-
Acta Obstetricia Et Gynecologica... Dec 2018Women with miscarriage experience several negative emotional feelings such as grief, isolation, coping, and despair. However, less is known about how the type of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Women with miscarriage experience several negative emotional feelings such as grief, isolation, coping, and despair. However, less is known about how the type of treatment and diagnosis of miscarriage influence the emotional experience.
MATERIAL AND METHODS
The present study was a randomized prospective longitudinal cohort study, in which women with spontaneous miscarriage (n = 35), and women with missed miscarriage (n = 67), were included to answer three validated questionnaires: Revised Impact of Miscarriage Scale, Perinatal Grief Scale, and Montgomery and Åsberg Depression Rating Scale, concerning experience of miscarriage, psychological well-being, and mental health 1 week and 4 months after finalized treatment.
RESULTS
There was no difference between the 2 diagnosis groups in feelings as measured by Revised Impact of Miscarriage Scale, Montgomery and Åsberg Depression Rating Scale, and Perinatal Grief Scale 1 week after the miscarriage. However, the psychological well-being improved significantly 4 months after the miscarriage. Separated by treatment, women treated with misoprostol alone had more depressive symptoms than women treated with misoprostol and subsequent vacuum aspiration.
CONCLUSIONS
It can be concluded that diagnosis of miscarriage had limited influence on the experiences of miscarriage, but shorter duration of treatment with misoprostol and subsequent vacuum aspiration resulted in fewer depressive symptoms.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Spontaneous; Adult; Combined Modality Therapy; Depression; Female; Grief; Humans; Longitudinal Studies; Misoprostol; Pregnancy; Prospective Studies; Psychiatric Status Rating Scales; Risk Factors; Time Factors; Treatment Outcome; Vacuum Curettage
PubMed: 30063247
DOI: 10.1111/aogs.13432 -
Seminars in Reproductive Medicine Jul 2023Obesity affects nearly 40% of reproductive-aged women and has serious implications for women's overall and reproductive health. Women with an elevated body mass index... (Review)
Review
Obesity affects nearly 40% of reproductive-aged women and has serious implications for women's overall and reproductive health. Women with an elevated body mass index (BMI) have higher rates of anovulation and irregular menses, lower success with fertility treatment, and significantly higher rates of pregnancy complications, such as hypertension/preeclampsia, gestational diabetes, and preterm delivery. Many studies have also shown an association between obesity and early pregnancy loss. However, the causal association between BMI and miscarriage has not been elucidated, likely due to the multifactorial effects that BMI may have on early pregnancy development. In addition, BMI as an isolated variable fails to capture other relevant confounding health risk factors, such as nutrition, physical activity, and insulin resistance. In this review, we will summarize the current literature demonstrating the association between BMI and miscarriage, highlight the research that attempts to explain the association, and finally provide data on therapeutic interventions to improve reproductive outcomes in women suffering from obesity and early pregnancy loss.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Adult; Abortion, Spontaneous; Obesity; Risk Factors; Fertility; Infertility, Female; Body Mass Index
PubMed: 38101448
DOI: 10.1055/s-0043-1777759 -
JAMA Psychiatry Apr 2024Benzodiazepine use during pregnancy has raised significant concerns due to the potential harmful effects of this drug class on neonates. Studies on the association...
IMPORTANCE
Benzodiazepine use during pregnancy has raised significant concerns due to the potential harmful effects of this drug class on neonates. Studies on the association between benzodiazepine use and the risk of miscarriage are limited.
OBJECTIVE
To quantify the risk of miscarriage associated with benzodiazepine use during pregnancy after controlling for unmeasured confounders and exposure time trends.
DESIGN, SETTING, AND PARTICIPANTS
This was a nationwide, population-based case-time-control study using Taiwan's National Birth Certificate Application database and the National Health Insurance database. Pregnancies resulting in miscarriage between 2004 and 2018 were included in the case group and were 1:1 matched with exposure time-trend control individuals using disease risk score, considering demographic characteristics and prepregnancy comorbidities. Data were analyzed from August 2022 to March 2023.
EXPOSURES
Discordant exposures to benzodiazepines during risk period (1-28 days before miscarriage) and 2 reference periods (31-58 days and 181-208 days before the last menstrual period) were compared for each pregnancy.
MAIN OUTCOMES AND MEASURES
Miscarriage was defined as any pregnancy loss occurring between the first prenatal care visit (usually 8 weeks) and the 19th completed week of pregnancy.
RESULTS
This study comprised a total of 3 067 122 pregnancies among 1 957 601 women, 136 134 of which (4.4%) resulted in miscarriage. The mean (SD) age of the study population was 30.61 (5.91) years. The use of benzodiazepines during pregnancy was associated with an increased risk of miscarriage (odds ratio [OR], 1.69; 95% CI, 1.52-1.87), and consistent findings were observed across multiple sensitivity analyses considering different time windows and accounting for misclassification. In subgroup analyses, an increased risk of miscarriage was associated with each commonly used individual benzodiazepine, ranging from case-time-control ORs of 1.39 (95% CI, 1.17-1.66) for alprazolam to 2.52 (95% CI, 1.89-3.36) for fludiazepam.
CONCLUSIONS AND RELEVANCE
This nationwide case-time-control study revealed an increased risk of miscarriage associated with benzodiazepine use during pregnancy after accounting for measurable confounders, and results were unlikely to be due to unmeasured confounding. These findings underscore the necessity for health care professionals to meticulously balance the risk-benefit ratio when considering the use of benzodiazepines to treat psychiatric and sleep disorders during pregnancy.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Adult; Abortion, Spontaneous; Benzodiazepines; Risk Factors; Case-Control Studies; Risk Assessment
PubMed: 38150230
DOI: 10.1001/jamapsychiatry.2023.4912 -
Human Reproduction Update Jun 2022There is a wealth of information regarding interventions for treating subfertility. The majority of studies exploring interventions for improving conception rates also... (Review)
Review
BACKGROUND
There is a wealth of information regarding interventions for treating subfertility. The majority of studies exploring interventions for improving conception rates also report on pregnancy outcomes. However, there is no efficient way for clinicians, researchers, funding organizations, decision-making bodies or women themselves to easily access and review the evidence for the effect of adjuvant therapies on key pregnancy outcomes in subfertile women.
OBJECTIVE AND RATIONALE
The aim was to summarize all published systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions in the subfertile population, specifically reporting on the pregnancy outcomes of miscarriage and live birth. Furthermore, we aimed to highlight promising interventions and areas that need high-quality evidence.
SEARCH METHODS
We searched the Cochrane Database of Systematic Reviews and PubMed clinical queries SR filter (inception until July 2021) with a list of key words to capture all SRs specifying or reporting any miscarriage outcome. Studies were included if they were SRs of RCTs. The population was subfertile women (pregnant or trying to conceive) and any intervention (versus placebo or no treatment) was included. We adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for determining the quality of the evidence. Exclusion criteria were overview reviews, reviews that exclusively reported on women conceiving via natural conception, reviews including non-randomized study designs or reviews where miscarriage or live birth outcomes were not specified or reported.
OUTCOMES
The primary outcome was miscarriage, defined as pregnancy loss <24 weeks of gestation. Data were also extracted for live birth where available. We included 75 published SRs containing 121 251 participants. There were 14 classes of intervention identified: luteal phase, immunotherapy, anticoagulants, hCG, micronutrients, lifestyle, endocrine, surgical, pre-implantation genetic testing for aneuploidies (PGT-As), laboratory techniques, endometrial injury, ART protocols, other adjuncts/techniques in the ART process and complementary interventions. The interventions with at least moderate-quality evidence of benefit in reducing risk of miscarriage or improving the chance of a live birth are: intrauterine hCG at time of cleavage stage embryo transfer, but not blastocyst transfer, antioxidant therapy in males, dehydroepiandrosterone in women and embryo medium containing high hyaluronic acid. Interventions showing potential increased risk of miscarriage or reduced live birth rate are: embryo culture supernatant injection before embryo transfer in frozen cycles and PGT-A with the use of fluorescence in situ hybridization.
WIDER IMPLICATIONS
This review provides an overview of key pregnancy outcomes from published SRs of RCTs in subfertile women. It provides access to concisely summarized information and will help clinicians and policy makers identify knowledge gaps in the field, whilst covering a broad range of topics, to help improve pregnancy outcomes for subfertile couples. Further research is required into the following promising interventions: the dose of progesterone for luteal phase support, peripheral blood mononuclear cells for women with recurrent implantation failure, glucocorticoids in women undergoing IVF, low-molecular-weight heparin for unexplained subfertility, intrauterine hCG at the time of cleavage stage embryo or blastocyst transfer and low oxygen concentrations in embryo culture. In addition, there is a need for high-quality, well-designed RCTs in the field of reproductive surgery. Finally, further research is needed to demonstrate the integrated effects of non-pharmacological lifestyle interventions.
Topics: Abortion, Spontaneous; Female; Humans; Infertility; Live Birth; Male; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Systematic Reviews as Topic
PubMed: 35137098
DOI: 10.1093/humupd/dmac001 -
Fertility and Sterility Nov 2023The physical and psychological impact of miscarriage can be devastating. There are many lifestyle and therapeutic interventions that may prevent a miscarriage. In this... (Review)
Review
The physical and psychological impact of miscarriage can be devastating. There are many lifestyle and therapeutic interventions that may prevent a miscarriage. In this review, we have outlined the key areas for health optimization to prevent pregnancy loss, drawing on the most up-to-date evidence available. The 3 key areas identified are lifestyle optimization in women, lifestyle optimization in men, and therapeutic interventions. The evidence demonstrates that the treatments to consider are first-trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Abortion, Habitual; Aspirin; Heparin; Thyroxine; Hypothyroidism
PubMed: 37648141
DOI: 10.1016/j.fertnstert.2023.08.955 -
Obstetrics and Gynecology Clinics of... Sep 2022First trimester miscarriage, or early pregnancy loss, is a common occurrence in the United States. Miscarriage management includes expectant, medical, or surgical... (Review)
Review
First trimester miscarriage, or early pregnancy loss, is a common occurrence in the United States. Miscarriage management includes expectant, medical, or surgical approaches. Decisions about management options should be approached through shared decision making between the patient and provider and with consideration of patient's preferences, hemodynamic stability, cost, gestational age, and effectiveness. Emergencies requiring immediate interventions are rare. Newer developments in management, including a more effective medical regimen with the addition of mifepristone and cost-effective and convenient in-office surgical interventions, have expanded treatment options.
Topics: Abortion, Spontaneous; Cost-Benefit Analysis; Female; Gestational Age; Humans; Mifepristone; Pregnancy; Pregnancy Trimester, First
PubMed: 36122989
DOI: 10.1016/j.ogc.2022.04.004 -
Human Reproduction (Oxford, England) Apr 2023In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth? (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY QUESTION
In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth?
SUMMARY ANSWER
In women with threatened miscarriage, 400 mg vaginal progesterone nightly, from onset of bleeding until 12 weeks, did not increase live birth rates.
WHAT IS KNOWN ALREADY
Limited evidence has indicated that vaginal micronized progesterone may make little or no difference to the live birth rate when compared with placebo in women with threatened miscarriage. Subgroup analysis of one recent randomized trial reported that in women with bleeding and at least one previous miscarriage, progesterone might be of benefit.
STUDY DESIGN, SIZE, DURATION
We performed a randomized, double-blinded, placebo-controlled trial between February 2012 and April 2019. Eligible pregnant women under 10 weeks gestation, experiencing a threatened miscarriage as apparent from vaginal bleeding were randomized into two groups in a 1:1 ratio: the intervention group received 400 mg progesterone as vaginal pessaries, the control group received placebo vaginal pessaries, both until 12 weeks gestation. The primary endpoint was live birth. We planned to randomize 386 women (193 per group). The study was stopped at a planned interim analysis for futility after randomization of 278 women.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This trial was conducted at the Mater Mothers' Hospital, a tertiary centre for maternity care in South Brisbane, Queensland, Australia. We randomized 139 women to the intervention group and 139 women to the placebo group. Primary outcome data were available for 136 women in the intervention group and 133 women in the placebo group.
MAIN RESULTS AND THE ROLE OF CHANCE
The live birth rates were 82.4% (112/136) and 84.2% (112/133) in the intervention group and placebo group, respectively (risk ratio (RR) 0.98, 95% CI 0.88 to 1.09; risk difference -0.02, 95% CI -0.11 to 0.07; P = 0.683). Among women with at least one previous miscarriage, live birth rates were 80.6% (54/67) and 84.4% (65/77) (RR 0.95, 95% CI 0.82-1.11; P = 0.550). No significant effect was seen from progesterone in women with two (RR 1.28, 95% CI 0.96-1.72; P = 0.096) or more (RR 0.79, 95% CI 0.53-1.19; P = 0.267) previous miscarriages. Preterm birth rates were 12.9% and 9.3%, respectively (RR 1.38; 95% CI 0.69 to 2.78; P = 0.361). Median birth weight was 3310 vs 3300 g (P = 0.992). There were also no other significant differences in obstetric and perinatal outcomes.
LIMITATIONS, REASONS FOR CAUTION
Our study was single centre and did not reach the planned sample size because it was stopped prematurely at an interim analysis.
WIDER IMPLICATIONS OF THE FINDINGS
We did not find evidence supporting the treatment effect of vaginal progesterone in women with threatened miscarriage. Progesterone in this setting should not be routinely used for threatened miscarriage. The treatment effect in women with threatened miscarriage after previous miscarriages warrants further research.
STUDY FUNDING/COMPETING INTEREST(S)
Mothers' and babies Golden Casket Clinical Fellowship (L.A.M.). Progesterone and placebo pessaries were provided by Perrigo Australia.B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work.
TRIAL REGISTRATION NUMBER
ACTRN12611000405910.
TRIAL REGISTRATION DATE
19 April 2011.
DATE OF FIRST PATIENT’S ENROLMENT
06 February 2012.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Progesterone; Abortion, Spontaneous; Abortion, Threatened; Premature Birth; Maternal Health Services; Pregnancy Rate
PubMed: 36806843
DOI: 10.1093/humrep/dead029 -
Ultrasound in Obstetrics & Gynecology :... Oct 2019To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta-analysis.
METHODS
A search of MEDLINE, EMBASE and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. Eligible for inclusion were large controlled studies reporting data for pregnancy loss prior to 24 weeks' gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had an invasive procedure and controls were inputted into contingency tables and the risk of miscarriage was estimated for each study. Summary statistics based on a random-effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Subgroup analyses were performed according to the similarity in risk levels for chromosomal abnormality between the invasive-testing and control groups. Heterogeneity was assessed using the I statistic. Egger's bias was estimated to assess reporting bias in published studies.
RESULTS
The electronic search yielded 2943 potential citations, from which 12 controlled studies for amniocentesis and seven for CVS were selected for inclusion in the systematic review. A total of 580 miscarriages occurred following 63 723 amniocentesis procedures, resulting in a weighted risk of pregnancy loss of 0.91% (95% CI, 0.73-1.09%). In the control group, there were 1726 miscarriages in 330 469 pregnancies with a loss rate of 0.58% (95% CI, 0.47-0.70%). The weighted procedure-related risk of miscarriage following amniocentesis was 0.30% (95% CI, 0.11-0.49%; I = 70.1%). A total of 163 miscarriages occurred following 13 011 CVS procedures, resulting in a risk of pregnancy loss of 1.39% (95% CI, 0.76-2.02%). In the control group, there were 1946 miscarriages in 232 680 pregnancies with a loss rate of 1.23% (95% CI, 0.86-1.59%). The weighted procedure-related risk of miscarriage following CVS was 0.20% (95% CI, -0.13 to 0.52%; I = 52.7%). However, when studies including only women with similar risk profiles for chromosomal abnormality in the intervention and control groups were considered, the procedure-related risk for amniocentesis was 0.12% (95% CI, -0.05 to 0.30%; I = 44.1%) and for CVS it was -0.11% (95% CI, -0.29 to 0.08%; I = 0%).
CONCLUSIONS
The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions were compared to control groups of the same risk profile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Abortion, Spontaneous; Adult; Amniocentesis; Chorionic Villi Sampling; Chromosome Aberrations; Embryo Loss; Female; Gestational Age; Humans; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 31124209
DOI: 10.1002/uog.20353 -
Human Reproduction Update Sep 2020Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has long been recognised as a major risk factor for miscarriage, being strongly related with fetal chromosomal abnormalities. The relation between paternal age and the risk of miscarriage is less evident, yet it is biologically plausible that an increasing number of genetic and epigenetic sperm abnormalities in older males may contribute to miscarriage. Previous meta-analyses showed associations between advanced paternal age and a broad spectrum of perinatal and paediatric outcomes. This is the first systematic review and meta-analysis on paternal age and spontaneous miscarriage.
OBJECTIVE AND RATIONALE
The aim of this systematic review and meta-analysis is to evaluate the effect of paternal age on the risk of spontaneous miscarriage.
SEARCH METHODS
PubMed, Embase and Cochrane databases were searched to identify relevant studies up to August 2019. The following free text and MeSH terms were used: paternal age, father's age, male age, husband's age, spontaneous abortion, spontaneous miscarriage, abortion, miscarriage, pregnancy loss, fetal loss and fetal death. PRISMA guidelines for systematic reviews and meta-analysis were followed. Original research articles in English language addressing the relation between paternal age and spontaneous miscarriage were included. Exclusion criteria were studies that solely focused on pregnancy outcomes following artificial reproductive technology (ART) and studies that did not adjust their effect estimates for at least maternal age. Risk of bias was qualitatively described for three domains: bias due to confounding, information bias and selection bias.
OUTCOMES
The search resulted in 975 original articles. Ten studies met the inclusion criteria and were included in the qualitative synthesis. Nine of these studies were included in the quantitative synthesis (meta-analysis). Advanced paternal age was found to be associated with an increased risk of miscarriage. Pooled risk estimates for miscarriage for age categories 30-34, 35-39, 40-44 and ≥45 years of age were 1.04 (95% CI 0.90, 1.21), 1.15 (0.92, 1.43), 1.23 (1.06, 1.43) and 1.43 (1.13, 1.81) respectively (reference category 25-29 years). A second meta-analysis was performed for the subgroup of studies investigating first trimester miscarriage. This showed similar pooled risk estimates for the first three age categories and a slightly higher pooled risk estimate for age category ≥45 years (1.74; 95% CI 1.26, 2.41).
WIDER IMPLICATIONS
Over the last decades, childbearing at later ages has become more common. It is known that frequencies of adverse reproductive outcomes, including spontaneous miscarriage, are higher in women with advanced age. We show that advanced paternal age is also associated with an increased risk of spontaneous miscarriage. Although the paternal age effect is less pronounced than that observed with advanced maternal age and residual confounding by maternal age cannot be excluded, it may have implications for preconception counselling of couples comprising an older aged male.
Topics: Abortion, Spontaneous; Adult; Aged; Fathers; Female; Humans; Male; Maternal Age; Middle Aged; Paternal Age; Pregnancy; Pregnancy Outcome; Prenatal Care; Risk Factors; Young Adult
PubMed: 32358607
DOI: 10.1093/humupd/dmaa010 -
The Journal of Medicine and Philosophy May 2023The frequency of death from miscarriage is very high, greater than the number of deaths from induced abortion or major diseases. Berg (2017 , Philosophical Studies...
The frequency of death from miscarriage is very high, greater than the number of deaths from induced abortion or major diseases. Berg (2017 , Philosophical Studies 174:1217-26) argues that, given this, those who contend that personhood begins at conception (PAC) are obliged to reorient their resources accordingly-towards stopping miscarriage, in preference to stopping abortion or diseases. This argument depends on there being a basic moral similarity between these deaths. I argue that, for those that hold to PAC, there are good reasons to think that there is no such similarity. There is a morally relevant difference between preventing killing and letting die, giving PAC supporters reasons to prioritize reducing abortion over reducing miscarriage. And the time-relative interest account provides a morally relevant difference in the badness of death of miscarriages and deaths of born adults, justifying attempts to combat major diseases over attempts to combat miscarriage. I consider recent developments in the literature and contend that these new arguments are unsuccessful in establishing moral similarities between deaths from miscarriage and abortion, and deaths from miscarriage and disease.
Topics: Pregnancy; Adult; Female; Humans; Abortion, Spontaneous; Abortion, Induced; Personhood; Morals; Dissent and Disputes; Value of Life; Moral Obligations; Beginning of Human Life
PubMed: 37078977
DOI: 10.1093/jmp/jhad012