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European Journal of Endocrinology Jan 2024Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism.
DESIGN
Systematic review and meta-analysis.
METHODS
A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713).
RESULTS
After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high.
CONCLUSIONS
This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.
Topics: Humans; Male; Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Hypogonadism; Klinefelter Syndrome; Spermatogenesis; Testis; Testosterone; Young Adult
PubMed: 38128110
DOI: 10.1093/ejendo/lvad166 -
Current Opinion in Obstetrics &... Mar 2012Vitamin D is part of a complex steroid hormone system long known to be involved in bone metabolism. Recently, vitamin D has been implicated in physiologic processes as... (Review)
Review
PURPOSE OF REVIEW
Vitamin D is part of a complex steroid hormone system long known to be involved in bone metabolism. Recently, vitamin D has been implicated in physiologic processes as diverse as vascular health, immune function, metabolism and placental function. This review summarizes the current evidence for the role of vitamin D in pregnancy and perinatal outcomes A systematic review of articles published in PubMed between May 2010 and October 2011 was undertaken using key words for vitamin D and pregnancy. Seventy-eight studies were reviewed.
RECENT FINDINGS
The biologic evidence regarding a role for vitamin D in reproductive outcomes is strong, and rates of vitamin D deficiency may be high among pregnant women. However, no consensus exists regarding optimum vitamin D levels in pregnancy or standard measurement of vitamin D deficiency. Clinical studies establishing an association between vitamin D levels and adverse pregnancy outcomes such as preeclampsia, gestational diabetes, low birthweight, preterm labor, cesarean delivery and infectious diseases have conflicting results. This is likely due to a paucity of randomized trials, heterogeneity of populations studied and low sample size with poor adjustment for confounding among observational studies.
SUMMARY
Further research should focus on defining optimum 25-hydroxy vitamin D levels in pregnancy as well as among various subgroups of the population. Randomized trials are needed to determine whether vitamin D supplementation can improve pregnancy outcomes. Currently, the American College of Obstetrics and Gynecology and the Institute of Medicine recommend 600 IU of daily vitamin D supplementation during pregnancy to support maternal and fetal bone metabolism.
Topics: Bone Density; Dietary Supplements; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Reproductive Health; Sunlight; United States; Vitamin D; Vitamin D Deficiency
PubMed: 22327734
DOI: 10.1097/GCO.0b013e3283505ab3 -
European Journal of Obstetrics,... Oct 2023To conduct a systematic review andmeta-analysis of all randomized controlled trials (RCTs) that investigated whether dual triggering [a combination of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review andmeta-analysis of all randomized controlled trials (RCTs) that investigated whether dual triggering [a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG)] of final oocyte maturation can improve the number of oocytes retrieved and clinical pregnancy rate in low or normal responders undergoing in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles using a GnRH-antagonist protocol.
STUDY DESIGN
Studies up to October 2022 were identified from PubMed, Scopus, Cochrane Library and Web of Science. The risk of bias of included studies was assessed. Dichotomous outcomes were reported as relative risks (RR), and continuous outcomes were reported as weighted mean differences (WMD) with 95% confidence intervals (CI). The primary outcomes were number of oocytes retrieved, number of mature [metaphase II (MII)] oocytes, clinical pregnancy rate and ongoing pregnancy rate; other IVF outcomes were considered as secondary outcomes.
RESULTS
Seven studies were identified, and 898 patients were eligible for inclusion in this meta-analysis. The results showed that the number of oocytes retrieved [WMD = 1.38 (95% CI 0.47-2.28), I = 66%, p = 0.003, low evidence], number of MII oocytes [WMD = 0.7 (95% CI 0.35-1.05), I = 42%, p < 0.0001, moderate evidence], number of embryos [WMD = 0.68 (95% CI 0.07-1.3), I = 67%, p = 0.03, low evidence] and number of good-quality embryos [WMD = 1.14 (95% CI 0.35-1.93), I = 0%, p = 0.005, moderate evidence] in the dual trigger group were significantly higher than in the hCG trigger group. The results of the ovarian response subgroup analysis showed significant differences in all of these outcomes in normal responders, and no differences in any of the outcomes in low responders, except for the number of MII oocytes. In low responders, clinical pregnancy rates may be improved in the dual trigger group [RR = 2.2 (95% CI 1.05-4.61), I = 28%, p = 0.04, low evidence].
CONCLUSION
Dual triggering by GnRH agonist and hCG improved oocyte maturity and embryo grading for normal responders in GnRH-antagonist cycles. Dual triggering for final oocyte maturation may improve clinical pregnancy rates in low responders.
Topics: Female; Pregnancy; Humans; Sperm Injections, Intracytoplasmic; Randomized Controlled Trials as Topic; Ovulation; Fertilization in Vitro; Chorionic Gonadotropin; Hormone Antagonists; Gonadotropin-Releasing Hormone
PubMed: 37639817
DOI: 10.1016/j.ejogrb.2023.08.014 -
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 -
Journal of Gynecology Obstetrics and... Sep 2021Maternal thyroid hormones are vital for a normal pregnancy and the development of fetus and childhood; inadequate availability of thyroid hormones during pregnancy is...
Maternal thyroid hormones are vital for a normal pregnancy and the development of fetus and childhood; inadequate availability of thyroid hormones during pregnancy is associated with adverse pregnancy outcomes. Isolated maternal hypothyroxinemia (IMH) is defined as a low maternal T4 in the absence of TSH elevation. This systematic review aimed to investigate the association between IMH and adverse pregnancy outcomes. PubMed, Scopus and Web of science were searched for retrieving observational studies published up to September 2020, investigating the association of IMH with adverse pregnancy outcomes. From a total of 308 articles, 17 met our eligibility criteria and were used for the purpose of the present study. Definition of IMH varied in different studies. While some studies reported no adverse pregnancy outcomes for IMH, other studies found a positive association between first trimester IMH and feto-maternal outcomes including gestational hypertension, gestational diabetes, preterm delivery, fetal distress, small for gestational age, musculoskeletal malformations, spontaneous abortion, placental abruption and macrosomia. IMH, identified in the second trimester was associated with an increase in the risk of gestational diabetes, and hypertensive disorders of pregnancy in one study. There is no consensus on the adverse effects of IMH on pregnancy outcomes. Further comprehensive cohort studies using one standard definition for IMH, with large sample size and control of important confounders such as iodine status and maternal Thyroid peroxidase antibody (TPOAb) are needed for precise assessment of this association.
Topics: Adult; Female; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 33401029
DOI: 10.1016/j.jogoh.2020.102057 -
BJOG : An International Journal of... May 2013Several biomarkers for predicting intrauterine growth restriction (IUGR) have been proposed in recent years. However, the predictive performance of these biomarkers has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several biomarkers for predicting intrauterine growth restriction (IUGR) have been proposed in recent years. However, the predictive performance of these biomarkers has not been systematically evaluated.
OBJECTIVE
To determine the predictive accuracy of novel biomarkers for IUGR in women with singleton gestations.
SEARCH STRATEGY
Electronic databases, reference list checking and conference proceedings.
SELECTION CRITERIA
Observational studies that evaluated the accuracy of novel biomarkers proposed for predicting IUGR.
DATA COLLECTION AND ANALYSIS
Data were extracted on characteristics, quality and predictive accuracy from each study to construct 2×2 tables. Summary receiver operating characteristic curves, sensitivities, specificities and likelihood ratios (LRs) were generated.
MAIN RESULTS
A total of 53 studies, including 39,974 women and evaluating 37 novel biomarkers, fulfilled the inclusion criteria. Overall, the predictive accuracy of angiogenic factors for IUGR was minimal (median pooled positive and negative LRs of 1.7, range 1.0-19.8; and 0.8, range 0.0-1.0, respectively). Two small case-control studies reported high predictive values for placental growth factor and angiopoietin-2 only when IUGR was defined as birthweight centile with clinical or pathological evidence of fetal growth restriction. Biomarkers related to endothelial function/oxidative stress, placental protein/hormone, and others such as serum levels of vitamin D, urinary albumin:creatinine ratio, thyroid function tests and metabolomic profile had low predictive accuracy.
CONCLUSIONS
None of the novel biomarkers evaluated in this review are sufficiently accurate to recommend their use as predictors of IUGR in routine clinical practice. However, the use of biomarkers in combination with biophysical parameters and maternal characteristics could be more useful and merits further research.
Topics: Biomarkers; Female; Fetal Growth Retardation; Humans; Pregnancy; Pregnancy Complications; Sensitivity and Specificity
PubMed: 23398929
DOI: 10.1111/1471-0528.12172 -
Reproductive Sciences (Thousand Oaks,... Dec 2022The objective of this study is to investigate whether kisspeptin levels in early pregnancy have a better diagnostic value on early pregnancy outcome as compared with... (Meta-Analysis)
Meta-Analysis Review
The objective of this study is to investigate whether kisspeptin levels in early pregnancy have a better diagnostic value on early pregnancy outcome as compared with human chorionic gonadotropin (hCG). This study was a systematic review and meta-analysis aiming to investigate the diagnostic value of kisspeptin levels on early pregnancy outcome. The primary outcome was miscarriage or viable intrauterine pregnancy. Five studies were included for systematic review, and three studies were included for meta-analysis. Meta-analysis showed kisspeptin levels had a good diagnostic value with the area under the curve (AUC) 0.902 (0.866, 0.937) when kisspeptin was measured after 6 weeks of gestation. Sensitivity analysis demonstrated kisspeptin levels had a diagnostic value with AUC = 0.881 (0.855, 0.906). hCG levels had a diagnostic value with AUC = 0.834 (0.785, 0.883), which was inferior to the diagnostic value of kisspeptin (mean difference = 0.09 (0.02, 0.16)). Kisspeptin measurement has a potential for comparable or even higher accuracy than hCG in differentiating between miscarriage and viable intrauterine pregnancy after 6 weeks of gestation.
Topics: Female; Pregnancy; Humans; Kisspeptins; Chorionic Gonadotropin; Abortion, Spontaneous; Pregnancy Outcome; Pregnancy Trimester, First
PubMed: 35212930
DOI: 10.1007/s43032-022-00856-8 -
Reviews in Endocrine & Metabolic... Apr 2023Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity... (Review)
Review
Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity can unravel pathophysiologic mechanisms and identify individuals at risk of adverse clinical outcomes. The literature was systematically reviewed to identify periconceptional biomarkers of the endocrine, inflammatory and one-carbon metabolic pathways influenced by maternal obesity. A search was conducted in Embase, Ovid Medline All, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases, complemented by manual search in PubMed until December 31, 2020. Eligible studies were those that measured biomarker(s) in relation to maternal obesity, overweight/obesity or body mass index (BMI) during the periconceptional period (14 weeks preconception until 14 weeks post conception). The ErasmusAGE score was used to assess the quality of included studies. Fifty-one articles were included that evaluated over 40 biomarkers. Endocrine biomarkers associated with maternal obesity included leptin, insulin, thyroid stimulating hormone, adiponectin, progesterone, free T4 and human chorionic gonadotropin. C-reactive protein was associated with obesity as part of the inflammatory pathway, while the associated one-carbon metabolism biomarkers were folate and vitamin B12. BMI was positively associated with leptin, C-reactive protein and insulin resistance, and negatively associated with Free T4, progesterone and human chorionic gonadotropin. Concerning the remaining studied biomarkers, strong conclusions could not be established due to limited or contradictory data. Future research should focus on determining the predictive value of the optimal set of biomarkers for their use in clinical settings. The most promising biomarkers include leptin, adiponectin, human chorionic gonadotropin, insulin, progesterone and CRP.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Leptin; C-Reactive Protein; Obesity, Maternal; Adiponectin; Progesterone; Obesity; Biomarkers; Insulin; Chorionic Gonadotropin; Carbon
PubMed: 36520252
DOI: 10.1007/s11154-022-09762-5 -
International Journal of Gynaecology... May 2018An ectopic pregnancy after hysterectomy is a rare but potentially life-threatening event. Women with this condition might not be appropriately investigated, resulting in... (Review)
Review
BACKGROUND
An ectopic pregnancy after hysterectomy is a rare but potentially life-threatening event. Women with this condition might not be appropriately investigated, resulting in delays in diagnosis and treatment.
OBJECTIVES
To characterize cases of ectopic pregnancy occurring after hysterectomy.
SEARCH STRATEGY
PubMed, Embase, Scopus, and Web of Science were searched using the terms "pregnancy, abdominal" or "pregnancy, tubal" or "pregnancy, ectopic" and "hysterectomy" or "post-hysterectomy" or "post hysterectomy."
SELECTION CRITERIA
Case reports or case series published in English up to October 10, 2016, were included. Patients were included if the diagnosis was confirmed by definitive tests such as serum or urine β-human chorionic gonadotropin (β-hCG) testing, ultrasonography evidence of pregnancy, or histology.
DATA COLLECTION AND ANALYSIS
Patient characteristics were extracted via a standard spreadsheet.
MAIN RESULTS
A total of 57 patients were included in the analysis. Abdominal pain was the predominant symptom. Implantation in a remaining fallopian tube was common. Most patients were managed surgically.
CONCLUSIONS
A high index of suspicion and a low threshold for performing a β-hCG pregnancy test is recommended in all women presenting with clinical symptoms of ectopic pregnancy, regardless of the hysterectomy status. This could lead to earlier diagnosis and fewer complications.
Topics: Abdominal Pain; Adult; Chorionic Gonadotropin, beta Subunit, Human; Fallopian Tubes; Female; Humans; Hysterectomy; Pregnancy; Pregnancy, Ectopic; Pregnancy, Tubal; Ultrasonography
PubMed: 29119546
DOI: 10.1002/ijgo.12385 -
American Journal of Obstetrics and... Aug 2014Currently, there is no consensus on the definition of hyperemesis gravidarum (HG; protracted vomiting in pregnancy) and no single widely used set of diagnostic criteria... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Currently, there is no consensus on the definition of hyperemesis gravidarum (HG; protracted vomiting in pregnancy) and no single widely used set of diagnostic criteria for HG. The various definitions rely on symptoms, sometimes in combination with laboratory tests. Through a systematic review, we aimed to summarize available evidence on the diagnostic value of biomarkers for HG. This could assist diagnosis and may shed light on the, as yet, not understood cause of the disorder.
STUDY DESIGN
We searched Medline and Embase for articles about diagnostic biomarkers for either the presence or severity of HG or nausea and vomiting of pregnancy. We defined HG as any combination of nausea, vomiting, dehydration, weight loss, or hospitalization for nausea and/or vomiting in pregnancy, in the absence of any other obvious cause for these complaints.
RESULTS
We found 81 articles on 9 biomarkers. Although 65% of all studies included only HG cases with ketonuria, we did not find an association between ketonuria and presence or severity of HG in 5 studies reporting on this association. Metaanalysis, with the use of the hierarchical summary receiver operating characteristics model, yielded an odds ratio of 3.2 (95% confidence interval, 2.0-5.1) of Heliobacter pylori for HG, as compared with asymptomatic control subjects (sensitivity, 73%; specificity, 55%). Studies on human chorionic gonadotropin and thyroid hormones, leptin, estradiol, progesterone, and white blood count showed inconsistent associations with HG; lymphocytes tended to be higher in women with HG.
CONCLUSION
We did not find support for the use of ketonuria in the diagnosis of HG. H pylori serology might be useful in specific patients.
Topics: Biomarkers; Chorionic Gonadotropin; Estradiol; Female; Helicobacter pylori; Humans; Hyperemesis Gravidarum; Ketosis; Leptin; Leukocyte Count; Lymphocytes; Pregnancy; Progesterone; Severity of Illness Index; Thyroid Hormones
PubMed: 24530975
DOI: 10.1016/j.ajog.2014.02.012