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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 -
The Cochrane Database of Systematic... May 2022Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently,... (Review)
Review
BACKGROUND
Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently, synthesis inhibitors of oestrogen (such as letrozole) have also been used to enhance efficacy. The most widely researched drugs are prostaglandins (such as misoprostol, which has a strong uterotonic effect), mifepristone, mifepristone with prostaglandins, and letrozole with prostaglandins. More evidence is needed to identify the best dosage, regimen, and route of administration to optimise patient outcomes. This is an update of a review last published in 2011.
OBJECTIVES
To compare the effectiveness and side effects of different medical methods for first trimester abortion.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Global Health, and LILACs on 28 February 2021. We also searched Clinicaltrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform, and reference lists of retrieved papers.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) that compared different medical methods for abortion before the 12th week of gestation. The primary outcome is failure to achieve complete abortion. Secondary outcomes are mortality, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the method.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected and evaluated studies for inclusion, and assessed the risk of bias. We processed data using Review Manager 5 software. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 99 studies in the review (58 from the original review and 41 new studies). 1. Combined regimen mifepristone/prostaglandin Mifepristone dose: high-dose (600 mg) compared to low-dose (200 mg) mifepristone probably has similar effectiveness in achieving complete abortion (RR 1.07, 95% CI 0.87 to 1.33; I = 0%; 4 RCTs, 3494 women; moderate-certainty evidence). Prostaglandin dose: 800 µg misoprostol probably reduces abortion failure compared to 400 µg (RR 0.63, 95% CI 0.51 to 0.78; I= 0%; 3 RCTs, 4424 women; moderate-certainty evidence). Prostaglandin timing: misoprostol administered on day one probably achieves more success on complete abortion than on day three (RR 1.94, 95% CI 1.05 to 3.58; 1489 women; 1 RCT; moderate-certainty evidence). Administration strategy: there may be no difference in failure of complete abortion with self-administration at home compared with hospital administration (RR 1.63, 95% CI 0.68 to 3.94; I = 84%; 2263 women; 4 RCTs; low-certainty evidence), but failure may be higher when administered by nurses in hospital compared to by doctors in hospital (RR 2.69, 95% CI 1.39 to 5.22; I = 66%; 3 RCTs, 3056 women; low-certainty evidence). Administration route: oral misoprostol probably leads to more failures than the vaginal route (RR 2.38, 95% CI 1.46 to 3.87; I = 39%; 3 RCTs, 1704 women; moderate-certainty evidence) and may be associated with more frequent side effects such as nausea (RR 1.14, 95% CI 1.03 to 1.26; I = 0%; 2 RCTs, 1380 women; low-certainty evidence) and diarrhoea (RR 1.80 95% CI 1.49 to 2.17; I = 0%; 2 RCTs, 1379 women). Compared with the vaginal route, complete abortion failure is probably lower with sublingual (RR 0.68, 95% CI 0.22 to 2.11; I = 59%; 2 RCTs, 3229 women; moderate-certainty evidence) and may be lower with buccal administration (RR 0.71, 95% CI 0.34 to 1.46; I = 0%; 2 RCTs, 479 women; low-certainty evidence), but sublingual or buccal routes may lead to more side effects. Women may experience more vomiting with sublingual compared to buccal administration (RR 1.33, 95% CI 1.01 to 1.77; low-certainty evidence). 2. Mifepristone alone versus combined regimen The efficacy of mifepristone alone in achieving complete abortion compared to combined mifepristone/prostaglandin up to 12 weeks is unclear (RR of failure 3.25, 95% CI 0.81 to 13.09; I = 83%; 3 RCTs, 273 women; very low-certainty evidence). 3. Prostaglandin alone versus combined regimen Nineteen studies compared prostaglandin alone to a combined regimen (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate). Compared to any of the combination regimens, misoprostol alone may increase the risk for failure to achieve complete abortion (RR of failure 2.39, 95% CI 1.89 to 3.02; I = 64%; 18 RCTs, 3471 women; low-certainty evidence), and with more diarrhoea. 4. Prostaglandin alone (route of administration) Oral misoprostol alone may lead to more failures in complete abortion than the vaginal route (RR 3.68, 95% CI 1.56 to 8.71, 2 RCTs, 216 women; low-certainty evidence). Failure to achieve complete abortion may be slightly reduced with sublingual compared with vaginal (RR 0.69, 95% CI 0.37 to 1.28; I = 87%; 5 RCTs, 2705 women; low-certainty evidence) and oral administration (RR 0.58, 95% CI 0.11 to 2.99; I = 66%; 2 RCTs, 173 women). Failure to achieve complete abortion may be similar or slightly higher with sublingual administration compared to buccal administration (RR 1.11, 95% CI 0.71 to 1.74; 1 study, 401 women).
AUTHORS' CONCLUSIONS
Safe and effective medical abortion methods are available. Combined regimens (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate) may be more effective than single agents (prostaglandin alone or mifepristone alone). In the combined regimen, the dose of mifepristone can probably be lowered to 200 mg without significantly decreasing effectiveness. Vaginal misoprostol is probably more effective than oral administration, and may have fewer side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all studies were conducted in settings with good access to emergency services, which may limit the generalisability of these results.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Spontaneous; Diarrhea; Drug Therapy, Combination; Estradiol; Female; Humans; Letrozole; Methotrexate; Mifepristone; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, First; Prostaglandins; Tamoxifen
PubMed: 35608608
DOI: 10.1002/14651858.CD002855.pub5 -
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 -
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 -
JAMA Network Open Jun 2023Adenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Adenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment.
OBJECTIVE
To determine whether mifepristone is effective and safe for adenomyosis treatment.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020.
INTERVENTIONS
Participants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks.
MAIN OUTCOMES AND MEASURES
The primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations.
RESULTS
In total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was -6.63 (1.92) in the mifepristone group and -0.95 (1.75) in the placebo group (P < .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P < .001), CA125 (mean [SD] change from baseline: -62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P < .001), platelet count (mean [SD] change from baseline: -28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P < .001), and uterine volume (mean [SD] change from baseline: -29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P < .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03520439.
Topics: Humans; Female; Adult; Middle Aged; Adenomyosis; Mifepristone; Hormone Antagonists; Dysmenorrhea; Pain; China; Treatment Outcome
PubMed: 37307001
DOI: 10.1001/jamanetworkopen.2023.17860 -
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 -
The Cochrane Database of Systematic... Jun 2021Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime. An estimated 15% of pregnancies end in miscarriage. Miscarriage can lead to serious morbidity, including haemorrhage, infection, and even death, particularly in settings without adequate healthcare provision. Early miscarriages occur during the first 14 weeks of pregnancy, and can be managed expectantly, medically or surgically. However, there is uncertainty about the relative effectiveness and risks of each option.
OBJECTIVES
To estimate the relative effectiveness and safety profiles for the different management methods for early miscarriage, and to provide rankings of the available methods according to their effectiveness, safety, and side-effect profile using a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register (9 February 2021), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (12 February 2021), and reference lists of retrieved studies.
SELECTION CRITERIA
We included all randomised controlled trials assessing the effectiveness or safety of methods for miscarriage management. Early miscarriage was defined as less than or equal to 14 weeks of gestation, and included missed and incomplete miscarriage. Management of late miscarriages after 14 weeks of gestation (often referred to as intrauterine fetal deaths) was not eligible for inclusion in the review. Cluster- and quasi-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded non-randomised trials.
DATA COLLECTION AND ANALYSIS
At least three review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for the primary outcomes of complete miscarriage and composite outcome of death or serious complications. The certainty of evidence was assessed using GRADE. Relative effects for the primary outcomes are reported subgrouped by the type of miscarriage (incomplete and missed miscarriage). We also performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available methods.
MAIN RESULTS
Our network meta-analysis included 78 randomised trials involving 17,795 women from 37 countries. Most trials (71/78) were conducted in hospital settings and included women with missed or incomplete miscarriage. Across 158 trial arms, the following methods were used: 51 trial arms (33%) used misoprostol; 50 (32%) used suction aspiration; 26 (16%) used expectant management or placebo; 17 (11%) used dilatation and curettage; 11 (6%) used mifepristone plus misoprostol; and three (2%) used suction aspiration plus cervical preparation. Of these 78 studies, 71 (90%) contributed data in a usable form for meta-analysis. Complete miscarriage Based on the relative effects from the network meta-analysis of 59 trials (12,591 women), we found that five methods may be more effective than expectant management or placebo for achieving a complete miscarriage: · suction aspiration after cervical preparation (risk ratio (RR) 2.12, 95% confidence interval (CI) 1.41 to 3.20, low-certainty evidence), · dilatation and curettage (RR 1.49, 95% CI 1.26 to 1.75, low-certainty evidence), · suction aspiration (RR 1.44, 95% CI 1.29 to 1.62, low-certainty evidence), · mifepristone plus misoprostol (RR 1.42, 95% CI 1.22 to 1.66, moderate-certainty evidence), · misoprostol (RR 1.30, 95% CI 1.16 to 1.46, low-certainty evidence). The highest ranked surgical method was suction aspiration after cervical preparation. The highest ranked non-surgical treatment was mifepristone plus misoprostol. All surgical methods were ranked higher than medical methods, which in turn ranked above expectant management or placebo. Composite outcome of death and serious complications Based on the relative effects from the network meta-analysis of 35 trials (8161 women), we found that four methods with available data were compatible with a wide range of treatment effects compared with expectant management or placebo: · dilatation and curettage (RR 0.43, 95% CI 0.17 to 1.06, low-certainty evidence), · suction aspiration (RR 0.55, 95% CI 0.23 to 1.32, low-certainty evidence), · misoprostol (RR 0.50, 95% CI 0.22 to 1.15, low-certainty evidence), · mifepristone plus misoprostol (RR 0.76, 95% CI 0.31 to 1.84, low-certainty evidence). Importantly, no deaths were reported in these studies, thus this composite outcome was entirely composed of serious complications, including blood transfusions, uterine perforations, hysterectomies, and intensive care unit admissions. Expectant management and placebo ranked the lowest when compared with alternative treatment interventions. Subgroup analyses by type of miscarriage (missed or incomplete) agreed with the overall analysis in that surgical methods were the most effective treatment, followed by medical methods and then expectant management or placebo, but there are possible subgroup differences in the effectiveness of the available methods. AUTHORS' CONCLUSIONS: Based on relative effects from the network meta-analysis, all surgical and medical methods for managing a miscarriage may be more effective than expectant management or placebo. Surgical methods were ranked highest for managing a miscarriage, followed by medical methods, which in turn ranked above expectant management or placebo. Expectant management or placebo had the highest chance of serious complications, including the need for unplanned or emergency surgery. A subgroup analysis showed that surgical and medical methods may be more beneficial in women with missed miscarriage compared to women with incomplete miscarriage. Since type of miscarriage (missed and incomplete) appears to be a source of inconsistency and heterogeneity within these data, we acknowledge that the main network meta-analysis may be unreliable. However, we plan to explore this further in future updates and consider the primary analysis as separate networks for missed and incomplete miscarriage.
Topics: Abortion, Incomplete; Abortion, Missed; Abortion, Spontaneous; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Network Meta-Analysis; Oxytocics; Placebos; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic; Suction; Vacuum Curettage; Watchful Waiting
PubMed: 34061352
DOI: 10.1002/14651858.CD012602.pub2 -
Journal of Investigative Medicine High... 2023Medications are known to affect the thyroid physiology and are a known cause of hypothyroidism. There is an ever-growing list of medications that affect the thyroid by 1...
Medications are known to affect the thyroid physiology and are a known cause of hypothyroidism. There is an ever-growing list of medications that affect the thyroid by 1 or more mechanisms. Mifepristone is presently used for the treatment of mild autonomous cortisol secretion (MACS). Hypothyroidism is not a known side effect of this medication. We present a 71-year-old woman with newly diagnosed impaired fasting glucose, dyslipidemia, and osteopenia presenting with a 3-year history of unintentional 15-pound weight gain (despite exercise and a good diet) and increased anxiety. Her physical examination was pertinent for mild lower extremity edema, easy bruising, and skin thinning. Workup revealed adrenocorticotropic hormone (ACTH)-independent MACS from bilateral micronodular hyperplasia of the adrenals. Since she was not a surgical candidate, medical management with mifepristone was chosen. While on mifepristone, she complained of excessive fatigue, a workup done revealed new-onset hypothyroidism. Given her symptoms and bloodwork, she was started on levothyroxine. After stopping mifepristone, she was biochemically and clinically euthyroid and was eventually off levothyroxine. The mechanism by which mifepristone induces hypothyroidism is unknown. Except for a multicenter case series suggesting that mifepristone increases thyroid hormone requirements in patients with central hypothyroidism, to the best of our knowledge, the literature on euthyroid patients developing hypothyroidism secondary to mifepristone is scarce. In conclusion, while the hypothyroidism seems reversible our case highlights the importance of getting baseline thyroid function tests (TFTs) and repeating them while on the medication. Treatment of hypothyroidism is based on symptoms and bloodwork.
Topics: Female; Humans; Aged; Thyroxine; Mifepristone; Hypothyroidism; Thyroid Function Tests
PubMed: 37565673
DOI: 10.1177/23247096231191874 -
Science Advances Jul 2023To understand the mechanism of acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib, we induced the formation of polyploid giant cancer cells...
To understand the mechanism of acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib, we induced the formation of polyploid giant cancer cells (PGCCs) in ovarian and breast cancer cell lines, high-grade serous cancer (HGSC)-derived organoids, and patient-derived xenografts (PDXs). Time-lapse tracking of ovarian cancer cells revealed that PGCCs primarily developed from endoreplication after exposure to sublethal concentrations of olaparib. PGCCs exhibited features of senescent cells but, after olaparib withdrawal, can escape senescence via restitutional multipolar endomitosis and other noncanonical modes of cell division to generate mitotically competent resistant daughter cells. The contraceptive drug mifepristone blocked PGCC formation and daughter cell formation. Mifepristone/olaparib combination therapy substantially reduced tumor growth in PDX models without previous olaparib exposure, while mifepristone alone decreased tumor growth in PDX models with acquired olaparib resistance. Thus, targeting PGCCs may represent a promising approach to potentiate the therapeutic response to PARPi and overcome PARPi-induced resistance.
Topics: Polyploidy; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Humans; Female; Mifepristone; Drug Resistance, Neoplasm; Cellular Senescence; Cell Line, Tumor; Apoptosis
PubMed: 37478190
DOI: 10.1126/sciadv.adf7195