La anticoncepción de emergencia es menos efectiva en mujeres con obesidad / Emergency contraception is less effective in women with obesity

La anticoncepción de emergencia se refiere al uso de medicación o a la inserción de un dispositivo intrauterino de cobre para prevenir el embarazo luego de una relación sexual no protegida o del fallo de un método anticonceptivo, en una mujer que no desea el embarazo. De entre las alternativas farmacológicas del método, se estima que el uso de levonorgestrel prevendría el 50% de los embarazos. A partir de una viñeta clínica, en la cual se describe el caso de una paciente obesa que resultó embarazada luego de utilizar anticoncepción hormonal de emergencia tras una relación sexual no protegida, se realizó una búsqueda bibliográfica para establecer la efectividad del método en pacientes con esta característica (obesidad). La búsqueda identificó un metaanálisis que relacionó al triple la probabilidad de embarazo en pacientes con índice de masa corporal superior a 30 kg/m2 que utilizaron anticoncepción de emergencia hormonal. (AU)

Emergency contraception refers to the use of medication or the insertion of a copper intrauterine device to prevent pregnancy after the occurance of unprotected sex intercourse or failure of a contraceptive method in a woman who does not desire pregnancy. Among the pharmacological alternatives of the method it is estimated that the use of levonorgestrel prevents 50% of pregnancies. From a clinical vignette, in which the case of an obese patient who became pregnant using hormonal emergency contraception after unprotected sex intercourse is described, a literature search was conducted to establish the effectiveness of the method in patients with this feature (obesity). The search identified a metaanalysis that shows an incresed probability (threetimes) of pregnancy in patients with body mass index greater than 30 kg/m2 that used hormonal emergency contraception. Emergency contraception is less effective in women with obesity. (AU)

Coadministration of HMG-CoA reductase inhibitors, atorvastatin and rosuvastatin, does not affect contraceptive efficacy of centchroman.

OBJECTIVE: The study aimed to investigate the effect of concomitant use of atorvastatin or rosuvastatin on the pharmacokinetic and pharmacodynamic profile of centchroman, a non-steroidal female oral contraceptive. METHODS: A rat model was used to predict pharmacokinetic drug-drug interactions between centchroman and atorvastatin or rosuvastatin. A dried blood spot sampling technique followed by liquid chromatography-tandem mass spectrometry detection was employed for analysis of the pharmacokinetic interaction study samples. Sperm-positive female rats were investigated for postcoital contraceptive activity of centchroman with or without coadministration of atorvastatin or rosuvastatin. RESULTS: Coadministration of atorvastatin or rosuvastatin may increase the systemic availability of centchroman in blood, but it does not affect the pharmacodynamic profile of centchroman. CONCLUSION: Atorvastatin or rosuvastatin may be prescribed with centchroman without compromising the contraceptive efficacy of centchroman.

Postcoital administration of RU486 induces a hormonally under-stimulated rat endometrium.

RU486 is a partial progesterone and estrogen receptor antagonist, functioning to actively silence progesterone receptor gene-associated transcription. For this reason, it has been used as both a contraceptive and an abortive agent. In the present study, cellular and gene specific effects of RU486 were investigated in a rat model of early pregnancy, including key phases of the window of receptivity and early implantation. As these stages are hormonally regulated by progesterone and estrogens, the focus here was to elucidate the mechanism of action of a single dose of RU486, used as a postcoital contraceptive, to successfully prevent implantation of a viable blastocyst. Immunofluorescent techniques were used to examine the change in protein levels of PR in RU486-treated endometria at days 4.5, 5.5 and 6.5 of pregnancy. Changes in the Pgr gene expression level as a consequence of RU486 administration was evaluated using quantitative real-time reverse transcription polymerase chain reaction. The progesterone receptor gene and protein expression was ubiquitously decreased throughout pregnancy as a direct consequence of RU486 administration. The overall effects of postcoital RU486 administration during early pregnancy indicate highly effective inhibition of progesterone and estrogen effects on the endometrium, mediated by their receptors. More specifically, the expression and localization of the progesterone receptor mirrors that described in ovariectomized animal models, suggesting a hormonally under-stimulated endometrium. Clearly from the present study, the precise priming of the endometrium by progesterone, in preparation for blastocyst implantation, is severely impaired by RU486, thus predisposing the uterus to pregnancy failure.

Anticoncepção de emergência: método levonorgestrel

Material utilizado na unidade 1 do Curso de Capacitação em Atenção Integral à Saúde Sexual e Reprodutiva II (curso autoinstrucional), produzido pela UNA-SUS/UFMA e voltado para médicos que atuam na Atenção Básica. Este material descreve, de forma interativa, o uso do Levonorgestrel como método contraceptivo emergencial, abordando sua indicação para uso. Traz, também, o protocolo para a utilização do Levonorgestrel na anticoncepção hormonal de emergência.

Anticoncepção de emergência: método yuzpe

Material utilizado na unidade 1 do Curso de Capacitação em Atenção Integral à Saúde Sexual e Reprodutiva II (curso autoinstrucional), produzido pela UNA-SUS/UFMA e voltado para médicos que atuam na Atenção Básica. Este material descreve, de forma interativa, o método Yuzpe na contracepção emergencial, abordando as duas opções de uso desse método. Traz, também, orientações aos profissionais de saúde para condução durante as consultas, efeitos adversos e/ou colaterais e contraindicações.

RU OK? The acceptability and feasibility of remote technologies for follow-up after early medical abortion.

OBJECTIVES: We tested the effectiveness and feasibility of remote communication technologies to increase follow-up after early medical abortion. STUDY DESIGN: Women (n=999) were randomized to 'remote' follow-up incorporating a low-sensitivity pregnancy test and standardized symptom questionnaire administered online, by text message or telephone by a non-clinical call center operator 2 weeks after treatment, or to 'clinic-based' follow-up with ultrasound at 1 week. Women in the clinic-based group who could not return performed a high-sensitivity pregnancy test at 3 weeks and had a telephone call with clinic staff. The primary outcome was completion of follow-up. Rates of complications, acceptability and preferences were compared. RESULTS: The overall follow-up rate did not differ by group {clinic-based, 73% vs. remote, 69%; risk ratio (RR) 1.0 [95% confidence interval (CI) 0.9-1.2]}. In the clinic-based group, 83% did not return for an ultrasound scan and were followed up by phone. In the remote group, follow-up by phone or text was more successful than online (text: 75.4%; phone: 73.7%; online: 46.5%, p<.001). The proportion of women receiving additional care was 9% in the clinic-based group and was 4% in the remote group [RR 1.8 (95% CI 1.1-3.1)]. Most women found their follow-up method acceptable but would prefer follow-up by phone or text message if needed in future. CONCLUSIONS: Follow-up after medical abortion using remote communication is feasible and, for most women, preferable to a clinic visit. IMPLICATIONS: Medical abortion protocols typically use follow-up visits to ensure early identification of complications. This study demonstrates that follow-up can be achieved using remote communication technologies. This model may reduce the burden of multiple clinic visits on patients and providers.

Mifepristone: a potential clinical agent based on its anti-progesterone and anti-glucocorticoid properties.

Nowadays, unwanted pregnancy is a major globe tragedy for millions of women, associated with significant direct and indirect costs, no matter for individuals or society. The progesterone receptor antagonist steroid, mifepristone has been widely and effectively using throughout the world for medical abortion, but to a lesser extent for emergency contraception. In this review, we hope to explore the role of mifepristone as a contraceptive, particularly for emergency contraception. Studies of mifepristone have also been expanding to the fields of endometriosis and uterine fibroids. Furthermore, this initially considered reproductive medicine has been investigated in some psychotic diseases and various disorders of hypercortisolism, because of its glucocorticoid receptor antagonism. Mifepristone was approved suitable for patients with hyperglycemia secondary to Cushing's syndrome by the United States Food and Drug Administration (FDA) in 2012. The aim of this article is to review published reports on the anti-progesterone and anti-glucocorticoid properties of mifepristone as a clinical agent. There is a new insight into systematically describing and evaluating the potential efficiency of mifepristone administrated in the field of endocrine and neuroendocrine, not only in obstetrics and gynecology.

Effects of ulipristal acetate on sperm DNA fragmentation during in vitro incubation.

OBJECTIVE: Ulipristal acetate (UPA) acts as an emergency contraceptive by inhibiting ovulation. This study explores possible additional effects on the fragmentation of sperm DNA during in vitro incubation. METHODS: Motile spermatozoa from healthy donors were selected by swim-up and incubated under capacitating conditions in control medium or with UPA (1, 10, 100, 1,000 or 10,000 ng/ml). In some experiments, 200 µM of H2O2 were added to induce oxidative stress. The sperm chromatin dispersion test was performed to analyse DNA integrity (400 cells; 1000×). Lipid peroxidation (thiobarbituric acid assay), induced-acrosome reaction (AR) and sperm vitality (Eosin Y) were also evaluated in spermatozoa exposed to UPA and/or H2O2. RESULTS: During sperm incubation, the percentage of fragmented DNA increased significantly, from 15.0 ± 1.3 to 41.0 ± 4.5% (p < 0.001). In the presence of UPA, DNA fragmentation decreased significantly (p < 0.05), in a dose-dependent manner. At 100 and 1000 ng/ml, UPA also counteracted the effect of H2O2 and prevented DNA fragmentation. No effect on sperm vitality, lipid peroxidation or induced-AR was found with any treatment. CONCLUSIONS: During in vitro sperm capacitation DNA fragmentation increased but the latter was counteracted in the presence of UPA, which possibly acted as a scavenger of reactive oxygen species produced by spermatozoa.

Ulipristal acetate prevents ovulation more effectively than levonorgestrel: analysis of pooled data from three randomized trials of emergency contraception regimens.

BACKGROUND: The days just prior to ovulation are the most crucial for emergency contraception (EC) efficacy. Ulipristal acetate (UPA) and levonorgestrel's (LNG) capacity to inhibit follicular rupture have never been compared directly at this time of the cycle. STUDY DESIGN: Raw data from three pharmacodynamics studies with similar methodology were pooled to allow direct comparison of UPA, LNG and LNG + meloxicam's ability to prevent ovulation when administered orally in the advanced follicular phase, with a leading follicle of ≥ 18 mm. RESULTS: Forty eight LNG-treated (1.5 mg) cycles, 31 LNG (1.5 mg) + meloxicam (15 mg), 34 UPA (30 mg) cycles and 50 placebo cycles were compared. Follicle rupture was delayed for at least 5 days in 14.6%, 38.7%, 58.8% and 4% of the LNG-, LNG + meloxicam-, UPA- and placebo-treated cycles, respectively. UPA was more effective than LNG and placebo in inhibiting follicular rupture (p = .0001), while LNG, when administered at this time of the cycle, was not different than placebo. The addition of meloxicam improved the efficacy of LNG in preventing follicular rupture (p = .0292 vs. LNG; p = .0001 vs. placebo; non-significant vs. UPA). UPA was effective in preventing rupture in the 5 days following treatment, even when administered at the time of the luteinizing hormone (LH) surge (UPA 79%, LNG 14% and placebo 10%). None of the treatments were effective when administered on the day of the LH peak. The median time from treatment to rupture was 6 days during the ulipristal cycles and 2 days in the placebo and LNG/LNG + meloxicam cycles (p = .0015). CONCLUSION: Although no EC treatment is 100% effective in inhibiting follicular rupture when administered in the late follicular phase, UPA is the most effective treatment, delaying ovulation for at least 5 days in 59% of the cycles. LNG is not different from placebo in inhibiting follicular rupture at this advanced phase of the cycle. No treatment was effective in postponing rupture when administered on the day of LH peak.

Emergency contraception.

There have been numerous attempts to control fertility after unprotected sexual intercourse (UPSI). From very bizarre methods like the vaginal application of Coca Cola to the more serious attempts using calcium antagonists influencing fertility parameters in sperm to hormonal methods or intrauterine devices. So far, hormonal methods preventing or delaying ovulation have proved to be the most popular starting with the combination of ethinyl estradiol and levonorgestrel (LNG), known as the Yuzpe regimen. The first dose had to be taken within 72 hours of UPSI, a second one 12 hours later. Later on, LNG alone, at first in a regimen similar to the Yuzpe method (2 × 0.75 mg 12 hours apart) showed to be more successful, eventually resulting in the development of a 1.5 mg LNG pill that combined good efficacy with a high ease of use. Several efficacious and easy to use methods for emergency contraception (EC) are available on the market today with the most widely spread being LNG in a single dose of 1.5 mg (given as one tablet of 1.5 mg or 2 tablets of 0.75 mg each) for administration up to 3 days (according to WHO up to 5 days) after UPSI. Its limitations are the non-optimal efficacy which is decreasing the later the drug is taken and the fact that it is only approved for up to 72 hours after UPSI. This regimen has no effect on the endometrium, corpus luteum function and implantation, is not abortive and don't harm the fetus if accidentally taken in early pregnancy. It has no impact on the rate of ectopic pregnancies. It has become the standard method used up to this day in most countries. Since the mid 1970s copper IUDs have been used for EC, which show a high efficacy. Their disadvantages lie in the fact that EC is considered an off label use for most IUDs (not for the GynFix copper IUD in the European Union) and that they might not be acceptable for every patient. Furthermore IUD-insertion is an invasive procedure and it is required trained providers and sterilized facilities. Mifepristone in the dosages of 10 or 25 mg is used with good results as an emergency contraceptive in China for up to 120 hours after UPSI, but has never received any significant consideration in Western countries. While high doses of mifepristone has an effect on endometrial receptivity and will inhibit ovulation if given in the follicular phase and prevent implantation if given in the early luteal phase, low doses such as 10 mg has no impact on the endometrium. Mifepristone does not increase the rate of ectopic pregnancies. The most recent development is the approval of the selective progesterone receptor modulator ulipristal acetate (UPA) in the dosage of 30 mg for EC up to 5 days after UPSI, combining the safe and easy application of the single dose LNG pill with an even higher efficacy. It has shown to be more efficacious than LNG and can be used for up to 120 hours after UPSI; the difference in efficacy is highest for 0-24 hours, followed by 0-72 hours following UPSI. No VTE has been reported following UPA-administration or any progesterone receptor modulator. No effect on endometrium, corpus luteum function and implantation has been observed with doses used for EC. Independent of the substance it should be noted that, if there is a choice, the intake of an oral emergency contraceptive pill should happen as soon as possible after the risk situation. A pre-existing pregnancy must be excluded. Possible contraindications and drug interactions must be considered according to the individual special product informations.

Effect of exposure to ulipristal acetate on sperm function.

OBJECTIVE: A pill containing ulipristal acetate (UPA) is used for emergency contraception (EC). Considering that, following its intake, spermatozoa may be exposed to UPA in the female genital tract we intended to evaluate sperm functions after incubation with this compound. METHODS: Motile spermatozoa were selected by swim-up and were incubated under capacitating conditions with UPA (at concentrations of 1, 10, 100, 1,000, and 10,000 ng/ml) or control medium. The main outcome measures were sperm vitality, sperm protein tyrosine phosphorylation (TyrP), spontaneous acrosomal reaction (AR), and human follicular fluid (hFF)-induced AR. RESULTS: Sperm vitality and TyrP pattern were similar between spermatozoa exposed to UPA or control. In addition, spontaneous AR ranged from 14.0 ±1.5% to 18.0 ±1.9% after exposure to UPA or control medium without significant differences, and UPA did not prevent hFF-induced AR. CONCLUSIONS: Incubation of sperm with UPA at concentrations around the expected plasma levels after ingestion of this EC pill (˜100-200 ng/ml) did not modify the signal transduction of TyrP involved in sperm capacitation. Moreover, UPA showed no agonist effect on progesterone receptors because it did not induce AR. Considering that progesterone in hFF is essential for AR induction, and UPA did not prevent the hFF-induced AR, an antagonist action of UPA on the AR is unlikely.

Métodos anticonceptivos utilizados por población inmigrante y condicionantes que influyen en su elección en un área sanitaria de Zaragoza / Contraceptive methods used by immigrant populations and conditions that influence the choice in a health area in Zaragoza

Introducción. En los últimos años el porcentaje de mujeres inmigrantes ha aumentado provocando el surgimiento de necesidades específicas referentes a su salud sexual y reproductiva. El objetivo fue conocer los métodos anticonceptivos utilizados por ellas y los condicionantes que influyen en su elección. Estimar como indicadores de alerta: uso de píldora poscoital y prevalencia de abortos. Material y métodos. Estudio descriptivo transversal, mediante encuesta realizada en el primer trimestre del año 2011 en el Centro de Salud Delicias Sur (Zaragoza). La población diana fueron mujeres inmigrantes en edad fértil (15-45 años) que acudieron al centro, previo consentimiento informado. Muestreo accidental por cuotas. Resultados. La edad media fue de 29,35 años (IC al 95% = 27,95-30,75 años). El país de origen mayoritario fue Ecuador. Casi la mitad de las mujeres estaban solteras y trabajaban por cuenta ajena, y su nivel de instrucción era medio. La media de años de residencia en España fue de 5,68 años (IC al 95% = 4,99-6,37 años). Un 42% de las mujeres (IC al 95% = 32,62-51,83) no utilizaba ningún método anticonceptivo. El método más utilizado fue el preservativo, seguido de la píldora. Más de la mitad de las mujeres habían sido informadas en atención primaria. Un 32% (IC al 95% = 23,42-41,60) de ellas tenían un antecedente de aborto. Respecto al uso de la píldora poscoital (PPC), había recurrido a ella el 19,39% (IC al 95% = 12,46-28,10). Conclusiones. El 42% no utilizaba ningún método anticonceptivo y los indicadores de alerta sobre el fracaso de medidas preventivas en salud reproductiva son elevados (AU)

Background. The percentage of women immigrants in Spain has increased in these last years, resulting in the emergence of specific needs related to sexual and reproductive health. The objective of this article was to define the contraceptive methods used by immigrant women and the determining factors that influence their choice. To estimate the use of emergency post-coital contraception and prevalence of abortion. Methods. A descriptive cross-sectional study using a survey was carried out in the first quarter of 2011 at the "Centro de Salud Delicias Sur" in Zaragoza, Spain. The target population were immigrant women of childbearing age between 15 and 45 years who attended the clinic. Non probability sampling was used. Results. The mean age was 29.35 years (95% confidence interval (CI) = 27.95 to 30.75 years). The majority country of origin was Ecuador. Almost half the women were single and worked in paid employment. The educational level was considered as average. The average duration of residence in Spain was 5.68 years (95% CI = 4.99 to 6.37 years) and 42% of them (95% CI = 32.62 to 51.83) did not use any contraceptive method. The most used contraceptive method was the condom, followed by oral hormonal contraceptives. More than half of the women had been informed in Primary Care. Almost one third (32%) (95% CI = 23.42 to 41.60) of the women had a history of abortion. More than 19% of women (95% CI = 12.46 to 28.10) had used the emergency contraceptive method. Conclusion. Contraceptive methods were not used by 42% of women. The alert indicators on the failure of preventive measures in sexual health are still too high (AU)

Results from pooled Phase III studies of ulipristal acetate for emergency contraception.

BACKGROUND: Ulipristal acetate (UPA) is a new effective option to prevent unintended pregnancies up to 5 days after unprotected intercourse. We used pooled data from two Phase III studies to refine our understanding of the efficacy of UPA by time from unprotected intercourse and the effects of other factors on pregnancy rates. STUDY DESIGN: Data from two Phase III studies were pooled to create a larger analysis population. Analyses were performed on the first participation of 2183 women. RESULTS: A total of 41 women became pregnant despite the use of UPA, yielding an overall proportion pregnant of 1.9% (1.3%-2.5%). Proportions of pregnant women were higher among those with further acts of unprotected intercourse in the same cycle and among obese women. These varied from 1.3% (0.9%-2.0%) among nonobese women who had no further acts of unprotected intercourse (n=1704) to 8.3% (0.2%-38.5%) among obese women who had subsequent unprotected intercourse (n=12). CONCLUSIONS: UPA is effective and safe in preventing pregnancy after unprotected intercourse. Its effectiveness is lower among women who have subsequent unprotected intercourse and among obese women.

Emergency contraception and RU-486 (mifepristone): do bioethical discussions improve learning and retention?

To systematically investigate whether the inclusion of a bioethical discussion improves the learning and retention of biological content, students in two sections of an introductory zoology class were taught the biology behind emergency contraception and RU-486. Students in one section of the course participated in a bioethical discussion, whereas students in the other section participated in a content-only discussion. Pre- and postsurveys, response paragraphs, and a final exam were collected and used to examine the learning and retention of content knowledge. Results suggested that students who participated in a bioethical discussion of emergency contraception and RU-486 learned and retained information better than students who received content-only instruction. Interestingly, students who participated in the bioethical discussion also appeared to be more confident in their answers. The results of this study may inform the teaching practices and goals of science educators who would like to incorporate a discussion of bioethical issues into their curriculum but often feel that content coverage is paramount.

Serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) inhibits the rat embryo implantation in vivo and interferes with cell adhesion in vitro.

BACKGROUND: This study was conducted to observe the in vivo effect of 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) on embryo implantation in rats and its in vitro effect on cell adhesion. STUDY DESIGN: The anti-implantation efficacy of AEBSF in rats was determined by counting the number of visible implanted embryos on day 8 of pregnancy following intrauterine (5 mg and 10 mg AEBSF per horn) or tail vein (10 mg AEBSF per rat) administration on day 3 of pregnancy. The effects of AEBSF on cell adhesion were detected, respectively, by using the mouse blastocysts-endometrial cells or the human umbilical vein endothelial cells (HUVECs)-HeLa cells co-culture model. The alteration in protein secretion pattern of HUVECs and HeLa cells was detected by the proteome analysis. RESULTS: 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride showed an in vivo inhibitory effect on embryo implantation in rat. In vitro, AEBSF could disturb the growth of blastocysts on endometrial cells and inhibit the adhesion of HeLa cells on HUVECs. The treatment of AEBSF could alter the protein secretion pattern of co-cultured HUVEC-HeLa cells. CONCLUSION: 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride might be a potential leading compound for novel contraceptives, and its inhibitory effect on implantation might result from the interference in extracellular matrix remodeling process.