What is ICSI or Intracytoplasmic Sperm Injection?

ICSI is a procedure used for in vitro fertilization (IVF) by which a spermatozoon is microinjected directly into an egg to create viable embryos. After that, the resulting embryos are transferred so that pregnancy is hopefully achieved.

Given that it is a type of IVF, we often refer to it with the name IVF-ICSI.

It is used to treat the most severe cases of sterility, especially male sterility, as there is no need for a semen sample of an elevated quality when this is the technique of choice. It was first used in 1989, when the first child conceived with this technique was born in Singapore.

The various sections of this article are assembled in the following table of contents.

What is difference between ICSI and IVF?

ICSI is the abbreviation of Intracytoplasmic Sperm Injection. This technique allows us to choose the best spermatozoon to insert it inside a microinjection needle. Then, while the oocyte is being held from one side, the needle is carefully inserted in the opposite side, so that the sperm is injected into the cytoplasm of the egg.

ICSI and conventional IVF are similar infertility treatments which differ in the way the sperm is inserted inside the oocyte. In the case of conventional IVF, it is the sperm cell which penetrates the egg coat by itself.

Conversely, with ICSI the sperm is directly injected into the egg with a microneedle. It makes this process a way more complex one than IVF.

Another major difference between them is related to the cost of each: the more technical level of complexity, the higher the price of infertility treatments, as it happens with ICSI.

You can visit the following post to find out more differences: IVF or ICSI?

Indications for intracytoplasmic sperm injection

ICSI is used when the male’s sperm cells have trouble penetrating the egg by themselves. Although it is usually done with the husband’s or partner’s sperm, donor semen samples can be used as well.

The following are some of the most important indications for ICSI:

Azoospermia

This male fertility problem occurs when the sperm count in the ejaculate is zero. There exist two types of azoospermia:

  • Obstructive azoospermia: The sperms are prevented from mixing with the remaining seminal fluid due to a blockage in any of the ejaculatory ducts. Sperm production occurs, yet the sperms are not expelled.
  • Non-obstructive azoospermia: No sperm is produced, as the problem remains in the testis, which is the location where spermatozoa are created.

Oligozoospermia

It refers to poor sperm quality caused by the absence of sperm concentration in the ejaculate. The WHO (World Health Organization) uses a cut-off of not less than 15 million sperm per milliliter as a general recommendation.

This male infertility problem is also known as oligospermia.

Obviously, oligozoospermia has different degrees of severity. As a general rule, the further away it is from the WHO’s reference value, the more severe the semen sample is.

The most severe cases are referred to as cryptozoospermia, a condition in which the sperm concentration is below 100.000 sperm/ml of semen.

Asthenozoospermia

Also known as asthenospermia, this parameter measures sperm quality according to how motile they are. In accordance with the WHO, this pathology is diagnosed whenever the amount of progressive spermatozoa or able to move forward is less than 32%.

Besides, the total count of motile sperms should be above 40%.

Teratozoospermia

Teratozoospermia or teratospermia refers to a problem in sperm morphology. According to the Kruger strict criteria, the presence of more than 85% abnormal sperm in the ejaculate indicates male sterility. In these cases, ICSI is the most advisable treatment to achieve parenthood.

If the WHO’s criteria is followed, then a semen sample is considered to have teratospermia if more than 96% of sperm are morphologically abnormal.

Several abnormal sperm test values

In addition to the above listed sperm pathologies, it is possible for various sperm values to appear altered in the semen analysis.

Taking this into account, the following combinations are possible:

  • Oligoasthenozoospermia: alterations in sperm concentration and motility.
  • Oligoteratospermia: alterations in sperm concentration and morphology.
  • Asthenoteratospermia: alterations in sperm motility and morphology.
  • Oligoasthenoteratospermia: alterations in sperm motility, morphology and concentration.

ICSI is also advisable after vasectomy or in males diagnosed with an infectious disease (HIV, hepatitis, etc.).

Males who have had their semen cryopreserved due to cancer treatments (radiotherapy or chemotherapy) or those unable to ejaculate under normal conditions are recommended to undergo ICSI as well.

ICSI is not so common in cases of female infertility. It is used in cases where a scarce number of oocytes have been obtained after ovum pick-up, if there is an enlargement of the zona pellucida, or in women producing poor-quality eggs.

How does it work?

The steps to follow in an ICSI procedure are the same as in IVF, but differ in the way the eggs are inseminated:

  • Controlled ovarian stimulation (COS): Patients are given hormone fertility medications to promote the maturation of multiple egg cells with good quality in a single cycle. Regular ultrasound monitoring is necessary to assess follicle growth.
  • Ovum pick-up or follicle puncture: When ultrasounds show the follicles have almost reached the right size for ovulation, egg collection is scheduled. It is a simple surgical procedure which is done with mild anesthesia and takes around 30 minutes. During this process, the follicular fluid (FF) containing the eggs is aspirated.
  • Oocyte denudation: It is done at the laboratory and consists in examining the FF obtained after egg harvesting in search of oocytes. After some time resting, the eggs are “stripped”, which is to say, the cumulus cells surrounding them are removed.
  • Sperm collection and preparation: The semen sample is generally obtained by masturbation and washed prior to fertilization. The washing process is known as sperm capacitation and involves “mixing” only those sperms with the highest quality. When collection cannot be done by means of masturbation, sperms can be obtained through testicular biopsy or epididymal aspiration.
  • Egg insemination: A sperm is selected, aspirated with a microinjection needle, and injected into the ovum. The ultimate goal is to ensure that the fusion between both partner’s DNAs (i.e. fertilization) occurs.
  • Embryo culture: After fertilization, the resulting embryos are cultured in an incubator so that they continue developing. IVF incubators keep the optimum conditions of temperature, light and humidity for embryo growth.
  • Preparation of the uterine lining: Estrogens and progesterone are administered through vaginal, mouth or patch route to get her uterine lining to be receptive and in excellent conditions for embryo development.
  • Embryo transfer (ET): The best embryo(s) is selected for the transfer according to its quality. ET is a simple step that takes only a few minutes, and anesthesia/sedation is not required. The embryos are placed in the uterine fundus with a fine catheter, so that they are hopefully able to implant to the endometrial lining and lead to a successful pregnancy.
  • Embryo freezing: High-quality unused embryos are cryopreserved (frozen) for later use.

What is the success rate for ICSI?

Although the success rates of IVF with ICSI depend on each particular case, the main factor to determine its success rate is the woman’s age. It is established according to the following age ranges:

  • 40% in women under 35
  • 27-36% in women between 35 and 37
  • 20-26% in women between 38 and 40
  • 10-13% in women above 40

Nevertheless, it should be clear that these are just standard rates, and may vary not only from patient to patient, but also depending on the fertility clinic chosen.

What is taken as a reference also matters when it comes to talking about success rates. For instance, while some consider it has been successful after obtaining a positive pregnancy test (fertilization rate), others refer to the live birth rate solely. This is the reason why one should pay special attention when comparing between the success rates of infertility treatments.

The following post will provide you with more information about it: Success rate for ICSI.

What are the potential risks and side effects?

The potential risks derived from ICSI are:

  • Ovarian Hyperstimulation Syndrome (OHSS): It is due to an excessive response to hormone therapy for ovarian stimulation. It can cause the woman to feel physical discomfort, bloating, etc. However, today it occurs rarely and with a low degree of severity in the vast majority of cases. Ultrasound monitoring is crucial while on ovulation induction for this reason.
  • Multiple births: With two-embryo transfers, the twin rate reaches 6%. When three embryos are transferred, this rate rises to 12%, and the likelihood of having triplets to 3%. Current research focuses on improving the embryo selection process to choose only those with an excellent quality. This means they aim to improve the success rate with single embryo transfers (SET).
  • Miscarriage: It is estimated that miscarriage occurs in 20-22% of the cycles. It usually happens while the woman is on the earliest stages of pregnancy.
  • Ectopic pregnancy: It occurs when the embryo implants in a location outside the uterus. Statistical data has shown that 2 to 5 women per every 100 undergoing in vitro fertilization can have an ectopic pregnancy. Chances drop to 1-1.5% in the case of natural pregnancies.

If you want to learn more about the risks of IVF-ICSI, please visit the following post: Risks of in vitro fertilization.

What is the cost of ICSI?

Like any other fertility treatment, the prices of IVF with ICSI are variable and can range between different figures depending on the clinic, country, and particularities of each infertility case.

Special features such as the use of donor eggs and donor sperm or the need for PGD (preimplantation genetic diagnosis) or a testicular biopsy, etc. can increase or decrease the overall cost of ICSI.

Broadly speaking, the cost of ICSI ranges from €3,000 to €5,000. Normally, there is no difference between the fees for conventional IVF and those of ICSI procedures. Some clinics may offer different prices depending on the method they use for egg fertilization, though.

More often than not, medications for ovarian stimulation are not included in the total estimate cost, which makes it crucial to get as many information as possible beforehand. Although medication fees vary according to the protocol established for each patient, the approximate price is €1,000-1,200.

Another aspect to keep in mind when estimating the cost of ICSI is related to the personal situation the couple or individual is living currently. While it can work on the first attempt, sometimes it fails, in which case more cycles would be necessary. So, it should be taken into account that costs can vary depending on the severity of the infertility problem and the number of attempts needed.

Difference between ICSI, IMSI and pICSI

Both IMSI and pICSI derive from ICSI, that is to say, they are two different ways to carry out the microinjection.

IMSI stands for Intracytoplasmic Morphologically Selected Sperm Injection. After examining its morphological characteristics, a sperm is selected for being microinjected. To do so, spermatozoa are observed with an ultra-high magnification microscopy in order for their morphology to be analyzed and selected accordingly before being injected into the oocyte. While standard ICSI is done at x400 magnification, with IMSI a magnification up to x6300 is achieved.

On the other hand, pICSI or physiological ICSI is another way of sperm selection which allows us to choose the best spermatozoon, that is, the one with the highest fertilization potential.

With pICSI, the semen sample is placed in a PICSI dish containing samples on its surface of a similar material to the hyaluronan hydrogel (HA) that covers the oocytes. High-quality sperms will be able to bind to HA, thereby making it easier for the specialist to identify them.

FAQs from users

What is assisted hatching in IVF with ICSI?

Assisted Hatching (AH) is a state-of-the-art technique that is used both in conventional IVF an ICSI procedures. It involves the artificial disruption of the ZP (zona pellucida) after the egg is fertilized in the laboratory.

AH is performed after IVF and ICSI procedures, right before the embryo transfer. The embryologist creates a small hole in the ZP by means of micromanipulation under a microscope. By doing this, we make it easier for the embryo to hatch out of the zona pellucida and implant to the uterine lining.

According to the ASRM (American Society for Reproductive Medicine), it is used in cases of women with advanced maternal age, poor embryo quality or after the failure of two or more previous IVF cycles.

What is the difference between ICSI and IUI?

IUI (intrauterine insemination) is the simplest of all fertility treatments, while ICSI is way more complex, as it is a more direct approach at egg fertilization.

With IUI, the sperm is placed inside the uterine cavity and allowed to move forward by themselves toward the oocyte. Broadly speaking, they penetrate it under their own “power”.

Conversely, with ICSI there is no need for the sperms to travel through the vaginal cavity by themselves, as a spermatozoon is injected directly into the oocyte, which causes fertilization to occur artificially.

Another difference is that ICSI occurs outside the female body, after egg retrieval. In the case of IUI, the process of fertilization and egg insemination occurs as it would occur naturally inside the woman’s reproductive system.

When PGD/PGS is required, what is better, ICSI or IVF?

If PGD (preimplantation genetic diagnosis) is to be used as well, egg fertilization is done via ICSI to avoid harmful interferences with PGD outcomes.

In IVF procedures, a percentage of the sperms that tried to penetrate the egg remain adhered to its surface. Because of that, some of their genetic material can be dragged during the embryo biopsy for PGD, which could alter the final result of this technique.

How effective is ICSI with testicular biopsy?

It depends on each case. If an sperm per each egg available for fertilization is obtained, then there are chances for success. Conversely, if no alive spermatozoon is collected, ICSI cannot be performed.

How many tries with ICSI before getting pregnant?

While some achieve pregnancy on the first attempt, others need two, three or more attempts to finally become pregnant. Since a number of factors could have an impact on the outcome of ICSI, we cannot provide you with an specific figure.

Egg and sperm quality, embryo quality, the cause of infertility, and the conditions of the endometrial lining are some factors that could influence the success rate of ICSI.

Why not using ICSI in all IVF procedures? What are its pros and cons?

Infertility treatments always aim to imitate the natural process of conception as much as possible as the first option. With conventional IVF, the sperm reaches and penetrates the egg by itself. However, in IVF with ICSI procedures, the embryologists injects the sperm directly into the egg. This is the reason why conventional IVF is more similar to natural conception.

Also, the sperm is chosen by natural selection, while with ICSI it is done following the criterion of the specialist. A sperm capable of fertilizing the egg with their own power is a healthy one, and therefore one able to create viable embryos.

What are my chances of having twins with ICSI?

No, it basically depends on the number of embryos to transfer. The chances of having a multiple pregnancy with single embryo transfers (SET) are very low. However, with two embryos, it rises to 6%.

My husband’s sperm count is zero, yet we have some sperms after a testicular biopsy, what are our chances with ICSI?

As explained earlier, a single sperm per egg retrieved is enough, so there is no need for it to have an excellent quality. This is the reason why obtaining viable embryos is possible by removing the sperms directly from the testis.

2 comments

  1. usuario
    Alisia

    Hi there! Thanks for so useful article. It is really important info. I am having my appointment in the clinic for Egg donation and ICSI in Kyiv. Now I am feeling more confident about the whole thing. As I got to know the theory of the process. The only thing in my opinion you should not have avoided is an approximate price…at least starting from. As it is not such a cheap treatment

  2. usuario
    kylie-090

    Hello. The truth is I don’t find this technique useful at all. I think it basically consists of forcing a sperm to penetrate the egg even if it wasn’t naturally able to do so. I mean, if it was unable, it should have a reason, right? By doing this, maybe you are fertilizing the egg with some anomalies or something like that. I underwent an IVF because my hormone system was a chaos. My clinic recommended me that, with the eggs I obtained, I should undergo a two-stage process: half IVF and half ICSI. This way I could try both technologies. I said no and asked for a conventional IVF, since I prefer the sperm penetrate the egg by themselves and not to be forced… Not so sure, but from my point of view I think this technique is way more natural than ICSI, although in both cases you are infertile 🙁 Well, this is just my humble opinion. Bye!

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