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1.
Adv Mater ; 36(25): e2313306, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38593372

RESUMO

Monochorionic twinning of human embryos increases the risk of complications during pregnancy. The rarity of such twinning events, combined with ethical constraints in human embryo research, makes investigating the mechanisms behind twinning practically infeasible. As a result, there is a significant knowledge gap regarding the origins and early phenotypic presentation of monochorionic twin embryos. In this study, a microthermoformed-based microwell screening platform is used to identify conditions that efficiently induce monochorionic twins in human stem cell-based blastocyst models, termed "twin blastoids". These twin blastoids contain a cystic GATA3+ trophectoderm-like epithelium encasing two distinct inner cell masses (ICMs). Morphological and morphokinetic analyses reveal that twinning occurs during the cavitation phase via splitting of the OCT4+ pluripotent core. Notably, each ICM in twin blastoids contains its own NR2F2+ polar trophectoderm-like region, ready for implantation. This is functionally tested in a microfluidic chip-based implantation assay with epithelial endometrium cells. Under defined flow regimes, twin blastoids show increased adhesion capacity compared to singleton blastoids, suggestive of increased implantation potential. In conclusion, the development of technology enabling large-scale formation of twin blastoids, coupled with high-sensitivity readout capabilities, presents an unprecedented opportunity for systematically exploring monochorionic twin formation and its impact on embryonic development.


Assuntos
Gemelaridade Monozigótica , Humanos , Feminino , Gravidez , Blastocisto/citologia , Embrião de Mamíferos/citologia , Córion/citologia , Bioengenharia/métodos , Modelos Biológicos , Implantação do Embrião
2.
FEMINA ; 51(1): 43-48, jan. 31, 2023. ilus
Artigo em Português | LILACS | ID: biblio-1428680

RESUMO

A perfusão arterial reversa gemelar é uma anormalidade rara que pode ocorrer em gestações gemelares monocoriônicas. Consiste em uma alteração na circulação fetoplacentária, com desvio de sangue de um dos gemelares para o outro, por meio de anastomoses arterioarteriais e venovenosas na superfície placentária e anastomoses arteriovenosas em áreas de circulação placentária compartilhada. O feto bombeador pode desenvolver insuficiência cardíaca devido ao aumento do débito cardíaco, e o feto receptor, perfundido por sangue pobre em oxigênio por meio do fluxo reverso, é severamente malformado, incompatível com a vida extrauterina. Este artigo apresenta o caso de uma gestação gemelar monocoriônica diamniótica, com manejo clínico conservador. O objetivo é relatar um caso de complicação rara de gestações monozigóticas e revisar condutas para diagnóstico e manejo adequado.(AU)


Twin reverse arterial perfusion is a rare abnormality that can occur in monochorionic twin pregnancies. It consists of an alteration in the fetal-placental circulation, with blood diversion from one of the twins to the other, through arterio-arterial and veno- venous anastomosis on the placental surface and arterio-venous anastomosis in areas of shared placental circulation. The pumping fetus may develop heart failure due to increased cardiac output, and the recipient fetus, perfused by oxygen-poor blood through reverse flow, is severely malformed, incompatible with extrauterine life. This article presents the case of a monochorionic diamniotic twin pregnancy, with conservative clinical management. The objective is to report a case of rare complication of monozygotic pregnancies and review procedures for diagnosis and adequate management.(AU)


Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Complicações na Gravidez/fisiopatologia , Anastomose Arteriovenosa/anormalidades , Artérias Umbilicais/anormalidades , Anormalidades Congênitas/diagnóstico por imagem , Gravidez de Alto Risco , Gemelaridade Monozigótica , Transfusão Feto-Fetal/complicações , Brasil , Circulação Placentária , Morte Fetal , Monitorização Fetal , Clampeamento do Cordão Umbilical , Trabalho de Parto Prematuro
3.
Twin Res Hum Genet ; 24(3): 155-159, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34308812

RESUMO

Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.


Assuntos
Defeitos do Tubo Neural , Gemelaridade Monozigótica , Doenças em Gêmeos/genética , Epigênese Genética , Feminino , Humanos , Defeitos do Tubo Neural/genética , Placenta , Gravidez , Gemelaridade Monozigótica/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
4.
Placenta ; 111: 26-32, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34146967

RESUMO

INTRODUCTION: Thanks to shared circulation in monochorionic twins, single intrauterine fetal death (IUD) may lead to acute feto-fetal transfusion (aFFTR). The objective of the study was to describe our model of aFFTR simulation after IUD in monochorionic (MC) twins. METHODS: Prospective study analyzed 99 fresh MC placentas with the physiological course. A specially designed protocol was used for the preparation and analysis of the placentas. A pair of infusion sets fixed together using a mechanical mercury sphygmomanometer cuff was connected to the cannulated umbilical arteries. The tonometer was pressurized up to 30 and 40 mmHg. A positive finding of aFFTR was determined as the amount exceeding 1 ml of dye flowed out of the umbilical cord simulating a dead fetus. The number and types of anastomoses, types, and distances between cords insertions, and the size of the placental areas for each fetus were also statistically analyzed. The placental angioarchitecture with and without proven aFFTR was statistically compared, odds ratio (OR) and multivariable logistic analysis were performed. RESULTS: A total of 49/99 (49.5%) cases of aFFTR was proven, and the average transfusion time of 1 ml was 30 s (19-46 s). aFFTR was present in 49/78 (62.8%) of placentas with arterio-arterial (AA) anastomosis. The median diameter of AA anastomoses with the present, and absent aFFTRF was 2.0 mm and 1.0 mm, respectively. The proven interfetal transfusion was 8%, 31%, and 61% in AA anastomoses with a diameter below 0,5 mm, 0,5-1,5 mm, and above 1,5 mm, respectively (p < 0,001). AA anastomoses diameter >1.5 mm had OR of 44.2 (95% CI 5.54-352.39). In the case of coexistence of AA anastomosis and umbilical cord distance ≤5th percentile, the aFFTRF occurred in 90.9%. DISCUSSION: The potential risk of aFFTR in monochorionic twins is mainly due to the presence and nature of AA anastomoses. The diameter and length of the vessels play a crucial role, which is clinically related to the distance of the umbilical cords insertions.


Assuntos
Morte Fetal , Transfusão Feto-Fetal/etiologia , Modelos Cardiovasculares , Placenta/irrigação sanguínea , Fístula Vascular/complicações , Adulto , Feminino , Seguimentos , Humanos , Gravidez , Estudos Prospectivos , Gemelaridade Monozigótica
5.
Reprod Sci ; 28(5): 1421-1427, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33258063

RESUMO

In vitro fertilization (IVF) is associated with a higher incidence of monozygotic twin pregnancies, which are known to be burdened by a higher risk of main obstetric complications. The reasons behind this association are still unclear. In the present study, we therefore investigate the risk factors for monozygotic twinning in pregnancies achieved by IVF. We conducted a multicenter retrospective case-control study. All IVF cycles performed between 2014 and 2019 at the infertility units of two Italian academic institutes were retrospectively reviewed. Only pregnancies obtained with single embryo transfer were eligible. A total of 50 monozygotic twin pregnancies (cases) were identified and matched in a 1:5 ratio to 250 singleton pregnancies (controls) by study center and study period. Monozygotic twin pregnancies were diagnosed by ultrasound. Women experiencing miscarriage could be included provided that the pregnancy loss occurred after a definitive diagnosis of monozygotic twin pregnancy. Demographic, clinical, and embryological characteristics were retrieved from patients' charts. Overall, the incidence of monozygotic twin pregnancies was 1.2% (50 out of 4016 single embryo transfers). At univariate analyses, statistically significant differences emerged for BMI, peripheral levels of estradiol and progesterone at the time of hCG administration, total number of retrieved suitable oocytes, freezing-thawing cycles, and assisted hatching. After performing a multivariate logistic analysis, only assisted hatching remained significantly associated with monozygotic twinning (adjusted odds ratio 2.32, 95%CI 1.03-5.25). Blastomere separation during the passage through this artificial hole or interference with the signaling pathway within the embryo could be the mechanisms involved.


Assuntos
Fertilização in vitro/efeitos adversos , Gemelaridade Monozigótica , Gêmeos Monozigóticos , Adulto , Estudos de Casos e Controles , Estrogênios/análise , Feminino , Humanos , Oócitos/fisiologia , Progesterona/análise , Estudos Retrospectivos , Fatores de Risco
6.
JBRA Assist Reprod ; 25(1): 122-127, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-32969212

RESUMO

OBJECTIVE: Monozygotic twinning incidence following preimplantation genetic testing in embryos at cleavage-stage does not appear to increase; however, data regarding the possible impact of the blastocyst-stage preimplantation genetic testing is lacking. We compared the incidence of monozygotic twinning in preimplantation genetic testing cycles performed at the blastocyst-stage, versus cycles without PGT, following single embryo transfer. METHODS: In this retrospective cohort study, we analyzed the incidence of twin pregnancies in patients undergoing intracytoplasmic sperm injection and blastocyst-preimplantation genetic testing (253 cycles), versus a period-matched control population of patients undergoing intracytoplasmic sperm injection and single embryo transfer without preimplantation genetic testing (606 cycles). RESULTS: The overall monozygotic twinning rate was 14/859 (1.6%) per clinical pregnancy. The incidence of zygotic splitting following intracytoplasmic sperm injection and preimplantation genetic testing was 3.5% (95% Confidence interval 1.8%-6.6%) versus 0.8% (95% Confidence interval 0.3%-1.9%) following intracytoplasmic sperm injection without preimplantation sperm injection. After adjusting for potential confounders, preimplantation genetic testing cycles were associated with an increase in the incidence of monozygotic twinning when compared to cycles without embryo biopsy (Odd ratio 3.44, 95% Confidence interval 1.05-11.27, p=0.041). CONCLUSIONS: Our findings indicate that embryo biopsy for preimplantation genetic testing performed at the blastocyst stage is associated to an increase in the incidence of monozygotic twinning. Further validation in larger sample size studies is warranted. Patients undergoing preimplantation genetic testing must receive proper counselling about the potential risks of the technique.


Assuntos
Transferência Embrionária , Gemelaridade Monozigótica , Biópsia , Blastocisto , Feminino , Humanos , Gravidez , Estudos Retrospectivos
8.
BJOG ; 127(5): 562-569, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31828906

RESUMO

OBJECTIVE: To evaluate the risk of monozygotic splitting with embryo biopsy during in vitro fertilisation (IVF). DESIGN: A cohort study. SETTING: Anonymised assisted reproductive technology national data from the Human Fertilisation and Embryology Authority, UK. POPULATION: Women undergoing single-embryo transfer (SET) following either pre-implantation genetic testing (PGT) involving embryo biopsy or IVF without PGT. METHODS: Data on women undergoing SET either following PGT and non-PGT IVF treatment in 2000-2016 were analysed to compare the risk of zygotic splitting and monozygotic twining. Logistic regression analysis was performed adjusting for potential confounders. MAIN OUTCOMES: Monozygotic spitting, monozygotic twin birth. RESULTS: Data comprising a total of 207 697 SET cycles (4544 following PGT and 203 153 following non-PGT IVF) were analysed. The live birth rate per embryo transfer was 31.9% (95% confidence interval [CI] 30.5-33.2%) following PGT and 26.9% (95% CI 26.7-27.1%) following non-PGT IVF. The incidence of zygotic splitting following PGT was 2.4% (95% CI 1.7-3.3%) versus 1.5% (95% CI 1.4-1.6%) following non-PGT IVF. There was a significantly higher risk of zygotic splitting with PGT versus non-PGT IVF cycles (odds ratio [OR] 1.64, 95% CI 1.19-2.27). The higher risk of zygotic splitting with PGT cycles remained significant after adjusting for potential confounders (adjusted OR 1.51, 95% CI 1.06-2.15). CONCLUSIONS: The present study demonstrated an increased risk of monozygotic splitting with embryo biopsy. Given the current sparse literature, it is important to accumulate further evidence to validate the findings. TWEETABLE ABSTRACT: A likely increased risk of monozygotic splitting following embryo biopsy.


Assuntos
Fertilização in vitro , Diagnóstico Pré-Implantação , Transferência de Embrião Único , Gemelaridade Monozigótica , Adolescente , Adulto , Biópsia , Estudos de Coortes , Feminino , Humanos , Nascido Vivo , Modelos Logísticos , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
9.
Mol Hum Reprod ; 25(11): 729-744, 2019 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-31504820

RESUMO

It is widely held that the first two blastomeres of mammalian embryos are equally totipotent and that this totipotency belongs to the group of regulative properties. However, this interpretation neglects an important aspect: evidence only came from successful monozygotic twins which can speak only for those pairs of half-embryos that are able to regulate in the first place. Are the frequently occurring incomplete pairs simply an artefact, or do they represent a real difference, be it in the imperfect blastomere's ability to regulate growth or in the distribution of any compound X that constrains regulation? Using the model system of mouse embryos bisected at the 2-cell stage after fertilization, we present evidence that the interblastomere differences evade regulation by external factors and are already latent in oocytes. Specifically, an interblastomere imbalance of epiblast production persists under the most diverse culture conditions and applies to the same extent in parthenogenetic counterparts. As a result, cases in which twin blastocysts continued to develop in only one member account for 65 and 57% of zygotic and parthenogenetic pairs, respectively. The interblastomere imbalance is related to the subcellular distribution of gene products, as documented for the epiblast-related gene Cops3, using mRNA FISH in super-resolution mode confocal microscopy. Blastomere patterns of Cops3 mRNA distribution are α-amanitin-resistant. Thus, the imbalance originates not from de novo transcription, but from influences which are effective before fertilisation. These data expose previously unrecognized limits of regulative capacities of 2-cell stage blastomeres and point to aspects of cytoplasmic organization of the mouse oocyte that segregate unequally to blastomeres during cleavage.


Assuntos
Blastômeros/citologia , Fase de Clivagem do Zigoto/fisiologia , Embrião de Mamíferos/embriologia , Desenvolvimento Embrionário/fisiologia , Gemelaridade Monozigótica/fisiologia , Amanitinas/farmacologia , Animais , Complexo do Signalossomo COP9/genética , Técnicas de Cultura Embrionária , Feminino , Camundongos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , Gemelaridade Monozigótica/genética
10.
Fertil Steril ; 111(2): 302-317, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30691632

RESUMO

OBJECTIVES: To establish the risk factors for monozygotic twin (MZT) and monochorionic twin (MCT) pregnancies after in vitro fertilization (IVF). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women who achieved MZT and non-MZT pregnancies through IVF. INTERVENTION(S): Systematic search of Medline from January 1995 to October 2018 with cross-checking of references from relevant articles in English. MAIN OUTCOME MEASURE(S): Possible risk factors for MZT or MCT pregnancies after IVF, comprising extended embryo culture, insemination method (conventional IVF and intracytoplasmic sperm injection [ICSI]), embryo biopsy for preimplantation genetic testing for aneuploidies or for monogenic/single-gene defects (PGT-A or PGT-M) programs, assisted hatching (AH), oocytes donation, female age, and embryo cryopreservation. RESULT(S): A total of 40 studies were included. Blastocyst transfer compared with cleavage-stage embryo transfer, and female age <35 years were associated with a statistically significant increase in the MZT and MCT pregnancy rate after IVF: (23 studies, OR 2.16, 95% CI, 1.74-2.68, I2=78%; 4 studies, OR 1.29; 95% CI, 1.03-1.62, I2=62%; and 3 studies, OR 1.90, 95% CI, 1.21-2.98, I2=59%; 2 studies, OR 2.34; 95% CI, 1.69-3.23, I2=0, respectively). Conventional IVF compared with ICSI and assisted hatching were associated with a statistically significantly increased risk of MZT pregnancy (9 studies, OR 1.19, 95% CI, 1.04-1.35, I2=0; 16 studies, OR 1.17, 95% CI, 1.09-1.27, I2=29%, respectively). Embryo biopsy for PGT-A or PGT-M, embryo cryopreservation, and oocytes donation were not associated with MZT pregnancies after IVF. CONCLUSION(S): Blastocyst transfer is associated with an increased risk of both MZT and MCT pregnancies after IVF. Further evidence is needed to clarify the impact of female age, insemination method and AH on the investigated outcomes.


Assuntos
Técnicas de Cultura Embrionária , Transferência Embrionária/efeitos adversos , Fertilização in vitro/efeitos adversos , Gravidez de Gêmeos , Gemelaridade Monozigótica , Gêmeos Monozigóticos , Adulto , Feminino , Humanos , Idade Materna , Gravidez , Medição de Risco , Fatores de Risco , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Resultado do Tratamento
11.
Stem Cells Dev ; 28(5): 303-309, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30608032

RESUMO

In vitro embryo twinning can be used to increase the number of the human embryos available for production of human embryonic stem cell (hESC) lines. The aim of this study was to generate hESCs following the production of the twin embryos by in vitro embryo splitting procedures. In total 21 chromosomally abnormal (three pronuclei) embryos underwent in vitro embryo twinning and were allowed to develop to the blastocyst stage. As a result, 42 twin embryos were obtained, of which 24 developed to blastocyst stage. Using micromanipulation technique, the zona-free blastocysts were recovered and plated onto mitotically inactivated Yazd human foreskin fibroblast (Batch18; YhFF#18) feeder layers in microdrops. After 3 to 5 days of blastocyst culture onto human foreskin fibroblast feeder layers, the hESC-like outgrowths were passaged onto new feeders in microdrops. The initial outgrowths of hESC-like cells were generated, and cells were proliferated, passaged, and some of them expressed hESC and trophoblastic markers; however, no cell lines were established. This might be due to the low cell number and poor quality of inner cell mass within these twin blastocysts. In vitro embryo twinning by increasing the number of the human embryos could be useful in the future for the generation of new pluripotent stem cell lines. However, the challenge remains to optimize the methods.


Assuntos
Células-Tronco Embrionárias Humanas/citologia , Gemelaridade Monozigótica , Blastocisto/citologia , Células Cultivadas , Humanos
12.
BMJ ; 357: j2249, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28559234

RESUMO

Objective To assess causation and clinical presentation of major birth defects.Design Population based case cohort.Setting Cases of birth defects in children born 2005-09 to resident women, ascertained through Utah's population based surveillance system. All records underwent clinical re-review.Participants 5504 cases among 270 878 births (prevalence 2.03%), excluding mild isolated conditions (such as muscular ventricular septal defects, distal hypospadias).Main outcome measures The primary outcomes were the proportion of birth defects with a known etiology (chromosomal, genetic, human teratogen, twinning) or unknown etiology, by morphology (isolated, multiple, minors only), and by pathogenesis (sequence, developmental field defect, or known pattern of birth defects).Results Definite cause was assigned in 20.2% (n=1114) of cases: chromosomal or genetic conditions accounted for 94.4% (n=1052), teratogens for 4.1% (n=46, mostly poorly controlled pregestational diabetes), and twinning for 1.4% (n=16, conjoined or acardiac). The 79.8% (n=4390) remaining were classified as unknown etiology; of these 88.2% (n=3874) were isolated birth defects. Family history (similarly affected first degree relative) was documented in 4.8% (n=266). In this cohort, 92.1% (5067/5504) were live born infants (isolated and non-isolated birth defects): 75.3% (4147/5504) were classified as having an isolated birth defect (unknown or known etiology).Conclusions These findings underscore the gaps in our knowledge regarding the causes of birth defects. For the causes that are known, such as smoking or diabetes, assigning causation in individual cases remains challenging. Nevertheless, the ongoing impact of these exposures on fetal development highlights the urgency and benefits of population based preventive interventions. For the causes that are still unknown, better strategies are needed. These can include greater integration of the key elements of etiology, morphology, and pathogenesis into epidemiologic studies; greater collaboration between researchers (such as developmental biologists), clinicians (such as medical geneticists), and epidemiologists; and better ways to objectively measure fetal exposures (beyond maternal self reports) and closer (prenatally) to the critical period of organogenesis.


Assuntos
Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/etiologia , Pré-Escolar , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Idade Materna , Exposição Materna/efeitos adversos , Vigilância da População , Gravidez , Prevalência , Gemelaridade Monozigótica , Utah/epidemiologia
13.
J Pediatr Surg ; 52(5): 807-809, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28202184

RESUMO

PURPOSE: Previous studies have hypothesized that cloacal exstrophy may be caused by errors early in embryological development related to monozygotic twinning. This study reports the prevalence of twins in a large cohort of patients with cloacal exstrophy. METHODS: Patients with cloacal exstrophy treated 1974-2015 were reviewed for reports of multiple gestation or conjoined twinning. The genetic sex of the patient and their twin, and any mention of anomaly in the twin were recorded. Neither placental exam nor genetic testing results were available to definitively determine zygosity. RESULTS: Of 71 patients, 10 had a live born twin (14%), all of whom were of the same genetic sex as the affected patient. One additional patient's twin suffered intrauterine fetal demise, and another patient had a conjoined heteropagus twin. None of the twins were affected by exstrophy-epispadias complex. The rate of twin birth in this cohort was 4.4-7.7 higher than that reported by the Centers for Disease Control in the general population time period (P<0.001), with a striking preponderance of same-sex pairs. CONCLUSIONS: The highly significant prevalence of same-sex twin pairs within this cohort supports the hypothesis that the embryogenesis of cloacal exstrophy may be related to errors in monozygotic twinning. LEVEL OF EVIDENCE: 2b.


Assuntos
Anus Imperfurado/embriologia , Hérnia Umbilical/embriologia , Escoliose/embriologia , Gemelaridade Monozigótica , Gêmeos Monozigóticos/estatística & dados numéricos , Anormalidades Urogenitais/embriologia , Anus Imperfurado/epidemiologia , Feminino , Hérnia Umbilical/epidemiologia , Humanos , Recém-Nascido , Masculino , Massachusetts/epidemiologia , Prevalência , Estudos Retrospectivos , Escoliose/epidemiologia , Fatores Sexuais , Anormalidades Urogenitais/epidemiologia
14.
Hum Reprod Update ; 23(2): 156-165, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27852683

RESUMO

BACKGROUND: Embryo splitting or twinning has been widely used in veterinary medicine over 20 years to generate monozygotic twins with desirable genetic characteristics. The first human embryo splitting, reported in 1993, triggered fierce ethical debate on human embryo cloning. Since Dolly the sheep was born in 1997, the international community has acknowledged the complexity of the moral arguments related to this research and has expressed concerns about the potential for reproductive cloning in humans. A number of countries have formulated bans either through laws, decrees or official statements. However, in general, these laws specifically define cloning as an embryo that is generated via nuclear transfer (NT) and do not mention embryo splitting. Only the UK includes under cloning both embryo splitting and NT in the same legislation. On the contrary, the Ethics Committee of the American Society for Reproductive Medicine does not have a major ethical objection to transferring two or more artificially created embryos with the same genome with the aim of producing a single pregnancy, stating that 'since embryo splitting has the potential to improve the efficacy of IVF treatments for infertility, research to investigate the technique is ethically acceptable'. OBJECTIVE AND RATIONALE: Embryo splitting has been introduced successfully to the veterinary medicine several decades ago and today is a part of standard practice. We present here an overview of embryo splitting experiments in humans and non-human primates and discuss the potential of this technology in assisted reproduction and research. SEARCH METHODS: A comprehensive literature search was carried out using PUBMED and Google Scholar databases to identify studies on embryo splitting in humans and non-human primates. 'Embryo splitting' and 'embryo twinning' were used as the keywords, alone or in combination with other search phrases relevant to the topics of biology of preimplantation embryos. OUTCOMES: A very limited number of studies have been conducted in humans and non-human primates. The published material, especially the studies with human embryos, is controversial. Some reports suggest that twinning technology will find clinical use in reproductive medicine in the future, whereas others conclude the opposite that human twin embryos created in vitro are unsuitable not only for clinical, but also for research, purposes. WIDER IMPLICATIONS: The blastomere biopsy technique of embryo splitting seems to be unsuitable for either clinical or research purposes; however, embryo bisection, a preferable method of cloning in veterinary medicine, has not yet been tested on human embryos.


Assuntos
Blastocisto , Transferência Embrionária/métodos , Gemelaridade Monozigótica , Animais , Bovinos , Clonagem de Organismos/ética , Clonagem de Organismos/legislação & jurisprudência , Desenvolvimento Embrionário , Feminino , Humanos , Infertilidade/terapia , Infertilidade/veterinária , Primatas , Gêmeos
15.
Hum Reprod ; 31(11): 2435-2441, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27664211

RESUMO

STUDY QUESTION: Does the manipulation of gametes or embryos during ARTs increase the risk for monozygotic twinning (MZT)? SUMMARY ANSWER: Frozen embryo transfer (ET) is associated with a lower MZT rate, while blastocyst culture is associated with an increased risk of monozygotic pregnancy. WHAT IS KNOWN ALREADY: Monozygotic twins have a higher risk for perinatal complications. Although an increased incidence of monozygotic pregnancies after ART has been previously reported, data regarding the possible impact of different laboratory procedures are conflicting. STUDY DESIGN, SIZE, DURATION: All clinical pregnancies after single ET carried out in our centre between 2004 and 2013 (n = 6096) were retrospectively analysed for the incidence of MZT. The effect of different laboratory procedures on the incidence of MZT was evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The following ART risk factors were assessed: maternal age, type of ET (fresh versus frozen), zona pellucida (ZP) manipulation (specifically, ICSI, embryo biopsy and assisted hatching), use of donor oocytes, embryo stage at time of ET (cleavage, compaction, early or advanced blastocyst) and culture media. MAIN RESULTS AND THE ROLE OF CHANCE: The overall MZT rate was 2.2% (136/6096). Frozen ET was associated with a significant reduction in MZT incidence (adjusted odds ratio (aOR) 0.48, 95% CI 0.29-0.80), while blastocyst transfer (early or advanced blastocyst) was associated with a significant increase in MZT risk (aOR 2.70, 95% CI 1.36-5.34; aOR 2.05, 95% CI 1.29-3.26, respectively). No significant differences were found between the MZT and singleton (non-MZT) groups regarding maternal age, the use of different ZP manipulation techniques, not type of culture media used. LIMITATION, REASONS FOR CAUTION: This study is limited by its retrospective nature and the fact that monozygosity was not confirmed by genetic testing. Furthermore, since monozygotic pregnancy is a rare event, other ART parameters that may influence its incidence could not be assessed during our analysis. WIDER IMPLICATION OF THE FINDINGS: Our findings warrant future studies designed to investigate the association between specific ART procedures and MZT, namely the potential risk of blastocyst transfer to increase MZT. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. There are no conflicts of interest.


Assuntos
Técnicas de Cultura Embrionária , Técnicas de Reprodução Assistida , Transferência de Embrião Único , Gemelaridade Monozigótica , Adulto , Feminino , Humanos , Incidência , Doação de Oócitos , Gravidez , Estudos Retrospectivos
16.
J Assist Reprod Genet ; 33(1): 27-32, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26564016

RESUMO

PURPOSE: The purpose of this study is to report two cases of monozygotic quadruplet and triplet pregnancies following single embryo transfer (ET). METHODS: A 29-year-old woman and a 34-year-old woman underwent ART treatment in two affiliated University based ART units. The first woman underwent ICSI with day 3 embryo biopsy for pre-implantation genetic diagnosis (PGD) followed by day 4 transfer, which resulted in a monochorionic quadramniotic (MCQA) quadruplet pregnancy. The second woman underwent conventional IVF with transfer of a single blastocyst, which resulted in a monochorionic triamniotic (MCTA) triplet pregnancy. RESULTS: The first patient underwent successful selective foetal reduction at 16 + 3 and 17 + 4 weeks of gestation. Two healthy twin girls were delivered by elective caesarean section at 35 + 6 weeks of gestation. The second patient underwent successful selective foetal reduction at 14 + 1 weeks of gestation. The remaining monochorionic diamniotic (MCDA) twins are well at the time of writing this article. CONCLUSIONS: To our knowledge, these cases represent the first case of viable MCQA pregnancy following single ET in the world and the third case of a viable MCTA pregnancy following conventional IVF with single ET. Several factors including blastocyst stage transfer and zona pellucida manipulation have been thought to contribute to monozygotic twinning in the context of ART. These two cases add to the growing literature of monozygotic multiple pregnancies following ART.


Assuntos
Gravidez de Quadrigêmeos , Gravidez de Trigêmeos , Técnicas de Reprodução Assistida , Transferência de Embrião Único/métodos , Adulto , Feminino , Humanos , Gravidez , Diagnóstico Pré-Implantação , Transferência de Embrião Único/efeitos adversos , Injeções de Esperma Intracitoplásmicas/métodos , Gemelaridade Monozigótica/fisiologia , Gêmeos Monozigóticos , Ultrassonografia Pré-Natal
17.
Obstet Gynecol ; 125(1): 118-123, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25560113

RESUMO

Because they share a common placenta, monochorionic gestations are subject to unique pregnancy complications that can threaten the life and health of both fetuses and therefore impose a disproportionate disease burden on overall perinatal morbidity and mortality. Early detection of these unique disease processes may allow for prompt referral to a regional treatment center, comprehensive counseling, and better patient outcomes. The North American Fetal Therapy Network is a consortium of 30 medical institutions in the United States and Canada with established expertise in fetal surgery and other forms of multidisciplinary care for complex fetal disorders. The goal of this publication is to briefly describe complications of monochorionic gestations and to provide multidisciplinary, evidence-based, and consensus-driven recommendations for surveillance of uncomplicated monochorionic gestations.


Assuntos
Doenças em Gêmeos/diagnóstico por imagem , Vigilância da População , Gravidez de Gêmeos , Ultrassonografia Pré-Natal , Córion , Anormalidades Congênitas/diagnóstico por imagem , Consenso , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/diagnóstico por imagem , Humanos , Policitemia/diagnóstico por imagem , Gravidez , Gemelaridade Monozigótica
18.
Adv Neonatal Care ; 13(1): 31-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23360857

RESUMO

Twin-to-twin transfusion syndrome (TTTS) is a disease that affects roughly 15% of monochorionic twins. Although TTTS is not extremely prevalent, the rate of mortality and morbidly approaches 100% without early detection and treatment. The following case study is a triplet pregnancy that included a set of monochorionic twins affected by TTTS. Typically, it is assumed that monochorionicity can identify the zygosity of twins, which was disproven in this case. Research indicates that there has been an increased rate of monochorionic twins with in vitro fertilization. There is great debate about the most appropriate treatment modality for TTTS. Perinatal treatment followed by neonatal management is the standard of care for TTTS. Implications for the neonatal nurse practitioner and care for the patients are discussed.


Assuntos
Betametasona/administração & dosagem , Fertilização in vitro/efeitos adversos , Monitorização Fetal/métodos , Transfusão Feto-Fetal , Terapia a Laser/métodos , Gemelaridade Monozigótica/fisiologia , Adulto , Diagnóstico Precoce , Intervenção Médica Precoce/métodos , Feminino , Transfusão Feto-Fetal/diagnóstico , Transfusão Feto-Fetal/etiologia , Transfusão Feto-Fetal/fisiopatologia , Transfusão Feto-Fetal/terapia , Aconselhamento Genético , Idade Gestacional , Glucocorticoides/administração & dosagem , Humanos , Recém-Nascido , Enfermagem Neonatal , Assistência Perinatal/métodos , Placenta/irrigação sanguínea , Placenta/fisiopatologia , Gravidez , Resultado da Gravidez , Ultrassonografia Pré-Natal/métodos
19.
PLoS One ; 7(6): e39147, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22723952

RESUMO

Embryo development in plants initiates following the transverse division of a zygote into an apical, proembryo cell and a basal cell that gives rise to the suspensor. Although mutants affected in embryo development through changes in cell division have been described, little is known about the control of the first zygotic division that gives rise to the proembryo. Ascorbic acid (Asc) promotes cell division by inducing G(1) to S progression but its role in embryo development has not been examined. In this study, we show that the level of dehydroascorbate reductase (DHAR) expression, which recycles Asc and regulates Asc pool size, affects the rate of monozygotic twinning and polycotyly. DHAR-induced twinning resulted from altered cell polarity and longitudinal instead of transverse cell division that generated embryos of equal size. Direct injection of Asc into ovaries phenocopied DHAR-induced twinning. Twinning induced by Asc was developmentally limited to the first two days after pollination whereas polycotyly was induced when the level of Asc was elevated just prior to cotyledon initiation. This work describes the first example of gene-directed monozygotic twinning and shows that Asc regulates cell polarity during embryo development.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Nicotiana/efeitos dos fármacos , Nicotiana/genética , Gemelaridade Monozigótica , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Citoesqueleto/efeitos dos fármacos , Expressão Gênica , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Polinização/fisiologia , Sementes/citologia , Fatores de Tempo , Nicotiana/metabolismo , Zigoto/citologia
20.
Rev. méd. Minas Gerais ; 21(1)jan.-mar. 2011. ilus
Artigo em Português | LILACS | ID: lil-589470

RESUMO

Este trabalho descreve a gemelaridade conjugada tipo onfalópagos em que os métodos de imagem foram essenciais para a definição da fusão anatômica e o diagnóstico de possíveis anormalidades associadas, com o objetivo de conferir o correto planejamento cirúrgico e sobrevida adequada aos pacientes.


This paper reports on the omphalopagus conjoined twins in which imaging methods were essential for defining anatomical connection and diagnosis of possible associated abnormalities with the objective of providing accurate surgical planning and their survival.


Assuntos
Humanos , Recém-Nascido , Gemelaridade Monozigótica , Gêmeos Monozigóticos , Gêmeos Unidos/cirurgia , Anormalidades Congênitas , Espectroscopia de Ressonância Magnética , Radiografia
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