# Temperature Dynamics in Early Pregnancy: Implications for Improving In Vitro Fertilization Outcomes
## 1 Introduction  
In assisted reproductive technology (ART), in vitro fertilization (IVF) involves cultivating embryos in an artificial environment outside the body (in vitro) for approximately five days before implantation into the mother's womb. Embryos developed in vitro are generally considered to be of lower quality than those developed in the natural environment of the fallopian tube (in vivo). Although IVF represents a significant advancement in infertility treatment, the pregnancy rate following a single fresh embryo transfer remains relatively low, at 21.7% in Japan in 2021 [1]. This low rate may be attributed, at least in part, to the lower quality of embryos resulting from in vitro culture [2]. While it is challenging to determine the exact quality differences between in vivo and in vitro-developed human embryos, a study on mouse embryos reported a 53% reduction in blastocyst cell numbers with in vitro culture [3]. Consequently, one of the most significant challenges in ART is developing new culture methods to improve embryo quality. The fundamental approach to improving even today's highly optimized culture methods is to replicate the internal environment of the body as closely as possible [4]. Consequently, it is recommended to use a culture medium similar to oviductal fluid and to incubate the embryos under hypoxia at a temperature of 37 \({}^{\circ}\)C, which is believed to bethe deep-body temperature [2]. Particularly important here is that in embryo culture, any environmental change is considered a stressor, resulting in accumulating embryo damage. Therefore, minimizing the number of times the incubator door is opened and closed and rapidly performing ART procedures outside the incubator is paramount. This is because incubator-based in vitro culture systems are fundamentally designed to minimize temperature fluctuations, with the actual fluctuation range typically maintained within \(\pm\)0.1 \({}^{\circ}\)C. However, opening the door for 10 s results in a temperature drop of approximately 5 \({}^{\circ}\)C in air-jacketed systems and 0.7 \({}^{\circ}\)C in water-jacketed systems, with recovery times of 3 min and 30 min, respectively [5]. In contrast, the natural environment for embryonic development in the fallopian tube is subject to fluctuations, which is an essential distinction from in vitro culture and is typically considered a phenomenon to be avoided, even in the most optimized culture methods. Nevertheless, it is remarkable that the dynamic physiology of the fallopian tube creates an optimal and potentially stress-free environment for embryos. It is widely recognized that a temperature gradient is present within the fallopian tubes [6; 7]. Additionally, the core body temperature (CBT) fluctuates over time [8; 9; 10]. Therefore, it has been postulated that temperature fluctuations during transport through the fallopian tubes promote oocyte development [6; 7; 11; 12]. [PERSON] et al. conducted experiments with human embryos in which the culture temperature was varied in 24 h cycles to mimic the circadian rhythm and concluded that this approach did not improve embryo quality [12]. [PERSON] et al. examined how culture temperature fluctuations (37/35.5 \({}^{\circ}\)C cycled over 24 h at 12 h intervals in the low-temperature group and 38.5/37 \({}^{\circ}\)C in the high-temperature group) influenced mouse embryo development [11]. The authors concluded that mouse embryo development in the lower-temperature group was consistently negatively affected, but not in the higher-temperature group. The results of these studies seem to indicate that a constant 37 \({}^{\circ}\)C static culture environment is optimal. However, a closer examination of the data revealed that the percentage of blastocysts rated morphologically good in the control group was 14.5%, whereas the percentage was lower in the low-temperature variation (1.9%) but highest in the high-temperature variation (26.4%).