This section of The Fertility Guide provides essential information for when you experience prolonged difficulties conceiving, failed IVF, miscarriage or have absolute infertility due to age or other factors. We know this is a heart-breaking place to be and we hope that providing reliable, evidence-based information, it will make the journey a little easier and allow you to get the help you need.
Problems Conceiving
If you’ve been trying to conceive for a year or more and you haven’t been able to get pregnant, or have experienced miscarriage, it’s really important to be fully investigated to understand why you’re having problems. We cover the many different reasons why people may not be able to conceive and the investigations and treatments you may need in The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy. In this section we look at:
- Medical investigations
- Underlying health and fertility
- Why can’t I get pregnant?
- The microbiome and fertility
- The vaginal microbiome
- Oral health and fertility
- The immune system
- Inflammation
- Biological function and fertility
- Why mitochondria are important for egg and sperm quality
- Epigenetics and fertility
- Telomeres
- The common factors that impact biological processes
- MTHFR mutations and infertility
- Secondary infertility – infertility after a previous pregnancy
- Getting fit for fertility and pregnancy
Medical investigations
Knowing when to get help and ensuring you have the right medical investigations are both very important if you haven’t been able to conceive naturally or if you have symptoms that suggest there might be a problem such as irregular periods. Don’t delay in speaking to your doctor and ensure you also have the appropriate routine preconception screening tests such checking for rubella immunity if you are to carry the pregnancy and a sexual health check for both partners that should be done irrespective of whether or not you have experiencing difficulties.
Underlying health and fertility
Alongside ensuring you are receiving the right medical care, if you’ve been working on your diet and lifestyle but haven’t yet conceived, there are other aspects of your health that can be looked into. Fertility investigations are usually very focused on reproductive health, but there are many aspects of general health that can have an impact on reproductive health.
Therefore, if you do not have a medical condition and you haven’t conceived, there are likely to be underlying issues that may contribute to difficulty conceiving aside from a known diagnosis. There is increasing recognition that infertility is associated with other general health issues and disease risk later in life. Gestational diabetes, preeclampsia (a dangerous pregnancy complication that causes high blood pressure and other problems including with other organs in the body) and male infertility are all associated with an increased risk of cardiovascular disease, for instance, and women with irregular periods have been shown to have poorer health outcomes than women with a regular menstrual cycle.
Addressing underlying health issues when trying to conceive may therefore offer significant protection against future illnesses for both parents as well as your child and during pregnancy as part of a comprehensive preconception care programme.
We cover how diet, nutrients, exercise, weight and metabolism can impact reproductive health in our Fertility and Preconception Care course and in The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy.
Other things that can impact fertility and pregnancy include gut health, inflammation and oral health; factors that are often overlooked in typical medical treatments.
Why can’t I get pregnant?
As well as symptoms related to reproductive health such as irregular periods and severe pain (that can signal endometriosis) that be directly linked to subfertility, other symptoms can be a sign of other problems that may affect fertility indirectly. Many people tolerate ongoing symptoms including headaches, digestive complaints, fatigue or low mood, and accept them as normal aspects of modern living. It’s also common for patients to experience these concerns with general health and well-being being dismissed by doctors, and find conventional medicine often has little to offer. In the gap between, many opt for treatments that may not have an evidence base or can be very expensive. So it’s important to understand what the science can tell us and how much research has been done on particular topics, remembering of course that it’s complicated, not all research is done perfectly, there is much we don’t know and science is constantly evolving. Having a basic understanding of the evidence and some of the issues, however, means you can then choose to do things that make you feel better and may improve your symptoms in an informed way.
Understanding the potential underlying causes of any symptoms you are experiencing can help provide important clues as to what we need to work on to improve fertility. The aim with fertility treatments should be to understand why you are not conceiving and optimise your overall health, not simply to artificially engineer a pregnancy through in vitro fertilisation (IVF). Otherwise we can end up treating the sperm, eggs and uterus and forget about the person. Infertility is classed as a disease by the World Health Organisation (WHO) and not being able to have children is one part of it. The impact on general and mental health are the other components of infertility that should be addressed. Of course, taking care of your emotional wellbeing and mental health is a very important part of this.
We cover underlying causes of infertility in more detail in our Fertility and Preconception Care course and in The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy.
The microbiome and fertility
Having good digestive health is an important aspect of general health and many conditions that can affect male and female fertility go undiagnosed including coeliac disease, which can impact sperm health, delay natural conception and increase the risk of miscarriage. Another aspect of digestive health is the gut microbiome (the ‘good’ bacteria essential for health). The microbiome is the population of microorganisms that live in your body (including bacteria, viruses and fungi) that support the digestive system and other bodily functions. Different parts of the body have their own microbiome including the gut, vagina, nose and mouth. The gut microbiome affects all aspects of health: immune function, mental health, hormones, weight and metabolism, and fertility. A healthy gut microbiome is also important for pregnancy, childbirth and the future health of a child so looking after your gut health before pregnancy as part of a preconception care programme is important for you and your baby.
The vaginal microbiome
The vaginal microbiome has become a significant focus of fertility research, especially in an IVF setting where the process of conception is highly controlled. Certain species of bacteria have been shown to be associated with better outcomes, notably lactobacillus species. In the vagina, low diversity has shown to be beneficial, in contrast to the gut, and higher diversity is associated with worse outcomes in fertility treatment. A high percentage of lactobacillus species in the vagina along with the presence of one particular species – lactobacillus crispatus – are associated with increased rates of pregnancy following embryo transfer in IVF treatment.
Specific microbes are also associated with conditions such as bacterial vaginosis (BV) and thrush and can signal underlying vaginal microbiome problems. BV is a common cause of adverse outcomes including spontaneous preterm birth and endometritis (inflammation of the lining of the womb).
However, we advise caution when it comes to vaginal microbiome testing unless you are under the care of a teaching hospital or an academic research programme. Unless you test daily for a prolonged period, it is very difficult to gain an insight into your unique microbial make-up and there is no clinically validated intervention to address an impaired vaginal microbiome, though this is the focus of intense research.
There are studies to indicate benefit of probiotic supplements, for instance, many of which are available commercially. The most commonly researched probiotics for modulating the vaginal microbiome in fertility studies are lactobacillus fermentum, lactobacillus salivarius, lactobacillus casei, lactobacillus reuteri RC-14, lactobacillus gasseri, lactobacillus rhamnosus, lactobacillus acidophilus and lactobacillus crispatus. Evidence from these studies has demonstrated changes to the vaginal microbiome and improvements in IVF outcomes but, again, there isn’t sufficient evidence from large-scale trials to make universal recommendations at this stage and we don’t fully understand the long-term implications of these interventions.
If you have repeated infections such as thrush or BV, or any symptoms that may indicate you have an infection, such as strong-smelling discharge, itchiness or discomfort during sex, see your GP for advice or speak to your fertility specialist.
You can find out more about things that my help the vaginal microbiome in our Fertility and Preconception Care course and The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy.
Oral health and fertility
Another surprising area of general health is oral health – the health of your mouth and teeth. Gum disease is associated with both a delay to natural conception and reduced IVF success. There are various mechanisms at play. One is through inflammation in the mouth causing inflammation throughout the body that ultimately impacts reproductive pathways. Another possible mechanism is through an imbalance in the oral microbiome resulting in dysbiosis in the gut.
Mineral deficiency is also a significant cause of tooth decay, and fat-soluble vitamins A, D and K are also important to build and maintain healthy teeth and for the development of the fetal teeth, face and jaw bones. Mineral malabsorption can lead to problems with the teeth (as with coeliac disease), so problems in the mouth often signal other health issues.
Having a healthy diet to promote healthy teeth, being up to date with dental health checks and aiming to resolve any issues, including bleeding gums, prior to conceiving is a vital component of preconception care that many overlook. Taking care of your oral health and visiting the dentist when you are pregnant is important too.
The immune system
Good immune function is needed to achieve a successful pregnancy and is especially important for normal implantation and placentation (development of the placenta). Research shows that a deficiency of particular immune cells known as T regulatory cells is associated with unexplained infertility and recurrent miscarriage, for instance. Balanced immunity is also important for an embryo to implant.
Immune response is affected by numerous factors including nutrition, obesity, stress, infection, smoking, alcohol and environmental toxins, so optimising all of these factors at the very least eliminates the potential for negative consequences of lifestyle habits on implantation. Medical conditions that can trigger an overreactive immune response and rejection of the embryo include infection, autoimmune conditions, diabetes, glucose intolerance, endometriosis and micronutrient deficiency.
Inflammation
Inflammation is the body’s natural, first-line response to infection or injury. Acute inflammation is a necessary component of immune function and healing that involves a complex biological response to harmful invaders, such as bacteria, viruses, damaged cells or irritants.
Chronic inflammation occurs when the immune system gets a faulty distress signal and mobilises its defence by triggering the release of white blood cells as though you were sick or injured, but because there’s no infection to attack or injury to repair, they end up causing damage to healthy bodily tissues and processes. This kind of inflammation is associated with increased risk of various diseases including cardiovascular disease, cancer and Alzheimer’s, and may even reduce life expectancy overall.
There are various causes of chronic inflammation including poor diet and lifestyle, stress and being overweight. Chronic inflammation can delay natural conception, reduce the chance of success with IVF, affect menstrual cycle regularity, affect the production of sex hormones and ovulation.
You can find out more about the causes of chronic inflammation, how this may impact fertility and what you can do to help in our Fertility and Preconception Care course and in The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy.
Biological function and fertility
As well as things like immune function and the microbiome that affect the functioning of our whole bodies, there are processes taking place in individual cells that can affect sperm and egg quality. These things are relevant because they are also affected by diet and lifestyle so we can do something about them.
Mitochondria
Mitochondria (the ‘batteries’ of the cell) produce the energy needed for the body to function. They essentially convert energy from the calories in food to a form of energy that cells need to fuel biochemical processes – ATP (adenosine triphosphate) – in the same way we need to convert crude oil into petrol to fuel a car’s engine.
Why mitochondria are important for egg and sperm quality
Mitochondria are important for egg and sperm quality as both cells need lots of energy. The egg is the largest cell in the body and it provides the energy that fuels development of the early embryo. Sperm have a long way to swim so need energy for this journey. The more mitochondria that work well within each egg, the better the oocyte quality and the more energy the embryo it forms after fertilisation will have for early development, so the more ‘competent’ it will be. Poor mitochondrial function in the oocyte and embryo can therefore contribute to infertility and developmental abnormalities because a damaged mitochondrion produces less energy. As well as worsening with age (just as a torch light fades as the batteries start to wear out), mitochondrial function can be affected by damaging lifestyle habits, toxic environmental exposures, high-fat diets, being overweight and nutrient deficiencies – factors that can all lead to increased oxidative stress. Conversely, mitochondrial function may be protected through dietary restriction, so optimising weight and avoiding over-eating and too much fat may help.
Epigenetics and fertility
Epigenetics is the study of how your behaviours and environment can cause changes that affect the way your genes work. Having a faulty gene is one way for disease or health problems to arise; the other is for a healthy gene to stop working effectively. This can be caused by anything you put in or do to your body: from diet and exercise to the pesticides in food and smoking. There is growing evidence to show that epigenetic changes can impact reproductive health, including egg and sperm quality. One study found that certain phthalates (preservatives commonly used in toiletries and cosmetics) caused changes to the genes in sperm that resulted in worse outcomes from IVF treatment for the couple. Another study found that what a woman eats around the time of conception can change the genes that control development in a newly formed embryo.
Telomeres
Telomeres are the caps at the end of strands of DNA. In the same way caps on the end of shoelaces prevent fraying, telomeres protect DNA as it replicates by helping to ensure that an exact copy of DNA is made when it replicates (e.g. during cell division) so that mutations do not arise. Telomeres shorten with age and with damaging lifestyle factors and, as they shorten, mutations in DNA become more likely during replication.
This increased tendency towards DNA mutation has a direct impact on fertility and is another mechanism through which age impacts both male and female fertility. Mutations in sperm DNA cause poor morphology and motility, while telomere length in combination with mitochondrial function is important for egg quality.
The common factors that impact biological processes
There is growing evidence to show the principles of good diet, nutrient status and other lifestyle factors that we describe can help support these biological processes that underpin good health and fertility. Our Fertility and Preconception Care course and The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy both explain the evidence and dietary and lifestyle factors that may help. Understanding the complexities of fertility research can also be helpful when deciding the best approach for you.
MTHFR mutations and infertility
The MTHFR (methylenetetrahydrofolate reductase) enzyme is critical for folate metabolism in the body and is needed to convert the supplemental form, folic acid, into its bioavailable form used by the body, folate. Folate is important for fertility and pregnancy, with deficiencies causing neural tube defects (such as spina bifida) in the baby. MTHFR gene variants are recognised as having the potential to impact both male and female fertility including the risk of miscarriage.
In simple terms, having an MTHFR mutation means that if you supplement with folic acid, although easily absorbed, it will be harder for your body to convert folic acid into folate. The data is mixed in terms of exactly how this may impact fertility, and routine testing is not currently recommended by guidelines from the National Institute for Health and Care Excellence (NICE) for fertility.
From our observations, it seems some are more affected than others. If you have been taking folic acid or a multivitamin containing folic acid for at least three months and your folate is low on testing, speak to your GP or fertility specialist. We explain more about these kinds of gene variants in our Fertility and Preconception Care course and The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy.
Secondary infertility – infertility after a previous pregnancy
If you already have at least one child and you are struggling to conceive again, it is possible that previous pregnancies may be contributing. Pregnancy is very depleting on the body, with nutrients preferentially diverted to the fetus over the mother, and it can easily lead to postnatal deficiencies. If you then add breastfeeding into the equation, which is also very demanding on the body, it is easy for a woman to slip into a state of multiple deficiencies.
Poor sleep that often comes with a new baby and the stress related to new parenthood can also have an impact. This once again highlights the importance of preconception care as ensuring body stores of nutrients are adequate prior to pregnancy helps protect against depletion and also prepares you for breastfeeding. Where this is a factor in subsequent infertility, it often can be corrected through a sufficient preconception period of testing, supplementation and suitable focus on a healthy, nutrient-rich diet. Seeking advice and support if your child is not sleeping in order to improve your own sleep can also be helpful in addressing secondary infertility.
Getting fit for fertility and pregnancy
We have many success stories from couples who had faced lengthy struggles to conceive, often experiencing miscarriages and failed IVF along the way, only to conceive naturally and go on to have healthy pregnancies and healthy babies by making some of these changes. We can’t offer guarantees that you will be able to conceive naturally, but we can tell you this work will get you in the best possible health for pregnancy and parenthood, improve the health of any babies you go on to have and put you in the best place for a successful outcome of any fertility treatment you may need.
You can find out more about underlying causes of infertility and what you can do about them in our Fertility and Preconception Care course and The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy.
References
- Adam Balen and Grace Dugdale. The Fertility Book: Your Definitive Guide to Achieving a Healthy Pregnancy. Penguin Random House (Vermilion) 2021
- López-Moreno, A., & Aguilera, M. (2020). Probiotics dietary supplementation for modulating endocrine and fertility microbiota dysbiosis. Nutrients, 12(3), 757.
- Robertson, S. A., Care, A. S., & Moldenhauer, L. M. (2018). Regulatory T cells in embryo implantation and the immune response to pregnancy. The Journal of Clinical Investigation, 128(10), 4224–35.
- Marcho, C., Oluwayiose, O. A., & Pilsner, J. R. (2020). The preconception environment and sperm epigenetics. Andrology, 8(4), 924–42.
- Wu, H., Estill, M. S., Shershebnev, A., Suvorov, A., Krawetz, S. A., Whitcomb, B. W., Dinnie, H., Rahil, T., Sites, C. K., & Pilsner, J. R. (2017). Preconception urinary phthalate concentrations and sperm DNA methylation profiles among men undergoing IVF treatment: A cross-sectional study. Human Reproduction, 32(11), 2159–69.
- Waterland, R. A., Kellermayer, R., Laritsky, E., Rayco-Solon, P., Harris, R. A., Travisano, M., Zhang, W., Torskaya, M. S., Zhang, J., Shen, L., & Manary, M. J. (2010). Season of conception in rural Gambia affects DNA methylation at putative human metastable epialleles. PLoS Genetics, 6(12), e1001252.
- Chen, Y., Michalak, M., & Agellon, L. B. (2018). Focus: Nutrition and food science: Importance of nutrients and nutrient metabolism on human health. The Yale Journal of Biology and Medicine, 91(2), 95.
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