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Lancet (London, England) May 2021Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44... (Review)
Review
Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5-18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3-11·4%), two miscarriages is 1·9% (1·8-2·1%), and three or more miscarriages is 0·7% (0·5-0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need to be available. We recommend that miscarriage data are gathered and reported to facilitate comparison of rates among countries, to accelerate research, and to improve patient care and policy development.
Topics: Abortion, Habitual; Abortion, Spontaneous; Anxiety; Depression; Endometritis; Female; Fetal Growth Retardation; Humans; Premature Birth; Prevalence; Risk Factors; Stillbirth; Stress Disorders, Post-Traumatic; Suicide; Uterine Hemorrhage
PubMed: 33915094
DOI: 10.1016/S0140-6736(21)00682-6 -
Best Practice & Research. Clinical... Nov 2020Progesterone is essential for the maintenance of pregnancy, and progesterone deficiency is associated with miscarriage. The subject of whether progesterone... (Review)
Review
Progesterone is essential for the maintenance of pregnancy, and progesterone deficiency is associated with miscarriage. The subject of whether progesterone supplementation in early pregnancy can prevent miscarriage has been a long-standing research question and has been investigated and debated in the medical literature for over 70 years. During this time, several different progestogens have been synthesised and tested for the prevention of miscarriage. In this chapter, we describe the prior evidence alongside the latest research using micronized natural progesterone as well as synthetic progestogens, which were used to treat both recurrent and threatened miscarriage. The totality of evidence indicates that women with a past history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone. The clinical implications of the findings are discussed.
Topics: Abortion, Habitual; Abortion, Spontaneous; Abortion, Threatened; Female; Humans; Pregnancy; Progesterone; Progestins; Vagina
PubMed: 32978069
DOI: 10.1016/j.bpobgyn.2020.09.002 -
BMC Medicine Jun 2013Sporadic miscarriage is the most common complication of early pregnancy. Two or three consecutive pregnancy losses is a less common phenomenon, and this is considered a... (Review)
Review
Sporadic miscarriage is the most common complication of early pregnancy. Two or three consecutive pregnancy losses is a less common phenomenon, and this is considered a distinct disease entity. Sporadic miscarriages are considered to primarily represent failure of abnormal embryos to progress to viability. Recurrent miscarriage is thought to have multiple etiologies, including parental chromosomal anomalies, maternal thrombophilic disorders, immune dysfunction and various endocrine disturbances. However, none of these conditions is specific to recurrent miscarriage or always associated with repeated early pregnancy loss. In recent years, new theories about the mechanisms behind sporadic and recurrent miscarriage have emerged. Epidemiological and genetic studies suggest a multifactorial background where immunological dysregulation in pregnancy may play a role, as well as lifestyle factors and changes in sperm DNA integrity. Recent experimental evidence has led to the concept that the decidualized endometrium acts as biosensor of embryo quality, which if disrupted, may lead to implantation of embryos destined to miscarry. These new insights into the mechanisms behind miscarriage offer the prospect of novel effective interventions that may prevent this distressing condition.
Topics: Abortion, Habitual; Abortion, Spontaneous; Animals; DNA Fragmentation; Embryo Implantation; Female; Humans; Polymorphism, Genetic; Pregnancy
PubMed: 23803387
DOI: 10.1186/1741-7015-11-154 -
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 -
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 -
Alcoholism, Clinical and Experimental... Aug 2019To systematically review and critically evaluate studies reporting alcohol exposure during pregnancy and miscarriage. We searched PubMed, EMBASE, PsycINFO, and ProQuest... (Meta-Analysis)
Meta-Analysis
To systematically review and critically evaluate studies reporting alcohol exposure during pregnancy and miscarriage. We searched PubMed, EMBASE, PsycINFO, and ProQuest Theses for publications from January 1970 to January 2019. We identified studies about alcohol exposure during pregnancy and miscarriage. Information about study population, alcohol exposure assessment, outcome definition, covariates, and measures of association was collected. We assessed study quality using an adapted Newcastle-Ottawa Scale. Data were abstracted by 2 investigators independently. We conducted a random-effects meta-analysis to calculate the association between alcohol exposure and miscarriage risk and performed subgroup analyses to determine robustness of results to study differences. For studies reporting dose-specific effects, a pooled dose-response association was estimated using generalized least squares regression with and without restricted cubic spline terms for number of drinks consumed per week. Of 2,164 articles identified, 24 were eligible for inclusion. Meta-analysis of data from 231,808 pregnant women finds those exposed to alcohol during pregnancy have a greater risk of miscarriage compared to those who abstained (odds ratio [OR] 1.19, 95% confidence intervals [CI] 1.12, 1.28). Estimates did not vary by study design, study country, or method of alcohol ascertainment. For alcohol use of 5 or fewer drinks per week, each additional drink per week was associated with a 6% increase in miscarriage risk (OR 1.06, 95% CI 1.01, 1.10). Common study limitations reflect challenges inherent to this research, including difficulty recruiting participants early enough in pregnancy to observe miscarriage and collecting and quantifying information about alcohol consumption during pregnancy that accurately reflects use. This review provides evidence that alcohol consumption during pregnancy is associated with a dose-mediated increase in miscarriage risk. Future studies evaluating change in alcohol use in pregnancy are needed to provide insight into how alcohol consumption prior to pregnancy recognition impacts risk.
Topics: Abortion, Spontaneous; Alcohol Drinking; Dose-Response Relationship, Drug; Female; Humans; Pregnancy
PubMed: 31194258
DOI: 10.1111/acer.14124 -
Fertility and Sterility Nov 2023Infections with certain pathogens can lead to perinatal complications. Several infections have been also associated with an increased likelihood of miscarriage. This... (Review)
Review
Infections with certain pathogens can lead to perinatal complications. Several infections have been also associated with an increased likelihood of miscarriage. This manuscript discusses these infections, their modes of transmission, the evidence linking them to an increased risk of miscarriage, and whether prevention or treatment strategies are available.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Pregnancy Outcome
PubMed: 37625478
DOI: 10.1016/j.fertnstert.2023.08.719 -
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 -
Hormone Molecular Biology and Clinical... Aug 2016Progestational agents are often prescribed to prevent threatened miscarriage progressing to miscarriage, and subsequent miscarriages in recurrent pregnancy loss.... (Review)
Review
Progestational agents are often prescribed to prevent threatened miscarriage progressing to miscarriage, and subsequent miscarriages in recurrent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. A recent Cochrane review reported that progestogens were effective for treating threatened miscarriage with no harmful effects on mother or fetus. The results were not statistically different when vaginal progesterone was compared to placebo, (RR=0.47, 95% CI 0.17-1.30), whereas oral progestogen (dydrogesterone) was effective (RR=0.54, CI 0.35-0.84). The review concluded, that the small number of eligible studies, and the small number of the participants, limited the power of the metaanalysis. A later metaanalysis of five randomised controlled trials of threatened miscarriage comprised 660 patients. The results of 335 women who received dydrogesterone were compared to 325 women receiveing either placebo or bed rest. There was a 47% reduction in the odds ratio for miscarriage, (OR=0.47, CI 0.31-0.7). There was a 13% (44/335) miscarriage rate after dydrogesterone administration compared to 24% in control women. Recurrent miscarriage affects approximately 1% of women of child bearing age. A metaanalysis of progestational agents shows a 26% increase in the live birth rate. Again, dydrogesterone was associated with a more significant increase in the live birth rate than the other progestogens included in the metaanalysis.
Topics: Abortion, Spontaneous; Clinical Trials as Topic; Female; Humans; Pregnancy; Progestins
PubMed: 26677905
DOI: 10.1515/hmbci-2015-0058 -
Gynecologie, Obstetrique, Fertilite &... 2017In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriage. The aim of this study is to evaluate the association between endometriosis and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriage. The aim of this study is to evaluate the association between endometriosis and miscarriage in spontaneous pregnancy.
METHODS
We searched the Cochrane Library, Medline of eligible studies from inception to December 2016, without any restriction. We selected studies that compared endometriosis-affected pregnant women to disease-free pregnant women. To ensure the quality of the methodology, the PRISMA criteria have been met at all stages of the development of this meta-analysis. The primary adverse pregnancy outcomes studied was miscarriage. Three reviewers independently extracted the studies' characteristics and outcome data.
RESULTS
Of 225 identified abstracts, 4 primary studies met our inclusion criteria by comparing spontaneous pregnant patients with endometriosis to disease-free women. Miscarriage rate was higher in the endometriosis group (OR 1.77 [CI 95% 1.13-2.78]).
CONCLUSION
In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriages (almost 80% increased risk). Further prospective studies are needed to confirm these results in order to establish the exact impact of endometriosis on spontaneous pregnancy course.
Topics: Abortion, Spontaneous; Endometriosis; Female; Humans; MEDLINE; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Risk Factors
PubMed: 28712793
DOI: 10.1016/j.gofs.2017.06.003