Micromanipulation (ICSI)

Micromanipulation: Introducing the sperm cell into the egg (ICSI)
History of micromanipulation

The spread of in vitro fertilization solved the infertility issues of those couples in which previous fallopian tube diseases or the lack of the tubes caused infertility, and when behind infertility lays a mild andrological problem.

In the case of some high degree andrological deficiencies and in some immunologic infertility situations, during IVF the fertilization rate was incredibly low. Because in this case the sperm cell cannot cross the glycoprotein membrane (the pellucid area) of the egg, first scientists attempted to break the membrane with a thin needle, after which they developed the technique of introducing sperm under the glycoprotein membrane. However, the fertilization rate and the pregnancy rate was still low, until 1992 when Italian scientists decided to introduce the sperm directly into the ovule with the use of a micromanipulator (Intra Cytoplasmic Sperm Injection-ICSI). In 1995, spreading of the method gained large popularity due to the scientific confirmation of the fact that through intracytoplasmic sperm injection (ICSI) we can obtain a fertilization rate similar to that of a traditional IVF procedure using normal sperm cells. 

Types and indications of ICSI

Soon it was discovered that in order to be introduced in the ovule, sperm can be obtained not only by ejaculating, but also through the epididymis (MESA - ICSI), or directly from the surface of the Sertoli cells located in the seminal epithelium, which produce spermatozoa (TESE - ICSI). In parallel to these discoveries, the range of indications for this intervention changed too. Its use was also extended to cases where the sperm cell could not attach to the egg, and subsequently fertilization did not occur. In immunological infertilities (the husband produces antibodies against his own spermatozoa, or the anti-spermatozoa antibodies in the wife’s body prevent fertilization), with the help of the ICSI a high pregnancy rate was obtained.

The method was applied also in some cases when during traditional in vitro fertilization fewer ovules were fertilized – in an inexplicable way. Spermatozoa obtained from the epididymis or the testicle represented a solution to infertility caused by the presence of closed spermatic cord due to a previous infection or when it didn’t develop due to congenital reasons. The method was spread even more due to the fact that the freezing technique for the spermatozoa aspired from the seminal epithelium and from the epididymis was elaborated as early as 1995, and thus performing a surgical intervention on the mail partner before each intervention was no more necessary. 

The sequences ofan ICSI procedure

The used drugs, the stimulating treatment of the ovaries, the monitoring of the cycles, the ultrasound controlled aspiration technique of the ovules fully complies with those described at the traditional in vitro fertilization procedure. (However it is worth mentioning that in many cases before ICSI we will perform a detailed chromosomal examination of the future father.)

The preparation technique of the ovules and the fertilization method differ fundamentally. After a short maturation phase the ovules discovered under the stereomicroscope are subjected to an enzymatic treatment, we clean the egg from the surrounding cells. The injection takes place afterwards. The prepared ovule (and magnified 400 times) is first fixed with a capillary device, after which using a thin capillary needle (inner diameter of 5 microns) we introduce the immobilized spermatozoon in the cytoplasm of the ovule. Checking fertilization takes place the following day and the pre-embryos are transferred in the uterine cavity on the third day – exactly like in the case of the traditional in vitro fertilization.

The expected success rate corresponds to the pregnancy rate of the traditional IVF, some fertility centers having reported a slightly higher pregnancy rate than during the IVF.
The thicker glycoprotein membrane (the pellucid area) makes it harder not only for the spermatozoon to reach the ovule, but also for the developed embryo to exit the possibly fertilized ovule. In order to ease the process, the assisted hatching technique was developed.

Is there any enhanced risk?

Based on the previously described facts, justified question arises regarding the health of the future newborn, considering that the gametes have been subjected to numerous mechanical and biochemical effects. Should we worry about a possibly increased number of congenital anomalies? As a foreign genetic material (DNA) is introduced in the egg, won’t this cause the increase of the chromosomal anomalies?

Well, the first study published in 1996, including data from 877 infants conceived with ICSI demonstrated that the number of developmental anomalies in newborn children conceived with micromanipulation did not increase and it was similar to that of the average population. The other follow-up study performed in 1999 gathered data from 2995 IVF babies and 2840 ICSI newborn. The length of the pregnancy, birth weight and the frequency of premature births were similar in both groups. There was no statistically significant difference in the frequency of the congenital developmental anomalies or in the rate of the chromosomal anomalies.

The development of ICSI children, learning issues, their adjustment to their environment, and their integration was not different from the normal population. The complete presentation of the study would overpass our possibilities, but to summarize we can say the following: there is no evidence that the ICSI or the IVF newborn have any kind of mental or physical problems compared to the average population. Our purpose is to apply the safest techniques, adapted to the current status of medicine, so we can help infertile couples to have physically and psychically healthy children.

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