The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer.

The selenoenzyme type I iodothyronine deiodinase (DIO1) catalyzes removal of iodine atoms from thyroid hormones. Although DIO1 action is reported to be disturbed in several malignancies, no work has been conducted in high-grade serous ovarian carcinoma (HGSOC), the most lethal gynecologic cancer. We studied DIO1 expression in HGSOC patients [The Cancer Genome Atlas (TCGA) data and tumor tissues], human cell lines (ES-2 and Kuramochi), normal Chinese hamster ovarian cells (CHO-K1), and normal human fallopian tube cells (FT282 and FT109). To study its functional role, DIO1 was overexpressed, inhibited [by propylthiouracil (PTU)], or knocked down (KD), and cell count, proliferation, apoptosis, cell viability, and proteomics analysis were performed. Lower DIO1 levels were observed in HGSOC compared to normal cells and tissues. TCGA analyses confirmed that low DIO1 mRNA expression correlated with worse survival and therapy resistance in patients. Silencing or inhibiting the enzyme led to enhanced ovarian cancer proliferation, while an opposite effect was shown following DIO1 ectopic expression. Proteomics analysis in DIO1-KD cells revealed global changes in proteins that facilitate tumor metabolism and progression. In conclusion, DIO1 expression and ovarian cancer progression are inversely correlated, highlighting a tumor suppressive role for this enzyme and its potential use as a biomarker in this disease.

Changes in maternal heart rate in delayed post-partum preeclampsia.

AIM: Delayed-onset postpartum preeclampsia (PET) is defined as a new diagnosis of preeclampsia presenting 48 h to 6 weeks postpartum. This disorder is infrequent and associated with a higher incidence of complications as compared to antepartum PET. There seems to be a need to further characterize this disorder. The aim of the study was to investigate the difference of maternal heart rate in women with delayed onset postpartum preeclampsia as compared to healthy controls. METHODS: The medical files of all women who were readmitted with delayed onset postpartum preeclampsia during 2014-2020 were reviewed. Data on maternal physiological characteristics were compared to healthy control group of women at the same post-partum day, with uncomplicated pregnancies. RESULTS: Included 45 women with the diagnosis of delayed onset of preeclampsia at 6.3 ± 2.86 post-partum day. As compared to controls (n = 49), women with delayed post-partum were older, 34.6 ± 5.4 vs. 32.3 ± 4.7 years, p = 0.003. There were no differences between groups regarding maternal gravidity, parity, BMI (kg/m2) or Hb level at delivery day. Women with delayed post-partum preeclampsia had lower mean pulse rate as compared to controls, 58 ± 15 bpm vs. 83 ± 11.6 bpm, respectively, P < 0.0001. Only 17% of the women in the delayed onset group had pulse rate above 70 bpm as compared to 83% in the control group. CONCLUSIONS: Maternal low heart rate in cases with delayed onset of post-partum preeclampsia is an important clinical characteristic that may reflect baroreceptors response to maternal hypertension.

Physiological and psychological stress responses to labor and delivery during COVID-19 pandemic: a cohort study.

OBJECTIVE: To evaluate objective (saliva cortisol) and subjective (questionnaire) stress levels during the Coronavirus disease (COVID-19) pandemic compared to before the pandemic and their effects on obstetric and neonatal outcomes. METHODS: This cohort study included 36 women with low-risk, singleton, term deliveries at a tertiary academic center during the COVID-19 pandemic and 49 who delivered before. Physiological stress was evaluated with salivary cortisol measurements, and emotional stress with stress scale questionnaires (0-10) during active and full dilation stages of labor, and 2-min postpartum. Cord blood cortisol and pH were obtained. Delivery mode, complications, and neonatal outcomes were evaluated. RESULTS: Psychological stress was higher for the COVID-19 group compared to controls during full dilation (6.2 ± 3.4 vs. 4.2 ± 3, p = .009). The COVID-19 group had significantly lower cord cortisol levels (7.3 vs. 13.6 mcg/dl, p = .001). No differences were found regarding salivary cortisol level assessments at active, full dilation and 2-min post-delivery (p = .584, p = .254, p = .829, respectively). No differences were found regarding pH < 7.1 (p = .487), 1- and 5-min Apgar scores < 7 (p = .179) and neonatal weight (p = .958). CONCLUSIONS: Women who delivered during COVID-19 pandemic had higher stress levels at full dilation and lower cord cortisol levels, as may be expected after exposure to a chronic stressor.

Intrahepatic cholestasis of pregnancy: machine-learning algorithm to predict elevated bile acid based on clinical and laboratory data.

PURPOSE: Applying machine-learning models to clinical and laboratory features of women with intrahepatic cholestasis of pregnancy (ICP) and creating algorithm to identify these patients without bile acid measurements. METHODS: This retrospective study included 336 pregnant women with a chief complaint of pruritis without rash during the second/third trimesters. Data extracted included: demographics, obstetric, clinical and laboratory features. The primary outcome was an elevated bile acid measurement ≥ 10 µmol/L, regardless of liver enzyme levels. We used different machine-learning models and statistical regression to predict elevated bile acid levels. RESULTS: Among 336 women who complained about pruritis, 167 had bile acids ≥ 10 µmol/L and 169 had normal levels. Women with elevated bile acids were older than those with normal levels (p = 0.001), higher parity (p = 0.001), and higher glutamic oxaloacetic transaminase ( GOT) (p = 0.001) and glutamic-pyruvic transaminase (GPT) levels (p = 0.001). Using machine-learning models, the XGB Classifier model was the most accurate (area under the curve (AUC), 0.9) followed by the K-neighbors model (AUC, 0.86); and then the Support Vector Classification (SVC) model (AUC, 0.82). The model with the lowest predicative ability was the logistic regression (AUC, 0.72). The maximum sensitivity of the XGB model was 86% and specificity 75%. The best predictive parameters of the XGB model were elevated GOT (Importance 0.17), elevated GPT (Importance 0.16), family history of bile disease (0.16) and previous pregnancy with ICP (0.13). CONCLUSION: Machine-learning models using clinical data may predict ICP more accurately than logistic regression does. Using detection algorithms derived from these techniques may improve identification of ICP, especially when bile acid testing is not available.

High grade, advanced, serous ovarian cancer with low serum CA125 levels.

This study compares characteristics of advanced stage, high grade serous ovarian cancer, presenting with high or low serum CA125 level. This was a retrospective cohort of 118 patients with high grade serous ovarian, fallopian tube or primary peritoneal cancer, stages IIIC-IV diagnosed from January 1 1997 through January 9 2017. Patient demographics, tumour characteristics, surgical findings, chemotherapy protocols and clinical outcomes were collected. Three groups were evaluated: group A: 21 patients with CA125 serum level ≤152 U/ml, group B: 97 patients with CA125 serum level >152 U/ml, group C: 43 patients from group B with CA125 serum level >500 U/ml and <1000 U/ml. No significant difference was found between groups regarding age, stage at diagnosis, extent of residual disease or disease volume. More group A patients had surgery as primary treatment compared to groups B and C (p=.003, p=.022, respectively). CA125 level at recurrence was lower in group A as compared to the other groups (162.2 vs. 851.7 and 603.4, p=.003, p=.006). Overall survival and progression-free survival did not differ based on CA125 levels. We conclude that patients with advanced stage, high grade, serous ovarian cancer with low CA125 serum levels had the same clinical outcome as patients with higher levels.Impact StatementWhat is already known on this subject? It is known that CA125 level is a prognostic and predictive factor for epithelial ovarian cancer (EOC) outcome. It is elevated in 80% of the patients and within normal range in only 10% of women with advanced stage EOC. Various studies had addressed the patients with advanced stage serous EOC who had high serum CA125 levels at time of diagnosis. But, no study has addressed the 10% of patients with advanced stage who had low serum CA125 levels at time of diagnosis.What the results of this study add? To the best of our knowledge, this is the first study addressing patients with advanced stage EOC who had low serum CA125 levels at time of diagnosis. According to the results of this study, patients with advanced stage, high grade serous EOC presenting with low serum CA125 levels have similar clinical outcomes as do patients with high serum CA125 levels.What the implications are of these findings for clinical practice and/or further research? Further translational research is encouraged for this group of tumours to identify specific molecular markers that might lead to better understanding and treatment for the disease.

Time interval from biopsy to surgery and risk for adjuvant therapy in patients with low-risk endometrial cancer.

OBJECTIVE: Among patients with endometrial cancer, longer wait times to surgery were associated with decreased survival. Although endometrial cancer survival rate is high, about 45% of patients receive adjuvant therapy. The aim of this study was to examine whether a longer interval from diagnosis to surgery is associated with increased need for adjuvant treatment among patients with low-risk endometrial cancer. METHODS: A retrospective cohort study of endometrioid endometrial cancer patients treated with surgery between the years 1999 and 2013 was conducted. Patients with pre-operative histology of hyperplasia, grade 1/2 cancers were included. Patients with stage IV disease were excluded. Demographic, clinicopathologic and surgical parameters were collected and correlation with wait time was evaluated. The risk for adjuvant therapy was in two-week intervals from biopsy to hysterectomy. RESULTS: 468 patients were included in the final cohort. 84.3% had stage I disease and 43.8% patients received adjuvant treatment. Mean time from diagnosis to surgery was 63.88 days (SD 10.3, 31-94). The risk for adjuvant therapy was not increased at any of the time intervals that were examined. CONCLUSION: In low risk endometrial cancer, longer time interval between diagnosis and surgery did not increase the need for adjuvant therapy.

Induction of labor, and physiological and psychological stress responses as expressed by salivary cortisol: a prospective study.

PURPOSE: To describe patterns of physiological and psychological stress during induced labor and their correlation to obstetrical and neonatal outcomes. METHODS: This prospective, observational study included 167 women, with low-risk, singleton pregnancies, who delivered at term, at a tertiary academic center from 2015 through 2018. Among them, 72 (43%) underwent induction and 95 (57%) had spontaneous labor onset. Physiological stress was evaluated by salivary cortisol measurements and emotional stress by questionnaires (visual analogue stress scale 0-10) during latent phase, active phase and full dilation stages of labor, as well as 2 min and 2 h postpartum. Cord blood cortisol and pH were obtained. Stress patterns were compared between parturients who did or did not undergo induction. Modes of delivery, labor and delivery complications, and early neonatal outcomes were compared. Mothers completed the Hospital Anxiety and Depression Scale. RESULTS: Induced women had lower cortisol concentrations during the latent phase compared to spontaneous onset of labor (p = 0.003), with no differences during active (p = 0.237), full dilation (0.668), 2 min and 2 h after delivery (p = 0.666). Stress scale and Hospital Anxiety and Depression Scale scores were similar between groups. Cord cortisol (p = 0.294), 1-min Apgar score ≤ 7 (p = 0.502) and 5-min Apgar score ≤ 7 (p = 0.37) were similar. All had cord pH > 7. CONCLUSIONS: Induction does not increase stress during labor. Moreover, it might have a positive effect on reducing cortisol during the latent phase. These findings might reassure women who are concerned about induction of labor.

The possibility of integrating motile sperm organelle morphology examination (MSOME) with intracytoplasmic morphologically-selected sperm injection (IMSI) when treating couples with unexplained infertility.

PURPOSE: To examine the efficacy of motile sperm organelle morphology examination (MSOME) and intracytoplasmic morphologically-selected sperm injection (IMSI) for unexplained infertility. METHODS: This historical study, included 271 couples with primary, unexplained infertility/male subfertility, treated at an outpatient, IVF clinic, 2015-2018. These couples underwent MSOME after ≥3 failed intrauterine insemination (IUI) cycles and ≥1 failed IVF-ICSI cycle. They proceeded to intracytoplasmic morphologically-selected sperm injection (IMSI) within 6 months of MSOME. IMSI is conducted on the day of oocyte pick-up with a fresh semen sample. Pregnancy and delivery rates were analyzed. RESULTS: The cohort was divided based on percentage of normal cells at MSOME: Group A included 55 with no normal cells, Group B, 184 with 0.5%≤ normal cells ≤1.5% and Group C, 32 with ≥2% normal cells. Normal spermatozoa were found in 49 (89%) of Group A after extensive search. Group A had higher pregnancy rate (62.7%) compared to B (47.2%, P = 0.05) and C (28.1%, P = 0.002). Group B had higher pregnancy rate than C (p = 0.045). Delivery rate was higher in Group A (52.1%) compared to B (34.1%, p = 0.023) and C (21.9%, p = 0.007). Pregnancy and delivery rates were higher in A compared to B+C (p = 0.018, p = 0.01, respectively). CONCLUSIONS: MSOME may be useful for evaluating unexplained infertility. IMSI can be recommended for men with <2% normal spermatozoa at MSOME.

Does cognitive flexibility affect the course of labor? A prospective study.

OBJECTIVE: To evaluate cognitive flexibility and labor and delivery outcomes. METHODS: A prospective study was conducted of nulliparas with singleton term pregnancy, admitted for labor to a tertiary referral center from 1 January to 31 July, 2017. After epidural anesthesia, parturients completed the validated Psychological Flexibility Questionnaire (20 questions that evaluate a person's level of cognitive flexibility) before delivery. They were asked to grade (from 1 to 10) their hope for vaginal delivery (Hope score). Within 2 hours after delivery, they graded (1-10) the similarity between their delivery and their expectations (Expectation score). Outcomes of the flexible versus less flexible group were compared. RESULTS: Among the flexible (n=120) versus less flexible (n=40) group, vaginal delivery was more common (74.2% vs 20.8%) than vacuum extraction (20.8% vs 35%) or cesarean delivery (5% vs 12.5%) (P=0.031). High Expectation score and delivery without grade III-IV perineal tear (P=0.032) were correlated. Groups were similar regarding Expectation (P=0.163) and Hope scores (P=0.591). The mode of delivery of parturients was not correlated with their mothers' (P=0.836) or sisters' (P=0.758). CONCLUSION: High cognitive flexibility increases the likelihood of vaginal delivery. These findings support the mind-body correlation. Maternal cognitive perceptions can influence labor and delivery and should be considered when counseling patients during labor.

Does music during labor affect mode of delivery in first labor after epidural anesthesia? A prospective study.

KEY MESSAGE: Listening to music during labor increases the likelihood that primiparas will have a spontaneous vaginal delivery. PURPOSE: To examine the effects of exposure to music during labor on the mode of delivery and parturients' stress levels. METHODS: This prospective, interventional study included 124 low-risk women who were recruited during latent phase of their first labor after epidural anesthesia. Patients were grouped according to their preference to receive music intervention or not. The music intervention included two subgroups: soft classical music and rhythmic music. We evaluated cortisol levels in saliva as a surrogate for stress level and State-Trait Personality Inventory at enrollment and 1-3 h later in all women who were still in labor. Delivery and perinatal outcomes were collected from electronic medical records. Correlations between the music intervention and maternal and perinatal outcomes were evaluated. RESULTS: Spontaneous vaginal delivery was significantly more frequent among women listening to music compared to the non-music group (P = 0.035). A trend towards lower rates of cesarean delivery was noted in the music group (P = 0.08), with no difference in instrumental vaginal delivery rates. Stress levels, as measured by questionnaires and by cortisol levels, blood pressure and pulse rate, remained similar throughout the study. No differences were noted between the different genres of music when examining obstetric and perinatal outcomes and stress levels. CONCLUSION: Listening to music during labor, improves the likelihood of primiparas to have a vaginal delivery regardless of stress level. As this treatment is simple, easy, and harmless to administer, we suggest it may be offered to all patients during labor.

Can we predict the need for antihypertensive treatment during the early postpartum period for women with preeclampsia or gestational hypertension?

OBJECTIVES: To determine factors that predict the need for antihypertensive treatment during early postpartum period among women with preeclampsia or gestational hypertension. STUDY DESIGN: Retrospective cohort of 358 women. MAIN OUTCOME MEASURES: Demographic, clinical and laboratory data of 63 women diagnosed with preeclampsia or gestational hypertension during a singleton pregnancy and who needed antihypertensive agents during early postpartum period were compared to 295 who did not. RESULTS: No difference was found between groups regarding age, parity, body mass index, or weight gain (p = 0.95, 0.19, 0.56, and 0.078, respectively). Early onset preeclampsia or gestational hypertension was diagnosed among 28.6% of the women who subsequently needed antihypertensive treatment, as compared to 4.1% who did not (p < 0.001). Antepartum, mean maximum blood pressure in the treated vs. untreated group was 165/109 mmHg vs. 150/100 mmHg, respectively (p = 0.001). Groups did not differ regarding symptoms of preeclampsia (38.7% vs. 31.5%, p = 0.273) or laboratory abnormalities. The group that received antihypertensive treatment during early postpartum period, had more preterm deliveries (p < 0.001) and Cesarean deliveries (p < 0.001), and more received magnesium sulfate during labor (p < 0.001). During the early postpartum period, mean maximum blood pressure was higher among the treated group (167/106 vs. 143/92, p = 0.001), as were symptoms of preeclampsia (p = 0.001). The groups were similar regarding laboratory abnormalities that define preeclampsia. CONCLUSIONS: Early onset preeclampsia or gestational hypertension, severe antepartum hypertension, magnesium sulfate during labor, preterm, and Cesarean delivery might be good predictors of the need for antihypertensive treatment during early postpartum period.

Physiological and psychological stress responses to labor and delivery as expressed by salivary cortisol: a prospective study.

BACKGROUND: Labor is considered a stressful event, yet no study has described the course of stress measured by cortisol during labor and postpartum. OBJECTIVE: The objective of the study was to describe the patterns of physiological and psychological stress during labor as measured by salivary cortisol concentrations and stress questionnaires and their correlation to obstetric and neonatal outcomes. STUDY DESIGN: This prospective, observational study included 167 women with low-risk, singleton, term deliveries at a tertiary academic center. Physiological stress was evaluated by salivary cortisol measurements and emotional stress by questionnaire (stress scale ranging from 0 to 10) during the latent phase, active phase, and full dilation stages of labor as well as 2 minutes, 2 hours, and 24 hours after delivery. Cord blood cortisol and pH were also obtained. Modes of delivery, complications during labor and delivery, and early neonatal outcomes were evaluated. RESULTS: Salivary cortisol concentrations increased gradually from latent phase to active phase. The maximum increase was observed within 2 minutes of the delivery (from an average of 1.06 µg/dL to 1.67 µg/dL; 57% increase). Within 2 hours after delivery, cortisol decreased and reached a nongravid concentration after 24 hours (0.16 µg/dL). Cortisol concentrations during labor and up to 2 hours postpartum were above the average concentration of nongravid women (0.5 µg/dL). Women with epidural anesthesia had lower cortisol concentrations at complete dilation (P = .026) and 2 hours postpartum (P = .016) compared with women without epidural. Psychological stress peaked during latent and full dilation phases (mean 4.56 and 4.29, respectively). Maximum decrease from 4.29 to 2.04 (52%) occurred immediately postpartum. Cord cortisol was higher among women delivered by vacuum extraction compared with spontaneous vaginal delivery (17 ± 2 vs 11 ± 3.8, P = .03). CONCLUSION: This study reveals the course of cortisol concentrations during labor for low-risk pregnancies, with maximum increase immediately postpartum. Subjective stress levels decreased over the course of labor. Salivary cortisol portrays stress during labor and may be used as a reference to evaluate complicated pregnancies and to evaluate the role of cortisol during these deliveries.

Twin pregnancies and perinatal outcomes: a comparison between fresh and frozen embryo transfer: a two-centre study.

RESEARCH QUESTION: To assess the perinatal and obstetric outcomes of twin pregnancies resulting from IVF frozen embryo transfer (FET) in comparison with fresh embryo transfer. DESIGN: A retrospective cohort study of 773 twin pregnancies conceived via IVF treatment. Data were collected from the records of two outpatient fertility IVF clinics of cycles conducted between 2006 and 2016. RESULTS: A total of 773 pregnancies were evaluated: 614 (79.4%) following FET and 159 (20.6%) following fresh embryo transfer. The FET group had a significantly higher mean birthweight (P = 0.002), and lower rates of small for gestational age (P = 0.003), low (P = 0.003) and very low birthweight (P = 0.006) infants. Also, a significantly lower rate of spontaneous second trimester miscarriage compared with the fresh embryo transfer group was observed (P = 0.001). No significant difference was found between groups regarding gestational age at delivery, term birth (after 37 weeks of gestation), twin discordancy rate, fetal major malformation rate, and hospitalization duration. CONCLUSION: In twin pregnancies, FET might have better perinatal outcomes compared with fresh embryo transfer in regards to birthweight and spontaneous second trimester miscarriages. Further research is needed to evaluate these results.

Neutrophils to lymphocytes ratio and platelets to lymphocytes ratio in pregnancy: A population study.

BACKGROUND: Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are both inflammatory ratios that can be easily calculated from a simple blood count. They are frequently reported and tested as prognostic factors in several medical disciplines. Pregnancy involves special reference values for laboratory assays. OBJECTIVE: The aim of this study was to define pregnancy-related reference values for NLR and PLR according to trimester, background morbidity and according to the patient's age. STUDY DESIGN: A retrospective analysis of a large cohort undergoing community-based pregnancy surveillance between the years 2011-2016. Data were analyzed according to high-risk patient versus normal-risk patient. RESULTS: A total of 11,415 patients were included. Mean PLR and NLR values were 136.3±44.3, 2.6±1, respectively during the first trimester, 144.6±47.1, 4.0±1.4 respectively during the second trimester and 118.1±42.0, 3.5±1.2 respectively during the third trimester. No difference was detected between the high-risk and the normal population (P-values 0.3, 0.5 and 0.4 for PLR in each trimester respectively and 0.3, 0.4, 0.6 for NLR in each trimester, respectively). No differences were detected among parity categories. The correlation between patient's age and either PLR and NLR was a weak positive correlation (though statistically significant). Both PLR and NLR reached a maximum value during the second trimester. The differences between mean NLR and PLR between trimesters were significant (P <0.01 for all differences tested). PLR rises in the presence of anemia, reaching statistical significance (P-value for PLR in each trimester was <0.01). NLR showed an opposite trend (P-values for NLR were 0.4, 0.005 and 0.06 in each trimester, respectively). CONCLUSIONS: In our cohort, there were generally no differences between the high-risk and the normal population, excluding patients with a fibroid uterus or inflammatory bowel disease who presented a significantly elevated PLR through all trimesters. Both PLR and NLR reached a maximum value during the second trimester and were positively correlated with age. We anticipate that the population-based data will assist in providing accurate reference values for future research testing NLR and PLR measures during pregnancy.