnormal liver function tests and liver metastasis predicted variation in polyamine excretion in cancer patients (p < 0.01), but this was unrelated to survival. Our results demonstrate that increased polyamine excretion in cancer patients is related more to host factors than to tumour growth itself.