Preimplantation Genetic Diagnosis Procedure Research Articles

Prospects for the inclusion of the preimplantation genetic diagnosis procedure in the compulsory health insurance program taking into account the cost characteristics and foreign experience

Objectives. The purpose of this study is to determine the prospects for the inclusion of the preimplantation genetic diagnosis (PGD) procedure in the compulsory health insurance (CHI) program, taking into account the cost characteristics of the procedure and the existing foreign experience in this field. Material. The regulatory legal acts, the practice of the use of PGD in Russia, UK, Germany, Israel, Netherlands, and USA are studied. Methods used: general philosophical, general scientific, private scientific (statistical, mathematical and financial analysis, factor analysis method), special (structural-legal, comparativelegal, formal-legal). Results. The prospects for the inclusion of the PGD procedure in the compulsory medical insurance program are determined taking into account the cost characteristics of the procedure and the existing foreign experience in this field. It has been established that the total cost of PGD during IVF as part of infertility treatment consists mainly of the costs of the basic stages of IVF — among the total costs, the cost of IVF cycles in this case is about 75%, while the cost of the study itself is about 20%, additional services and research — 5%. In other cases, the main factors affecting the total cost of PGD will be the cost of embryo biopsy (about 25%), molecular genetic research using the chosen method (about 70%), preliminary and subsequent genetic counseling (about 5%). It has been proved that in order to provide normative support for such a step, it seems necessary to differentiate the grounds for free PGD depending on the goals of diagnosis and research methods in each case. Couples undergoing infertility treatment should be given the right to include such diagnostics in the package of services available within a limited number of free cycles. The decision to conduct PGD should be made solely on the basis of the results of medical genetic counseling and be completely voluntary. Conclusions. The inclusion of the cost of PGD in the CHI programs to assess the risks of developing genetically caused diseases and chromosomal abnormalities in fertile couples should be based on the development of a single list of the most common genetically determined disorders, for which PGD can be performed free of charge. In this case, each disease or chromosomal abnormality in the list should correspond to a specific research method.

Formation of the concept of legal regulation of preimplantation genetic diagnosis in the Russian Federation in the context of ensuring and protecting reproductive freedom of the individual

Objectives. The aim of this study is the formation of a concept of preimplantation genetic diagnosis (PGD) in the Russian Federation in the context of ensuring and protecting reproductive freedom of the individual. Material. The regulatory legal acts, the doctrinal sources of the Russian Federation are examined to identify key problems that impede the formation of the desired concept. Methods used: general philosophical, general scientific, private scientific, special (structural-legal, formal-legal). Results. The basic postulates of the concept of legal regulation of PGD in the Russian Federation are substantiated. As part of the analysis of domestic legislation, key problems are identified that impede the formation of the desired concept that meets the level of development of medical science and the needs of consumers of medical services. The conclusion is justified that it is necessary to fix at the legislative level the place of pre-plantation genetic tests in the assisted reproductive technologies system, thus giving PGD independent significance outside the context of the problems of infertility treatment. It has been argued that, in addition to the norms of the basic law on protecting the health of citizens, a separate sub-legislative normative legal act of the Ministry of Health of the Russian Federation should be developed in the system of legal regulation of PGD in Russia, forming a set of mandatory requirements for the PGD procedure, depending on diagnostic goals, as well as determining which methods are preferable depending on the goal and what results the consumer can count on. Conclusions. It is noted that in the system of norms on genetic research, special attention should be paid to genetic counseling, establishing mandatory requirements for the content of the consultation - in relation to PGD, this should include explanations regarding the algorithm and method of the study, the possibilities and limitations of this type of diagnosis for each a particular case, the features of its application to solve a single genetic problem.

The experience of legal regulation of the pre-implantation genetic diagnosis procedure in Israel and the prospects for its borrowing in Russian conditions

Objectives. The purpose of this study was to study the legal regime of pre-implantation genetic diagnosis (PGD) procedures in Israel in the context of the formation of the concept of legal regulation of this diagnosis in the Russian Federation. Materials. The legal acts and doctrinal sources of Israel on the problems of PGD and genetic research are examined. Methods used: general philosophical, general scientific, private scientific, special (structural-legal, comparative-legal, formal-legal). Results. The features of the legal regulation of the PGD procedure in Israel are determined, the ways of partial borrowing of such in Russia are proposed. Conclusions. It has been established that the general concept of legal regulation of PGD in Israel can be proposed for borrowing due to the following components: 1) an integrated approach to legal regulation of PGD in which the recommendations for diagnostics are formulated based on the results of the implementation of state programs to support genetic studies and the fight against congenital diseases; 2) a combination of legislative regulation of basic guarantees in the field of PGD with subjective by-law regulation of indications and conditions for each stage of diagnosis; 3) a combination of legislative and by-laws regulation with regulation at the level of professional guidelines; 4) the flexibility of normative legal regulation, which allows authorizing the implementation of PGD in certain non-standard cases; 5) the existence of special requirements for the content of genetic counseling in PGD, which serves as an important guarantee of protecting the rights of consumers of medical services.

Preimplantation genetic diagnosis: a national multicenter obstetric and neonatal follow-up study

To study whether women conceiving after preimplantation genetic diagnosis (PGD) and their children have greater risks of adverse pregnancy and birth outcomes compared with children conceived spontaneously or after IVF with or without intracytoplasmic sperm injection (ICSI). Historical cohort study. Not applicable. All deliveries following PGD treatment for single gene and sex-linked disorders or structural chromosomal aberrations (n = 126 deliveries/149 children), IVF/ICSI treatment (n = 30,418 deliveries/36,115 children), and spontaneous conception (n = 896,448 deliveries/909,624 children). None. Adverse obstetric and neonatal outcomes, such as pre-eclampsia, preterm primary rupture of membranes, placenta previa, abruption of placenta, preterm birth, low birth weight, malformations, and neonatal admission. Compared with spontaneously conceived pregnancies, PGD pregnancies were at significantly increased risk of placenta previa (adjusted odds ratio [ORa] 9.1; 95% confidence interval [95% CI] 3.4, 24.9), cesarean section (ORa 2.0; 95% CI 1.3, 2.9), preterm birth (ORa 1.6; 95% CI 1.0, 2.7), shorter gestation (mean difference -3.4days; 95% CI -5.7, -1.1days), and longer neonatal admission (mean difference 21days; 95% CI 15, 28days). The risks were comparable to that of pregnancies following IVF/ICSI. In subanalyses, adverse outcomes were only present in children conceived by PGD owing to parental monogenetic disorder and comparable to those of children born to parents with monogenic disorders conceiving without PGD, except for a higher risk of placenta previa. In this cohort study, the risk of adverse obstetric and neonatal outcomes was mainly related to the underlying parental condition rather than the PGD procedure.

Preimplantation genetic diagnosis and rational choice under risk or uncertainty

In this paper I present an argument in favour of a parental duty to use preimplantation genetic diagnosis (PGD). I argue that if embryos created in vitro were able to...

Assessment of the Risk of Blastomere Biopsy during Preimplantation Genetic Diagnosis in a Mouse Model: Reducing Female Ovary Function with an Increase in Age by Proteomics Method

Preimplantation genetic diagnosis (PGD) is important for screening genetic and chromosome mutations in embryos so that the efficiency of assisted reproductive treatment can be increased and birth defects can be decreased; however, some studies have reported a risk from this technology as well as other assisted reproductive technologies. We have developed a blastomere biopsy mouse model to assess the potential effects of blastomere biopsy that was one key procedure in PGD on the fertility of female mice at different ages. We showed that female fertility was decreased in the biopsied mouse model with an increase in age. Moreover, the ovarian weight, serum hormone levels, and the number of primordial, primary, preantral, and antral stage follicles were also decreased in the middle-aged biopsied mouse model. To elucidate the underlying molecular mechanism, we did proteomics analysis on ovarian tissues from puberty biopsied and nonbiopsied mice of the 23 differentially expressed proteins that were screened for in both groups, 3 proteins (PSMB8, ALDH1A1, and HSPA4) were selected and identified by Western blotting and quantitative RT-PCR methods, which showed the 3 proteins to regulate 12 cellular pathways. Furthermore, these three proteins were shown to be located in ovarian tissues, and the dynamic changes of expression profiling in middle-aged biopsied and nonbiopsied mice were demonstrated. The present study showed that blastomere biopsy technology impairs fertility when mice are middle-aged, which possibly resulted in abnormal expression profiling of PSMB8, ALDH1A1, and HSPA4 proteins. Thus, additional studies should be performed to assess the overall risk of blastomere biopsies during PGD procedures.

Aberrant Epigenetic Modification in Murine Brain Tissues of Offspring from Preimplantation Genetic Diagnosis Blastomere Biopsies1

Preimplantation genetic diagnosis (PGD) has been prevalent in the field of assisted reproductive technology, yet the long-term risks of PGD to offspring remain unknown. In the present study, the early development of PGD embryos, postimplantation characteristics, and birth rate following PGD were determined. Moreover, the behavior of the offspring conceived from the biopsied embryos was evaluated with the Morris water maze and pole climbing tests. Finally, the epigenetic modification of the global genome and methylation patterns for the H19, Igf2, and Snrpn imprinted genes were identified. The results indicated a significant delay in the blastocoel formation of PGD embryos and a decrease in the implantation ability of these embryos, which was related to the decreased number of cells in the PGD blastocysts. The PGD mice spent more time on both the nontrained quadrant of the water maze and climbing down the pole. Furthermore, the 5-hydroxymethylcytosine content in the brain tissues of PGD mice was significantly increased, but no difference was found in 5-methylcytosine content. The differentially methylated regions of H19/Igf2 exhibited decreased methylation patterns, but that of Snrpn was normal, compared to the control group. Quantitative RT-PCR indicated that Igf2 mRNA expression was significantly decreased but that H19 and Snrpn mRNAs were expressed normally. In conclusion, blastomere biopsies in PGD procedures carry potential risks to embryo development and the behavior of resulting offspring; these risks may arise from aberrant epigenetic modification and methylation patterns in brain tissues. Further studies are needed to better understand the risks associated with PGD.

Preimplantation genetic diagnosis (PGD) influences adrenal development and response to cold stress in resulting mice

Preimplantation genetic diagnosis (PGD) has gained widespread application in clinical medicine and hence the health of PGD offspring needs to be systematically assessed. Given the critical role of the stress response in growth and health, assessments of the development and function of the stress system might help to clarify the health outcomes of PGD. In this study, we constructed a PGD-conceived mouse model and used naturally conceived mice as controls; we used this model to evaluate the potential effect of PGD procedures on the stress system of the offspring. Serum and tissues of stress organs, namely the hypothalamus, locus coeruleus and adrenal gland, were collected from 5-week-old mice in the basal state or after cold stress. The serum levels of stress-related hormones and the structural and functional indices of the stress organs were then examined. In the basal state, ultrastructural abnormalities and low expression of genes involved in steroid hormone synthesis were found in the adrenals of the PGD mice, which had low corticosterone and high epinephrine levels compared with those of control mice. After acute cold stress, the PGD mice continued to show structural and glucocorticoid secretion abnormalities resulting in a late response to the environmental change. Thus, our study indicates that PGD manipulations affect adrenal development, result in structural and functional abnormalities of the adrenals in the offspring and influence their reactivity and adaptability to cold stress.

Pre-Implantation Genetic Diagnosis and Rational Choice Under Risk and Uncertainty

In this paper I present an argument in favour of a parental duty to use pre-implantation genetic diagnosis (PGD). I argue that we should assume that if embryos created in vitro were able to decide for themselves, they would choose PGD as a method of selection. Therefore we should respect their hypothetical choices on the principle similar to the principle of patient autonomy. My thesis shows that no matter which moral doctrine parents subscribe to, they ought to conduct the PGD procedure in the situations when it is impossible to implant all of the created embryos and if there is a significant risk for giving birth to a child with a serious genetic disorder.

Preimplantation genetic diagnosis for Charcot-Marie-Tooth disease

ObjectivePreimplantation genetic diagnosis (PGD) is an assisted reproductive technique for couples carrying genetic risks. Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy, with a prevalence rate of 1/2,500. In this study, we report on our experience with PGD cycles performed for CMT types 1A and 2F.MethodsBefore clinical PGD, we assessed the amplification rate and allele drop-out (ADO) rate of multiplex fluorescent polymerase chain reaction (PCR) followed by fragment analysis or sequencing using single lymphocytes. We performed six cycles of PGD for CMT1A and one cycle for CMT2F.ResultsTwo duplex and two triplex protocols were developed according to the available markers for each CMT1A couple. Depending on the PCR protocols, the amplification rates and ADO rates ranged from 90.0% to 98.3% and 0.0% to 11.1%, respectively. For CMT2F, the amplification rates and ADO rates were 93.3% and 4.8%, respectively. In case of CMT1A, 60 out of 63 embryos (95.2%) were diagnosed and 13 out of 21 unaffected embryos were transferred in five cycles. Two pregnancies were achieved and three babies were delivered without any complications. In the case of CMT2F, a total of eight embryos were analyzed and diagnosed. Seven embryos were diagnosed as unaffected and four embryos were transferred, resulting in a twin pregnancy. Two healthy babies were delivered.ConclusionThis is the first report of successful pregnancy and delivery after specific PGD for CMT disease in Korea. Our PGD procedure could provide healthy babies to couples with a high risk of transmitting genetic diseases.

Assessing pre‐implantation embryo development in mice provides a rationale for understanding potential adverse effects of ART and PGD procedures

Although the molecular events controlling human pre-implantation development remain unclear, mechanisms have been identified by analyzing these stages in mice. Through this approach, considerable insight has been gained into the events that operate to determine the first two cell fate decisions, occurring from zygote formation to the blastocyst prior to implantation. These mechanisms are related to cell polarization, cell division, cell-cell contact, and cell spatial position. Two developmental stages are essential for these processes to proceed adequately. Firstly, the second polar body must anchor to the external membrane during the first mitotic divisions of the embryo as its position is strongly biased to determine the plane of polarity. This in turn has important influence on the fate of the early blastomeres. Secondly, in the transition from the 8- to 16-cell stage, the cells that will form the inner cell mass are determined. Moreover, analyses performed on human oocytes and embryos have identified similar processes to those reported in mice and thus are evolutionarily conserved. Therefore, the understanding of mice pre-implantation embryo development provides a rationale to interpret current results of potential long-term adverse outcomes of Assisted Reproductive Technologies and Pre-implantation Genetic Diagnosis (PGD).

Abnormal Development at Early Postimplantation Stage in Mouse Embryos After Preimplantation Genetic Diagnosis

Preimplantation genetic diagnosis (PGD) is an established procedure for the genetic analysis of embryos. To assess the effect of the procedure on early embryonic development, we generated a murine experimental system, including mice implanted with biopsied in vitro cultured embryos, control mice implanted with in vitro cultured embryos without biopsy, and mice with naturally conceived embryos. Embryos at the 7.5-dpc stage were isolated from all three groups and the embryo implantation rate, the survival rate of implanted embryos, and the developmental stage of surviving embryos were carefully assessed and compared among all three groups. We found the implantation rate was similar between biopsied and control group embryos (67.92% vs. 66.67%). However, the survival rate of implanted embryos in the biopsied group (49.31%) was significantly lower than that of the control (60.91%) and normal groups (96.24%) at 7.5 dpc. In addition, the survival rate of control group embryos was significant lower than that of normal group embryos. Classification of the precise developmental stages of randomly selected live implanted embryos at 7.5 dpc revealed no differences among the three groups. Our results indicate that blastomere biopsy does not adversely affect embryo implantation. The PGD procedure, in particular blastomere biopsy, increases the rate of embryo death at 4.5-7.5 dpc, but does not affect the development of surviving 7.5 dpc embryos.

Diagnostic pré-implantatoire : dix ans d’expérience en région parisienne : impasse actuelle et solutions à venir

Preimplantation genetic diagnosis (PGD) has been authorized in France since 1999. Encouraging results have been obtained during the past 10 years in our Paris center, where 832 patients have undergone 1056 IVF-PGD procedures. With the advent of new techniques for the identification of genetic disease markers, our center can now offer PGD procedures for aneuploidy and 75 single-gene diseases. New indications for PGD have also been developed, such as mitochondrial DNA diseases, amyloid neuropathy, pulmonary arterial hypertension, and HLA typing The implantation rate is currently 29,6% and, by 31 December 2009, 151 healthy babies had been born. Unfortunately, demand for PGD procedures far outstrips available technical capacity, and the waiting period is longer than 18 months. Increased funding is urgently needed

Preimplantation genetic diagnosis (PGD) for HLA typing: bases for setting up an open international collaboration when PGD is not available

In severe forms of Diamond-Blackfan anemia, preimplantation genetic diagnosis (PGD) of histocompatibility leukocyte antigen-compatible embryos for enabling the next sibling in the family to be a stem-cell transplantation donor constitutes the sole lasting cure capable of terminating the enduring need for iterative transfusions. We report here an open collaboration between two renowned institutions to provide a family desiring this treatment even though they resided where the preimplantation genetic diagnosis procedure is banned.

Average size of blastomere should be biopsied from day 3 embryos to chose mononucleate cell suitable for PGD

OBJECTIVE: A single blastomere is usually biopsied from day 3 embryos for preimplantation genetic diagnosis (PGD) using fluorescence in situ hybridization (FISH). In the preparation of blastomeres, specimen without nucleus is often encountered. Not only the loss of cells during fixation process, but also the fixation of anucleate blastomere causes this problem. The aim of the present study was to determine the relationship between the incidence of mononucleate blastomeres and the size of blastomeres in day 3 embryos. DESIGN: Experimental laboratory study. MATERIALS AND METHODS: Totally 60 day 3 embryos (448 blastomeres) to be discarded were applied for the present study under informed consent with patients after approval of IVF JAPAN IRB committee. Zona pellucida of the embryo was removed by acid Tyrode's solution and blastomeres were separated from each other. The average diameters of the blastomere were measured using a micrometer attached to inverted microscope. The presence of nucleus in each blastomere on the slide was assessed by fluorescent microscope, after staining with Hoechst 33342 for 10 minutes in incubator. RESULTS: The presence of mononucleate blastomeres in 8 cell embryos was 0% from the blastomeres less than 35μm in diameter, 40.0% between 35μm and 40μm, 42.9% between 40μm and 45μm, 82.6% between 45μm and 50μm, 94.3% between 50μm and 55μm, 94.4% between 55μm and 60μm, 100% between 60μm and 65μm and 33.3% over 65μm in diameter. The blastomeres between 45μm and 65μm in diameter had mononucleus significantly higher to the blastomeres either less than 45μm or over 65μm. The rates of mononucleate blastomere in 7 cell and 9 cell embryos were similar to that in 8 cell embryos. However, the size of blastomeres with mononucleus shifted to the larger in 6 cell embryos and smaller in 10 cell embryos. CONCLUSIONS: The results of the present study indicate that average size of blastomeres should be selected for biopsy in day 3 embryos to select mononucleate blastomere efficiently in PGD procedure.

Evaluation of Blastomere Biopsy Using a Mouse Model Indicates the Potential High Risk of Neurodegenerative Disorders in the Offspring

Preimplantation genetic diagnosis (PGD), used in clinical practice, is offered to couples that may suffer from a monogenetic disorder, chromosome aneuploidy, or X-linked disease. However, blastomere biopsy, as an indispensable manipulation during the PGD procedure has not been assessed for its long term health implications. Using a mouse model, we investigated the effect of blastomere biopsy of in vitro cultured four-cell embryos on preimplantation development efficiency, postnatal growth, and physiological and behavioral activity compared with control, non-biopsied embryos. The mice generated after blastomere biopsy showed weight increase and some memory decline compared with the control group. Further protein expression profiles in adult brains were analyzed by a proteomics approach. A total of 36 proteins were identified with significant differences between the biopsied and control groups, and the alterations in expression of most of these proteins have been associated with neurodegenerative diseases. Furthermore hypomyelination of the nerve fibers was observed in the brains of mice in the biopsied group. This study suggested that the nervous system may be sensitive to blastomere biopsy procedures and indicated an increased relative risk of neurodegenerative disorders in the offspring generated following blastomere biopsy. Thus, more studies should be performed to address the possible adverse effects of blastomere biopsy on the development of offspring, and the overall safety of PGD technology should be more rigorously assessed.

Preimplantation genetic diagnosis for BRCA1/2—a novel clinical experience

To describe our 2-year experience with preimplantation genetic diagnosis (PGD) for carriers of mutations in the genes BRCA1 and BRCA2, the dilemmas incurred and the lessons learned. We collected data on those carriers of BRCA1/2 mutations who applied for PGD counseling and who decided to proceed. We describe the PGD procedures that were conducted and their outcome. Ten carriers of BRCA1/2 mutations applied for PGD counseling, seven were healthy, and three were BC survivors. Eight women needed in vitro fertilization (IVF) because of coexisting infertility. After counseling, six opted for the procedure and five of them underwent PGD for the BRCA mutation. In one of these PGD, fluorescence in situ hybridization (FISH) analysis for chromosomes 21, X and Y was also performed. Three women conceived, each in the first treatment attempt. One of them gave birth to twins, the second to a singleton and the third is currently pregnant. During the pregnancies, dilemmas concerning PGD confirmation were discussed. PGD is an acceptable reproductive option for BRCA mutation carriers, especially for those who require IVF due to fertility problems. Discussion of this option should be carried out with sensitivity, taking into account the age of the woman, her health, fertility status and emotional state. Confirmatory prenatal diagnosis may not always be encouraged.

Preimplantation genetic diagnosis for gender selection in the USA

Preimplantation genetic diagnosis (PGD) for gender selection for non-medical reasons has been considered an unethical procedure by several authors and agencies in the Western society on the basis that it could disrupt the sex ratio, that it discriminates against women and that it leads to disposal of normal embryos of the non-desired gender. In this study, the analysis of a large series of PGD procedures for gender selection from a wide geographical area in the USA shows that, in general, there is no deviation in preference towards any specific gender except for a preference of males in some ethnic populations of Chinese, Indian and Middle Eastern origin that represent a small percentage of the US population. In cases where only normal embryos of the non-desired gender are available, 45.5% of the couples elect to cancel the transfer, while 54.5% of them are open to have embryos transferred of the non-desired gender, this fact being strongly linked to cultural and ethnic background of the parents. In addition this study adds some evidence to the proposition that, in couples with previous children of a given gender, there is no biological predisposition towards producing embryos of that same gender. Based on these facts, it seems that objections to gender selection formulated by ethics committees and scientific societies are not well founded.

MULTIDISCIPLINARY MEDICAL EVALUATION OF CHILDREN YOUNGER THAN 7.5 YEARS BORN AFTER PREIMPLANTATION GENETIC DIAGNOSIS FOR MONOGENIC DISEASES

INTRODUCTION: The growing cohort of children conceived after preimplantation genetic diagnosis (PGD) techniques underlines the importance of evaluating potential risks for their developmental outcome. There are some data concerning the incidence of congenital anomalies, medical status, and cognitive development of children conceived after PGD techniques, based mainly on reports and not on objective medical evaluation. OBJECTIVE: We sought to perform multidisciplinary evaluation (physical, genetic, and developmental) of 31 children conceived after PGD techniques (aged 30 days to 7.5 years) and the stress level of parents who used PGD regarding their parental role. METHODS: Among 24 couples at risk for transmitting monogenic diseases and with an unsuccessful reproductive history, 31 children conceived after PGD techniques were examined. Genetic examination was performed by 2 independent geneticists, and developmental assessment included formal testing of cognitive and motor skills (Bayley scales, Griffiths scales, Athina test). Parental stress was measured by using the Parent Stress Index-Short Form (PSI-SF), a self-report questionnaire that assesses parental stress. The PSI-SF was also completed by 35 parents of naturally conceived, healthy children matched for age, gender, and socioeconomic level. RESULTS: A high rate of cesarean deliveries were reported, but no higher risk was found for perinatal complications. The increased incidence of prematurity and low birth weight among children conceived after PGD techniques did not seem to affect their growth development later in life. Major malformations (cardiac, gastrointestinal, urogenital, skeletal) were present in 4 (12.9%) of 31 children, with a discrepancy between singletons and multiples. A significant number of children conceived after PGD techniques (6 of 31 [19%]), mostly multiple, premature, and small-for-gestational-age infants, experienced low levels of cognitive, verbal, and perceptual abilities (Global Development Quotient scores of <85). Parents who used PGD experienced lower levels of parenting stress compared with controls (P < .05). CONCLUSIONS: Children conceived after PGD techniques seem to be at greater risk for exhibiting congenital malformations and lower cognitive skills. Whether these observations are linked to the PGD procedure itself, rather than to subfertility, multiplicity, or prematurity, is a question that is difficult to answer. An unexpected finding was that once parents who used PGD finally had what they struggled for (a healthy infant), the stresses of parenthood may have been offset by a broader sense of fulfillment.

O-138: Preimplantation genetic diagnosis (PGD) is indicated for recurrent miscarriage even in cycles producing five or fewer embryos

PGD is indicated for patients suffering from infertility or recurrent miscarriage when sufficient numbers of embryos are available. We have studied PGD in groups of patients with low egg yields and varying etiologies. Here we focus on patients with recurrent miscarriages. Previous studies have shown that couples with a history of idiopathic recurrent pregnancy loss (RPL) have a high incidence of chromosomally abnormal embryos. PGD for this indication has proven to significantly reduce the risk of miscarriage while producing high pregnancy rates. However, PGD is a selection tool, and when an IVF cycle produces as many or fewer embryos as the number expected to be replaced, the selection power of PGD is diminished; the same number of normal embryos may be replaced with or without PGD. The objective of this study was to determine whether PGD is indicated in patients producing 5 or fewer embryos. This study is a retrospective analysis of PGD patients with recurrent pregnancy loss in an IVF program. Patients with two or more consecutive miscarriages scheduled for PGD were included in the study. Patients with 5 or fewer embryos that were suitable for biopsy on Day 3 were asked whether or not they wished to continue with PGD analysis. Embryos were determined to be suitable for biopsy if there were at least 4 cells, with fewer than 30% fragmentation. Those who cancelled PGD were considered the “control” group, and those who decided to proceed were the ”test“ group. For the test group, single-cell biopsy was performed on Day 3, followed by fixation and PGD using FISH with probes for 9 chromosomes. Embryo replacement occurred on Day 4 for the test group. Replacement was performed on Day 3 for patients in the control group. Implantation and pregnancy rates were determined by fetal cardiac activity/number of embryos transferred or the number of retrievals. A total of 70 RPL couples produced 5 or fewer embryos that were suitable for biopsy. Of those, 47 decided to continue with the PGD procedure. The implantation and delivery rates were significantly higher in the group that received PGD (p<0.05; see Table 1). Although the spontaneous abortion rate was lower in the PGD group (4/22, 18.1% vs. 3/6, 50%), this difference was not statistically significant.Tabled 1 Even when 5 or fewer embryos were produced, the utilization of PGD was effective in increasing the delivery rate. PGD is therefore indicated for patients with idiopathic RPL irrespective of the number of embryos produced in the cycle. This finding may not be applicable to other poor responder patient groups; the effect of embryo number on other types of poor responders is under active investigation.