At least 40% of fertility challenges have a male factor...
Fertility challenges are rising globally for both men and woman, and this trend is expected to continue.
Right now about 8-12% of couples have challenges conceiving with around 10-15% of pregnancies ending in miscarriage.
The fertility rate has halved in the past fifty years.
Approximately 50% of infertility problems are solely due to female factors.
20% to 30% of infertility problems are solely down to male factors.
And 20% to 30% are due to both male and female factors (1).
Table of Contents
This means that if you’re a man and you’re having fertility challenges, in at least 40% of cases, you are a factor.
The take home point is that fertility isn’t just down to the lady.
If you have fertility challenges, you need to be involved in the investigative process from day 1.
Fertility success starts with a proper analysis
Our experience of working with hundreds of men who are suffering fertility challenges suggests you probably haven’t had a thorough investigation of the factors at play.
The situation we often come across is that you may have had a basic hormone test, for instance a testosterone test, and a semen analysis.
These tests are not good enough, and are not capable of identifying the root causes and critical underlying factors involved in your male fertility issues.
Click here to book your free 15 minute Fertility Success Call with Dee Brereton-Patel now
Infertility: the male factor
At Coho we have been lucky enough to work with amazing men who are totally on this journey with their partner.
But there are also some who don’t want to make the lifestyle and nutrition changes required to get the job done, handing their partner the extra work just when they need it least.
We’ve even seen some who refuse to take a supplement.
And this at the same time that the female partner is potentially having many investigative processes, taking various fertility related medications (including hormonal medications), that’s making them feel so unwell, and making huge efforts with their nutrition and lifestyle.
If you’re one of the 40% of infertility cases where male factors play a role, and you’re not currently doing all you can, your involvement isn’t optional and you need to get in the game.
Your role doesn’t start and end with the provision of one healthy looking sperm – and we’ll get into more detail about that below.
Male structural abnormalities affecting fertility
Here are some common structural issues that can compromise male fertility:
Varicoceles
Varicoceles are the commonest structural issue in male infertility (2).
A varicocele is an enlarged vein, specifically the veins on the scrotum that are responsible for taking oxygen depleted blood away from the testicles.
What happens is that the enlarged veins lead to increased temperature in the testes, and this impacts the sperm cells (which are sensitive to environmental changes like temperature, oxidative stress, and pressure (3)) that are produced there.
This can lead to problems such as:
- Decreased sperm motility
- Decreased sperm count
- Increased sperm DNA damage / DNA fragmentation (4) (which we test for in our male clients)
Retrograde ejaculation
Retrograde ejaculation happens in men when the neck of the bladder doesn’t close during orgasm.
Instead of moving out through the penis, semen moves back into the bladder, and while you might not notice that this is happening, it results in low sperm count (5).
Retrograde ejaculation can be caused by:
- Depression
- Diabetes
- High blood pressure medication
- Prostate surgery
Signs of retrograde ejaculation you might notice are:
- Little or no semen being produced
- After orgasm, your urine is cloudy
Defects in tubules that transport sperm
The tubes where sperm are produced in the testes (vas deferens) and where sperm are stored (epididymis) can be affected by infections, surgeries or genetic conditions, and in some cases can lead to obstructions that halt sperm delivery.
Obstructions in these tubes that deliver sperm cells can affect sperm count.
Around 4-10% of men with low or no sperm count may have an obstruction.
Semen analysis
A semen analysis measures the quantity and quality of semen and sperm and is a very routine test performed by doctors and fertility clinics.
It is a first step in identifying common causes of male fertility issues.
A semen analysis can identify the following (in addition to some other markers):
- Amount of semen in the sample (semen volume)
- Number of sperm cells (sperm concentration)
- Size and shape of sperm cells (morphology)
- Ability of sperm cells to swim forwards (sperm motility)
- pH of sample – an acidic environment can be detrimental to sperm cells
- White blood cells – pointing to a potential infection
There are common reasons for why there may be issues with semen volume, sperm concentration, morphology and motility.
A thorough Functional Medicine analysis can help pinpoint factors that we can address.
In our clients we frequently see semen analysis results improve in a 3 month period, and this makes sense because the sperm production process (spermatogenesis) takes around 72 days from start to finish.
Consistent nutrition and lifestyle changes for a 2 to 3 month period is reflected in your sperm quality.
If you’re taking positive steps to improve your fertility, repeating the semen analysis after 72 days can provide you with a good indication on whether you’re on the right track.
Sperm DNA fragmentation
A semen analysis test provides key information – are there enough sperm cells (count), do they have the right form (morphology) and are they moving well (motility).
A vital piece of additional information is knowing if the quality of the DNA being carried in the sperm cells (in the head portion of the sperm cell) is good enough.
Ultimately, male fertility is all about the quality of the DNA in the sperm cells, and how well this is transferred to the female egg during fertilisation.
It’s important to understand that sperm DNA integrity affects:
- Fertilisation rates (time to conception)
- Implantation success (the fertilised egg must implant itself to the wall of the uterus where it can receive support for growth and development)
- Pregnancy duration
- The health of your baby
DNA is unfortunately highly unstable and prone to damage.
This is known as ‘fragmentation’.
Some degree of sperm DNA fragmentation is normal and expected, however if there is too high a level of sperm DNA fragmentation, it’s an issue.
High sperm DNA fragmentation affects natural conception and outcomes of assisted fertility treatment.
So it’s just as important to assess if you’re in an IVF cycle, or if you’re trying to conceive naturally.
Sperm DNA fragmentation tests are performed in some clinics but not as often as semen analysis tests.
We recommend that both are performed.
The good news is that increased sperm DNA fragmentation can be improved, in as little as 72 days (remember, this is how long it takes to produce mature sperm cells).
Causes of sperm DNA fragmentation
Causes of sperm DNA fragmentation can include structural abnormalities as described above, and are relatively straight forward to address.
Infections can increase sperm DNA fragmentation, and this can be easily identified and addressed.
One of the biggest factors affecting sperm DNA fragmentation is a process called oxidative stress (where there are too many free radicals, and insufficient antioxidants to fix this).
Oxidative stress can be caused by:
- Increased scrotal temperature
- Smoking
- High insulin
- Obesity
- Chronic systemic inflammation
- Air pollution
- Heavy metals
- Pesticides
- Bisphenol A (‘BPA’ - a type of plastic)
- Alcohol consumption
- Electromagnetic waves (6) e.g. from mobile phones and radiation therapy (for cancer)
The good news is that most factors that cause oxidative stress (which in turn damages sperm DNA), are modifiable factors.
Nutrition and lifestyle interventions, including a significant increase in dietary antioxidants, can help reduce oxidative stress and we regularly see improvements in sperm DNA fragmentation test results when repeated.
Adrenal stress hormones
In our Functional Medicine approach to male fertility issues, experience suggests that stress hormones play an important role in reducing fertility.
We know that when stress goes down, fertility improves.
Why? Because stress hormones are deeply connected to so many other processes in your body such as:
- Sperm quality
- Sex hormone levels
- Thyroid hormones
- Pituitary hormones
- Circadian rhythm
- Melatonin levels
Stress can come from many varied sources;
- Mental
- Physical
- Emotional
- Infections
- Poor immune system
- Melatonin levels
- Low mood
- Hidden food sensitivities
- Inflammation
- Environmental toxins
- Low thyroid
- Blood sugar dysregulation
- Poor sleep
So while you might not obviously feel ‘stressed’, you can still be having a response to one or more of the different stressors above, and this triggers your stress hormones, in particular cortisol and DHEA (7).
And as studies show, psychological stress can result in a reduction of sperm motility, morphology, and concentration (8).
We often recommend the comprehensive DUTCH hormone tests by Precision Analytical as it gives us a complete picture of what’s happening with all the hormones that can impact male fertility.
Some ways we can help in a Functional Medicine approach to supporting stress hormones include:
- Helping to put in place good sleep-wake cycles
- Balancing blood sugar levels
- Introducing regular stress reduction routines
- Recommending the right kind of exercise at the right time of day (guided by the cortisol results over a 24 hour period)
- Recommending herbs or nutrients or herbs that support stress hormones
- Addressing any underlying factors causing stress in the body, where possible
In our Functional Medicine approach to male fertility, the supplements we recommend are always carefully tailored to individual symptoms and test results.
Low thyroid hormones (hypothyroidism) & male fertility
Low thyroid hormones impact male fertility by impeding the development of new sperm (spermatogenesis), as well as resulting in compromised sperm count and motility, low sex drive, and erectile dysfunction (9).
Pituitary hormones in fertility
Pituitary hormones are often checked in conventional medicine, and it’s something we always ensure have been checked, as these hormones are important signals between the brain and the testes.
These hormones (Luteinising Hormone (LH), Follicle-Stimulating Hormone (FSH) and prolactin) control sex hormone levels and reproductive processes.
Luteinising Hormone tells the testes to produce testosterone, while FSH is responsible for spermatogenesis.
High prolactin levels can also affect male fertility, by inhibiting the release of FSH and LH from the pituitary gland.
While it’s often missed, high prolactin could be an issue in up to 11% of infertile men (10).
See the section in red in the Luteinising Hormone & FSH in Men infographic above to see a visualisation of how this works.
Book your free 15 minute Discovery Call with Dee Brereton-Patel now
High insulin, men, and fertility
In the Coho Functional Medicine approach to male fertility, insulin is often a real problem.
Insulin is needed for our cells to use the glucose that’s released from food.
When insulin is consistently too high, our cells become resistant to it, leading to insulin resistance.
This doesn’t have to present as diabetes or prediabetes – much lower levels of insulin resistance can still lead to significant male fertility problems.
This is because insulin resistance causes:
- Inflammation (11)
- Oxidative stress (12)
- Metabolic syndrome (13)
- Higher blood pressure (14)
- Low sperm count (15)
The wider impact of insulin resistance can be serious for male fertility.
Insulin is produced when you eat sugars or carbohydrates, and high insulin results in increased levels of testosterone and DHEA.
For men, high insulin increases the conversion of testosterone to oestrogen (via a process called aromatisation), which throws out the oestrogen to testosterone ratio.
Increased aromatisation results in high oestrogen, and this in turn causes SHBG (Sex Binding Hormone Globulin) a binding protein, to increase.
SHBG binds to oestrogen and testosterone and reduces how much functional testosterone your body can use.
The low functional testosterone that high insulin causes is often catastrophic for male fertility.
The earliest indicator of a problem with insulin, is a high fasting insulin test.
High fasting insulin in this test usually means insulin sensitivity is being compromised, and you’d see this long before a high fasting glucose or HbA1c test result.
The take home: insulin resistance drives infertility via several mechanisms.
To find out more about blood sugar and insulin:
Improving insulin sensitivity
The good news is that research has demonstrated how insulin resistance can be reversed through straightforward nutrition and lifestyle changes:
– Reduce carbohydrate / sugar intake. This normalises blood sugar and reduces high levels of insulin.
Simple carbohydrate foods that quickly raise blood sugar and insulin levels include cakes, cookies, chocolate, ice cream, desserts, maple syrup, honey, bread, pastries, biscuits, pizza.
Starchy carbohydrates can also be a problem, for example potatoes (and things made from potatoes), white rice, parsnips and squash.
Drinks that contain sugar, as well as alcohol, can also be a problem.
– Increase fibrous vegetables to improve nutrient and fibre intake.
Fibrous vegetables are those that grow above ground, including bell peppers, broccoli, chard, spinach, cabbage, green beans, cauliflower, aubergine, radish, cucumber, tomato.
– Reduce inflammation by eating more foods high in antioxidants
Raised inflammation can promote insulin resistance. Get more foods like ginger, cherries, tomato puree, turmeric, blueberries, green tea, blackberries, wild oily fish, and extra virgin olive oil.
– Exercise
Exercise, and especially regular aerobic exercise and / or resistance training helps to improve insulin sensitivity by promoting the uptake of blood glucose by the muscles.
– Fix nutritional deficiencies
Some nutrient deficiencies have been linked with insulin resistance, and vitamin D, berberine, omega 3 fatty acids, alpha lipoic acid, magnesium have been widely studies in both type 2 diabetes and insulin resistance.
The take home: optimal insulin sensitivity is an important factor in male fertility. Nutrition and lifestyle are the main causes of suboptimal insulin sensitivity.
No supplement can compensate for poor nutrition, and no supplement can compensate for all the effects of stress.
Supplementing with testosterone
Testosterone replacement is usually not helpful for male fertility.
Taking testosterone can switch off your pituitary hormones, as your own body’s signals to produce testosterone are suppressed (15).
Breaking this mechanism isn’t always reversible, and testosterone treatment can lead to infertility.
The immune system link to fertility
In our clinical experience, a good number of the more complex infertility cases have an immune system imbalance, and in many cases, it could be the main factor causing the fertility problem.
What we’re really looking for here are chronic, long term immune system stressors such as:
- Psychological, physiological, or physical stress
- Trauma
- Infections
- Chemical or environmental toxins
- Poor liver detoxification
- High levels of adipose (fat) tissue
- Microbiome imbalances
- Poor digestion
- Food sensitivities
- Chronic pain
- High oestrogen levels
- Medications
Autoimmunity in male fertility
Autoimmune conditions happen when your immune system (mistakenly) attacks the tissues of your body, but they can be hidden and you may not know you have one.
ln autoimmune conditions, a Functional Medicine approach to male fertility would include:
– Identifying and addressing infections, such as chronic viral infections, yeast overgrowth, or bacterial infections
– Reducing stress
– Optimising the endocrine (hormone), gastrointestinal and detoxification systems and ‘modulating’ immune system function
– Identifying and addressing any food allergies or sensitivities
– Limiting exposure to environmental chemicals
– Supporting immune modulation
If you have an autoimmune condition it can affect the quality of your sperm, and there are some specific autoimmune conditions that should be explored in a Functional Medicine approach to male infertility.
Anti-sperm antibodies
Anti-sperm antibodies (ASA) are produced by men and women, and in men are found in the semen (16).
ASA binds to sperm and causes fertility issues even where other sperm health parameters are normal, and testing for anti-sperm antibodies can usually easily be added to a semen analysis test.
Studies show that ASA can cause male infertility through a process of molecular mimicry involving the E. coli bacteria (17), but there are likely to be many other causal factors for ASA.
Seminal microbiome
Yes it’s true, the semen fluid has its own microbiome consisting largely of lactobacillus specific strains of beneficial bacteria.
It’s an area of ongoing research, and fascinating to know how the bacteria balance in the seminal fluid impacts fertility.
Unfavourable bacteria in the semen can impair the sperm motility and the initial step in fertilisation when the sperm cell meets the egg, called the acrosome reaction.
Bacteria can also alter sperm morphology (form) and promote oxidative stress (18).
Lower levels of particular lactobacillus species have been found in patients with no sperm (azoospermia), low sperm count (oligoasthenozoospermia) and low morphology (teratozoospermia) (19).
Dietary modifications and specific probiotic supplementation can help to improve the seminal microbiome, as well as testing for any ‘bad’ bacteria and addressing them.
MicroGen testing has proven to be extremely helpful for our male fertility clients in recent years.
This highly specific bacteria testing using a semen swab and urine sample, allows us to gain a deep insight into seminal microbiome health, what imbalances may exist, and what needs to be done to address it.
Environmental chemicals and pollutants
Environmental toxins are an important factor to consider in a Functional Medicine approach to male fertility, and have been extensively studied.
Increased exposure to or reduced detoxification of undesirable environmental substances can negatively impact both male and female fertility (and birth outcomes).
Some of these everyday chemicals include:
- Pesticides
- Air pollution
- Cigarette smoke
- Recreational drugs
- Heavy metals
- Phthalates (plastics)
- Dioxins
- Chemicals in cosmetics
- Triclosan
- Parabens
- Growth hormones in animal produce
All of these can act as ‘hormone disrupters’ (20), by acting on the hormone receptors, leading to altered signalling.
Most people are exposed to hormone disrupters daily as they are so ubiquitous in the environment.
For instance, the NIH stated that BPA (found in plastics like plastic bottles) likely increases cancer risk and poses a risk to human development, while exposure to BPA in early life has been linked to the development of behavioural issues.
And while industry has made major progress in eliminating BPA, there are over 20 other types of plastics that are thought to be problematic.
For instance, significantly higher levels of phthalates have been found in semen and urine samples from men suffering with infertility (21).
Increased phthalate exposure is associated with reduced sperm count, morphology, and motility.
Going plastic-free, or as close to it as possible, is the best way forward.
These synthetic chemicals can result in increased oxidative stress and inflammation.
In turn, this can:
- Increase pro-inflammatory molecules in the peritoneal fluid
- Injure testicular Leydig and Sertoli cells (which produce testosterone and sperm cells, respectively)
- Promote autoimmunity
Studies show that air pollution by itself can increase infertility rates through triggering increased oxidative stress (22).
Environmental chemicals can affect many pathways in the body, causing:
- Inflammation (23)
- Endocrine disruption (24)
- Oxidative stress (25)
- Interference with normal DNA methylation processes (processes that keep DNA stable) (26)
- The minimisation of epigenetic changes (changes to how your body reads DNA, without there actually being a change to the DNA sequence, which can also be inheritable changes) (26)
This can affect not only conception rate, IVF success, and pregnancy duration, but can also affect the offspring.
Due to a reduced expression of detoxification enzymes, some men (and women) may genetically be at greater risk of being affected by chemicals and pollutants than others.
Reduced capacity to detoxify and eliminate environmental chemicals from the body can mean they build up, causing more damage compared to people who detoxify efficiently.
Through the advanced testing we use in our Functional Medicine approach to male fertility, we can gain deep insights into how well these detoxification pathways are working.
Testing options include genetic testing to understand if genes could be producing low levels of specific detoxification enzymes (for example the SOD, NAT, CYP1, CYP1, CYP2, CYP3, COMT, and GST genes).
Detoxification pathways that may not be functioning optimally can then be supported appropriately, through nutrition and nutritional supplements.
An internal environmental clean-up is an often essential aspect of our Functional Medicine approach to male fertility (and even where there are no infertility issues, as undesirable chemicals can also impact the health of the baby) (27, 28).
We recommend:
- Eliminating all plastics
- Replacing plastic (even if BPA free) with stainless steel or glass bottles
- For take out coffee, remove the plastic lid before drinking it
- Don’t use cling film
- Invest in non-plastic food storage solutions
- Use cookware without non-stick coatings
- Switch to natural home care and personal products
Investing in natural, chemical free household products can have a significant positive impact on your fertility and your all-round health.
As you can see, environmental chemicals should always be considered in a Functional Medicine approach to male fertility.
Methylation in fertility
Methylation has a role to play in areas such as:
- Fertility
- Detoxification
- DNA stability
- Cancer risk
- Epigenetic changes
- Neurotransmitter synthesis
- Mood
Experts estimate that up to 40% of humans may not be methylating optimally, due to genetic factors.
In methylation, the most widely studied genetic variance is the MTHFR gene (at gene locations A1298 and C677).
In fertility related genetic testing, these genes are one factor we often test for, and methylation can be supported through nutrition and supplementation.
In thinking about supplementation, it’s important to know that if you over-supplement, you can over-methylate, which can be just as problematic as under-methylating.
Body composition, body fat percentage, and fertility
In men, a healthy body fat percentage is an important factor in hormone signalling, and either too high, or too low, of a low body fat percentage can cause problems.
Some body fat is required to help regulate hormones and synthesise healthy levels of oestrogen.
Obesity in men can impair sperm production and cause increased DNA fragmentation, which is an important factor both in conception rates and miscarriages (29).
Too low of a BMI or body fat percentage in men can cause reduced testosterone levels.
Tailored nutrition support can help you achieve an optimal body weight and fat percentage in order to support fertility.
Book your free 15 minute Discovery Call with Dee Brereton-Patel now
The wrap...
As you can see, there are a number of factors that can come into male fertility, and it can be complex.
The male factor in fertility is super important, not only for becoming pregnant in the first place, but the quality of your DNA is a critical factor in maintaining pregnancy and the health of your baby.
Through our Functional Medicine approach to male fertility, you can ensure that becoming pregnant and maintaining pregnancy is possible, and that your DNA is the best quality it can be.
We think that’s a journey worth committing to.
And if you want to learn about the Functional Medicine approach to female fertility, we definitely recommend checking that out too.
To your baby, love, and joy filled future,
Dee & the Coho Fertility team
How can we help you? Send us a message below and we’ll come right back to you…
1.
Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015 Apr 26;13:37. doi: 10.1186/s12958-015-0032-1. PMID: 25928197; PMCID: PMC4424520
2.
Kupis Ł, Dobroński PA, Radziszewski P. Varicocele as a source of male infertility – current treatment techniques. Cent European J Urol. 2015;68(3):365-70. doi: 10.5173/ceju.2015.642. Epub 2015 Oct 15. PMID: 26568883; PMCID: PMC4643713.
3.
Kantartzi PD, Goulis ChD, Goulis GD, Papadimas I. Male infertility and varicocele: myths and reality. Hippokratia. 2007 Jul;11(3):99-104. PMID: 19582201; PMCID: PMC2658802
4.
Lavranos G, Balla M, Tzortzopoulou A, Syriou V, Angelopoulou R. Investigating ROS sources in male infertility: a common end for numerous pathways. Reprod Toxicol. 2012 Nov;34(3):298-307. doi: 10.1016/j.reprotox.2012.06.007. Epub 2012 Jun 28. PMID: 22749934.
5.
Jefferys A, Siassakos D, Wardle P. The management of retrograde ejaculation: a systematic review and update. Fertil Steril. 2012 Feb;97(2):306-12. doi: 10.1016/j.fertnstert.2011.11.019. Epub 2011 Dec 15. PMID: 22177462.
6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502318/
7.
Grande G, Barrachina F, Soler-Ventura A, Jodar M, Mancini F, Marana R, Chiloiro S, Pontecorvi A, Oliva R, Milardi D. The Role of Testosterone in Spermatogenesis: Lessons From Proteome Profiling of Human Spermatozoa in Testosterone Deficiency. Front Endocrinol (Lausanne). 2022 May 19;13:852661. doi: 10.3389/fendo.2022.852661. PMID: 35663320; PMCID: PMC9161277.
8.
Gollenberg AL, Liu F, Brazil C, Drobnis EZ, Guzick D, Overstreet JW, Redmon JB, Sparks A, Wang C, Swan SH. Semen quality in fertile men in relation to psychosocial stress. Fertil Steril. 2010 Mar 1;93(4):1104-11. doi: 10.1016/j.fertnstert.2008.12.018. Epub 2009 Feb 24. PMID: 19243749.
9.
Sengupta P, Dutta S, Karkada IR, Chinni SV. Endocrinopathies and Male Infertility. Life (Basel). 2021 Dec 22;12(1):10. doi: 10.3390/life12010010. PMID: 35054403; PMCID: PMC8779600.
10.
Singh P, Singh M, Cugati G, Singh AK. Hyperprolactinemia: An often missed cause of male infertility. J Hum Reprod Sci. 2011 May;4(2):102-3. doi: 10.4103/0974-1208.86094. PMID: 22065670; PMCID: PMC3205532.
11.
Shimobayashi M, Albert V, Woelnerhanssen B, Frei IC, Weissenberger D, Meyer-Gerspach AC, Clement N, Moes S, Colombi M, Meier JA, Swierczynska MM, Jenö P, Beglinger C, Peterli R, Hall MN. Insulin resistance causes inflammation in adipose tissue. J Clin Invest. 2018 Apr 2;128(4):1538-1550. doi: 10.1172/JCI96139. Epub 2018 Mar 12. PMID: 29528335; PMCID: PMC5873875.
12.
Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. 2016 Sep;24(5):547-553. doi: 10.1016/j.jsps.2015.03.013. Epub 2015 Mar 21. PMID: 27752226; PMCID: PMC5059829.
13.
Guo S. Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms. J Endocrinol. 2014 Jan 8;220(2):T1-T23. doi: 10.1530/JOE-13-0327. PMID: 24281010; PMCID: PMC4087161.
14.
Mansour R, El-Faissal Y, Kamel A, Kamal O, Aboulserour G, Aboulghar M, Fahmy I. Increased insulin resistance in men with unexplained infertility. Reprod Biomed Online. 2017 Nov;35(5):571-575. doi: 10.1016/j.rbmo.2017.08.020. Epub 2017 Aug 24. PMID: 28888863.
15.
Sukegawa G, Tsuji Y. [Risk of Male Infertility Due to Testosterone Replacement Therapy for Late-Onset Hypogonadism (LOH)]. Hinyokika Kiyo. 2020 Nov;66(11):407-409. Japanese. doi: 10.14989/ActaUrolJap_66_11_407. PMID: 33271659.
16.
A S V, Dhama K, Chakraborty S, Samad HA, Latheef SK, Sharun K, Khurana SK, K A, Tiwari R, Bhatt P, K V, Chaicumpa W. Role of Antisperm Antibodies in Infertility, Pregnancy, and Potential forContraceptive and Antifertility Vaccine Designs: Research Progress and Pioneering Vision. Vaccines (Basel). 2019 Sep 16;7(3):116. doi: 10.3390/vaccines7030116. PMID: 31527552; PMCID: PMC6789593.
17.
Thaper D, Prabha V. Molecular mimicry: An explanation for autoimmune diseases and infertility. Scand J Immunol. 2018 Jun 23:e12697. doi: 10.1111/sji.12697. Epub ahead of print. PMID: 29935034.
18.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647872/pdf/pj9-6-e151.pdf
19.
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647872/pdf/pj9-6-e151.pdf)
20.
Chiang C, Mahalingam S, Flaws JA. Environmental Contaminants Affecting Fertility and Somatic Health. Semin Reprod Med. 2017 May;35(3):241-249. doi: 10.1055/s-0037-1603569. Epub 2017 Jun 28. PMID: 28658707; PMCID: PMC6425478.
21.
Radke EG, Braun JM, Meeker JD, Cooper GS. Phthalate exposure and male reproductive outcomes: A systematic review of the human epidemiological evidence. Environ Int. 2018 Dec;121(Pt 1):764-793. doi: 10.1016/j.envint.2018.07.029. Epub 2018 Oct 16. Erratum in: Environ Int. 2019 Apr;125:606-607. PMID: 30336412.
22.
Conforti A, Mascia M, Cioffi G, De Angelis C, Coppola G, De Rosa P, Pivonello R, Alviggi C, De Placido G. Air pollution and female fertility: a systematic review of literature. Reprod Biol Endocrinol. 2018 Dec 30;16(1):117. doi: 10.1186/s12958-018-0433-z. PMID: 30594197; PMCID: PMC6311303.
23.
Vitti M, Di Emidio G, Di Carlo M, Carta G, Antonosante A, Artini PG, Cimini A, Tatone C, Benedetti E. Peroxisome Proliferator-Activated Receptors in Female Reproduction and Fertility. PPAR Res. 2016;2016:4612306. doi: 10.1155/2016/4612306. Epub 2016 Jul 31. PMID: 27559343; PMCID: PMC4983391.
24.
Gonsioroski A, Mourikes VE, Flaws JA. Endocrine Disruptors in Water and Their Effects on the Reproductive System. Int J Mol Sci. 2020 Mar 12;21(6):1929. doi: 10.3390/ijms21061929. PMID: 32178293; PMCID: PMC7139484.
25.
Al-Gubory KH. Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development. Reprod Biomed Online. 2014 Jul;29(1):17-31. doi: 10.1016/j.rbmo.2014.03.002. Epub 2014 Mar 21. PMID: 24813750.
26.
Singh S, Li SS. Epigenetic effects of environmental chemicals bisphenol A and phthalates. Int J Mol Sci. 2012;13(8):10143-53. doi: 10.3390/ijms130810143. Epub 2012 Aug 15. PMID: 22949852; PMCID: PMC3431850.
27.
Smith LE, Prendergast AJ, Turner PC, Humphrey JH, Stoltzfus RJ. Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes. Am J Trop Med Hyg. 2017 Apr;96(4):770-776. doi: 10.4269/ajtmh.16-0730. PMID: 28500823; PMCID: PMC5392618.
28.
Padula AM, Monk C, Brennan PA, Borders A, Barrett ES, McEvoy CT, Foss S, Desai P, Alshawabkeh A, Wurth R, Salafia C, Fichorova R, Varshavsky J, Kress A, Woodruff TJ, Morello-Frosch R; program collaborators for Environmental influences on Child Health Outcomes. A review of maternal prenatal exposures to environmental chemicals and psychosocial stressors-implications for research on perinatal outcomes in the ECHO program. J Perinatol. 2020 Jan;40(1):10-24. doi: 10.1038/s41372-019-0510-y. Epub 2019 Oct 15. PMID: 31616048; PMCID: PMC6957228.
29.
Campbell JM, Lane M, Owens JA, Bakos HW. Paternal obesity negatively affects male fertility and assisted reproduction outcomes: a systematic review and meta-analysis. Reprod Biomed Online. 2015 Nov;31(5):593-604. doi: 10.1016/j.rbmo.2015.07.012. Epub 2015 Aug 10. PMID: 26380863.
