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Preimplantation Genetic Diagnosis for Gender Selection: You Don't Always

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Preimplantation Genetic Diagnosis for Gender Selection: You Don't Always Open Journal of Obstetrics and Gynecology, 2012, 2, 291-297 OJOG http://dx.doi.org/10.4236/ojog.2012.23062 Published Online September 2012 (http://www.SciRP.org/journal/ojog/) Preimplantation genetic diagnosis for gender selection: You don’t always get what you want Tanmoy Mukherjee1,2*, Eric Flisser1, Alan B. Copperman1,2, Lawrence Grunfeld1,2, Benjamin Sandler1,2, Jason Barritt1,2 1Reproductive Medicine Associates of New York, New York, USA 2Reproductive Endocrinology, Mount Sinai School of Medicine, New York, USA Email: *[email protected] Received 16 May 2012; revised 20 June 2012; accepted 2 July 2012 ABSTRACT of lethal genetic diseases in cycles of assisted reproduc- tion (ART) produced the first human live births in 1990 Parenting children of opposite genders is a powerful [1]. PGD testing has since been utilized to identify a motive for parents to seek “sex-selection” services. Medical beneficence and patient autonomy support range of diseases (e.g. cystic fibrosis, sickle cell disease, making these services available. Our goals in this hemophilia A and B, Lesch-Nyhan syndrome, Duche- study included data to permit proper patient educa- nne’s Muscular Dystrophy), and the detection of addi- tion, assess outcome, and evaluation of potential bi- tional genetic disorders is increasingly possible as the ases in this technology. IVF/PGD cases from August genetic loci of diseases are identified [2-6]. In addition to 2004 to December 2009 were studied (n = 122). FISH detection of single gene defects, technical advances in was used to analyze nuclear DNA of biopsied em- single-cell genetic analysis, including single nucleotide bryos. The variables analyzed were patient age, Day 3 polymorphism (SNP) array, comparative genomic hybri- Fluorescent In Situ Hybridization (FISH), the num- dization (CGH), and whole genome amplification (WGA), ber of fertilized embryos, the number of embryos bi- may improve diagnostic precision and permit useful opsied, Preimplantation Genetic Diagnosis (PGD) re- preimplantation genetic screening (PGS) in patients with sults, the number of embryos transferred, and the recurrent pregnancy loss and unexplained in vitro ferti- fate of remaining embryos. Female embryos were lization (IVF) treatment failure, where chromosomal sought in 84 cycles, and male embryos desired in 38 errors are the result of potentially de novo mutations or cycles. Couples seeking female offspring had a re- meiotic and mitotic aberrations [2,7-11]. duced likelihood of a female-only transfer vs. those Elective sex “selection” is a controversial variant of seeking males (p < 0.001). No transfer was performed PGD, enabling patients to identify the genetic gender of in 32 cases for lack of normal embryos of desired embryos prior to transfer to the uterus, thus allowing gender. Clinical pregnancy rate per embryo transfer preferential selection in the absence of medical necessity. was 30.4%. PGD success rates for gender variety The incidence of patient interest in non-medical elective were lower than expected comparative to traditional sex selection in the United States is difficult to estimate IVF. In this report we present our clinical experience because the Society for Assisted Reproductive Techno- with IVF/PGD for gender selection. We attempt to logy (SART), the agency tasked with tracking the use analyze which patients seek this specialized treatment and outcomes of in vitro fertilization (IVF) treatment in and to provide direct clinical and laboratory outcome the US, does not specifically denote PGD cycles under- data from our completed cycles. taken for the purposes of gender selection [8-11]. How- ever, there is significant interest in this non-medical ap- Keywords: IVF; PGD; Gender Preference; Sex plication. Dahl found that 8% of respondents would use Selection; Family Balancing preconception sex selection services [12] and Jain et al. found that 40.8% of women undergoing IVF would se- lect the gender of their child if they could easily do so 1. INTRODUCTION [13]. In contrast to preconception techniques for gender Application of preimplantation genetic diagnosis (PGD) selection, such as sperm-sorting protocols, the issue of during embryonic development to identify the presence gender selection during cycles of assisted reproduction, and especially so in the absence of infertility or genetic *Corresponding author. disease, is additionally complicated by cost scale, alloca- OPEN ACCESS 292 T. Mukherjee et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 291-297 tion of limited resources, and ethical considerations re- cur, a number of prerequisites are necessary. First, a garding the fate of supernumerary embryos, both of the strong preference for one gender over another must exist. preferred gender and otherwise. Alternative options, such And, second, child bearing must preclude conceiving a as preconception techniques to influence embryo gender child of the opposite gender. using sperm sorting protocols including gradients or cen- Couples seeking gender variety may constitute a spe- trifugation, however, lack the specificity and superior cial case of elective gender selection. The experience of outcomes of IVF-PGD [14]. parenting a child of the opposite gender is unique and Gender variety or “family balancing” as it is some- may present a powerful motivator for parents whose off- times known, is a particular form of PGD that is under- spring are comprised of a single gender [25-30]. As dis- taken in families in which all offspring are of the same cussion of PGD utilization for gender variety evolves, gender. Patients pursuing this option are interested in the not only is it essential to discuss ethical arguments in the unique experience of raising a child of the unrepresented abstract, it is also necessary to analyze empiric practice gender [15,16]. The motivation of couples seeking this data in order to reconcile practical and theoretical aspects application of PGD in this setting may be different from of this controversial therapeutic intervention. In this re- that of other patients seeking gender selection, suggest- port we present our clinical experience with IVF/PGD ing that gender variety and sex selection may be consi- for gender selection. We attempt to analyze which pa- dered distinct applications of PGD/ART [15,17]. Increas- tients seek this specialized treatment and to provide di- ing utilization of gender variety has prompted various rect clinical and laboratory outcome data from our com- ART regulatory organizations to formulate criteria for pleted cycles. permitting application of PGD in this scenario. In 2002, the Human Fertilization and Embryology Authority (HFEA) 2. MATERIALS AND METHODS of the United Kingdom attempted to codify the practice by limiting its application to families in which no chil- All IVF/PGD cases for gender selection performed in our dren of a given gender existed, but conceded that a gen- clinic from August 2004 to December 2009 were in- der imbalance of more than two when both genders were cluded in this study (n = 122). All patients were coun- represented in an existing family would also fulfill the seled by their medical providers and then provided in- prerequisite [18]. formed consent to participate in IVF/PGD. Patients un- The ethics committees of both the American Congress derwent ovarian stimulation with gonadotropins using of Obstetricians and Gynecologists (ACOG) and the GnRH-antagonist or GnRH-agonist luteal-phase down American Society for Reproductive Medicine (ASRM) regulation with or without birth control pill overlap to have established acceptable medical justifications for sex prevent premature luteinization of follicles. Serial moni- selection. However, the committees differ on the ethics toring by a physician was performed for controlled ova- of gender selection for non-medical indications [19]. The rian stimulation by hormone and ultrasound analysis. ACOG Ethics Committee opposes sex selection for per- When at least two follicles measured 18 mm in diameter, sonal and family reasons, including family balancing, Human Chorionic Gonadotropin (HCG) (5000 - 10,000 because of the concern that such requests may ultimately IU intramuscularly) or ovidrel (250 mcg subcutaneously) support sexist practices. The ASRM committee recog- was administered by injection and transvaginal ultra- nizes the serious ethical concerns that the application of sound-guided oocyte retrieval was performed 36 hours these techniques raise and counsels against their wide- later. In all cases, intracytoplasmic sperm injection (ICSI) spread use while additionally emphasizing that practitio- was performed. All patients had embryo biopsy per- ners offering assisted reproductive services are not under formed on Day 3 after oocyte retrieval, by direct aspira- legal or ethical obligation to provide non-medically in- tion of a single blastomere through an opening created by dicated methods of gender selection. The committee, acidified Tyrodes degradation of the zona pellucida. The however, concludes that, “Until a more clearly persua- biopsied blastomere was fixed to a glass microscope sive ethical argument emerges, or there is stronger em- slide and the cytoplasm was removed before PGD analy- pirical evidence that most choices to select the gender of sis. offspring would be harmful, policies to prohibit or con- Nuclear DNA was analyzed by Fluorescent In Situ demn as unethical all uses of non-medically indicated Hybridization (FISH). 2-chromosome (X, Y), 3-chro- preconception gender selection are not justified [20,21].” mosome (21, X, Y), 5-chromosome (13, 18, 21, X, Y) or A primary concern is that when widely applied, services 10-chromosome (9, 13, 14, 15, 16, 18, 21, 22, X, Y) for gender selection can distort the natural sex ratio and probes were used for FISH. PGD results were evaluated lead to gross societal gender imbalance, as has occurred by geneticists, embryologists and the physician response- in China and India through the use of abortion [22-24]. ble for embryo transfer on Day 5 of embryo development. In the United States, for a gross gender imbalance to oc- Patients were counseled about the FISH results prior to Copyright © 2012 SciRes. OPEN ACCESS T. Mukherjee et al.
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