Correspondence

Selection of Spermatozoa with Normal Nuclei to Improve the Pregnancy Rate with Intracytoplasmic Sperm Injection

N Engl J Med 2001; 345:1067-1068October 4, 2001

Article

To the Editor:

Intracytoplasmic injection of sperm is the recommended treatment for male infertility, associated with an average pregnancy rate per cycle of about 30 percent.1 Although sperm count and motility were found to have no effect on the outcome of intracytoplasmic sperm injection,2 scanning and transmission electron microscopy indicated that the achievement of pregnancy may depend on normal morphology of the sperm nucleus.3

We therefore introduced the motile-sperm organelle-morphology examination (MSOME), by which the fine nuclear morphology of motile spermatozoa is examined in real time with an inverted light microscope equipped with high-power differential interference contrast (Nomarski/DIC) optics (magnification, ×150) enhanced by digital imaging (magnification, ×44) to achieve a total magnification of over 6000. This method can identify a motile spermatozoon with a normal nucleus, defined by an oval shape with a smooth configuration (length, 4.75±0.28 μm; width, 3.28±0.20 μm) and a normal nuclear content (with <4 percent of the nucleus occupied by vacuoles). In a preliminary study, the pregnancy rate was assessed in 24 couples who underwent a single cycle of intracytoplasmic sperm injection with spermatozoa with normal nuclei that were selected by the MSOME. Inclusion criteria were an age of less than 37 years for the woman, more than three retrieved ova, a diagnosis of male infertility, and the previous failure of at least 5 consecutive routine cycles of in vitro fertilization and intracytoplasmic sperm injection (mean, 7.6±2.1 cycles). Written informed consent was obtained from all participants.

No significant differences were found in the average number of retrieved, injected, and fertilized ova; the number of transferred embryos; or the fertilization rate per cycle between the previous routine in vitro fertilization and intracytoplasmic sperm injection procedures and the MSOME-based intracytoplasmic preselected-sperm injection. However, the mean pregnancy rate after intracytoplasmic preselected-sperm injection was 58 percent (Table 1Table 1Outcomes for Previous Routine in Vitro Fertilization and Intracytoplasmic Sperm Injection Procedures and Intracytoplasmic Preselected-Sperm Injection.).

It is noteworthy that in three men we were unable to retrieve spermatozoa with normal nuclei, and in these cases intracytoplasmic preselected-sperm injection was performed with sperm cells with subtle nuclear malformations. None of the women in these couples became pregnant. The rates of pregnancy, implantation, and abortion in the remaining 21 couples were 67 percent, 47 percent, and 5 percent, respectively. Seventeen infants have been delivered so far, and all are normal and healthy. Considering that the chances of pregnancy after five consecutive routine trials of intracytoplasmic sperm injection are less than 3 percent,4 this study indicates that the fine morphology of the sperm nucleus is an important factor in embryo survival following intracytoplasmic sperm injection. Thus, intracytoplasmic preselected-sperm injection may be an efficient treatment for couples with male infertility for whom routine in vitro fertilization and intracytoplasmic selected-sperm injection have failed.

Benjamin Bartoov, Ph.D.
Bar Ilan University, 52900 Ramat Gan, Israel
bartoob@mail.biu.ac.il

Arie Berkovitz, M.D.
Meir Hospital, 44281 Kfar Saba, Israel

Fina Eltes, M.Sc.
Bar Ilan University, 52900 Ramat Gan, Israel

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