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Current Opinion in Obstetrics &... Apr 2022Postpartum hemorrhage (PPH) is the leading preventable cause of maternal morbidity and mortality worldwide. Uterine atony is identified as the underlying etiology in up... (Review)
Review
PURPOSE OF REVIEW
Postpartum hemorrhage (PPH) is the leading preventable cause of maternal morbidity and mortality worldwide. Uterine atony is identified as the underlying etiology in up to 80% of PPH. This serves as a contemporary review of the epidemiology, risk factors, pathophysiology, and treatment of uterine atony.
RECENT FINDINGS
Rates of postpartum hemorrhage continue to rise worldwide with the largest fraction attributed to uterine atony. A simple 0-10 numerical rating score for uterine tone was recently validated for use during cesarean delivery and may allow for more standardized assessment in clinical and research settings. The optimal prophylactic dose of oxytocin differs depending on the patient population, but less than 5 units and as low as a fraction of one unit is needed for PPH prevention, with an increased requirements within that range for cesarean birth, those on magnesium, and advanced maternal age. Carbetocin is an appropriate alternative to oxytocin. Misoprostol shows limited to no efficacy for uterine atony in recent studies. Several uncontrolled case studies demonstrate novel mechanical and surgical interventions for treating uterine atony.
SUMMARY
There is a critical, unmet need for contemporary, controlled studies to address the increasing threat of atonic PPH.
Topics: Female; Humans; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Uterine Inertia
PubMed: 35102109
DOI: 10.1097/GCO.0000000000000776 -
Journal of General Internal Medicine Aug 2020Abortion and miscarriage are common, affecting millions of US women each year. By age 45, one in four women in the USA will have had an abortion, and at least as many... (Review)
Review
Abortion and miscarriage are common, affecting millions of US women each year. By age 45, one in four women in the USA will have had an abortion, and at least as many will have had a miscarriage. Most individuals seeking abortion services do so before 10 weeks' gestation when medication abortions are a safe and effective option, using a regimen of oral mifepristone followed by misoprostol tablets. When a pregnancy is non-viable before 13 weeks' gestation, it is referred to as an early pregnancy loss or miscarriage and can be managed using the same mifepristone and misoprostol regimen. Given their safety and efficacy, mifepristone and misoprostol can be offered in ambulatory settings without special equipment or on-site emergency services. As more patients find it difficult to access clinical care when faced with an undesired pregnancy or a miscarriage, it is important for general internists and primary care providers to become familiar with how to use medications to manage these common conditions. We summarize the most recent evidence regarding the use of mifepristone with misoprostol for early abortion and miscarriage. We discuss clinical considerations and resources for integrating mifepristone and misoprostol into clinical practice. By learning to prescribe mifepristone and misoprostol, clinicians can expand access to time-sensitive health services for vulnerable populations.
Topics: Abortion, Induced; Abortion, Spontaneous; Female; Gestational Age; Humans; Middle Aged; Mifepristone; Misoprostol; Pregnancy
PubMed: 32410127
DOI: 10.1007/s11606-020-05836-9 -
European Journal of Obstetrics,... Jan 2023Identification of patients at risk for postpartum hemorrhage (PPH) may allow for prompt diagnosis and intervention. Individual risk factors, risk assessment tools and... (Review)
Review
Identification of patients at risk for postpartum hemorrhage (PPH) may allow for prompt diagnosis and intervention. Individual risk factors, risk assessment tools and prediction models have been used for determining a patient's risk of PPH. Measures for the prevention of PPH include identification and management of iron deficiency anemia, unit readiness and preparedness through performing regular simulations and having a PPH cart or medication kit readily available, prophylactic uterotonic - carbetocin alone or dual agents such as oxytocin and misoprostol or oxytocin and methylergometrine or antifibrinolytic (oxytocin and tranexamic acid) use in the third stage of labor immediately after fetal head delivery, and controlled cord traction.
Topics: Pregnancy; Female; Humans; Postpartum Hemorrhage; Oxytocin; Oxytocics; Delivery, Obstetric; Misoprostol
PubMed: 36455391
DOI: 10.1016/j.ejogrb.2022.11.021 -
American Journal of Obstetrics and... Mar 2022Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during cesarean delivery. However, some randomized controlled trials suggest that other uterotonics are superior.
OBJECTIVE
We conducted a network meta-analysis comparing the ability of pharmacologic agents to reduce blood loss and minimize the need for additional uterotonics during cesarean delivery.
DATA SOURCES
We searched the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE databases from inception to May 2020.
STUDY ELIGIBILITY CRITERIA
We included randomized controlled trials that compared oxytocin, carbetocin, misoprostol, ergometrine, carboprost, or combinations of these in the prevention of postpartum hemorrhage during cesarean delivery.
METHODS
We performed a systematic review followed by an NMA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quality of the evidence was assessed with the Confidence in Network Meta-Analysis approach and Grading of Recommendations, Assessment, Development and Evaluations tool within the summary of findings table. Our primary outcomes were the estimated blood loss and need for additional uterotonics. Secondary outcomes included nausea and postpartum hemorrhage of >1000 mL. We performed sensitivity analyses to explore the influence of surgical context and oxytocin administration strategy.
RESULTS
A total of 46 studies with 7368 participants were included. Of those, 21 trials (6 agents and 3665 participants) formed the "estimated blood loss" network and, considering the treatment effects, certainty in the evidence, and surface under the cumulative ranking curve scores, carbetocin was assessed to probably be superior to oxytocin, but only in reducing the estimated blood loss by a clinically insignificant volume (54.83 mL; 95% confidence interval, 26.48-143.78). Misoprostol, ergometrine, and the combination of oxytocin and ergometrine were assessed to probably be inferior, whereas the combination of oxytocin and misoprostol was assessed to definitely be inferior to oxytocin. A total of 37 trials (8 agents and 6193 participants) formed the "additional uterotonic" network and, again, carbetocin was assessed to probably be superior to oxytocin, requiring additional uterotonics 185 (95% confidence interval, 130-218) fewer times per 1000 cases. Oxytocin plus misoprostol, oxytocin plus ergometrine, and misoprostol were assessed to probably be inferior, whereas carboprost, ergometrine, and the placebo were definitely inferior to oxytocin. For both primary outcomes, oxytocin administration strategies had a higher probability of being the best uterotonic, if initiated as a bolus.
CONCLUSION
Carbetocin is probably the most effective agent in reducing blood loss and the need for additional uterotonics. Oxytocin appears to be more effective when initiated as a bolus.
Topics: Carboprost; Ergonovine; Female; Humans; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 34534498
DOI: 10.1016/j.ajog.2021.08.060 -
American Family Physician Feb 2022Induction of labor is a common obstetric procedure, and approximately one-fourth of pregnant patients undergo the procedure. Although exercise and nipple stimulation can...
Induction of labor is a common obstetric procedure, and approximately one-fourth of pregnant patients undergo the procedure. Although exercise and nipple stimulation can increase the likelihood of spontaneous labor, sexual intercourse may not be effective. Acupuncture has been used for labor induction; however, it has not been shown to increase vaginal delivery rates. There is strong evidence that membrane sweeping can increase the likelihood of spontaneous labor within 48 hours. Cervical preparation or ripening is often needed before induction. Some evidence shows that the use of nonpharmacologic approaches such as osmotic dilators and cervical ripening balloons reduce time to delivery. The effect of amniotomy on labor is uncertain. Pharmacologic intervention with oxytocin or prostaglandins is effective for cervical ripening and induction of labor. Combining a balloon catheter with misoprostol is a common practice and has been shown to decrease time to delivery in a small study.
Topics: Cervical Ripening; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Pregnancy
PubMed: 35166491
DOI: No ID Found -
Lancet (London, England) Sep 2020The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.
METHODS
MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/mvs ≥35 kg/m), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024.
FINDINGS
Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups.
INTERPRETATION
Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery.
FUNDING
UK National Institute for Health Research Health Technology Assessment Programme.
Topics: Abortion, Missed; Adult; Double-Blind Method; Drug Therapy, Combination; Humans; Mifepristone; Misoprostol; Oxytocics; Treatment Outcome
PubMed: 32853559
DOI: 10.1016/S0140-6736(20)31788-8 -
American Journal of Obstetrics &... Aug 2020Induction of labor is indicated for many obstetrical, maternal, and fetal indications. Induction can be offered for pregnancy at 39 weeks' gestation. No prediction... (Review)
Review
Induction of labor is indicated for many obstetrical, maternal, and fetal indications. Induction can be offered for pregnancy at 39 weeks' gestation. No prediction method is considered sensitive or specific enough to determine the incidence of cesarean delivery after induction. A combination of 60- to 80-mL single-balloon Foley catheter for 12 hours and either 25-μg oral misoprostol initially, followed by 25 μg every 2-4 hours, or 50 μg every 4-6 hours (if no more than 3 contractions per 10 minutes or previous uterine surgery), or oxytocin infusion should be recommended for induction of labor. Adding membrane stripping at the beginning of induction should be considered. Once 5-6 cm of cervical dilation is achieved during the induction of labor, consideration can be given to discontinue oxytocin infusion if in use at that time and adequate contractions are present. Induction with oxytocin immediately (as soon as feasible) or up to 12 hours of term prelabor rupture of membranes if labor is not evident is recommended. Outpatient Foley ripening can be considered for low-risk women. Cesarean delivery should not be performed before 15 hours of oxytocin infusion and amniotomy if feasible and ideally after 18-24 hours of oxytocin infusion.
Topics: Cervical Ripening; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Time Factors
PubMed: 33345875
DOI: 10.1016/j.ajogmf.2020.100136 -
Obstetrics and Gynecology May 2022To compare immediate initiation with delayed initiation of medication abortion among patients with an undesired pregnancy of unknown location.
OBJECTIVE
To compare immediate initiation with delayed initiation of medication abortion among patients with an undesired pregnancy of unknown location.
METHODS
This retrospective cohort study used electronic medical record data from the Planned Parenthood League of Massachusetts (2014-2019) for patients who requested medication abortion with a last menstrual period (LMP) of 42 days or less and pregnancy of unknown location (no gestational sac) on initial ultrasonogram. Clinicians could initiate medication abortion with mifepristone followed by misoprostol while simultaneously excluding ectopic pregnancy with serial serum human chorionic gonadotropin (hCG) testing (same-day-start group) or establish a diagnosis with serial hCG tests and repeat ultrasonogram before initiating treatment (delay-for-diagnosis group). We compared primary safety outcomes (time to diagnosis of pregnancy location [rule out ectopic], emergency department visits, adverse events, and nonadherence with follow-up) between groups. We also reported secondary efficacy outcomes: time to complete abortion, successful medication abortion (no uterine aspiration), and ongoing pregnancy.
RESULTS
Of 5,619 medication abortion visits for patients with an LMP of 42 days or less, 452 patients had pregnancy of unknown location (8.0%). Three patients underwent immediate uterine aspiration, 55 had same-day start, and 394 had delay for diagnosis. Thirty-one patients (7.9%), all in the delay-for-diagnosis group, were treated for ectopic pregnancy, including four that were ruptured. Among patients with no major ectopic pregnancy risk factors (n=432), same-day start had shorter time to diagnosis (median 5.0 days vs 9.0 days; P=.005), with no significant difference in emergency department visits (adjusted odds ratio [aOR] 0.90, 95% CI 0.43-1.88) or nonadherence with follow-up (aOR 0.92, 95% CI 0.39-2.15). Among patients who proceeded with abortion (n=270), same-day start had shorter time to complete abortion (median 5.0 days vs 19.0 days; P<.001). Of those who had medication abortion with known outcome (n=170), the rate of successful medication abortion was lower (85.4% vs 96.7%; P=.013) and the rate of ongoing pregnancy was higher (10.4% vs 2.5%; P=.041) among patients in the same-day-start group.
CONCLUSION
In patients with undesired pregnancy of unknown location, immediate initiation of medication abortion is associated with more rapid exclusion of ectopic pregnancy and pregnancy termination but lower abortion efficacy.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Abortion, Spontaneous; Chorionic Gonadotropin; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy, Ectopic; Retrospective Studies
PubMed: 35576336
DOI: 10.1097/AOG.0000000000004756 -
Obstetrics and Gynecology Oct 2020Medication abortion, also referred to as medical abortion, is a safe and effective method of providing abortion. Medication abortion involves the use of medicines rather...
Medication abortion, also referred to as medical abortion, is a safe and effective method of providing abortion. Medication abortion involves the use of medicines rather than uterine aspiration to induce an abortion. The U.S. Food and Drug Administration (FDA)-approved medication abortion regimen includes mifepristone and misoprostol. The purpose of this document is to provide updated evidence-based guidance on the provision of medication abortion up to 70 days (or 10 weeks) of gestation. Information about medication abortion after 70 days of gestation is provided in other ACOG publications ().
Topics: Abortifacient Agents; Abortion, Induced; Clinical Protocols; Female; Gestational Age; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First; United States
PubMed: 32804884
DOI: 10.1097/AOG.0000000000004082 -
BMJ (Clinical Research Ed.) Mar 2022
Topics: Abortifacient Agents, Steroidal; Humans; Mifepristone; Misoprostol
PubMed: 35351689
DOI: 10.1136/bmj.o819