Infertility affects millions worldwide, and for those in our community struggling to grow their families, we're here to support you. We know that infertility is much more than a medical term—it's a journey marked by hope, followed by devastating setbacks. We've been there through the ups and downs. The more we understand how the vaginal and endometrial microbiome influences fertility, the more interested we are in delving into the studies linking the two.
In this post, we explore how our unique microbial communities play a crucial role in conception. We’ll also explore research connecting the vaginal microbiome with in-vitro fertilization (IVF) success, since IVF is a primary form of treatment for couples experiencing infertility. Whether infertility is a challenge that touches you personally or someone you love, we hope these insights open doors to new solutions and possibilities.
What is fertility and infertility?
Fertility refers to the ability to get pregnant or conceive naturally. Infertility is just the opposite. It refers to when you cannot conceive naturally for at least a year, despite having unprotected and frequent sexual activity [1], [2].
Despite its simplicity, modern society faces increased rates of infertility. It is estimated that around 48 million couples trying to conceive face infertility and 186 million individuals live with infertility globally [1]. About 19% of women with no prior births and 6% of women with one or more prior births in the United States are unable to conceive after one year of trying [2].
But infertility is not just a woman’s problem.
Both partners are involved. In fact, the CDC reports that male infertility is detected along with female issues in 35% of couples who struggle to conceive. And male-only problems are identified in about 8% of couples [2].
What are the risk factors for infertility?
Common risk factors for infertility in both men and women include:
- Age: This is the most common factor. Women's fertility gradually declines after 37 years of age. Male infertility increases over the age of 40.
- Weight: This goes both for being overweight and being underweight.
- Ongoing sexually transmitted infections (STIs) or a history of STIs
- Smoking or alcohol consumption [1], [2]
There are also specific risk factors for men and women.
Male infertility risk factors
Causes of male infertility may include the following conditions [1], [2]:
- Irregular sperm production or function: This can be due to genetic defects or chronic diseases, such as diabetes. Frequent exposure to heat (e.g., sauna) can increase body temperature and also affect sperm production
- Sexual problems (like premature ejaculation), genetic diseases (like cystic fibrosis), or structural problems (like blockage in the testicle) that impact sperm delivery
- Overexposure to pesticides, chemicals, radiation, smoking, alcohol, and anabolic steroids
- High blood pressure
- Depression
- Cancer or cancer treatment
Female infertility risk factors
Causes of female infertility may include the following conditions [1], [2]:
- Ovulation disorders that cause a problem in releasing eggs from your ovaries:
- Polycystic ovary syndrome (PCOS), which represents a hormone imbalance affecting ovulation
- Hypothalamic dysfunction affects hormones responsible for stimulating ovulation each month, leading to irregular menstruation
- Premature ovarian failure is a condition in which the ovary no longer produces eggs. It lowers estrogen production in women under the age of 40
- Tubal infertility, also known as damaged or blocked fallopian tubes. This prevents sperm from getting to the egg since the passage is blocked
- Endometriosis, a condition in which the endometrial tissue grows outside of the uterus
- Uterine or cervical abnormalities: This includes an abnormally shaped uterus or the presence of benign polyps or tumors, which interfere with the implantation of the fertilized egg
- Cancer or cancer treatment
Unexplained infertility
Sometimes there are no obvious issues found in either partner's reproductive health. This is called unexplained infertility, a diagnosis that suggests there may be underlying factors affecting fertility that are not easily detectable or explainable through standard testing. It’s often considered a combination of several factors that may affect fertility, including subtle hormonal imbalances, egg quality issues, sperm function abnormalities, or problems with embryo development or implantation.
What is in vitro fertilization?
Infertility is a serious and difficult problem for many couples trying to conceive. The good news is, couples facing this situation have options! You can choose between multiple different assisted reproductive technologies, including:
- In vitro fertilization (IVF)
- Intrauterine insemination (IUI)
- Fertility medications
In vitro fertilization (IVF) is known as the most effective assisted reproductive technology. The process includes fertilizing an egg by sperm in a test tube or elsewhere outside the human body. After that, fertilized eggs, or the embryo(s), are transferred to the uterus [3], [4].
IVF is offered as a primary treatment to couples with infertility issues, especially when they have been trying to conceive for over a year and there is advanced maternal age (over 40 years), and in cases of tubal infertility, ovulation disorders, endometriosis, uterine or cervical abnormalities, or impaired sperm production or function [3], [4].
The role of the microbiome in fertility and successful IVF
One lesser known factor that can play a role in fertility and successful IVF is the vaginal and endometrial microbiome.
These unique bacterial communities play an essential role in maintaining a woman's health throughout her life. They’re also crucial during pregnancy and provide a healthy start for a newborn baby.
Vaginal microbiome and fertility
The vaginal microbiome of a healthy premenopausal person is dominated by Lactobacillus bacteria.
Lactobacillus dominance is associated with low vaginal pH (below 4.5) and protection against unfriendly and unwanted guests [5]. The main types of Lactobacillus species that live in the vaginal canal are:
- Lactobacillus crispatus
- Lactobacillus iners
- Lactobacillus jensenii
- Lactobacillus gasseri
These species help to determine the vaginal Community State Type (CST) [5], [6]. Knowing your CST provides clues about your general vaginal wellness.
Having a healthy vaginal microbiome, dominated by Lactobacillus bacteria, is crucial for those trying to conceive or undergoing IVF. Research shows that a Lactobacillus-dominated CST is associated with higher fertility and successful IVF outcomes [7], [8], [9], [10], [11], [12]. Specifically, a vaginal microbiome dominated by L. crispatus has been significantly associated with increased rates of embryo implantation and live births after IVF [12], [13].
Conversely, an imbalanced vaginal microbiome—with low levels of Lactobacillus and high levels of unfriendly bacteria—can negatively impact fertility and IVF success [9], [10], [11], [14]. Unfriendly bacteria commonly found in women with recurrent implantation failure or poor pregnancy outcomes include Gardnerella, Prevotella, Atopobium (associated with bacterial vaginosis, or BV), as well as Escherichia, Enterococcus, and Streptococcus (linked with aerobic vaginitis, or AV) [15], [16]. Additionally, women diagnosed with BV and with high levels of Gardnerella vaginalis and Atopobium vaginae face increased risks of poor pregnancy outcomes [17].
How does this look for each vaginal community state type?
- CST1 is dominated by Lactobacillus crispatus, and is clearly associated with fertility and successful IVF [7], [8], [12]. These beneficial bacteria also prevent the growth of harmful microbes that cause vaginal infections [18] and may affect fertility or IVF success [17], [19].
- CST2 is dominated by Lactobacillus gasseri, one of the main Lactobacillus species associated with good vaginal health [5], [6]. While we know L. gasseri prevents the growth of harmful microbes that cause vaginal infections [20], its role in fertility or IVF success is not that clear [11], [17].
- CST3 is dominated by Lactobacillus iners, one of the most commonly isolated bacteria from the vaginal microbiome [5], [6]. While some studies point out that L. iners is associated with successful IVF [7], [8], [12], others found out that a microbiome dominated by L. iners was linked to infertility [21], [22]. Besides, L. iners can sometimes hang out with harmful microbes [23], [24]. If you have disruptive species in your vaginal microbiome and experience symptoms, these conditions may affect fertility or IVF success [17], [19].
- CST4 is not dominated by Lactobacillus. Instead, this community is characterized by high species diversity and a less acidic (less protective) pH [5], [6]. Bacteria associated with CST 4 play an important role in the development of BV [25] or AV [26], which might be a risk factor for infertility, IVF failure, and pregnancy complications like preterm birth [17], [19], [27]. Of note, in many cases BV and AV may be asymptomatic and the only way of detecting such imbalances is by looking at your vaginal microbiome.
- CST5 is dominated by Lactobacillus jensenii, another Lactobacillus associated with good vaginal health [5], [6]. L. jensenii prevents the growth of harmful microbes that cause vaginal infections [20], but its role in infertility is less clear [8], [12].
- CST ‘Other’ is a vaginal community that doesn’t fit neatly into the other types. This uniqueness is not necessarily negative. A vaginal microbiome dominated by an uncommon Lactobacillus species is still beneficial for vaginal health since all Lactobacillus are able to maintain a low pH and keep unfriendly bacteria at bay. Although there isn’t enough evidence linking these uncommon CSTs to fertility, having high levels of Lactobacillus is better than not having them at all.
Endometrial microbiome and fertility: the unexpected hidden microbes
The endometrium is the inner lining of the uterus, where a fertilized egg can implant and grow during pregnancy. For a long time the uterus was thought to be sterile, and the presence of bacteria in it was associated with disease [28]. However, recent research suggests that the endometrium hosts its own unique microbiome and that beneficial bacteria in it may influence fertility [29], although this is still under debate. So far it seems that the endometrium of healthy women is dominated by Lactobacillus and Flavobacterium [30], [31].
Some study findings:
- Low amounts of Lactobacillus in the endometrium have been linked to infertility [32], but not all studies agree [16], [33].
- Women whose endometrial microbiome is dominated by Lactobacillus achieve higher rates of successful embryo implantation and live birth [34], [35].
- It’s not clear whether high levels of Lactobacillus in the endometrium lead to higher pregnancy rates after a frozen embryo transfer [36], [37].
- Women with low levels of Lactobacillus and higher amounts of unfriendly bacteria such as Gardnerella, Prevotella, and Streptococcus tend to have an unsuccessful IVF [34], [38], [39].
A “Silent” infection: About chronic endometritis
Women with chronic endometritis (an inflammation of the endometrium), caused by unfriendly bacteria that invade the uterus, experience recurrent reproductive failure. This condition often presents itself as an asymptomatic or “silent” infection. Unfriendly bacteria present in the vaginal and endometrial microbiome that have been linked to endometritis include Group B Streptococcus, Ralstonia, Gardnerella, Escherichia coli, Prevotella, Ureaplasma, and Chlamydia [40], [41], [42]. These bacteria create a hostile environment that disturbs normal endometrial receptivity and leads to lower egg implantation rate.
Some IVF clinics offer the option of endometrial microbiome testing. This can help identify potential imbalances that may impact fertility outcomes. If you are interested in learning more about this option, be sure to ask your fertility doctor about it.
What about the male microbiome?
The vaginal and the endometrial microbiomes are not the only players when it comes to successful reproduction. Semen also has a microbial community, and depending on the exact bacteria present, semen quality (and fertility) may be affected.
Bacteria in semen that have been linked to lower semen quality and infertility include Anaerococcus, Prevotella, and Pseudomonas. Conversely, Lactobacillus bacteria have been associated with healthier semen, normal sperm morphology, and better fertility outcomes [43], [44], [45], [46]. While species like Ureaplasma urealyticum, Enterococcus faecalis, and Mycoplasma hominis seem to impact sperm quality, their direct link to infertility is less clear [47].
Interestingly, men with prostatitis, which is associated with low semen quality, tend to have a more diverse semen microbiome with lower levels of Lactobacillus. This suggests that Lactobacillus species, similar to the vaginal microbiome, play a beneficial role in semen health [48].
Commercial testing for the semen microbiome is not yet widely available in the US. However, men undergoing fertility assessments or treatments can access laboratory tests that detect infection-causing bacteria in semen. These tests help identify bacterial infections that could impact fertility.
Support for your fertility journey
There is so much complex information about the microbiome to consider while navigating conception challenges. That's why our Fertility, Pregnancy & Postpartum Program is designed with your unique journey in mind. It offers personal insights and support, guiding moms-to-be from conception through the postpartum period.
We provide resources like two gut or vaginal testing kits and personalized one-on-one coaching to help you track your progress. Getting tailored advice on diet, lifestyle, and supplements means one less thing to worry about. The detailed health reports will deepen your understanding of how your microbiome may impact your ability to support a healthy pregnancy.
For those struggling to conceive or start a family, you're not alone in this journey. Our Tiny community has been there through the ups and downs—connect with other parents in our Tiny Health Fam Facebook group.
