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Risks of ICSI

Intracytoplasmic Sperm Injection (ICSI) is a procedure performed in the Laboratory where micro-manipulation is used to literally insert a spermatozoa into an egg. This procedure has been widely used world-wide for over a decade. The primary indications for ICSI are abnormal sperm number, motility, morphology (shape), previous failed fertilization in IVF, or unexplained infertility (normal work-up and negative laparoscopy). Other indications include sperm-egg binding problems, anti-sperm antibodies, frozen sperm with poor motility and quality as well as sperm obtained from the male surgically through MESA/PESA in the case of occlusion of the vas deferens (vasectomy, congenital absence of the vas deferens). Occasionally sperm are extracted directly from the testes and used in ICSI. Not all laboratories use the same criteria as indications for the procedure. Some ART labs will perform ICSI on a few of the mature eggs to ‘assure fertilization.’ This may assure that the patient will have an embryo transfer. Hershalg et al (1) found that IVF-ICSI split cycles rescued 10 % of cycles that would likely have failed due to fertilization failure, yet Staessen et al (2) and Fishel et al (3) were unable to show convincing data that there was a significant increase in pregnancy rates when the semen parameter were normal. Most of the studies are small in number so generalizations are difficult to make. Therefore, couples must make informed decisions based on their unique case and incomplete data from studies.

In a review of over 8000 children born from ICSI, Van Steirteghem et al (4) found a slight but significant increase in de novo sex chromosome aneuploidies (abnormal chromosme numbers; 0.6% instead of 0.2%) and an increase structural chromosome abnormalities (0.4% instead of 0.07%) as well as an increase in paternally inherited chromosome deletions, mostly on the Y chromosome. 40 % were twins, 4 % triplets and the rest singletons. The increase may be due to the underlying infertility cause. A man may have a balanced chromosome translocation, CF mutation, or Y chromosome microdeletion causing the infertility and ICSI could pass it on. Therefore, we suggest genetic testing of the husband for karyotype and Y deletions and the wife for CF mutations. The congenital anomaly rate appears to be the same as conventional IVF (about 4%), with a slight increase in hypospadias (i.e. urogenital malformation; 5). The potential exists to incorporate sperm mitochondria into the eggs (i.e. mitochondrial diseases) and to fertilize an egg that may not normally fertilize. The above would be considered ICSI procedure independent. Procedure dependent risks to the eggs include disruption of the spindle apparatus, injection of foreign substances, and imprinting diseases like Beckwith-Weidemann Syndrome (see our page on genetic imprinting and ART). This is a condition where there may be abnormal DNA methylation leading to a potential increase in rare syndromes. For instance, the risk of Angelman Syndrome increases from 1/300,000 to 1/30,000 with ICSI (6). Many years and large studies are needed to confirm these findings. The obstetrical outcome is no different with respect to miscarriages (16%), and low-birth weight is seen in both IVF and ICSI. Developmentally, at least up to two years, the children to not seem to suffer any delays.

References:

1. Hershlag A, Paine T, Kvapil G, Feng H, Napolitano B. Invitro fertilization-intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure. 2002. Fertility Sterility. 77(2):229-232.

2. Staessen C, Camus M, Claen K, De Vos A, Van Steirteghem A. Conventional in-vitro fertilization versus intracytoplasmic sperm injection in sibling oocytes from couples with tubal infertility and normozoospermic semen. 1999. Hum. Reprod. 14(10):2474-9.

3. Fishel S, Aslam I, Lisi F, Rinaldi L, Timson J, Jacobson M, Gobetz L, Green S, Campbell A, Lisi R. Should ICSI be the treatment of choice for all cases of in-vitro conception? 2000. Hum. Reprod 15(6):1278-83.

4. Van Steirteghem A, Bonduelle M, Devroey P, Liebaers I. Follow-up of children born after ICSI. 2002. Hum. Reprod. 8(2):111-116.

5. Retzloff MG, Hornstein MD. Is intracytoplasmic sperm injection safe? 2003. Fertil. Steril. 80(4):851-859.

6. Kurinczuk J. From theory to reality-just what are the data telling us about ICSI offspring health and future fertility and should we be concerned. 2003. Hum. Reprod. 18(5):925-931.
 

 

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