Early pregnancy loss incidence in high-income settings: a protocol for a systematic review and meta-analysis.

BACKGROUND: Early pregnancy loss (unintended pregnancy loss before 20 completed weeks of gestation) is a common adverse pregnancy outcome, with previous evidence reporting incidence ranging from 10 to 30% of detected pregnancies. The objective of this systematic review and meta-analysis is to determine the incidence and range of early pregnancy loss in contemporary pregnant populations based on studies with good internal and external validity. Findings may be useful for clinical counseling in pre-conception and family planning settings and for people who experience early pregnancy loss. METHODS: We will search MEDLINE, EMBASE, and CINAHL databases using combinations of medical subject headings and keywords. Peer-reviewed, full-text original research articles that meet the following criteria will be included: (1) human study; (2) study designs: controlled clinical trials or observational studies with at least 100 pregnancies in the denominator, or systematic reviews of studies using these designs; (3) conducted in high-income countries; (4) reporting early pregnancy loss incidence, defined as unintended early pregnancy loss occurring prior to 20 weeks' gestation expressed as the number of losses among all pregnancies in the study period; (5) among a contemporary (1990 or later) general population of pregnancies; and (6) published between January 1, 1990, and August 31, 2021. We will assess the quality of included studies according to the United States Preventive Services Task Force Criteria for Assessing Internal and External Validity of Individual Studies. If appropriate, based on methodological comparability across included studies, we will conduct meta-analyses using random effects models to estimate the pooled incidence of early pregnancy loss among all studies with both good internal and external validity, with meta-analyses stratified by study design type (survey-based or self-reported and medical record-based), by induced abortion restrictions (restricted vs. unrestricted), and by gestational age (first trimester only vs. all gestational ages before 20 weeks). DISCUSSION: This systematic review will synthesize existing evidence to calculate a current estimate of early pregnancy loss incidence and variability in reported incidence estimates in high-income settings. The findings of this review may inform updates to clinical counseling in pre-conception and family planning settings, as well as for patients experiencing early pregnancy loss. SYSTEMATIC REVIEW REGISTRATION: We have registered this review with the International Prospective Register of Systematic Reviews (PROSPERO #226267 ).

Abortion training in Canadian obstetrics and gynecology residency programs.

OBJECTIVE: To evaluate the current state of abortion training in Canadian Obstetrics and Gynecology residency programs. STUDY DESIGN: Surveys were distributed to all Canadian Obstetrics and Gynecology residents and program directors. Data were collected on inclusion of abortion training in the curriculum, structure of the training and expected competency of residents in various abortion procedures. RESULTS: We distributed and collected surveys between November 2014 and May 2015. In total, 301 residents and 15 program directors responded, giving response rates of 55% and 94%, respectively. Based on responses by program directors, half of the programs had "opt-in" abortion training, and half of the programs had "opt-out" abortion training. Upon completion of residency, 66% of residents expected to be competent in providing first-trimester surgical abortion in an ambulatory setting, and 35% expected to be competent in second-trimester surgical abortion. Overall, 15% of residents reported that they were not aware of or did not have access to abortion training within their program, and 69% desired more abortion training during residency. CONCLUSION: Abortion training in Canadian Obstetrics and Gynecology residency programs is inconsistent, and residents desire more training in abortion. This suggests an ongoing unmet need for training in this area. Policies mandating standardized abortion training in obstetrics and gynecology residency programs are necessary to improve delivery of family planning services to Canadian women. IMPLICATIONS: Abortion training in Canadian Obstetrics and Gynecology residency programs is inconsistent, does not meet resident demand and is unlikely to fulfill the Royal College of Physicians and Surgeons of Canada objectives of training in the specialty.

Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice.

The Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca(2+) signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca(2+)/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These results support an important role for CaMKIV/Gr in Ca(2+)-regulated neuronal gene transcription and synaptic plasticity and suggest that the contribution of other signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.

Spinophilin regulates the formation and function of dendritic spines.

Spinophilin, a protein that interacts with actin and protein phosphatase-1, is highly enriched in dendritic spines. Here, through the use of spinophilin knockout mice, we provide evidence that spinophilin modulates both glutamatergic synaptic transmission and dendritic morphology. The ability of protein phosphatase-1 to regulate the activity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors was reduced in spinophilin knockout mice. Consistent with altered glutamatergic transmission, spinophilin-deficient mice showed reduced long-term depression and exhibited resistance to kainate-induced seizures and neuronal apoptosis. In addition, deletion of the spinophilin gene caused a marked increase in spine density during development in vivo as well as altered filopodial formation in cultured neurons. In conclusion, spinophilin appears to be required for the regulation of the properties of dendritic spines.

Altered stress-induced anxiety in adenylyl cyclase type VIII-deficient mice.

Stress results in alterations in behavior and physiology that can be either adaptive or maladaptive. To define the molecular pathways involved in the response to stress further, we generated mice deficient (KO) in the calcium-stimulated adenylyl cyclase type VIII (AC8) by homologous recombination in embryonic stem cells. AC8 KO mice demonstrate a compromise in calcium-stimulated AC activity in the hippocampus, hypothalamus, thalamus, and brainstem. Hippocampal slices derived from AC8 KO mice fail to demonstrate CA1-region long-term depression after low-frequency stimulation, and AC8 KO mice also fail to activate CRE-binding protein in the CA1 region after restraint stress. To define the behavioral consequences of AC8 deficiency, we evaluated AC8 KO mice in the elevated plus-maze and open field. Although naive AC8 KO mice exhibit indices of anxiety comparable with that of wild-type mice, AC8 KO mice do not show normal increases in behavioral markers of anxiety when subjected to repeated stress such as repetitive testing in the plus-maze or restraint preceding plus-maze testing. These results demonstrate a novel role for AC8 in the modulation of anxiety.