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Diagnostic evaluation & management of male infertility

Medically verified
Dr Héctor Izquierdo
Gynaecologist & Fertility Specialist
From this event you will find out:
  • What are the key parameters analysed in a spermiogram?
  • What are the different types of semen analysis, and how do they differ in their approach?
  • What is Comet Fertility, and how does it contribute to the assessment of sperm quality?
  • How does ChromoSperm analysis help in understanding genetic factors affecting male fertility?
  • When and why should semen and urine culture tests be conducted in the evaluation of male infertility?

Table of Contents - Quick Navigation

Dr Héctor Izquierdo, Gynaecologist & Fertility Specialist at Clínica Tambre discussed the latest advancements in male infertility diagnosis and treatment. He explained the complexities of male infertility and provided innovative approaches to help couples achieve their dream of parenthood.

Male infertility is responsible for 1 in every 3 infertility issues in families. It’s also a topic that often suffers from late diagnosis because, most of the time, fertility assessments are less accessible for men than for women. Women regularly visit gynaecologists, midwives, and nurses, so they are more aware and in touch with their fertility and health. Men, however, don’t typically visit andrologists or urologists regularly. They typically start going very late, so most people are not aware that male fertility might be an issue. Late diagnosis makes treatment more complicated. 50% of fertility issues can be related to the male factor, so it’s crucial to have a basic diagnosis for men.

A basic diagnosis includes semen analysis, karyotype, hormone tests if needed, and an examination of the male genitalia to ensure everything is functioning properly. A good anamnesis and thorough questioning about the patient’s history, such as ejaculation volume, are also important.

Basic diagnosis of male factor – assessment process

Most good fertility clinics offer assessments for both men and women. During the appointment, the first thing you need to do is ask questions about your previous history, such as whether your testicles took too long to descend, if any surgery was needed, or if there was any operation on the genitalia. Sometimes issues like pain in the testicles, lumps, or other structures can go unnoticed. In cases like these, some clinics allow you to go directly to an andrologist who is also a gynaecologist, or they offer a urologist’s assessment as part of the diagnostic process.

At Clínica Tambre, it is recognized that the male factor is an important aspect of fertility, therefore the embryology lab has been divided into 2 sections: an andrology laboratory and an IVF or egg laboratory. The andrology laboratory is busy all day addressing male factor issues. At Clínica Tambre, you’ll also find the oldest sperm bank in Spain. It is also crucial that patients are informed and empowered with information so they understand if there’s an issue, what the issue is, and how to deal with it.

Seminogram

The andrology lab is where we process, collect, assess, study, and treat sperm to be used in fertility treatments. The first assessment technique is the seminogram. The seminogram is an observational technique that allows us to evaluate three major factors:

  1. Concentration – how many sperm are in a sample?
  2. Total Volume – this is concentration multiplied by the volume of the sperm sample.
  3. Motility – how much of the sperm in the sample can move, divided into active motility (sperm that move properly in the right direction), reduced motility, and non-motility. The total motility percentage should be about 42-32%. The third factor assessed in sperm analysis is how many of the sperm look normal—these are the normal forms. This often concerns patients because the percentage of sperm with a normal structure can be low. This is due to male factor issues, as sperm production is not as structured or adequate as egg production.

A lot of sperm can be produced all the time, and in that very much production of sperm, failures can happen. A normal sperm sample has more than 4% normal sperm. Sperm samples can vary a lot; the samples are not always the same. Many factors can influence a sample, so each sample is different.

Advanced sperm assessment techniques

There are other things that we can study in the sperm in the andrology laboratory. Sperm carries DNA, and if you compare a picture of a sperm together with an egg, you’ll realize that the sperm is much smaller than the egg. They carry about the same amount of DNA material. That means that to fit that DNA material in that tiny space, the DNA in the sperm has to be rolled a lot so it can be squeezed in there, so it’s easy to break. Therefore, a certain amount of DNA fragmentation, or broken DNA in the sperm, is normal, but if it becomes too much, it becomes very complicated for the egg to take the DNA of the sperm, pull it back together, and start the first division and production of an embryo.

That’s why the DNA fragmentation assessment test is very important. It might allow us to choose a better technique to select those sperm with lower rates of DNA fragmentation to fertilize eggs, leading to better results. The techniques available to select sperm with lower DNA fragmentation rates depend on the situation—whether it’s a fresh sample, a frozen sample, or if it’s DNA fragmentation from a local strain or a single strain. You might have one or the other technique as the most efficient for you.

In the andrology laboratory, there is also a possibility of testing the male for hereditary diseases that they might not know they carry. If a patient needs a sperm sample because the couple doesn’t have a sperm quality that can be used in the treatment, whether due to repeated implantation failure or other issues or if it’s a couple of women or a single woman needing a sperm donor, it’s mandatory to ensure that all these factors are matched. This way, it’s possible to ensure that a baby will not be born with a genetic condition that could have been avoided.

Sperm analysis overview

How is the sperm analysis performed? Various aspects such as colour, viscosity, pH, concentration, motility, and morphology are evaluated. These factors are important.

  • sperm concentration is checked by counting sperm one by one using a microscope with squares on it. The number of sperm is counted in those squares, and then the average concentration is based on these counts.
  • sperm morphology, as I mentioned before, refers to the shape of the sperm. A normal sperm has a specific structure seen on the left side. However, it can have defects such as two heads, a large or small head, or a rounded shape. We know that a sperm lacking an acrosome, which is the cap on the front of the sperm responsible for penetrating the egg, cannot fertilize an egg.
  • the midpiece is the part responsible for making the tail move; it’s like the engine of the tail. If the midpiece is defective, the tail won’t move properly, affecting the sperm’s ability to swim. A tail that is too long, too twisted, or too short also hinders movement.
  • RIM test allows us to evaluate how well sperm will perform after concentration, which can improve concentration, motility, or sperm forms.

Terminologies of semen analysis

Understanding the terminology used in semen analysis is essential for accurately diagnosing and treating male infertility.

  • Aspermia: complete lack of semen, indicating no sperm production.
  • Azoospermia: the absence of sperm in the semen, meaning an empty ejaculation.
  • Asthenozoospermia: when less than 32% of the sperms are moving progressively, or overall motility is under 40%.
  • Oligospermia: sperm concentration below the desired level.
  • Necrozoospermia: more than 60% of sperms are dead in the sample.
  • Teratozoospermia: more than 4% of sperms have abnormal morphology.
  • Leukocytospermia: a high number of leukocytes (white blood cells) in the sperm, which could indicate an infection or inflammation.

Some of these conditions can be treated easily, for example, oligospermia (low sperm concentration) and asthenozoospermia. Azoospermia is a major challenge for fertility doctors, but if sperm production can be induced with hormone treatment, it may be possible to treat the condition. However, if the damage is to the stem cells responsible for producing sperm, there may not be much that can be done.

Complementary analyses

Other complementary analyses include DNA fragmentation tests, and Comet sperm, which is similar but checks the single strand of DNA. There are also culture tests to detect infections, which could be causing poor sperm quality. Treatment with antibiotics and anti-inflammatories may improve sperm quality.

If there is a genetic issue, such as high DNA fragmentation, techniques like PICSI (Physiological intracytoplasmic sperm injection) or IMSI (Intracytoplasmic Morphologically Selected Sperm Injection) are available, and they help to select the best sperm for fertilization, whether using fresh or frozen samples. Another test, FISH, helps us assess the percentage of sperm with normal chromosome numbers, which may indicate the need for further embryo testing.

Fertility enhancement approaches

Increasing fertility can involve various approaches, including antioxidant intake (vitamins E, C, D, and coenzyme Q10) or addressing underlying issues like inflammation or chronic infection. In some cases, problems with sperm transport from the testicle, as in cystic fibrosis, may require retrieving sperm directly from the testicles.

After diagnosis, the best approach is determined based on the specific needs of the patient. This could involve using a sperm DNA fragmentation technique, preparing the sperm in a certain way, or in some cases, using a sperm donor.

Related reading:

Diagnostic evaluation & management of male infertility | FAQ

High pH in sperm, other than it may indicate infection, are there any other indicators that may cause raised levels?

Yes, it may also be a sign of low sugar concentration in sperm, which can reduce motility. It may also indicate improper sperm production because if the pH is not adequate, there might be an issue with the testicles producing sperm. So, it’s not just a sign of inflammation; pH is a very important feature in sperm analysis.

I have had 3 rounds of IVF, 9 embryo transfers, and 3 IUIs. I only got implantation twice with IVF, but it ended in early loss. I’ve been trying for 8 years, and every month my tests came back normal. I ovulate, my tubes are open, and my husband had a normal sperm test, with morphology at 3%. I was able to get pregnant once before meeting my husband, but it ended in a 5-week loss. I recently tried again and got pregnant, but it ended in another 5-week loss. How can my husband have a normal test and not be able to get me pregnant? Any advice?

I’m very sorry to hear about your situation. It’s important to note that it’s not appropriate to place blame on either partner when it comes to fertility. Getting pregnant is a journey that both partners go through together. Many other assessments should be done, such as a DNA fragmentation test. A morphology of 3% is not normal and can be tested further. Age is also a factor, as it’s different trying to conceive at 25, 30, 35, or 38 years old.

Additionally, it’s crucial to check if both partners’ karyotypes are normal. In your specific case, since there have been multiple implantations but no successful pregnancies, other causes for repeated implantation failure or miscarriages should be investigated. Women’s fertility factors might also be involved in this situation.

Are “round cells” the same as leukocytes?

Yes, that is correct. Embryologists and doctors sometimes use different terms, but they often mean the same thing. Round cells are non-sperm cells, and they are mostly leukocytes. It could also be other cells, but when we refer to “round cells,” we generally mean leukocytes, which can be a sign of infection or inflammation.

What are the methods used to count the shape of spermatozoa and the percentage of normal shapes? What is the most reliable method? I have been told that my lab performs a visual analysis and count, so it’s not very reliable.

Yes, you are right; assessing the shape of sperm is a rather subjective process. However, when a sample is taken, some features must be assessed. The sperm are counted in a way that is statistically representative of the whole sample. While the analysis is observational and somewhat subjective, it’s still a good way to assess sperm shape.

Currently, we don’t have other techniques like flow cytometry that could identify sperm shapes more precisely. We are working on artificial intelligence tools to assess the whole sample actively, but this is complicated because the sample used cannot be frozen for later use. We sometimes freeze a sample that has been assessed, which allows us to use the best technique for fertilization later. This is important because the characteristics of a sperm sample can vary.

If there is 60% DNA fragmentation in sperm cells, what could be the cause of this, and is it still possible to achieve pregnancy naturally? My partner is 39 and has chronic inflammation, chronic infection, and autoimmune diseases.

In this specific case, we might be better to consider aspirating sperm from the testicles because they are in a more immature form there. It’s important to understand that the main role of sperm in fertility is to provide DNA to the egg. Therefore, aspirating sperm from the testicles in their very fresh and mature form may help avoid issues related to high DNA fragmentation.

How problematic is 1% normal shape in sperm? Here are the other parameters: volume 3.9, pH, etc. Anything in this specific case, knowing that the only issue is the normal forms, would this be something easy to treat?

Yes, this would be something easier to treat because we have normal concentration and normal motility. Progressive motility is outstanding, so in those terms, picking the 5, 10, or 15 sperm needed to achieve fertilization out of 22 million can work.

What is the purpose of medication like Clomid and HCG?

One reason for sperm issues might be a hormonal imbalance. Just as women have FSH, men do too, and this FSH should go from the brain to the testicles and stimulate the Sertoli and Leydig cells to produce sperm. If FSH is low, then using Clomid as a GnRH analogue will go to the hypothalamus and promote the production of FSH, which will then go to the testicles to promote sperm production and quality. That’s the reason for Clomid, and HCG do the same.

My doctor suggested trying normal IVF with ICSI despite 1% normal shape and 98% abnormal shape of the sperm head. I’m sceptical about the success rates, but he says ICSI has a high risk of miscarriage. What are your thoughts?

First, there aren’t many clear things in infertility, but this is one of them: 1% of normal forms are a clear indication of ICSI. IVF might lead to fertilization failure, and if the egg does not fertilize, it is a lost egg, which we cannot afford. Studies claiming that ICSI increases the risk of miscarriage should be taken very carefully. These concerns mostly refer to ICSI in cases where eggs are not genetically tested, especially in women over a certain age.

After 35, it is good to perform ICSI together with PGT-A testing of embryos to avoid miscarriages due to genetic abnormalities. We need the best laboratory assessment to produce the maximum number of embryos and then select the best ones. Claiming that with just one embryo, the best one is dangerous and can lead to more cycles, which is inconvenient. The best cycle is the most accurate one to produce the maximum number of eggs, and then we select the best embryos once we have them.

Can you explain karyotype and compatibility? If we both do our karyotypes, how can we interpret compatibility or incompatibility?

There is no such thing as “karyotype compatibility.” A karyotype is either normal or not normal. What they might be referring to is genetic matching or genetic incompatibility, which involves checking for recessive mutations. Recessive mutations do not show unless 2 carriers pass them on together. When we do genetic matching, we check both parties for any recessive mutations that, if combined, could result in a baby with a medical condition.

Is there anything that can be done to improve the shape of sperm to have a higher percentage of normal shapes?

There are some theories suggesting that sperm produced in the testicles might be damaged due to obstruction or chronic inflammation, resulting in sperm with defects. Reducing inflammation, checking for obstructions, and treating conditions like prostatitis may help improve sperm shape.

If the percentage is high, is there anything we can do to reduce DNA fragmentation?

As I said before, one of the causes of DNA fragmentation might be the unpacking of the DNA in the sperm. Another cause of high fragmentation could be oxidative stress, which includes too much stress, inflammation, or infection. Once again, checking for infections, reducing oxidative stress, and avoiding bad habits like smoking, tight underwear, very hot baths, and long bike rides can help. Reducing inflammation taking vitamins, eating healthy, and wearing loose underwear are all measures that can increase sperm quality.

Are there any supplements you might suggest?

The clinical indications for supplements are as follows: Vitamin C 1000 mg/day, vitamin E 600 units, Coenzyme Q10 (Ubiquinol) 200 mg. DHA or Omega-3, and Omega-6 are also indicated. Any of these supplements are very beneficial.

What if there is low sperm count after a vasectomy reversal—what can help?

We need to understand the morphology of the sperm’s conduct. Once you cut the tubes that carry sperm from the testicles to ejaculation, trying to rebuild them might work, but it can produce a scar, making it difficult for sperm to pass through. In such cases, I would recommend TESE (testicular sperm extraction), both as a diagnostic and a treatment technique. If we find better concentration in the sperm when taken from the testicle, we will know the issue. I’m not a huge fan of vasectomy reversal for patients trying to get pregnant unless the woman is very young, say under 35 years old. Otherwise, TESE and IVF are often the better option because it’s a single procedure.

I’ve been told there’s no need to do a DNA fragmentation test since we have to do ICSI due to very low sperm count and low motility. What are your thoughts?

We can have both low sperm count, low motility, and high DNA fragmentation. Some techniques work with a small amount of sperm concentration. For example, sperm is slow, which allows us to do DNA fragmentation selection with a very small amount of sperm. Therefore, it’s false to assume a DNA fragmentation test is unnecessary.

Are supplements for women also effective for men?

Yes, some supplements that are useful for women are also useful for men. Fertility is a shared issue, and it’s important to consider male fertility as well when discussing options and treatments.

Regarding DHEA, do you need a prescription for it?

DHEA is used by many women to help preserve egg quality. DHA (docosahexaenoic acid) is Omega-3, which is a normal fish oil acid. DHEA does need a prescription in many countries, but it’s not indicated for men.

Could you tell us which supplements are good for men what doses?

The supplements I mentioned earlier are vitamin C 1000 mg/day, vitamin E 600 units, Coenzyme Q10 (Ubiquinol) 200 mg, DHA/Omega-3, and Omega-6. These are recommended for improving sperm quality.

Does DHEA increase the number of follicles?

DHEA may affect the antral follicle count or the number of eggs retrieved. Some studies claim it helps in the maturation of eggs during stimulation, but the number of eggs is an absolute number that women are born with and can’t be affected by medical treatments. While DHEA might increase the ovarian response and egg maturation, it doesn’t increase the total number of eggs. Stem cell therapy and PRP therapy are very critical at the moment, and we haven’t had positive results so far.

Could you clarify what CoQ10 (200 mg) is?

CoQ10 is one of the most used vitamins in fertility. It’s a supplement that increases antioxidant activity, improves metabolic activity, and is good for blood sugar issues, overweight, and enhancing the quality of both eggs and sperm. CoQ10 is also known as Ubiquinol.

Is Zymot recommended for improving sperm quality?

Zymot is a very new technique and is only indicated if there is high DNA fragmentation. If no sperm issues are found and DNA fragmentation isn’t tested, using Zymot might reduce the number of motile, normal sperm, making the work harder with no extra benefit. Therefore, if there’s no indication of its use, it’s not recommended.

When is DNA fragmentation considered high?

The value considered high depends on the test performed. For example, if you’re using an AO (Acridine Orange) and Flow Cytometry test, it’s around 16%. For other techniques like the Comet assay, it could be 30% or 40%, depending on whether you’re doing ICSI or normal IVF. There’s no single value—it depends on the test you’re using.

 

 

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