Impact of Regulatory Interventions on Ulipristal Acetate 5 mg (Esmya) Use in Spain: An Interrupted Time-Series Analysis.

PURPOSE: Since late 2017, the use of ulipristal acetate 5 mg (UPA; Proprietary name: Esmya) has been under review in the European Union, due to an emerging hepatic risk. In February 2018 and in July 2018, the Spanish Agency of Medicines and Medical Devices and the marketing authorization holder put two risk minimization measures (RMM) in place, in order to inform about new safety information and to mitigate this risk. This study aims to assess RMM effectiveness in Spain, by performing an interrupted time-series (ITS) analyses, between 2014 and 2019. METHOD: Two quasi-experimental ITS analyses to examine the use of UPA before and after the RMM release were performed: (a) an ecological study using aggregated data from a drug consumption database; and (b) a study using primary healthcare data gathered from electronic clinical records. RESULTS: Regulatory interventions were associated with an immediate and significant decrease level of DID (the number of DDD dispensed per 100 000 inhabitants and day) and incidence. The DID was 70% less than expected 12 months after the interventions. This value was 59% for the incidence. However, a change in the slope was not observed and the use started rising again in the last segment of the study period. CONCLUSION: Despite RMM had an immediate strong impact on UPA use, the last segment upward trend in the long-term might have been affected by the lack of comparable therapeutic alternatives. Further studies should be performed to confirm the increase trend observed and analyze subsequent measures and additional data.

[Is there still a place for progesterone receptor modulators in chronic use ?] / Cas clinique. Y a-t-il encore une place pour les modulateurs du récepteur de la progestérone en continu ?

Selective progesterone receptor modulators (SPRMs) are synthetic steroid compounds that interact with the progesterone receptor, inducing various agonist, antagonist or mixed responses. First identified with mifepristone, they are now represented by ulipristal acetate (UPA), used for emergency contraception and uterine fibroids. Despite a few rare cases of severe hepatic insufficiency, SPRMs offer advantages in the treatment of uterine fibroids, reducing their volume without the hypoestrogenic side-effects of GnRH agonists, thus preserving patients' bone capital and quality of life. Despite temporary suspension of UPA administrated on a daily basis, research is exploring the potential of SPRMs in the management of endometriosis, adenomyosis and breast cancer. Despite certain concerns, SPRMs offer promising prospects in gynecological pathologies, opening up new therapeutic avenues to improve women's health and quality of life. This article describes the case of a patient with peritoneal leiomyomatosis for whom UPA significantly alleviated symptoms, reduced disease progression and improved quality of life, even allowing a pregnancy.

Les modulateurs sélectifs des récepteurs de la progestérone (SPRMs) sont des composés stéroïdiens synthétiques qui interagissent via le récepteur de la progestérone, induisant diverses réponses, agonistes, antagonistes ou mixtes. Les SPRMs ont d'abord été représentés par la mifépristone, utilisée pour ses propriétés antagonistes dans la gestion de l'interruption de la grossesse, puis par l'acétate d'ulipristal, qui est indiqué en contraception d'urgence, mais aussi pour la gestion de myomes utérins symptomatiques. Les SPRMs permettent de réduire le volume des myomes utérins, sans induire les effets secondaires d'hypo-œstrogénie des agonistes de la GnRH, préservant ainsi le capital osseux et la qualité de vie des patientes. Néanmoins, quelques cas graves d'insuffisance hépatique ont conduit à la suspension temporaire de l'acétate d'ulipristal en traitement chronique. En dépit de certaines réserves, les SPRMs offrent des perspectives dans les affections gynécologiques, ouvrant de nouvelles voies thérapeutiques pour améliorer la santé et la qualité de vie des femmes. Des recherches explorent leur potentiel dans l'endométriose, l'adénomyose et la chimioprévention du cancer du sein. Nous décrivons ici le cas d'une patiente avec léiomyomatose péritonéale pour laquelle l'acétate d'ulipristal a significativement réduit les symptômes et l'évolution de la maladie, tout en améliorant la qualité de vie de la patiente, avec même l'obtention d'une grossesse menée à terme.

Using transvaginal ultrasounds for the identification of follicle-like structures ≥10 mm in a multi-center randomized contraceptive clinical trial of three 84-day oral ulipristal acetate regimens.

PURPOSE: We examine the use of transvaginal sonography in imaging ovarian follicles among non-pregnant reproductive-aged women enrolled in a contraceptive clinical trial. METHODS: Ten sites conducted a clinical trial comparing three oral ulipristal acetate regimens for ovulation inhibition. Enrollees underwent twice weekly transvaginal sonography and hormonal blood testing throughout treatment and until the second menses post-treatment. The primary outcome of the present analysis was success in identifying follicles ≥10 mm in a subgroup of sonograms performed at times of likely follicular activity (estradiol <100 pg/ml and progesterone >3 ng/ml). Secondarily, an overall analysis assessed all sonograms regardless of timing. RESULTS: At times of likely follicular activity, 135 women underwent 969 sonograms. The proportion of sonograms without follicles ≥10 mm ranged from 8.3% to 46.3% when stratified by site (p = .01). The odds of no follicle among higher-body mass index (BMI) women were 1.91 times those among lower-BMI women after controlling for site and treatment arm (95% CI: 1.13, 3.22). Results were similar for the overall population. CONCLUSION: Sonographers were less likely to identify follicles for higher-BMI women and results varied by site. Machine quality slightly impacted sonogram results, but did not sufficiently explain site differences.

The progesterone-receptor modulator, ulipristal acetate, drastically lowers breast cell proliferation.

PURPOSE: The proliferation of breast epithelial cells increases during the luteal phase of the menstrual cycle, when they are exposed to progesterone, suggesting that ulipristal acetate, a selective progestin-receptor modulator (SPRM), may reduce breast cell proliferation with potential use in breast cancer chemoprevention. METHODS: Women aged 18-39 were randomized 1:1 to ulipristal 10-mg daily or to a combination oral contraceptive (COC) for 84 days. Participants underwent a breast biopsy and breast MRI at baseline and at end of study treatment. Proliferation of breast TDLU cells was evaluated by Ki67 immunohistochemical stain. We evaluated the breast MRIs for background parenchymal enhancement (BPE). All slides and images were masked for outcome evaluation. RESULTS: Twenty-eight treatment-compliant participants completed the study; 25 of whom had evaluable Ki67 results at baseline and on-treatment. From baseline to end of treatment, Ki67 % positivity (Ki67%+) decreased a median of 84% in the ulipristal group (N = 13; 2-sided p (2p) = 0.040) versus a median increase of 8% in the COC group (N = 12; 2p = 0.85). Median BPE scores decreased from 3 to 1 in the ulipristal group (p = 0.008) and did not decrease in the COC group. CONCLUSION: Ulipristal was associated with a major decrease in Ki67%+ and BPE. Ulipristal would warrant further investigation for breast cancer chemoprevention were it not for concerns about its liver toxicity. Novel SPRMs without liver toxicity could provide a new approach to breast cancer chemoprevention. TRIAL REGISTRATION: NCT02922127, 4 October 2016.

Evaluation of marketing authorization and clinical implementation of ulipristal acetate for uterine fibroids.

Ulipristal acetate (UPA) is a medical treatment for uterine fibroids and was authorized for surgical pre-treatment in 2012 after the conduct of the PEARL I and II randomized controlled trials and for intermittent treatment after the observational PEARL III and IV trials. However, UPA came into disrepute due to its temporary suspension in 2017 and 2020 because of an apparent association with liver injury. This clinical opinion paper aims to review the process of marketing authorization and implementation of UPA, in order to provide all involved stakeholders with recommendations for the introduction of future drugs. Before marketing authorization, the European Medicines Agency (EMA) states that Phase III registration trials should evaluate relevant outcomes in a representative population, while comparing to gold-standard treatment. This review shows that the representativeness of the study populations in all PEARL trials was limited, surgical outcomes were not evaluated and intermittent treatment was assessed without comparative groups. Implementation into clinical practice was extensive, with 900 000 prescribed treatment cycles in 5 years in Europe and Canada combined. Extremely high costs are involved in developing and evaluating pre-marketing studies in new drugs, influencing trial design and relevance of chosen outcomes, thereby impeding clinical applicability. It is vitally important that the marketing implementation after authorization is regulated in such way that necessary evidence is generated before widespread prescription of a new drug. All stakeholders, from pharmaceutical companies to authorizing bodies, governmental funding bodies and medical professionals should be aware of their role and take responsibility for their part in this process.

The Potential of Transforming Growth Factor-beta Inhibitor and Vascular Endothelial Growth Factor Inhibitor as Therapeutic Agents for Uterine Leiomyoma.

Background: Uterine leiomyoma is the most common benign tumor in women of reproductive age, and it can cause infertility. The growth of uterine leiomyoma is mediated by various steroids and growth factors. The purpose of this study was to evaluate the expression of various growth factors in uterine leiomyoma. Additionally, comparing the effects of existing medication and specific growth factor inhibitors on leiomyoma and the normal myometrium, we aimed to see the potential of transforming growth factor-beta (TGF-ß) inhibitors and vascular endothelial growth factor (VEGF) inhibitors as therapeutic drugs for uterine leiomyoma. Methods: This in vitro study included uterine leiomyoma samples from 12 patients who underwent hysterectomy by laparoscopy or laparotomy at Seoul St. Mary's Hospital between May 2016 and March 2018. Normal myometrium and uterine leiomyoma tissue were obtained from each patient and the expression of growth factors was compared using immunohistochemical staining. After the primary culture of normal myometrial and leiomyoma cells, cell viability was evaluated following treatment with 100 nM ulipristal acetate (UPA) and mifepristone for 48 h. Western blot analysis was performed to determine the protein expression of each growth factor. Cell viability was determined following treatment with a 10-µM TGF-ß inhibitor (LY364947) and a 5-µM VEGF inhibitor (axitinib) for 24 h in cultured normal myometrium and leiomyoma cells. Results: Immunohistochemical staining revealed the significantly higher intensity of TGF-ß and VEGF in the leiomyoma tissue than in the normal myometrium (P < 0.05). Mifepristone treatment decreased VEGF expression by 62% in the leiomyoma cells (P < 0.05). According to the cell counting kit-8 (CCK-8) assay, cell viability was decreased after UPA, mifepristone, TGF-ß1 inhibitor, and VEGF inhibitor treatments in the normal myometrium and leiomyoma tissue. The effects of the TGF-ß1 inhibitor significantly differed between normal myometrium and leiomyoma tissue, with a greater decrease in cell survival in the leiomyoma tissue (P < 0.05). Post-hoc analysis showed that the TGF-ß1 and VEGF inhibitors had a greater inhibitory effect on leiomyoma tissue compared with that of UPA. Conclusion: TGF-ß and VEGF inhibitors significantly decreased the viability of uterine leiomyoma cells, showing stronger effects than the conventional drug, UPA. TGF-ß1 inhibitors affect both leiomyoma tissue and the normal uterus; thus, targeted local treatment rather than systemic treatment should be considered.

Emergency contraception subsidy in Canada: a comparative policy analysis.

BACKGROUND: In Canada, cost prohibits access to emergency contraception (EC) which may assist to prevent unintended pregnancy. The drug, ulipristal acetate (UPA-EC), is more clinically effective and cost-effective than the prior standard levonorgestrel (LNG-EC). We analyzed provincial EC subsidization policies and examined underlying decision-making processes. METHODS: We undertook documentary analysis of provincial EC subsidization policies in publicly available drug formularies. We conducted semi-structured interviews with key informants to explore the processes underlying current policies. RESULTS: Quebec is the only province to subsidize UPA-EC, whilst all ten provinces subsidize LNG-EC. As such, provincial EC subsidization policies do not align with the latest UPA-EC evidence. Interviews revealed that evidence was valued in the policymaking process and formulary decisions were made through interdisciplinary consensus. CONCLUSIONS: We identify a gap between EC subsidization policies and the latest evidence. Institutional structures affect policies reflecting evolving evidence. Increasing interdisciplinary mechanisms may encourage evidence-based policies.

Effect of ulipristal acetate on gene expression profile in endometrial cells in culture and in vivo upon post-ovulatory administration in fertile women.

PURPOSE: To analyse the effect of ulipristal acetate (UPA) as emergency contraception (EC) on the gene expression of human endometrial cell line (HEC-1A) and endometrium from fertile women treated with UPA after ovulation. MATERIALS AND METHODS: HEC-1A cells were treated with UPA, and endometrial tissue from four healthy women was collected in cycles before, during and 2 months after post-ovulation pill intake. Ovulation and luteal phase were monitored, and endometrial biopsies were obtained at day LH + 7 in each cycle. In all cases, we analysed the expression profile of 192 genes associated to endometrial receptivity. RESULTS: We observed a significant change in total transcriptomic activity of UPA-treated HEC-1A cells compared to controls. In vivo, we also observed a trend to down-regulation of genes in the UPA-treated cycle that was partially restored in the post-treatment cycle. Altogether, our results supported a partially reversible effect of UPA in gene expression associated with uterine receptivity. CONCLUSIONS: When UPA was administered after ovulation, it seems to induce a down-regulation of the main genes involved in conditioning the endometrium for implantation. This effect is partially restored two months after pill intake. The action of UPA on the endometrium for users of EC should be further investigated.

Ultrasonographic appearance of the endometrium after saline infusion in women presenting with PRM-associated endometrial changes, due to the use of ulipristal acetate.

Ulipristal acetate (UPA), used for the treatment in women with symptomatic fibroids, is associated with endometrial changes visualised on ultrasound as thickening up to more than 16 mm in approximately 10% of the patients. Is saline infusion sonography (SIS) a good alternative for more invasive techniques, to evaluate the presence of intrauterine pathology? Ten patients, presenting with UPA associated endometrial changes at their follow up ultra-sonographic evaluation, were included. Our study demonstrated that SIS is feasible and painless in patients presenting with UPA associated endometrial changes. The thickened endometrium appears to divide at the midline, making it possible to study both layers separately and exclude any suspected intrauterine pathology. Our findings suggest that SIS may be a first choice, non-invasive, painless technique to provide a proper visualisation to rule out intrauterine pathology when UPA associated endometrial changes are diagnosed after fibroid treatment. This is especially of clinical interest in front of assisted reproductive technology treatment. Invasive techniques can be withheld for patients in whom SIS examination is not contributive.Impact StatementWhat is already known on this subject? Reversible endometrial changes after ulipristal acetate (UPA) treatment in patients with symptomatic fibroids have been described. In patients who receive UPA, especially if planned to undergo ART, assessment of potential endometrial pathology is important as such interfere with proper implantation after ART. Consequently, clinicians may consider ruling out intrauterine pathology by invasive examinations such as biopsy or hysteroscopy after visualisation of the thickened endometrium.What do the results of this study add? Saline infusion sonography (SIS) was feasible and painless in patients presenting with UPA associated endometrial changes.What are the implications of these findings for clinical practice and/or further research? SIS may be a first choice, non-invasive, painless technique to provide a proper visualisation to rule out intrauterine pathology when UPA associated endometrial changes are diagnosed after fibroid treatment. This is especially of clinical interest in front of assisted reproductive technology treatment. Invasive techniques can be withheld for patients in whom SIS examination is not contributive in excluding intrauterine pathology.

Hysteroscopic and ultrasonographic evaluation of ulipristal acetate treatment for symptomatic myomas in premenopausal women: a prospective study.

OBJECTIVE: This study aimed to analyze the effects of a six-month therapy with ulipristal acetate (UPA) on myoma size and endometrial thickness in premenopausal women. MATERIAL AND METHODS: Seventy-four women undergoing conservative therapy with UPA were enrolled for this study. All women underwent transvaginal ultrasound evaluation to assess the endometrial thickness, and the number and size of myomas at the beginning and after six months. Hysteroscopy and biopsy were performed after six months, if necessary. RESULTS: After six months of treatment, sonographic examination showed a statistically significant (p < .05) reduction of the size of the largest myoma (56.3 ± 5.1 vs. 31.7 ± 10.1 mm) and a statistically significant (p < .05) increase in endometrial thickness (5.9 ± 2.1 vs. 9.7 ± 3.4 mm). Twenty-two patients with endometrial thickness >10 mm or nonhomogeneous pattern and ten patients with metrorrhagia underwent hysteroscopy: the most frequent finding was the combination of endometrial hypotrophy, floating surface, and chicken-wire vascular pattern aspect (14 cases, 43.7%). Histologic findings showed no case of complex hyperplasia. CONCLUSION: UPA is a safe, effective and assured method to decrease symptoms, reduce the need for surgery in premenopausal women suitable for the treatment.

Pharmacokinetics, toxicological and clinical aspects of ulipristal acetate: insights into the mechanisms implicated in the hepatic toxicity.

Ulipristal acetate is a drug used as emergency contraceptive (30 mg) and for the treatment of moderate to severe symptoms of uterine myomas (5 mg). After commercialization, and although the exact number is unknown, serious cases implying ulipristal acetate 5 mg as a contributing factor of liver injury, some leading to transplantation, were reported. These cases prompted to a restrict use of the drug in January 2021 by the European Medicines Agency. This work aimed to fully review pharmacokinetic aspects, namely focusing in the ulipristal acetate metabolism and other hypothetical toxicological underlying mechanisms that may predispose to drug-induced liver injury (DILI). The high lipophilicity, the extensive hepatic metabolism, the long half-life of the drug and of its major active metabolite, the long-term course of treatment, and possibility due to the formation of epoxide reactive may be contributing factors. Scientific results also points evidence to consider monitorization of liver function during ulipristal acetate treatment.

Progression of adenomyosis magnetic resonance imaging features under ulipristal acetate for symptomatic fibroids.

RESEARCH QUESTION: What is the evolution of adenomyosis on magnetic resonance imaging (MRI) after a 3-month treatment course of daily 5 mg doses of ulipristal acetate (UPA) for symptomatic fibroids? DESIGN: A monocentric prospective pilot study on patients who underwent a 3-month treatment course of UPA for symptomatic fibroids between January 2014 and December 2017. Patients underwent pelvic MRI shortly before (pre-MRI) and after treatment (post-MRI). The diagnosis of adenomyosis on MRI was defined by the observation of intramyometrial cysts and/or haemorrhagic foci within these cystic cavities and/or a thickening of the junctional zone >12 mm. The progression of adenomyosis was defined by the presence of at least one of the aforementioned criteria of adenomyosis on the pre-MRI and by at least one of the following on the post-MRI: (i) increased thickness of the junctional zone ≥20% and/or (ii) increased number of intramyometrial cysts. The appearance of adenomyosis was defined by the absence of the aforementioned criteria of adenomyosis on the pre-MRI and the presence of at least one of these criteria on the post-MRI. RESULTS: Seventy-two patients were included. The MRI features of adenomyosis progressed for 12 of 15 patients (80.0%) for whom adenomyosis was identified on the pre-MRI. An appearance of adenomyosis was identified after treatment for 15 of 57 patients (26.3%) for whom adenomyosis was not identified on the pre-MRI. CONCLUSIONS: A 3-month treatment course of daily 5 mg doses of UPA could provoke a short-term progression or an emergence of typical adenomyosis intramyometrial cysts on MRI examinations.

Risk-efficacy balance of ulipristal acetate compared to surgical alternatives.

AIMS: Uterine fibroids are benign tumours that cause various complaints. These complaints may significantly compromise quality of life, necessitating a clinical intervention in 25-50% of the affected women. Hysterectomy, myomectomy or embolization may offer symptomatic relief, but are costly, include a recovery period, can cause serious side-effects, sometimes fail to treat symptoms completely and are not always desired by patients. Ulipristal is a conservative long-term treatment that has a fibroid-volume decreasing effect, acceptable side-effects while preserving fertility and may be an alternative to surgical alternatives. Currently, ulipristal is investigated by the European Medicine Agency and suspended from marketing authorization because it may cause drug-induced liver injury (DILI). However, many drugs can cause severe DILI and prospective studies estimate 14-19 DILI cases/100 000 people. METHODS: This overview will discuss the risk-benefit balance between ulipristal and DILI, describe the safety-efficacy balance of ulipristal and its alternative treatments and the arguments that led to the suspension of its marketing authorization. RESULTS: Ulipristal may be associated with DILI resulting in a risk of severe liver injury in 1.5:100 000 patients and fatal liver injury in 0.1:100 000 patients. This risk needs to be weighed against the higher mortality risk of >1:1000 and higher incidence of severe complications after surgery. CONCLUSION: The DILI risk of ulipristal is considerably lower than that of other medicines that are not suspended, nor need additional safety measures. When evaluating drugs and drug safety, risks that apply to the alternative nonpharmacological treatment options should be taken into consideration.

Management of symptomatic uterine fibroids after ulipristal acetate suspension and identification of high risk patients for surgery at 6-months of follow-up.

OBJECTIVE: The use of ulipristal acetate (UPA) was indicated for the treatment of uterine fibroids. Following UPA suspension in March 2020, some patients presented worsening and required surgery. We aimed to identify patients at high-risk for undergoing surgery after UPA suspension. METHODS: We evaluated 85 women receiving intermittent UPA treatment until March 2020. Following UPA suspension, patients received other medical treatments or surgery. The clinico-pathological features were recoded and a quality of life health survey was completed by patients at the time of UPA suspension and at 6-months thereafter. RESULTS: After the suspension of UPA, 17 of the 85 patients receiving intermittent UPA (20%) required surgery, and 68 (80%) required other medical treatments. Patients who underwent surgery were younger and had greater fibroid volume. CONCLUSIONS: In our series, 20% of clinically stable patients receiving intermittent UPA required surgery following UPA suspension. These women should be considered for future medical strategies.

Phase III long-term study to evaluate the efficacy and safety of ulipristal acetate in Japanese patients with uterine fibroids.

AIM: To assess the efficacy and safety of long-term intermittent administration of 10-mg ulipristal acetate (UPA) for symptomatic uterine fibroids in Japanese women. METHODS: Open-label, noncomparative study (Japan Primary Registries Network identifier: JapicCTI-173737) conducted at 32 gynecological centers (November 2017-December 2019). Premenopausal women diagnosed with uterine fibroids associated with heavy menstrual bleeding received three 12-week courses of 10-mg UPA once daily. Amenorrhea, fibroid volume, endometrial histology, and safety were assessed. RESULTS: Of 155 patients enrolled, 140 received ≥1 dose of UPA and were analyzed. Across all courses, the rates of patients with amenorrhea for 35 days were >90%, and >99% of patients achieved uterine bleeding normalization. Median time to amenorrhea after each course started was 4-5 days; menstruation returned after treatment within a median of 25-27 days. Mean changes in fibroid volume from baseline were -21.5%, -31.4%, and -35.0% for Courses 1, 2, and 3, respectively. Patients experienced sustained improvements in anemia, pain, and quality of life during treatment. Most adverse events were mild/moderate in severity and decreased in frequency with each course. Seven serious adverse events (six patients) were reported; anemia, embolic cerebral infarction, and pituitary apoplexy (one patient each) were considered UPA-related. Nonphysiological changes in endometrial histology were transient and benign. No safety concerns were detected in hormone concentrations or liver function tests. CONCLUSIONS: Long-term administration of 10-mg UPA is effective for reducing symptoms associated with uterine fibroids in Japanese women. UPA was well tolerated and few safety concerns were reported.

What happens after randomised controlled trials? Uterine fibroids and ulipristal acetate: systematic review and meta-analysis of "real-world" data.

PURPOSE: "Real-world" data incorporates studies performed outside of controlled environments, allowing for a better understanding of the effects of treatment in routine clinical practice. We, therefore, performed a systematic review to summarise available "real-world studies" reporting on the use of ulipristal acetate (UPA) for management of uterine fibroids. METHODS: We designed a prospective protocol according to PRISMA guidelines and registered it with PROSPERO (ID: CRD42019151393). We searched all major databases for relevant citations until 20th September 2019. Our screen included studies for risk of bias using an adapted structured quality assessment tool. Random-effects meta-analysis was used to calculate proportion estimates for each outcome including 95% confidence interval. Reported heterogeneity was assessed using I2. RESULTS: Initial search yielded 755 studies and 13 were included in the final synthesis. Administration of UPA resulted in reduction in the size of fibroids in 56.5% of women, improved menorrhagia in 83% of women, improved perception of pain in 80.1% of women and lead to an improvement in global symptom scores in 85.2% of women. Mean reduction in surgical blood loss and surgical time with use of UPA was 59.85 ml and 12.47 min, respectively. Qualitative analysis suggested that there was no difference in overall surgical experience for patients treated with UPA compared to those without pre-treatment. CONCLUSIONS: Our findings are consistent with previously reported data that UPA is an acceptable management option for women with fibroids. However, it provides limited benefits when used as a pre-operative adjunct, in terms of blood loss and surgical time.

Unplanned pregnancy and awareness of emergency contraception: a postpartum period survey.

OBJECTIVES: The study aimed to determine the awareness of emergency contraception (EC) and knowledge of its use as well as the unplanned pregnancy rate among women in the immediate postpartum period in Ankara, Turkey's second largest city. METHODS: Interviews were carried out among 1955 women on their first or second day postpartum. The interview was based on a questionnaire containing 19 questions covering participants' awareness and experience of using EC as well as their future approach to its use. RESULTS: The rate of unplanned pregnancy was 18.2% and the rate of EC awareness was 26.0%; 89.4% of those who were aware of EC knew how to use it correctly. In the multivariate regression analysis, employment, household income and level of education were independently associated with EC awareness; gravidity, household income, level of education and number of abortions were independently associated with unplanned pregnancy. Awareness of EC increased significantly (p < .05) with age, household income and educational level; knowledge about the correct use of EC increased with age and educational level (p < .05). CONCLUSION: EC awareness among the study population was low and was related to household income and educational level. Household income, educational level and gravidity were the most important factors associated with unplanned pregnancy. Governments must therefore establish appropriate health policies and provide contraceptive education to women from adolescence onwards.

An evaluation of the quality of online information on emergency contraception.

OBJECTIVES: The increasing availability of health information online combined with reduced access to health care providers due to the coronavirus pandemic means that more people are using the internet for health information. However, with no standardised regulation of the internet, the population is vulnerable to misinformation regarding important health information. This review aimed to evaluate the quality and readability of the online information available on emergency contraception (EC) options. STUDY DESIGN: In this descriptive study, a Google search was performed using the term 'emergency contraception options' on 13 April 2020 yielding 232 results. Seventy-one results were excluded (34 inaccessible, 37 contained no medical information). The remaining 161 results were categorised by typology and assessed for credibility (JAMA criteria and HONcode), reliability (DISCERN tool) and readability (Flesch-Kincaid Grade Level and Simple Measure of Gobbledygook). RESULTS: Of all webpages evaluated, the most common typology was governmental. Credibility of web pages was poor (average JAMA score of 1.47 out of 4). Only 10.6% of webpages were HONcode certified. The most common DISCERN category was Fair (29.81%), closely followed by Poor (27.95%) reliability. On average, readability levels were above the recommended grade level for health information. The intrauterine device was discussed least frequently (86.96%) of all the EC options. CONCLUSION: Online information was of low credibility, reliability and written above the recommended reading level. Clinicians should be aware of the poor quality of online information on EC options, and actively educate patients on what makes a source credible.

Safety and efficacy of two repeated cycles of ulipristal acetate in the management of symptomatic uterine fibroid among Indian women.

INTRODUCTION: To evaluate the safety and efficacy along with the impact on uterine and fibroid vascular indices of 2 repeat 12-week courses of ulipristal acetate (UPA) among Indian women. MATERIAL AND METHODS: Ninety-four premenopausal women aged 18-45 years with at least 1 symptomatic fibroid of size ranging from 1 cm to 10 cm were included in the study. All participants received 2 courses of 5 mg of UPA orally for 12 weeks starting from the 5th day of their menstrual cycle with a 2-menstrual-cycle break in between. The efficacy was measured in terms of time to amenorrhoea, percentage of women who achieved amenorrhoea for the last 35 consecutive days, reduction in uterine and fibroid volume, as well as its vascularity at the end of the first and second treatment cycle. RESULTS: Eighty-six women completed the first treatment cycle whereas only 65 women completed the second treatment course. Seventy-nine per cent of women achieved amenorrhoea for 35 consecutive days during the first treatment cycle. Median time to amenorrhoea was 7 days and 5 days during the first and second treatment cycle, respectively. Percentage reduction of the mean fibroid volume was 32% and 52% after the first and second treatment cycle, respectively. We observed an increase in fibroid vascular indices (pulsatility index and resistive index) suggesting reduction in fibroid vascularity. Serum oestradiol remained at mid-follicular phase. No serious drug emergent side effect was noted. CONCLUSIONS: Two interrupted repeat course of 5mg UPA is well tolerated efficient and safe in symptomatic fibroid among Indian women.

Ulipristal acetate and pregnancy outcome-an observational study.

STUDY QUESTION: Is the failure of the selective progesterone receptor modulator ulipristal acetate (UPA) as emergency contraception (EC; 30 mg, single) or inadvertent exposure for myoma treatment (5 mg/d) in pregnancy associated with a higher risk of birth defects, spontaneous abortion (SAB) or elective termination of pregnancy (ETOP)? SUMMARY ANSWER: We did not find an increased risk for birth defects, SABs or ETOPs after UPA exposure during implantation and early embryogenesis. WHAT IS KNOWN ALREADY: Pregnancy outcome data after exposure to UPA are very limited. In cases of EC failure or unplanned pregnancy during myoma treatment, women need well-grounded risk assessment to minimize anxiety and prevent unjustified termination of pregnancy. STUDY DESIGN, SIZE, DURATION: Observational study of prospectively ascertained pregnancies from the German Embryotox institute with UPA exposure (EC, n = 95; myoma, n = 7). Four retrospectively reported pregnancy outcomes were evaluated separately. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 226 requests on ulipristal were directed to the German Embryotox institute during the study period 2010-2018. Outcomes of pregnancies exposed-(i) precycle, (ii) preconceptional or (iii) first trimester-were ascertained using standardized questionnaires. Descriptive statistics were applied. MAIN RESULTS AND THE ROLE OF CHANCE: Failed EC with UPA resulted in 95 prospectively ascertained pregnancies, of which 56 had completed follow-up: 37 live births, 7 SABs and 12 ETOPs. There was no major birth defect. Just 34% of women had taken UPA during the fertile window. Seven prospectively enrolled pregnancies were treated for myoma and had known pregnancy outcomes: five healthy live births and two SABs. Among the four retrospectively reported pregnancies after EC, there was one child diagnosed with Beckwith-Wiedemann syndrome (BWS). LIMITATIONS, REASONS FOR CAUTION: Our limited sample size does not allow concluding safety of UPA use in pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: We provide a preliminary basis for reassuring women who wish to carry their pregnancy to term after EC or myoma treatment with UPA. However, because of the report of a BWS after UPA exposure, a possible epigenetic effect could not be excluded and requires further evaluation. STUDY FUNDING/COMPETING INTEREST(S): This work was performed with financial support from the German Federal Institute for Drugs and Medical Devices (BfArM). All authors declare that they have no conflicts of interest. TRIAL REGISTRATION NUMBER: Registered with the German Clinical Trial Register (DRKS00015155).