Postfertilization Effect of Hormonal Emergency Contraception
Abstract
To assess the possibility of a postfertilization effect in regard to the most common types of hormonal emergency contraception (EC) used in the US and to explore the ethical impact of this possibility.
A MEDLINE search (1966-November 2001) was done to identify all pertinent English-language journal articles. A review of reference sections of the major review articles was performed to identify additional articles. Search terms included emergency contraception, postcoital contraception, postfertilization effect, Yuzpe regimen, levonorgestrel, mechanism of action, Plan B.
The 2 most common types of hormonal EC used in the US are the Yuzpe regimen (high-dose ethinyl estradiol with high-dose levonorgestrel) and Plan B (high-dose levonorgestrel alone). Although both methods sometimes stop ovulation, they may also act by reducing the probability of implantation, due to their adverse effect on the endometrium (a postfertilization effect). The available evidence for a postfertilization effect is moderately strong, whether hormonal EC is used in the preovulatory, ovulatory, or postovulatory phase of the menstrual cycle.
Based on the present theoretical and empirical evidence, both the Yuzpe regimen and Plan B likely act at times by causing a postfertilization effect, regardless of when in the menstrual cycle they are used. These findings have potential implications in such areas as informed consent, emergency department protocols, and conscience clauses.
... He claimed that post-fertilization action was possible because of the capacity of the drug to act 5-6 days after treatment. Therefore, it was ethically necessary to communicate this possibility to patients for their informed consent (FDA 2003, p. 271;Larimore and Stanford 2000;Kahlenborn et al. 2002). Despite alternative interpretations of the research, five committee members supported a label on the outside carton to inform patients "at the point of purchase" (FDA 2003, pp. ...
... However, its effect on fertilization was not as well studied or evidenced (limited to Kesserü et al. 1974Kesserü et al. , 1975, and its effects on implantation were difficult to replicate consistently (for positive findings, see Landgren et al. 1989;Moggia et al. 1974;Shirley et al. 1995;Ugocsai et al. 1984; for negative findings, see Durand et al. 2001;Marions et al. 2002). This mixed state of the evidence enabled several scientific reviewers (including Stanford in the US) to claim that post-coital progestin might act after fertilization and that patients and providers deserve to know such (Kahlenborn et al. 2002;Larimore and Stanford 2000;Wilks 2000). ...
Philosophers of science and medicine now aspire to provide useful, socially relevant accounts of mechanism. Existing accounts have forged the path by attending to mechanisms in historical context, scientific practice, the special sciences, and policy. Yet, their primary focus has been on more proximate issues related to therapeutic effectiveness. To take the next step toward social relevance, we must investigate the challenges facing researchers, clinicians, and policy makers involving values and social context. Accordingly, we learn valuable lessons about the connections between mechanistic processes and more fundamental reasons for (or against) medical interventions, particularly moral, ethical, religious, and political concerns about health, agency, and power. This paper uses debates over the controversial morning-after pill (emergency contraception) to gain insight into the deeper reasons for the production and use of mechanistic knowledge throughout biomedical research, clinical practice, and governmental regulation. To practice socially relevant philosophy of science, I argue that we need to account for mechanistic knowledge beyond immediate effectiveness, such as how it can also provide moral guidance, aid ethical categorization in the clinic, and function as a political instrument. Such insights have implications for medical epistemology, including the value-laden dimensions of mechanistic reasoning and the “epistemic friction” of values. Furthermore, there are broader impacts for teaching research ethics and understanding the role of science advisors as political advocates.
... Emergency contraception (EC) has been available in Italy since the year 2000, when levonorgestrel 1.5 mg specifically labelled for EC was first marketed under medical prescription. At the time, its mechanism of action (whether or not it should be considered an abortifacient) [1] was amply debated, and the Italian National Committee on Bioethics issued a statement in favour of the right to conscientious objection to prescribing levonorgestrel for EC by physicians and pharmacists. [2] As a result, a number of physicians and private clinics initially did not routinely provide EC, which forced women to go to a hospital emergency department to obtain a prescription. ...
Objectives: The aim of the study was to retrieve data on the characteristics and profile of women attending an emergency service (ES) to receive a prescription (mandatory until May 2015) for emergency contraception (EC).
Methods: In a retrospective study the following data were collected for all women requesting EC between January 2014 and June 2015: demographic characteristics, time between unprotected sexual intercourse (USI) and arrival at the ES, time between the last menstrual period and the USI, and type of EC prescribed. In a prospective study starting January 2015, a questionnaire was administered requesting the following information: reasons for requiring EC, previous EC use, source of knowledge about EC, prior contraception and age at first intercourse.
Results: During the whole study period, 1773 women requested EC: their mean age was 26.0 years; 78.5% were Italian; 91.5% were unmarried; 55.2% were still studying and 51.9% had high school education; 61.2% reached the ES within 12 h of the USI; and 42.4% had a USI during days 9–16 of their menstrual cycle. Levonorgestrel was prescribed in 81.4% of women and ulipristal acetate in 17.7%. In the prospective part of the study (382 women), the majority (57.9%) requested EC for condom rupture; 49.5% reported previous use of EC; and 41.6% received information on the subject through friends. The vast majority (83.8%) reported prior use of contraception; in 25.4% the reason for not using it was the absence of a relationship.
Conclusion: An exact profile of women requesting EC can help women in their choice of permanent contraception, and help clinicians in counselling women on appropriate contraception.
... Kahlenborn and colleagues, in their 2002 publication, summarize early studies regarding the post-fertilization effects of EC agents. 20 Based on a combination of theoretical and empirical arguments, the authors argue that the efficacy of EC agents cannot be explained by ovulatory inhibition or the inhibition of sperm transport alone. Thus, they surmise that endometrial effects must also be present. ...
The debate over conscience rights and emergency contraceptive agents among pharmacists and other healthcare professionals centers on the potential abortifacient potential of such agents. Such an important ethical and scientific question should be guided by established facts. This paper reviews the available evidence for post-fertilization effects of the emergency contraception drug levonorgestrel, and demonstrates that such evidence is uniformly lacking. The authors then discuss the ethical implications of these findings. This lack of any substantial evidence for post-fertilization effects may significantly weaken conscience claims, and may militate against refusals to dispense or to refer.
While the Value-Free Ideal of science has suffered compelling criticism, some advocates like Gregor Betz continue to argue that science policy advisors should avoid value judgments by hedging their hypotheses. This approach depends on a mistaken understanding of the relations between facts and values in regulatory science. My case study involves the morning-after pill Plan B and the “Drug Fact” that it “may” prevent implantation. I analyze the operative values, which I call zygote-centrism, responsible for this hedged drug label. Then, I explain my twofold account of value-ladenness, involving the constitutive role of value judgments in science and the social function of facts as political tools. Because this drug fact is ineliminably value-laden in both senses, I conclude that hedged hypotheses are not necessarily value-free. https://philpapers.org/go.pl?id=CHODFV&u=https%3A%2F%2Fphilpapers.org%2Farchive%2FCHODFV.pdf
This analysis examines the precise moral question whether healthcare professionals and survivors of sexual assault can have moral certitude that in any given case the use of Levonorgestrel [LNG], in its clinical dosage for emergency contraception, constitutes a legitimate act of self-defense by suppressing ovulation, and failing that goal does not remove, destroy, or interfere with the implantation of an embryo. This question is examined first by giving a brief overview of the pharmacological design of LNG and its known mechanisms of action to date. Second, it is argued that reducing the moral question to an interminable exchange of opposing scientific views is not consistent with the Catholic moral tradition on moral certitude. Rather, it is shown that the question pivots on how both scientific and non-scientific factors must be taken into account in reaching moral certitude on the issue. To this end, a brief historical account of the Catholic manualist tradition on moral certitude is provided. Third, this tradition is applied to various aspects of the moral question. The analysis concludes that the opinion in favor of using LNG in any given case as an act of self-defense against the lingering effects of sexual assault is consistent with the Catholic moral tradition on moral certitude.
The flourishing of the individual human person, the health of human society, and the ecological well being of planet earth are inextricably connected with the issues of human population, sexuality, and reproduction. Many academic disciplines have strong interests in these issues, approaching them from different perspectives and with different emphases. However, these areas of study are also infused with controversy and strong ideological positions arising from cultural, religious, political, and social traditions that sometimes clash with each other. To address these issues, two things are needed: (1) data that address questions from different underlying assumptions; (2) open and respectful discussion among scientists, clinicians, and policy makers who have different backgrounds, narrative frameworks, and conceptual perspectives (1). The new Section on Population, Reproductive and Sexual Health, Frontiers in Public Health will contribute constructively to these critical needs.
TESIS DOCTORAL
La contracepción de emergencia: Aspectos farmacológicos y de información pública implicados en su valoración bioética.
Realizada por Julio Tudela Cuenca
Dirigida por: Justo Aznar Lucea.
Palabras clave: Contracepción de emergencia, mecanismo anovulatorio, mecanismo antiimplantatorio, embarazo, aborto, información farmacológica.
Resumen
La irrupción de la contracepción de emergencia como una opción para evitar embarazos no deseados ha abierto nuevos campos de investigación y diseño de nuevos métodos que merecen una reflexión desde el punto de vista ético. La sustitución de un disciplinado ritmo de tratamiento farmacológico, con la toma de múltiples dosis de un fármaco, por otro que no supone la administración diaria de un tratamiento, sino su toma esporádica, con la intención de evitar un embarazo después de una relación sexual “desprotegida”, parece un alternativa interesante, que está promoviendo la aparición de nuevos fármacos destinados a este fin.
En este trabajo se ha realizado una revisión bibliográfica de la literatura científica y medios de comunicación divulgativos sobre trabajos publicados relacionados con la contracepción de emergencia en general, así como los contenidos disponibles en las agencias de evaluación de medicamentos u organismos reguladores de su aprobación o responsables de su control, con el fin de evaluar los mecanismos de acción de estos métodos, su eficacia para la reducción de embarazos no deseados y abortos, las consecuencias de su libre dispensación y la existencia de posibles sesgos, inexactitudes o errores en la elaboración y difusión de la información técnica que acompaña a la distribución de este tipo de tratamientos farmacológicos.
Contraceptivos de emergencia analizados:
Método Yuzpe.
Resulta el más obsoleto y menos eficaz como contraceptivo. Utiliza una combinación de estrógenos y progesterona.
Dispositivo Intrauterino.
El único método no farmacológico utilizable en la contracepción de emergencia es el dispositivo intrauterino (DIU), con o sin cobre o medicación hormonal incorporada.
Levonorgestrel.
El LNG es un progestágeno con una afinidad por los receptores de progesterona tres veces mayor que ésta. Puede administrarse como una dosis única de 1.5 mg o dos dosis de 0.75 mg separadas 12 horas, dentro de las setenta y dos horas siguientes a una relación sexual sin protección.
Es, a día de hoy, el único contraceptivo de emergencia que, en determinados países, puede obtenerse sin receta médica.
Mifepristona.
La mifepristona o píldora abortiva (RU-486) se utiliza, además de como contraceptivo de emergencia, como método abortivo en embarazos consolidados, esto es, cuando el embrión ya ha sido implantado en el endometrio de la madre. No es generalmente considerado como una opción real en contracepción de emergencia salvo en algunas excepciones.
Ulipristal acetato.
Se trata de un modulador selectivo de los receptores de progesterona sintético, con actividad antagonista sobre los receptores de progesterona en humanos.
Conclusiones .
Sobre el mecanismo de acción:
Todos los contraceptivos de emergencia analizados en este trabajo muestran distintos mecanismos de acción, entre los que se encuentran la intercepción en el proceso implantatorio. Esta evidencia, que es asumida por la gran mayoría de la comunidad científica para el caso del método Yuzpe, el dispositivo intrauterino en sus distintas modalidades y la mifepristona, es abiertamente rechazada en muchos casos para los métodos que utilizan levonorgestrel y ulipristal.
De los datos analizados en este trabajo puede concluirse que en los métodos contraceptivos de emergencia autorizados a base de levonorgestrel y ulipristal, el mecanismo antiimplantatorio no solo existe, sino que es responsable, en mayor proporción, de su eficacia como contraceptivo, si son analizadas todas las circunstancias en que pueden ser utilizados.
Sobre la eficacia para reducir el número de embarazos no deseados y abortos:
De los datos analizados en este trabajo puede deducirse que estas cifras no se han reducido, antes al contrario, siguen un proceso de crecimiento en líneas generales. Además, se detectan incrementos en las cifras de determinadas enfermedades de transmisión sexual en algunas poblaciones en las que se ha promocionado y facilitado el consumo de determinados contraceptivos de emergencia, como el levonorgestrel.
Sobre la libre dispensación:
El estatus de libre dispensación aplicado, a día de hoy, solo al caso del levonorgestrel, eliminando toda barrera para su obtención, como la prescripción, límite de edad o coste económico, ha producido un efecto multiplicador en la cifra de sus dispensaciones, pero sin traducirse en un incremento de eficacia en cuanto a lograr los fines descritos en el punto anterior.
Los intentos de facilitar el libre acceso a estos métodos, han eliminado la posibilidad de llevar a cabo un control en la prescripción, dispensación y seguimiento farmacoterapéutico, siendo que no están libres de contraindicaciones, incompatibilidades, riesgo de sobredosificación y efectos secundarios. Algunos de ellos, aunque infrecuentes, son graves, como el caso del tromboembolismo venoso o el embarazo ectópico.
Sobre la información pública:
La información referente a los métodos contraceptivos de emergencia, suministrada tanto desde las publicaciones y sociedades científicas, como desde autoridades sanitarias y medios divulgativos, muestran, en muchos casos, graves sesgos, inexactitudes, omisiones y falsedades.
Los más graves son los referidos al mecanismo de acción, dada la trascendencia de que los facultativos prescriptores, los farmacéuticos dispensadores y las posibles usuarias conozcan si estos métodos impiden una fecundación o terminan con la vida de un ser humano.
Sobre la objeción de conciencia:
Para finalizar, de todo lo expuesto anteriormente, puede concluirse que los resultados de este trabajo ayudan a legitimar el derecho al planteamiento de la objeción de conciencia por parte del personal sanitario implicado en la prescripción y dispensación de los métodos contraceptivos de emergencia. El respeto al derecho a la vida del nasciturus, sobre el que atentan estos métodos, constituye una razón suficiente para su planteamiento.
The use of levonorgestrel for emergency post coital contraception after rape, has raised strong and recurring discussions during 2004 and 2005 in Chile. The debate has been centered in its presumed post fertilization or anti implantation effect, that some consider an abortive action. There are no scientific evidences supporting this effect, with divergences about the ontological status of the embryo. Therefore, the use of levonorgestrel implies bioethical decisions that, in a democratic and pluralistic society, should be solved considering individual and collective responsibilities, conditions of equity and the informed autonomy of the affected women. Their moral values and their capacity to assume the consequences of an assault on their dignity, honor and self-esteem, in addition to physical and mental injuries, should also be considered (Rev Méd Chile 2005; 133: 841-6).
Introdução: A anticoncepção de emergência (AE) é método contraceptivo reservado para situações especiais em que outros métodos não são utilizados, falham ou não podem ser empregados. Sua inclusão nas políticas públicas de saúde é estratégica para reduzir a incidência da gravidez indesejada e diminuir a ocorrência do abortamento induzido, clandestino e inseguro. Contudo, persistem barreiras contra o método pautadas no desconhecimento
de seu mecanismo de ação e na suposição de efeito abortivo. Objetivo: Revisão dos mecanismos de ação demonstráveis da AE, incluindo efeitos parao endométrio e relação com a implantação do blastocisto. Método: Consulta nas bases de dados do Medline, Lilacs, Scielo e JCR-ISL, incluindo artigos indexados publicados entre 1970 e 2011. Resultados: Evidências diretas e indiretas indicam que a AE impede exclusivamente a fecundação por suprimir ou postergar a ovulação, e/ou por interferir na migração sustentada e capacitação dos espermatozoides. Não há evidência de efeito para a morfologia
ou receptividade do endométrio, ou efeito sobre a nidação do blastocisto. Conclusão: O mecanismo de ação da AE não interfere nos eventos posteriores à fecundação, não impede ou prejudica a nidação e não se associa com a eliminação precoce do embrião.
OBJECTIVE: To compare the effectiveness and acceptability of three regimens of postcoital contraception. DESIGN: Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose. SETTING: Community family planning clinic. SUBJECTS: 616 consecutive women with regular cycles aged 16 to 45 years. MAIN OUTCOME MEASURES: Number of pregnancies, incidence of side effects, and timing of next period. RESULTS: The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group. CONCLUSIONS: Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed.
Mifepristone (RU 486) is a synthetic steroid with potent antiprogestational and antiglucocorticoid properties that provides an effective medical method of inducing abortion in early pregnancy. Since progesterone is essential for implantation, we tested the use of mifepristone for emergency postcoital contraception.
We studied 800 women and adolescents requesting emergency postcoital contraception who had had unprotected intercourse within the preceding 72 hours. A total of 398 women and adolescents were randomly assigned to treatment with 100 micrograms of ethinyl estradiol and 1 mg of norgestrel, each given twice 12 hours apart (standard therapy), and 402 women and adolescents were randomly assigned to receive 600 mg of mifepristone.
None of the women and adolescents who received mifepristone became pregnant, as compared with four of those who received standard therapy; the difference in failure rates between the two regimens was not statistically significant. The number of pregnancies in each group was significantly lower than the number expected according to calculations based on the day of the cycle during which intercourse had taken place (P less than 0.001). In many subjects the stage of the cycle as calculated by menstrual history was inconsistent with measurements of plasma progesterone or urinary pregnanediol excretion. The subjects treated with mifepristone reported less nausea (40 percent vs. 60 percent) and vomiting (3 percent vs. 17 percent) on the day of treatment, as well as lower rates of other side effects, than the subjects treated with the standard regimen, but they were more likely to have a delay in the onset of the next menstrual period (42 percent vs. 13 percent).
Mifepristone is a highly effective postcoital contraceptive agent that, if used more widely, could help reduce the number of unplanned and unwanted pregnancies.
Background A previous randomised study suggested that the progestagen, levonorgestrel, given alone in two separate doses each of 0.75 mg caused nausea and vomiting in fewer women and might be more effective than the Yuzpe regimen of combined oral contraceptives for emergency contraception, although the difference was not significant. We compared these two regimens when started within 72 h of unprotected coitus. Methods We enrolled in the double-blind, randomised trial 1998 women at 21 centres worldwide. Women with regular menses, not using hormonal contraception, and requesting emergency contraception after one unprotected coitus, received levonorgestrel (0.75 mg, repeated 12 h later) or the Yuzpe regimen (ethinyloestradiol 100 mu g plus levonorgestrel 0.5 mg, repeated 12 h later). Findings Outcome was unknown for 43 women (25 assigned levonorgestrel, 18 assigned Yuzpe regimen). Among the remaining 1955 women, the crude pregnancy rate was 1.1% (11/976) in the levonorgestrel group compared with 3.2% (31/979) in the Yuzpe regimen group. The crude relative risk of pregnancy for levonorgestrel compared with the Yuzpe regimen was 0.36 (95% CI 0.18-0.70). The proportion of pregnancies prevented (compared with the expected number without treatment) was 85% (74-93) with the levonorgestrel regimen and 57% (39-71) with the Yuzpe regimen. Nausea (23.1 vs 50.5%) and vomiting (5.6 vs 18.8%) were significantly less frequent with the levonorgestrel regimen than with the Yuzpe regimen (p<0.01). The efficacy of both treatments declined with increasing time since unprotected coitus (p=0.01). Interpretation The levonorgestrel regimen was better tolerated and more effective than the current standard in hormonal emergency contraception. With either regimen, the earlier the treatment is given, the more effective it seems to be.
Abstract Data on 1898 menstrual cycles, for 241 married women, were analysed by means of a quantal regression programme. The locations of the day of ovulation was determined by the basal body temperature method. Estimates were obtained of the risk of conception from an act of coitus on each day, as measured from the day of ovulation. The relationship between fecundability and coital frequency was also examined.
The secretion rate and plasma concentration of the adrenocortical steroid cortisol is modified in subjects treated with estrogenic and/or progestational steroids. The effects of contraceptive steroids on the secretion of ACTH are poorly documented, however, In the current investigation, we found that concentrations of ACTH and cortisol in plasma obtained at 0800--0900 h from a group of women with normal cyclic menses (n = 4) ranged from 78--120 pg/ml and 77--137 ng/ml, respectively. Although significant cyclic changes in the plasma levels of LH, FSH, 17 beta-estradiol, and progesterone occurred during the ovarian cycle, no obvious cyclic fluctuations in plasma levels of ACTH or cortisol were observed. In women treated with Norinyl 1 + 80 (1.0 mg norethindrone plus 0.08 mg mestranol), plasma concentrations of LH, FSH, 17 beta-estradiol, and progesterone were significantly lower (P less than 0.001) than plasma levels of these hormones in normal women during the ovarian cycle. The mean daily plasma concentrations of ACTH were significantly lower (P less than 0.001), whereas plasma cortisol levels were significantly higher (P less than 0.001) in women treated with oral contraceptive steroids compared to the levels of these hormones in the untreated ovulatory women.
Possible mechanisms of action of a combination of ethinylestradiol (EE) and dl-norgestrel as a postcoital contraceptive agent were studied in 12 healthy female volunteers. An oral dose of 0.1 mg of EE and 1.0 mg of dl-norgestrel was given at the predicted time of ovulation and again 12 hours later. Serum luteinizing hormone, prolactin, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by specific radioimmunoassays in blood samples obtained daily from the 8th day of the menstrual cycle to the 1st day of menses. Hormone profiles suggested that the medication elicited a range of individual variations in pituitary and/or ovarian responses. Histologic examination of the endometrium consistently showed significant alteration in endometrial development with a dissociation in maturation of glandular and stomal components. This postcoital contraceptive acts either by (1) suppressing ovulation or (2) disrupting luteal function by acting directly on the corpus luteum or by interfering with appropriate endometrial responses to ovarian steroids.
Inseminations were carried out according to a protocol which recommended, during the first two menstrual cycles, a single intracervical insemination, using one dose of semen and no accompanying therapy. For 821 such cycles, the success rate per cycle was 12%. Cycle days were numbered with respect to the last day of hypothermia, and the highest success rates were obtained on days -1 (21%) and -3 (20%). Three other factors were studied: dilation of the cervix, abundance of cervical mucus, and spinnbarkheit. For these factors, conception rates were 14% when the cervix was dilated (versus 8%, P<0.05), 15% when there was abundant mucus (versus 6%, P<0.001), and 18% when spinnbarkheit was ≥ 10 cm (versus 9%, P<0.001). Combinations of these factors are considered.
Uterine zonal anatomy as visualized on T2-weighted (repetition time, 2,500 msec; echo time, 80 msec) magnetic resonance (MR) images consists of a high-intensity central (endometrial) zone, a subjacent low-intensity junctional zone of myometrium, a moderately intense zone of myometrium, and a thin, low-intensity subserosal zone of myometrium. To better define the histologic correlates of these diagnostically significant zones, T2-weighted MR images of 17 in vivo and 13 extirpated human uteri were compared with histologic sections of 17 uteri stained with hematoxylin-eosin, Mallory trichrome, and immunofluorescence staining for actin. Morphometric and electron microscopic observations of uterine surgical specimens were also made. The observations indicate that both the junctional zone and the subserosal zone consist of compact smooth muscle fibers with little extracellular matrix compared with the myometrium proper. Also, the junctional zone is divided into a compact region and a transitional region. The compact region correlates well with the hypointense MR appearance of the junctional zone.
To attempt the monitoring of ovulation induction solely with ultrasound (US).
Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle.
Specialist Reproductive Endocrine Unit.
Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients.
Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations.
Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008).
Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase.
The ethinylestradiol-norgestrel combination (EE-NG) for postcoital contraception, as described by Yuzpe, has been shown to be an effective method but with frequent side effects. To overcome the problem of adverse effects a new approach using danazol was proposed, but the efficacy and acceptability of this treatment have not yet been tested in large studies. In a 5-year period at the AIECS Family Planning Centre in Milan we treated 2448 women requesting postcoital contraception using Yuzpe's regimen and two danazol regimens (800 mg/1200 mg). The patients' acceptability for danazol treatment was higher than for Yuzpe's regimen due to fewer, milder and shorter side effects. Nine pregnancies occurred in the EE-NG group (2.21%), 17 in the 800 mg group (1.71%) and 6 in the 1200 mg group (0.82%). Our study shows a statistically significant efficacy against expected pregnancy rates both with Yuzpe's regimen and with danazol. The 1200 mg danazol treatment seems to be more effective and can be considered a valid alternative to the EE-NG combination for hormonal postcoital contraception.