Directive clinique No 315 : Prévention du syndrome d'hyperstimulation ovarienne.

DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

The prevention of ovarian hyperstimulation syndrome.

OBJECTIVE: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its prevention. OPTIONS: Preventative measures, early recognition, and prompt systematic supportive care will help avoid poor outcomes. OUTCOMES: Establish guidelines to assist in the prevention of ovarian hyperstimulation syndrome, early recognition of the condition when it occurs, and provision of appropriate supportive measures in the correct setting. EVIDENCE: Published literature was retrieved through searches of Medline, Embase, and the Cochrane Library from 2011 to 2013 using appropriate controlled vocabulary ([OHSS] ovarian hyperstimulation syndrome and: agonist IVF, antagonist IVF, metformin, HCG, gonadotropin, coasting, freeze all, agonist trigger, progesterone) and key words (ovarian hyperstimulation syndrome, ovarian stimulation, gonadotropin, human chorionic gonadotropin, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to February 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Summary Statements 1. The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I) 2. Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III) 3. Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2) 4. The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I) 5. There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III) 6. Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2) 7. Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2) 8. Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) Recommendations 1. The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A) 2. Gonadotropin dosing should be carefully individualized, taking into account the patient's age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B) 3. Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C) 4. Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B) 5. A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C) 6. Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E) 7. Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C) 8. Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A) 9. Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B).

Objectif : Passer en revue les aspects cliniques du syndrome d'hyperstimulation ovarienne et fournir des recommandations quant à sa prévention. Options : La mise en œuvre de mesures de prévention, la constatation précoce de la présence de ce syndrome et l'offre sans délai et systématique de soins de soutien nous aideront à éviter l'obtention de piètres issues. Issues : Établir des lignes directrices permettant d'orienter la prévention du syndrome d'hyperstimulation ovarienne, la constatation précoce de la présence du syndrome lorsque ce dernier se manifeste et l'offre de mesures de soutien appropriées dans le bon contexte. Résultats : La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans Medline, Embase et The Cochrane Library entre 2011 et 2013 au moyen d'un vocabulaire contrôlé (« ovarian hyperstimulation syndrome ¼, « agonist IVF ¼, « antagonist IVF ¼, « metformin ¼, « HCG ¼, « gonadotropin ¼, « coasting ¼, « freeze all ¼, « agonist trigger ¼, « progesterone ¼) et de mots clés (« ovarian hyperstimulation syndrome ¼, « ovarian stimulation ¼, « gonadotropin ¼, « human chorionic gonadotropin ¼, « prevention ¼) appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais. Aucune restriction n'a été imposée en matière de date. Les recherches ont été mises à jour de façon régulière et ont été intégrées à la directive clinique jusqu'en février 2013. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Déclarations sommaires 1. La formulation particulière d'hormone folliculostimulante qui est utilisée aux fins de la stimulation ovarienne n'affecte pas l'incidence du syndrome d'hyperstimulation ovarienne. (I) 2. La pratique du « coasting ¼ pourrait atténuer l'incidence du syndrome d'hyperstimulation ovarienne grave. (III) 3. Le maintien de la pratique du « coasting ¼ pendant plus de trois jours entraîne la baisse des taux de grossesse de la fécondation in vitro. (II-2) 4. L'utilisation d'hormone lutéinisante ou de gonadotrophine chorionique humaine aux fins de la maturation finale des ovocytes n'influence pas l'incidence du syndrome d'hyperstimulation ovarienne. (I) 5. Aucune donnée probante publiée n'indique clairement que le fait d'abaisser la dose de gonadotrophine chorionique humaine entraîne une atténuation du taux de syndrome d'hyperstimulation ovarienne. (III) 6. Le cabergoline, administrée à partir du jour du déclenchement au moyen de gonadotrophine chorionique humaine, atténue l'incidence du syndrome d'hyperstimulation ovarienne chez les patientes exposées à des risques élevés et ne semble pas entraîner une baisse des taux de fécondation in vitro. (II-2) 7. Le fait d'éviter la grossesse en procédant à la congélation de tous les embryons permet de prévenir la manifestation d'un syndrome d'hyperstimulation ovarienne grave et prolongé chez les patientes exposées à des risques élevés. (II-2) 8. Lorsque les embryons sont congelés par vitrification aux fins d'un transfert à une date ultérieure, l'utilisation d'agonistes de la gonadolibérine (dans le cadre de protocoles faisant appel à des antagonistes de la gonadolibérine) pour la maturation finale des ovocytes n'affecte pas les taux de grossesse. (II-2) Recommandations 1. L'ajout d'un traitement à la metformine devrait être envisagé chez les patientes présentant le syndrome des ovaires polykystiques qui ont recours à la fécondation in vitro, puisqu'il pourrait mener à une baisse de l'incidence du syndrome d'hyperstimulation ovarienne. (I-A) 2. La posologie de gonadotrophines devrait être rigoureusement personnalisée, en tenant compte de l'âge de la patiente, de sa masse corporelle, de sa numération des follicules antraux et de sa réaction précédente aux gonadotrophines. (II-3B) 3. L'annulation du cycle avant l'administration de gonadotrophine chorionique humaine constitue une stratégie permettant de prévenir efficacement le syndrome d'hyperstimulation ovarienne; toutefois, le fardeau affectif et financier qu'une telle pratique impose aux patientes devrait être pris en considération au préalable. (III-C) 4. L'utilisation de protocoles de stimulation au moyen d'un antagoniste de la gonadolibérine est recommandée chez les patientes exposées à des risques élevés de syndrome d'hyperstimulation ovarienne. Chez les patientes qui font l'objet de protocoles aux antagonistes de la gonadolibérine et qui réagissent de façon très robuste à la stimulation ovarienne, le risque de syndrome d'hyperstimulation ovarienne grave peut être atténué en utilisant un agoniste de la gonadolibérine à titre de substitut à la gonatrophine chorionique humaine pour le déclenchement de la maturation finale des ovocytes. (I-B) 5. Pour ce qui est des donatrices d'ovocytes et dans le cadre des cycles de préservation de la fertilité, la mise en œuvre d'un protocole qui fait appel à un antagoniste de la gonadolibérine (et à un agoniste de la gonadolibérine pour le déclenchement de la maturation finale des ovocytes) est recommandée. (III-C) 6. L'utilisation d'albumine ou d'autres succédanés du plasma au moment de la récupération d'ovules n'est pas recommandée aux fins de la prévention du syndrome d'hyperstimulation ovarienne. (I-E) 7. Le transfert sélectif d'un seul embryon est recommandé aux patientes qui sont exposées à un risque élevé de syndrome d'hyperstimulation ovarienne. (III-C) 8. Pour assurer le soutien de la phase lutéale, l'utilisation de progestérone devrait être préférée à celle de gonadotrophine chorionique humaine. (I-A) 9. La tenue d'une culdocentèse en clinique externe devrait être envisagée pour la prévention de l'évolution de la maladie, en présence d'un syndrome d'hyperstimulation ovarienne grave. (II-2B).

Does an intraabdominally placed LNG-IUS have an adverse effect on fertility? A case report.

This case of secondary infertility with an associated intraabdominal levonorgestrel intrauterine system (LNG-IUS) demonstrates the importance of adequate imaging in women with a missing intrauterine contraceptive device and the possible fertility implications of an extrauterine LNG-IUS.

Access to fertility services for lesbian women in Canada.

OBJECTIVE: To determine reproductive services offered to lesbian patients by Canadian fertility clinics, policies of practice, ease of access to these services, and sensitivity of clinics to this population of patients. DESIGN: Survey sent to assisted reproductive technology (ART) clinic directors. SETTING: Academic medical center, university-based ethics institute. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The percentage of Canadian fertility clinics that will provide reproductive services to lesbian patients; services offered; the presence of clinic policies on lesbian care; and the presence on web sites of heteronormative material. RESULT(S): Completed surveys were received from 71% (24/34) of clinics. All clinics surveyed provided reproductive services to lesbian patients, with the exception of one clinic. Five of 24 (21%) clinics have a written policy on care for lesbian patients; 29% (7/24) will provide services to lesbian patients without prior investigations. All clinics will offer IUI and cycle monitoring to lesbian patients. Twenty-three of 24 clinics (96%) will offer IVF services when required. Fourteen of 32 clinic web sites (44%) make mention of lesbian patients and 27% (8/30) have heteronormative information only. CONCLUSION(S): Lesbians encounter several barriers to accessing reproductive services in Canada. Addressing these issues could improve experiences of lesbian women and couples seeking care at fertility clinics.

MRI biomarkers for evaluation of treatment efficacy in preclinical diabetic retinopathy.

INTRODUCTION: One sober consequence of the current epidemic of diabetes mellitus is that an increasing number of people world-wide will partially or completely lose their sight to diabetic retinopathy. Clinically, the sight-threatening complications of diabetes are diagnosed and treated based on visible retinal lesions (e.g., dot-blot hemorrhages or retinal neovascularization). However, such anatomical microvascular lesions are slow to respond with treatment. Thus, there remains an urgent need for imaging biomarkers that are abnormal before retinal lesions are visibly apparent and are responsive to treatment. AREAS COVERED: Here, the development of new MRI methods, such as manganese-enhanced MRI, for evaluating early diabetes-evoked retinal pathophysiology, and its usefulness in guiding new treatments for diabetic retinopathy are reviewed. EXPERT OPINION: In diabetic retinopathy, not all important diagnostic and prognostic needs are well served by optical methods. In the absence of gross anatomy changes, critical times when drug intervention is most likely to be successful at reducing vision loss are missed by most light-based methods and thus provide little help in guiding diagnosis and treatment. For example, before clinical symptoms, is there an optimal time to intervene with drug therapy? Is a drug reaching its target? How does one assess optimal drug dose, schedule, and routes? How well do current experimental models mimic the clinical condition? As discussed herein, MRI is as an analytical tool for addressing these unmet needs. Future clinical applications of MRI can be envisioned such as in clinical trials to assess drug treatment efficacy, or as an adjunct approach to refine or clarify a difficult clinical case. New MRI-generated hypotheses about the pathogenesis of diabetic retinopathy and its treatment are discussed. In the coming years, a substantial growth in the development and application of MRI is expected to address relevant question in both the basic sciences and in the clinic.

Vulvar inflammation as the only clinical manifestation of Crohn disease in an 8-year-old girl.

Recognition of Crohn disease in children who present with cutaneous vulvar lesions as their initial clinical manifestation is often difficult. We report here the case of an 8-year-old girl with chronic vulvar edema, which on biopsy revealed granulomatous inflammation of the vulva. Further investigation and biopsy of the terminal ileum demonstrated similar findings and was consistent with a diagnosis of Crohn disease.

Substance use in female adolescents with eating disorders.

To determine the prevalence of substance use in adolescents with eating disorders, compare the results with a data set of Ontario high school students, and explore why adolescents with eating disorders do, or do not, use various substances. From January 1999 to March 2000, 101 female adolescents who met the DSM-IV criteria for an eating disorder were followed up in a tertiary care pediatric treatment center. They were asked to participate in a cross-sectional study using a self-administered questionnaire assessing substance use and investigating reasons for use and nonuse; 95 agreed to participate and 77 completed the questionnaire (mean age, 15.2 years). The patients were divided into two groups: 63 with restrictive symptoms only, 17 with purging symptoms. The rates of drug use between subjects and their comparison groups were compared by z-scores, with the level of significance set at.05. During the preceding year, restrictors used significantly less tobacco, alcohol, and cannabis than grade- and sex-matched comparison populations, and purgers used these substances at rates similar to those of comparison subjects. Other drugs seen frequently in the purgers included hallucinogens, tranquilizers, stimulants, LSD, PCP, cocaine, and "ecstasy." Both groups used caffeine and laxatives, but few used diet pills. Restrictors said they did not use substances because they were bad for their health, tasted unpleasant, were contrary to their beliefs, and were too expensive. Purgers generally used substances to relax, relieve anger, avoid eating, and "get away" from problems. Female adolescents with eating disorders who have restrictive symptoms use substances less frequently than the general adolescent population but do not abstain from their use. Those with purging symptoms use substances with a similar frequency to that found in the general adolescent population. Because the sample size for the purging group was small, firm conclusions cannot be drawn from our analysis. Health care providers who treat adolescents with eating disorders are in a good position to identify those who use substances and may be at risk for substance abuse.