Gut and vaginal microflora are probably not the first things you think about when working with a couple struggling to conceive a child, but perhaps they should be.
Jean-Jacques Dugoua, ND, a naturopathic physician from Toronto who specializes in fertility and hormonal balance, has found that presence or absence of particular strains of beneficial bacteria in the female digestive and reproductive tracts have a much greater influence on fertility than most clinicians realize.
Strategies aimed at balancing the GI and vaginal microbiome hold huge promise for optimizing fertility—both with and without in vitro fertilization (IVF) interventions—while simultaneously influencing the health of mother and child in a positive manner.
In order to understand how the microenvironment influences fertility, Dr. Dugoua believes it is essential to recognize the human body as a symbiotic organism, a system that is reliant upon the presence and proper activity of other species for optimal functioning.
The Symbiotic Human
Distinctly human cells are outnumbered 10 to 1 by microbial cells representing thousands of different strains of commensal bacteria. Flora in the GI tract are responsible for many essential metabolic and physiologic processes including: proper digestion of food, bioavailability of many types of vitamins, sleep cycle and immune system regulation, and primary defense against incoming pathogens.
Though research in this field is still in its infancy, there is an increasing body of evidence that suggests that bacterial populations play an important role in the perpetuation of our species.
Researchers exploring the potential of probiotic organisms to positively influence human fertility have looked at this issue from three main angles: improving IVF outcomes and fertility through management of pathogenic bacterial infections; use of probiotics to minimize pregnancy complications, reduce systemic inflammation and decrease pre-term births; and supporting the future health of the child and mother through optimal states of health during pregnancy.
Infections and Infertility
Infections within any organ system can be extremely detrimental to fertility and pregnancy; reproductive system infections are an obvious threat. Several studies have shown that Bacterial Vaginosis (BV) increases the risk of spontaneous preterm delivery of a low birth-weight infant, decreases the possibility of successful implantation through IVF, and greatly raises the risk of other adverse pregnancy outcomes and complications (Hillier et al, N Engl J Med 1995; 333:1737-1742, 1995).
A vaginal infection related to imbalances in vaginal pH, BV is characterized by a lack of Lactobacilli —a genus normally found in high numbers in the vaginal tract—and increased numbers of facultative or anaerobic organisms that decrease the normal acidity of the vagina.
Researchers at Ghent University in Belgium, reported that presence of BV is a strong and negative factor in overall fecundity. They point to the large percentage of IVF patients who test positive for BV (Verstraelen, H, Senok AC: Reprod. Biomed 2005 Dec;11(6):674-5).
The mechanism linking BV with preterm birth is unknown, though Dr. Dugoua hypothesizes that it relates to stimulation of the fetal adrenal system, a process normally activated only when gestation is complete. In response to an environmental stressor such as the presence of infection, it is possible that the fetal endocrine system initiates the birthing process in order to escape a potential threat. Dr. Dugoua acknowledged that this explanation is entirely hypothetical at this point, but it is plausible. He anticipates future research outlining the precise physiological correlation between infections and preterm delivery.
Along with BV, there are countless other infections that may potentially affect fertility and pregnancy, all of which are related to the presence or absence of beneficial bacterial populations.
Probiotic organisms in the gut produce lactic acid as well as their own endogenous antibiotic (called bacteriocin) which can counter pathogenic organisms (Isolauri et al, Am. J Clin Nutr. 2001 Feb;73(2 Suppl):444S-450S). They also act as a physical barrier to shield the GI mucosa from pathogens, literally 'taking up all the space' so that colonization is not possible.
Without adequate numbers of these bacterial populations, a woman's overall immune system is compromised, making her far more susceptible to viruses, parasites, and other invading pathogens that can be detrimental to fertility and pregnancy.
Previously thought to be entirely sterile, the follicular fluid surrounding the developing fetus can harbor pathogenic species of bacteria in large numbers of women undergoing IVF treatment. In an Australian study, women who tested positive for follicular bacteria had only a 25% IVF success rate, as compared to the standard accepted rate of 47-50%.
The bacterial presence was hypothesized at first to be a side effect of transvaginal oocyte retrieval (TVOR), the process by which eggs are retrieved for fertilization. This procedure allows for the possibility of cross-contamination between the vaginal tract and the follicular fluid. However, in a third of the women tested, the species of bacteria found were unlike anything present in the lower vaginal tract!
Further research is necessary in order to fully understand how these follicular bacterial infections arise, where the organisms originate, and how they affect the course of pregnancy. One can assume that the presence of infection so close to a developing fetus cannot be beneficial.
Inflammation & Infertility
Infertility correlates with increased systemic inflammation (as seen in patients with endometriosis and other gynecologic disease), as do pregnancy complications such as preeclampsia and preterm birth (Weiss et al, Reproductive Sciences 2009 16: 216-229). Several studies have shown that probiotic supplementation can attenuate inflammatory biomarkers. It is plausible to suppose that use of probiotics to down-regulate non-specific chronic inflammation could potentially enhance fertility.
Investigators in Helsinki found that serum hsCRP levels were significantly reduced in people given a milk-drink containing one of the following probiotic species: Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis, or Propionibacterium freudenreichii subsp. Shermanii.
It is interesting that Interleukin-2 (IL-2) was also significantly reduced through the consumptionKekkonen et al, World J Gastroenterol. 2008 Apr 7;14(13):2029-36.)of particular strains, suggesting that bacterial populations have a direct effect on systemic inflammatory cascades. (
Bifidobacterium lactis has been found to reduce TNF-α and systemic cytokines all of which are important biomarkers in inflammation expression and treatment. (Matsumoto, Benny, Biosci Biotechnol Biochem. 2006 Jun;70(6):1287-92.)
Probiotics may also have a role in the modification of placental trophoblast inflammation. This has clinical relevance in the context of preeclampsia. A recent cohort study of over 33,000 women in Norway found a significant correlation between consumption of probiotic dairy products and reduced likelihood of pregnancy complications such as a preeclampsia, increasing the potential for full-term births and reduced chance of birth defects and miscarriage.
There are many reasons to consider probiotics in the management of infertility, but Dr. Dugoua cautioned against simplistic approaches and exaggerated expectations. Probiotic supplementation does not always succeed in rectifying imbalances in commensal flora, and may not translate directly into improved fertility.
Research on this subject is fairly limited, and hardly conclusive. Investigators at Tel Aviv University looked at intravaginal supplementation with Lactobacillus species, and found that it had no effect on IVF outcomes in women with BV.
That said, if probiotics are used judiciously in the context of an overall lifestyle intervention aimed at improving a woman's total health status, they can sometimes make a difference. Dr. Dugoua said that in order to approach imbalances in the female reproductive system, one must look at the functioning of her whole body. Merely supplementing with species that seem to be lacking will not address the underlying causes for why those bacterial populations were diminished in the first place.
"Antibiotics, stress, poor eating habits—these throw our bacterial species out of balance", he affirms. Effective fertility treatment—with or without IVF---requires a whole-person approach. The state of the GI and vaginal flora is, in effect, a biomarker for the overall health of the whole body.
While probiotics are in no way a "cure" for infertility, Dr. Dugoua does have several recommendations for women attempting to get pregnant or maintain a pregnancy. He has found that supplementation with Lactobacillus rhamnosus GG, Bifidobacterium bifidum, Lactococcus lactis, and Bifido breve have been found to be beneficial in optimizing fertility and preventing complications of pregnancy. He recommends that women take the probiotics throughout pregnancy.
If BV infection is present, he prescribes probiotics to be administered vaginally as a suppository, as it appears that oral probiotic intake doesn't always lead to significant increases in the vaginal bacterial population. In all other cases, he suggests that patients take oral probiotics--preferably a blend of several recommended bacterial species.
Since probiotics are living organisms that interact with one another, and with the biological "environment" into which they're placed, probiotic supplementation is by nature an inexact science. Dr. Dugoua emphasized that, "You'll never really know how each species behaves in an individual until they try it." (read Strategies for Establishing a Healthy Gut Microbiome, by Dr. Leo Galland).
A Challenge and Opportunity
The causes of infertility are not always obvious, and in many cases, the picture is complicated. One thing, however, is very clear: the problem is common. According to the Center for Disease Control, over 7 million Americans—nearly 12% of the reproductive age population—experiencing difficulty conceiving.
In the absence of obvious reasons for infertility, or when those reasons are insurmountable, many couples are opting for Assisted Reproductive Technology (ART). IVF is the most common approach, and considered to be the most effective.
However, even among 20-29 year olds—the most fertile age for women—the success rate of IVF is only 47%, and these figures don't even reflect live births, only the maintenance of a transplanted fetus. Success decreases significantly with age, moving to a low of 11% for women aged 40-44. The procedure is also physically and emotionally stressful, time-consuming, and expensive.
Clearly, we need a wider spectrum of options to help enhance fertility. Diet and lifestyle factors may be the keys to increasing fertility and successful complication-free pregnancy.
In the search for future fertility treatments, we may find that the answer doesn't even lie within our own cells, but within those of the commensal organisms that continually support our existence. Research on the microbiome's influence on human reproduction is still in very early stages, yet the discoveries to date are promising.
It makes sense to at least consider probiotic supplementation as part of a broader lifestyle intervention aimed at improving fertility; the potential for side effects is nearly nonexistent, and there are reasons to think that it could be helpful.