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How can IVF, IMSI, MACS, PICSI, or other procedures help with the male factor problem?

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8 fertility expert(s) answered this question

Answer from: Saghar Kasiri, Clinical Embryologist

Embryologist, Director of European Operations
Cryos International
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Usually ICSI or micro injection is used for male infertility however, if we have had IVF cycles that have failed, failed fertilization, is one big factor that also tells us next round we need to use ICSI. Sometimes the egg and the sperm don’t bind with each other so, where we put an egg for an IVF with, for example, a hundred thousand sperm, we see hardly any sperm attached to the shell or the zona of the egg. As a result of this lack of binding what we call, we can decide that we would proceed with an ICSI next round. Sometimes, we also see that the one sperm only getting inside the egg, more than one sperm frequently getting inside the egg is what we call polyspermic fertilization – in that case also this is an indication that we need to intervene and next round do ICSI. So ICSI is not just purely used for male infertility, it is also used in what we have called failed fertilization as well. For some genetic testing as well we use ICSI, for example, if we are doing PGD, we want to make sure that there’s only one sperm that has penetrated the egg and formed the embryo we regularly use ICSI to make sure that there is no other sperm attached to the zona of the embryo when we want to test it for genetic diseases.

Answer from: Andrew Thomson, FRCPath

Embryologist, Consultant Clinical Embryologist & Laboratory Manager
Centre for Reproduction and Gynaecology Wales (CRGW)
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PICSI an interesting one. PICSI is another variation of ICSI like IMSI but the difference is there’s a special protein mixed with the sperm. It’s actually in the dishes and it’s a protein called hyaluronan and the mature sperm with the best intact DNA, will actually bind to this hyaluronan and the immature sperm or the sperm that’s not as good or highly fragmented sperm, doesn’t bind to it. So when you’re doing the PICSI procedure and you’re selecting your sperm, you only select those sperm that are bound and that way you’re putting in the sperm with the highest intact DNA. There was a recent multi-sited randomized controlled trial which looked to see whether it increased live birth rate, which it didn’t, hence why it is red lighted by the HFEA but it did find a significant reduction in miscarriage rates and which is a really interesting finding but because that wasn’t the primary end point of the study, that’s not what they were looking for the HFEA won’t amber lighted, it the only red light it because that wasn’t what they were looking for, they just found it by chance. So there is some indication that PICSI would be of benefit but again it would only be for those men who have had a DNA fragmentation and shown an elevated results but yeah it’s an interesting topic and certainly I think it will pick up more credibility over the next few years.

Answer from: Alexia Chatziparasidou,  MSc, PMI-RMP

Embryologist, Consultant Clinical Embryologist, Director of Embryolab Academy, Co-Founder of Embryolab Fertility Clinic
Embryolab Fertility Clinic
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Every technique has its own unique characteristic. All of them belong to our clinical embryologists tool box and it is upon us to choose what is best for our couples in terms of improving their chances for a successful outcome. So, in my opinion, I would say that each case, each couple may have unique characteristics and that we have to adapt our approach for treating, preparing, washing and selecting the sperm according to these characteristics in a tailor-made fashion.

Answer from: Yacoub Khalaf, Professor

Gynaecologist, Professor of Reproductive Medicine and Surgery at King’s College
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These are all experimental techniques really. Their place is in research laboratory until they are validated. I will be reluctant to advocate using something experimental that’s not validated to pay a lot of money and without really much return.

Answer from: Alessandra Parrella

Embryologist, Andrologist, Embriologist
IVF-Life Group
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PICSI is a procedure that is utilized in men with high DNA fragmentation. In this case in laboratory, the spermatozoa is mixed with hyaluronic acid and only spermatozoa that attach to hyaluronic acid are selected to be injected in the oocytes because only the spermatozoa that interact with the hyaluronic acid is the one that do not present any fragmentation, any damage in the DNA.

Answer from: Ruth Sánchez, MD

Gynaecologist, Fertility Specialist
UR Vistahermosa
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IMSI, basically, consists of making a preliminary selection of the sperm through a microscope 15 times more powerful than those that are usually used to perform ICSI. Although this improvement in sperm selection could make us think about an increase in pregnancy and implantation rates and a decrease in the rate of abortions, the reality is different. Some studies have shown the ineffectiveness of this technique in the selection to improve pregnancy rates. Besides, it is a very expensive method that requires too much time searching for sperm, which harms the oocyte to microinject.

Currently, IMSI is a technique that needs well-designed studies to show us with sufficient scientific evidence if it works for a certain group of patients. For now, its validity is limited to the commercial marketing of the centre that offers it.

PICSI is another technique that involves placing the sperm on an ICSI plate, treating it with a synthetic material similar to the characteristics of the pellucid zone of the oocyte so that mature sperm that isn’t so damaged in terms of DNA will remain attached to this synthetic material. Subsequently, the sperm is recovered to be used for microinjection, which is an old method easily performed with the current technique of straining through Annexin columns that select non-apoptotic sperm without going through these methods. It’s important to say that the Annexin selection is cheaper than PICSI, and the rate of pregnancy success is similar.

Answer from: Aldo Isaac Meneses Rios, MD

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IMSI basically consists of making a preliminary selection of the sperm through a microscope 15 times more powerful than those that are usually used to perform ICSI. Although this improvement in sperm selection could make us think about an increase in pregnancy and implantation rates and a decrease in the rate of abortions, the reality is different. Some studies have shown the ineffectiveness of this technique in the selection to improve pregnancy rates. Besides, it is a very expensive method that requires too much time searching for sperm, which harms the oocyte to microinject.

Currently, IMSI is a technique that needs well-designed studies to show us with sufficient scientific evidence if it works for a certain group of patients. For now, its validity is limited to the commercial marketing of the centre that offers it.

PICSI is another technique that involves placing the sperm on an ICSI plate, treating it with a synthetic material similar to the characteristics of the pellucid zone of the oocyte so that mature sperm that isn’t so damaged in terms of DNA will remain attached to this synthetic material. Subsequently, the sperm is recovered to be used for microinjection, which is an old method easily performed with the current technique of straining through Annexin columns that select non-apoptotic sperm without going through these methods. It’s important to say that the Annexin selection is cheaper than PICSI, and the rate of pregnancy success is similar.

Answer from: Evi Timotheou, BSc, MSc

Embryologist, Lab Director
Assisting Nature
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Sperm selection before fertilization is a crucial step for IVF success. When the male factor is present, among other fertility causes, selecting the best and most prominent sperm can be challenging. Such cases require a different approach. As a result, there are several techniques utilized, and each of them has a purpose. To select the optimal sperm, the most common techniques used for this purpose are:

  • Intracytoplasmic morphologically selected sperm injection called IMSI
  • Physiological Intracytoplasmic sperm injection called PICSI
  • Magnetic activation cell sorting called MACS
  • A hypo-osmotic swelling test called HOS
  • Fertile microfluidic sperm sorting chips

Apart from these techniques, others are not used so often. A method that allows the intracytoplasmic injection of morphologically selected sperm is called IMSI. The sperm image is maximized up to 6,600 times allowing the embryologist to choose only the ones that are the healthiest and have the best morphology. Finding from IMSI imaging helps to discard spermatozoa with mitochondrial dysfunction or DNA damage and helps to identify spermatozoa with a normal nucleus and nuclear content.

IMSI can contribute to improving the success rates of patients who appear to have bad sperm morphology and have been diagnosed with Oligo-asthenoteratozoospermia. According to studies, it has been shown that this particular method can lead to better fertilization rates, better embryo quality, and, as a consequence, better pregnancy rates. Besides, IMSI is a useful technique for couples with unexplained infertility or couples with repeated implantation failures.

Another method is PICSI. PICSI offers new assessment criteria for sperm selection as it is based on the ability of the sperm to bind to the hyaluronic acid. Specifically, in this method, special dishes are used which contain special culture media with hyaluronic acid. When the sperm sample is added to the dish, only the spermatozoa with the best quality can bind to the acid and, as a consequence, are sorted by the embryologist for micro-fertilization. The principle of the method is based on the fact that hyaluronic acid naturally occurs in the substance that surrounds the oocyte and plays a critical role in sperm-oocyte fusion. Therefore, spermatozoa that appear to have the ability to bind with the hyaluronic acid are supposed to be mature and have fewer chromosomal abnormalities. This method is useful in cases of failure or low success rates after previous acceptance, in couples with low embryo quality, repeated implantation failures, with embryos that do not develop sufficiently as well as those who come forward regarding miscarriages or when the man is diagnosed with sub-fertility and a high rate of sperm DNA fragmentation.

Another technique that we used is the MACS technique. This method is based on the use of magnetic nanoparticles that have surface-specific antibodies to recognize and adhere to the apoptotic spermatozoa. The sample then passes through a magnetic filter that binds the apoptotic sperm while allowing the normal one to pass. This method is useful in cases of couples with poor embryo quality as well as couples that come forward regarding miscarriages or when the man is diagnosed with sub-fertility and a high rate of sperm DNA fragmentation.

HOS is a method to estimate chromatin integrity based on the degree of swelling of the cytoplasm and curling of the tail in live sperm when exposed to hypo-osmotic conditions. The assay is based on the fact that fluid transport occurs across an intact cell membrane under hypo-osmotic conditions until an equilibrium is reached. Due to the influx of the fluid, the cell will expand and bulge—especially the tail—and this change can be observed with a phase-contrast microscope. This method is highly indicated for couples with total immotile sperm.

The last method that we use is the fertile chip, which is a flow for a single-use device with 5 lanes. It consists of an inlet port connected to a larger outlet collection port by a micro-fluid channel. The limited depth of the channel constrains the migration of compromised sperm while allowing the most motile, healthy sperm to migrate to the outlet where they are ready for harvest. FERTILE slides can help eliminate the damaging procedures correlated with sperm washing and gradient centrifugation. Also, the sperm sorted by fertile chip exhibits better morphology, lower levels of reactive oxygen species, and less DNA fragmentation than the original semen sample. So, as a conclusion, we have to keep in mind that male factor fertility may be one or a combination of low sperm concentration, poor sperm motility, or abnormal morphology. Using the methods mentioned before, we can improve the fertilization rate after ICSI, the embryo quality, the blastulation, implantation, and pregnancy rate. But our purpose, of course, using all these techniques—other than just the rates—is to help you take home a healthy baby.

About this question:

Is there anything we can do about the male factor using IVF lab techniques: IMSI, MACS, PICSI, and others?

There are many success factors for IVF. The most crucial is to determine the causes. Although every case is different and requires a different approach, there are well- established procedures in use. When the male factor comes into play, sperm selection techniques are chosen for a specific purpose to help improve the results.

Multiple studies show that sperm quality has a direct impact on embryo development, so sperm selection is extremely important. There are several techniques used for sperm selection. The most common ones are: IMSI – Intracytoplasmic morphologically selected sperm injection, PICSI – Physiological Intracytoplasmic sperm injection, MACS – Magnetic-activated cell sorting, HOS – hypo-osmotic swelling test, Fertile – microfluidic sperm sorting chips.

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