Birth Defects After Assisted Reproduction
The bypass of natural barriers to fertilization, possible genetic defects in men with severe male infertility, and the use of severely abnormal sperm for intracytoplasmic sperm injection has engendered concern over the impact of ICSI on the genetic complement of the offspring . Previous studies have suggested no increase in birth defect rates when IV-F alone was used to induce conception. Van Steirteghem reported no increase in the congenital malformation rate in their center after ICSI when compared with the general population. Of 877 children born after ICSI procedures, 23 (2.6 percent) had major congenital malformations compared to 2.0 to 2.8 percent in the general population and 1.9 to 2.9 percent of children resulting from assisted reproductive techniques.
Sex chromosomal abnormalities have also been reported in ICSI cases. In’t Veld et al. reported on 12 patients with ICSI pregnancies who underwent prenatal diagnosis for advanced matemal age. Three of the 12 women had twin pregnancies for a total of 15 diagnostic procedures by amniocentesis or chorionic villus sampling. A total of five chromosomal abnormalities were detected: two cases of XXY, one complex mosaic 45,X/46,X.dic(Y)(q11)/46.X.del(Y)(qll), and two cases of 45 XO. This high rate of sex chromosome abnormalities has not been corroborated by other studies. The Brussels group reported on a total of 585 prenatal diagnoses performed in pregnancies established by ICSI. A total of six sex chromosome abnormalities (1.0 percent) were detected compared to 0.2 percent in the general population. This difference did not achieve statistical significance. Govaerts et al. reported on 55 karyotypes obtained by amniocentesis or chorionic villus sampling in pregnancies from ICSI and found no sex chromosome abnormalities. When sex chromosome abnormalities have been identified it is unclear whether they are related to the ICSI procedure itself or can be ascribed to advanced matemal age. What is reassuring is that the rates of nonsex chromosomal abnormalities in the ICSI population published to date do not exceed the rates seen in the general population. The relationship of ICSI to sex chromosomal abnormalities in offspring may be related to the association between Y chromosomal abnormalities and severe male factor infertility. Several investigators have reported that up to- 13% of men with azoospermia or severe oligospermia may have deletions of 15,000 to 200,000 base pair lengths of Y chromosome. At least one gene (DAZ; deleted in azoospermia) is deleted in 13 percent of patients with non-obstructive azoospermia.
Although chromosomal abnormality rates in offspring after these procedures have not exceeded those in the general population, experience with these techniques is brief. Genetic counseling, preimplantation genetic diagnosis, and state of the art prenatal diagnosis must also be available to couples enrolled in assisted reproductive programs. Genetic counseling should be available to all couples. All couples undergoing micromanipulation procedures are strongly urged.to have prenatal diagnosis with amniocentesis or chorionic villus sampling. The need for prenatal diagnosis is dependent on whether the couple would consider terminating the pregnancy if the results are abnormal. If the couple would carry a pregnancy to term regardless of the results of prenatal diagnosis, then the procedure of prenatal intervention would carry risks to the fetus without benefit and therefore cannot be required.
