Reply of the Authors

Abstract

In response to the letter from Dr. Gleicher, we make the following points for consideration by the readers.A critical pre-requisite before any randomized controlled trial (RCT) is equipoise between two apparently similar treatments. At 8.8% triplet and higher order multiples, using Dr. Gleicher's method, there is no equipoise with our COH-IUI treatment. Any RCT by us using Dr. Gleicher's regimen would be considered unethical by our Institutional Human Research and Ethics Committee.Paragraph three in the letter from Dr. Gleicher is a summation of the paper published by Dr. Gleicher and his colleagues in the New England Journal of Medicine in 2000. At 8.8% triplets and above, we can understand Dr. Gleicher's statement that IVF should replace COH-IUI for his patients.Four ASRM presidents (references 25–27 in our manuscript) said there were no guidelines to avoid high-order multiple pregnancies caused by ovulation induction. After our publication (1Healy D. Rombauts L. Vollenhoven B. Kovacs G. Burmeister L. One triplet pregnancy in 510 controlled ovarian hyperstimulation and intrauterine insemination cycles.Fertil Steril. 2003; 79: 1449-1451Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar), some guidelines are now available.The Chairman of the European Society of Human Reproduction and Embryology (ESHRE) stated in 2002 in The Lancet that multiple pregnancy is the most frequent and most serious iatrogenic complication of ART (2Evers J.L.H. Female subfertility.Lancet. 2002; 360: 151-159Abstract Full Text Full Text PDF PubMed Scopus (516) Google Scholar).World Health Organization (WHO) authorities have classified triplet pregnancies as a major pathology (3Ozturk O. Templeton A. Multiple pregnancy in assisted reproduction techniques.in: Vayena E. Rowe P.J. Griffin P.D. Current practices and controversies in assisted reproduction Report of a WHO meeting. WHO Publications, 2002: 220-234Google Scholar). The single, live birth rate per cycle started is the outcome measure advocated by ESHRE and WHO for all COH-IUI or IVF programs (2Evers J.L.H. Female subfertility.Lancet. 2002; 360: 151-159Abstract Full Text Full Text PDF PubMed Scopus (516) Google Scholar, 3Ozturk O. Templeton A. Multiple pregnancy in assisted reproduction techniques.in: Vayena E. Rowe P.J. Griffin P.D. Current practices and controversies in assisted reproduction Report of a WHO meeting. WHO Publications, 2002: 220-234Google Scholar). It is our Table 1. It is these authorities, not us, that suggest all other outcomes should be regarded as treatment failures. In response to the letter from Dr. Gleicher, we make the following points for consideration by the readers. A critical pre-requisite before any randomized controlled trial (RCT) is equipoise between two apparently similar treatments. At 8.8% triplet and higher order multiples, using Dr. Gleicher's method, there is no equipoise with our COH-IUI treatment. Any RCT by us using Dr. Gleicher's regimen would be considered unethical by our Institutional Human Research and Ethics Committee. Paragraph three in the letter from Dr. Gleicher is a summation of the paper published by Dr. Gleicher and his colleagues in the New England Journal of Medicine in 2000. At 8.8% triplets and above, we can understand Dr. Gleicher's statement that IVF should replace COH-IUI for his patients. Four ASRM presidents (references 25–27 in our manuscript) said there were no guidelines to avoid high-order multiple pregnancies caused by ovulation induction. After our publication (1Healy D. Rombauts L. Vollenhoven B. Kovacs G. Burmeister L. One triplet pregnancy in 510 controlled ovarian hyperstimulation and intrauterine insemination cycles.Fertil Steril. 2003; 79: 1449-1451Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar), some guidelines are now available. The Chairman of the European Society of Human Reproduction and Embryology (ESHRE) stated in 2002 in The Lancet that multiple pregnancy is the most frequent and most serious iatrogenic complication of ART (2Evers J.L.H. Female subfertility.Lancet. 2002; 360: 151-159Abstract Full Text Full Text PDF PubMed Scopus (516) Google Scholar). World Health Organization (WHO) authorities have classified triplet pregnancies as a major pathology (3Ozturk O. Templeton A. Multiple pregnancy in assisted reproduction techniques.in: Vayena E. Rowe P.J. Griffin P.D. Current practices and controversies in assisted reproduction Report of a WHO meeting. WHO Publications, 2002: 220-234Google Scholar). The single, live birth rate per cycle started is the outcome measure advocated by ESHRE and WHO for all COH-IUI or IVF programs (2Evers J.L.H. Female subfertility.Lancet. 2002; 360: 151-159Abstract Full Text Full Text PDF PubMed Scopus (516) Google Scholar, 3Ozturk O. Templeton A. Multiple pregnancy in assisted reproduction techniques.in: Vayena E. Rowe P.J. Griffin P.D. Current practices and controversies in assisted reproduction Report of a WHO meeting. WHO Publications, 2002: 220-234Google Scholar). It is our Table 1. It is these authorities, not us, that suggest all other outcomes should be regarded as treatment failures.