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Drug Design, Development and Therapy 2015Induction of labor is one of the most commonly performed obstetric procedures and will likely become more common as the reproductive population in developed nations... (Review)
Review
Induction of labor is one of the most commonly performed obstetric procedures and will likely become more common as the reproductive population in developed nations changes. As the proportion of women undergoing induction grows, there is a constant search for more efficacious ways to induce labor while maintaining fetal and maternal safety as well as patient satisfaction. With almost half of induced labors requiring cervical ripening, methods for achieving active labor and vaginal delivery are constantly being investigated. Prostaglandins have been shown to be effective induction agents, and specifically vaginal misoprostol, used off-label, have been widely utilized to initiate cervical ripening and active labor. The challenge is to administer this medication accurately while maintaining the ability to discontinue the medication when needed. The misoprostol vaginal insert initiates cervical ripening utilizing a delivery system that controls medication release and can be rapidly removed. This paper reviews the design, development, and clinical utility of the misoprostol vaginal insert for induction of labor as well as patient considerations related to the delivery system.
Topics: Administration, Intravaginal; Adult; Cervical Ripening; Chemistry, Pharmaceutical; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Delivery Systems; Drug Implants; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy
PubMed: 25960635
DOI: 10.2147/DDDT.S64227 -
BMC Pregnancy and Childbirth Nov 2019Community distribution of misoprostol to pregnant women in advance of labor is one of the compelling strategies for preventing postpartum hemorrhage. Concerns have been... (Review)
Review
INTRODUCTION
Community distribution of misoprostol to pregnant women in advance of labor is one of the compelling strategies for preventing postpartum hemorrhage. Concerns have been reported that misoprostol distribution could reduce facility delivery or lead to misuse of the medication. This scoping review was conducted to synthesize the evidence on the effect of community-based misoprostol distribution on rates of facility delivery, and to assess the frequency of mothers taking distributed misoprostol before delivery, and any harmful outcomes of such misuse.
METHODS
We included peer-reviewed articles on misoprostol implementation from PubMed, Cochrane Review Library, Popline, and Google Scholars. Narrative synthesis was used to analyze and interpret the findings, in which quantitative and qualitative syntheses are integrated.
RESULTS
Three qualitative studies, seven observational studies, and four experimental or quasi-experimental studies were included in this study. All before-after household surveys reported increased delivery coverage after the intervention: ranging from 4 to 46 percentage points at the end of the intervention when compared to the baseline. The pooled analysis of experimental and quasi-experimental studies involving 7564 women from four studies revealed that there was no significant difference in rates of facility delivery among the misoprostol and control groups [OR 1.011; 95% CI: 0.906-1.129]. A qualitative study among health professionals also indicated that community distribution of misoprostol for the prevention of postpartum hemorrhage is acceptable to community members and stakeholders and it is a feasible interim solution until access to facility birth increases. In the community-based distribution of misoprostol programs, self-administration of misoprostol by pregnant women before delivery was reported in less than 2% of women, among seven studies involving 11,108 mothers. Evidence also shows that most women who used misoprostol pills, used them as instructed. No adverse outcomes from misuse in either of the studies reviewed.
CONCLUSIONS
The claim that community-based distribution of misoprostol would divert women who would have otherwise had institutional deliveries to have home deliveries and promote misuse of the medication are not supported with evidence. Therefore, community-based distribution of misoprostol can be an appropriate strategy for reducing maternal deaths which occur due to postpartum hemorrhages, especially in resource-limited settings.
Topics: Delivery of Health Care; Female; Global Health; Humans; Incidence; Labor, Obstetric; Misoprostol; Oxytocics; Postpartum Hemorrhage; Pregnancy; Risk Factors; Survival Rate
PubMed: 31694580
DOI: 10.1186/s12884-019-2539-5 -
American Journal of Obstetrics and... Jun 2024A cesarean scar pregnancy is an iatrogenic consequence of a previous cesarean delivery. The gestational sac implants into a niche created by the incision of the previous... (Comparative Study)
Comparative Study
BACKGROUND
A cesarean scar pregnancy is an iatrogenic consequence of a previous cesarean delivery. The gestational sac implants into a niche created by the incision of the previous cesarean delivery, and this carries a substantial risk for major maternal complications. The aim of this study was to report, analyze, and compare the effectiveness and safety of different treatments options for cesarean scar pregnancies managed in the first trimester through a registry.
OBJECTIVE
This study aimed to evaluated the ultrasound findings, disease behavior, and management of first-trimester cesarean scar pregnancies.
STUDY DESIGN
We created an international registry of cesarean scar pregnancy cases to study the ultrasound findings, disease behavior, and management of cesarean scar pregnancies. The Cesarean Scar Pregnancy Registry collects anonymized ultrasound and clinical data of individual patients with a cesarean scar pregnancy on a secure, digital information platform. Cases were uploaded by 31 participating centers across 19 countries. In this study, we only included live and failing cesarean scar pregnancies (with or without a positive fetal heart beat) that received active treatment (medical or surgical) before 12+6 weeks' gestation to evaluate the effectiveness and safety of the different management options. Patients managed expectantly were not included in this study and will be reported separately. Treatment was classified as successful if it led to a complete resolution of the pregnancy without the need for any additional medical interventions.
RESULTS
Between August 29, 2018, and February 28, 2023, we recorded 460 patients with cesarean scar pregnancies (281 live, 179 failing cesarean scar pregnancy) who fulfilled the inclusion criteria and were registered. A total of 270 of 460 (58.7%) patients were managed surgically, 123 of 460 (26.7%) patients underwent medical management, 46 of 460 (10%) patients underwent balloon management, and 21 of 460 (4.6%) patients received other, less frequently used treatment options. Suction evacuation was very effective with a success rate of 202 of 221 (91.5%; 95% confidence interval, 87.8-95.2), whereas systemic methotrexate was least effective with only 38 of 64 (59.4%; 95% confidence interval, 48.4-70.4) patients not requiring additional treatment. Overall, surgical treatment of cesarean scar pregnancies was successful in 236 of 258 (91.5%, 95% confidence interval, 88.4-94.5) patients and complications were observed in 24 of 258 patients (9.3%; 95% confidence interval, 6.6-11.9).
CONCLUSION
A cesarean scar pregnancy can be managed effectively in the first trimester of pregnancy in more than 90% of cases with either suction evacuation, balloon treatment, or surgical excision. The effectiveness of all treatment options decreases with advancing gestational age, and cesarean scar pregnancies should be treated as early as possible after confirmation of the diagnosis. Local medical treatment with potassium chloride or methotrexate is less efficient and has higher rates of complications than the other treatment options. Systemic methotrexate has a substantial risk of failing and a higher complication rate and should not be recommended as first-line treatment.
Topics: Humans; Female; Pregnancy; Cicatrix; Cesarean Section; Pregnancy Trimester, First; Pregnancy, Ectopic; Registries; Adult; Abortifacient Agents, Nonsteroidal; Methotrexate; Ultrasonography, Prenatal; Vacuum Curettage; Misoprostol; Uterine Artery Embolization
PubMed: 37865390
DOI: 10.1016/j.ajog.2023.10.028 -
Equine Veterinary Journal May 2019Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits...
BACKGROUND
Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro.
OBJECTIVE
Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model.
STUDY DESIGN
Pharmacokinetic study, ex vivo experimental study.
METHODS
Six healthy adult horses of mixed breeds were used. In phase one, horses were given 5 μg/kg misoprostol orally, and blood was collected at predetermined times for determination of misoprostol free acid (MFA) by UHPLC-MS/MS. Pharmacokinetic parameters were calculated. In phase two, horses were dosed as in phase one, and blood was collected at T0, 0.5, 1 and 4 h following misoprostol administration for leucocyte isolation. Leucocytes were stimulated with 100 ng/mL LPS, and TNFα mRNA concentrations were determined via quantitative real-time PCR.
RESULTS
About 5 μg/kg oral misoprostol produced a rapid time to maximum concentration (T ) of 23.4 ± 2.4 min, with a maximum concentration (C ) of 0.29 ± 0.07 ng/mL and area under the curve (AUC ) of 0.4 ± 0.12 h ng/mL. LPS stimulation of equine leucocytes ex vivo significantly increased TNFα mRNA concentrations, and there was no significant effect of misoprostol even at the T .
MAIN LIMITATIONS
Only a single dose was used, and sample size was small.
CONCLUSIONS
Misoprostol is rapidly absorbed following oral administration in horses, and a single 5 μg/kg dose had no significant inhibitory effect on ex vivo LPS-stimulated TNFα mRNA production in leucocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti-inflammatory drugs, are warranted.
Topics: Abortifacient Agents, Nonsteroidal; Administration, Oral; Animals; Area Under Curve; Cells, Cultured; Horse Diseases; Horses; Inflammation; Leukocytes; Misoprostol
PubMed: 30256450
DOI: 10.1111/evj.13024 -
BMC Pregnancy and Childbirth Nov 2019Early pregnancy failure (EPF) is a common complication of pregnancy. If women do not abort spontaneously, they will undergo medical or surgical treatment in order to... (Comparative Study)
Comparative Study
Mifepristone and misoprostol versus misoprostol alone for uterine evacuation after early pregnancy failure: study protocol for a randomized double blinded placebo-controlled comparison (Triple M Trial).
BACKGROUND
Early pregnancy failure (EPF) is a common complication of pregnancy. If women do not abort spontaneously, they will undergo medical or surgical treatment in order to remove the products of conception from the uterus. Curettage, although highly effective, is associated with a risk of complications; medical treatment with misoprostol is a safe and less expensive alternative. Unfortunately, after 1 week of expectant management in case of EPF, medical treatment with misoprostol has a complete evacuation rate of approximately 50%. Misoprostol treatment results may be improved by pre-treatment with mifepristone; its effectiveness has already been proven for other indications of pregnancy termination. This study will test the hypothesis that, in EPF, the sequential combination of mifepristone with misoprostol is superior to the use of misoprostol alone in terms of complete evacuation (primary outcome), patient satisfaction, complications, side effects and costs (secondary outcomes).
METHODS
The trial will be performed multi-centred, prospectively, two-armed, randomised, double-blinded and placebo-controlled. Women with confirmed EPF by ultrasonography (6-14 weeks), managed expectantly for at least 1 week, can be included and randomised to pre-treatment with oral mifepristone (600 mg) or oral placebo (identical in appearance). Randomisation will take place after receiving written consent to participate. In both arms pre-treatment will be followed by oral misoprostol, which will start 36-48 h later consisting of two doses 400 μg (4 hrs apart), repeated after 24 h if no tissue is lost. Four hundred sixty-four women will be randomised in a 1:1 ratio, stratified by centre. Ultrasonography 2 weeks after treatment will determine short term treatment effect. When the gestational sac is expulsed, expectant management is advised until 6 weeks after treatment when the definitive primary endpoint, complete or incomplete evacuation, will be determined. A sonographic endometrial thickness < 15 mm using only the allocated therapy by randomisation is considered as successful treatment. Secondary outcome measures (patient satisfaction, complications, side effects and costs) will be registered using a case report form, patient diary and validated questionnaires (Short Form 36, EuroQol-VAS, Client Satisfaction Questionnaire, iMTA Productivity Cost Questionnaire).
DISCUSSION
This trial will answer the question if, in case of EPF, after at least 1 week of expectant management, sequential treatment with mifepristone and misoprostol is more effective than misoprostol alone to achieve complete evacuation of the products of conception.
TRIAL REGISTRATION
Clinicaltrials.gov (d.d. 02-07-2017): NCT03212352. Trialregister.nl (d.d. 03-07-2017): NTR6550. EudraCT number (d.d. 07-08-2017): 2017-002694-19. File number Commisie Mensgebonden Onderzoek (d.d. 07-08-2017): NL 62449.091.17.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Incomplete; Adolescent; Adult; Cost-Benefit Analysis; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Multicenter Studies as Topic; Patient Satisfaction; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Randomized Controlled Trials as Topic; Ultrasonography; Watchful Waiting; Young Adult
PubMed: 31775677
DOI: 10.1186/s12884-019-2497-y -
The New England Journal of Medicine Jun 2018Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss.
METHODS
We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 μg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 μg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment.
RESULTS
Complete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group.
CONCLUSIONS
Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .).
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Spontaneous; Administration, Intravaginal; Administration, Oral; Adult; Drug Therapy, Combination; Embryo, Mammalian; Female; Fetal Death; Gestational Sac; Hemorrhage; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First; Ultrasonography
PubMed: 29874535
DOI: 10.1056/NEJMoa1715726 -
BMC Women's Health Jan 2020Prior research has shown that a small proportion of U.S. women attempt to self-manage their abortion. The objective of this study is to describe Texas women's...
BACKGROUND
Prior research has shown that a small proportion of U.S. women attempt to self-manage their abortion. The objective of this study is to describe Texas women's motivations for and experiences with attempts to self-manage an abortion. The objective of this study is to describe Texas women's motivations for and experiences with attempts to self-manage an abortion.
METHODS
We report results from two data sources: two waves of surveys with women seeking abortion services at Texas facilities in 2012 and 2014 and qualitative interviews with women who reported attempting to self-manage their abortion while living in Texas at some time between 2009 and 2014. We report the prevalence of attempted self-managed abortion for the current pregnancy among survey respondents, and describe interview participants' decision-making and experiences with abortion self-management.
RESULTS
6.9% (95% CI 5.2-9.0%) of abortion clients (n = 721) reported they had tried to end their current pregnancy on their own before coming to the clinic for an abortion. Interview participants (n = 18) described multiple reasons for their decision to attempt to self-manage abortion. No single reason was enough for any participant to consider self-managing their abortion; however, poverty intersected with and layered upon other obstacles to leave them feeling they had no other option. Ten interview participants reported having a complete abortion after taking medications, most of which was identified as misoprostol. None of the six women who used home remedies alone reported having a successful abortion; many described using these methods for several days or weeks which ultimately did not work, resulting in delays for some, greater distress, and higher costs.
CONCLUSION
These findings point to a need to ensure that women who may consider self-managed abortion have accurate information about effective methods, what to expect in the process, and where to go for questions and follow-up care. There is increasing evidence that given accurate information and access to clinical consultation, self-managed abortion is as safe as clinic-based abortion care and that many women find it acceptable, while others may prefer to use clinic-based abortion care.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adult; Aftercare; Ambulatory Care Facilities; Decision Making; Female; Humans; Misoprostol; Motivation; Needs Assessment; Poverty; Pregnancy; Pregnancy Outcome; Self-Management; Texas
PubMed: 31906937
DOI: 10.1186/s12905-019-0877-0 -
BJOG : An International Journal of... Oct 2017Given the overall safety profile and increasing availability of medical pregnancy termination drugs, we asked: would the mifepristone-misoprostol regimen for medical... (Review)
Review
UNLABELLED
Given the overall safety profile and increasing availability of medical pregnancy termination drugs, we asked: would the mifepristone-misoprostol regimen for medical termination at ≤10 weeks of gestation meet US Food and Drug Administration regulatory criteria for over-the-counter (OTC) approval, and if not, what are the present research gaps? We conducted a literature review of consumer behaviours necessary for a successful OTC application for medical termination at ≤10 weeks of gestation and identified crucial research gaps. If we were to embark on a development programme for OTC or more generally, self-use of medical termination, the critical elements missing are the label comprehension, self-selection and actual use studies.
TWEETABLE ABSTRACT
Considering medical pregnancy termination through the over-the-counter regulatory lens clarifies critical evidence gaps.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Drug Approval; Drug Therapy, Combination; Female; Health Knowledge, Attitudes, Practice; Humans; Mifepristone; Misoprostol; Nonprescription Drugs; Pregnancy; Pregnancy Trimester, First; United States; United States Food and Drug Administration
PubMed: 28317327
DOI: 10.1111/1471-0528.14646 -
American Journal of Perinatology Dec 2021Studies demonstrate shorter time to delivery with concurrent use of misoprostol and cervical Foley catheter. However, concurrent placement may not be feasible. If...
OBJECTIVE
Studies demonstrate shorter time to delivery with concurrent use of misoprostol and cervical Foley catheter. However, concurrent placement may not be feasible. If misoprostol is used to start an induction, little is known regarding the benefit of sequentially using Foley catheter. We examine obstetrical outcomes in women with Foley catheter placed after misoprostol compared with those only requiring misoprostol.
STUDY DESIGN
Retrospective cohort study of singleton pregnancies, intact membranes, and an unfavorable cervix (Bishop score of ≤6 and dilation ≤2 cm) undergoing term induction May 2013 to June 2015. We compared obstetrical outcomes between women receiving misoprostol alone versus those that had a Foley catheter placed after misoprostol. Outcomes are mode of delivery, time to delivery, chorioamnionitis, admission to neonatal intensive care unit, and maternal morbidity. Chi-square and Fisher's exact tests were used for categorical variables, Mann-Whitney -tests compared continuous variables.
RESULTS
Among 364 women, 281 began induction with misoprostol alone. A total of 135 (48%) subsequently had a Foley catheter placed. Characteristics were similar between the groups, although nulliparity and cervical dilation <1 cm at start of induction were more likely to have subsequent Foley catheter. Women with Foley catheter placement after misoprostol had a longer median time to delivery (15 vs. 11 hours, < 0.001), twofold higher rate of cesarean (42 vs. 26%, odds ratio: 2.1, 95% confidence interval: 1.26-3.44, = 0.004), and increased risk of neonatal intensive care unit (NICU) admission (21 vs. 11%, = 0.024). There was a nonsignificant increased risk of chorioamnionitis (12 vs. 7%, = 0.1) and maternal morbidity (15 vs. 8%, = 0.08) in the misoprostol followed by Foley catheter group.
CONCLUSION
In women receiving misoprostol for induction, nulliparas and those with dilation <1 cm are more likely to have subsequent Foley catheter placement. Sequential use of cervical Foley catheter after misoprostol is associated with longer labor, higher cesarean rate, and increased NICU admission. Requirement of Foley catheter after misoprostol confers higher risk and may guide counseling.
KEY POINTS
· Little is known regarding efficacy of misoprostol followed by cervical Foley catheter.. · Nulliparas and dilation <1 cm increases need for Foley after misoprostol.. · Complications were more common in women requiring Foley after misoprostol..
Topics: Adult; Catheterization; Catheters; Cesarean Section; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Pregnancy Outcome; Retrospective Studies
PubMed: 32594510
DOI: 10.1055/s-0040-1713818 -
BMC Pregnancy and Childbirth Sep 2022Various methods are used for cervical ripening during the induction of labor. Mechanical and pharmacological methods are commonly used for cervical ripening. A... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Various methods are used for cervical ripening during the induction of labor. Mechanical and pharmacological methods are commonly used for cervical ripening. A double-balloon catheter was specifically developed to ripen the cervix and induce labor; however, the efficacy of the double-balloon catheter in cervical ripening compared to other methods is unknown.
METHODS
We searched five databases and performed a Bayesian network meta-analysis. Six interventions (double-balloon catheter, Foley catheter, oral misoprostol, vaginal misoprostol, dinoprostone, and double-balloon catheter combined with oral misoprostol) were included in the search. The primary outcomes were cesarean delivery rate and time from intervention-to-birth. The secondary outcomes were as follows: Bishop score increment; achieving a vaginal delivery within 24 h; uterine hyperstimulation with fetal heart rate changes; need for oxytocin augmentation; instrumental delivery; meconium staining; chorioamnionitis; postpartum hemorrhage; low Apgar score; neonatal intensive care unit admission; and arterial pH.
RESULTS
Forty-eight randomized controlled trials involving 11,482 pregnant women were identified. The cesarean delivery rates of the cervical ripening with a double-balloon catheter and oral misoprostol, oral misoprostol, and vaginal misoprostol were significantly lower than cervical ripening with a Foley catheter (OR = 0.48, 95% CI: 0.23-0.96; OR = 0.74, 95% CI: 0.58-0.93; and OR = 0.79, 95% CI: 0.64-0.97, respectively; all P < 0.05). The time from intervention-to-birth of vaginal misoprostol was significantly shorter than the other five cervical ripening methods. Vaginal misoprostol and oral misoprostol increased the risk of uterine hyperstimulation with fetal heart rate changes compared to a Foley catheter. A double-balloon catheter with or without oral misoprostol had similar outcomes, including uterine hyperstimulation with fetal heart rate changes compared to a Foley catheter.
CONCLUSION
Double-balloon catheter did not show superiority when compared with other single method in primary and secondary outcomes of labor induction. The combination of double-balloon catheter with oral misoprostol was significantly reduced the rate of cesarean section compared to Foley catheter without increased risk of uterine hyperstimulation with fetal heart rate changes, which was shown in oral or vaginal misoprostol.
Topics: Administration, Intravaginal; Bayes Theorem; Cervical Ripening; Cesarean Section; Female; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Network Meta-Analysis; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic; Urinary Catheters
PubMed: 36068489
DOI: 10.1186/s12884-022-04988-2