Potential Influence of the Microbiome on Infertility and ART
Potential Influence of the Microbiome on Infertility and ART
The majority of data pertaining to the reproductive-tract microbiome in ART have been gleaned from studies on the cervicovaginal flora. The upper genital tract is generally considered to be sterile, but previous studies using endometrial cultures obtained via surgical hysterotomy have demonstrated growth of one or more microorganisms in the uterus, with Lactobacillus species, M. hominis, G. vaginalis, and Enterobacter species the most frequently recovered. Svenstrup et al further supported the concept of a nonsterile uterine environment; they demonstrated the ability of certain bacteria to attach to spermatozoa and be transported into the uterine cavity.
In the era of metagenomic studies, the molecular-based techniques have revolutionized our knowledge of the vaginal microbiome. With the combination of cultivation-dependent and independent molecular-based techniques, we are now able to explore microorganisms that were not detected previously, adding missing pieces to the puzzle called "the reproductive-tract microbiome."
Our ability to discover different species of lactobacilli, previously underappreciated, has shed light on the composition of the reproductive-tract flora during IVF-ET cycles. It is now clear that only specific Lactobacillus species are present with numerical supremacy in the healthy flora; these species are likely to play a pivotal role in maintaining a supportive environment for implantation and future pregnancy outcome.
Several studies have supported the hypothesis that the reproductive-tract microbiome on the day of embryo transfer affects pregnancy outcome, but no study has used the metagenomic approach for analyzing samples from the transfer-catheter tip. Therefore, further studies are needed to evaluate the association of H2O2-producing Lactobacillus recovered from the transfer-catheter tip with implantation and LBR by using the cultivation-independent molecular-based techniques, and compare results to those measured with the cultivation-dependent techniques.
The idea of colonizing the reproductive tract flora with different species of Lactobacillus to achieve healthy, "normal" flora has been a topic of interest. Probiotic species not numerically dominant in the vagina were used to colonize the already-infected vaginal environment, but unfavorable results were observed. When a more common species, H2O2-producing L. crispatus, was used to colonize vaginas of sexually active healthy women, the success rate was 69 to 90%. This result may support the hypothesis that colonizing the transfer-catheter tip with L. crispatus at the time of IVF-ET would increase the rates of implantation and LBR while decreasing the rate of infection.
It is unclear if the use of prophylactic antibiotics in IVF-ET cycles has an effect on implantation and LBR. Previous studies have recommended using broad-spectrum antibiotics for prophylaxis, but by doing so, there is always a risk of diminishing the dominant H2O2-producing Lactobacillus species in the reproductive tract. Another potential direction for future research would be to identify prophylactic antibiotics that are specific for the virulent microorganisms in the flora of the reproductive tract, while not affecting the H2O2-producing lactobacilli, and compare rates of implantation, infection, and LBR with and without the use of these antibiotics.
On the basis of the previous studies on the progesterone-resistant endometrium, it is possible that failure of implantation might be explained, in part, by alteration in the uterine microbiome in response to inflammation, leading to the development of a progesterone-resistant endometrium. Many questions about the interaction between genes and environment are still to be answered. When these answers are in hand, we envision that appropriately controlling for these factors and the common environmental factors described earlier would create a supportive habitat for the embryo in cases of IVF-ET, resulting in a successful implantation, healthy pregnancy, and healthy neonate.
Conclusions
The majority of data pertaining to the reproductive-tract microbiome in ART have been gleaned from studies on the cervicovaginal flora. The upper genital tract is generally considered to be sterile, but previous studies using endometrial cultures obtained via surgical hysterotomy have demonstrated growth of one or more microorganisms in the uterus, with Lactobacillus species, M. hominis, G. vaginalis, and Enterobacter species the most frequently recovered. Svenstrup et al further supported the concept of a nonsterile uterine environment; they demonstrated the ability of certain bacteria to attach to spermatozoa and be transported into the uterine cavity.
In the era of metagenomic studies, the molecular-based techniques have revolutionized our knowledge of the vaginal microbiome. With the combination of cultivation-dependent and independent molecular-based techniques, we are now able to explore microorganisms that were not detected previously, adding missing pieces to the puzzle called "the reproductive-tract microbiome."
Our ability to discover different species of lactobacilli, previously underappreciated, has shed light on the composition of the reproductive-tract flora during IVF-ET cycles. It is now clear that only specific Lactobacillus species are present with numerical supremacy in the healthy flora; these species are likely to play a pivotal role in maintaining a supportive environment for implantation and future pregnancy outcome.
Several studies have supported the hypothesis that the reproductive-tract microbiome on the day of embryo transfer affects pregnancy outcome, but no study has used the metagenomic approach for analyzing samples from the transfer-catheter tip. Therefore, further studies are needed to evaluate the association of H2O2-producing Lactobacillus recovered from the transfer-catheter tip with implantation and LBR by using the cultivation-independent molecular-based techniques, and compare results to those measured with the cultivation-dependent techniques.
The idea of colonizing the reproductive tract flora with different species of Lactobacillus to achieve healthy, "normal" flora has been a topic of interest. Probiotic species not numerically dominant in the vagina were used to colonize the already-infected vaginal environment, but unfavorable results were observed. When a more common species, H2O2-producing L. crispatus, was used to colonize vaginas of sexually active healthy women, the success rate was 69 to 90%. This result may support the hypothesis that colonizing the transfer-catheter tip with L. crispatus at the time of IVF-ET would increase the rates of implantation and LBR while decreasing the rate of infection.
It is unclear if the use of prophylactic antibiotics in IVF-ET cycles has an effect on implantation and LBR. Previous studies have recommended using broad-spectrum antibiotics for prophylaxis, but by doing so, there is always a risk of diminishing the dominant H2O2-producing Lactobacillus species in the reproductive tract. Another potential direction for future research would be to identify prophylactic antibiotics that are specific for the virulent microorganisms in the flora of the reproductive tract, while not affecting the H2O2-producing lactobacilli, and compare rates of implantation, infection, and LBR with and without the use of these antibiotics.
On the basis of the previous studies on the progesterone-resistant endometrium, it is possible that failure of implantation might be explained, in part, by alteration in the uterine microbiome in response to inflammation, leading to the development of a progesterone-resistant endometrium. Many questions about the interaction between genes and environment are still to be answered. When these answers are in hand, we envision that appropriately controlling for these factors and the common environmental factors described earlier would create a supportive habitat for the embryo in cases of IVF-ET, resulting in a successful implantation, healthy pregnancy, and healthy neonate.
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