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Human Reproduction Update Nov 2023Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks... (Review)
Review
The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester.
BACKGROUND
Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure and complications, including hypertensive disorders and low birthweight babies. However, the role of estrogens in the periconceptional period and early pregnancy is still understudied.
OBJECTIVE AND RATIONALE
This review aims to summarize the current evidence on the role of maternal estrogens during the periconceptional period and the first trimester of pregnancies conceived naturally and following ART. Detailed molecular mechanisms and related clinical impacts are extensively described.
SEARCH METHODS
Data for this narrative review were independently identified by seven researchers on Pubmed and Embase databases. The following keywords were selected: 'estrogens' OR 'estrogen level(s)' OR 'serum estradiol' OR 'estradiol/estrogen concentration', AND 'early pregnancy' OR 'first trimester of pregnancy' OR 'preconceptional period' OR 'ART' OR 'In Vitro Fertilization (IVF)' OR 'Embryo Transfer' OR 'Frozen Embryo Transfer' OR 'oocyte donation' OR 'egg donation' OR 'miscarriage' OR 'pregnancy outcome' OR 'endometrium'.
OUTCOMES
During the periconceptional period (defined here as the critical time window starting 1 month before conception), estrogens play a crucial role in endometrial receptivity, through the activation of paracrine/autocrine signaling. A derailed estrogenic milieu within this period seems to be detrimental both in natural and ART-conceived pregnancies. Low estrogen levels are associated with non-conception cycles in natural pregnancies. On the other hand, excessive supraphysiologic estrogen concentrations at time of the LH peak correlate with lower live birth rates and higher risks of pregnancy complications. In early pregnancy, estrogen plays a massive role in placentation mainly by modulating angiogenic factor expression-and in the development of an immune-tolerant uterine micro-environment by remodeling the function of uterine natural killer and T-helper cells. Lower estrogen levels are thought to trigger abnormal placentation in naturally conceived pregnancies, whereas an estrogen excess seems to worsen pregnancy development and outcomes.
WIDER IMPLICATIONS
Most current evidence available endorses a relation between periconceptional and first trimester estrogen levels and pregnancy outcomes, further depicting an optimal concentration range to optimize pregnancy success. However, how estrogens co-operate with other factors in order to maintain a fine balance between local tolerance towards the developing fetus and immune responses to pathogens remains elusive. Further studies are highly warranted, also aiming to identify the determinants of estrogen response and biomarkers for personalized estrogen administration regimens in ART.
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Estrogens; Pregnancy Trimester, First; Placentation; Fertilization in Vitro; Estradiol
PubMed: 37353909
DOI: 10.1093/humupd/dmad016 -
Nature Jul 2023Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large,...
Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with the maternal decidua to promote a tissue microenvironment conducive to spiral artery remodelling (SAR). However, it remains a matter of debate regarding which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here we used a multiomics approach, combining the strengths of spatial proteomics and transcriptomics, to construct a spatiotemporal atlas of the human maternal-fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight and a 37-plex antibody panel to analyse around 500,000 cells and 588 arteries within intact decidua from 66 individuals between 6 and 20 weeks of gestation, integrating this dataset with co-registered transcriptomics profiles. Gestational age substantially influenced the frequency of maternal immune and stromal cells, with tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 and IDO-1 becoming increasingly enriched and colocalized at later time points. By contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting distinct monotonic and biphasic trends. Last, we developed an integrated model of SAR whereby invasion is accompanied by the upregulation of pro-angiogenic, immunoregulatory EVT programmes that promote interactions with the vascular endothelium while avoiding the activation of maternal immune cells.
Topics: Female; Humans; Pregnancy; Arteries; Decidua; Pregnancy Trimester, First; Trophoblasts; Uterus; Maternal-Fetal Exchange; Time Factors; Proteomics; Gene Expression Profiling; Datasets as Topic; Gestational Age
PubMed: 37468587
DOI: 10.1038/s41586-023-06298-9 -
Clinical Obstetrics and Gynecology Dec 2023In 2019, the US Centers for Disease Control reported that 7% of abortions were performed after 13 weeks of pregnancy, a small proportion of all terminations. However,...
In 2019, the US Centers for Disease Control reported that 7% of abortions were performed after 13 weeks of pregnancy, a small proportion of all terminations. However, the need for second-trimester abortions will increase commensurate with restrictions to access nationwide. Second-trimester abortions are performed with medications or through a procedure. Health care practitioners serving persons at risk of pregnancy should understand how abortions are performed and how to deliver evidence-based postabortion care. The purpose of this article is to provide a foundation for caring for individuals before, during, and after second-trimester abortion.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, Second; Abortion, Induced; Abortion, Spontaneous
PubMed: 37910075
DOI: 10.1097/GRF.0000000000000825 -
Hypertension (Dallas, Tex. : 1979) Nov 2023Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional...
BACKGROUND
Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers.
METHODS
Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption).
RESULTS
A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]).
CONCLUSIONS
Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pregnancy Trimester, First; Placenta; alpha-Fetoproteins; Down Syndrome; Pregnancy-Associated Plasma Protein-A; Retrospective Studies; Cohort Studies; Placenta Growth Factor; Pregnancy Complications; Pregnancy Trimester, Second; Biomarkers; Pre-Eclampsia
PubMed: 37671572
DOI: 10.1161/HYPERTENSIONAHA.123.21568 -
Low-dose aspirin therapy for the prevention of preeclampsia: time to reconsider our recommendations?American Journal of Obstetrics and... Oct 2023The American College of Obstetricians and Gynecologists recommends initiation of 81 mg of aspirin daily for women at risk of preeclampsia between 12 and 28 weeks'...
The American College of Obstetricians and Gynecologists recommends initiation of 81 mg of aspirin daily for women at risk of preeclampsia between 12 and 28 weeks' gestation, optimally before 16 weeks, with continuation until delivery. The World Health Organization recommends that 75 mg of aspirin should be initiated before 20 weeks of gestation for women at high risk of preeclampsia. Both the Royal College of Obstetricians and Gynaecologists and the National Institute of Health and Care Excellence quality statement on "Antenatal Assessment of Pre-eclampsia Risk" request that healthcare providers prescribe low-dose aspirin to pregnant women at increased risk of preeclampsia daily from 12 weeks of gestation. The Royal College of Obstetricians and Gynaecologists recommends 150 mg of aspirin daily, and the National Institute of Health and Care Excellence guidelines suggest risk stratification with a dosage of 75 mg for those at moderate risk of preeclampsia and 150 mg for those at high risk of preeclampsia. The International Federation of Gynecology and Obstetrics initiative on preeclampsia recommends 150 mg of aspirin to be initiated at 11 to 14+6 week's gestation and also proposes that 2 tablets of 81 mg is an acceptable alternative. Review of the available evidence suggests that both the dosage and timing of aspirin initiation is key to its effectiveness at reducing the risk of preeclampsia. Doses of >100 mg of aspirin daily initiated before 16 weeks' gestation seem to be most effective at reducing the risk of preeclampsia and thus dosages recommended by most major societies and organizations may not be effective. Randomized control trials examining 81 mg vs 162 mg of aspirin daily for the prevention of preeclampsia are required to assess the safety and efficacy of aspirin dosages available in the United States.
Topics: Female; Pregnancy; Humans; Pre-Eclampsia; Platelet Aggregation Inhibitors; Aspirin; Pregnancy Trimester, First; Gestational Age
PubMed: 37120049
DOI: 10.1016/j.ajog.2023.04.031 -
The Journal of Maternal-fetal &... Dec 2023Preliminary research suggests that maternal prenatal stress may alter the development of the fetal microbiome and resulting microbial composition after birth. However,...
OBJECTIVES
Preliminary research suggests that maternal prenatal stress may alter the development of the fetal microbiome and resulting microbial composition after birth. However, the findings of existing studies are mixed and inconclusive. The purpose of this exploratory study was to assess whether maternal stress during pregnancy is associated with the overall number and diversity of various microbial species in the infant gut microbiome or the abundance of specific bacterial taxa.
METHODS
Fifty-one women were recruited during their third trimester of pregnancy. The women completed a demographic questionnaire and Cohen's Perceived Stress Scale at recruitment. A stool sample was collected from their neonate at one month of age. Data on potential confounders, such as gestational age and mode of delivery, were extracted from medical records to control for their effects. 16s rRNA gene sequencing was used to identify the diversity and abundance of microbial species, along with multiple linear regression models to examine the effects of prenatal stress on microbial diversity. We employed negative binomial generalized linear models to test for differential expression of various microbial taxa among infants exposed to prenatal stress and those not exposed to prenatal stress.
RESULTS
More severe symptoms of prenatal stress were associated with a greater diversity of microbial species in the gut microbiome of neonates (β = .30, = .025). Certain microbial taxa, such as and were enriched among infants exposed to greater maternal stress in utero, while others, such as and , were depleted in contrast to infants exposed to less stress.
CONCLUSIONS
Findings suggest that mild to moderate stress exposure in utero could be associated with a microbial environment in early life that is more optimally prepared to thrive in a stressful postnatal environment. Adaptation of gut microbiota under conditions of stress may involve upregulation of bacterial species, including certain protective microorganisms (e.g. ), as well as downregulation of potential pathogens (e.g. ) epigenetic or other processes within the fetal/neonatal gut-brain axis. However, further research is needed to understand the trajectory of microbial diversity and composition as infant development proceeds and the ways in which both the structure and function of the neonatal microbiome may mediate the relationship between prenatal stress and health outcomes over time. These studies may eventually yield microbial markers and gene pathways that are biosignatures of risk or resilience and inform targets for probiotics or other therapies in utero or during the postnatal period.
Topics: Infant, Newborn; Infant; Pregnancy; Child; Humans; Female; Pregnancy Trimester, Third; RNA, Ribosomal, 16S; Bacteria; Fetus; Gastrointestinal Microbiome
PubMed: 37217447
DOI: 10.1080/14767058.2023.2214835 -
Clinical Obstetrics and Gynecology Dec 2023First-trimester abortion is a common and safe procedure. A focused history and physical examination are essential for providing this care. Laboratory assessment can...
First-trimester abortion is a common and safe procedure. A focused history and physical examination are essential for providing this care. Laboratory assessment can include Rh typing, hemoglobin, and cervicitis testing as indicated by a patient's risk factors. Procedural abortion in the first trimester includes cervical dilation with or without cervical preparation, and uterine evacuation utilizing a manual vacuum aspirator or electric vacuum aspirator. Complications occur rarely and are often easily managed at the time of diagnosis.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, First; Vacuum Curettage; Abortion, Induced; Abortion, Spontaneous; Cervix Uteri; Pregnancy Trimester, Second
PubMed: 37750678
DOI: 10.1097/GRF.0000000000000808 -
Best Practice & Research. Clinical... Feb 2024Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. It is important to identify women who are at high risk of developing this disorder in... (Review)
Review
Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. It is important to identify women who are at high risk of developing this disorder in their first trimester of pregnancy to allow timely therapeutic intervention. The use of low-dose aspirin initiated before 16 weeks of gestation can significantly reduce the rate of preterm preeclampsia by 62 %. Effective screening recommended by the Fetal Medicine Foundation (FMF) consists of a combination of maternal risk factors, mean arterial pressure, uterine artery pulsatility index (UtA-PI) and placental growth factor (PLGF). The current model has detection rates of 90 %, 75 %, and 41 % for early, preterm, and term preeclampsia, respectively at 10 % false-positive rate. Similar risk assessment can be performed during the second trimester in all pregnant women irrespective of first trimester screening results. The use of PLGF, UtA-PI, sFlt-1 combined with other investigative tools are part of risk assessment.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pre-Eclampsia; Placenta Growth Factor; Gestational Age; Pregnancy Trimester, First; Aspirin; Biomarkers; Uterine Artery
PubMed: 38056380
DOI: 10.1016/j.bpobgyn.2023.102436 -
Current Opinion in Obstetrics &... Dec 2023To review the evidence-informed options for cervical preparation prior to second-trimester dilation and evacuation (D&E). (Review)
Review
PURPOSE OF REVIEW
To review the evidence-informed options for cervical preparation prior to second-trimester dilation and evacuation (D&E).
RECENT FINDINGS
As abortion restrictions increase and the number of abortion clinics and providers decreases, pregnant people are facing more barriers to abortion access. Those in need are now often required to travel for second-trimester abortion care, only to be faced with additional restrictions, such as mandatory waiting periods. Cervical preparation is recommended prior to D&E and takes time for effect. Given the increasing time required to obtain an abortion, patients and providers may prefer same-day cervical preparation to decrease the total time required. Options for same-day cervical preparation include misoprostol alone with single or serial doses, and misoprostol combined with osmotic dilators or transcervical balloon (Foley catheter). Same-day preparation may require additional clinical space to accommodate people after initiation of cervical preparation to manage side-effects and timing of the abortion. Overnight options are also used and more frequently later in the second trimester. Overnight options include mifepristone, osmotic dilators, and transcervical balloon and are often combined with same-day misoprostol. Medication alone preparation is well tolerated and effective in the second trimester, with the addition of mechanical methods with advancing gestation. With many options and combinations being safe and effective, providers can be dynamic and alter approach with supply shortages, adjust to different clinical settings, consider patient medical and surgical factors, and accommodate provider and patient preferences.
SUMMARY
Multiple pharmacologic and mechanical options have been shown to be safe and effective for cervical preparation prior to D&E. Consideration for multiple factors should influence the method of cervical preparation and methods may vary by patient, provider and setting.
Topics: Pregnancy; Female; Humans; Misoprostol; Pregnancy Trimester, Second; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Mifepristone
PubMed: 37678155
DOI: 10.1097/GCO.0000000000000912 -
Irish Journal of Medical Science Aug 2023Second-trimester loss is pregnancy loss after the 12th and before the 24th completed weeks of pregnancy. This study aims to review cases of second-trimester miscarriage... (Review)
Review
BACKGROUND
Second-trimester loss is pregnancy loss after the 12th and before the 24th completed weeks of pregnancy. This study aims to review cases of second-trimester miscarriage who attended a large maternity hospital and to examine pregnancy outcomes in this group of women.
METHODS
This study is a review of cases of second-trimester miscarriage using descriptive, exploratory design, involving a retrospective chart review.
RESULTS
In this study, 106 cases of second-trimester miscarriage were reviewed. The cause of the miscarriage was found in 42.5% (n = 45) of cases. The majority of women, 84.5% (n = 82) had a normal pelvic ultrasound scan and 18.3% (n = 17) of cases were diagnosed with antiphospholipid syndrome. In women who became pregnant again, 60.9% (n = 39) had a live birth.
CONCLUSIONS
Establishing the cause of second-trimester miscarriage can be challenging, despite completing all recommended investigations. Outcomes in subsequent pregnancies are reassuring. This review highlights the need to undertake all recommended investigations to elicit the cause of second-trimester miscarriage and underpins the need for further research in this area.
Topics: Female; Pregnancy; Humans; Abortion, Spontaneous; Pregnancy Outcome; Pregnancy Trimester, Second; Retrospective Studies; Pregnancy Trimester, First
PubMed: 36396810
DOI: 10.1007/s11845-022-03227-z