Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
Department of Obstetrics and Gynaecology, Princess Anne Hospital, Room F86, Level F, Coxford Road, Southampton SO16 5YA, UK.
Hum Reprod Update. 2018 Jan 1;24(1):15-34. doi: 10.1093/humupd/dmx028.
Despite advances in ART, implantation and pregnancy rates per embryo transfer still remain low. IVF laboratories strive to ensure that the process of handling gametes in vitro closely mimics the in vivo environment. However, there remains a lack of knowledge regarding the in vivo regulation and dynamic variation in biophysical parameters such as oxygen concentration, pH and temperature within the reproductive tract.
To undertake a systematic review of the current understanding of the physico-chemical parameters of oxygen tension (pO2), pH and temperature within the female reproductive tract, and their potential implications in clinical and pathological processes related to fertility and those pertaining to limited reproductive capacity.
A comprehensive literature search was performed using electronic databases including Medline, Embase, Cochrane Library and Pubmed to identify original and review articles addressing the biophysical parameters (pO2, pH and temperature) in the female reproductive tract of any species. The search included all studies published between 1946 and November 2015. Search terms included 'oxygen', 'pH', 'hydrogen ion concentration', 'acid base' and others terms. We also used special features and truncations to identify synonyms and broaden the search. Studies were excluded if they only assessed embryo culture conditions, fetal acid-base status, oxidative stress, outcomes of pregnancy and measurements of these parameters in non-reproductive organs.
Our search generated 18 685 records and 60 articles were included. pO2 within the female reproductive tract shows cyclical variation and minute-to-minute oscillations, which may be influenced by uterine contractility, hormones, the autonomic system, cardiac pulsatility, and myometrial and smooth muscle integrity. Fine balanced control of pO2 and avoidance of overwhelming oxidative stress is crucial for embryogenesis and implantation. The pH in the female reproductive tract is graduated, with lowest pH in the vagina (pH 4.42) increasing toward the Fallopian tubes (FTs) (pH 7.94), reflecting variation in the site-specific microbiome and acid-base buffering at the tissue/cellular level. The temperature variation in humans is cyclical by day and month. In humans, it is biphasic, increasing in the luteal phase; with the caudal region of the oviduct 1-2 degrees cooler than the cranial portion. Temperature variation is influenced by hormones, density of pelvic/uterine vascular beds and effectiveness of heat exchange locally, crucial for sperm motility and embryo development. We have identified significant deficiencies and inconsistencies in the methods used to assess these biophysical factors within the reproductive tract. We have suggested that the technological solutions including the development of methods and models for real time, in vivo recordings of biophysical parameters.
The notion of 'back to nature' in assisted conception suggested 20 years ago has yet to be translated into clinical practice. While the findings from this systematic review do not provide evidence to change current in vitro protocols, it highlights our current inability to assess the in vivo reproductive tract environment in real time. Data made available through future development of sensing technology in utero may help to provide new insights into how best to optimize the in vitro embryo environment and allow for more precise and personalized fertility treatment.
尽管辅助生殖技术（ART）不断发展，胚胎移植的着床率和妊娠率仍然很低。体外受精实验室努力确保体外处理配子的过程尽可能模拟体内环境。然而，人们对生殖管道内氧浓度、pH 值和温度等生物物理参数的体内调节和动态变化知之甚少。
对女性生殖管道内氧张力（pO2）、pH 值和温度等理化参数的现有认识进行系统综述，并探讨其在与生育力相关的临床和病理过程以及与有限生育力相关的过程中的潜在意义。
使用电子数据库（包括 Medline、Embase、Cochrane 图书馆和 Pubmed）全面检索文献，以确定涉及任何物种女性生殖管道内生物物理参数（pO2、pH 值和温度）的原始和综述文章。检索包括 1946 年至 2015 年 11 月发表的所有研究。检索词包括“氧”、“pH 值”、“氢离子浓度”、“酸碱”等。我们还使用了特殊功能和截断来识别同义词并扩大检索范围。如果研究仅评估胚胎培养条件、胎儿酸碱状态、氧化应激、妊娠结局以及这些参数在非生殖器官中的测量，则将其排除在外。
我们的检索生成了 18685 条记录，纳入了 60 篇文章。女性生殖管道内的 pO2 呈周期性变化和分钟级波动，可能受子宫收缩性、激素、自主神经系统、心脏搏动、子宫和平滑肌完整性的影响。pO2 的精细平衡控制和避免过度氧化应激对胚胎发生和着床至关重要。女性生殖管道内的 pH 值呈梯度变化，阴道内 pH 值最低（pH4.42），向输卵管（FTs）方向增加（pH7.94），反映了特定部位微生物组和组织/细胞水平酸碱缓冲的变化。人类的温度变化呈周期性，按日和月变化。在人类中，它呈双相性，在黄体期增加；输卵管尾部比头部低 1-2 度。温度变化受激素、盆腔/子宫血管床密度和局部热交换效率的影响，这对精子活力和胚胎发育至关重要。我们已经确定了在生殖管道内评估这些生物物理因素的方法中存在的显著缺陷和不一致性。我们建议采用包括开发实时、体内记录生物物理参数的方法和模型在内的技术解决方案。
20 年前提出的辅助受孕“回归自然”的理念尚未转化为临床实践。尽管这项系统综述的结果并没有提供改变当前体外方案的证据，但它突出了我们目前无法实时评估体内生殖管道环境的能力。未来通过胎儿感应技术的发展提供的数据可能有助于深入了解如何优化体外胚胎环境，并实现更精确和个性化的生育治疗。
