Understanding the Risks of ICSI in In Vitro Fertilization

Updated February 2024

A Friendly Introduction to ICSI in Fertility Care

Think of Intracytoplasmic Sperm Injection (ICSI) as a personal concierge in the realm of fertility treatments - there for you when the usual path to conception needs a bit of help. This guide will walk you through ICSI in plain language, showing that though it may sound complex, it's simply another hopeful stride toward growing your family.

Deciphering ICSI for Prospective Parents

Picture yourself a tiny, yet powerful helping hand - that’s what ICSI is in the world of fertility treatments. Perfect for situations where sperm face a bit of trouble, ICSI is there to ensure that even the most determined little swimmers get where they’re needed and do what they exist for.

ICSI Steps Unwrapped:

• Getting Ready: The egg (oocyte) is prepared by removing it from its natural protective barriers, making it more accessible.
• Sperm Audition: Picture a talent show where the judges pick out the best cotenants - that's where the healthiest and quickest sperm swimmers are chosen.
• The Special Delivery: Like a skilled artist, the chosen sperm is precisely inserted into the egg with a medical tool that’s much more than just a needle.
• Success awaiting: Now it is time for the medical team to watch over the fertilized egg, that is embarking on its transformation into a new life, fingers crossed for success.

The "Why" Behind Choosing ICSI

Going straight to the finish line without any detours, that’s the essence of ICSI. It’s the go-to for:

• Men with low sperm count.
• Cases where sperm just don’t swim like they should.
• Couples who've tried other fertility treatments without success.

ICSI’s Considerations

Sure, ICSI is a marvel, but it’s not done without careful thought. Discussing the possible what-ifs with a medical fertility specialist is a must. Damaged eggs, sperm negative conditions, problems with mother-to-be uterus, etc. All of this could have a huge impact on the success of the pregnancy. Remember, ICSI is a marvel, but not a panacea.

Wrapping Up: ICSI as a Journey of Hope

In short, ICSI is a simple, accessible, and popular fertility treatment. Just keep in mind the risks that go with it. For example: a damaged egg during the procedure can lead to an unsuccessful pregnancy. 

From an ethical point of view, most countries and fertility institutions allow this treatment. Men and women want to have a baby and they will have a baby, it just conception would not be in the woman's uterus but in clean laboratory conditions, it is as simple as that. 

One of the rumors that intended parents frequently ask about - is whether there are risks that babies that concept this way are more prone to genetic diseases, for example, Down Syndrome. Well, this is utter nonsense that has no statistical or medical confirmation so far. Medical institutions usually offer genetic testing treatments, not just for intended parents but for sperm and egg also, so future parents can rest assured that only the best gametes are used in ICSI.

As you weigh your options, lean on OVU.com. We're your guide to the best fertility clinics and a source of wisdom you can trust. In the myriad ways of assisted reproduction, we're your steadfast partner, lighting the path to the family you yearn for. 

Full Article

The intracytoplasmic sperm injection (ICSI) technique is successfully used to resolve the most severe cases of male infertility, enabling fertilizing of the oocytes using the partner’s sperm. While being effective for overcoming low or absent fertilization in couples with abnormal semen parameters, ICSI is also frequently used in combination with assisted reproductive technologies for treating the other causes of infertility. The average fertilization rates with ICSI range from 70% to 80%, depending on the case.

Being a microsurgical procedure performed on a single oocyte, ICSI involves using a glass ICSI micropipette with a–long parallel taper (glass needle) to aspirate and inject the one living spermatozoon directly into the oocyte), a micromanipulator (precision positioning device) to control the movement of the ICSI micropipette and a microinjector. During ICSI, the Embryologist microinjects a single motile spermatozoon directly into the center of an oocyte, bypassing a thick extracellular coat called the zona pellucida (ZP). 

Indications for ICSI technique 

Male factor infertility:

• Obstructive azoospermia (the absence of sperm cells in the ejaculate despite the testes producing enough sperm, but there is a plumbing problem that prevents the sperm from traveling out of the testes)
• Non–obstructive (secretory) azoospermia (the absence of sperm cells in the ejaculate because the testes do not produce the sperm)
• Oligospermia, also called oligozoospermia (low sperm count and severely low sperm count in the semen) 
• Cryptozoospermia (an extremely low concentration of sperm in semen)
• Asthenozoospermia (sperm cells with low or absent motility)
• Teratozoospermia (abnormal sperm morphology)
• Anejaculation (ejaculation dysfunction)
• Immune infertility: the presence of elevated levels of anti-sperm antibodies (immunoglobulins) binding to antigens of the gametes and interfering sperm–-sperm-oocyte interaction 

Female factor infertility: 

• Retrieval of a low number of oocytes during follicular aspiration
• Poor oocyte quality, including the cases of thick zona pellucida.

The other cases when ICSI is performed: 

• Previous fertilization failures with conventional IVF
• In cases requiring PGT (preimplantation genetic or chromosomal testing) of embryos 
• Cycles with epididymal or testicular sperm samples (cryopreserved and fresh)
• Cycles with cryopreserved semen samples
• Cycles with vitrified oocytes
• Cycles with cryopreserved ovarian tissue 
• Cycle with oocytes after IVM (in vitro maturation)

Revealing the mystery of ICSI 

ICSI is done in the Ivf lab using a Multi–Zone ART/Ivf Workstation. The Workstation is usually equipped with an inverted microscope, which has a CCD camera that is linked to a monitor to allow for real–time visualization, micromanipulators, and microinjectors for performing fertilization. 

Intracytoplasmic sperm injection can be described with the following steps: (1) denudation of the oocyte from the surrounding cells, (2) selection and immobilization of a viable sperm cell, (3) aspiration of the spermatozoon before injection; (4) positioning and fixing the oocyte with the holding pipette before injection, (5) aspiration of the oocyte; (6) rupture of the oolemma before the release of the sperm into the oocyte; (7) slow release of the spermatozoon in the ooplasm; (8) accurate removal of the ICSI micropipette from the oocyte; (9) release of the oocyte after injection. 

ICSI involves microinjecting a single motile spermatozoon into the oocyte, bypassing the Zona Pellucida, and introducing the sperm cell into either the cytoplasm or the oocyte's nucleus. The oocytes, denuded from their surrounding cells (cumulus and corona cells), are placed in several surrounding medium microdroplets in the ICSI dish. After that, an Embryologist drops into the ICSI dish a special solution that slows sperm motility and adds ±1 μL of the sperm. 

In the ICSI micropipette, which is filled with a special solution that prevents sperm cells from sticking to it, a single motile (the motility of the sperm cell, even if it is only a slight twitching of the tail, indicates that it is living), and morphologically normal sperm cell is aspirated. Then the sperm cell is then released perpendicular to the ICSI pipette, which facilitates immobilization.

Immobilization of a sperm cell can be done with the ICSI needle or with a laser (laser–induced immobilization). Both techniques result in identical fertilization rates. Immobilization is essential for oocyte activation and is achieved by releasing sperm cytosolic factors via the ruptured membrane. It involves rubbing the tail with the ICSI micropipette against the bottom of the dish, which results in breakage in the midpiece region or cutting the tail below the midpiece region, or cutting halfway between the head and the tip of the tail, or dissecting the tail at the tip.

After immobilization, the sperm cell is again aspirated (but now tail–first) to allow the injection of a minimal volume of medium together with the sperm cell. The oocyte is held in position with minimal close touch by the holding pipette and its polar body is located at the 6 o’clock position to avoid damage to the oocyte’s spindle. 

The ICSI microinjection needle will be positioned just over the oocyte and then lowered slowly until a slight depression can be seen on the cell surface. After the correct needle position has been visualized, the needle is then moved slightly to prepare for an injection. Preparation for injection allows the microinjector to introduce the sperm into the oocyte using computer–controlled settings.

If both the holding pipette and the oocyte are in perfect focus, the injection microneedle, containing the immobilized sperm cell near the tip, can be introduced into the oocyte. The ICSI microneedle gets past the barrier of the cell (the plasma membrane) by drilling a hole in it. Passing through the zona pellucida is seamless and done by advancing the injection pipette with positive pressure. If drilling is done correctly, the oocyte membrane will close when the ICSI needle is removed, leaving minimal cellular damage.

In contrast, the oolemma is not always pierced by a simple injection of the ICSI needle and usually needs a little bit more pressure. If the ooplasm enters the injection micropipette and sudden acceleration of the flow is visible, it indicates that the membrane has been ruptured. At this moment, aspiration is immediately stopped, the sperm cell is slowly released into the oocyte with a minimal medium volume, and the ICSI pipette is accurately removed.

While doing intracytoplasmic sperm injection, the Embryologist controls the injection volume, injection pressure, and post–injection pressure for minimal cellular damage after fertilization. The injection volume is limited to only spermatozoon and some solution that is to be introduced, or the oocyte could burst. The injection pressure should be higher when introducing the sperm cell inside the oocyte, and the post–injection pressure should be lower for removing the microneedle accurately but higher than the pressure used for drilling the oocyte. 

Without pressure control, the contents from the cytoplasm or nucleus would be forced back into the ICSI needle by a positive pressure created by the introduction of the injected material. Such a loss of cytoplasmic or nuclear material could entail the death of an oocyte.

 Risks while doing ICSI 

• If visualization of the ICSI process is not clear (for ex., the low–resolution microscope is used), it would interfere with fixing or releasing an oocyte using the holding pipette, as well as aspiring and injecting a spermatozoon with the injection pipette. 
• ICSI micropipette should be filled with a special solution to prevent sticking of the sperm cell to the pipette; otherwise, the manipulation won’t be successful, and it would also be hard to control the fluid in the microinjection needle. 
• Motility is a vital indicator of sperm viability. If there is not even a slight twitching of the tail, it seems that the spermatozoon is not alive or nearly dead and cannot be used for fertilization. In such a case, the new one should be selected for ICSI. 
• Despite achieving higher ICSI fertilization rates after aggressive damage to the sperm tail plasma membrane during immobilization, too aggressive damage or damage to the other regions may lead to the death of spermatozoon.
• If, after immobilization, the sperm cell is aspired head, it may first lead to the injection of a maximum volume of medium together with spermatozoon, causing the burst of the oocyte. 
• If both the holding pipette and the oocyte are not in perfect focus, it would be easy to puncture the oocyte. 
• Too much pressure while penetrating the oocyte’s ZP may result in undesirable results. If drilling is done incorrectly, the oocyte membrane won’t close back up when the ICSI needle is removed, leaving behind maximum cellular damage.
• Sperm cell should be introduced at the moment when ooplasm enters the injection micropipette, and sudden acceleration of the flow is visible, indicating that the oolemma membrane has been ruptured. 
• The volume of microinjection must be limited to only sperm and some solution that is to be introduced or the oocyte could burst. The same thing for the injection pressure, the sperm cell should be slowly released into the oocyte.
• If the Embryologist doesn’t control the injection volume, injection pressure, and post–injection pressure while doing ICSI, the oocyte damage will be maximum. 

Risks after performing ICSI

• While ICSI has overcome many fertilization problems, it has not eliminated total fertilization failure (TFF).
• Embryonic arrest 
• Reduced number of top–quality embryos
• Delayed embryo transfer
• Cancelled embryo transfer
• Not all IVF–ICSI embryos left after the transfer can be vitrified for future FET cycle(s)
• Implantation failure & miscarriage or ectopic pregnancy
• Negative pregnancy test after embryo transfer
• No heartbeat detected on high–resolution ultrasound after a positive pregnancy test 
• Multiple pregnancies resulting into multiple births