ICSI Technique for Male Infertility

What is ICSI?

Intracytoplasmic sperm injection, better known by the acronym ICSI, is a relatively recent assisted reproductive technology (ART) technique. ICSI is a well-established and widespread ART technique. However, it is not the first choice technique in cases of infertility problems because it has a more invasive impact on the oocyte with the risk of irreversibly damaging it. However, it is a technique that has overcome serious male infertility problems that, before its advent, could only be solved using donor sperm. Today, ICSI has achieved success rates similar to those of IVF and has become a benchmark even in case of failure. Alongside ICSI, intracytoplasmic injection of morphologically selected sperm or IMSI is a laboratory technique used in in vitro fertilization (IVF) treatments and consists of introducing morphologically selected sperm into the ovum. IMSI involves selecting sperm using a microscope five times more powerful than that used for ICSI. Selecting sperm without morphological alterations increases the chances of successful embryo implantation and reduces the risk of miscarriage. This is a technique that still requires specific studies to properly assess its real effectiveness and decide to use it routinely in assisted reproduction laboratories. However, it is recommended for couples who have had several unsuccessful attempts at IVF.

When to use ICSI?

ICSI is recommended when clinical examinations show a severe reduction in male reproductive capacity, i.e., a significant deficit in sperm concentration (oligospermia), motility (asthenospermia) and/or shape (teratospermia). ICSI has therefore become the technique of choice when the semen analysis shows values that make it impossible to fertilize the oocyte naturally or with simpler assisted reproductive techniques such as intrauterine insemination or IVF. ICSI is also recommended in the presence of anti-sperm antibodies in the ejaculate that could block penetration of the oocyte with IVF, or in case of reduced or failed fertilization of oocytes during a previous IVF for unknown reasons, or when the number of oocytes retrieved is extremely low. Intracytoplasmic insemination is also necessary when a situation of azoospermia (i.e., the absence of sperm in the ejaculate) is resolved by techniques such as TESE (testicular sperm extraction) and MESA (microsurgical epididymal sperm aspiration). The first consists of extracting sperm by testicular biopsy; the second consists of microsurgically aspirating sperm from the epididymis.

Intracytoplasmic insemination is also used in most patients with retrograde ejaculation, a condition in which sperm is ejaculated into the urinary bladder. Finally, ICSI is the technique of choice when oocytes are thawed. We are talking here about situations of female fertility preservation by oocyte cryopreservation.

ICSI Procedure: Characteristics and Possibilities

The procedure takes place in several steps:

• Ovarian stimulation: In order to obtain the oocytes necessary for ICSI, the ovaries are stimulated by the daily administration of hormones for about 2 to 3 weeks. During this period, ultrasounds and blood tests are performed to check both the hormone level and the development of the follicles (the small cystic formations containing the eggs) in the ovaries;
• Oocyte collection: In the ICSI technique, the eggs are extracted by puncture and aspiration of the follicles. This procedure requires sedation anesthesia for the patient. Once extracted, the eggs are kept in culture for a few hours and during this time, the sperm is prepared to extract the motile sperm. The eggs are then prepared by removing the outer layer of cells covering them and, by intracytoplasmic micro-injection, introducing a sperm into each oocyte;
• In vitro fertilization: The day after the oocyte retrieval, fertilization is checked and the number of oocytes that have been correctly fertilized is assessed, showing the presence of two pronuclei (2pn), one of maternal origin and the other of paternal origin. In the following days, the fertilized oocytes undergo the physiological divisions characteristic of correct embryonic development (cleavage), until the moment when, by selecting the embryos with the best developmental characteristics, they are transferred to the uterus. Normally, one or two embryos are transferred to the uterus depending on the characteristics of the couple and by personalizing the choice, in agreement with the couple, based on the clinical history and the characteristics of the embryos obtained to be transferred. The embryos are inserted into a thin catheter and are introduced into the uterus. At this stage, the woman is awake and, as the procedure is totally painless, no anesthesia is needed. If two embryos are transferred, only one is normally implanted, but it should be kept in mind that both embryos can implant, resulting in a twin pregnancy;

How does ICSI fertilization take place?

In vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology that allows fertilizing an oocyte in the laboratory using a single sperm. The IVF-ICSI protocol generally begins with ovarian stimulation to produce several mature oocytes. The oocytes are then retrieved by ovarian puncture and placed in a specific culture medium in the laboratory. Meanwhile, the sperm are prepared for ICSI by selecting, cleaning, and immobilizing them. ICSI consists of injecting a single sperm directly into the cytoplasm of an oocyte using a microneedle. Once the oocytes are fertilized, they are placed in an incubator to allow their development. The embryos are then transferred to the woman's uterus a few days after fertilization to continue their development. The course of IVF-ICSI may vary from one ART center to another, but the main steps include ovarian stimulation, follicular aspiration, sperm preparation, ICSI, embryo culture, and embryo transfer.

What are the postoperative consequences of ICSI?

The postoperative consequences of ICSI are generally well tolerated by patients. After the procedure, it is possible for the woman to experience mild pain in the pelvic region or slight discomfort for a few days. However, these symptoms usually disappear quickly. Women can resume their usual activities the day after the procedure, but it is recommended to avoid strenuous physical activity for at least one week. It is also necessary to avoid sexual intercourse for a few days after the procedure to avoid infection. The success rate of IVF-ICSI depends on many factors, including the woman's age, the quality of the oocytes and sperm, and the competence of the ART team. However, the overall success rate of IVF-ICSI is approximately 40 to 50%, which can vary depending on each individual case. It is essential to discuss the risks and benefits of ICSI with your ART specialist before making a decision.

ICSI Results

Since the sperm used for ICSI are not naturally selected from those contained in the ejaculate, and therefore do not compete with others for fertilization, it has been suggested that this technique could increase congenital anomalies. However, several studies conducted on children born using this technique have not revealed any concerns.

Therefore, children born by ICSI for serious male infertility problems may have a slightly increased risk of chromosomal alterations due to sperm quality. On the other hand, data on cognitive and psychomotor development have not shown any difference between children conceived spontaneously, by intrauterine insemination or after ICSI or IVF. The latter, however, due to its less invasive nature, should remain the first choice for couples without an absolute indication for ICSI.

In summary, if a woman becomes pregnant through anterological means, there is a 1.5 to 3% risk that the baby will have a serious congenital anomaly. The risk of congenital anomalies associated with ICSI is similar to that of in vitro fertilization, but slightly higher than that of natural conception. The slightly higher risk of congenital anomalies may in fact be due to infertility and not to the treatments used to overcome it. Some of the problems causing infertility may be genetic. Thus, male babies conceived by ICSI may have the same infertility problems as their father.

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