The HERA (Hyper-response Risk Assessment) Delphi consensus definition of hyper-responders for in-vitro fertilization.

PURPOSE: To provide an agreed upon definition of hyper-response for women undergoing ovarian stimulation (OS)? METHODS: A literature search was performed regarding hyper-response to ovarian stimulation for assisted reproductive technology. A scientific committee consisting of 5 experts discussed, amended, and selected the final statements in the questionnaire for the first round of the Delphi consensus. The questionnaire was distributed to 31 experts, 22 of whom responded (with representation selected for global coverage), each anonymous to the others. A priori, it was decided that consensus would be reached when ≥ 66% of the participants agreed and ≤ 3 rounds would be used to obtain this consensus. RESULTS: 17/18 statements reached consensus. The most relevant are summarized here. (I) Definition of a hyper-response: Collection of ≥ 15 oocytes is characterized as a hyper-response (72.7% agreement). OHSS is not relevant for the definition of hyper-response if the number of collected oocytes is above a threshold (≥ 15) (77.3% agreement). The most important factor in defining a hyper-response during stimulation is the number of follicles ≥ 10 mm in mean diameter (86.4% agreement). (II) Risk factors for hyper-response: AMH values (95.5% agreement), AFC (95.5% agreement), patient's age (77.3% agreement) but not ovarian volume (72.7% agreement). In a patient without previous ovarian stimulation, the most important risk factor for a hyper-response is the antral follicular count (AFC) (68.2% agreement). In a patient without previous ovarian stimulation, when AMH and AFC are discordant, one suggesting a hyper-response and the other not, AFC is the more reliable marker (68.2% agreement). The lowest serum AMH value that would place one at risk for a hyper-response is ≥ 2 ng/ml (14.3 pmol/L) (72.7% agreement). The lowest AFC that would place one at risk for a hyper-response is ≥ 18 (81.8% agreement). Women with polycystic ovarian syndrome (PCOS) as per Rotterdam criteria are at a higher risk of hyper-response than women without PCOS with equivalent follicle counts and gonadotropin doses during ovarian stimulation for IVF (86.4% agreement). No consensus was reached regarding the number of growing follicles ≥ 10 mm that would define a hyper-response. CONCLUSION: The definition of hyper-response and its risk factors can be useful for harmonizing research, improving understanding of the subject, and tailoring patient care.

The HERA (Hyper-response Risk Assessment) Delphi consensus for the management of hyper-responders in in vitro fertilization.

PURPOSE: To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS) METHODS: A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori, it was decided that consensus would be reached when ≥66% of the participants agreed, and ≤3 rounds would be used to obtain this consensus. A total of 28/31 experts responded (selected for global coverage), anonymous to each other. RESULTS: A total of 26/28 statements reached consensus. The most relevant are summarized here. The target number of oocytes to be collected in a stimulation cycle for IVF in an anticipated hyper-responder is 15-19 (89.3% consensus). For a potential hyper-responder, it is preferable to achieve a hyper-response and freeze all than aim for a fresh transfer (71.4% consensus). GnRH agonists should be avoided for pituitary suppression in anticipated hyper-responders performing IVF (96.4% consensus). The preferred starting dose in the first IVF stimulation cycle of an anticipated hyper-responder of average weight is 150 IU/day (82.1% consensus). ICoasting in order to decrease the risk of OHSS should not be used (89.7% consensus). Metformin should be added before/during ovarian stimulation to anticipated hyper-responders only if the patient has PCOS and is insulin resistant (82.1% consensus). In the case of a hyper-response, a dopaminergic agent should be used only if hCG will be used as a trigger (including dual/double trigger) with or without a fresh transfer (67.9% consensus). After using a GnRH agonist trigger due to a perceived risk of OHSS, luteal phase rescue with hCG and an attempt of a fresh transfer is discouraged regardless of the number of oocytes collected (72.4% consensus). The choice of the FET protocol is not influenced by the fact that the patient is a hyper-responder (82.8% consensus). In the cases of freeze all due to OHSS risk, a FET cycle can be performed in the immediate first menstrual cycle (92.9% consensus). CONCLUSION: These guidelines for the management of hyper-response can be useful for tailoring patient care and for harmonizing future research.

Hyper response to ovarian stimulation affects the follicular fluid metabolomic profile of women undergoing IVF similarly to polycystic ovary syndrome.

INTRODUCTION: During in vitro fertilization (IVF), the hyper response to controlled ovarian stimulation (COS) is a common characteristic among patients diagnosed with polycystic ovary syndrome (PCOS), although non-diagnosed patients may also demonstrate this response. OBJECTIVES: In an effort to investigate follicular metabolic characteristics associated with hyper response to COS, the present study analyzed follicular fluid (FF) samples from patients undergoing IVF. METHODS: FF samples were obtained from patients with PCOS and hyper response during IVF (PCOS group, N = 15), patients without PCOS but with hyper response during IVF (HR group, N = 44), and normo-responder patients receiving IVF (control group, N = 22). FF samples underwent Bligh and Dyer extraction, followed by metabolomic analysis by ultra-performance liquid chromatography mass spectrometry, considering two technical replicates. Clinical data was analyzed by ANOVA and chi-square tests. The metabolomic dataset was analyzed by multivariate statistics, and the significance of biomarkers was confirmed by ANOVA. RESULTS: Clinical data showed differences regarding follicles production, oocyte and embryo quality. From the 15 proposed biomarkers, 14 were of increased abundance in the control group and attributed as fatty acids, diacylglycerol, triacylglycerol, ceramide, ceramide-phosphate, phosphatidylcholine, and sphingomyelin. The PCOS patients showed increased abundance of a metabolite of m/z 144.0023 that was not attributed to a class. CONCLUSION: The clinical and metabolic similarities observed in the FF of hyper responders with and without PCOS diagnosis indicate common biomarkers that could assist on the development of accessory tools for assessment of IVF parameters.

Assessing ovarian response: antral follicle count versus anti-Müllerian hormone.

Oocyte number and quality decline with age; however, fertility varies significantly even among women of the same age. Various measures have been developed to predict response to ovarian stimulation and reproductive potential. Evaluation of ovarian reserve can identify patients who may experience poor response or hyper-response to exogenous gonadotrophins and can aid in the personalization of treatment to achieve good response and minimize risks. In recent years, two key methods, antral follicle count (AFC), an ultrasound biomarker of follicle number, and the concentration of serum anti-Müllerian hormone (AMH), a hormone biomarker of follicle number, have emerged as preferred methods for assessing ovarian reserve. In this review, a live debate held at the American Society for Reproductive Medicine 2013 Annual Meeting is expanded upon to compare the predictive values, merits, and disadvantages of AFC and AMH level. An ovarian reserve measure without limitations has not yet been discovered, although both AFC and AMH have good predictive value. Published evidence, however, as well as the objectivity and potential standardization of AMH level and the convenience of testing any time throughout the menstrual cycle, leans towards AMH level becoming the gold-standard biomarker to evaluate ovarian reserve and predict ovarian response to stimulation.

Obesity and cumulative inflammatory burden: a valuable risk assessment parameter in caring for dental patients.

UNLABELLED: A new model of risk assessment that recognizes the importance of reducing patients' cumulative inflammatory burden by targeting overweight and obesity, in individuals with periodontal disease, may be a valuable risk assessment parameter in caring for dental patients. BACKGROUND: The growing body of evidence that suggests obesity, Metabolic Syndrome and periodontal disease are interrelated offers an unprecedented opportunity to adopt a new model of risk assessment that has the potential to beneficially influence not only the periodontal health of obese and overweight patients, but simultaneously may also reduce a person's overall risk for developing heart disease and type 2 diabetes, and perhaps other inflammatory driven disease states. METHODS: This paper presents an overview of research that builds the case for a new model of risk assessment that focuses on the cumulative inflammatory burden that may be elevated by the presence of periodontal disease in obese patients. In addition, the biological plausibility of the concepts of inflammatory priming and inflammatory loading is discussed, and several simple ideas are suggested for identifying at-risk patients. CONCLUSIONS: Given the significant rise in obesity and the impact that obesity has on periodontal health and other inflammatory driven, systemic disease states, adoption of a new model of risk assessment is suggested-one that considers an individual's cumulative inflammatory burden which may be amplified as a result of coexisting obesity and other components of Metabolic Syndrome and periodontal disease. Knowledge gathered thus far combined with further clinical research must be translated into better ways to treat and maintain obese periodontal patients. These measures may pave the way for prevention of metabolic diseases and obesity with a relevant impact on patients' periodontal status.

Evaluation of the Elecsys® anti-Müllerian hormone assay for the prediction of hyper-response to controlled ovarian stimulation with a gonadotrophin-releasing hormone antagonist protocol.

OBJECTIVE: This non-interventional study aimed to validate a pre-specified anti-Müllerian hormone (AMH) cut-off of 15 pmol/L (2.10 ng/mL) for the prediction of hyper-response to controlled ovarian stimulation (COS) using the fully automated Elecsys® AMH immunoassay. STUDY DESIGN: One hundred and forty-nine women aged <44 years with regular menstrual cycles underwent COS with 150 IU/day follicle-stimulating hormone in a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Response to COS (poor vs normal vs hyper-response) was defined by number of oocytes retrieved and occurrence of ovarian hyper-stimulation syndrome (OHSS). RESULTS: Significant differences were seen between response classes for the number of follicles prior to follicle puncture (p < 0.001), the number of retrieved oocytes (p < 0.001) and the occurrence of OHSS (p < 0.001), which were all highest in hyper-responders. The area under the receiver operating characteristic curve for AMH to predict hyper-response was 82.1% (95% confidence interval [CI]: 72.5-91.7). When applying the AMH cut-off of 15.0 pmol/L, a sensitivity of 81.3% (95%CI: 54.4-96.0) to predict hyper-response and a specificity of 64.7% (95%CI: 55.9-72.8) to identify poor/normal responders was reached. CONCLUSION: The Elecsys® AMH assay can reliably predict hyper-response to COS in women undergoing a GnRH antagonist treatment protocol.

The effect of premature luteinizing hormone increases among high ovarian responders undergoing a gonadotropin-releasing hormone antagonist ovarian stimulation protocol.

OBJECTIVE: To explore factors causing a premature rise in luteinizing hormone among high ovarian responders undergoing the gonadotropin-releasing hormone (GnRH) antagonist ovarian stimulation protocol. METHODS: The present retrospective study included healthy women undergoing fresh cycles using a fixed GnRH antagonist protocol with a predicted high response and antral follicle count (AFC) of at least 15 at the Reproductive Medicine Center of Tongji Hospital, China, between January 1 and December 31, 2016. Treatment-related characteristics, hormone changes, and pregnancy outcomes were compared between patients who did or did not experience a premature luteinizing hormone rise. RESULTS: There were 314 patients included; 49 experienced premature luteinizing hormone increases. Among patients who experienced a premature rise in luteinizing hormone, a lower two pronuclear embryo rate (P=0.038); fewer high-quality embryos (P=0.020); higher serum luteinizing hormone (P=0.006), progesterone (P=0.013), and estradiol (E2) levels (P=0.003) on the day of human chorionic gonadotropin administration; a lower clinical pregnancy rate (P=0.031); and a higher cancellation rate (P=0.006) were observed. AFC of at least 22 (P=0.001) and E2 of 669 pg/mL or higher at the start of GnRH antagonist administration were predictive of early (P=0.036) and late (P=0.033) premature luteinizing hormone increases. CONCLUSION: Earlier administration of GnRH antagonist could avoid premature luteinizing hormone increases among high ovarian responders, especially those with a starting AFC of 22 or more.

Serum AMH Level to Predict the Hyper Response in Women with PCOS and Non-PCOS Undergoing Controlled Ovarian Stimulation in ART.

BACKGROUND: It is essential to determine the cut-off value of serum anti-Mullerian hormone (AMH) to predict the hyper response in assisted reproductive technology (ART). There are few studies mentioning the cut-off value for the hyper response in infertile women but not specifically for polycystic ovary syndrome (PCOS) and non-PCOS groups. With this in background, this study was conducted. AIM: To determine the cut-off value of serum AMH to predict the hyper response in women with PCOS and non-PCOS undergoing a controlled ovarian stimulation (COS) in ART. OBJECTIVE: To compare the outcome of stimulation in PCOS and non-PCOS groups. MATERIALS AND METHODS: All 246 women enrolled for Intra Cytoplasmic Sperm Injection (ICSI) fulfilling the selection criteria were recruited. On the day 3 of the cycle, the serum AMH, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol and antral follicle count (AFC) were measured. They underwent COS as per the unit protocol. They were divided into PCOS and non-PCOS groups as per the Rotterdam's criteria. The mean age, duration of infertility, Body Mass Index (BMI), Ovarian reserve markers and outcome of stimulation were compared. Using the Statistical Package for the Social Sciences version 16.0 software, the significant difference was measured by multivariate analysis, as well as a one-way analysis of variance with Tukey's post-hoc test was used. RESULTS: Among 246 women, 31.3% were in PCOS group, and 68.7% were in non-PCOS group. Comparison of PCOS and non-PCOS groups showed a significant difference in the age with the mean age being 29.2 and 31.5 years, respectively. The mean AMH and AFC were 2-fold higher in PCOS group. The mean number of follicles, oocytes retrieved, MII and oocytes fertilised were significantly higher in PCOS group. The pregnancy rate was 52.6% in PCOS and 30.9% in non-PCOS group. In the PCOS group, 22.1% had ovarian hyper stimulation syndrome (OHSS), and only 4.7% had OHSS in non-PCOS group (P = 0.0005). Receiving Operator Curve (ROC) curve was plotted to predict the hyper response, which showed a cut-off value of 6.85 ng/ml with a sensitivity of 66.7% and a specificity of 68.7% for PCOS group and 4.85 ng/ml with a sensitivity of 85.7% and a specificity of 89.7% in non-PCOS group. CONCLUSION: The cut-off value of serum AMH to predict the hyper response in PCOS group is 6.85 ng/ml and in non-PCOS group is 4.85 ng/ml.

Comportamiento del asma bronquial en un área de salud del policlínico Cerro / Behavior of bronchial asthma in a health area of the Cerro polyclinic

Introducción: el asma bronquial es la enfermedad crónica más frecuente en pediatría y una de las principales causas de consulta. Objetivo: describir el comportamiento del asma bronquial como problema de salud. Métodos: trabajo descriptivo, prospectivo, de corte longitudinal, en 309 niños con edades comprendidas entre 0 y 19 años con el diagnóstico de asma bronquial, atendidos en los 15 consultorios médicos del grupo básico de trabajo A del policlínico universitario Cerro, en el período comprendido entre el 1º de enero de 2007 y el 31 de diciembre de 2007. Método empírico para la obtención de los datos clínicos epidemiológicos, y como técnica, la encuesta a través de un cuestionario. Resultados: 148 pacientes (48 por ciento) se encontraban entre 10 y 14 años, 175 (56,6 por ciento) del sexo masculino, 136 (44 por ciento) fueron clasificados como persistentes ligeros, 140 (58 por ciento) presentaron rinitis y 57 (24 por ciento) dermatitis. Había fumadores en las viviendas de 303 pacientes (98 por ciento), hacinamiento en 290 casos (94 por ciento) y el polvo en el hogar 284 (92 por ciento). Conclusiones: predominio en el grupo de edades de 10 a 14 años, sexo masculino. En cuanto a la severidad de la enfermedad predominó la forma persistente ligera, las manifestaciones atópicas más frecuentes fueron la rinitis y la dermatitis, los principales factores de riesgo fueron el humo del tabaco, el polvo en el hogar y el hacinamiento, y el tratamiento de elección fue el de la crisis. Se observó la falta de organización y unidad de criterios para el enfoque integral de la política intercrisis o de sostén en la atención de los pacientes

Introduction: bronchial asthma is the more frequent chronic disease in Pediatrics and one of the major causes of consultation. Objective: to describe the behavior of bronchial asthma as a health problem. Methods: a longitudinal, prospective and descriptive study was conducted in 309 children aged between 0 and 19 diagnosed with bronchial asthmas seen in the 15 medical consulting rooms of A basic work group of Cerro University polyclinic from January 1, 2007 to December, 31, 2007. An empirical method was used to obtain the epidemiologic clinical data, and as technique, survey using a questionnaire. Results: one hundred and forty eight patients (48 percent) were aged 10 and 14, 175 (56,6 percent) of male sex, 136 (44 percent) were classified as slight persistent, 140 (58 percent) had rhinitis and 57 (24 percent) had dermatitis. There were smoker relatives at home of 203 patients (98 percent), overcrowding in 290 cases (94 percent) and a high level of dust at home of 284 patients (92 percent). Conclusions: there was male sex predominance in the 10-14 age groups. As regards disease severity the slight persistent way was more prevalent, the more frequent atopic manifestations were rhinitis and dermatitis, the major risk factors were cigarette smoke, dust at home and overcrowding, the choice treatment was that of crisis. There was a lack or organization and unity of criteria for an integral approach of the inter-crisis politic or of support in patients care