For personal use. Only reproduce with permission from The Lancet Publishing Group. 1270 THE LANCET • Vol 358 • October 13, 2001 CORRESPONDENCE 3 Lopalco L, Barassi C, Pastori C, et al. CCR5-reactive antibodies in seronegative partners of HIV-seropositive individuals down-modulates surface CCR5 in vivo and neutralize the infectivity of R5 strains of HIV-1 in vitro. J Immunol 2000; 164: 3426–33. transmission of chromosomal or genetic disease has serious concerns, since male infertility is frequently associated with genetic defects, such as karyotype abnormalities, microdeletions of the Y chromosome long arm, and sperm aneuploidy. 2-4 Sperm of severely infertile men might carry genetic alterations because a constitutional aberration exists or because sperm are altered by mitotic or meiotic errors caused by impaired spermatogenesis. Chromosomal and DNA abnormalities confined to sperm cannot yet be studied to select sperm before ICSI. However, many constitutional genetic anomalies affecting spermatogenesis can be analysed during the diagnostic work-up. Genetic screening has, therefore, become mandatory in severely infertile individuals and genetic counselling is necessary in all ICSI candidates. Since 1996 we have screened for genetic anomalies in 680 severely oligozoospermic men (sperm count <5 million/mL) who were candidates for ICSI. We did genetic tests for the most common causes of male infertility (table). The overall prevalence of genetic abnormalities was 12·2%. Genetic alterations represent a major cause of spermatogenic impairment in infertile male candidates for assisted repro- duction techniques, and our findings concur with those of Sutcliffe and colleagues. The higher frequency of genitourinary defects in ICSI children found in that study and by other workers 5 might also be explained by our results. Genetic alterations that cause infertility in the father, could produce a more evident phenotype in their children. We stress the need for a careful diagnosis of male infertility to avoid transmission, persistence, or even an increase of genetic defects in future generations. *Carlo Foresta, Alberto Ferlin University of Padova, Department of Medical and Surgical Sciences, Clinica Medica 3, Centre for Male Gametes Cryopreservation, Via Ospedale 105, 35128 Padova, Italy (e-mail: forestac@protec.it) 1 Sutcliffe AG, Taylor B, Saunders K, Thornton S, Lieberman BA. Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case-control study. Lancet 2001; 357: 2080–84. 2 Foresta C, Ferlin A, Moro E, Scandellari C. Y chromosome. Lancet. 2000; 355: 234–35. 3 Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev 2001; 22: 226–39. 4 Martin RH. Genetics of human sperm. J Assist Reprod Genet 1998; 15: 240–45. 5 Wennerholm UB, Bergh C, Hamberger L, et al. Incidence of congenital malformations in children born after ICSI. Hum Reprod 2000; 15: 944–48. Chemotherapy for non- small-cell lung cancer Sir—V Georgoulias and colleagues (May 12, p 1478) 1 report a comparison of platinum-based and non-platinum- based chemotherapy regimens for advanced non-small-cell lung cancer (NSCLC). Although the two combinations had similar activity, the investigators recommend the gemcitabine and docetaxel combination in view of the convenience of administration. In the 1990s, several new chemotherapeutic drugs for lung cancer emerged but results of large phase III studies were disappointing. 2,3 A standard treatment for advanced lung cancer, especially for NSCLC, has not been established. Several well designed clinical trials have been reported, however the prognosis of lung cancer remains poor in the real world. Regimens designed for selected patients might be inappropriate in clinical practice. Many of our patients have coexistent disorders and may be too sick to be enrolled into clinical trials. We appreciate hearing from Georgoulias and colleagues about how the regimen can be applied to patients with NSCLC in clinical practice. The investigators also report that patients with non-adenocarcinoma histology had a better response to cisplatin and docetaxel than did patients with adenocarcinomas, where- as the opposite was seen in the gem- citabine and docetaxel regimen. Adenocarcinoma and non-adeno- carcinoma are treated as NSCLC, and the same chemotherapeutic regimen is generally indicated for both. We question the indication of the recommended regimen only for patients with adenocarcinoma of the lung. Are separate regimens needed for adenocarcinoma and non-adeno- carcinoma of the lung? *Hiroaki Satoh, Kiyohisa Sekizawa Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki 305-8575, Japan (e-mail: hirosato@md.tsukuba.ac.jp) 1 Georgoulias V, Papadakis E, Alexopoulos A, et al. Platinum-based and non-platinum- based chemotherapy in advanced non-small- cell lung cancer: a randomised multicentre trial. Lancet 2001; 357: 1478–84. 2 Kelly K, Crowey J, Bunn PA, et al. A randomized phase III trial of paclitaxel plus carboplatin (PC) versus vinorelbine plus cisplatin (VC) in untreated advanced non- small cell lung cancer (NSCLC): Southwest Oncology Group (SWOG) trial. Proc Am Soc Clin Oncol 1999; 18: 461. 3 Johnson DH, Zhu J, Schiller J, et al. Randomized phase III trial in metastatic Offspring conceived by intracytoplasmic sperm injection Sir—A Sutcliffe and colleagues (June 30, p 2080) 1 report follow-up of children conceived naturally or by intracytoplasmic sperm injection (ICSI). Neurodevelopmental scores and perinatal outcome did not differ significantly between groups. The rate of congenital anomalies was similar overall, but seem higher in ICSI-derived children. The subgrouping of ICSI children according to paternal sperm analysis outlined that congenital anomalies were significantly higher in children conceived to oligozoospermic men than in children conceived to fathers who had other indications for ICSI (20·7 vs 8·0%). A more detailed analysis of the data allows us to derive further considerations. Major congenital anomalies were present in eight (6·6%) of 121 ICSI children conceived to oligozoospermic men, and two (2·3%) of 87 children conceived to non-oligozoospermic men. Eight (80·0%) of ten major anomalies and 17 (77·3%) of 22 minor anomalies in the ICSI group were recorded in children conceived to oligozoospermic men. Furthermore, the rate of geni- tourinary defects (such as hypospadia or cryptorchidism) was higher in the group of ICSI children (five [2·4%] of 208) compared with the group of 221 naturally conceived children, in which they were totally absent. In the ICSI group, genitourinary anomalies were present only in children of oligo- zoospermic men (five of 121 vs 0 of 87). Congenital anomalies in ICSI children are not related to the ICSI technique, but to the seminal disorder (oligozoospermia). The risk of Causes of infertility Number of patients (n/total [%]) Chromosomal alterations 32/680 (4·7) (karyotype analysis) Y chromosome 38/680 (5·6) microdeletions CFTR gene mutations 6/680 (0·9) Androgen-receptor gene 7/680 (1·0) mutations Genetic screening in 680 severely oligozoospermic candidates for ICSI (sperm count <5 million/mL)