In vivo human uterine temperature, pH, and uterine fluid composition analysis

Abstract

Study questionWhat are the temperature, pH and uterine fluid composition in the human uterus three days following a positive LH test or ovum pick-up? Summary answerThe mean uterine temperature was 36.94{+/-}0.26{degrees}C, the mean uterine pH was 6.76{+/-}0.22, and the concentrations of 37 components in aspirated uterine fluid were successfully determined. What is known alreadyEmbryo culture conditions in the laboratory impact key outcomes of IVF/ICSI treatments, such as the quality of the embryos and the live birth rate after treatment, and child outcomes, such as birth weight. Currently used conditions, including temperature, pH, and culture medium composition, are largely derived from clinical experience and experimental studies using animal models. Limited studies have been performed to determine the natural human preimplantation embryo environment in vivo during the physiologically relevant time of the menstrual cycle. This type of fundamental knowledge is required for evidence-based optimization of the in vitro embryo culture environment and improving IVF/ICSI outcomes. Study design, size, durationIn this cross-sectional study, conducted between April 2015 and March 2016, temperature and pH were measured in the human uterine cavity on the third day following a positive LH test or ovum pick-up, and uterine fluid was simultaneously aspirated for composition analysis. Uterine temperature was measured in fifty eight women, uterine pH was determined in fifty three women, and twenty two samples of aspirated uterine fluid were analysed for the concentrations of thirty-seven components. Participants/materials, setting, methodsThis study involved 61 healthy reproductive-aged women: 53 without ovarian stimulation and 8 who underwent ovarian stimulation. We measured uterine temperature using a probe inserted into the uterine cavity directly, and uterine pH after inserting a probe through the outer sheath of an IVF catheter. Uterine fluid was then aspirated using this outer IVF catheter and a 10 ml syringe, and subsequently analysed with a Cobas 8000 chemistry analyser and ultra-performance liquid chromatography-tandem mass spectrometry. Main results and the role of chanceThe mean uterine temperature on the third day following a positive LH test or ovum pick-up was 36.94 {+/-} 0.26{degrees}C and correlated with the womens core body temperature. The mean pH in the uterine cavity was pH 6.76 {+/-} 0.22, clearly lower than the standard pH used for human preimplantation embryo culture in vitro (pH 7.3 {+/-} 0.1). Concentrations of important energy sources were 0.8 {+/-} 0.02 mM pyruvate, 5.1 {+/-} 1.78 mM glucose and 6.60 {+/-} 1.12 mM lactate. Glutamic acid (1162 {+/-} 183 M), glycine (955 {+/-} 156 M) and alanine (513 {+/-} 82 M) were the most abundant amino acids in uterine fluid. Limitations, reasons for cautionIn absence of a preimplantation embryo, synergistic influences on the uterine environment may be overlooked. Single centre and specific population limitations may hinder broader generalization of the results. Uterine fluid likely contains additional components. Wider implications of the findingsThe in vivo uterine characteristics identified in this study are foundational to develop an in vivo evidence-based culture medium for human embryos. Further research is necessary to evaluate whether such a medium can improve human preimplantation embryo development and quality, thereby increasing cumulative live birth rates and improving child outcomes.