To ICSI or Not to ICSI: Should ICSI Be Considered in Every IVF Cycle?

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Intracytoplasmic sperm injection (ICSI), a pioneering technique introduced in the 1990s, marked a turning point in fertility treatment. This innovative procedure, developed as a solution to cases in which fertilisation could not be achieved by conventional in vitro fertilisation (IVF), consists of the direct introduction of a spermatozoon into the egg.

To ICSI or Not to ICSI: Should ICSI Be Considered in Every IVF Cycle?

The development of the ICSI technique marked a milestone in assisted reproduction and specifically in the treatment of male infertility problems. In contrast to conventional IVF, ICSI is a targeted and more complex technique that consists of injecting a sperm directly into the cytoplasm of an oocyte. It was in 1992 when Gianpiero Palermo developed this new assisted reproduction technique that revolutionised assisted reproduction and was quickly adopted by the scientific community due to its efficacy. Today, its success rates are very high.

Many patients are seeking IVF abroad due to the ICSI technique availability or the significant cost of the technique in their home country.

What is ICSI?

ICSI is one of the most common assisted reproduction techniques used in the embryology laboratory and developed at many IVF laboratories by experienced embryologists. It was developed to help men with a low sperm count or low motility to become fathers with their own gametes before artificial insemination with donor sperm. It is currently one of the most widely used techniques. When we are trying to conceive there are two basic elements we have, oocytes and spermatozoa. In in vitro fertilisation, we must bring the oocytes and the sperm together and there are different ways of carrying out this fertilisation process.

With ICSI we introduce a sperm into the egg. It is a technique that allows us to select the best sperm from the sample left by the couple or the donor and artificially introduce it through the membrane of the egg into the oocyte, so that the egg is activated, takes the genetics of the sperm, generates fertilisation, and starts cell division.

For this process to be complete, the cells surrounding the oocyte are removed in the laboratory, a step known as decumulation. Previously, the oocytes have spent a few hours in a culture medium. The morphology of the oocyte is analysed and those that are mature or suitable for fertilisation are selected.

IVF vs IVF ICSI – the difference

Both traditional IVF and ICSI are in vitro fertilisation techniques, i.e. fertilisation takes place in the laboratory. The main difference is the way in which the gametes are joined together to create the embryo. In classical IVF, on the one hand we have an undenuded egg, i.e. with all the granulosa cells still present. On the other hand, we have the spermatozoa that have undergone the capacitation process, which is their preparation for fertilising the egg. This is generally done by the swim-up technique, which involves separating the seminal fluid and grouping the sperm according to their motility and morphology. The egg is placed in a laboratory dish along with the semen so that one of the sperm can penetrate the oocyte. This process will not occur if the sperm are of poor quality.

Whereas in the ICSI technique, what we do is to artificially select through the microscope the spermatozoa with the best structure and greater mobility to introduce it with a microinjector directly through the membrane of the oocyte so that it can be fertilised. Although its use is becoming increasingly widespread, it is usually used when we have a lower percentage of motile spermatozoa, we find abnormalities in the spermatozoa or we suspect a fertilisation failure.

ICSI success rates

The success rates of ICSI are very high and are especially indicated in women with low ovarian reserve or in men with a seminal pathology that makes a classic IVF unfeasible. In this way we have the guarantee that we choose the best egg and the best sperm and with this union we know that it improves the rates of fertilisation and embryo reaching the blastocyst stage. ICSI is a technique widely used in assisted reproduction centres and offers very good results, with a fertilisation rate of around 80-90%.

Currently, around 97% of in vitro fertilisation treatments in Clinica Tambre in Spain are performed using ICSI and the remaining 3% by conventional IVF.
Dr. Héctor Izquierdo, Fertility specialist at Clínica Tambre

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To ICSI or not to ICSI

ICSI is a technique that revolutionised the way we approach infertility. Unlike traditional in vitro fertilisation, where the sperm has to penetrate the egg by its own means, ICSI allows us to select a sperm and inject it directly into the egg. This is especially useful in cases where fertilisation cannot be achieved conventionally. The impact has been monumental. ICSI has opened doors for many couples who would otherwise have very few options to conceive biologically. By overcoming natural barriers to fertilisation, we have achieved significant success rates in cases that were previously considered almost impossible. It is undoubtedly one of the greatest innovations in our field, bringing hope and real possibilities to those who face challenges in their desire to start a family.

Generally speaking, the question of whether to do classical IVF or ICSI should be answered in the assisted reproduction consultation with the patient. It must be understood that this is a medical decision, guided by the results of embryology, the patient’s ovarian reserve and andrology, not a random choice. It must be chosen with a general vision that allows us to decide which is the most appropriate technique. In cases of previous fertilisation failure, ICSI is usually recommended. If however we have patients with a high ovarian reserve and good sperm quality a traditional IVF techniques may be employed. This allows for a more natural selection of eggs and sperm and will generate fewer embryos.

Should ICSI Be Considered in Every IVF Cycle?

The ICSI fertilisation technique is mainly used when we have a low ovarian reserve in order not to lose eggs or when we have a seminal factor, and we have to select the sperm in order to fertilise the egg.

Why to use ICSI

ICSI was developed to solve the problems of men with severe male factor and in those cases of fertilisation failure after conventional IVF, as it manages to introduce the sperm directly into the egg, avoiding the previous stages. It is currently a widely used technique in reproductive medicine clinics as it allows the best spermatozoa to be selected in terms of motility and morphology. The use of ICSI or IVF depends on each case and on the medical evaluation, which will decide which method is the most appropriate. There are some moments when we may think that using ICSI is more effective, if we have few eggs or a poor quality of the sperm sample.

ICSI risks explained

Currently, the ICSI fertilisation technique is very safe. At Clinica Tambre we have the capacity, safety and the best equipment to be able to perform ICSI safely. Fears about ICSI come from the past and the possibility of not having well tuned microscopes and injection needles, which could mean that this process, which is microscopic, could be carried out in the safest way for the oocyte. But a fertility laboratory such as Tambre’s, with the best technology available, is a safe laboratory, where we can know if the oocytes will pass ICSI if their quality allows it.

IVF process with ICSI

In the ICSI process, mature eggs are first prepared using enzymatic and mechanical techniques to remove surrounding cells and determine their degree of maturity. Only those eggs that have reached metaphase II are chosen for injection. Using a special microscope with microinjectors, the sperm are carefully selected under significant magnification, discarding those with severe defects. The injection of each sperm into the egg is performed following a standard method. The total time required to perform ICSI on each patient depends on the number of eggs ready to be injected, with at least 20 minutes estimated to complete the procedure.


The voice from an embryologist – Dr. Susana Cortés, Directory of Laboratory at Clinica Tambre, Spain

What are the main technical challenges faced by biologists when performing the ICSI procedure, how are these challenges overcome and who is trained to perform them?

Learning to operate IVF laboratory equipment involves an implicit skill of the embryologist. However, the real challenge is not the technique itself, but the nature of the gametes we are going to work with. It is not the same to have a normal semen sample and good quality oocytes, as it is to have a sample in which it is difficult to find spermatozoa, where the motility or morphology is null or very low. Furthermore, the quality and nature of the oocytes sometimes makes this technique complicated, as there are occasions when, at the moment of microinjection, due to the hardness or fragility of the plasma membrane that surrounds this large cell, the oocyte does not survive the microinjection. So it is not only enough to know how to handle the equipment, but it is also necessary to have the necessary training to know how and when it is better to perform one technique or another.

What are the criteria used to select viable sperm during the ICSI process and what considerations should be taken into account to maximise the effectiveness of the procedure?

Sperm selection can vary depending on the sperm selection technique used. In general, embryologists select the sperm to be microinjected according to their motility and morphology. The sperm with the best morphology and motility is selected. Only in the case of slow sperm, this form of selection changes. The sperm-slow selects the spermatozoa according to the presence of receptors in the plasma membrane of the spermatozoa, so that the spermatozoa that have these receptors (those that are mature) are slowed down by the environment, observing that they cannot move forward despite the movement of the flagellum. Those sperm that move freely through the medium do so because they do not have receptors (they are immature) and must be rejected.


ICSI procedure costs

The decision to perform a treatment using the ICSI technique is primarily a medical one, together with the patient. Depending on the treatment that the couple or the woman needs, the decision will be one or the other. Currently in Spain, and due to its good results, it is one of the most widely used techniques, and the big difference between Spain and other countries is that in most centres, as is the case at Clinica Tambre, there is no extra charge for using this technique. It’s included in all IVF packages.

Should ICSI always be included in the IVF cycle?

My recommendation to all patients is that when they go to an assisted reproduction clinic they should not have to decide on IVF or ICSI for financial reasons. At Tambre, we believe that this is a medical decision that should not be linked to the patient’s purchasing power. For this reason, all treatments include both techniques, IVF and ICSI, at no extra cost. In this way, we eliminate the tension that this type of decision can generate. We want our patients to be at ease and to develop their assisted reproduction process in the most natural way possible, always accompanied by our team.

Why in some countries ICSI is not included in most of the IVF cycles?

One of the reasons why in Spain more ICSI is done than IVF compared to other European countries is that in most European countries it is a decision made by the patient and it is a financial decision. They are charged extra for doing ICSI, and this makes the patient feel limited in their decision. In Spain this is a decision that should be a medical one and should not condition the success of a treatment.

The use of the ICSI technique has spread rapidly and according to data from the Spanish Fertility Society (SEF), in 2004 60% of all cycles used ICSI and according to the last SEF registry of 2020, 88.5% of the treatments carried out in Spanish clinics used this technique.
The situation is similar in other popular IVF countries abroad – Greece, Czech Republic, North Cyprus, Portugal, Latvia and Estonia.

IVF ICSI – FAQ

How does ICSI differ from IVF?

Both traditional IVF and ICSI are in vitro fertilization techniques, meaning fertilization occurs in the laboratory. The main difference is the way in which the gametes are united to form the embryo. In classic IVF, we have the egg unstripped, that is, with all the granulosa cells still present. On the other hand, we have sperm that have undergone the capacitation process, which is their preparation to fertilize the egg. This is generally done by the swim-up technique, which involves separating the seminal fluid and grouping the sperm by their motility and morphology. The egg is placed on a laboratory plate along with the semen so that one of the sperm can penetrate the oocyte. A process that will not occur if the sperm are of poor quality. Whereas in the ICSI technique, what we do is artificially select, through the microscope, the sperm that has a better structure and greater motility to introduce it with a microinjector directly through the membrane of the oocyte for it to be fertilized. Although its use is becoming more widespread, it is usually used when we have a lower percentage of motile sperm, find abnormalities in the sperm, or suspect a failure of fertilization.

What are the success rates with ICSI?

The success rates of ICSI are very high and are particularly indicated for women with low ovarian reserve or men with seminal pathology that makes conventional IVF unfeasible. In this way, we have the assurance that we are choosing the best egg and the best sperm, and with this union, we know that it improves the rates of fertilization and embryos reaching the blastocyst stage. ICSI is a technique widely used in assisted reproduction centers and offers very good results, with a fertilization rate of around 80-90%. Currently, at Clínica Tambre, 97% of in vitro fertilization treatments are performed using ICSI, and the remaining 3% by conventional IVF.

Is IVF more successful with ICSI?

Currently, ICSI is a widely used technique in reproductive medicine clinics because it allows for the selection of the best sperm based on motility and morphology. The use of ICSI or IVF depends on each case and medical evaluation, which will decide which method is most suitable. There are some instances where we might consider using ICSI to be more effective, such as when we have few eggs or poor quality of the semen sample.

Why does ICSI fail sometimes?

Intracytoplasmic sperm injection (ICSI) is a specialized form of in vitro fertilization (IVF) that involves the direct injection of a single sperm into an egg to facilitate fertilization. Despite its effectiveness in overcoming certain infertility issues, ICSI does not guarantee success and can fail for several reasons. Some of the common reasons why ICSI may fail include:

Egg Quality:
Poor egg quality can significantly reduce the chances of successful fertilization and embryo development. Factors such as the woman’s age, ovarian reserve, and lifestyle choices can affect egg quality.

Sperm Quality:
Even though ICSI can overcome issues with sperm count or motility by directly injecting a sperm into an egg, the genetic quality of the sperm is still important. Sperm with DNA fragmentation or other genetic abnormalities may lead to fertilization failure or poor embryo development.

Embryo Development:
After fertilization, the embryo must grow and develop to a stage suitable for transfer to the uterus. Sometimes, embryos may fail to develop properly due to genetic or chromosomal abnormalities, or issues with the laboratory conditions.

Laboratory Conditions:
The success of ICSI also depends on the conditions within the IVF laboratory. Factors such as temperature, air quality, and the culture medium can affect embryo development. In Tambre this procedure is performed by experienced embryologists.

Implantation Failure:
Even if fertilization and embryo development are successful, the embryo must implant in the uterine lining to establish a pregnancy. Factors such as uterine abnormalities, immune system issues, or hormonal imbalances can prevent successful implantation.

Genetic or Chromosomal Issues:
Both the egg and sperm can carry genetic or chromosomal abnormalities that may not affect fertilization but can prevent the embryo from developing normally, leading to failed implantation or early miscarriage.

Age:
The age of the woman is a significant factor in ICSI success rates. As women age, the quality and quantity of their eggs decline, reducing the chances of successful pregnancy.

Lifestyle Factors:
Lifestyle factors such as smoking, excessive alcohol consumption, obesity, and high levels of stress can negatively affect the success rates of ICSI.

Does ICSI improve embryo quality?

ICSI does not inherently improve the quality of embryos in terms of their genetic makeup or potential for development. The quality of an embryo is determined by the health and genetic material of both the egg and the sperm. However, ICSI can significantly increase the chances of fertilization, especially in cases where fertilization would be unlikely or impossible with conventional IVF or natural conception due to male-factor infertility. This can lead to the creation of viable embryos that might not otherwise have been possible.

Several studies have evaluated the outcomes of ICSI compared to conventional IVF, with mixed results regarding embryo quality. Some research suggests that there may be slight differences in development rates and outcomes between embryos created via ICSI and those created via standard IVF methods, but these differences are often minimal or context-dependent.

It’s also important to note that the use of ICSI has expanded beyond male-factor infertility to include cases with unexplained infertility, previous fertilization failure with IVF, and other scenarios. In these cases, the impact of ICSI on embryo quality may vary and should be considered in the context of the specific circumstances of each couple.

Does ICSI pick the best sperm?

ICSI is a technique that allows us to select the best sperm from the sample provided by the couple or the donor and artificially introduce it through the egg’s membrane into the interior of the oocyte, so that the egg is activated, takes the genetics of the sperm, generates fertilization, and starts cell division.

Does sperm quality matter for ICSI?

Better sperm quality is generally associated with higher fertilization rates and better embryo development, even in ICSI procedures.

Are IVF ICSI babies healthy?

Babies born through IVF (In Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection) are generally healthy. Most children conceived using these techniques do not have any more health problems than children conceived naturally. However, IVF and ICSI pregnancies may have a slightly higher risk of certain complications, such as low birth weight and preterm birth, but most of these babies are healthy.

Does ICSI increase the chance of autism?

The question of whether Intracytoplasmic Sperm Injection (ICSI) increases the risk of autism has been explored in several studies, but the findings have been mixed and do not conclusively establish a direct link between ICSI and an increased risk of autism. Some research suggests a slightly higher incidence of autism spectrum disorders (ASD) in children conceived through assisted reproductive technologies (ART), including ICSI, compared to natural conception. However, it’s important to note that these findings could be influenced by various factors, including parental age, genetic predispositions, and other environmental factors, rather than the ART procedures themselves.

A comprehensive understanding of autism’s causes remains complex and suggests that both genetic and environmental factors play roles. The slight increase in ASD rates observed in some studies of children conceived through ART may also reflect the characteristics of the population using these treatments, such as older parental age, which is independently associated with a higher risk of autism in offspring.

Overall, while some studies suggest a potential association, there is no conclusive evidence that ICSI directly increases the risk of autism.

Couples considering ICSI are encouraged to discuss any concerns with their fertility specialist, who can provide guidance based on the latest research and the specific circumstances of the couple.

Can ICSI cause chromosomal abnormalities?

Concerns about the potential for ICSI to cause chromosomal abnormalities stem from the bypassing of natural selection mechanisms that would normally prevent sperm with chromosomal abnormalities or poor quality from fertilizing an egg.

Despite these concerns, many children conceived through ICSI are healthy and do not have chromosomal abnormalities.

It’s also worth mentioning that preimplantation genetic testing (PGT) can be used alongside IVF and ICSI to screen embryos for chromosomal abnormalities before implantation, potentially reducing the risk of chromosomal abnormalities in the resulting pregnancy.

Couples considering ICSI are advised to discuss the benefits and risks with their fertility specialist, including any concerns about chromosomal abnormalities, to make informed decisions about their fertility treatments.

Can ICSI damage embryos?

During ICSI, a single sperm is injected directly into an egg to facilitate fertilization. While ICSI has significantly improved the chances of pregnancy for many couples, there are technical risks involved, including the potential for physical damage to the egg (oocyte) during the injection process.

The primary concern regarding embryo damage during ICSI relates to the potential for mechanical injury to the egg. This can include damage to the oocyte’s membrane or internal structure, which may affect its viability and the development of the embryo. The skill and experience of the embryologist performing the procedure are crucial in minimizing this risk. Despite these concerns, the success rates of ICSI indicate that the majority of eggs survive the procedure and can develop into healthy embryos.

It’s also important to note that advancements in ICSI technique and technology continue to improve the safety and efficiency of the procedure, reducing the risk of damage to eggs and embryos. Preimplantation genetic testing (PGT) can also be used alongside ICSI to help identify and select embryos with the best potential for healthy development.

Do ICSI babies look like their parents?

Babies conceived through ICSI, just like those conceived naturally, can look like their parents. The physical appearance of a child is determined by the genetic information inherited from both parents. ICSI is a technique used in assisted reproductive technology that involves injecting a single sperm directly into an egg to facilitate fertilization. This method does not alter the genetic material that the sperm and egg contribute to the baby. Therefore, the traits that determine a child’s physical appearance, such as eye color, hair color, facial features, and height, are all influenced by the genes passed down from the parents.

The resemblance of a child to their parents is a complex interplay of genetics, with each parent contributing approximately half of the child’s genetic material. The way these genes express themselves in the child can lead to a mix of features, with some resembling one parent more closely, others resembling the other parent, and some being a unique combination of both.

In summary, the process of ICSI does not affect the genetic factors that determine familial resemblance. Children born through ICSI have the same potential to resemble their parents as children conceived naturally.

How much does ICSI treatment cost?

ICSI treatment varies widely depending on several factors, including the country where the treatment is performed, the specific fertility clinic, and any additional services or treatments that may be required alongside ICSI.

In Tambre we consider that it is a medical decision that should not be associated with the purchasing power of the patient. For this reason, all treatments include both IVF and ICSI techniques at no additional cost. In this way we eliminate the tension that can generate such decisions. We want our patients to be calm and develop their assisted reproduction process in the most natural way possible, always accompanied by our team.

Are all the eggs collected used for ICSI?

Not all eggs collected during an IVF cycle are used for ICSI (Intracytoplasmic Sperm Injection). The number of eggs used depends on several factors such as egg quality or sperm quality, for example. quality of the Eggs or Sperm Quality, for example.

In practice, the goal is to optimize the number of quality embryos for transfer and possibly freezing, while balancing the risks and ethical considerations. The fertility specialist and embryology team will make recommendations based on the couple’s unique circumstances, the condition of the collected eggs, and the overall treatment goals.

Does ICSI guarantee fertilization?

ICSI significantly improves the chances of fertilization, especially in cases of severe male infertility or when previous IVF attempts have failed due to fertilization issues. By directly injecting a single sperm into an egg, ICSI bypasses many of the barriers to fertilization that can occur with traditional IVF or natural conception.

However, ICSI does not guarantee fertilization. While the technique ensures that the sperm reaches the interior of the egg, fertilization still depends on several factors: Egg Quality; Sperm Quality; Embryo Development; Laboratory Conditions.

Statistically, ICSI has a high fertilization rate. However, these rates can vary based on the factors mentioned above, and some eggs may not fertilize despite the use of ICSI.

How do embryologists choose the sperm for ICSI?

Embryologists select sperm for ICSI using a meticulous process that aims to choose the best possible sperm for fertilization. This selection is crucial because ICSI bypasses the natural selection process that occurs during conventional fertilization.

The goal of this selection process is to use a sperm that is most likely to fertilize the egg successfully and support normal embryo development. However, despite the careful selection process, not all ICSI procedures result in fertilization, and success rates can vary depending on several factors, including the underlying cause of infertility, the age of the female partner, and the quality of the eggs.

What are the risks associated with ICSI?

Intracytoplasmic Sperm Injection is a commonly used procedure in assisted reproductive technology, particularly for cases of male infertility. While ICSI has helped many couples conceive, it is associated with certain risks and potential complications, similar to other medical treatments.

It’s crucial for couples considering ICSI to discuss these risks thoroughly with their fertility specialist, who can provide personalized information based on their specific medical history, the quality of sperm and eggs, and other relevant factors. This discussion can help couples make informed decisions about their fertility treatment options.

Who should consider ICSI?

ICSI is an advanced technique that’s part of the IVF process. This method involves the direct insertion of a sperm into an egg to help with fertilization. Situations where ICSI might be recommended include:

Male factor infertility: This is the most common reason to use ICSI. It is recommended for couples where the male partner has low sperm count, low sperm motility (the ability of sperm to move), or poor sperm morphology (abnormal form).

Previous failures of in vitro fertilization: Couples who have undergone IVF but have experienced poor rates of fertilization or complete fertilization failure may be advised to test ICSI in subsequent cycles.

Obstructive azoospermia: This condition involves an obstruction in the male reproductive tract that prevents sperm from being ejaculated. Sperm can be recovered directly from the testicles or epididymis through surgical procedures and then used in the ICSI.

Nonobstructive azoospermia: Men who produce very few sperm that cannot reach ejaculation may have sperm recovered directly from the testicles for use in ICSI.

Use of frozen sperm: ICSI is often used when sperm has previously frozen, especially if there is a concern about the quality or quantity of sperm when thawing.

Use of sperm extracted from testicular biopsy: This includes cases in which sperm is extracted directly from the testicles due to the absence of sperm in ejaculation (azoospermia).

Advanced Maternal Age: Women of advanced maternal age may have a reduced number of eggs available. ICSI can maximize the chances of fertilization per retrieved egg.

Preimplantation Genetic Testing (PGT): Couples undergoing PGT to screen for genetic conditions might opt for ICSI to ensure each embryo has a clear origin from a single sperm, reducing the risk of sample contamination.

Unexplained Infertility: Some couples with unexplained infertility choose ICSI after unsuccessful attempts with conventional IVF or other fertility treatments.

What happens after ICSI?

After Intracytoplasmic Sperm Injection (ICSI) is performed, the process follows several key steps leading up to the potential implantation of the embryo. Here’s a general overview of what happens after ICSI:

Observation of Fertilization: The eggs are monitored to check for signs of fertilization. This usually involves observing the eggs under a microscope around 16 to 24 hours after the ICSI procedure to see if fertilization has occurred. Successful fertilization is indicated by the presence of two pronuclei – one from the sperm and one from the egg.

Embryo Development: Once fertilization is confirmed, the embryos are cultured in the laboratory for several days (typically 3 to 5 days) to allow them to develop. During this period, embryologists monitor the embryos to assess their quality, growth rate, and development. The goal is to select the healthiest and most viable embryo(s) for transfer.

Embryo Grading: Embryos are graded based on specific criteria, including their appearance, the number of cells, and the degree of fragmentation. This grading helps determine the best embryos for transfer or freezing.

Embryo Transfer: The next step is the embryo transfer, where one or more selected embryos are placed into the woman’s uterus.
Luteal Phase Support: After the embryo transfer, progesterone is often given to help support the uterine lining and increase the chances of implantation and pregnancy. This phase is crucial for establishing a pregnancy.

Pregnancy Test: Approximately two weeks after the embryo transfer, a blood test is conducted to measure the levels of human chorionic gonadotropin (hCG), the hormone produced in early pregnancy. A positive test indicates that implantation has occurred and pregnancy has begun.

Follow-up: If the pregnancy test is positive, additional follow-up, including ultrasound, will be scheduled to confirm the viability of the pregnancy and monitor its progression. If the cycle does not result in a pregnancy, the fertility team will review the cycle to provide guidance on the next steps, which may include another round of IVF/ICSI or consider other options.

Throughout the process, emotional support and counselling are often available to help couples manage the stress and emotional impact of fertility treatment. In Clinica Tambre, we have a Psychological Support Unit to help patients in this process that affects emotions so much. Travel after ICSI can vary significantly from couple to couple, depending on several factors, including the reasons for infertility, embryo quality, and the woman’s body’s response to treatment.