IVF Techniques For Treatment of Male Factor Infertility Explained

What is Male Factor Infertility? What IVF Treatments Have Been Developed to Treat It?

“Many men assume that a woman’s ability to produce eggs that can be fertilized by the male is not something they personally need to worry about. But the fact is that in around a third of infertility cases the failure of a couple to conceive a child is due to a problem on the male side,” says Tomáš Rieger, Ph.D., embryologist at Gynem Fertility Clinic.

If the woman also has a fertility problem then the chances of not conceiving at all can significantly increase. IVF treatments for women are many and varied but did you know that a variety of IVF techniques have also been developed to help solve or reduce male problems with infertility? You may be surprised and a bit perplexed, but sit back, relax, and we’ll go through some of the currently available techniques.

ICSI (Intracytoplasmic Sperm Injection)

As the name might suggest this method involves the direct injection of a single sperm directly into an egg. ‘Cutting to the chase’ as it were, this method increases the chances of a successful fertilization where the natural process of conception has not been successful because of issues such as low or absent sperm count (azoospermia), poor sperm motility (liveliness!) or some abnormality, perhaps genetic, in the sperm itself.

The ICSI Procedure

ICSI can be integrated into the standard IVF procedure, as follows:

1. Ovarian Stimulation and Egg Retrieval: The female partner undergoes hormonal stimulation to encourage the ovaries to produce multiple eggs. Mature eggs are then retrieved through a minor surgical procedure under ultrasound direction.
2. Sperm supplied by the male partner is collected. Or, if necessary, it can be extracted directly from the testes – painlessly I hasten to add – through a small incision (TESE: Testicular Sperm Extraction). The sperm is processed in the laboratory and the most viable (healthiest) sperm is selected for injection.
3. This prize-winning sperm is injected directly into the cytoplasm (the inside) of the female’s mature egg using a tiny needle (a micropipette).
4. Fertilization: The injected egg or eggs are then placed in an incubator to allow fertilization to take place. After fertilization the embryos are cultured (basically, nourished and observed) for 3 to 5 days and then assessed for quality.
5. Embryo Transfer: The healthiest embryos are chosen and transferred to the woman’s uterus. Any high-quality embryos remaining can be frozen for future use.
6. Pregnancy Test: 10 to 14 days after transfer a blood sample is taken to check for pregnancy.

It sounds pretty straightforward, but what are the pros and cons?

Pros of ICSI

1. High Success Rate: As mentioned above, where the main problem is with male factors like low or absent sperm count, poor motility, or damaged sperm, ICSI significantly improves the chances of successful fertilization.
2. Applicable for Severe Cases: ICSI can be effective even when only a small number of viable sperm are available.
3. Fertilization Control: As the sperm is injected directly into the egg, the sperm is spared the hazardous journey into the woman’s ovaries and the necessity of breaking into the egg.
4. Versatility: ICSI can be used in conjunction with frozen or thawed eggs and sperm, allowing a lot of flexibility in treating any other fertility problems.

Cons of ICSI

1. Cost: ICSI is generally more expensive than traditional IVF due to the specialized skills required.
2. Complexity: The requisite technical expertise, involving specialized equipment, might not be available at many fertility clinics.
3. Success Not Guaranteed: While ICSI can improve fertilization rates, there’s no guarantee of a successful pregnancy. The success of the treatment is still dependent on factors such as egg and sperm quality, and the woman’s overall uterine condition.

Any and every medical procedure involves a level of risk, so what risks are involved in ICSI?

Risks of ICSI

1. Potential for Birth Defects: Some studies have indicated a slightly higher risk of birth defects with ICSI, though these risks are generally low.
2. Egg Damage:  The process of injecting sperm directly into an egg can sometimes damage the egg, this may prevent fertilization or affect the development of the embryo.
3. Multiple Pregnancies: As with standard IVF, ICSI can lead to multiple pregnancies if multiple embryos are transferred, increasing the risk of complications such as preterm birth or low birth weight.
4. Physical and Emotional Stress: ICSI treatment can be physically and emotionally demanding on a couple, particularly the hormonal treatments involved in preparing the woman’s ovaries and the egg retrieval process. Though this kind of stress is no more common than in standard IVF and other male fertility treatments.

Overall, according to The American Society for Reproductive Medicine:

“ICSI has been associated with increased fertilization rates and decreased risk of failed fertilization in some studies.”

IMSI (Intracytoplasmic Morphologically Selected Sperm Injection)

Don’t be put off by this miles-long definition. It’s basically ICSI, only a more highly developed version. ‘Morphologically Selected’ just means  that sperm is selected according to its form and structure. With IMSI the sperm is subjected to highly detailed scrutiny by a very high-powered microscope. Obviously with the aim of selecting the ‘crème de la crème’ of a man’s sperm, to multiply the chances of a successful egg fertilization and healthy embryo development.

The IMSI Procedure

IMSI follows the same general procedure as ICSI, there is just the difference of the ‘morphological’ element. So we’ll just highlight that step. Here we go:

1. Ovarian Stimulation and Egg Retrieval
2. Sperm Supplied by partner selected
3. Morphological Selection of Sperm: Using a high-magnification microscope (up to 6,000 times, compared to 200 to 400 times in standard ICSI) the embryologist rigorously examines individual sperm cells and chooses only the absolute fittest (in terms of shape, size, structure) for injection into the egg. MSOME: Motile Sperm Organelle Morphology is the acronym for this, most crucial part of the procedure.
4. Fertilization
5. Embryo Transfer
6. Pregnancy Test: after 10 – 14 days

Pros of IMSI

1. Increased Chance of Fertilization: By allowing embryologists to pick out the best-quality sperm, based on detailed morphology, the chances of fertilization and improved embryo quality are higher.
2. Improved Pregnancy rates: Some studies suggest that IMSI can lead to higher pregnancy and live birth rates compared to standard ICSI, especially in situations involving severe male factor infertility or previous IVF failure.
3. Lower Miscarriage Rates:  Enhanced sperm selection may reduce the risk of miscarriage, as only the healthiest sperm are used.
4. Useful in Recurrent IVF Failures: IMSI is often recommended for couples who have, sadly, experienced multiple failed IVF cycles, as this technique addresses sperm-related issues that may be the cause of such failures.

In a study published in Reproductive Biology and Endocrinology produced by Katja Knez, Branco Zorn et al in 2011:

“The IMSI procedure improved embryo development and the laboratory and clinical outcomes of sperm microinjection in the same infertile couples with male infertility and poor embryo development over the previous ICSI attempts.”

 Cons of IMSI

1. Increased Cost: IMSI can incur additional cost than ICSI due to the extra examination time needed, level of expertise and equipment (those 6,000 magnifications!) required for sperm selection.
2. Time-Consuming: the detailed examination and assessment of sperm morphology is incredibly labour-intensive, which can extend the time needed for the procedure. But, considering the end goal, time worth paying for.
3. Limited Availability: Again, not all fertility clinics offer IMSI, due to the cost and acquisition of trained operators for the equipment.
4. No Guarantee of Success: While IMSI may improve the chances of successful fertilization, there is no guarantee of pregnancy, other factors including egg quality and the woman’s overall health are still very important.

MACS (Magnetic Activated Cell Sorting)

MACS is an advanced sperm selection technique, specifically designed to improve sperm quality by separating healthy, viable sperm from sperm which is apoptotic, that is, likely to die, or which have weak DNA structure.

“The technique harnesses magnetic fields to target and remove sperm cells with markers indicating poor health, leaving only the healthiest for fertilization,” explains Tomáš Rieger, Ph.D., embryologist at Gynem Fertility Clinic.

This method is ideal for women with poor embryo quality or who have endured several miscarriages, and for men diagnosed with a high rate of DNA sperm fragmentation. It can also benefit older men who have exceeded a certain age.

MACS – The Procedure

1. Ovarian stimulation and egg retrieval
2. Sperm Collection: Sperm is collected through ejaculation or, if necessary, directly from testes using a procedure such as TESE (Testicular Sperm Extraction).
3. MACS Sperm Sorting:
   • Labeling of Apoptotic Sperm: The collected sperm is first incubated with a reagent (Annexin V) a protein which binds to phosphatidylserine, a marker for apoptosis.
   • The treated sperm is passed through a magnetic filter. The marked cells remain in the filter and the healthy sperm cells through and collected.
   • Once collected the sperm is then prepared for its task of fertilization.
4.  Fertilization: This high-quality sperm is used to fertilize the retrieved eggs, either through standard IVF, in which sperm and eggs are incubated together, or ICSI, detailed above.
5. Embryo Culture: The fertilized eggs are cultured for 3 – 5 days.
6. Embryo transfer: The best quality embryos are selected and transferred to the woman’s uterus.
7. Pregnancy test: After 10- 14 days.

Pros of MACS

1. An enhanced selection of high-quality sperm and embryos
2. There is, potentially, a reduction in miscarriage rates.
3. The procedure also potentially improves the success rate in IVF cycles.
4. It can contribute to the healthy formation and development of embryos.

Cons of MACS

1. Once again, not all fertility clinics are able to afford the expensive equipment necessary, and treatment can be costly for couples.
2. Successful birth is not guaranteed, though this applies to most IVF and male fertility treatments.

A recent study from 2020, by Alberto Pacheco, Arancha Blanco et al, published in The Journal of Clinical Medicine, concluded that:

“The MACS sperm selection of human spermatozoa is a safe, easy, and suitable method for sperm preparations for ICSI use in a clinical setting. Results presented in this study indicated that the MACS selection technique may help to improve reproductive outcomes…”

PICSI (Physiological Intracytoplasmic Sperm Injection)

PICSI is a variant of standard ICSI (see above), but it enhances ICSI by using a method that selects sperm based on their ability to bind to hyaluronic acid, a chemical naturally present in the outer layer of a woman’s egg. Sperms that can attach themselves to hyaluronic acid are typically more mature and genetically strong and cohesive, and thus improve fertilization rates and embryo quality. PICSI can be recommended for males with a high rate of sperm DNA fragmentation or couples experiencing some unexplained form of infertility. It is also recommended in cases of repeated miscarriages, previous failed IVF cycles or couples with several failed IVF attempts behind them.

PICSI – The Procedure

1. Ovarian Stimulation and Egg Retrieval.
2. Sperm supplied by the male partner is collected: through ejaculation or TESE.
3. PICSI Sperm Selection:
   • Hyaluronic Acid Binding (HAB): the sperm is deposited in a special dish coated with the acid gel which mimics the environment of an egg’s outer layer.
   • Selection of Mature Sperm: only sperm with receptors for the acid will bind to the gel – those with less chromosomal abnormalities and DNA fragmentation. The bound sperm are then selected for the next step.
4. ICSI Procedure: these healthier sperm are suitable for direct injection into the cytoplasm of mature eggs using the standard ICSI procedure (detailed above).
5. Embryo Culture: The fertilized eggs are cultured for 3 – 5 days
6. Embryo transfer: The best quality embryos are selected and transferred to the woman’s uterus.
7. Pregnancy test: After 10- 14 days.

Pros of PICSI

1. Improved sperm selection.
2. Higher Fertilization and Pregnancy Rates
3. Reduced risk of genetic abnormalities in resultant embryos: PICSI selected sperm are more likely to have normal chromosomal structure due to higher sperm quality.
4. Lower miscarriage rates: some studies suggest that PICSI contributes to lower miscarriage rates.
5. A More natural selection process: PICSI mimics a natural selection process by relying on the sperm’s ability to bind to hyaluronic acid.

Cons OF PICSI

1. Increased cost: PICSI is generally more expensive than standard ICSI because of the additional steps and the specialized equipment necessary for sperm selection.
2. Limited Availability: Not all fertility clinics offer PICSI, due to the expense and specialist expertise required, though there are specialized clinics which offer the procedure.
3. No Guarantee of Success: PICSI can improve the chances of fertilization and a healthy embryo, but of course, as we’ve already established, pregnancy cannot be guaranteed with any procedure.
4. Time Consuming: The additional steps necessary with PICSI can lengthen the IVF process.

A study carried out in 2020 by Roisin Ni Dhuifin and Darren K. Griffin et al. published in DNA concluded that:

“While there is little evidence to suggest that HAB-sperm selection improves fertilization or live birth rates, this technique reportedly improves the incidence of pregnancy loss following ART (Assisted Reproductive Technologies) in an unselected infertility population.” Though the researchers admit that “the results of this study are probably impacted by low study quality.”

TESE and MESA

We’ve already mentioned the first two of this hip-sounding trio, but as they are closely related let’s look at them together.

TESE (Testicular Sperm Extraction) and MESA (Microsurgical Epididymal Sperm Aspiration) are surgical procedures used to retrieve sperm directly from the testes or epididymis in cases of male infertility, particularly when there is no sperm present in the ejaculate (azoospermia) or when sperm cannot be retrieved through more conventional means.  Azoospermia is associated with up to 20% of male infertility cases, and can act as a real obstacle to effective IVF.

As we’ve seen above these procedures are commonly used in tandem with Intracytoplasmic Sperm Injection (ICSI) in IVF cycles.

TESE: This procedure involves making a small incision in the testes and directly extracting small amounts of testicular tissue, from which sperm can then be isolated.

MESA: Here sperm are retrieved from the epididymis, a coiled tube where sperm mature and are stored, using microsurgical techniques.

The Procedure:

TESE and MESA are typically performed when a male partner has obstructive or non-obstructive azoospermia. They are usually carried out in an outpatient setting under local anaesthesia, sedation, or general anaesthesia. Here’s how they fit into the IVF/ICSI process:

1. Ovarian Stimulation and Egg Retrieval (Female Partner): The female partner undergoes ovarian stimulation to produce multiple eggs, which are retrieved via a minor surgical procedure.
2. Sperm Retrieval (Male Partner):
   • TESE: After administering anaesthesia, the surgeon makes a small incision in the scrotum and testis to access the testicular tissue. Small biopsies are taken, and sperm are extracted from these tissue samples.
   • MESA: Using a surgical microscope, the surgeon carefully opens the epididymis and aspirates fluid containing sperm. This method is often used when there is a blockage preventing sperm from entering the ejaculate.
3. Sperm Processing: The retrieved sperm are processed and assessed in the laboratory. If viable sperm are found, they are prepared for injection into the eggs.
4. ICSI Procedure: The retrieved sperm are injected directly into the cytoplasm of the retrieved eggs, increasing the likelihood of fertilization.
5. Fertilization and Embryo Culture
6. Embryo Transfer
7. Pregnancy Test: Approximately 10-14 days after the embryo transfer to confirm pregnancy.

Pros, Cons, and Risks of TESE and MESA Procedures

TESE (Testicular Sperm Extraction)

Pros:

1. Direct Sperm Retrieval: TESE allows for the extraction of sperm directly from the testicular tissue, which can be critical for men with azoospermia (absence of sperm in the ejaculate).
2. Useful for Non-Obstructive Azoospermia: It is particularly effective in cases of non-obstructive azoospermia where sperm production is impaired but not completely absent.
3. Possibility of Sperm Production: TESE can identify areas in the testicular tissue where sperm production is ongoing, even in cases of very low sperm count.

Cons:

1. An invasive Procedure: TESE requires a small incision in the scrotum, which may lead to postoperative discomfort and longer recovery time compared to less invasive methods.
2. Lower Sperm Yield: The procedure may yield a limited number of viable sperm, especially in cases of severe spermatogenic failure.

Risks:

1. Infection: As with any surgical procedure, there is a risk of infection at the incision site.
2. Bleeding and Haematoma: There is a risk of bleeding or formation of a haematoma (blood clot) in the scrotum.
3. Scarring: The incision may lead to scarring, which could potentially affect testicular function or future fertility.

MESA (Microsurgical Epididymal Sperm Aspiration)

Pros:

1. High-Quality Sperm Retrieval: MESA is effective for obtaining high-quality sperm from the epididymis, which can be beneficial for IVF/ICSI.
2. Less Invasive than TESE: MESA is less invasive than TESE and involves using microsurgical techniques to access the epididymis through small incisions.

Cons:

1. Requires Specialized Skills: MESA requires specialized microsurgical skills and equipment, which may not be available at all fertility centres.
2. Potential for Scar Tissue: Repeated procedures can lead to scar tissue formation, potentially affecting future sperm retrieval.

Risks:

1. Surgical Risks: As with any surgical procedure, there are risks of infection, bleeding, and complications related to anaesthesia.
2. Long-Term Impact: There is a potential risk of long-term effects on the epididymis, which could impact sperm transport and future fertility.

The NHS (National Health Service) in the UK concluded in 2016 that

“there is sufficient evidence to support a proposal for the routine commissioning of MESA for males with obstructive azoospermia and TESE for males with non-obstructive azoospermia to assist conception.”

SpermMobil in IVF Treatment

This slightly odd-sounding name refers to a specialized medium used to enhance sperm motility in cases of male factor infertility. It is designed to improve the movement of sperm, making them more capable of reaching and fertilizing eggs. SpermMobil is a unique solution that optimizes the environment for sperm motility and functionality. It is particularly useful in cases where sperm have low motility, which can significantly impact fertilization rates. And also for men who have undergone sperm retrieval procedures like TESE, SpermMobil can optimize the motility of the retrieved sperm. Doctor Tomȧṥ Rieger of the Gynem Clinic is enthusiastic:

“SpermMobil is a medium which contains theophylline and other constituents that, for a short time, accelerate the movement of otherwise immobile sperm. This serum usually helps when sperm has been extracted surgically from the testis (TESE) because some sperm may move very little, if at all, but retain the health and capability to produce a baby. The energizing effect of SpermMobil can therefore help us to identify slow, but still living and viable sperm for ICSI treatment. Using this medium, we can avoid the risk of overlooking healthy sperm simply because it appears dead at first glance,” explains Tomáš Rieger, Ph.D., embryologist at Gynem Fertility Clinic.

The Procedure

1. Ovarian Stimulation and Egg Retrieval
2. Sperm Collection: Sperm is collected from the male partner. In cases of severe male factor infertility, sperm may be extracted directly from the testes or epididymis using procedures like TESE or MESA.
3. Sperm Preparation with SpermMobil:
   • Sperm Processing: The collected sperm is mixed with SpermMobil, a medium designed to enhance sperm motility. This medium provides nutrients and a supportive environment that helps improve the movement of sperm.
   • Motility Enhancement: Spermmobil optimizes the sperm’s ability to swim and move effectively, increasing their chances of reaching and fertilizing the egg.
4. ICSI Procedure: The enhanced sperm, prepared with SpermMobil, are then used in the Intracytoplasmic Sperm Injection (ICSI) procedure. A single washed sperm is injected directly into the cytoplasm of the egg to facilitate fertilization.
5. Fertilization and Embryo Culture: After injection, the eggs are cultured to allow fertilization and embryo development. The embryos are monitored for quality and development.
6. Embryo Transfer: The best-quality embryos are selected and transferred into the woman’s uterus. Any remaining viable embryos can be frozen for future use.
7. Pregnancy Test: After approximately 10-14 days after the embryo transfer to confirm pregnancy.

SpermMobil – Pros, Cons, and Risks

Pros:

• Enhanced Sperm Motility: SpermMobil improves sperm movement, which can be particularly beneficial for cases of low sperm motility (azoospermia).
• Increased Fertilization Rates: By optimizing sperm motility, SpermMobil can enhance the chances of successful fertilization, leading to higher pregnancy rates.
• Supportive Environment: The medium used in SpermMobil provides a supportive environment for sperm, potentially improving their overall functionality.

Cons:

• Not a Standalone Solution: SpermMobil is not a cure for all male infertility issues; it is specifically aimed at improving sperm motility and may not address other underlying causes of infertility.
• Additional Cost: The use of specialized media like SpermMobil can increase the overall cost of the IVF treatment.

Hormonal Treatments for Male Infertility

There are also certain medications that can be used to address hormonal imbalances that may be affecting sperm production and quality.

The Procedure

Hormonal treatments are prescribed based on specific diagnoses, such as low testosterone levels (hypogonadism) or other hormonal issues affecting sperm production.

Pros:

• Can improve sperm count and quality in cases where hormonal imbalances are identified.
• Non-surgical approach to addressing some infertility issues.

Cons:

• Effectiveness varies based on the underlying cause of infertility.
• May require ongoing monitoring and adjustments.

Risks:

• Possible side effects from hormonal medications.
• Hormonal treatments may not resolve all fertility issues.

Male Factor Infertility – Prevention is Better Than Cure?

There definitely is some truth in the old proverb. With recent studies from around the world confirming that the habits of modern life can reduce the number and quality of male sperm, it makes sense for men to look after their health, as male fertility – or spermatogenesis – can be enhanced by a healthy lifestyle. She here are a few areas we can all look at:

• Smoking: stop if you can, reduce if you can’t as smokers accumulate heavy metals in the body which inhibit the repair work done by our DNA.
• Reduce alcohol consumption: alcohol negatively affects the function of the pituitary gland, which regulates the hormones involved in spermatogenesis.
• Recreational drugs: there are better forms of recreation chaps: tennis, football, the gym for example.
• Stress and lack of sleep: find ways, such as mindfulness, meditation, or just a slow walk in the country to reduce stress and improve sleep patterns. Lack of sleep and stress has a direct impact on testosterone production.
• Obesity: being overweight has negative health impacts across your whole organism

You can also help your fertility with a healthier diet and a visit to the chemist and treating yourself to some

• vitamins and supplements such as vitamin C, B12, zinc, selenium, vitamin D, folate, acetyl coenzyme Q10.
• herbs: ground anemone, St. John’s Wort, two-lobed ginseng.

We hope that this article has helped you to make the right treatment decision on your way to becoming a father. If you have more questions about any of the above techniques, we recommend speaking with a male infertility specialist at Gynem Fertility Clinic.

 

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922320/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185595/

https://academic.oup.com/jcem/article/82/3/709/2656193

https://www.sciencedirect.com/topics/medicine-and-dentistry/in-vitro-fertilisation