In vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is the leading method of treatment for male-factor infertility because of its ability to achieve fertilization regardless of semen characteristics. Even the use of immature spermatozoa recovered from the epididymus or testes results in reasonable pregnancy rates. This study by Palermo et al reports on the largest case series on ICSI in the United States from the group at The New York Hospital-Cornell Medical Center. There were 751 couples treated in 987 cycles of IVF with ICSI. The number of embryos transferred was dependent on maternal age. There were 547 positive b-hCG tests (55.4%), of which 7.8% were biochemical pregnancies and 3.3% were blighted ovum. The remaining 437 pregnancies developed a fetal heartbeat, resulting in a 44.3% clinical pregnancy rate per oocyte retrieval. There were 44 miscarriages, seven elective terminations for chromosomal trisomies (only one of which was a sex chromosome abnormality) and four ectopic pregnancies, resulting in a delivery rate of 38.7%. The frequency of multiple gestation at six weeks was 43.7%.
The proportion of pregnancies with fetal heartbeats that were miscarried or terminated was age-dependent: 6.3% in women younger than 35 years; 13.6% in women between 35-39 years; and 33.8% in women older than 39 years. In 11 of the 44 miscarriages, fetal tissue was examined, and eight of the 11 had chromosomal abnormalities. The degree of sperm maturity had no influence on outcome, although only 94 cycles were done following surgical retrieval of sperm.
Only 2.6% of the 578 newborns exhibited congenital abnormalities at birth. Only 1.6% had major malformations, compared to 3.5% for conventional IVF at the same program and 3.7% in the normal fertile population in the state of New York. (Palermo GD, et al. JAMA 1996;276:1893-1897.)
COMMENT BY SARAH L. BERGA, MD
This report is, for the most part, reassuring. Couples contemplating IVF with ICSI are quite concerned about the invasiveness of injecting sperm into an oocyte. Apparently, this fertilization technique successfully overcomes sperm deficits without compromising the offspring in any major way. The major problem revealed by this report is the high rate of multiple gestation. The number of fertilized oocytes transferred was apparently individualized according to maternal age. While this approach makes good sense, there is always a tendency to transfer more rather than fewer embryos simply because the pregnancy rates go up along with the multiple gestation rates. This is an expensive and time-consuming procedure, so it is to the benefit of all to maximize its return. The authors do remark that they "are considering reducing the number of embryos replaced in selected couples for whom this reduction would not jeopardize their chances for a successful outcome." A crystal ball would be helpful for this task.
Are there any hidden downsides to ICSI? The world’s experience is still not large. A formal power analysis was not done for any of the parameters examined, but one would guess that a larger sample size would be needed to determine whether chromosomal trisomies and translocations were increased by this technique. In the present report, chromosomal abnormalities were largely attributed to oocyte age. A major hidden risk, however, is the transmission to the embryo of other genetic defects that do not result in miscarriage or malformation. The authors comment on the increased risk of mutations in the cystic fibrosis transmembrane-conductance regulator (CFTR) gene in men requiring epididymal aspiration. Also, as reviewed earlier (OB/GYN Clin Alert 1996;13:29), about 20% of men with idiopathic azoospermia have microdeletions in a region of the Y chromosome thought to play a critical role in human spermatogenesis (Najmabadi H, et al. J Clin Endocrinol Metab 1996;81:1347-1352). Clearly, the male offspring of men requiring ICSI for microdeletions of the Y chromosome are likely to inherit the same microdeletions. At the present time, however, testing for Y-chromosome microdeletions is not widely available. Further, the cause of male infertility is frequently occult, so it is difficult to determine whether there is a transmissible cause of male infertility. Nonetheless, this topic should be broached in a supportive fashion with couples contemplating ICSI so that they have the chance to factor it into their decision-making process.
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