Sex Selection Dr Devora Lieberman MD MPH FRANZCOG Outline • • • • • • History of sex selection Some more “modern” ideas Assisted conception techniques Demographic issues Ethical issues Sex selection in Australia pre- and post-2004 Aristotle, 330 BC For a boy, ligate your left testicle 13th century Chinese Conception Chart French Noblemen Cut a testicle off to conceive a boy “Drink the blood of a lion by a full moon in a cold wind with a woman dressed in a man’s clothing…” The 21st Century • Surveys of the general population favour regulating sex selection – HFEA found 68% of 2,165 adults in favour in faceto-face survey1 – 82% in favour of 642 respondents to selfadministered survey1 – Germany- 92% not interested in sex selection2 1 www.hfea.gov.uk/AboutHFEA/Consultations et al. Hum Reprod 2003 2 Dahl Ask Dr Google • “conceive a girl”- 1,970,000 results • “conceive a boy”- 1,710,000 results • 750,000 on-line forums Shettles Method • Based on concept that the y chromosome is lighter than the X chromosome • Y-bearing sperm swim faster and die sooner than X-bearing sperm • For a girl, time intercourse in advance of ovulation • For a boy, time intercourse at ovulation • Sexual position, diet, pH Gender Disappointment Assisted Conception Techniques • Sperm separation • Preimplantation genetic diagnosis (PGD) Sex Selection Among Infertility Patients1 • Cross-sectional survey of 1,500 women who presented for infertility care (1,385 reached correct address • 561 completed questionnaires (41% response rate) • 40.8% wanted to choose the sex pf their next child if there was no added cost 1 Jain et al. Fert & Ster 2005 Sex Selection Among Infertility Patients • A significant preference in women who were: – Younger – Single – African American – Hispanic/Latina – Less educated – Nonreligious – Less wealthy – Had never been pregnant – Had children of one sex Sperm Selection (Microsort®) • Uses a flow cytometer that separates the 2.8% heavier sperm sample for artificial insemination or IVF • Efficacy*: – 80-90% for X-bearing sperm – 60-70% for Y-bearing sperm *Johnson et al. Hum Reprod 1993 What is PGD ? Uses a test, or group of tests to identify the embryo’s genetic/chromosomal status Why use PGD? • Avoidance of therapeutic abortion or spontaneous miscarriage for couples at high risk of fetal abnormality • Avoidance of moral/ethical dilemmas about termination of pregnancy • Refinements of techniques allow us to offer patients a 95-99% rate of successful analysis giving patients a greater degree of confidence as they approach a prenatal diagnostic test. What can PGD test for? • Translocations • Aneuploidy screening • Single gene disorders – autosomal dominant eg. Huntington disease – autosomal recessive eg. Cystic Fibrosis – X-linked eg. Haemophilia • HLA matching • Sex selection How is PGD done? 1. Removal of genetic material – either day 3 biopsy or day 5 biopsy 2. Analysis of the biopsied material – CGH or PCR 3. Interpretation of results 4. Selection of embryos for transfer ICSI Embryo Development Blastocyst Biopsy Blastocyst Biopsy DNA is extracted from the cells ... PCR: DNA is amplified to get usable quantity PCR based PGD: developed to date A.R. polycystic kidney disease Adrenoleukodystrophy Alpers disease alpha 1 anti Trypsin alpha thalassaemia anti-kell antibodies ARPKD. PKHD Gene Batten disease Becker Muscular Dystrophy. beta thalassemia CADASIL disease CDG 1A central core disease Charcot-Marie-Tooth choroideremiachronic granulomatosis disease congenital adrenal hyperplasia congenital nephrotic syndrome Connexin 26 Crigler-Naijar syndrom(+SSM) Crouzon Syndrome cystic fibrosis D-Loop Duchenne muscular dystrophy early onset Alzheimer's disease Kell Antibody Zellweger syndrome X-linked myotubuar myopathy X-linked Lowe oculocerebrorenal syndrome X-linked adrenoleukodystrophy Von Hippel-Lindau medium-chain acyl-CoA dehydrogenase deficiency E-cadherin Medullary Thyroid Cancer RET ectodermal dysplasia MELAS Emery-Dreifuss Metachromatic Leucodystrophy muscular dystrophy Mitochondrial diorders facioscapulohumeral muscular MPS II Hunter dystrophy MTHFR FV familial adenomatous polyposis mucopolysaccharide III familial amytrophic lateral sclerosis multiple endocrine neoplasia 2A family history of deafness multiple hereditary exotoses (EXT1) fragile X muscular dystrophy FSH MD nail-patella syndrome Goldberg-Shprintzen syndrome nemaline myopathy Gorlin Syndrome neurofibromatosis type 2 granulomatosis disease Treacher Collins Haemophilia Norrie disease Helitz Epidermolysis Bullosa OCRL on Chromosome X HLA Match oculocutaneous albinism 2 HLA Match for Diamond Blackfan Parental (3PN Inv) Anaemia Pendred syndrome HLA match/ hyper IgM Pericentric Inversion on X chromosome HLA matching, Aplastic anaemia POC - Turners Mosaicism;partial del Chromosome X HLA matching, Juvenile proximal myotonic myopathy Myelomonocytic Leukemia Retinoblastoma HLA matching, Leukaemia rhesus determination Huntingdon disease Saethre-Chotzen Syndrome Hypochondroplasia Sandhoff disease incontinentia pigmenti sickle cell anaemia juvenile neuronal ceroid lipofuscinosis spinal muscular atrophy Wolman disease thyroid cancer Wiskott-Aldrich syndrome tuberous sclerosis Ullrich congenital muscular dystrophy Hybridisation Challenges • • • • • Ovaries must respond to stimulation Mature eggs must be collected Eggs must fertilise Embryos must be suitable for biopsy Embryo of desired sex Demographic and Ethical Issues Demographic Issues • China and India • India has outlawed sex selection • Sex ratio for newborns in China- 118:100, and as high as 130:100 in rural areas • 2003 US Gallup Poll of 1,003 adults:1 – 35% boy – 28% girl – 34% no preference 1 Lyons. The Gallup Organization 2003. Sydney IVF Experience • 286 cycles completed between 1996 and June 2004 • Compulsory counselling introduced in 2001 for all PGD patients, including those requesting sex selection • Questionnaire introduced April 2002 – 164 surveys completed in 2 years • Medicare has never subsidised this elective treatment. Parent’s main reason for sex selection 11% 13% 7% 69% Mother Father Ethical Issues • In 2004 the Australian Health Ethics Committee stated that it found the practice of sex selection to be unethical • On 9 February 2005 Sydney IVF suspended sex selection for non-medical reasons to comply with AHEC Guidelines AHEC’s reasons given for opposing the availability of sex selection • Sex selection is incompatible with the parent–child relationship being one that involves unconditional acceptance. • Sex selection may be an expression of sexual prejudice, in particular against girls. As practised today around the world, it generally reflects and contributes to bias and discrimination against women. • Sex selection harms men in some cultural groups (by contributing to the shortage of women for men to marry). AHEC’s reasons given in support of the availability of sex selection • Sex selection permits ‘family balancing’. • Sex selection may enable parents to fulfill religious obligations or cultural expectations. • Sex selection is properly thought of as a matter for individual autonomy. Sydney IVF’s Ethics Committee • “Sex selection is incompatible with the parent-child relationship being one that involves unconditional acceptance.” “Unconditional acceptance” is an abstract and arguable concept at best – and completely meaningless for a child still to be conceived. Sydney IVF’s Ethics Committee • “Sex selection may be an expression of sexual prejudice, in particular against girls. As practised today around the world, it generally reflects and contributes to bias and discrimination against women.” AND “Sex selection harms men in some cultural groups (by contributing to the shortage of women for men to marry).” These observations may be true in China and India but do not apply in Australia. In our experience the object of sex selection in just under 60% of cases was to have a girl. Conclusion • The desire to influence the sex of one’s children is ancient and deep-seated. • Couples turn to many methods, with more or less cost and effectiveness. • IVF with PGD is the latest and most effective of these, and removes the element of chance.