Cost-effectiveness of Mifepristone Pretreatment for the Medical Management of Nonviable Early Pregnancy: Secondary Analysis of a Randomized Clinical Trial.

Importance: Early pregnancy loss (EPL) is the most common complication of pregnancy. A multicenter randomized clinical trial compared 2 strategies for medical management and found that mifepristone pretreatment is 25% more effective than the standard of care, misoprostol alone. The cost of mifepristone may be a barrier to implementation of the regimen. Objective: To assess the cost-effectiveness of medical management of EPL with mifepristone pretreatment plus misoprostol vs misoprostol alone in the United States. Design, Setting, and Participants: This preplanned. prospective economic evaluation was performed concurrently with a randomized clinical trial in 3 US sites from May 1, 2014, through April 30, 2017. Participants included 300 women with anembryonic gestation or embryonic or fetal demise. Cost-effectiveness was computed from the health care sector and societal perspectives, with a 30-day time horizon. Data were analyzed from July 1, 2018, to July 3, 2019. Interventions: Mifepristone pretreatment plus misoprostol administration vs misoprostol alone. Main Outcomes and Measures: Costs in 2018 US dollars, effectiveness in quality-adjusted life-years (QALYs), and treatment efficacy. Incremental cost-effectiveness ratios (ICERs) of mifepristone and misoprostol vs misoprostol alone were calculated, and cost-effectiveness acceptability curves were generated. Results: Among the 300 women included in the randomized clinical trial (mean [SD] age, 30.4 [6.2] years), mean costs were similar for groups receiving mifepristone pretreatment and misoprostol alone from the health care sector perspective ($696.75 [95% CI, $591.88-$801.62] vs $690.88 [95% CI, $562.38-$819.38]; P = .94) and the societal perspective ($3846.30 [95% CI, $2783.01-$4909.58] vs $4845.62 [95% CI, $3186.84-$6504.41]; P = .32). The mifepristone pretreatment group had higher QALYs (0.0820 [95% CI, 0.0815-0.0825] vs 0.0806 [95% CI, 0.0800-0.0812]; P = .001) and a higher completion rate after first treatment (83.8% vs 67.1%; P < .001) than the group receiving misoprostol alone. From the health care sector perspective, mifepristone pretreatment was cost-effective relative to misoprostol alone with an ICER of $4225.43 (95% CI, -$195 053.30 to $367 625.10) per QALY gained. From the societal perspective, mifepristone pretreatment dominated misoprostol alone (95% CI, -$5 111 629 to $1 801 384). The probabilities that mifepristone pretreatment was cost-effective compared with misoprostol alone at a willingness-to-pay of $150 000 per QALY gained from the health care sector and societal perspectives were approximately 90% and 80%, respectively. Conclusions and Relevance: This study found that medical management of EPL with mifepristone pretreatment was cost-effective when compared with misoprostol alone. Trial Registration: ClinicalTrials.gov Identifier: NCT02012491.

Early versus delayed follow-up after misoprostol treatment for early pregnancy loss.

RESEARCH QUESTION: Does extending the follow-up after misoprostol treatment for early pregnancy loss increase the success rate? DESIGN: Patients who had experienced early pregnancy loss (<12 weeks) and were treated with misoprostol in a single university-affiliated medical centre were prospectively followed before and after the implementation of a new treatment protocol extending the follow-up from 1 to 2 weeks. All patients received misoprostol 800 µg vaginally on day 1 and a second dose, when needed, on day 4 or 8. Patients underwent surgical aspiration after 1 week in the early follow-up group (n = 84) or 2 weeks in the delayed follow-up group (n = 85) if complete expulsion was not achieved (defined as endometrial thickness ≤15 mm and absence of gestational sac on transvaginal sonography). The primary outcome was treatment success, defined as no need for surgical aspiration. RESULTS: Women in the delayed follow-up group had a higher rate of successful treatment compared with women in the early follow-up group (88.2% versus 76.2%, respectively; P = 0.040), and a lower rate of second dose administration (32.9% versus 51.2%, respectively; P = 0.016). The incidence of non-expulsion of the gestational sac was also lower in the delayed follow-up group (1.2% versus 10.7%; P = 0.009). Treatment acceptability did not differ between the study groups. CONCLUSION: In women with early pregnancy loss treated with misoprostol, extending the follow-up protocol from 1 to 2 weeks resulted in an increase in treatment success.

[Recurrent early pregnancy loss: What the life-birth chances are? A 10-years retrospective study]. / Fausses couches précoces à répétition : quelles sont les chances de naissance vivante ? Étude rétrospective sur 10ans.

OBJECTIVES: Recurrent miscarriages are a current consultation pattern. Etiologic evaluation is classically proposed and preventive therapy should be discussed. We wanted to study our University Hospital pregnancies outcomes, following 3 repetitive early miscarriages, and how those patients are managed. MATERIALS AND METHODS: A 10-years retrospective study has been performed in our center, with 296 patients found having a three-repetitive miscarriage experience. Information about diagnostic evaluation following miscarriages, preventive therapy initiation, and next pregnancy outcome has been provided. RESULTS: Around 62.5% of the patients experienced a life-birth. When investigations were done (n=148), a 64.9% part of the patients had abnormal results. Life-birth rate was more important when there were normal karyotypes or no thrombophilia found (respectively p equal 0.30 and 0.45). We noticed a better prognostic in the group of patients with normal investigations results who had a preventive therapy (n=20, 85% of life-birth, P=0.19). CONCLUSION: When done, investigations for recurrent miscarriages, allow the finding of an abnormality in two thirds of cases. Wonderingly, outcomes are very encouraging since that almost two thirds of the patients experienced life-birth. Investigations indications, results interpretations, and consecutive therapy should be well thought but preventive therapy seems to be efficient in the normal results patient group.

Clinical observations of sequential therapy with Chinese medicine and hysteroscopic mechanical stimulation of the endometrium in infertile patients with repeated implantation failure undergoing frozen-thawed embryo transfer.

OBJECTIVES: To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. METHODS: In the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometrial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. RESULTS: Endometrial thickness, E2 and P levels, and the E2/P ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P<0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. CONCLUSIONS: Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of rif-fet cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.

Diagnosis and control of an outbreak of leptospirosis in goats with reproductive failure.

This study presents a Brazilian goat herd with reproductive failure over 2009-2010, in which there were abortions (22/50; 44%), embryonic resorption (6/50; 12%) and neonatal deaths (2/50; 4%). A diagnosis of leptospirosis was made, based on serology (microscopic agglutination test - MAT), bacterial culture, and polymerase chain reaction (PCR). Antibiotic therapy, specific vaccination protocols and changes in management practices were instigated. One year after the outbreak, diagnostic methods were repeated and reproductive performance re-analysed. Soon after the outbreak, 61/125 (48.8%) of the goats were seropositive for Leptospira. Pure isolates of Leptospira were not obtained, but Leptospira PCR testing was positive in 48/50 (96%) urine samples. After 1 year only 4.2% were seropositive and the occurrence of reproductive problems decreased roughly 10-fold, although five goats (10.4%) remained PCR-positive. A broad-based management approach, including serological and molecular diagnostic methods, vaccination, antibiotic treatment, and alteration of some environmental aspects, were critical to the control of this outbreak, thereby minimising subsequent reproductive failures and economic losses.

Treatment of early pregnancy failure: does induced abortion training affect later practices?

OBJECTIVE: The objective of the study was to examine the relationship between induced abortion training and views toward, and use of, office uterine evacuation and misoprostol in early pregnancy failure (EPF) care. STUDY DESIGN: We surveyed 308 obstetrician-gynecologists on their knowledge and attitudes toward treatment options for EPF and previous training in office-based uterine evacuation. RESULTS: Sixty-seven percent of respondents reported training in office uterine evacuation, and 20.3% reported induced abortion training. Induced abortion training was associated with strongly positive views toward both office-based uterine evacuation and misoprostol as treatment for EPF compared with those with office uterine evacuation training in other settings (odds ratio [OR], 2.64; P < .004 and OR, 3.22; P < .003, respectively). Furthermore, induced abortion training was associated with the use of office uterine evacuation for EPF treatment compared with those with office evacuation training in other settings (OR, 2.90; P = .004). CONCLUSION: Training experiences, especially induced abortion training, are associated with the use of office uterine evacuation for EPF.

Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss.

OBJECTIVE: We hypothesized that the thrombophilic G1691A factor V Leiden (FVL) gene mutation was a common, significant, and treatable cause of sporadic and recurrent pregnancy loss (RPL). DESIGN: We compared the frequency of the FVL mutation in 141 women with >or=1 pregnancy and 1 sporadic pregnancy loss (308 live births, 141 pregnancy losses), 44 women with >or=1 pregnancy and >or=3 pregnancy losses (105 live births, 180 pregnancy losses), and 638 women with >or=1 live birth pregnancy and 0 pregnancy loss (1553 live births). SETTING: Outpatient Clinical Research Center. PATIENT(S): A total of 823 caucasian women with consecutive measures of the FVL mutation. MAIN OUTCOME MEASURE(S): We used polymerase chain reaction techniques to characterize the thrombophilic FVL G1691A gene mutation. RESULT(S): Of the 638 controls, 47 (7.4%) had FVL heterozygosity versus 16 heterozygous and 2 homozygous FVL cases (18/141, 12.8%) in 141 women with 1 sporadic pregnancy loss versus 9/44 RPL cases (20.5%, 8 heterozygous and 1 homozygous FVL). The FVL frequency in cases with 1 sporadic pregnancy loss (18/141, 12.8%) did not differ from RPL cases (9/44, 20.45%). CONCLUSION(S): After unexplained sporadic pregnancy loss, as well as after RPL, to provide the option to prospectively optimize subsequent live birth outcomes with low-molecular-weight heparin thromboprophylaxis, we suggest that measurements be done of the FVL mutation, a treatable etiology for sporadic pregnancy loss as well as for RPL.

Management strategies for abnormal early pregnancy: a cost-effectiveness analysis.

OBJECTIVE: To assess the potential effectiveness and costs of 4 commonly used strategies to manage abnormal early pregnancies (AEPs). STUDY DESIGN: A decision analysis model was constructed to compare 4 strategies to manage AEPs: (1) observation, (2) medical management, (3) manual vacuum aspiration (MVA), and (4) dilation and curettage (D&C). RESULTS: MVA was the most cost-effective strategy, at dollar 793 per cure, for a total cost of dollar 377 million per 500,000 women and a cure rate of 95%. D&C was more effective than MVA, with a cure rate of 99%, but was more expensive (dollar 2,333 per cure, for a total cost of dollar 1.2 billion). D&C cured 20,000 more patients than MVA; however, at a substantial cost of dollar 38,925 per additional cure. With other estimates at baseline, MVA remained more cost-effective than D&C until the efficacy of MVA was < 82% or the cost of D&C was < dollar 240. CONCLUSION: MVA is the most cost-effective strategy for managing AEP and would be appropriate in settings in which resources are limited. D&C remains a reasonable strategy; however, one must spend dollar 38,925 per additional cure. In the United States, MVA would save dollar 779 million per year relative to D&C.

Therapy with dendritic cells influences the spontaneous resorption rate in the CBA/J x DBA/2J mouse model.

PROBLEM: DBA/2J-mated CBA/J female mice are prone to a high incidence of fetal abortions. This fetal wastage can be dramatically reduced by immunizing the female mice with BALB/c, but not with DBA/2J spleen cells during early gestation. Nevertheless, the underlying mechanisms remain to be elucidated. Recently, dendritic cells (DC) have been described at the feto-maternal interface in the human uterus. In this work, we studied the effect of adoptive transfer of DC on the maintenance of pregnancy in the CBA/J x DBA/2J model. METHODS: Bone marrow-derived DC were generated from virgin female CBA/J mice (6-8 weeks old). CBA/J females were inoculated with DC twice before mating. Four different experimental groups were included: (i) no treatment control, (ii) mice injected with culture medium [granulocyte-macrophage colony-stimulating factor (GM-CSF)], (iii) immunized with DC and (iv) immunized with paternal DBA/2J antigens lisate-pulsed DC, n = 5. RESULTS: The control abortion rate was 23.8%, and with GM-CSF alone was 17.6%. Following inoculation of syngeneic DC abortion rates were reduced to 2.2%, but protection was short-lived. Abortion rates with DC pulsed with DBA/2J antigens was 5%. Serum of interleukin (IL)-6 levels were lower in the latter two groups up to the time of abortion. The kinetics of immunoglobulin G asymmetric antibodies synthesis was modified, but there was no correlation between asymmetric antibodies production and the lowering of abortions rates. CONCLUSION: Syngeneic DC prevented abortions and this was linked to a decrease in IL-6 levels, but not with levels of asymmetric antibodies.