by Dr. Sarah DiMunno, ND
In media today, inflammation is depicted as having a negative influence on health but for good reason. Inflammation is related to many disease processes especially those involved in auto-immune conditions such as Crohn’s disease, arthritis, & asthma (1). It is easy to forget that the inflammatory response as part of the immune system is itself an adaptive process to aid in healing. The inflammatory response involves a sequence of reactions including cytokines, neutrophils, adhesion molecules, etc. inducing remodeling of the affected tissue (1). It has been suggested that the role of inflammation in embryo implantation is necessary and increases the chances of successful conception.
Implantation occurs as a micro-trauma as the outer layer of the embryo burrows into the endometrium (1). A successful implantation can only occur when the uterus is receptive during the window of implantation (WOI), also known as the mid-secretory phase of the menstrual cycle (days 19-23). A number of chemical and cellular changes occur to the endometrium at this time such as expression of immune cells and development of microvilli to aid in attachment further suggesting the importance of an inflammatory role (2).
Science has been able to overcome many reproductive disorders through the development of in vitro fertilization, however implantation has remained the rate-limiting step for success with over half of human implantations failing (2). One study investigated the role of mechanical injury of the endometrium in improving uterine receptivity. It was discovered that when endometrial biopsies were performed during either the preceding or present IVF cycle, rates of implantation, clinical pregnancies, and live births improved (2).
Non-steroidal Anti-inflammatory Drugs (NSAIDs)
NSAIDs are one of the most commonly used drugs in the world developed with the sole purpose of supressing the inflammatory process. The risk of NSAID consumption on human reproduction has not been thoroughly investigated. However, it has been demonstrated that the use of indomethacin (anti-inflammatory) at or around the time of implantation either partially or completely prevents implantation in rats, mice, hamsters, and rabbits (3). The authors suggest that this is due to indomethacin’s affect on decreasing inflammatory prostaglandins normally released at the site of implantation (3). It has also been found that the anti-inflammatory diclofenac when injected one-hour pre-transfer, implantation and placentation is significantly inhibited (4).
These repercussions can also be seen later on in gestational outcomes. A Cohort study investigated the use of prenatal NSAID use in women around conception/during pregnancy and miscarriage rates. In this study, prenatal NSAID usage was associated with an 80% increased risk of miscarriage (5). The association was even stronger when the NSAIDs were taken around time of conception or taken for more than 1 week (5). The study provides evidence to support the positive role of inflammation on conception and highlights the need for more investigation in this matter.
Natural Anti-Inflammatories (AIs)
Many natural prescriptions act in a similar manner as pharmaceutical AIs and work to decrease inflammation in the body. Herbs such as turmeric and ginger are known for their AI properties and have been shown to act just as strongly as pharmaceuticals. For example, one study compared the use of curcuma extract and ibuprofen for the treatment of knee OA and found no difference in the efficacy and safety of treatment (6). If these herbal prescriptions have similar effects on the body as NSAIDs, should we be concerned about their usage and negative influence on implantation rates as well?
Chen and Chan conducted a study to investigate this question. The authors treated mice with 20 μ M curcumin during in vitro maturation and found the implantation ratio of embryos were significantly lower (30%) than that observed in the control group not given curcumin at all (7). In fact, oocytes given curcumin during maturation led to increased resorption after implantation and decreased fetal weight (7). In addition, an alternate study completed a review on omega 3 supplementation and inflammation in the placenta (8). The authors of this study found that levels of maternal pro-inflammatory mediators decrease with usage of omega 3, further suggesting natural AIs may also negatively impact implantation success.
It is evident that there is a pro-inflammatory role necessary for the implantation process. As seen above many NSAIDs are found detrimental when assessing implantation success and cessation of their usage should be considered. One hypothesize suggests that the variability of impact of AIs on implantation is due to the targeting of alternative inflammatory pathways. Thus, further investigation is necessary regarding specific pharmaceuticals and their mechanism of action. This is also true for natural AIs. However, based on the review above and until more research is conducted investigating the influence of natural AIs on implantation, their usage should be limited or stopped during the window of implantation (cycle days 19-23).
It is important to differentiate between the pro-inflammatory cascade that occurs during implantation and the inflammation that occurs as a part of a disease process. The recommendations above do not include the treatment of auto-immune conditions or inflammation caused by unhealthy lifestyle.