Progression Of Pregnancy Research Articles

Long non-coding RNAs: a summary of their roles in placenta development and pathology†.

Long non-coding RNAs are cellular transcripts that have ˃200 nucleotides in length and do not code for proteins. Due to their low expression levels, long non-coding RNAs were previously considered as mere transcriptional noise. However, current evidence indicates that they regulate a myriad of biological processes such as cell proliferation, invasion, and apoptosis. Hence, their expression patterns are crucial indicators of the physiological or pathological states of cells, tissues, and organs. The utilization of long non-coding RNAs as biomarkers and therapeutic targets for the clinical management of several diseases have been suggested. Gradually, long non-coding RNAs are gaining a substantial attention in the field of feto-maternal medicine. After embryo implantation, the interactions between the trophoblast cells from the embryo and the uterus of the mother facilitate placenta development and pregnancy progression. These processes are tightly regulated, and their impairments result in pregnancy pathologies such as miscarriage and preeclampsia. Accumulating evidence implicates long non-coding RNAs in these processes. Herein, we have summarized the roles of several long non-coding RNAs in human placenta development, have proposed some mechanisms by which they participate in physiological and pathological placentation, have revealed some knowledge deficits, and have recommended ideal experimental approaches that will facilitate the clarification of the mechanistic actions of each long non-coding RNA at the feto-maternal interface during healthy and pathological pregnancies.

The normality of the first-trimester placentae collected from elective terminations

Placentae collected from elective terminations during the first trimester are commonly used as control samples in research. However, it is widely acknowledged that many complications of pregnancies can occur or originate during the early stage of gestation. This raises the question that the placentae collected from the first trimester may not accurately reflect normal placental conditions. In this study, 95 placentae were collected from elective terminations and histology was performed. Out of these, 53 placentae (56 %) exhibited the typical structure of placental villi, indicating normal development. However, 42 placentae (44 %) showed placental hydrops, with varying degrees of severity (mild, moderate, or severe). Placental hydrops has been linked to several complicated pregnancies in the later stages of gestation. Our findings suggest that the development of pregnancy pathologies could start in the first trimester, as observed by the presence of hydrops. Placental researchers should be aware of when using first-trimester placentae from termination as controls in studies. However, it remains unclear whether pathological morphologies resolve or ameliorate as the pregnancy progression or whether such placentae continue to have such pathology, but clinical symptoms/signs do not manifest.

Ultrasonic Scanning for Placentome Size in Pregnant Maraz Goat in Sulaimani Province

The aim of the study was determination of the relationship between pregnancy age and placentome measurement by using an ultrasound technique. This study was conducted in some private farms in Sulaimani province. A total of seventy-two Maraz does were checked by using transabdominal and transrectal ultrasonic transducers for pregnancy status, 47.2% (34/72) of these goats were pregnant. Twenty-seven non-pregnant does were synchronized for estrus by using vaginal sponges for 11 days followed by injection of 500 IU of PMSG hormones after withdrawing the sponges and naturally served to obtain pregnancy. 63% (17/27) of the synchronized goats became pregnant, all synchronized goats were scanned every seven to ten days beginning from day 35 to 140 of gestation transabdominally (TA) with sector-probe (4-5MHz) and transrectally (TR) with linear-probe (7.5-9 MHz). The placentomes width and height increased significantly (P≤0.05) with the progress of the gestation period, and the first observation of placentomes were in 32 and 42 days by depended (TR) and (TA) respectively. The width and height were 10.2 mm and 9.8 mm respectively during 40-50 days of gestation and maximum sizes were 45 mm and 38 mm in 130 days of gestation period. There is a little significant difference (P≤0.05) between single and twin pregnancy just in 61-70 and 81-90 days of gestation period. In conclusion, there is a strong relationship between the size of placentome and the progress of pregnancy, there are no serious differences in the size of placentomes in single and multiple pregnancy goats, and using transrectal scanning is useful for early detection of pregnancy.

Evaluation of Molecular Interactions and Cellular Dynamics at the Maternal-Fetal Interface During Placental Morphogenesis.

Molecular events at the maternal-fetal interface establish successful pregnancies. Identifying and characterizing the heterogeneous cell population and their cross-talk at the cellular and molecular levels are essential to expand our knowledge on the progression and maintenance of pregnancy. In this chapter, we briefly discuss the organization of maternal-fetal interface in mice/rats and humans. We illustrate methods for studying the cell composition using flow cytometry, immunocytochemical and biochemical studies, intercellular interaction using co-culture system and spheroid assay, and function of trophoblast cells using ELISA, RNA sequencing, mass spectrometry (MS) to analyze the proteome, invasion assay, and scratch wound assay.

Phenotyping the autonomic nervous system in pregnancy using remote sensors: potential for complication prediction.

Objectives: The autonomic nervous system (ANS) plays a central role in dynamic adaptation during pregnancy in accordance with the pregnancy demands which otherwise can lead to various pregnancy complications. Despite the importance of understanding the ANS function during pregnancy, the literature lacks sufficiency in the ANS assessment. In this study, we aimed to identify the heart rate variability (HRV) function during the second and third trimesters of pregnancy and 1 week after childbirth and its relevant predictors in healthy pregnant Latina individuals in Orange County, CA. Materials and methods: N = 16 participants were enrolled into the study from which N = 14 (N = 13 healthy and n = 1 complicated) participants proceeded to the analysis phase. For the analysis, we conducted supervised machine learning modeling including the hierarchical linear model to understand the association between time and HRV and random forest regression to investigate the factors that may affect HRV during pregnancy. A t-test was used for exploratory analysis to compare the complicated case with healthy pregnancies. Results: The results of hierarchical linear model analysis showed a significant positive relationship between time (day) and average HRV (estimated effect = 0.06; p < 0.0001), regardless of being healthy or complicated, indicating that HRV increases during pregnancy significantly. Random forest regression results identified some lifestyle and sociodemographic factors such as activity, sleep, diet, and mental stress as important predictors for HRV changes in addition to time. The findings of the t-test indicated that the average weekly HRV of healthy and non-healthy subjects differed significantly (p < 0.05) during the 17weeks of the study. Conclusion: It is imperative to focus our attention on potential autonomic changes, particularly the possibility of increased parasympathetic activity as pregnancy advances. This observation may challenge the existing literature that often suggests a decline in parasympathetic activity toward the end of pregnancy. Moreover, our findings indicated the complexity of HRV prediction, involving various factors beyond the mere passage of time. To gain a more comprehensive understanding of this dynamic state, future investigations should delve into the intricate relationship between autonomic activity, considering diverse parasympathetic and sympathetic metrics, and the progression of pregnancy.

The Amount of Fluid Intake among Pregnant Women in China Increases with Pregnancy Progression: A Prospective Cohort Study.

Fluid intake and hydration status during pregnancy may have influences on maternal and infant health. However, few studies have recorded and analyzed total fluid intake (TFI) levels during the whole pregnancy. This study mainly aimed to investigate the TFI levels of pregnant women in three trimesters, and further to assess their hydration status. The relationships of TFI and hydration status were also analyzed. A convenience sampling method was used to recruit pregnant women from the Haikou Maternity and Child Health Hospital in China in this prospective cohort study. A 7-day 24 h fluid intake questionnaire was used for recording the fluid intake of the participants in their three trimesters. Fasting blood samples and first morning urine samples were also collected and tested. Hydration status was evaluated using urine osmolality. Finally, 142 pregnant women completed the study. The median TFIs in the first, second, and third trimesters were 1336, 1477, and 1584 mL, respectively. The TFI levels increased with pregnancy progression (χ2 = 134.155, p < 0.05). Out of 142 participants, 100.0%, 97.2%, and 85.2% of participants did not reach the recommendation amount for an adequate TFI among Chinese pregnant women in the three trimesters, respectively (χ2 = 29.840, p < 0.05). Plain water was the main source of fluid intake, accounting for 92.0%, 94.2%, and 93.4% of TFI, respectively. The median values of dairy product intake were 61, 57, and 59 mL in the three trimesters. The frequency of participants without an optimal hydration status in the three trimesters was 71.8%, 76.1%, and 83.1%, respectively (χ2 = 29.909, p < 0.05). The participants of each trimester were divided into four groups according to quartiles of TFI, including participants with a lower fluid intake (LFI1 and LFI2) and higher fluid intake (HFI1 and HFI2). As the TFI values increased from the LFI1 group to the HFI2 group, the urine osmolality decreased (all p < 0.05). Moderate-intensity negative correlations were found between urine osmolality, hydration status, and TFI (all p < 0.05). It is suggested that fluid intake strategies should be promoted and health education should be conducted to improve the hydration status of pregnant women.

On the Children Side. Overview of 194 Outcomes from Gimema Registry of Conception/Pregnancy in Chronic Myeloid Leukemia (CML)

Pregnancy in patients with chronic myeloid leukemia (CML) is no longer precluded. The literature published to date has mainly evaluated the management of CML and pregnancy with little mention of follow-up of children. This work aims to focus on the effects of the disease and of the drugs taken before conception and/or during pregnancy on fertility, gestation, pre-natal development of the fetus, and the growth of the child. GIMEMA has promoted an observational retrospective/prospective study to harvest and study detailed information on both pregnancies in female CML patients and pregnancies of partners of male patients followed at participating centers. The information requested addressed information on demographic, CML- related (CML therapy before/during/after pregnancy; transcript kinetics; outcome post delivery), pregnancy-related (type of conception; abortion rate; pregnancy progression, delivery, breastfeeding), and baby-related (birth, physical, intellectual, emotional, behavioral, social and sexual development) Data from 83 male patients (109 pregnancies) and 74 female patients (84 pregnancies) were evaluated for a total of 193 pregnancies at term. Fourteen (7 female and 7 male) conceptions were medically assisted, all the others spontaneous. One hundred ninety-four children were born (a twin pregnancy), 15 abortions were registered, 12 spontaneous and 3 voluntary all within the first trimester, while one pregnancy is still in progress. Eleven patients (1 male, 10 female) were diagnosed as having CML during pregnancy. Three patients interrupted pregnancy (2 electives). All male patients, with the exception of two (one undergoing assisted reproduction and one in TFR), conceived during treatment. TKI used were Imatinib (71%), Nilotinib (22%), Dasatinib (2%), Bosutinib (4%) and Ponatinib (1%). The pregnancies carried out by the partners of the male patients did not show any problems, neither pre-conception, nor during gestation, nor at birth. An initial speech delay in a child was reported, with recovery after speech therapy. Most pregnancies result in spontaneous delivery around the 39th week of gestation. Ninety-two/109 babies were breastfed (84%) The last TKI used in the female CML group was imatinib (43%), nilotinib (33%), dasatinib (22%), and Ponatinib (2%). Most patients stopped TKI at the FPT “first pregnancy test” (3-5 weeks). Cesarean deliveries amounted to 41%, just above the national average of 30%, with a mean of 38 weeks of gestation. Of the 84 babies born to women diagnosed with CML, only 20 were breastfed (23%). Three patients treated with IFN at the time of delivery breastfed for about a month, while one breastfed for 9 months and did not resume TKI as she was well-controlled by IFN and eager to start a new pregnancy. The lack of assimilation of IFN through breast milk orally does not contraindicate breastfeeding. In female patients, out of 84 pregnancies, and 1 in progress, 15 required antileukemic therapy during pregnancy. IFN was administered in 13 gestations, and also during organogenesis. In one case the patient introduced IFN at 7 weeks, then stopped due to poor disease control and started Nilotinib at 21 weeks, after placenta formation. In 2 gestations (including the one mentioned above) the patients took nilotinib (starting at 21 and 23 week of gestation). One patient was treated with imatinib at 20 week. The evaluation of the pediatric population under examination was divided into four age groups: 0-3 years for the evaluation of birth and psycho-physical development; 3-6 years for cognitive development; &amp;gt;6 years for socialization and interaction with the surrounding environment, including school performance; &amp;gt;12 years for sexual and hormonal development. Five infants were small for date. Of those, only one was exposed to imatinib from the 20th week of gestation. (Table 1). All children presented a rapid recovery after birth and their development is comparable to that of children belonging to the same age group. The oldest child is 15 years old, and was born at 39 weeks to a father on TFR after suspension of imatinib therapy; the youngest is a 15 days old girl, born at 38 week to a mother treated with IFN during pregnancy. From the results obtained from the study, children born to parents diagnosed with CML do not appear to show any difference compared to their peers in the general population, even if exposed to therapy in the prenatal period.

Results of Preclinical Animal Studies to Evaluate the Effect of Iptacopan on Pregnancy-Related Outcomes

Introduction: Iptacopan is a first-in-class, oral, selective inhibitor of factor B, a key component of the complement system alternative pathway. Inhibition of the complement system represents a potential mechanism for treatment of several complement-driven diseases including paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Here, we report results from the preclinical GLP toxicology studies of iptacopan on embryo-fetal development in rats and rabbits and pre- and postnatal development in rats. Methods: In the definitive embryo-fetal development studies,iptacopan was dosed orally via gavage to pregnant rats at 0, 100, 300, and 1000 mg/kg/day (N=24/group) and to pregnant rabbits at doses of 0, 100, 250, and 450 mg/kg/day (N=20/group) during the period of organogenesis (Gestation Day [GD] 6 to 17 and GD7 to 20, respectively). The progress and outcome of pregnancy were evaluated and fetuses were examined for external, visceral, and skeletal abnormalities. In a pre- and postnatal developmental toxicity study in pregnant rats, iptacopan was dosed orally via gavage at 0, 100, 300, and 1000 mg/kg/day (N=22/group) from GD6 to Lactation Day (LD) 21. The untreated offspring were allowed to mature and the effects on development, behavior, and reproductive performance were assessed. Results: In the rat embryo-fetal development study, maternal administration of iptacopan resulted in no adverse clinical observations, no effects on maternal body weights, and no adverse fetal findings. Non-adverse fetal variations of delayed ossification were observed in the skull. Two fetuses in one out of 22 litters at 1000 mg/kg/day had benign cysts on the left side of the parietal region of the head, with no impact on skeletal (skull), CNS (brain), or any other head-based structure. The no observed adverse effect level (NOAEL) for maternal toxicity and embryo-fetal development was 1000 mg/kg/day. In the definitive rabbit embryo-fetal development study, administration of iptacopan caused reduced maternal body weight gain and food consumption at 450 mg/kg/day. There were no treatment-related fetal malformations or variations. The NOAEL was 250 mg/kg/day for maternal toxicity and 450 mg/kg/day for embryo-fetal development. In the pre- and postnatal development study, no adverse findings were observed in the mated female rats during gestation, parturition, and lactation and there were no adverse effects on development of their offspring, including survival, physical development, behavior, and reproductive performance. The NOAEL for maternal (F0 generation) toxicity, maternal performance, and development of the F1 generation offspring was the highest dose of 1000 mg/kg/day. NOAEL and estimated AUC-based safety margins based on total plasma concentrations for all mentioned studies are shown in the Table. Conclusion: In nonclinical reproductive toxicity studies conducted in pregnant rats and rabbits, iptacopan was found to be generally safe with no teratogenic effects in the rat and rabbit. Estimated AUC-based safety margins were &amp;gt;5-fold for all developmental findings compared to exposure at the clinical dose of 200 mg twice daily. While these preclinical data do not provide definitive conclusions or guidance on the use of iptacopan in pregnant women, they do provide reassurance that there is no overt preclinical signal of embryo-fetal toxicity.

Longitudinal changes of oxidative stress and PON1 lactonase activity and status in older pregnant women undergoing assisted reproductive technology: a prospective nested case-control study

BackgroundChildbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART.MethodsThis prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed.ResultsLactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups.ConclusionsWomen with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.

The endometrial transcriptome transition preceding receptivity to embryo implantation in mice

BackgroundReceptivity of the uterus is essential for embryo implantation and progression of mammalian pregnancy. Acquisition of receptivity involves major molecular and cellular changes in the endometrial lining of the uterus from a non-receptive state at ovulation, to a receptive state several days later. The precise molecular mechanisms underlying this transition and their upstream regulators remain to be fully characterized. Here, we aimed to generate a comprehensive profile of the endometrial transcriptome in the peri-ovulatory and peri-implantation states, to define the genes and gene pathways that are different between these states, and to identify new candidate upstream regulators of this transition, in the mouse.ResultsHigh throughput RNA-sequencing was utilized to identify genes and pathways expressed in the endometrium of female C57Bl/6 mice at estrus and on day 3.5 post-coitum (pc) after mating with BALB/c males (n = 3–4 biological replicates). Compared to the endometrium at estrus, 388 genes were considered differentially expressed in the endometrium on day 3.5 post-coitum. The transcriptional changes indicated substantial modulation of uterine immune and vascular systems during the pre-implantation phase, with the functional terms Angiogenesis, Chemotaxis, and Lymphangiogenesis predominating. Ingenuity Pathway Analysis software predicted the activation of several upstream regulators previously shown to be involved in the transition to receptivity including various cytokines, ovarian steroid hormones, prostaglandin E2, and vascular endothelial growth factor A. Our analysis also revealed four candidate upstream regulators that have not previously been implicated in the acquisition of uterine receptivity, with growth differentiation factor 2, lysine acetyltransferase 6 A, and N-6 adenine-specific DNA methyltransferase 1 predicted to be activated, and peptidylprolyl isomerase F predicted to be inhibited.ConclusionsThis study confirms that the transcriptome of a receptive uterus is vastly different to the non-receptive uterus and identifies several genes, regulatory pathways, and upstream drivers not previously associated with implantation. The findings will inform further research to investigate the molecular mechanisms of uterine receptivity.

ВЕРОЯТНОСТЬ ИЗМЕНЕНИЯ ПОКАЗАТЕЛЕЙ ФУНКЦИИ ВНЕШНЕГО ДЫХАНИЯ ПРИ РАЗВИТИИ ХОБЛ В ЗАВИСИМОСТИ ОТ КОЛИЧЕСТВА ВЫКУРИВАЕМЫХ СИГАРЕТ НА ФОНЕ ГОРМОНАЛЬНЫХ ИЗМЕНЕНИЙ ПРИ БЕРЕМЕННОСТИ

Introduction. This is a study of possible changes in the respiration function indicators in the development of chronic obstructive pulmonary disease (COPD), depending on the number of cigarettes smoked and associated with pregnancy-related hormone fluctuations. Aim. Our study aimed to determine the dependence of changes in first- second forced expiratory volume upon the level of anti-inflammatory hormones cortisol and progesterone in female smokers with different number of cigarettes smoked. Materials and Methods. The study is based on the findings of the analysis of changes in the level of hormones cortisol and progesterone in 243 pregnant women in antenatal care and on how such changes affect the first-second forced exhalation volume. The control group consisted of healthy non-smoking female patients. 4 groups were formed. For each group, the expected values of the first-second forced exhalation volume were calculated, in parallel with changes in the cortisol and progesterone profile and with forming the relevant statistical data matrices. Results and Discussion. With an increase in cortisol and progesterone levels, there is an increase in the first-second of forced exhalation volume, which indicates an increase in the lung tissue elasticity and in the air flow rate in the first second under the influence of hormones that have a pronounced anti-inflammatory effect. Conclusion. Pregnancy progress in smokers consuming different amounts of cigarettes is accompanied by an increase in the cortisol and progesterone levels. Hormone fluctuations improve the functional state of external respiration in pregnant smokers with COPD, creating the illusion of preserving the physiological capabilities of lungs regardless of the number of cigarettes smoked. With this variant of the COPD developing during pregnancy, a temporary physiological increase in the anti-inflammatory hormonal profile masks the extent, to which the number of cigarettes smoked affects the COPD severity.

EP27.02: Unexpected progression of asymptomatic ectopic pregnancy with extremely low serum β‐hCG

EP27.02: Unexpected progression of asymptomatic ectopic pregnancy with extremely low serum β‐hCG

Deep representation learning identifies associations between physical activity and sleep patterns during pregnancy and prematurity

Preterm birth (PTB) is the leading cause of infant mortality globally. Research has focused on developing predictive models for PTB without prioritizing cost-effective interventions. Physical activity and sleep present unique opportunities for interventions in low- and middle-income populations (LMICs). However, objective measurement of physical activity and sleep remains challenging and self-reported metrics suffer from low-resolution and accuracy. In this study, we use physical activity data collected using a wearable device comprising over 181,944 h of data across N = 1083 patients. Using a new state-of-the art deep learning time-series classification architecture, we develop a ‘clock’ of healthy dynamics during pregnancy by using gestational age (GA) as a surrogate for progression of pregnancy. We also develop novel interpretability algorithms that integrate unsupervised clustering, model error analysis, feature attribution, and automated actigraphy analysis, allowing for model interpretation with respect to sleep, activity, and clinical variables. Our model performs significantly better than 7 other machine learning and AI methods for modeling the progression of pregnancy. We found that deviations from a normal ‘clock’ of physical activity and sleep changes during pregnancy are strongly associated with pregnancy outcomes. When our model underestimates GA, there are 0.52 fewer preterm births than expected (P = 1.01e − 67, permutation test) and when our model overestimates GA, there are 1.44 times (P = 2.82e − 39, permutation test) more preterm births than expected. Model error is negatively correlated with interdaily stability (P = 0.043, Spearman’s), indicating that our model assigns a more advanced GA when an individual’s daily rhythms are less precise. Supporting this, our model attributes higher importance to sleep periods in predicting higher-than-actual GA, relative to lower-than-actual GA (P = 1.01e − 21, Mann-Whitney U). Combining prediction and interpretability allows us to signal when activity behaviors alter the likelihood of preterm birth and advocates for the development of clinical decision support through passive monitoring and exercise habit and sleep recommendations, which can be easily implemented in LMICs.

Antenatal Diagnosis of Intestinal Mal-rotation: King Hamad University Hospital Approach to Congenital Fetal Anomalies

Antenatal diagnosis of congenital fetal anomalies is a major contributor to the outcome of the condition, the effects on the progression of pregnancy, and the quality of life of the child. Intestinal malrotation and duodenal atresia are some of the diagnoses that can be easily made. In this case, we are highlighting the importance of early detection and the factors that allow for an early diagnosis. The report will discuss the case of a 33-year-old pregnant woman whose complaint of antepartum hemorrhage was the key to diagnosing her fetus with intestinal mal-rotation. In addition, this case report will describe the approach of KHUH in managing congenital fetal anomalies.

Neural substrates underlying rhythmic coupling of female reproductive and thermoregulatory circuits.

Coordinated fluctuations in female reproductive physiology and thermoregulatory output have been reported for over a century. These changes occur rhythmically at the hourly (ultradian), daily (circadian), and multi-day (ovulatory) timescales, are critical for reproductive function, and have led to the use of temperature patterns as a proxy for female reproductive state. The mechanisms underlying coupling between reproductive and thermoregulatory systems are not fully established, hindering the expansion of inferences that body temperature can provide about female reproductive status. At present, numerous digital tools rely on temperature to infer the timing of ovulation and additional applications (e.g., monitoring ovulatory irregularities and progression of puberty, pregnancy, and menopause are developed based on the assumption that reproductive-thermoregulatory coupling occurs across timescales and life stages. However, without clear understanding of the mechanisms and degree of coupling among the neural substrates regulating temperature and the reproductive axis, whether such approaches will bear fruit in particular domains is uncertain. In this overview, we present evidence supporting broad coupling among the central circuits governing reproduction, thermoregulation, and broader systemic physiology, focusing on timing at ultradian frequencies. Future work characterizing the dynamics of reproductive-thermoregulatory coupling across the lifespan, and of conditions that may decouple these circuits (e.g., circadian disruption, metabolic disease) and compromise female reproductive health, will aid in the development of strategies for early detection of reproductive irregularities and monitoring the efficacy of fertility treatments.

Partner relationship quality and IL-6:IL-10 trajectories from pregnancy to a year after-birth

BackgroundInflammatory activity during pregnancy and the postpartum period shifts systematically due to pregnancy progression, delivery, and postpartum recovery. Factors that deregulate inflammatory activity increase the risk for adverse pregnancy outcomes and slower postpartum recovery. The IL-6:IL-10 or TNF-α:IL-10 ratio is potentially one way to capture peripheral inflammatory regulation; higher values indicate that anti-inflammatory IL-10 is less effective at regulating pro-inflammatory TNF-α or IL-6, skewing towards maladaptive pro-inflammatory profiles. Associations between partner relationship quality and IL-6:IL-10 or TNF-α:IL-10 trajectories during pregnancy and the postpartum period have not been assessed. The purpose of this study was to test whether partner relationship quality (support, conflict) is associated with attenuated IL-6, IL-10, TNF-α, TNF-α:IL-10 or IL-6:IL-10 trajectories from the third trimester to the postpartum period. MethodsA sample of 162 women from the Healthy Babies Before Birth study reported on partner relationship quality (support and conflict) using the Social Support Effectiveness Questionnaire during the third trimester. Plasma samples were collected in the third trimester and at 1-, 6- and 12-months postpartum, and assayed for TNF-α, IL-6 and IL-10. Associations between both indicators of relationship quality (support and conflict) and TNF-α, IL-6, IL-10, IL-6:IL-10, TNF-α:IL-10 trajectories were tested using multi-level modelling, controlling for sociodemographic, pregnancy and health variables. ResultsPartner support interacted with time to predict IL-6:IL-10 trajectories, linear: b = -0.176, SE = 0.067, p =.010, quadratic: b = 0.012, SE = 0.005, p =.009. Lower partner support was associated with steeper increases in IL-6:IL-10 from the third trimester to 6 months postpartum, followed by steeper decreases in IL-6:IL-10 from 6 months postpartum to a year after birth. Partner conflict was not associated with IL-6:IL-10 levels at study entry, b = 0.233, SE = 0.219, p =.290, or over time, p’s > 0.782. Neither indicator of partner relationship quality was associated with TNF-α, IL-6, IL-10, or TNF-α:IL-10 trajectories, p’s > 0.205. ConclusionLower partner support may be associated with reduced moderation of IL-6 by IL-10 between pregnancy and a year postpartum, with possible consequences for maternal health and well-being.

Modeling the relationship between heat stress, feed intake, and day relative to calving in nonlactating dairy cows

Heat stress (HS) during the dry period can affect animal welfare, health, dry matter intake (DMI), and milk production in the subsequent lactation, which will negatively affect the profitability of dairy farms. In this study, the objective was to model the changes in DMI in pregnant nonlactating heat-stressed dairy cows with or without access to evaporative cooling systems. A database composed of individual DMI records from 244 pregnant nonlactating heat-stressed dairy cows from 7 experiments averaging from -35 (-42 to -21 d) to -1 d relative to calving (DRC) and housed in environmental conditions in which temperature-humidity index (THI) ranged from 58.4 to 83.3, with or without access to evaporative cooling systems was built. Generalized additive mixed-effects models were used to describe the relationships of DMI with HS and DRC. Changes in DMI with the increase in THI and the progression of pregnancy in cows with or without evaporative cooling systems were estimated using differential equations. On average, cows housed in barns without evaporative cooling systems had a reduction in DMI of 1.30 kg/d and increased rectal temperature in 0.22°C in relation to those housed in barns with evaporative cooling systems. Dry matter intake decreased as THI increased, but the reduction was greater for non-cooled cows as THI values increased. In addition, regardless of the THI, DMI started to decrease at DRC = -14 for cooled cows, while for non-cooled cows it already started at DRC = -30 relative to the previous days evaluated. The intensity of the reduction was lesser for cows that had access to evaporative cooling systems and/or were in the dry period in May-June as compared with those that were in the dry period in July-August or September-October. The models generated in this study, which include environmental variables, should lead to more accurate predictions of DMI during heat stress that can be used to formulate diets to meet the needs of the late pregnant cow because it is possible to predict changes in DMI as the heat load and DRC change. Such models are also expected to help dairy nutritionists to decide when and how to apply the dietary strategies available to attenuate the reductions in DMI with the intensity of heat stress and progression of pregnancy.

A Challenging Case: Colorectal Cancer During Pregnancy

Introduction: Colorectal cancer (CRC) occurring in younger women can lead to an increased incidence of colorectal cancer during pregnancy. The estimated frequency of malignancy during pregnancy with colorectal cancer specifically estimated at 1 in 13,000 pregnancies. However, the exact causes of colorectal cancer during pregnancy are not yet fully understood. Diagnosing and managing colorectal cancer during pregnancy pose significant challenges because the symptoms can be masked by the normal signs and symptoms of pregnancy. Case Pesentation: A 42-year-old pregnant patient, Mrs. L, presented with abdominal pain, a history of dark-colored bowel movements, and a lump on the left side of her neck that had been present for a year. She had also experienced a weight loss of 5 kg both before and during pregnancy, and there was no previous history of malignancy. The patient underwent various diagnostic procedures, including pregnancy ultrasound, abdominal ultrasound, and colonoscopy biopsy. Based on the comprehensive evaluation of the patient's medical history, physical examination, and supporting tests, she was diagnosed with stage IV rectal adenocarcinoma with metastases to the liver, kidney, and lymph nodes. The patient was in her second pregnancy (G2P1Ab0) at 27-29 weeks of gestation. Conclusion: Colorectal cancer during pregnancy poses diagnostic and therapeutic challenges, as the signs and symptoms are often attributed to the normal progression of pregnancy, resulting in delayed diagnosis at an advanced stage. Early detection, evaluation, and monitoring of nonspecific symptoms are crucial, and a multidisciplinary approach is necessary for the management of colorectal cancer during pregnancy.

Pregnancy and long-term outcomes of female patients with chronic myeloid leukemia on tyrosine kinase inhibitors who experienced unplanned pregnancies

PurposeDespite the general recommendation to avoid Tyrosine Kinase Inhibitors (TKIs) for Chronic Myeloid Leukemia (CML) during pregnancy, unplanned pregnancies still occur, particularly among female patients residing in low- and middle-income countries (LMICs). We aimed to investigate the outcomes of pregnancy, foetal development, and disease progression among female CML patients in chronic phase (CML-CP) undergoing TKI therapy who encountered unplanned pregnancies in a tertiary care hospital in northern India. MethodsWe conducted a retrospective analysis of all pregnancies in female CML-CP between January 2002 and December 2022 at our hospital. Patients were included if they had a confirmed diagnosis of CML-CP, were receiving TKI therapy during conception, and had available medical records. We analysed the data on pregnancy outcomes, foetal development, and disease progression through a review of medical records. ResultsWe identified 36 pregnancies in female CML-CP patients on TKI therapy during the study period, with 33 (91.7%) being unplanned. Sixteen pregnancies (48.5%) were conceived at less than major molecular remission (MMR) status. Twelve pregnancies (36.4%) were electively terminated, 4 (12.1%) had miscarriages, and, 17 (51.5%) pregnancies resulted in childbirth. Out of the 17 childbirths, 10 were full-term deliveries, and 7 were preterm deliveries. Twin pregnancies had a high incidence (18.2%). Among the 21 pregnancies that were not electively terminated, TKI was stopped at the first pregnancy detection in 14 pregnancies, while imatinib was continued throughout 7 pregnancies. Patients who discontinued TKI had a higher but statistically non-significant incidence of adverse pregnancy outcomes compared to those who continued imatinib throughout pregnancy (64.2% vs. 28.6%, p = 0.18). Additionally, the risk of long-term disease progression among patients who discontinued TKI during pregnancy and those who continued imatinib throughout pregnancy was 21.4% and 16.7% (p = 0.9), respectively. The risk of long-term disease progression was significantly increased in those persistently at less than MMR pre- and post-gestation (p = 0.0002). ConclusionOur findings suggest that continuing imatinib therapy during pregnancy, may be a reasonable option for CML patients residing in low- and middle-income countries to reduce the risk of disease progression and adverse pregnancy outcomes. Patients persistently at less than MMR levels pre- and post-gestation should be closely monitored for the risk of long-term disease progression. Further studies with larger sample sizes are needed to confirm these results.

Empirical Mode Decomposition Based Measures for Investigating the Progression of Pregnancy from Uterine EMG.

The objective of this study is to analyze the uterine electromyography (uEMG) signals to study the progression of pregnancy under term condition (gestational age > 36 weeks) using EMD-based time-frequency features. uEMG signals are obtained from the multiple public datasets during two conditions, namely T1 (acquired < 26 gestational weeks) and T2 (acquired ≥ 26 gestational weeks). The considered signals are preprocessed. Empirical mode decomposition is applied to decompose the signals and time-frequency features, such as median frequency (MDF), mean frequency (MNF), peak frequency and peak magnitude, are extracted from each intrinsic mode functions and statistically analyzed. The results depict that the obtained time-frequency features are able to distinguish between T1 and T2 conditions. The extracted features, namely MNF and MDF, are observed to decrease from T1 to T2 conditions. These features are found to have higher effect size, confirming the better differentiation between T1 and T2 conditions. It appears that EMD-based time-frequency features can aid in studying the evolving changes in uterine contractions towards labor.