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The Western Journal of Emergency... May 2024Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic...
INTRODUCTION
Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic gonadotropin (β-hCG) level to qualify for diagnostic testing (pelvic ultrasound) can delay diagnosis and treatment. In this study we sought to determine the relationship between β-hCG level and the size of ectopic pregnancy with associated outcomes.
METHODS
We performed a retrospective case review of patients diagnosed with ectopic pregnancy in an urban, academic emergency department specializing in obstetrical care, from January 1, 2015-December 31, 2017. Variables extracted included presentation, treatment, adverse outcomes, and rates of rupture.
RESULTS
We identified 519 unique ectopic pregnancies. Of those ectopic pregnancies, 22.9% presented with evidence of rupture on ultrasound, and 14.4% showed evidence of hemodynamic instability (pulse >100 beats per minute; systolic blood pressure <90 millimeters of mercury; or evidence of significant blood loss) on presentation. Medical management outcomes were as follows: of 177 patients who received single-dose methotrexate, 14.7% failed medical management and required surgical intervention; of 46 who received multi-dose methotrexate, 36.9% failed medical management and required surgical intervention. Ultimately, 55.7% of patients required operative management of their ectopic pregnancy. Mean β-hCG level at initial presentation was 7,096 milli-international units per milliliter (mIU/mL) (SD 88,872 mIU/mL) with a median of 1,289 mIU/mL; 50.4% of ectopic pregnancies presented with β-hCG levels less than the standard discriminatory zone of 1,500 mIU/mL. Additionally, 44% of the patients who presented with evidence of rupture had β-hCG levels less than 1,500 mIU/mL. Comparison of size of ectopic pregnancy (based on maximum dimension in millimeters) to β-hCG levels revealed a very weak correlation (r = 0.144, ), and detection of ectopic pregnancies by ultrasound was independent of β-hCG levels.
CONCLUSION
Levels of β-hCG do not correlate with the presence or size of an ectopic pregnancy, indicating need for diagnostic imaging regardless of β-hCG level in patients with clinical suspicion for ectopic pregnancy. Almost one-sixth of patients presented with evidence of hemodynamic instability, and approximately one quarter of patients presented with evidence of rupture requiring emergent operative management. Ultimately, more than half of patients required an operative procedure to definitively manage their ectopic pregnancy.
Topics: Humans; Female; Pregnancy; Pregnancy, Ectopic; Retrospective Studies; Chorionic Gonadotropin, beta Subunit, Human; Adult; Emergency Service, Hospital; Methotrexate; Abortifacient Agents, Nonsteroidal; Pregnancy Trimester, First; Ultrasonography, Prenatal
PubMed: 38801051
DOI: 10.5811/westjem.18396 -
International Journal of Molecular... May 2024The trophoblast cells are responsible for the transfer of nutrients between the mother and the foetus and play a major role in placental endocrine function by producing...
The trophoblast cells are responsible for the transfer of nutrients between the mother and the foetus and play a major role in placental endocrine function by producing and releasing large amounts of hormones and growth factors. Syncytiotrophoblast cells (STB), formed by the fusion of mononuclear cytotrophoblasts (CTB), constitute the interface between the foetus and the mother and are essential for all of these functions. We performed transcriptome analysis of human placental samples from two control groups-live births (LB), and stillbirths (SB) with a clinically recognised cause-and from our study group, idiopathic stillbirths (iSB). We identified 1172 DEGs in iSB, when comparing with the LB group; however, when we compared iSB with the SB group, only 15 and 12 genes were down- and upregulated in iSB, respectively. An assessment of these DEGs identified 15 commonly downregulated genes in iSB. Among these, several syncytiotrophoblast markers, like genes from the and families, as well as , , and , were significantly downregulated in placental samples from iSB. The transcriptome analysis revealed underlying differences at a molecular level involving the syncytiotrophoblast. This suggests that defects in the syncytial layer may underlie unexplained stillbirths, therefore offering insights to improve clinical obstetrics practice.
Topics: Humans; Female; Trophoblasts; Pregnancy; Placenta; Stillbirth; Down-Regulation; Biomarkers; Gene Expression Profiling; Transcriptome
PubMed: 38791219
DOI: 10.3390/ijms25105180 -
The Journal of Maternal-fetal &... Dec 2024To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with fertilization (IVF)/intracytoplasmic sperm...
OBJECTIVE
To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (IVF/ICSI) using different rFSH options and the effectiveness of antagonist treatment to induce ovulation using gonadotropin-releasing hormone agonists (GnRH-a) in combination with an human chorionic gonadotropin (HCG) trigger.
METHODS
A total of 132 fresh cycles were selected for this study, which were treated with IVF/ICSI in our hospital from March 2022 to December 2022. Observations were made according to different subgroups and the effects of different triggering methods on the number of oocytes obtained, embryo quality, and clinical outcomes.
RESULTS
The initial gonadotropin (Gn) dose, the number of oocytes, and the number of MII oocytes were higher in group A than in group B ( < .05), and the clinical pregnancy rate was 29.41% in group A. Group B had a clinical pregnancy rate of 27.5%. The double-trigger group was superior to the HCG-trigger group in terms of the number of 2PN, the number of viable embryos, and the number of high-quality embryos ( < .05). The use of a double-trigger regimen (OR = 0.667, 95%CI (0.375, 1.706), = .024) was a protective factor for the clinical pregnancy rate, whereas AFC (OR = 0.925, 95%CI (0.867, 0.986), = .017) was an independent factor for the clinical pregnancy rate.
CONCLUSIONS
The use of a dual-trigger regimen of GnRH-a in combination with HCG using an appropriate antagonist improves pregnancy outcomes in fresh embryo transfer cycles in older patients.
Topics: Humans; Female; Pregnancy; Sperm Injections, Intracytoplasmic; Ovulation Induction; Gonadotropin-Releasing Hormone; Fertilization in Vitro; Pregnancy Rate; Chorionic Gonadotropin; Retrospective Studies; Middle Aged; Adult; Follicle Stimulating Hormone; Aged
PubMed: 38777799
DOI: 10.1080/14767058.2024.2352790 -
Revista Da Associacao Medica Brasileira... 2024We aimed to assess the impact of the coronavirus disease 2019 pandemic on the clinical presentation of tubal ectopic pregnancies.
OBJECTIVE
We aimed to assess the impact of the coronavirus disease 2019 pandemic on the clinical presentation of tubal ectopic pregnancies.
METHODS
This retrospective cohort study was conducted at a tertiary center and included 76 cases of tubal ectopic pregnancies. The study period was divided into two groups: the pre-coronavirus disease group (January 2018 to February 2020, Group 1; n=47, 61.8%) and the coronavirus disease group (March 2020 to February 2022, Group 2; n=29, 38.2%). Subgroup analysis was also performed for tubal ruptured ectopic pregnancies as Group 1 (n=15, 62.5%) and Group 2 (n=9, 37.5%).
RESULTS
No statistically significant differences were observed between the pre-coronavirus disease and coronavirus disease groups in terms of demographic characteristics. Although the serum beta-human chorionic gonadotropin level was found to be higher in Group 2, the difference was not statistically significant (p=0.7). The groups appeared to be similar in treatment management, duration of hospitalization, and blood transfusion needs (p=0.3, p=0.6, and p=0.5, respectively). Additionally, no significant difference was observed between the groups in the evaluation of ruptured ectopic pregnancies (p=0.5). In the subgroup analysis of tubal ruptured ectopic pregnancies, no significant difference was observed.
CONCLUSION
To the best of our knowledge, there are few studies evaluating the effect of the pandemic on tubal ectopic pregnancies in the literature. Although we did not report statistically significant differences between groups in our study, given the potential prolonged duration of the pandemic, healthcare professionals should actively prompt their patients to seek necessary medical assistance.
Topics: Humans; Female; Retrospective Studies; COVID-19; Pregnancy; Adult; Pregnancy, Tubal; SARS-CoV-2; Pandemics; Young Adult; Chorionic Gonadotropin, beta Subunit, Human
PubMed: 38775533
DOI: 10.1590/1806-9282.20231445 -
Reproductive Biology and Endocrinology... May 2024Ovarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces...
BACKGROUND
Ovarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer.
METHODS
This prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18-38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile.
RESULTS
Ninety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28-3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03-4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth.
CONCLUSIONS
These data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF.
TRIAL REGISTRATION
NCT04693624 ( www.
CLINICALTRIALS
gov ).
Topics: Humans; Female; Luteal Phase; Fertilization in Vitro; Adult; Pregnancy; Prospective Studies; Progesterone; Chorionic Gonadotropin; Ovulation Induction; Pregnancy Rate; Young Adult; 17-alpha-Hydroxyprogesterone; Cohort Studies; Embryo Transfer; Adolescent; Birth Rate; Treatment Outcome; Live Birth
PubMed: 38769552
DOI: 10.1186/s12958-024-01229-3 -
BioRxiv : the Preprint Server For... May 2024Vitamin D is a hormone regulating gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. To...
BACKGROUND
Vitamin D is a hormone regulating gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. To date, studies of vitamin D and placental gene expression have focused on a limited number of candidate genes. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D.
OBJECTIVE
We investigated the association between prenatal vitamin D levels and placental gene expression in a large, prospective pregnancy cohort.
METHODS
Participants were recruited in Shelby County, Tennessee in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D level (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at mid-pregnancy (16-28 weeks' gestation) and delivery. Placenta samples were collected at birth. RNA was isolated and sequenced. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene co-expression network analysis (WGCNA).
RESULTS
The median 25(OH)D of participants was 21.8 ng/mL at mid-pregnancy (=774, IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery (=753, IQR: 16.8-29.1 ng/mL). Placental expression of 25 DEGs was associated with 25(OH)D at mid-pregnancy, but no DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and RNA transcription. Using WGCNA, we identified 2 gene modules whose expression was associated with 25(OH)D at mid-pregnancy and 1 module associated with 25(OH)D at delivery. These modules were enriched for genes related to mitochondrial and cytoskeletal function, and were regulated by transcription factors including , , , , and .
CONCLUSIONS
Our results indicate that 25(OH)D during mid-pregnancy, but not at delivery, is associated with placental gene expression at birth. Future research is needed to investigate a potential role of vitamin D in programming placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.
PubMed: 38765981
DOI: 10.1101/2024.05.10.593571 -
American Journal of Obstetrics and... May 2024Gestational diabetes mellitus affects up to 10% of pregnancies and is classified into subtypes gestational diabetes subtype A1 (GDMA1) (managed by lifestyle...
BACKGROUND
Gestational diabetes mellitus affects up to 10% of pregnancies and is classified into subtypes gestational diabetes subtype A1 (GDMA1) (managed by lifestyle modifications) and gestational diabetes subtype A2 (GDMA2) (requiring medication). However, whether these subtypes are distinct clinical entities or more reflective of an extended spectrum of normal pregnancy endocrine physiology remains unclear.
OBJECTIVE
Integrated bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomics harbors the potential to reveal disease gene signatures in subsets of cells and tissue microenvironments. We aimed to combine these high-resolution technologies with rigorous classification of diabetes subtypes in pregnancy. We hypothesized that differences between preexisting type 2 and gestational diabetes subtypes would be associated with altered gene expression profiles in specific placental cell populations.
STUDY DESIGN
In a large case-cohort design, we compared validated cases of GDMA1, GDMA2, and type 2 diabetes mellitus (T2DM) to healthy controls by bulk RNA-seq (n=54). Quantitative analyses with reverse transcription and quantitative PCR of presumptive genes of significant interest were undertaken in an independent and nonoverlapping validation cohort of similarly well-characterized cases and controls (n=122). Additional integrated analyses of term placental single-cell, single-nuclei, and spatial transcriptomics data enabled us to determine the cellular subpopulations and niches that aligned with the GDMA1, GDMA2, and T2DM gene expression signatures at higher resolution and with greater confidence.
RESULTS
Dimensional reduction of the bulk RNA-seq data revealed that the most common source of placental gene expression variation was the diabetic disease subtype. Relative to controls, we found 2052 unique and significantly differentially expressed genes (-2
2 thresholds; q<0.05 Wald Test) among GDMA1 placental specimens, 267 among GDMA2, and 1520 among T2DM. Several candidate marker genes (chorionic somatomammotropin hormone 1 [CSH1], period circadian regulator 1 [PER1], phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [PIK3CB], forkhead box O1 [FOXO1], epidermal growth factor receptor [EGFR], interleukin 2 receptor subunit beta [IL2RB], superoxide dismutase 3 [SOD3], dedicator of cytokinesis 5 [DOCK5], suppressor of glucose, and autophagy associated 1 [SOGA1]) were validated in an independent and nonoverlapping validation cohort (q<0.05 Tukey). Functional enrichment revealed the pathways and genes most impacted for each diabetes subtype, and the degree of proximal similarity to other subclassifications. Surprisingly, GDMA1 and T2DM placental signatures were more alike by virtue of increased expression of chromatin remodeling and epigenetic regulation genes, while albumin was the top marker for GDMA2 with increased expression of placental genes in the wound healing pathway. Assessment of these gene signatures in single-cell, single-nuclei, and spatial transcriptomics data revealed high specificity and variability by placental cell and microarchitecture types. For example, at the cellular and spatial (eg, microarchitectural) levels, distinguishing features were observed in extravillous trophoblasts (GDMA1) and macrophages (GDMA2). Lastly, we utilized these data to train and evaluate 4 machine learning models to estimate our confidence in predicting the control or diabetes status of placental transcriptome specimens with no available clinical metadata. CONCLUSION
Consistent with the distinct association of perinatal outcome risk, placentae from GDMA1, GDMA2, and T2DM-affected pregnancies harbor unique gene signatures that can be further distinguished by altered placental cellular subtypes and microarchitectural niches.
PubMed: 38763341
DOI: 10.1016/j.ajog.2024.05.014 -
European Journal of Obstetrics,... Jul 2024The use of various methotrexate (MTX) protocols for the treatment of ectopic pregnancy is well established. This study aimed to evaluate the efficacy of single- and... (Comparative Study)
Comparative Study
OBJECTIVE
The use of various methotrexate (MTX) protocols for the treatment of ectopic pregnancy is well established. This study aimed to evaluate the efficacy of single- and double-dose MTX protocols for the treatment of pregnancy of unknown location (PUL).
STUDY DESIGN
This retrospective study was conducted in the Department of Gynaecological Endocrinology, University Hospital, Krakow, Poland. Haemodynamically stable women with PUL were enrolled between January 2014 and September 2023. Demographics, gestational age and treatment outcomes were compared between women in the single-dose MTX group and women in the double-dose MTX group. The primary outcome was the success rate, measured as the number of women treated without surgical intervention. The secondary outcome was the number of days of MTX needed to achieve an appropriate decrease in beta-human chorionic gonadotrophin (β-hCG).
RESULTS
Two hundred and eleven women (mean age 33 ± 1.8 years) with PUL were enrolled in the study, with an overall success rate of 89.1 %. Single- and double-dose MTX protocols were found to have comparable treatment success rates (93 % and 95 %, respectively). Women with lower initial serum β-hCG (<2000 mIU/ml) had higher treatment efficacy compared with women with higher initial serum β-hCG (96.5 % vs 71.4 %), regardless of protocol type. The length of hospital stay for the women treated with the single-dose MTX protocol was 1 day shorter compared with that for the women treated with the double-dose MTX protocol.
CONCLUSION
Single- and double-dose MTX protocols have comparable efficacy and safety, and should be equally considered in women with PUL with initial β-hCG < 2000 mIU/ml.
Topics: Humans; Female; Methotrexate; Pregnancy; Adult; Retrospective Studies; Abortifacient Agents, Nonsteroidal; Pregnancy, Ectopic; Chorionic Gonadotropin, beta Subunit, Human; Treatment Outcome
PubMed: 38762953
DOI: 10.1016/j.ejogrb.2024.05.016 -
Scientific Reports May 2024A significant number of pregnancies are lost in the first trimester and 1-2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant...
A significant number of pregnancies are lost in the first trimester and 1-2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin β (β-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of β-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations.
Topics: Humans; Female; Pregnancy; Adult; Pregnancy, Ectopic; Biomarkers; Prospective Studies; Pregnancy Trimester, First; Machine Learning; Abortion, Spontaneous; Pregnancy Outcome; Progesterone; Chorionic Gonadotropin, beta Subunit, Human
PubMed: 38750192
DOI: 10.1038/s41598-024-61690-3 -
Endocrine Journal May 2024The placenta secretes a prolactin (PRL)-like hormone PRL3B1 (placental lactogen II), a luteotropic hormone essential for maintaining pregnancy until labor in mice. A...
The placenta secretes a prolactin (PRL)-like hormone PRL3B1 (placental lactogen II), a luteotropic hormone essential for maintaining pregnancy until labor in mice. A report from 1984 examined the secretion pattern of PRL3B1 in prepartum mice. In the current study, we found contradictory findings in the secretion pattern that invalidate the previous report. By measuring maternal plasma PRL3B1 and PRL every 4 hrs from gestational day 17 (G17), we newly discovered that maternal plasma PRL3B1 levels decrease rapidly in prepartum C57BL/6 mice. Interestingly, the onset of this decline coincided with the PRL surge at G18, demonstrating a plasma prolactin axis shift from placental to pituitary origin. We also found that maternal plasma progesterone regression precedes the onset of the PRL shift. The level of Prl3b1 mRNA was determined by RT-qPCR in the placenta and remained stable until parturition, implying that PRL3B1 peptide production or secretion was suppressed. We hypothesized that production of the PRL family, the 25 paralogous PRL proteins exclusively expressed in mice placenta, would decrease alongside PRL3B1 during this period. To investigate this hypothesis and to seek proteomic changes, we performed a shotgun proteome analysis of the placental tissue using data-independent acquisition mass spectrometry (DIA-MS). Up to 5,891 proteins were identified, including 17 PRL family members. Relative quantitative analysis between embryonic day 17 (E17) and E18 placentas showed no significant difference in the expression of PRL3B1 and most PRL family members except PRL7C1. These results suggest that PRL3B1 secretion from the placenta is suppressed at G18 (E18).
PubMed: 38749736
DOI: 10.1507/endocrj.EJ23-0724