Predicting the need for blood transfusion requirement in postpartum hemorrhage.

OBJECTIVE: We aimed to assess the role of lactate and hemoglobin levels as predictors for the need for blood transfusion in post-partum hemorrhage (PPH). METHODS: A retrospective cohort study of women with PPH in a single university-affiliated tertiary medical center between August 2018 and June 2020. PPH was defined as an estimated excessive blood loss (of more than 500 ml following vaginal delivery and 1000 ml following a cesarean delivery) requiring at least one uterotonic drug and fluid resuscitation. Women were stratified by the need of requiring blood transfusion due to hemorrhage. The criteria for blood transfusion were: (1) clinically severe uncontrollable ongoing hemorrhage; (2) symptomatic anemia (maternal tachycardia >110 beats per minute, dizziness, syncope or presyncope) in the presence of Hb 7-8 g/dL; or (3) postpartum Hb level < 7 g/dL regardless of maternal symptoms or signs of anemia. Demographic, labor characteristics as well as laboratory data were collected. For all women the Shock Index (SI: heart rate divided by systolic blood pressure) was calculated. Women without available data on immediate (more than 15 min from the bleeding initiation) hemoglobin (Hb) level and lactate concentrations were excluded. RESULTS: Overall, out of 22,241 deliveries during the study, 94 women were included, of them 26 (23.4%) required blood transfusion. The antepartum Hb level was lower in the transfused group (11.7 ± vs 12.4 ± 1.0 re/dL, p = .01). No significant differences were found in demographic and labor characteristics. In multivariate logistic regression analysis, a lower immediate postpartum Hb and a higher SI higher were associated with blood transfusion requirement (adjusted odds ratio (aOR) 3.45 [CI] 1.82-7.69, p < .001] and aOR 1.25 [CI 1.03-1.55, p = .03], respectively). The combination of SI, immediate postpartum Hb and lactate concentration provided the best integration, with an area under the curve of 0.86, sensitivity 92.65%, specificity 61.54%, positive and negative predictive values of 86.3% and 76.2%, respectively. CONCLUSION: The combination of SI, immediate postpartum Hb and lactate levels is a good predictor for the need of blood requirement in PPH.

PAR1&2 driven placenta EVT invasion act via LRP5/6 as coreceptors.

While the involvement of protease-activated receptors (PARs) in the physiological regulation of human placenta development, as in tumor biology, is recognized, the molecular pathway is unknown. We evaluated the impact of PAR1 and PAR2 function in cytotrophoblast (CTB) proliferation and invasion in a system of extravillous trophoblast (EVT) organ culture and in human cell-lines. Activation of PAR1 - and PAR2 -induced EVT invasion and proliferation, while the shRNA silencing of low-density lipoprotein receptor-related protein 5/6 (LRP5/6) inhibited these processes. PAR1 and PAR2 effectively induce ß-catenin stabilization in a manner similar to that shown for the canonical ß-catenin stabilization pathway yet independent of Wnts. Immunoprecipitation analyses and protein-protein docking demonstrated the co-association between either PAR1 or PAR2 with LRP5/6 forming an axis of PAR-LRP5/6-Axin. Noticeably, in PAR1 -PAR2 heterodimers a dominant role is assigned to PAR2 over PAR1 as shown by inhibition of PAR1 -induced ß-catenin levels, and Dvl nuclear localization. This inhibition takes place either by shRNA silenced hPar2 or in the presence of a TrPAR2 devoid its cytoplasmic tail. Indeed, TrPAR2 cannot form the PAR1 -PAR2 complex, obstructing thereby the flow of signals downstream. Elucidation of the mechanism of PAR-induced invasion contributes to therapeutic options highlighting key partners in the process.

Comparison of pregnancy outcome between immigrant women in couples with same ethnicity to mixed ethnicity couples.

Aim: To compare the pregnancy outcome of immigrant women who became pregnant to the same ethnicity partner versus a partner from a different ethnicity.Methods: A retrospective cohort study on all singleton pregnancies of immigrant women who delivered between the years 2011-2015 in a single tertiary University Affiliated Hospital. Demographic and obstetrical data were collected. Same ethnicity couples and mixed couples were compared using the Pearson chi-square test for dichotomous variables, and Student's T-test for normally distributed continuous variables.Results: Overall, 443 immigrant women delivered during the study period, of them, 294 (66.37%) had the same ethnicity spouse and 149 (33.63%) were part of a mixed couple. Women of same ethnicity couples were significantly younger (32.7 versus 35.05 years, p < .0001) and more likely to be nulliparous (48 versus 32%, p = .001), compared to women of mixed couples. The rate of episiotomy was significantly higher among women with the same ethnicity spouse in comparison to women of mixed couples (37.22 versus 23.85%, p = .01). There was no significant difference in all other obstetrical or perinatal outcomes tested.Conclusions: Maternal component is the main factor for perinatal outcomes among immigrant mothers.

Morphokinetic characteristics of embryos originating from extremely small follicles: A prospective study.

OBJECTIVE: To investigate the developmental potential of oocytes and embryos derived from extremely small follicles (<10 mm) in comparison to those originated in larger follicles. STUDY DESIGN: A prospective study, undertaken in a university affiliated single center tertiary hospital. The study included 98 patients undergoing infertility treatments. On the day of ovum pickup (OPU) follicles were counted and measured. Aspiration of follicles larger and smaller than 10 mm was undertaken separately and the development of embryos originating from oocytes from these follicles was followed up using different wells for each embryo. There was no low limit of size for aspiration. Each oocyte retrieved was marked for its origin and numbered for further follow up. We recorded: Oocytes retrieved, maturation stage, fertilization rate, cleavage rate, morphokinetic parameters, embryo transfers, embryo freezing, oocyte freezing and biopsy rate for preimplantation genetic diagnosis (PGD). Quality was evaluated by the morphokinetic parameters of the embryos developed using time-lapse imaging technology. Day 3 KIDScore was calculated to all embryos. RESULTS: Small follicles compared to large follicles displayed lower recovery rate (45% vs. 74%, P < 0.0001), fewer matured oocytes (37.5% vs. 61.7%, P < 0.0001), higher rates of GV oocytes (20.7% vs., 3.7%, P < 0.0001), and lower fertilization rate (43.7% vs. 63.3%, P < 0.0001. However, morphokinetic variables were similar between embryos that originated from either small or large follicles. Median KIDscores were identical for embryos from small or large follicle origin. CONCLUSIONS: Embryos originated from small follicles were not different than embryos from larger follicles, as assessed by morphokinetic parameters in time lapse system. In view of our findings, physicians should bear in mind that small follicle aspiration might yield good quality embryos.

The ovarian response in fragile X patients and premutation carriers undergoing IVF-PGD: reappraisal.

STUDY QUESTION: What is the association between the ovarian response and the number of CGG repeats among full mutation and premutation carriers of fragile X (FMR1), undergoing controlled ovarian hyperstimulation (COH) for PGD? SUMMARY ANSWER: Ovarian response was normal in full mutation patients but decreased in premutation carriers, although the number of repeats was not statistically significantly associated with the number of oocytes retrieved. WHAT IS KNOWN ALREADY: There is inconsistent data in the literature regarding ovarian response in FMR1 carriers. Studies exploring the ovarian response of full mutation patients are lacking. STUDY DESIGN, SIZE, DURATION: Retrospective study, a university affiliated tertiary hospital, IVF unit, PGD referral center. PARTICIPANTS/MATERIALS, SETTING, METHODS: We examined the medical records of all women undergoing fresh IVF-PGD cycles due to fragile X. Data recorded included demography, duration of stimulation, amount of gonadotropins administered, number of dominant follicles, maximal E2 levels and number of oocytes retrieved. Data were analyzed using univariate and multivariate mixed models. P-values <0.05 were considered significant. Data were collected from the medical records of 21 patients with a full mutation on the FMR1 gene and 51 premutation carriers. Overall 309 fresh cycles were analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: Premutation carriers displayed reduced ovarian response, as demonstrated by fewer oocytes retrieved. In contrast, full mutation patients had a normal response. Comparison of premutation carriers and full mutation patients showed: mean oocytes retrieved per cycle (8.4 ± 1.1 versus 14.1 ± 1.7, P = 0.005), lower levels of estradiol (E2; 1756 ± 177, versus 2928 ± 263, P = 0.0004), respectively. There was no significant difference between premutation carriers and full mutation patients in regard to fertilization rate, cleavage rate or biopsy rate. No correlation was found between the number of repeats in the premutation carriers and the number of oocytes retrieved or E2 levels. Age and the type of protocol were the only factors found to be in correlation with the number of the oocyte retrieved (P = 0.037, and P = 0.003, respectively) among the premutation carriers. Similarly, no association was found between the number of repeats and the fertilization rate, cleavage rate or biopsy rate among premutation carriers. LIMITATIONS, REASONS FOR CAUTION: We had a relatively low number of premutation carriers with >100 repeats, which made it challenging to draw a firm conclusions from this group. WIDER IMPLICATIONS OF THE FINDINGS: Physicians must address the increased risk for reduced ovarian response and  primary ovarian insufficiency (POI) among carriers and consider surveillance of ovarian reserve markers. The last, might expedite family plans completion or fertility preservation. STUDY FUNDING/COMPETING INTEREST(S): None.

Methotrexate success rates in progressing ectopic pregnancies: a reappraisal.

OBJECTIVE: The purpose of this study was to determine the success rates of methotrexate in progressing ectopic pregnancies and to correlate them with beta-human chorionic gonadotropin (ß-hCG) levels. STUDY DESIGN: This retrospective cohort study that was carried out in a tertiary university-affiliated medical center included women who had been diagnosed with ectopic pregnancies between January 2001 and June 2013. Daily ß-hCG follow-up examinations were performed to determine the progression of the ectopic pregnancy. Women with hemodynamically stable progressing ectopic pregnancies received methotrexate (50 mg/m(2) of body surface). We measured the success and failure rates for methotrexate treatment in correlation to ß-hCG level. RESULTS: One thousand eighty-three women were candidates for "watchful waiting" (ß-hCG follow up). Spontaneous resolution and decline of ß-hCG levels occurred in 674 patients (39.5%); 409 women (24.0%) had stable or increasing ß-hCG levels and were treated with methotrexate. In 356 women (87.0%), the treatment was successful; 53 women (13.0%) required laparoscopic salpingectomy. Compared with prompt administration of methotrexate, our protocol resulted in lower overall success rates for all levels of ß-hCG in women with progressing ectopic pregnancies: 75% in women with ß-hCG levels of 2500-3500 mIU/mL, and 65% in women with ß-hCG levels >4500 mIU/mL. A mathematic model was found describing the failure rates for methotrexate in correlation with ß-hCG levels. CONCLUSION: The success rates for methotrexate treatment in progressing ectopic pregnancies after daily follow-up evaluation of ß-hCG levels are lower than previously reported. This reflects redundant administration of methotrexate in cases in which the ectopic pregnancy eventually will resolve spontaneously.