In vivo oxygen, temperature and pH dynamics in the female reproductive tract and their importance in human conception: a systematic review

Background: 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.

Objective and rationale: 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.

Search methods: 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.

Outcomes: 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.

Wider implications: 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.