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Endocrine Practice : Official Journal... Dec 2023Refractory hypothyroidism (RH) represents a challenge in the diagnosis and treatment within the field of thyroidology. It is defined as the inability to achieve disease... (Review)
Review
INTRODUCTION
Refractory hypothyroidism (RH) represents a challenge in the diagnosis and treatment within the field of thyroidology. It is defined as the inability to achieve disease control despite using levothyroxine (LT4) doses of 1.9 μg/kg/d or higher.
METHODS
A comprehensive review, encompassing 103 articles, was conducted using the Scielo, Scopus, and EMBASE databases, providing an approach to evaluation and diagnosis of this condition.
RESULTS
LT4 disintegrates and dissolves within an acidic gastric environment before being absorbed in the jejunum and ileum. It then extensively binds to serum transporter proteins and undergoes deiodination to yield tri-iodothyronine, the biologically active hormone. There are various nonpathological causes of RH, such as noncompliance with treatment, changes in the brand of LT4, food and drug interferences, as well as pregnancy. Pathological causes include lactose intolerance, Helicobacter pylori infection, giardiasis, among others. The diagnosis of RH involves conducting a thorough medical history and requesting relevant laboratory tests to rule out causes of treatment resistance. The LT4 absorption test allows for the identification of cases of malabsorption. The treatment of RH involves identifying and addressing the underlying causes of noncompliance or malabsorption. In cases of pseudomalabsorption, supervised and weekly administration of LT4 may be considered.
DISCUSSION
Early recognition of RH and correction of its underlying cause are of utmost importance, as this avoids the use of excessive doses of LT4 and prevents cardiovascular and bone complications associated with this condition.
Topics: Female; Pregnancy; Humans; Helicobacter Infections; Helicobacter pylori; Hypothyroidism; Thyroxine; Thyrotropin
PubMed: 37714332
DOI: 10.1016/j.eprac.2023.09.003 -
Frontiers in Endocrinology 2023Concerning contemporary fertilisation (IVF) practice, the use of frozen embryo transfer (FET) cycles has become more common than fresh transfers. Natural cycle (NC),... (Clinical Trial)
Clinical Trial
INTRODUCTION
Concerning contemporary fertilisation (IVF) practice, the use of frozen embryo transfer (FET) cycles has become more common than fresh transfers. Natural cycle (NC), programmed artificial cycle and mild stimulation cycle are primary endometrium preparation cycles. Monitoring serum progesterone levels in FET cycles are in the scope of current research focus. Low progesterone levels on the day of embryo transfer is presumed to negatively affect pregnancy outcomes, while progesterone supplementation may improve pregnancy rates. The purpose of our trial is to evaluate whether initiating subcutaneous (SC) progesterone supplementation on the day of embryo transfer when serum progesterone levels are below 10 ng/mL in tNC-FET will result in pregnancy rates comparable to those of patients with sufficient serum progesterone.
METHODS
Retrospective single centre study was conducted between August 2022 and April 2023 with 181 tNC-FETs. Patients were separated into groups according to serum progesterone concentrations (≥10 ng/mL and <10 ng/mL) on embryo transfer (ET) day. S.c progesterone (25 mg) was given on the day of ET when serum progesterone was <10 ng/mL, continuing until the 10th gestational week. Blood samples for pregnancy tests were collected 12 days after ET. Outcome parameters were pregnancy rate, clinical pregnancy rate (CPR), miscarriage rate, multiple pregnancy rate, biochemical pregnancy, and ongoing pregnancy rate (OPR).
RESULTS
About half (49.7%) had adequate progesterone concentrations (≥10ng/mL) on ET day. There was no significant difference between the groups regarding positive pregnancy test, OPR, multiple pregnancies, and miscarriage rates (57.8% versus 52.7%; 34.4% versus 29.7%, 1.1% versus 2.2%; 7.8% versus 5.5%; respectively, for progesterone concentrations on ET day ≥10 ng/mL and <10 ng/mL). With 55.2% of transfers leading to clinical pregnancy, significant differences emerged in biochemical pregnancy and CPR (3.3% vs 12.1%, P=0.02; 54.4% vs 40.7%, P=0.03, for ≥10 ng/mL and <10 ng/mL progesterone concentrations on ET day).
DISCUSSION
This study indicates that nearly half of the tNC-FETs may need luteal phase support due to low progesterone. However, 25 mc sc progesterone rescued the luteal support and yielded similar OPR as compared to normal progesterone group. Further studies are needed for understanding optimal progesterone levels, supplementation effectiveness, and potential benefits of earlier supplementation in FETs.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Embryo Transfer; Luteal Phase; Pregnancy Rate; Progesterone; Retrospective Studies
PubMed: 37937053
DOI: 10.3389/fendo.2023.1278042 -
Bratislavske Lekarske Listy 2024Toxoplasma gondii infection in pregnant women could lead to significant changes during the pregnancy, affect the outcomes of pregnancy and the timing of labour....
BACKGROUND
Toxoplasma gondii infection in pregnant women could lead to significant changes during the pregnancy, affect the outcomes of pregnancy and the timing of labour. Small‑for‑gestational‑age (SGA) newborns are defined by birthweight below the 10th percentile for gestational age. We tested an association between latent toxoplasmosis in pregnant women and deliveries of SGA babies.
MATERIAL AND METHODS
For testing, we included 1,647 women who gave birth to a singleton baby at ≥ 37 weeks of gestation. The complement-fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) tests for IgG and IgM were used. The latent form of toxoplasmosis was defined as a CFT titre of 1:8 or higher, together with index positivity IgG ELISA > 1.1 and negative IgM.
RESULTS
There were 406 (24.7 %) women positive, and 1,241 (75.3 %) women negative for latent toxoplasmosis. Of all deliveries. 190 were SGA‑positive and 1,457 were SGA‑negative. Our study found a statistically significant association between latent toxoplasmosis and SGA foetuses born at term. The Pearson chi-square model was statistically significant (χ2(1) = 7.365, p = .007). The odds ratio was 1.567.
CONCLUSION
Pregnant women with latent toxoplasmosis giving birth at ≥ 37 weeks of gestation have a 1.567 times higher risk of delivering an SGA baby (Tab. 2, Fig. 1, Ref. 30).
Topics: Pregnancy; Female; Infant, Newborn; Humans; Male; Toxoplasma; Toxoplasmosis; Birth Weight; Enzyme-Linked Immunosorbent Assay; Immunoglobulin G; Immunoglobulin M
PubMed: 38219061
DOI: 10.4149/BLL_2024_014 -
Ultrasound in Obstetrics & Gynecology :... Sep 2023To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre-eclampsia (PE) at various timepoints, using one of three... (Observational Study)
Observational Study
OBJECTIVE
To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre-eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio, or the competing-risks model, which combines maternal risk factors with biomarkers to estimate patient-specific risk.
METHODS
This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt-1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10 percentile); (ii) high sFlt-1/PlGF ratio (> 90 percentile); or (iii) the competing-risks model, in which maternal factors were combined with multiples of the median values of PlGF ('single test'), PlGF and sFlt-1 ('double test') or PlGF, sFlt-1 and MAP ('triple test'). Risk cut-offs corresponded to a screen-positive rate of 10%. DRs were compared between tests.
RESULTS
Of 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen-positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt-1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt-1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7-23.0%) and 12.4% (9.7-15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9-26.8%) and 12.9% (7.7-17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4-21.6%) and 5.4% (0.0-10.8%), respectively). The double test was superior to the sFlt-1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment.
CONCLUSION
At 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing-risks model triple test is superior to that of PlGF alone or the sFlt-1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, Third; Hypertension, Pregnancy-Induced; Placenta Growth Factor; Vascular Endothelial Growth Factor Receptor-1; Pre-Eclampsia; Vascular Endothelial Growth Factor A; Gestational Age; Biomarkers; Predictive Value of Tests
PubMed: 37329494
DOI: 10.1002/uog.26291 -
Acta Obstetricia Et Gynecologica... Sep 2023Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment.
MATERIAL AND METHODS
We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times.
TRIAL REGISTRATION NUMBER
PROSPERO: CRD42021214093.
RESULTS
1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group.
CONCLUSIONS
Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
Topics: Pregnancy; Humans; Female; Methotrexate; Watchful Waiting; Pregnancy, Tubal; Pregnancy, Ectopic; Chorionic Gonadotropin; Abortifacient Agents, Nonsteroidal; Retrospective Studies
PubMed: 37345445
DOI: 10.1111/aogs.14617 -
Alternative Therapies in Health and... Dec 2023To explore the prognostic significance of the Glucose Disposal Index (DI) concerning unfavorable pregnancy outcomes in mothers and newborns affected by Gestational...
OBJECTIVE
To explore the prognostic significance of the Glucose Disposal Index (DI) concerning unfavorable pregnancy outcomes in mothers and newborns affected by Gestational Diabetes Mellitus (GDM).
METHODS
Our investigation encompassed 75 GDM patients who received treatment at Anhui Mingguang People's Hospital between January 2019 and July 2023. Subjects were divided into two groups: those with adverse pregnancy outcomes (n = 18) and those without (n = 57). Between weeks 24 and 28 of gestation, all participants underwent a 75 g Oral Glucose Tolerance Test (OGTT), and relevant details such as height, weight, and complete pregnancy information were gathered. The Insulin Sensitivity Index (ISI) and the area beneath the insulin-to-glucose curve from 0 to 120 minutes (AUC_INS120/AUC_GLU120) were computed from the 75 g OGTT findings, and their multiplication was represented as DI. Comparisons between groups were made using t tests, Wilcoxon rank-sum tests, and χ2 tests. Binary logistic regression was applied to probe the relationship between DI and the risk of adverse pregnancy outcomes, and the Receiver Operating Characteristic (ROC) curve was employed to evaluate the predictive capacity of DI.
RESULTS
Statistically meaningful differences in FPG, HbA1c, and DI were noted between the groups (P < .05), whereas the difference in 2hPG was not significant (P > .05). Pearson correlation analysis revealed a negative correlation between DI and both FPG and HbA1c (P < .05). Multivariate logistic regression showed that DI (OR = 0.599) was a determining factor of adverse pregnancy outcomes (P < .05). The ROC curve disclosed an AUC of 0.837 for DI in forecasting adverse pregnancy outcomes (95% CI: 0.741-0.933), with a specificity of 82.10% and a sensitivity of 80.65% at the optimal threshold value of 2.1.
CONCLUSION
An elevation in DI among GDM patients is closely linked to a reduced risk of adverse pregnancy outcomes, corroborating DI's prognostic value for such outcomes in gestational diabetes.
PubMed: 38295312
DOI: No ID Found -
AJOG Global Reports Aug 2023Pregnancy of unknown location (PUL) is a term used when there is a positive pregnancy test but no sonographic evidence for an intrauterine pregnancy (IUP) or ectopic...
BACKGRO
Pregnancy of unknown location (PUL) is a term used when there is a positive pregnancy test but no sonographic evidence for an intrauterine pregnancy (IUP) or ectopic pregnancy (EP). This term is a classification and not a final diagnosis.
OBJECTIVE
This study aimed to evaluate the diagnostic value of the Inexscreen test on the outcome of patients with pregnancies of unknown location.
STUDY DESIGN
In this prospective study, a total of 251 patients with a diagnosis of pregnancy of unknown location at the gynecologic emergency department of the La Conception Hospital, Marseille, France, between June 2015 and February 2019 were included. The Inexscreen (semiquantitative determination of intact human urinary chorionic gonadotropin) test was performed on patients with a diagnosis of pregnancy of unknown location. They participated in the study after information and consent collection. The main outcome measures (sensitivity, specificity, predictive values, and the Youden index) of Inexscreen were calculated for the diagnosis of abnormal pregnancy (nonprogressive pregnancy) and ectopic pregnancy.
RESULTS
The sensitivity and specificity of Inexscreen for the diagnosis of abnormal pregnancy in patients with pregnancy of unknown location were 56.3% (95% confidence interval, 47.0%-65.1%) and 62.8% (95% confidence interval, 53.1%-71.5%), respectively. The sensitivity and specificity of Inexscreen for the diagnosis of ectopic pregnancy in patients with pregnancy of unknown location were 81.3% (95% confidence interval, 57.0%-93.4%) and 55.6% (95% confidence interval, 48.6%-62.3%), respectively. The positive predictive value and negative predictive value of Inexscreen for ectopic pregnancy were 12.9% (95% confidence interval, 7.7%-20.8%) and 97.4% (95% confidence interval, 92.5%-99.1%), respectively.
CONCLUSION
Inexscreen is a rapid, non-operator-dependent, noninvasive, and inexpensive test that allows the selection of patients at high risk of ectopic pregnancy in case of pregnancy of unknown location. This test allows an adapted follow-up according to the technical platform available in a gynecologic emergency service.
PubMed: 37334250
DOI: 10.1016/j.xagr.2023.100223 -
Human Fertility (Cambridge, England) Dec 2023We assessed whether estimation of follicular growth, rather than actual measurement of follicular size on the day of hCG trigger, affected pregnancy rates in...
We assessed whether estimation of follicular growth, rather than actual measurement of follicular size on the day of hCG trigger, affected pregnancy rates in intrauterine insemination (IUI) cycles. Patient and cycle characteristics were extracted from an existing database. Comparisons were made between the pregnant (defined as a positive beta hCG) and non-pregnant groups for the following variables: patient's age, number of previous IUI cycles, type of ovarian stimulation, endometrial thickness, number of follicles measuring 14 mm and above, pre and post wash sperm parameters, cycle day when IUI was done and number of days between last ultrasound scan and ovulation trigger. A total of 7302 cycles were included in the final analysis. In 4055 cycles (55.5%) the hCG trigger was on the day of the last ultrasound, in 2285 cycles (31.3%) the hCG trigger was 1 day after the last ultrasound, in 850 (11.6%) it was 2 days after the last ultrasound and in 112 (1.5%) it was 3 or more days after the last ultrasound. Sperm parameters, younger maternal age, and the number of follicles above 14 mm were all associated with pregnancy. No association was found between positive pregnancy test rates and the time from last ultrasound to hCG trigger. Planning IUI based on the estimation of follicular growth 1-4 days before trigger, does not affect pregnancy rates.
Topics: Female; Pregnancy; Humans; Male; Infant, Newborn; Insemination, Artificial; Semen; Pregnancy Rate; Fertilization in Vitro; Ovulation Induction; Chorionic Gonadotropin
PubMed: 36398709
DOI: 10.1080/14647273.2022.2145916 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2024Chronic myeloid leukemia (CML) has evolved from an invariably fatal disease to a chronic disorder that can be treated with targeted drugs and allows survival... (Review)
Review
Chronic myeloid leukemia (CML) has evolved from an invariably fatal disease to a chronic disorder that can be treated with targeted drugs and allows survival expectations approaching age-matched controls. Thus, pregnancy and conception in CML should not be precluded anymore; however, to ensure the well-being of both the mother and the developing fetus careful planning and management are required. Tyrosine Kinase Inhibitors (TKIs) are not genotoxic or carcinogenic but can pose a risk to the developing fetus, due to their teratogenic potential. The risk depends on the TKI and the stage of fetal development during exposure. Teratogenic risk is high in the first trimester of pregnancy when the baby's organs and structures are forming (5-12 weeks). If a female patient is on therapy it is advisable to stop therapy at the first positive pregnancy test (3-5 weeks) to maximize the length of treatment-free, and ideally to not treat until delivery. If needed, the medication plan during pregnancy may be adjusted. Interferons can be used at any time, imatinib and nilotinib have a reduced placental crossing and could be carefully used after 16 weeks, whereas dasatinib crosses the placenta and can induce problems throughout the whole gestation. Management of pregnancy in CML is complex. This manuscript is an update of the state of the art allowing healthcare providers to be informed of the different situations that can occur and their governance.
Topics: Female; Humans; Pregnancy; Protein Kinase Inhibitors; Placenta; Imatinib Mesylate; Dasatinib; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
PubMed: 38151389
DOI: 10.1016/j.clml.2023.11.011 -
BMJ Open Dec 2023Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be...
INTRODUCTION
Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth.
METHODS AND ANALYSIS
This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and at <27 weeks of gestation, confirmed by ultrasound. At enrolment and 30-34 weeks of pregnancy, participants receive on-site tests for and , with treatment if test results are positive. At these visits, additional vaginal specimens are taken for: PCR detection and quantification of , spp., , and ; microscopy and Nugent scoring; and for 16S ribosomal RNA gene sequencing and quantification. Pregnancy outcomes are collected from a postnatal visit and birth registers. The primary outcome is gestational age at birth. Statistical analyses will explore associations between specific microorganisms and gestational age at birth. To explore the association with the quantity of microorganisms, we will construct an index of microorganism load and use mixed-effects regression models and classification and regression tree analysis to examine which combinations of microorganisms contribute to earlier gestational age at birth.
ETHICS AND DISSEMINATION
This protocol has approvals from the University of Cape Town Research Ethics Committee and the Canton of Bern Ethics Committee. Results from this study will be uploaded to preprint servers, submitted to open access peer-reviewed journals and presented at regional and international conferences.
TRIAL REGISTRATION NUMBER
NCT06131749; Pre-results.
Topics: Child; Female; Pregnancy; Infant, Newborn; Humans; Child, Preschool; Premature Birth; Pregnant Women; Cohort Studies; HIV Infections; Gestational Age; Pregnancy Complications, Infectious; Reproductive Tract Infections; South Africa; Pregnancy Outcome; Chlamydia trachomatis; Mycoplasma Infections
PubMed: 38154893
DOI: 10.1136/bmjopen-2023-081562