RESUMO
The impact of gonadotropin-releasing hormone (GnRH) agonist long compared with GnRH antagonist protocols, under in vitro fertilization conditions on endometrial receptivity, is still debated. Therefore, we compared the effect of both GnRH antagonist and agonist long protocols on the endometrial receptivity by analyzing, to our knowledge for the first time, the global gene expression profile shift during the prereceptive and receptive stages of stimulated cycles under the two GnRH analogue protocols compared with natural cycles in the same patients. For the same normal-responder patients, endometrial biopsies were collected on the day of oocyte retrieval and on the day of embryo transfer after human chorionic gonadotropin administration of a stimulated cycle with either GnRH agonist long or GnRH antagonist protocols and compared with the prereceptive and receptive stages of a natural cycle. Samples were analyzed using DNA microarrays. Gene expression profiles and biological pathways involved during the prereceptive stage to the receptive endometrial transition of stimulated and natural cycles were analyzed and compared for each patient. Both protocols affect endometrial receptivity in comparison with their natural cycle in the same patients. Major differences in endometrial chemokines and growth factors under stimulated cycles in comparison with natural cycles were observed. Such an effect has been associated with gene expression alterations of endometrial receptivity. However, the endometrial receptivity under the GnRH antagonist protocol was more similar to the natural cycle receptivity than that under the GnRH agonist protocol.
Assuntos
Endométrio/fisiopatologia , Fertilização in vitro , Indução da Ovulação/efeitos adversos , Biomarcadores/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Gonadotropina Coriônica/administração & dosagem , Protocolos Clínicos/normas , Implantação do Embrião/efeitos dos fármacos , Implantação do Embrião/genética , Implantação do Embrião/fisiologia , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Feminino , Fertilização in vitro/efeitos adversos , Fertilização in vitro/métodos , Perfilação da Expressão Gênica , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/administração & dosagem , Humanos , Infertilidade/fisiopatologia , Infertilidade/terapia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Modelos Biológicos , Análise de Sequência com Séries de Oligonucleotídeos , Indução da Ovulação/métodosRESUMO
SUMMARY: We investigated 10 mother-newborn pairs and found a 90% rate of dengue virus (DENV) transmission during the perinatal period. Here, we describe DENV kinetics in the sera of newborns before the onset of disease. Of the breast-milk samples analyzed, 75% tested positive for DENV. BACKGROUND: Dengue is the most common mosquito-borne viral disease in humans. With this study, we aimed to investigate the risk of vertical (DENV) transmission during the peripartum period and to describe its viral kinetics in serum and breast milk. METHODS: We carried out a prospective study during the 2012-2013 dengue epidemic in New Caledonia, its most severe on record. All mothers hospitalized at the Centre Hospitalier Territorial in Nouméa, New Caledonia, with symptoms of dengue infection between 7 days before and 2 days after delivery and/or whose infant was infected during breastfeeding were investigated. DENV was detected and quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in sera and breast milk (mothers), sera and gastric fluid (newborns), cord blood, and placentas. DENV kinetics and sequences in sera and breast milk were studied. Clinical presentation and biological evolution in mother-newborn pairs were analyzed. RESULTS: Ten mother-newborn pairs were investigated over an 11-month period. One premature birth, 3 hemorrhagic complications, and 1 maternal death occurred. Nine newborns were infected and symptomatic. One case of deep thrombocytopenia and 1 case of anoxic encephalopathy occurred. DENV was detected in breast milk samples from 9 (75%) of 12 infected breastfeeding mothers. Original DENV kinetics in sera and breast milk were described. CONCLUSIONS: The occurrence of vertical DENV transmission was high (90%) in viremic mothers at delivery, and these mothers and their infants were at major risk for obstetric and neonatal complications. The modes of viral transmission are difficult to clarify. The risk of DENV transmission through breast milk seems plausible. Close follow-up of mothers and prolonged surveillance of their newborns are required for minimizing complications. Complementary studies are needed to elaborate preventive recommendations.