Strategies for improving outcome of assisted reproduction in women with polycystic ovary syndrome: systematic review and meta-analysis.

OBJECTIVES: To identify, appraise and summarize the current evidence regarding the efficacy of strategies aimed at improving assisted reproductive techniques in women with polycystic ovary syndrome (PCOS). METHODS: A comprehensive literature search of the standard medical databases was performed. The last electronic search was run in July 2015. The primary outcome measures were live birth/ongoing pregnancy and ovarian hyperstimulation syndrome (OHSS). The secondary outcome measures were clinical pregnancy and miscarriage. RESULTS: We screened 1021 records and completely assessed 173, finally including 66 studies in the quantitative analysis. Many different interventions were assessed, however the overall quality of the studies was low. We observed moderate-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (relative risk (RR), 0.95 (95% CI, 0.84-1.08)), or clinical pregnancy (RR, 1.02 (95% CI, 0.91-1.15)) when comparing antagonist and agonist protocols for ovarian stimulation. Additionally, we found low-quality evidence that metformin improves live birth/ongoing pregnancy (RR, 1.28 (95% CI, 1.01-1.63)) and clinical pregnancy rates (RR, 1.26 (95% CI, 1.04-1.53)) when compared with placebo or no intervention. We further found low-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (RR, 1.03 (95% CI, 0.80-1.34)) and clinical pregnancy rates (RR, 0.99 (95% CI, 0.81-1.22)) when comparing human menopausal gonadotropin for inducing ovulation and artificial preparation with estradiol valerate for endometrial preparation for frozen embryo transfer (FET). Low-quality evidence suggests that mannitol compared with no intervention (RR, 0.54 (95% CI, 0.39-0.77)) and antagonist protocols compared with agonist protocols (RR, 0.63 (95% CI, 0.49-0.80)) reduce rates of OHSS. CONCLUSION: There is low- to moderate-quality evidence suggesting that antagonist protocols are preferable to agonist ones, because they reduce the incidence of OHSS without interfering with clinical pregnancy and live birth for women with PCOS. Additionally there is low-quality evidence pointing to a benefit of metformin supplementation on clinical pregnancy and live birth; and that ovulation induction and administration of estradiol seem to be equally effective for endometrial preparation before FET for women with PCOS. For all other interventions, the evidence is of very low quality, not allowing any meaningful conclusions to be drawn. Estrategias para mejorar el resultado de la reproducción asistida en mujeres con síndrome de ovario poliquístico: revisión sistemática y metaanálisis RESUMEN OBJETIVOS: Identificar, evaluar y resumir la evidencia actual sobre la eficacia de las estrategias para mejorar las técnicas de reproducción asistida en mujeres con síndrome de ovario poliquístico (SOP). MÉTODOS: Se realizó una búsqueda exhaustiva de literatura en las bases de datos médicas estándar. La última búsqueda electrónica se realizó en julio de 2015. Las medidas de resultado primarias fueron los nacimientos vivos/embarazos en curso y el síndrome de hiperestimulación ovárica (SHO). Las medidas de resultado secundarias fueron el embarazo confirmado ecográficamente y el aborto. RESULTADOS: Se cribaron 1021 registros, de los que se evaluaron por completo 173, para finalmente incluir 66 estudios en el análisis cuantitativo. Aunque se evaluaron muchas intervenciones diferentes, en general la calidad de los estudios fue baja. Se observó evidencia de calidad moderada de que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (riesgo relativo (RR): 0,95 (IC 95%, 0,84-1,08)), o de embarazos confirmados ecográficamente (RR: 1,02 (IC 95%, 0,91-1,15)), cuando se comparan los protocolos de antagonistas y agonistas para la estimulación ovárica. Además, se encontró evidencia de baja calidad en que la metformina mejora las tasas de nacimientos vivos/embarazos en curso (RR: 1,28 (IC 95%, 1,01-1,63)) y de embarazos confirmados ecográficamente (RR: 1,26 (IC 95%, 1,04-1,53)) en comparación con un placebo o la no intervención. Se encontró también evidencia de baja calidad en que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (RR: 1,03 (IC 95%, 0,80-1,34)) y las tasas de embarazos confirmados ecográficamente (RR: 0,99 (IC 95%, 0.81-1,22)) al comparar la gonadotropina menopáusica humana para la inducción de la ovulación y la preparación artificial con el valerato de estradiol para preparar el endometrio para la transferencia de embriones congelados (TEC). La baja calidad de la evidencia sugiere que el manitol, en comparación con la no intervención (RR: 0,54 (IC 95%, 0,39-0,77)), y los protocolos de antagonistas, en comparación con los protocolos de agonistas (RR: 0,63 (IC 95%, 0,49-0,80)), reducen las tasas de SHO. CONCLUSIÓN: Hay evidencia de calidad baja a moderada que sugiere que los protocolos de antagonistas son preferibles a los de agonistas, ya que reducen la tasa de SHO sin interferir con el embarazo confirmado ecográficamente y los nacimientos vivos en las mujeres con SOP. Además, existe evidencia de baja calidad que indica un beneficio del uso de metformina como aporte suplementario en embarazos confirmados ecográficamente y en nacimientos vivos; y que la inducción de la ovulación y la administración de estradiol parecen ser igualmente eficaces para la preparación del endometrio antes de la TEC en mujeres con SOP. Para el resto de procedimientos, la evidencia es de muy baja calidad, y por ello no permite extraer conclusiones importantes.

Ovarian response is a better predictor of clinical pregnancy rate following embryo transfer than is thin endometrium or presence of an endometrioma.

OBJECTIVES: To examine whether endometrial thickness and the presence of endometrioma are independent predictors of clinical pregnancy rate or simply associated with poor ovarian response (POR). METHODS: This was a retrospective cohort study assessing the first cycle of all women undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in a university hospital in Brazil between January 2011 and December 2012. Only the first cycle of each woman within the study period was considered. Women over 40 years of age and those who used clomiphene citrate during controlled ovarian stimulation (COS) or did not undergo embryo transfer were excluded from analysis. POR was defined as ≤ three oocytes retrieved and a thin endometrium was defined as endometrial thickness ≤ 7.0 mm on the day of human chorionic gonadotropin (hCG) administration. We performed a multiple regression analysis to identify which of the following parameters were independent predictors of clinical pregnancy: age, number of oocytes retrieved, endometrial thickness or the presence of endometrioma. RESULTS: Within the study period, 787 women began COS, but 270 were excluded from analysis. Among the 517 women analyzed, those who achieved pregnancy were younger and yielded more oocytes. The proportion of POR was higher in women with a thin endometrium (17/57 (29.8%) vs 80/460 (17.4%); P = 0.03) and in women with endometrioma (15/39 (38.5%) vs 82/478 (17.2%); P = 0.002). The results of regression analysis showed that only age and the number of oocytes retrieved were independent predictors of pregnancy. Additionally, we observed higher clinical pregnancy rates in women with a thin endometrium from whom ≥ seven oocytes were retrieved (11/25 (44.0%)) compared to women with normal endometrial thickness (99/241 (41.1%)). Considering only women from whom ≥ four oocytes were retrieved, we observed reasonable pregnancy rates in those with a thin endometrium (14/40 (35.0%)) and in those with endometrioma (9/24 (37.5%)). CONCLUSION: Both a thin endometrium and the presence of endometrioma are associated with POR but are not important independent predictors of clinical pregnancy. Good pregnancy rates can be observed when these conditions are present in women with a good ovarian response.

Antigenic cross-reactivity among the venoms from several species of Brazilian scorpions

The venoms of seven species of scorpions living in different regions of Brazil were analysed with regard to their lethality, antigenic cross-reactivity and ability to induce antibody production. In mice, the tested scorpion venoms can be grouped as: (a) highly toxic: Tityus stigmurus Thorell (), Tityus bahiensis (Perty) , Tityus serrulatus Lutz and Mello (, and Tityus costatus (Karsch) ; (b) moderately toxic: Tityus cambridgei Pocock ; and (c) practically nontoxic: Rhopalurus agamemnon (Koch) , and Brotheas amazonicus Lourenço . On electrophoresis the venoms showed many protein bands displayed along the chromatogram, most of them cross-reacting in immunoelectrophoresis and immunoblotting using horse anti-T. serrulatus, anti-T. bahiensis or anti-T. serrulatus + T. bahiensis sera as probes. The antibodies present in these antivenoms combine with venom components as measured in vitro by the ELISA assay, and neutralize their lethal effects in vivo. These results indicate that horse antivenoms against a mixture of T. serrulatus and T. bahiensis venoms or only against T. serrulatus venom yield an antibody population able to neutralize the toxic effects found in all venoms studied.