RESUMO
RESEARCH QUESTION: Are intrinsic or extrinsic factors associated with embryo mosaicism prevalence in IVF cycles? DESIGN: Retrospective cohort study of preimplantation genetic testing for aneuploidy (PGT-A) cycles carried out at a university-affiliated IVF clinic between October 2017 and October 2019. Trophectoderm biopsies were analysed by next generation sequencing. Mosaicism prevalence, type of anomaly and the chromosomes involved were analysed. Intrinsic and extrinsic factors potentially inducing mosaicism were studied: maternal and paternal age, antral follicle count, cumulus-oocyte complexes retrieved, female body mass index, PGT-A indication, sperm concentration, total dosage of gonadotrophins, embryo quality and day of blastocyst formation, single-step commercial media used and biopsy operator. RESULTS: Overall prevalence of mosaicism in our PGT-A setting was 13.9%. In segmental mosaicism, larger chromosomes tended to be more affected, which was not observed in whole-chromosome mosaicism. Additionally, segmental mosaicism was mostly observed in monosomy (69.6%; P < 0.01) compared with whole-chromosome mosaicism (49.7% monosomies versus 50.3% trisomies; Pâ¯=â¯0.83). Although a high inter-patient variability was observed, only paternal age showed a positive association with mosaicism (adjusted OR 1.26, 95% CI 1.02 to 1.54) among the analysed variables. CONCLUSIONS: Our results suggest remarkable differences in the mechanisms generating segmental and whole-chromosome mosaicism, indicating that they may deserve different consideration when studying them and when prioritizing them for transfer. Male factor seems to be associated with mosaicism and may be worthy of specific assessment in future studies.
Assuntos
Aneuploidia , Blastocisto/patologia , Mosaicismo/estatística & dados numéricos , Diagnóstico Pré-Implantação/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
RESEARCH QUESTION: Preimplantation genetic testing for aneuploidies has increasingly been employed for embryo selection, resulting in a recent surge in mosaic embryos. According to the cytogenetic results, which types of mosaic embryo survive early pregnancy, progress to the second trimester and finally result in a live birth? DESIGN: This study evaluated 30,587 pregnant women undergoing amniocentesis from January 2004 to March 2020 at the cytogenic centre of Kaohsiung Chang Gung Memorial Hospital. Samples from amniocentesis were cultured using the in-situ method. The types and distribution of level III chromosomal mosaicism (two or more cells with the same abnormality in two or more colonies and both culture dishes, clinically referred to as 'true mosaicism') were retrospectively reviewed. RESULTS: Among the 30,587 women, 78 cases (0.26%) of level III chromosomal mosaicism were identified. The types of chromosomal mosaicism were classified as sex chromosome mosaicism (SCM), autosomal chromosome mosaicism (ACM) and marker chromosome mosaicism (MCM), with SCM, ACM and MCM accounting for 58.97%, 32.05% and 8.97% of cases, respectively. The most common mosaic cell lines were monosomy X and trisomy 21. The most common mosaic cell line progressing to live birth was monosomy X. CONCLUSIONS: Mosaic monosomy X and trisomy 21 are the most common cell lines of true mosaicism determined by amniocentesis. Monosomy X mosaicism is the most common cell line in live births. For women considering the transfer of these types of mosaic embryo in a circumstance where euploid embryos are unavailable, clinicians should provide careful prenatal counselling, detailed ultrasonography and amniocentesis.
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Síndrome de Down , Mosaicismo/estatística & dados numéricos , Diagnóstico Pré-Implantação/estatística & dados numéricos , Síndrome de Turner , Amniocentese/estatística & dados numéricos , Feminino , Humanos , Gravidez , Estudos RetrospectivosRESUMO
RESEARCH QUESTION: What is the incidence of complex mosaic in preimplantation genetic testing (PGT) blastocysts and can it be managed in clinical practice? DESIGN: A retrospective study of PGT cycles conducted between January 2018 and October 2019 at a single centre. Biopsies of blastocysts were collected and analysed by next-generation sequencing (NGS). Complex mosaic blastocysts were defined as those with three or more mosaic chromosomes. The cryopreserved complex mosaic blastocysts underwent a second round of biopsy, NGS analysis and vitrification. The euploid blastocysts identified by the re-biopsy were warmed again for embryo transfer. The main outcomes included the prevalence of the complex mosaic and the ongoing pregnancy rate. RESULTS: The prevalence of the complex mosaic was 2.4% (437/17,979). The prevalence of the complex mosaic was not associated with maternal age and morphological quality. A total of 89 complex mosaic blastocysts underwent re-biopsy and 96.6% (86/89) survived the first warming. For the re-biopsy samples, 61.6% (53/86) were euploid. The poor-quality blastocysts had higher rates of aneuploidy compared with good-quality blastocysts. The survival rate for blastocysts undergoing the second warming was 100% (18/18) and resulted in an ongoing pregnancy rate of 38.9% (7/18) as well as the birth of six healthy infants. CONCLUSION: Re-biopsy may rescue blastocysts with development potential for transfer and improve the cumulative pregnancy rate per stimulation cycle in patients containing complex mosaic blastocysts.
Assuntos
Blastocisto/patologia , Infertilidade/diagnóstico , Mosaicismo , Adulto , Biópsia , Blastocisto/metabolismo , Aberrações Cromossômicas/embriologia , Aberrações Cromossômicas/estatística & dados numéricos , Criopreservação , Transferência Embrionária/estatística & dados numéricos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Infertilidade/epidemiologia , Infertilidade/genética , Infertilidade/terapia , Mosaicismo/embriologia , Mosaicismo/estatística & dados numéricos , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Prevalência , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , VitrificaçãoRESUMO
OBJECTIVE: To determine whether preimplantation genetic testing (PGT) is associated with an increase in adverse maternal or neonatal outcomes in singleton and twin live births conceived via in vitro fertilization (IVF). METHOD: Retrospective cohort of live births resulting from IVF within a university health system between January 2014 and August 2019. Adverse maternal outcomes (e.g., hypertensive disorders of pregnancy, abnormal placentation, and preterm birth), and adverse neonatal outcomes were compared in singleton and twin pregnancies conceived after transfer of one or two PGT-screened euploid embryos versus untested embryos in separate analyses. Multivariate backwards-stepwise logistic regression was used to adjust for potential confounders. RESULTS: Of 1160 live births, 539 (46.5%) resulted from PGT-screened embryos, 1015 (87.5%) were singletons, and 145 (12.5%) were twins. After adjusting for potential confounders, there were no significant differences between the two groups with respect to hypertensive disorders of pregnancy, fetal growth restriction, preterm birth, and adverse neonatal outcomes in both analyses, as well as abnormal placentation for singletons. CONCLUSION: Our data suggest that IVF with PGT is not associated with an increased risk of adverse maternal or neonatal outcomes compared to IVF without PGT. Further research utilizing larger cohorts are needed before drawing definitive conclusions.
Assuntos
Fertilização in vitro/métodos , Resultado da Gravidez/epidemiologia , Diagnóstico Pré-Implantação/normas , Adulto , Estudos de Coortes , Feminino , Fertilização in vitro/estatística & dados numéricos , Testes Genéticos/métodos , Testes Genéticos/tendências , Humanos , Gravidez , Diagnóstico Pré-Implantação/métodos , Diagnóstico Pré-Implantação/estatística & dados numéricos , Estudos RetrospectivosRESUMO
BACKGROUND: Chromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion. METHODS: A total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed. RESULTS: There were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%, P = 0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%, P = 0.256). CONCLUSIONS: Due to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.
Assuntos
Inversão Cromossômica , Resultado da Gravidez/epidemiologia , Diagnóstico Pré-Implantação , Adulto , China/epidemiologia , Inversão Cromossômica/embriologia , Inversão Cromossômica/genética , Inversão Cromossômica/estatística & dados numéricos , Hibridização Genômica Comparativa , Características da Família , Feminino , Fertilização in vitro/métodos , Fertilização in vitro/estatística & dados numéricos , Testes Genéticos/métodos , Humanos , Recém-Nascido , Nascido Vivo/epidemiologia , Masculino , Pessoa de Meia-Idade , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/efeitos adversos , Diagnóstico Pré-Implantação/estatística & dados numéricos , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/métodos , Injeções de Esperma Intracitoplásmicas/estatística & dados numéricos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: The impact of bleeding for women with bleeding disorders (WBD) is of increasing focus and importance. Despite this, optimal management strategies are unclear and knowledge gaps persist. AIM: To examine practices and define research priorities on diagnosis and management of WBD in Europe. METHODS: An electronic survey on clinical management of WBD was sent to 136 European haemophilia treatment centres (HTCs), including open questions on knowledge gaps and research priorities. RESULTS: Fifty-nine HTCs from 12 Western (WE) and 13 Central/Eastern European (CEE) countries completed the survey. Less than half runs a joint clinic (24 HTCs, 42%). Most centres without a joint clinic have a named obstetrician (81%) and/or gynaecologist (75%) available for collaboration. Overall 18/54 (33%) European HTCs do not offer preimplantation genetic diagnosis. Third trimester amniocentesis to guide obstetric management is available 28/54 HTCs (52%), less frequent in CEE compared to WE countries (5/17 vs 23/37, P = .03). 53% of HTCs (28/53) reported that only 0%-25% of WBD seek medical advice for heavy menstrual bleeding (HMB). An algorithm managing acute HMB in WBD is lacking in 22/53 (42%) HTCs. The main reported knowledge and research gaps are lack of awareness & education on WBD among patients and caregivers, optimal diagnostic strategies and effective multidisciplinary management of pregnancy & HMB. CONCLUSION: Joint clinics, prenatal diagnostics and algorithms for managing acute HMB are lacking in many European HTCs. HMB may be an underestimated issue. This survey highlights the need to prioritize improvement of knowledge and patient care for WBD across Europe.
Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Hemofilia A/tratamento farmacológico , Menorragia/terapia , Doenças de von Willebrand/tratamento farmacológico , Algoritmos , Amniocentese/estatística & dados numéricos , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/epidemiologia , Aconselhamento , Europa (Continente)/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hemofilia A/complicações , Hemofilia A/diagnóstico , Humanos , Masculino , Menorragia/diagnóstico , Menorragia/etiologia , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Terceiro Trimestre da Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Diagnóstico Pré-Natal/normas , Inquéritos e Questionários , Doenças de von Willebrand/complicações , Doenças de von Willebrand/diagnósticoRESUMO
The risks of embryo/gamete mix-up are a threat to the integrity of the IVF process, with significant implications for affected families. The use of preimplantation genetic testing through single-nucleotide polymorphism array or next-generation sequencing technology can help to identify, characterize and ultimately help, in some cases, to find the root cause, and to mitigate the extent of these errors for a given patient or laboratory.
Assuntos
Erros de Diagnóstico , Destinação do Embrião , Fertilização in vitro , Diagnóstico Pré-Implantação , Análise de Causa Fundamental , Aneuploidia , Blastocisto , Erros de Diagnóstico/estatística & dados numéricos , Destinação do Embrião/normas , Feminino , Fertilização in vitro/normas , Fertilização in vitro/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , Humanos , Masculino , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/efeitos adversos , Diagnóstico Pré-Implantação/métodos , Diagnóstico Pré-Implantação/estatística & dados numéricos , Projetos de Pesquisa , Análise de Causa Fundamental/métodosRESUMO
RESEARCH QUESTION: Day of cryopreservation, inner cell mass (ICM) grade, trophectoderm grade and blastocyst expansion grade have been associated with differences in live birth rate in frozen embryo transfer (FET) cycles. This study sought to examine the likelihood of live birth and whether the morphological grade of the blastocyst is more or equally useful in FET cycles among preimplantation genetic testing for aneuploidies (PGT-A) tested and untested blastocysts. DESIGN: This was a retrospective cohort study of 6271 vitrified-warmed, autologous, single-embryo transfer cycles among patients undergoing IVF from July 2013 to December 2017 at a single, university-affiliated infertility practice. The primary outcome was live birth, calculated by generalized estimating equations. RESULTS: Among PGT-A tested embryos, inferior ICM grade was associated with a lower chance of live birth (ICM grade B versus A: adjusted risk ratio [aRR] 0.91, 95% confidence interval [CI] 0.84-0.99). Among untested blastocysts there was a lower live birth rate in blastocysts cryopreserved on day 6 versus day 5 (aRR 0.87, 95% CI 0.78-0.96), and those with inferior pre-vitrification trophectoderm grade (trophectoderm grade B versus A: aRR 0.86, 95% CI 0.79-0.94). Blastocysts with a higher pre-vitrification expansion grade (pre-vitrification expansion grade 5 versus 4: aRR 1.1, 95% CI 1.01-1.2) were associated, but ICM grade was not associated (ICM grade B versus A: aRR 0.93, 95% CI 0.86-1.02), with chance of live birth. CONCLUSIONS: Among PGT-A untested blastocysts, assessing embryo quality by day of cryopreservation, trophectoderm grade and expansion grade may help to identify embryos with the highest likelihood of live birth. Identifying euploid embryos by PGT-A appears to homogenize the cohort, making blastocyst morphological grade and day of cryopreservation less important.
Assuntos
Blastocisto/citologia , Transferência Embrionária/estatística & dados numéricos , Resultado da Gravidez/epidemiologia , Diagnóstico Pré-Implantação/estatística & dados numéricos , Adulto , Aneuploidia , Forma Celular , Estudos de Coortes , Criopreservação , Transferência Embrionária/métodos , Feminino , Testes Genéticos/estatística & dados numéricos , Humanos , Recém-Nascido , Masculino , Gravidez , Diagnóstico Pré-Implantação/métodos , Estudos Retrospectivos , Estados Unidos/epidemiologia , VitrificaçãoRESUMO
OBJECTIVE: Women with pregnancies resulting from in vitro fertilization (IVF) with normal pre-implantation genetic testing for aneuploidy (PGT-A) are advised to undergo prenatal screening and testing during pregnancy. It is not well known how many follow these recommendations. Our objective was to study prenatal testing decisions made by women with pregnancies conceived through IVF with PGT-A. METHODS: We performed a retrospective review of women who received genetic counseling during pregnancies conceived through IVF with normal PGT-A. We excluded those who received genetic counseling preconceptionally prior to IVF. Statistical analysis included descriptive statistics and after testing for normality by the Kolmogorov-Smirnov test, independent t test, Mann-Whitney U test, or Chi-square/Fisher's exact test. RESULTS: Data from 83 women were included. Of these, 53 (63.9%) had at least one of the following prenatal tests: first trimester combined screening (16.9%), non-invasive prenatal screening (NIPS) (45.8%), second trimester serum screening (6%), and invasive diagnostic testing (6%). 10.8% had more than one of the above tests and 36.1% declined all tests. CONCLUSION: Almost two-thirds of women who were pregnant after IVF with normal PGT-A had prenatal aneuploidy screening or testing. Future prospective studies with larger cohorts are needed to further ascertain decision making in this population.
Assuntos
Fertilização in vitro/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , Diagnóstico Pré-Implantação/estatística & dados numéricos , Diagnóstico Pré-Natal/estatística & dados numéricos , Adulto , Aneuploidia , Feminino , Testes Genéticos/métodos , Humanos , Padrões de Prática Médica/estatística & dados numéricos , Gravidez , Primeiro Trimestre da Gravidez/sangue , Primeiro Trimestre da Gravidez/genética , Diagnóstico Pré-Implantação/métodos , Diagnóstico Pré-Natal/métodos , Estudos RetrospectivosRESUMO
Reproductive carrier screening started in some countries in the 1970s for hemoglobinopathies and Tay-Sachs disease. Cystic fibrosis carrier screening became possible in the late 1980s and with technical advances, screening of an ever increasing number of genes has become possible. The goal of carrier screening is to inform people about their risk of having children with autosomal recessive and X-linked recessive disorders, to allow for informed decision making about reproductive options. The consequence may be a decrease in the birth prevalence of these conditions, which has occurred in several countries for some conditions. Different programs target different groups (high school, premarital, couples before conception, couples attending fertility clinics, and pregnant women) as does the governance structure (public health initiative and user pays). Ancestry-based offers of screening are being replaced by expanded carrier screening panels with multiple genes that is independent of ancestry. This review describes screening in Australia, Cyprus, Israel, Italy, Malaysia, the Netherlands, Saudi Arabia, the United Kingdom, and the United States. It provides an insight into the enormous variability in how reproductive carrier screening is offered across the globe. This largely relates to geographical variation in carrier frequencies of genetic conditions and local health care, financial, cultural, and religious factors.
Assuntos
Triagem de Portadores Genéticos , Testes Genéticos , Internacionalidade , Aborto Induzido/estatística & dados numéricos , Austrália , Chipre , Fibrose Cística/genética , Feminino , Triagem de Portadores Genéticos/métodos , Testes Genéticos/métodos , Hemoglobinopatias/genética , Heterozigoto , Humanos , Israel , Itália , Malásia , Países Baixos , Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Diagnóstico Pré-Natal/estatística & dados numéricos , Arábia Saudita , Doença de Tay-Sachs/genética , Talassemia/genética , Reino Unido , Estados UnidosRESUMO
INTRODUCTION: Assisted reproduction technologies are being rapidly developed and implementation of preimplantation genetic testing (PGT) has allowed patients with genetic disorders to initiate pregnancies while minimizing or eliminating the risk of transmitting these disorders to their offspring. Testing for numeric chromosomal anomalies has been proposed as a way to increase efficacy in assisted reproduction; however, this remains disputed. Legislation is lagging behind the rapid developments in this field. MATERIAL AND METHODS: We conducted a structured online survey of legislation and accessibility to preimplantation genetic testing in the Nordic countries to compare the regulation and uptake of this technique. The survey was designed and answered by the authors. RESULTS: Key elements in the regulation of preimplantation testing for monogenic disorders and structural rearrangements are similar in the Nordic countries, although accessibility varies since only Denmark, Finland, and Sweden have national clinics offering treatment. In addition, Denmark and Finland have private clinics offering PGT. Regulation is the most stringent in Norway where a national board evaluates all couples seeking treatment. Treatment volumes vary between the Nordic countries, with Norway and Finland having lowest treatment numbers. Preimplantation genetic testing for aneuploidy in the embryo varies between the Nordic countries: Finland and Iceland allow this form of treatment, Denmark and Sweden offer it only in the form of a research protocol, and Norway does not allow it at all. Therefore the number of treatment cycles involving testing for embryo aneuploidy are lower in the Nordic countries than in other countries where this treatment option is more common. CONCLUSIONS: Science needs to inform politics regarding the rapidly evolving field of reproductive medicine and we recommend harmonization of legislation and accessibility between the Nordic countries.
Assuntos
Testes Genéticos/legislação & jurisprudência , Testes Genéticos/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Diagnóstico Pré-Implantação/estatística & dados numéricos , Aneuploidia , Feminino , Rearranjo Gênico , Doenças Genéticas Inatas/diagnóstico , Humanos , Gravidez , Países Escandinavos e Nórdicos , Inquéritos e QuestionáriosRESUMO
Aim: The aim of this study is to summarize the outcomes of transfers of mosaic embryos, which were classified according to guidelines and in strong collaboration of reproductologists, clinical geneticists and patients approved as suitable for transfer. Material and Methods: Retrospective data were collected from 70 patients from a private IVF center to whom embryos with mosaic changes in chromosomal material were transferred from 2015 to 2019. Results and Conclusion: Implantation outcomes and continuing pregnancies showed slight differences, when compared to fully normal embryos. Artifacts have to be differentiated from undeniable aberrations, and correct interpretation of results must be done with following patient counselling and prenatal testing if necessary.
Assuntos
Transferência Embrionária/estatística & dados numéricos , Mosaicismo/estatística & dados numéricos , Resultado da Gravidez/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Clínicas de Fertilização , Fertilização in vitro/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , História do Século XXI , Humanos , Letônia/epidemiologia , Mosaicismo/embriologia , Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
STUDY QUESTION: What are the factors influencing the success rate for couples undergoing preimplantation genetic testing (PGT) for polycystic kidney disease (PKD)? SUMMARY ANSWER: In our study cohort, the live birth delivery rate is significantly associated with female age while the male infertility accompanying autosomal dominant PKD (ADPKD) does not substantially affect the clinical outcome. WHAT IS KNOWN ALREADY: While women with ADPKD have no specific fertility problems, male ADPKD patients may present with reproductive system abnormalities and infertility. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study involves 91 PGT cycles for PKD for 43 couples (33 couples for PKD1, 2 couples for PKD2 and 8 couples for autosomal recessive PKD (ARPKD)) from January 2005 until December 2016 with follow-up of transfers until end of 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixteen single-cell clinical tests for PKD based on multiplex PCR of short tandem repeat markers, with or without a specific mutation were developed and applied for diagnosis of 584 Day 3 cleavage stage embryos. In 18 couples, the male partner was affected with ADPKD (=Group A) and 12 of them had a documented infertility status. Group A underwent 52 cycles to oocyte retrieval. For 18 other couples, the female partner was affected with ADPKD (=Group B) and four male partners from this group had a documented history of infertility. This group underwent 31 cycles to OR. MAIN RESULTS AND THE ROLE OF CHANCE: Genetic analysis resulted in 545 embryos (93.3%) with a diagnosis, of which 215 (36.8%) were genetically transferable. Transfer of 74 embryos in 53 fresh cycles and of 34 cryopreserved embryos in 33 frozen-warmed embryo transfer cycles resulted in a live birth delivery rate of 38.4% per transfer with 31 singleton live births, two twin live births and one ongoing pregnancy. The observed cumulative delivery rate was 57.8% per couple after five treatment cycles. Thirty cryopreserved embryos still remain available for transfer. The clinical pregnancy rate per transfer (fresh + frozen; 45.9% in group A versus 60.0% in group B, P < 0.05) and the live birth delivery rate per transfer (fresh + frozen; 27.0% in group A versus 42.9% in group B, P < 0.05) was significantly lower for couples with the male partner affected with ADPKD compared with couples with the female partner affected with ADPKD. However, a multivariate logistic regression analysis showed that only female age was associated with live birth delivery rate (odds ratio = 0.87; 95% CI: 0.77-0.99; P = 0.032). LIMITATIONS, REASONS FOR CAUTION: This study is based on retrospective data from a single centre with Day 3 one-cell and two-cell biopsy. Further analysis of a larger cohort of PKD patients undergoing PGT is required to determine the impact of male infertility associated with ADPKD on the cumulative results. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge about factors affecting the clinical outcome after PGT can be a valuable tool for physicians to counsel PKD patients about their reproductive options. Males affected with ADPKD who suffer from infertility should be advised to seek treatment in time to improve their chances of conceiving a child. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.
Assuntos
Fertilização in vitro/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , Infertilidade/terapia , Doenças Renais Policísticas/diagnóstico , Diagnóstico Pré-Implantação/estatística & dados numéricos , Adulto , Coeficiente de Natalidade , Análise Mutacional de DNA , Transferência Embrionária/estatística & dados numéricos , Feminino , Aconselhamento Genético , Humanos , Infertilidade/genética , Nascido Vivo , Masculino , Pessoa de Meia-Idade , Mutação , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/genética , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Fatores Sexuais , Injeções de Esperma Intracitoplásmicas/estatística & dados numéricos , Canais de Cátion TRPP/genética , Resultado do TratamentoRESUMO
RESEARCH QUESTION: Does preimplantation genetic testing for aneuploidy (PGT-A) influence the discontinuation rate in women with advanced maternal age (AMA) undergoing IVF? DESIGN: Retrospective longitudinal cohort study carried out at a single IVF clinic in Turkey. In total, 401 consecutive AMA cases were included. Discontinuation rates of pre-intervention (conventional IVF; June 2013 to October 2014; 203 couples; 270 cycles) and post-intervention (PGT-A; April 2015 to June 2016; 198 couples; 285 cycles) periods were compared. To delineate the reason for discontinuation, a telephone survey was conducted. Primary outcome measure was cumulative discontinuation rate before completing three cycles of IVF treatment without achieving an ongoing pregnancy. RESULTS: The discontinuation rates after the first and second failed cycles were comparable between the two arms as were the cumulative discontinuation rates before completing three cycles. The cumulative ongoing pregnancy rate per embryo transfer was significantly higher in the PGT-A arm (43.2% versus 16.8%; P < 0.001). The cumulative ongoing pregnancy rate per patient was comparable between the two arms (20.7% versus 16.3%, respectively). Female age was the only significant contributor to treatment discontinuation (hazard ratio [HR] 1.07; 95% CI 1.09 to 1.13). Of the 296 couples discontinuing treatment in both arms, 179 (179/296 [60.5%]) participated in the survey; overall, psychological burden was the main reason for treatment discontinuation (37/179 [20.7%]). CONCLUSIONS: About 90% of AMA cases not achieving an ongoing pregnancy discontinue IVF treatment before completing three cycles. Discontinuation rate is not reduced by carrying out PGT-A. Female ageing is the only significant contributor, with a hazard of discontinuing further IVF treatment of 7% with female ageing of 1-year.
Assuntos
Aneuploidia , Fertilização in vitro/estatística & dados numéricos , Idade Materna , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Diagnóstico Pré-Implantação , Suspensão de Tratamento/estatística & dados numéricos , Adulto , Estudos de Coortes , Transferência Embrionária/estatística & dados numéricos , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/métodos , Diagnóstico Pré-Implantação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
RESEARCH QUESTION: To analyse why unbalanced viable offspring are derived mainly from the 3:1 segregation mode in t(11;22)(q23;q11.2) reciprocal translocation. DESIGN: Retrospective analysis of 24 pre-implantation genetic testing for chromosomal structural re-arrangements (PGT-SR) cycles was performed on seven male and five female carriers of t(11;22) translocation. Sperm analysis was performed on each male carrier. These patients were directed to the study centre after several years of miscarriages and/or abortions, primary infertility for male carriers or birth of an affected child. RESULTS: Twenty-four PGT-SR cycles were performed to exclude imbalances in both male and female carriers. The unbalanced embryos derived from the adjacent-1 segregation mode were the most represented in both male and female carriers (68.4% and 50%, respectively). These results were positively related with meiotic segregation analysis of reciprocal translocation in spermatozoa. A thorough analysis of the unbalanced embryo karyotypes determined that the expected viable +der22 karyotype resulting from 3:1 malsegregation was less represented at 5.3%. CONCLUSIONS: These findings highlight the divergence that may exist between meiotic segregation and post-zygotic selection. Post-zygotic selection would be responsible for the elimination of unbalanced embryos derived from the adjacent-1 segregation mode. The combined action of several factors occurs at the beginning of post-zygotic selection. Genetic counselling must consider the risk of a birth related to the adjacent-1 segregation mode, irrespective of the sex of the translocation carrier. These results will allow deeper understanding of the PGT results of t(11;22) carriers, which often include a high number of aneuploid embryos.
Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 22/genética , Padrões de Herança/genética , Diagnóstico Pré-Implantação/métodos , Translocação Genética , Adulto , Mapeamento Cromossômico/métodos , Mapeamento Cromossômico/estatística & dados numéricos , Feminino , Frequência do Gene , Triagem de Portadores Genéticos/métodos , Humanos , Hibridização in Situ Fluorescente/métodos , Hibridização in Situ Fluorescente/estatística & dados numéricos , Cariotipagem , Masculino , Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Estudos Retrospectivos , Análise do Sêmen/métodos , Análise do Sêmen/estatística & dados numéricos , Translocação Genética/genéticaRESUMO
OBJECTIVE: Outcomes from in vitro fertilization (IVF)/intrauterine insemination (ICSI) cycles for patients who underwent preimplantation genetic testing for monogenic/single gene (PGT-M) and structural chromosome rearrangements (PGT-SR) patients were reviewed. Patients pursuing PGT-M and PGT-SR often do not have pre-existing fertility issues and therefore may have uncertain expectations of successful outcomes. Before pursuing PGT-M and PGT-SR, patients require evidence-based counseling regarding the probability of having a healthy child. METHOD: Retrospective review from a single private IVF clinic of 73 PGT patients, from whom a total of 437 blastocysts were biopsied and screened. Embryo results and pregnancy outcomes were analyzed. RESULTS: Of the 45 PGT-M patients, 64.4% had at least one euploid unaffected embryo. The cumulative pregnancy rate for patients who had embryo transfers in this group was 89.7%, with an ongoing pregnancy or delivery rate of 48.9%. For the 28 PGT-SR patients, 60.7% had at least one euploid unaffected embryo. The cumulative pregnancy rate for patients who had embryo transfers in this group was 87.5%, with an ongoing pregnancy or delivery rate of 42.9%. CONCLUSION: This information can supplement the existing data in the literature to counsel new patients in terms of realistic expectations of success following PGT-M and PGT-SR.
Assuntos
Aberrações Cromossômicas , Doenças Genéticas Inatas/diagnóstico , Testes Genéticos/métodos , Resultado da Gravidez/epidemiologia , Diagnóstico Pré-Implantação/métodos , Adulto , Biópsia , Blastocisto/patologia , Canadá/epidemiologia , Aberrações Cromossômicas/estatística & dados numéricos , Transferência Embrionária/métodos , Transferência Embrionária/estatística & dados numéricos , Feminino , Clínicas de Fertilização , Fertilização in vitro/métodos , Fertilização in vitro/estatística & dados numéricos , Doenças Genéticas Inatas/epidemiologia , Testes Genéticos/estatística & dados numéricos , Humanos , Padrões de Herança , Masculino , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the preimplantation genetic diagnosis (PGD) service, for the period of January 2006 to December 2016, through a South African academic and diagnostic Human Genetics Unit, and to assess the outcomes and cost of PGD. METHODS: A retrospective review of PGD files available at the Human Genetics Unit was performed. Data was collected from genetic counseling, fertility, and PGD-specific records. RESULTS: Amongst the 22 couples who had PGD, 42 in vitro fertilisation cycles were completed with 228 embryos biopsied and included in the analysis. Most (59%) of the conditions for which PGD was requested were autosomal recessive. Of the biopsied embryos, 71/228 (31.1%) were suitable for transfer and 41/71 (57.7%) were transferred. Of these, 14/41 (34.0%) successfully implanted and 11/14 (78.6%) resulted in a liveborn infant. The clinical pregnancy rate per embryo transfer was 29.3%. Overall, 10/22 (45.5%) couples had a successful cycle resulting in a liveborn infant. On average, one cycle of PGD costs USD 9525. CONCLUSIONS: This is the first study to assess the success rates and the cost of PGD in South Africa and provides evidence for the feasibility in a low-to-middle-income country. The success rates in this sample are comparable to those achieved globally. South Africa has the infrastructure and expertise to provide PGD; the limiting factor is the lack of funding initiatives for PGD. Although the sample size was small, the findings from this study will enable genetic counselors to offer couples in South Africa evidence-based and locally accurate information regarding outcomes, success rates, and costs.
Assuntos
Fertilização in vitro/estatística & dados numéricos , Resultado da Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Adulto , Custos e Análise de Custo , Implantação do Embrião , Feminino , Humanos , Idade Materna , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/economia , Estudos Retrospectivos , África do Sul/etnologiaRESUMO
This study provides an overview of preimplantation genetic diagnosis (PGD) for single gene diseases and the management of expanding indications in the context of a fully financially covered service at Montpellier's regional hospital centre. Within the framework of a restrictive law ruling PGD in France, only the parental genetic risk can be studied in embryos (concurrent aneuploidy screening is not allowed). PCR-based techniques were developed combining mutation detection and closely linked short tandem repeat markers within or flanking the affected genes, and set up more than 100 different robust fluorescent multiplex assays for 61 monogenic disorders. This strategy was used to analyse blastomeres from cleavage-stage embryos. Overall, 893 cycles were initiated in 384 couples; 727 cycles proceeded to oocyte retrieval and 608 cycles to embryo transfer, resulting in 184 deliveries. Clinical pregnancy rate per transfer, implantation and miscarriage rates were 33.6%, 25.1% and 8.8%, respectively. Our PGD programme resulted in the birth of 214 healthy babies for 162 out of 358 couples (45.3%), constituting a relevant achievement within an organizational framework that does not allow aneuploidy screening but provides equal access to PGD, both geographically and socioeconomically. This is a rare example of a fully free-of-charge PGD service.
Assuntos
Diagnóstico Pré-Implantação/estatística & dados numéricos , Feminino , França , Doenças Genéticas Inatas/diagnóstico , Hospitais Públicos/estatística & dados numéricos , Humanos , Masculino , Programas Nacionais de Saúde , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: To examine the statewide utilisation of prenatal diagnosis (PNDx) and preimplantation genetic diagnosis (PGT-M) for single gene disorders. METHODS: Population-based study of all women utilising PNDx in the Australian state of Victoria from 1977 to 2016. Single gene disorders were categorised using a systematic approach that aimed to reflect aspects of the PNDx decision-making process. Data on PGT-M for single gene disorders from 2005 to 2016 were similarly examined for comparison. Statistical significance testing was performed with χ2 test. RESULTS: Following an initial uptake period, annual PNDx rates for single gene disorders stabilised between 1.3 and 2.2 per 1000 births after the year 2000. The majority of PNDx (72%) was performed for disorders that primarily impair physical ability, while PNDx for adult onset conditions was rare (3%). PGT-M for single gene disorders has seen rapid growth since its introduction, and annual numbers now equal that of PNDx. In contrast to PNDx, one quarter of PGT-M tests were performed for adult onset conditions. CONCLUSIONS: Our population-wide analysis has demonstrated a steady demand for PNDx for single gene disorders over the past decade, in contrast to the rapidly increasing utilisation of PGT-M. PGT-M appears to be the preferred testing modality for adult onset disorders.
Assuntos
Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/genética , Testes Genéticos/tendências , Diagnóstico Pré-Implantação/tendências , Diagnóstico Pré-Natal/tendências , Bases de Dados Factuais/estatística & dados numéricos , Bases de Dados Factuais/tendências , Feminino , Doenças Genéticas Inatas/diagnóstico , Testes Genéticos/estatística & dados numéricos , Humanos , Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Diagnóstico Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Vitória/epidemiologiaRESUMO
PURPOSE: This study aimed to determine the current percentage of United States (U.S.) assisted reproductive technology (ART) clinics offering sex selection via pre-implantation genetic screening (PGS) for non-medical purposes. METHODS: The authors conducted website review and telephone interview survey of 493 U.S. ART clinics performing in vitro fertilization (IVF) in 2017. Main outcome measures were pre-implantation genetic screening (PGS)/pre-implantation genetic diagnosis (PGD) practices and non-medical sex selection practices including family balancing. RESULTS: Of the 493 ART clinics in the USA, 482 clinics (97.8%) responded to our telephone interview survey. Among all U.S. ART clinics, 91.9% (n = 449) reported offering PGS and/or PGD. Furthermore, 476 clinics responded to survey questions about sex selection practices. Of those ART clinics, 72.7% (n = 346) reported offering sex selection. More specifically among those clinics offering sex selection, 93.6% (n = 324) reported performing sex selection for family balancing, and 81.2% (n = 281) reported performing for elective purposes (patient preference, regardless of rationale for the request). For couples without infertility, 83.5% (n = 289) of clinics offer sex selection for family balancing and 74.6% (n = 258) for non-specific elective reasons. CONCLUSIONS: The majority of U.S. ART clinics offer non-medical sex selection, a percentage that has increased substantially since last reported in 2006.