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Gender selection of embryos after PGD for other independent medical reasons – a viewpoint from Singapore
RBMOnline - Vol 12. No 3. 2006 392-393 Reproductive BioMedicine Online; www.rbmonline.com/Article/2256 on web 27 January 2006
Letter Gender selection of embryos after PGD for other independent medical reasons – a viewpoint from Singapore To the Editor In recent years, preimplantation genetic testing and diagnosis (PGD) of cleavage stage embryos has become increasingly commonplace in many ART laboratories throughout the world (Sermon et al., 2004), except for a handful of countries that explicitly prohibits this practice, among of which is Singapore. Recently, a public referendum on genetic testing and research was hosted by the Bioethics Advisory Committee (BAC) of Singapore throughout 2005, and it was finally decided to approve the legalization of PGD in Singapore, under certain guidelines. This includes licensing and monitoring by a relevant authority and prohibiting PGD to be explicitly used for the selection of desired traits and gender, as well as for other non-medical reasons (Genetic Testing and Genetic Research, a report by the Bioethics Advisory Committee, Singapore, November 2005). Nevertheless an issue that was largely overlooked is the gender selection of embryos after PGD for other independent medical reasons, e.g. autosomal genetic defects or for advanced maternal age to prevent Down syndrome (Blake et al., 1999; Katz et al., 2002). New developments in diagnostic technology, such as comparative genomic hybridization (Wilton, 2005), DNA microarray chips (Rickman et al., 2005) and spectral karyotyping (Liehr et al., 2004), will enable the sex of each individual embryo to be determined simultaneously with the presence or absence of chromosomal anomalies and genetic defects. A decision can then be made to transfer only normal embryos of a preferred sex. The fertility practitioner and embryologist involved can easily argue on the basis of transferring the ‘best’ embryos to maximize the chances of conception for the patient (Hu et al., 1998). Because the scoring of embryo quality based on morphology can be quite subjective (Scott, 2003; Baczkowski et al., 2004), this in turn can be easily exploited by medical professionals with few scruples about pandering to the personal ‘whims’ of patients. Moreover, it is difficult to dispute laboratory records on embryo scoring, written without any independent external observation or supervision.
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With increasing numbers of women in Singapore opting to delay marriage and childbearing in pursuit of educational and career goals (Graham, 1995), advanced maternal age as an indication for PGD to prevent Down syndrome (Blake et al., 1999; Katz et al., 2002) is likely to become more commonplace in the future, which in turn could provide a pretext and ‘handy excuse’ for sex selection of embryos. This issue is not trivial, considering the fact that in many Asian cultures, the preferred gender of a new-born baby is male (Li, 1997; Mojumdar, 1990); this in turn has led to prevalent selective abortion of female fetuses in many Asian countries (Miller, 2001; Allahbadia, 2002; Hesketh et al., 2005), as well as widespread infanticide and abandonment of new-born female babies (Weisskopf, 1985; Sharma, 2003). In western countries, non-medical sex selection through PGD is
also a highly controversial and hotly-debated topic, focused mainly on the issue of personal choice and liberty within a free and democratic society (Bahadur, 2005; Schulman and Karabinus, 2005). In any case, widespread gender selection on a non-medical basis would inevitably result in skewing of sex ratios, as well as reinforcement of gender stereotyping and discrimination, which could in turn have long-term detrimental consequences on society. Thankfully, the Health Ministry in Singapore has, in principle, always been vehemently opposed to gender selection in all forms (Tan, 2001). A solution may be to prohibit the sexing of embryos during the PGD procedure under all circumstances except for screening X-chromosome-linked recessive genetic disorders. Perhaps future commercially available diagnostic kits for PGD should be designed and marketed as two variants, with and without sex chromosome probes. Another alternative would be to make it mandatory for fertility practitioners, where possible, to equalize the sex ratio of PGD embryos transferred to the patient. Boon Chin Heng Stem Cell Laboratory, National University of Singapore, 5 Lower Kent Ridge Road, 119074 Singapore
References Allahbadia GN 2002 The 50 million missing women. Journal of Assisted Reproduction and Genetics 19, 411–416. Baczkowski T, Kurzawa R, Glabowski W 2004 Methods of embryo scoring in in-vitro fertilization. Reproductive Biology 4, 5–22. Bahadur G 2005 Concerns of sex selection and regulation in the report on Human Reproductive Technologies and the Law. Reproductive BioMedicine Online 11, 13–14. Blake D, Tan SL, Ao A 1999 Assessment of multiplex fluorescent PCR for screening single cells for trisomy 21 and single gene defects. Molecular Human Reproduction 5, 1166–1175. Genetic testing and genetic research, a report by the Bioethics Advisory Committee, Singapore, November 2005. Downloadable from http://www.bioethics-singapore.org/resources/pdf/ GT%20Report.pdf [accessed: 18 January 2006]. Graham E 1995 Singapore in the 1990s. Can population policies reverse the demographic transition? Applied Geography 15, 219–232. Hesketh T, Lu L, Xing ZW 2005 The effect of China’s one-child family policy after 25 years. New England Journal of Medicine 353, 1171–1176. Hu Y, Maxson WS, Hoffman DI et al. 1998 Maximizing pregnancy rates and limiting higher-order multiple conceptions by determining the optimal number of embryos to transfer based on quality. Fertility and Sterility 69, 650–657. Katz MG, Mansfield J, Gras L et al. 2002 Diagnosis of trisomy 21 in preimplantation embryos by single-cell DNA fingerprinting. Reproductive BioMedicine Online 4, 43–50.
Letter - Gender selection after PGD - BC Heng Li D 1997 Preference for sons: past and present. China Population Today 14, 15–16. Liehr T, Starke H, Weise A et al. 2004 Multicolor FISH probe sets and their applications. Histology and Histopathology 19, 229–237. Miller BD 2001 Female-selective abortion in Asia: patterns, policies, and debates. American Anthropology 103, 1083–1095. Mojumdar M 1990 The girl child and the family. Yojana 34, 13–14. Rickman L, Fiegler H, Carter NP, Bobrow M 2005 Prenatal diagnosis by array-CGH. European Journal of Medical Genetics 48, 232– 240. Schulman JD, Karabinus DS 2005 Scientific aspects of preconception gender selection. Reproductive BioMedicine Online 10 (suppl. 1), 111–115. Scott L 2003 The biological basis of non-invasive strategies for selection of human oocytes and embryos. Human Reproduction Update 9, 237–249. Sermon K, Van Steirteghem A, Liebaers I 2004 Preimplantation
genetic diagnosis. Lancet 363, 1633–1641. Sharma DC 2003 Widespread concern over India’s missing girls. Selective abortion and female infanticide cause girl-to-boy ratios to plummet. Lancet 362, 1553. Tan CC 2001 Guidelines for private healthcare institutions providing assisted reproduction services: Regulation 4 of the private hospitals and medical clinics regulations (CAP 248, Rg1), published in September 2001. Downloadable from http://www.moh.gov.sg/ cmaweb/attachments/publication/assisted_reproduction_services_ guidelines.pdf [accessed 18 January 2006]. Weisskopf M 1985 One couple, one child – China’s birth control policy drives some to kill baby girls. Washington Post. 8 January 1985; A1, A10. Wilton L 2005 Preimplantation genetic diagnosis and chromosome analysis of blastomeres using comparative genomic hybridization. Human Reproduction Update 11, 33–41.
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Letter Gender selection of embryos after PGD for other independent medical reasons – a viewpoint from Singapore To the Editor In recent years, preimplantation genetic testing and diagnosis (PGD) of cleavage stage embryos has become increasingly commonplace in many ART laboratories throughout the world (Sermon et al., 2004), except for a handful of countries that explicitly prohibits this practice, among of which is Singapore. Recently, a public referendum on genetic testing and research was hosted by the Bioethics Advisory Committee (BAC) of Singapore throughout 2005, and it was finally decided to approve the legalization of PGD in Singapore, under certain guidelines. This includes licensing and monitoring by a relevant authority and prohibiting PGD to be explicitly used for the selection of desired traits and gender, as well as for other non-medical reasons (Genetic Testing and Genetic Research, a report by the Bioethics Advisory Committee, Singapore, November 2005). Nevertheless an issue that was largely overlooked is the gender selection of embryos after PGD for other independent medical reasons, e.g. autosomal genetic defects or for advanced maternal age to prevent Down syndrome (Blake et al., 1999; Katz et al., 2002). New developments in diagnostic technology, such as comparative genomic hybridization (Wilton, 2005), DNA microarray chips (Rickman et al., 2005) and spectral karyotyping (Liehr et al., 2004), will enable the sex of each individual embryo to be determined simultaneously with the presence or absence of chromosomal anomalies and genetic defects. A decision can then be made to transfer only normal embryos of a preferred sex. The fertility practitioner and embryologist involved can easily argue on the basis of transferring the ‘best’ embryos to maximize the chances of conception for the patient (Hu et al., 1998). Because the scoring of embryo quality based on morphology can be quite subjective (Scott, 2003; Baczkowski et al., 2004), this in turn can be easily exploited by medical professionals with few scruples about pandering to the personal ‘whims’ of patients. Moreover, it is difficult to dispute laboratory records on embryo scoring, written without any independent external observation or supervision.
392
With increasing numbers of women in Singapore opting to delay marriage and childbearing in pursuit of educational and career goals (Graham, 1995), advanced maternal age as an indication for PGD to prevent Down syndrome (Blake et al., 1999; Katz et al., 2002) is likely to become more commonplace in the future, which in turn could provide a pretext and ‘handy excuse’ for sex selection of embryos. This issue is not trivial, considering the fact that in many Asian cultures, the preferred gender of a new-born baby is male (Li, 1997; Mojumdar, 1990); this in turn has led to prevalent selective abortion of female fetuses in many Asian countries (Miller, 2001; Allahbadia, 2002; Hesketh et al., 2005), as well as widespread infanticide and abandonment of new-born female babies (Weisskopf, 1985; Sharma, 2003). In western countries, non-medical sex selection through PGD is
also a highly controversial and hotly-debated topic, focused mainly on the issue of personal choice and liberty within a free and democratic society (Bahadur, 2005; Schulman and Karabinus, 2005). In any case, widespread gender selection on a non-medical basis would inevitably result in skewing of sex ratios, as well as reinforcement of gender stereotyping and discrimination, which could in turn have long-term detrimental consequences on society. Thankfully, the Health Ministry in Singapore has, in principle, always been vehemently opposed to gender selection in all forms (Tan, 2001). A solution may be to prohibit the sexing of embryos during the PGD procedure under all circumstances except for screening X-chromosome-linked recessive genetic disorders. Perhaps future commercially available diagnostic kits for PGD should be designed and marketed as two variants, with and without sex chromosome probes. Another alternative would be to make it mandatory for fertility practitioners, where possible, to equalize the sex ratio of PGD embryos transferred to the patient. Boon Chin Heng Stem Cell Laboratory, National University of Singapore, 5 Lower Kent Ridge Road, 119074 Singapore
References Allahbadia GN 2002 The 50 million missing women. Journal of Assisted Reproduction and Genetics 19, 411–416. Baczkowski T, Kurzawa R, Glabowski W 2004 Methods of embryo scoring in in-vitro fertilization. Reproductive Biology 4, 5–22. Bahadur G 2005 Concerns of sex selection and regulation in the report on Human Reproductive Technologies and the Law. Reproductive BioMedicine Online 11, 13–14. Blake D, Tan SL, Ao A 1999 Assessment of multiplex fluorescent PCR for screening single cells for trisomy 21 and single gene defects. Molecular Human Reproduction 5, 1166–1175. Genetic testing and genetic research, a report by the Bioethics Advisory Committee, Singapore, November 2005. Downloadable from http://www.bioethics-singapore.org/resources/pdf/ GT%20Report.pdf [accessed: 18 January 2006]. Graham E 1995 Singapore in the 1990s. Can population policies reverse the demographic transition? Applied Geography 15, 219–232. Hesketh T, Lu L, Xing ZW 2005 The effect of China’s one-child family policy after 25 years. New England Journal of Medicine 353, 1171–1176. Hu Y, Maxson WS, Hoffman DI et al. 1998 Maximizing pregnancy rates and limiting higher-order multiple conceptions by determining the optimal number of embryos to transfer based on quality. Fertility and Sterility 69, 650–657. Katz MG, Mansfield J, Gras L et al. 2002 Diagnosis of trisomy 21 in preimplantation embryos by single-cell DNA fingerprinting. Reproductive BioMedicine Online 4, 43–50.
Letter - Gender selection after PGD - BC Heng Li D 1997 Preference for sons: past and present. China Population Today 14, 15–16. Liehr T, Starke H, Weise A et al. 2004 Multicolor FISH probe sets and their applications. Histology and Histopathology 19, 229–237. Miller BD 2001 Female-selective abortion in Asia: patterns, policies, and debates. American Anthropology 103, 1083–1095. Mojumdar M 1990 The girl child and the family. Yojana 34, 13–14. Rickman L, Fiegler H, Carter NP, Bobrow M 2005 Prenatal diagnosis by array-CGH. European Journal of Medical Genetics 48, 232– 240. Schulman JD, Karabinus DS 2005 Scientific aspects of preconception gender selection. Reproductive BioMedicine Online 10 (suppl. 1), 111–115. Scott L 2003 The biological basis of non-invasive strategies for selection of human oocytes and embryos. Human Reproduction Update 9, 237–249. Sermon K, Van Steirteghem A, Liebaers I 2004 Preimplantation
genetic diagnosis. Lancet 363, 1633–1641. Sharma DC 2003 Widespread concern over India’s missing girls. Selective abortion and female infanticide cause girl-to-boy ratios to plummet. Lancet 362, 1553. Tan CC 2001 Guidelines for private healthcare institutions providing assisted reproduction services: Regulation 4 of the private hospitals and medical clinics regulations (CAP 248, Rg1), published in September 2001. Downloadable from http://www.moh.gov.sg/ cmaweb/attachments/publication/assisted_reproduction_services_ guidelines.pdf [accessed 18 January 2006]. Weisskopf M 1985 One couple, one child – China’s birth control policy drives some to kill baby girls. Washington Post. 8 January 1985; A1, A10. Wilton L 2005 Preimplantation genetic diagnosis and chromosome analysis of blastomeres using comparative genomic hybridization. Human Reproduction Update 11, 33–41.
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