Mònica Parriego - Academia.edu (original) (raw)
Papers by Mònica Parriego
Prenatal Diagnosis
ObjectiveTo assess patients' and embryonic characteristics that may have an influence on the ... more ObjectiveTo assess patients' and embryonic characteristics that may have an influence on the decision to transfer a mosaic embryo.MethodSingle centre retrospective cohort study including 1247 PGT‐A cycles. Demographic and clinical factors associated with a decision to transfer a mosaic embryo were studied. Female age, number of previous cycles, previous availability of euploid embryos, history of miscarriages and parity as well as percentage of mosaicism, type of anomaly and chromosome risk were studied in relation to decision‐making. Outcomes after mosaic embryo transfer were assessed.ResultsTo date, in 7.9% of cycles (99/1247), patients have had to make a decision on the fate of their mosaic embryos. In 23.2% of cycles (23/99), patients decided to transfer. In most cases (79.8%; 79/99), patients underwent genetic counselling before the decision. None of the variables analysed were associated with the patients' decision, although parity and the high‐degree mosaicism (>50...
Human Reproduction
Study question How do human embryos implant in physiological conditions and develop beyond blasto... more Study question How do human embryos implant in physiological conditions and develop beyond blastocyst stage? Summary answer Human embryos apply forces during invasion of the matrix, the mural trophectoderm undergoes a quick compaction leading to a fast radial expansion of polar side What is known already Human embryos can be cultured beyond blastocyst stage using supplements of animal origin, such as fetal bovine serum. However, two main issues limit our understanding of the implantation of the human embryo. First, human embryos do not express fluorescent proteins, severely limiting the access to advanced live-imaging tools. Second, the animal serums may not represent the physiological peri-implantation conditions of the human embryo, thus limiting the reproducibility of the in vitro experiments. Here we combine label-free multiphoton imaging with media formulations including clinical-grade protein supplements from human plasma unlocking the observation of the human embryo in 3D and...
Journal of Assisted Reproduction and Genetics, 2022
To determine whether embryo mosaicism prevalence in preimplantation genetic testing for aneuploid... more To determine whether embryo mosaicism prevalence in preimplantation genetic testing for aneuploidy (PGT-A) cycles is associated with the trophectoderm biopsy technique used (a. number of laser pulses or b. the use of flicking or pulling) or the time to tubing. Prospective observational study performed in a single IVF-PGT-A setting from May 2019 to May 2021. Trophectoderm biopsies were analysed by next-generation sequencing. Mosaicism was analysed in relation to the biopsy methodology (number of laser pulses and pulling vs flicking), time elapsed from biopsy to tubing (min), and time of sample cryostorage from tubing to amplification (days). As a secondary objective, the number of laser pulses and biopsy methodology were studied in relation to clinical outcomes of transferred euploid blastocysts. None of the analysed variables were associated to mosaicism prevalence. Multivariable regression analysis demonstrated that mosaicism prevalence was comparable either when > 3 laser pulses were used as compared to ≤ 3 (13.9% vs 13.8%, aOR = 0.8726 [0.60–1.28]) and pulling compared to flicking (13.1% vs 14.0%, aOR = 0.86 [0.60–1.23]). Moreover, neither the number of laser pulses during biopsy (> 3 vs ≤ 3) nor the technique used (pulling vs flicking) were associated with clinical pregnancy after the transfer of frozen-thawed euploid blastocysts (54.9% vs 55.2%, aOR = 1.05 [0.53–2.09]; 61.1% vs 52.9%, aOR = 1.11 [0.55–2.25], respectively). Our results suggest that, as long as the biopsy and tubing procedures are performed following standardized high quality procedures, no specific approach would increase the generation of artefactual mosaicism as a result of trophectoderm biopsy. Trophectoderm biopsies should be performed regardless of the methodology but always aiming on minimising blastocyst manipulation.
La indicacion de screening genetico preimplantacional (PGS) por factor masculino de origen geneti... more La indicacion de screening genetico preimplantacional (PGS) por factor masculino de origen genetico ha sido poco estudiada a pesar de suponer el 9% de los casos reportados en el registro de la Sociedad Europea de Reproduccion Humana y Embriologia (ESHRE PGD Consortium). En el presente estudio se han evaluado los resultados de los ciclos de PGS por factor masculino genetico en dos series distintas: una serie de 73 casos en la que se utilizo la tecnica de hibridacion in situ fluorescente (FISH) para el analisis genetico y otra de 55 casos en los que el analisis cromosomico se realizo mediante arrays de hibridacion genomica comparativa (a-CGH). Se ha observado un mayor poder de deteccion de anomalias cromosomicas en el grupo de a-CGH, lo que ha supuesto un porcentaje inferior de ciclos con transferencia en este grupo. No obstante, las tasas de implantacion y embarazo se han visto significativamente mejoradas en el grupo de a-CGH. A dia de hoy, la aplicacion de PGS mediante analisis cro...
Human Reproduction, 2021
STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesteron... more STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer? SUMMARY ANSWER Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels. WHAT IS KNOWN ALREADY The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low...
Reproductive BioMedicine Online, 2021
RESEARCH QUESTION Are intrinsic or extrinsic factors associated with embryo mosaicism prevalence ... more 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; P = 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.
Human Reproduction, 2021
Study question Does progesterone-supplementation (PS) from the day of β-hCG assessment improve pr... more Study question Does progesterone-supplementation (PS) from the day of β-hCG assessment improve pregnancy rates in embryo transfer-under hormonal replacement therapy (ET-HRT) in patient with Progesterone (P)<10.6 ng/mL? Summary answer Reduced P on the β-hCG day is associated with lower pregnancy-rates and higher miscarriage-rate. PS from the same day showed significant increase of reproductive outcomes. What is known already Up until now, in ART, very little has been done to understand whether the P intake should be personalized during the luteal phase. Most recent studies on the topic showed that low P levels on the day of ET-HRT or on the day before are associated with decreased pregnancy rates; however, when low P values are supplemented from the day before embryo-transfer (ET), similar results to cases with adequate P are reported. Nevertheless, little is known about the association between low P level, on the day of β-hCG (P- β-hCG) and PS from this day in ET-HRT, and pregnan...
Human Reproduction, 2020
STUDY QUESTION Are progesterone (P) levels on the day before natural cycle frozen embryo transfer... more STUDY QUESTION Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? SUMMARY ANSWER Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. WHAT IS KNOWN ALREADY The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients had regular menstrual cycles ...
Fertility and Sterility, 2018
carrier patients participated in this ongoing study.The attached table details results.Using SNP ... more carrier patients participated in this ongoing study.The attached table details results.Using SNP analysis, parental origin from the carrier and sperm source were confirmed.Quantification of mitochondrial heteroplasmy using Taqman PCR detected no mutation load in embryos.NGS data will be presented. CONCLUSIONS: MRT is an effective procedure for patients carrying disease causing mitochondrial mutations.We demonstrate the feasibility of MRT to remove disease causing mtDNA from pre-implantation embryos in an academic IVF center and have created high quality embryos.Our results are a step towards embryo transfer and establishing MRT as an option for women who carry disease causing mtDNA mutations. References: 1. Bai RK, Wong LJ.Detection and quantification of heteroplasmic mutant mitochondrial DNA by real-time amplification refractory mutation system quantitative PCR analysis: a single-step approach.Clin
Journal of Assisted Reproduction and Genetics, 2019
Purpose To determine the developmental competence of fast-cleaving D3 embryos. Methods Retrospect... more Purpose To determine the developmental competence of fast-cleaving D3 embryos. Methods Retrospective study including 4028 embryos from 513 PGT-A cycles performed between July 2014 and June 2017. Embryos were cultured in time-lapse incubators and biopsied at blastocyst stage. Embryos were classified in groups according to the number of cells on D3 (from 2-cell to ≥13-cell and compacted). A generalized linear mixed model adjusted for confounding factors was performed to assess the chance to give rise to an euploid blastocyst in each group compared with the chance of 8-cell embryos. Implantation and live birth rates were also analyzed. Results The statistical analysis showed that embryos with 9 to 11 cells had a slightly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.77 (0.61-0.96)) while embryos with more than 11 cells were found to be just as likely to give rise to an euploid blastocyst as the 8-cell embryos (OR (95% CI) 1.20 (0.92-1.56)). Conversely, slow-cleaving embryos had a significantly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.31 (0.24-0.39)). Moreover, euploid blastocysts derived from fast-cleaving embryos and from 8-cell embryos exhibit similar live birth rates. No significant differences were found in the chance to give rise a live birth between 8-cell and 9-to 11-cell embryos (OR (95% CI) 1.23 (0.70-2.15)) and > 11-cell embryos (OR (95% CI) 1.09 (0.57-2.09)). Conclusions Embryos with more than 11 cells exhibit similar developmental competence to 8-cell embryos. Their poor prognosis should be reconsidered.
Reproductive BioMedicine Online, 2019
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 17, 2018
This retrospective study was carried out to determine which strategy is associated with improved ... more This retrospective study was carried out to determine which strategy is associated with improved outcomes in two back-to-back cycles when undergoing embryo accumulation. Eighty patients with two stimulation cycles performed with <45 days between retrievals between Jan'16-Mar'17 were included. Patients were segregated according to the strategy used to link stimulations: spontaneous menses (SM), vaginal micronized progesterone (VMP) or oral contraceptive pills (OCP). Main outcome measure was oocytes retrieved. The oocytes retrieved difference between cycles was -0.9 in SM, -1.5 in VMP and +0.4 in OCPs. Although not statistically significant, more oocytes retrieved were observed in the 2ndcycle when OCPs were used (9.0 ± 3.7 vs. 9.4 ± 4.1)? whereas fewer oocytes retrieved were observed when SM (9.4 ± 3.9 vs. 8.5 ± .0) or VMP (9.8 ± 5.7 vs. 8.2 ± 4.4) were used. After adjusting for age, gonadotropins and stimulation days (2nd cycle) and treatment group in an ANCOVA model, no ...
Zygote (Cambridge, England), Jan 25, 2018
SummaryShortly after the implementation of comprehensive chromosome screening (CCS) techniques fo... more SummaryShortly after the implementation of comprehensive chromosome screening (CCS) techniques for preimplantation genetic testing for aneuploidies (PGT-A), the discussion about the transition from day 3 to blastocyst stage biopsy was initiated. Trophectoderm biopsy with CCS is meant to overcome the limitations of cleavage-stage biopsy and single-cell analysis. The aim of this study was to assess the results obtained in our PGT-A programme after the implementation of this new strategy. Comparisons between the results obtained in 179 PGT-A cycles with day 3 biopsy (D+3) and fresh embryo transfer, and 204 cycles with trophectoderm biopsy and deferred (frozen-thawed) embryo transfer were established. Fewer embryos were biopsied and a higher euploidy rate was observed in the trophectoderm biopsy group. No differences in implantation (50.3% vs. 61.4%) and clinical pregnancy rate per transfer (56.1% vs. 65.3%) were found. Although the mean number of euploid embryos per cycle did not diffe...
Journal of Assisted Reproduction and Genetics, 2017
Purpose The purpose of this study was to investigate the chromosomal constitution and the develop... more Purpose The purpose of this study was to investigate the chromosomal constitution and the developmental potential of intracytoplasmic sperm injection (ICSI) deriving embryos displaying a single pronucleus at the zygote stage. Methods Eighty-eight embryos from single pronucleus (1PN) t w o p o l a r b o d i e s (2 P B) I C S I z y g o t e s f r o m 6 4 preimplantational genetic screening (PGS) cycles (October 2012-December 2014), were retrospectively analyzed. Zygotes were cultured in a time-lapse incubator. Embryo biopsy was performed on day 3 and genetic analysis approached by array comparative genomic hybridization. Results Chromosomal analysis revealed that 17% (15/88) of embryos derived from 1PN 2PB zygotes were diagnosed as euploid. After blastomere biopsy at day 3, the blastocyst rate at day 5 was 3.4% (3/88). Only 2.3% (2/88) euploid blastocysts were obtained. In two couples and after counseling and patient agreement, the transfer of a euploid blastocyst from a 1PN 2PB ICSI zygote was performed resulting in the birth of a healthy child. Conclusions These results open the possibility to consider embryos coming from 1PN 2PB ICSI zygotes for transfer when no other embryos from 2PN 2PB ICSI zygotes are available and if a PGS diagnosis of euploidy is obtained. Confirmation of biparental inheritance is strongly recommended.
Folia Clinica En Obstetricia Y Ginecologia, 2006
Medicina Reproductiva y Embriología Clínica, 2015
Abstract Introduction The purpose of this study is to analyze the correlation between the occurre... more Abstract Introduction The purpose of this study is to analyze the correlation between the occurrence of early cleavage and chromosome constitution of embryos from preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). Material and methods A total of 595 embryos from 96 cycles were included in this retrospective study. Results When clinical pregnancy rates per transfer were compared, statistically significant differences were observed between patients that had at least one early cleavage (ECpos) embryo and patients no EC (ECneg) (35.7% vs. 6.7%; p p p p p Discussion Early cleavage has shown to correlate with embryo quality, with the capacity to develop up to blastocyst stage, as well as with euploid chromosome constitution.
Reproductive BioMedicine Online, 2008
and newborn babies. Statistical analysis of the chosen variables was performed using analysis of ... more and newborn babies. Statistical analysis of the chosen variables was performed using analysis of variance (ANOVA) for those variables with normal distribution and the Kruskal-Wallis test for the remainder (significance P < 0.05). Results: Male carriers of sexual chromosome alterations present significantly lower sperm concentration, motility and morphology than males in the other groups. The least affected group regarding sperm morphology are those with chromosomal inversions. The highest fertilization rate was observed in the group of males with reciprocal translocations. The most affected group was the miscarriage patients in whom reciprocal translocations, inversions and marker chromosomes were found. Those with Robertsonian translocations and polymorphisms (groups 6 and 7) were less affected. The difference between the group with reciprocal translocations compared with the polymorphism groups was significant. For the other parameters we did not find significant differences. Conclusion: Numerical and structural alterations that affect the sexual chromosomes disturb the different seminal parameters more than other chromosomal anomalies. The highest miscarriage rate is observed in carriers of reciprocal translocations. The clinical pregnancy and live birth rates do not differ between groups; therefore, treatment by ART and PGD when required, appears to be the best reproductive option for male carriers of chromosomal alterations.
She also has a BSc in Cellular Biology (2003) from the Universitat Autònoma de Barcelona. She has... more She also has a BSc in Cellular Biology (2003) from the Universitat Autònoma de Barcelona. She has been working at the IVF laboratory at Institut Universitari Dexeus since 1999. She is an active member of the Association for the Study of Reproductive Biology and the Spanish Society of Fertility. Her main interest is focused on oocyte maturation in vitro, and oocyte and early embryo morphology.
PloS one, 2014
Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation ... more Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH) and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array...
Prenatal Diagnosis
ObjectiveTo assess patients' and embryonic characteristics that may have an influence on the ... more ObjectiveTo assess patients' and embryonic characteristics that may have an influence on the decision to transfer a mosaic embryo.MethodSingle centre retrospective cohort study including 1247 PGT‐A cycles. Demographic and clinical factors associated with a decision to transfer a mosaic embryo were studied. Female age, number of previous cycles, previous availability of euploid embryos, history of miscarriages and parity as well as percentage of mosaicism, type of anomaly and chromosome risk were studied in relation to decision‐making. Outcomes after mosaic embryo transfer were assessed.ResultsTo date, in 7.9% of cycles (99/1247), patients have had to make a decision on the fate of their mosaic embryos. In 23.2% of cycles (23/99), patients decided to transfer. In most cases (79.8%; 79/99), patients underwent genetic counselling before the decision. None of the variables analysed were associated with the patients' decision, although parity and the high‐degree mosaicism (>50...
Human Reproduction
Study question How do human embryos implant in physiological conditions and develop beyond blasto... more Study question How do human embryos implant in physiological conditions and develop beyond blastocyst stage? Summary answer Human embryos apply forces during invasion of the matrix, the mural trophectoderm undergoes a quick compaction leading to a fast radial expansion of polar side What is known already Human embryos can be cultured beyond blastocyst stage using supplements of animal origin, such as fetal bovine serum. However, two main issues limit our understanding of the implantation of the human embryo. First, human embryos do not express fluorescent proteins, severely limiting the access to advanced live-imaging tools. Second, the animal serums may not represent the physiological peri-implantation conditions of the human embryo, thus limiting the reproducibility of the in vitro experiments. Here we combine label-free multiphoton imaging with media formulations including clinical-grade protein supplements from human plasma unlocking the observation of the human embryo in 3D and...
Journal of Assisted Reproduction and Genetics, 2022
To determine whether embryo mosaicism prevalence in preimplantation genetic testing for aneuploid... more To determine whether embryo mosaicism prevalence in preimplantation genetic testing for aneuploidy (PGT-A) cycles is associated with the trophectoderm biopsy technique used (a. number of laser pulses or b. the use of flicking or pulling) or the time to tubing. Prospective observational study performed in a single IVF-PGT-A setting from May 2019 to May 2021. Trophectoderm biopsies were analysed by next-generation sequencing. Mosaicism was analysed in relation to the biopsy methodology (number of laser pulses and pulling vs flicking), time elapsed from biopsy to tubing (min), and time of sample cryostorage from tubing to amplification (days). As a secondary objective, the number of laser pulses and biopsy methodology were studied in relation to clinical outcomes of transferred euploid blastocysts. None of the analysed variables were associated to mosaicism prevalence. Multivariable regression analysis demonstrated that mosaicism prevalence was comparable either when > 3 laser pulses were used as compared to ≤ 3 (13.9% vs 13.8%, aOR = 0.8726 [0.60–1.28]) and pulling compared to flicking (13.1% vs 14.0%, aOR = 0.86 [0.60–1.23]). Moreover, neither the number of laser pulses during biopsy (> 3 vs ≤ 3) nor the technique used (pulling vs flicking) were associated with clinical pregnancy after the transfer of frozen-thawed euploid blastocysts (54.9% vs 55.2%, aOR = 1.05 [0.53–2.09]; 61.1% vs 52.9%, aOR = 1.11 [0.55–2.25], respectively). Our results suggest that, as long as the biopsy and tubing procedures are performed following standardized high quality procedures, no specific approach would increase the generation of artefactual mosaicism as a result of trophectoderm biopsy. Trophectoderm biopsies should be performed regardless of the methodology but always aiming on minimising blastocyst manipulation.
La indicacion de screening genetico preimplantacional (PGS) por factor masculino de origen geneti... more La indicacion de screening genetico preimplantacional (PGS) por factor masculino de origen genetico ha sido poco estudiada a pesar de suponer el 9% de los casos reportados en el registro de la Sociedad Europea de Reproduccion Humana y Embriologia (ESHRE PGD Consortium). En el presente estudio se han evaluado los resultados de los ciclos de PGS por factor masculino genetico en dos series distintas: una serie de 73 casos en la que se utilizo la tecnica de hibridacion in situ fluorescente (FISH) para el analisis genetico y otra de 55 casos en los que el analisis cromosomico se realizo mediante arrays de hibridacion genomica comparativa (a-CGH). Se ha observado un mayor poder de deteccion de anomalias cromosomicas en el grupo de a-CGH, lo que ha supuesto un porcentaje inferior de ciclos con transferencia en este grupo. No obstante, las tasas de implantacion y embarazo se han visto significativamente mejoradas en el grupo de a-CGH. A dia de hoy, la aplicacion de PGS mediante analisis cro...
Human Reproduction, 2021
STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesteron... more STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer? SUMMARY ANSWER Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels. WHAT IS KNOWN ALREADY The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low...
Reproductive BioMedicine Online, 2021
RESEARCH QUESTION Are intrinsic or extrinsic factors associated with embryo mosaicism prevalence ... more 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; P = 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.
Human Reproduction, 2021
Study question Does progesterone-supplementation (PS) from the day of β-hCG assessment improve pr... more Study question Does progesterone-supplementation (PS) from the day of β-hCG assessment improve pregnancy rates in embryo transfer-under hormonal replacement therapy (ET-HRT) in patient with Progesterone (P)<10.6 ng/mL? Summary answer Reduced P on the β-hCG day is associated with lower pregnancy-rates and higher miscarriage-rate. PS from the same day showed significant increase of reproductive outcomes. What is known already Up until now, in ART, very little has been done to understand whether the P intake should be personalized during the luteal phase. Most recent studies on the topic showed that low P levels on the day of ET-HRT or on the day before are associated with decreased pregnancy rates; however, when low P values are supplemented from the day before embryo-transfer (ET), similar results to cases with adequate P are reported. Nevertheless, little is known about the association between low P level, on the day of β-hCG (P- β-hCG) and PS from this day in ET-HRT, and pregnan...
Human Reproduction, 2020
STUDY QUESTION Are progesterone (P) levels on the day before natural cycle frozen embryo transfer... more STUDY QUESTION Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? SUMMARY ANSWER Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. WHAT IS KNOWN ALREADY The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients had regular menstrual cycles ...
Fertility and Sterility, 2018
carrier patients participated in this ongoing study.The attached table details results.Using SNP ... more carrier patients participated in this ongoing study.The attached table details results.Using SNP analysis, parental origin from the carrier and sperm source were confirmed.Quantification of mitochondrial heteroplasmy using Taqman PCR detected no mutation load in embryos.NGS data will be presented. CONCLUSIONS: MRT is an effective procedure for patients carrying disease causing mitochondrial mutations.We demonstrate the feasibility of MRT to remove disease causing mtDNA from pre-implantation embryos in an academic IVF center and have created high quality embryos.Our results are a step towards embryo transfer and establishing MRT as an option for women who carry disease causing mtDNA mutations. References: 1. Bai RK, Wong LJ.Detection and quantification of heteroplasmic mutant mitochondrial DNA by real-time amplification refractory mutation system quantitative PCR analysis: a single-step approach.Clin
Journal of Assisted Reproduction and Genetics, 2019
Purpose To determine the developmental competence of fast-cleaving D3 embryos. Methods Retrospect... more Purpose To determine the developmental competence of fast-cleaving D3 embryos. Methods Retrospective study including 4028 embryos from 513 PGT-A cycles performed between July 2014 and June 2017. Embryos were cultured in time-lapse incubators and biopsied at blastocyst stage. Embryos were classified in groups according to the number of cells on D3 (from 2-cell to ≥13-cell and compacted). A generalized linear mixed model adjusted for confounding factors was performed to assess the chance to give rise to an euploid blastocyst in each group compared with the chance of 8-cell embryos. Implantation and live birth rates were also analyzed. Results The statistical analysis showed that embryos with 9 to 11 cells had a slightly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.77 (0.61-0.96)) while embryos with more than 11 cells were found to be just as likely to give rise to an euploid blastocyst as the 8-cell embryos (OR (95% CI) 1.20 (0.92-1.56)). Conversely, slow-cleaving embryos had a significantly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.31 (0.24-0.39)). Moreover, euploid blastocysts derived from fast-cleaving embryos and from 8-cell embryos exhibit similar live birth rates. No significant differences were found in the chance to give rise a live birth between 8-cell and 9-to 11-cell embryos (OR (95% CI) 1.23 (0.70-2.15)) and > 11-cell embryos (OR (95% CI) 1.09 (0.57-2.09)). Conclusions Embryos with more than 11 cells exhibit similar developmental competence to 8-cell embryos. Their poor prognosis should be reconsidered.
Reproductive BioMedicine Online, 2019
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 17, 2018
This retrospective study was carried out to determine which strategy is associated with improved ... more This retrospective study was carried out to determine which strategy is associated with improved outcomes in two back-to-back cycles when undergoing embryo accumulation. Eighty patients with two stimulation cycles performed with <45 days between retrievals between Jan'16-Mar'17 were included. Patients were segregated according to the strategy used to link stimulations: spontaneous menses (SM), vaginal micronized progesterone (VMP) or oral contraceptive pills (OCP). Main outcome measure was oocytes retrieved. The oocytes retrieved difference between cycles was -0.9 in SM, -1.5 in VMP and +0.4 in OCPs. Although not statistically significant, more oocytes retrieved were observed in the 2ndcycle when OCPs were used (9.0 ± 3.7 vs. 9.4 ± 4.1)? whereas fewer oocytes retrieved were observed when SM (9.4 ± 3.9 vs. 8.5 ± .0) or VMP (9.8 ± 5.7 vs. 8.2 ± 4.4) were used. After adjusting for age, gonadotropins and stimulation days (2nd cycle) and treatment group in an ANCOVA model, no ...
Zygote (Cambridge, England), Jan 25, 2018
SummaryShortly after the implementation of comprehensive chromosome screening (CCS) techniques fo... more SummaryShortly after the implementation of comprehensive chromosome screening (CCS) techniques for preimplantation genetic testing for aneuploidies (PGT-A), the discussion about the transition from day 3 to blastocyst stage biopsy was initiated. Trophectoderm biopsy with CCS is meant to overcome the limitations of cleavage-stage biopsy and single-cell analysis. The aim of this study was to assess the results obtained in our PGT-A programme after the implementation of this new strategy. Comparisons between the results obtained in 179 PGT-A cycles with day 3 biopsy (D+3) and fresh embryo transfer, and 204 cycles with trophectoderm biopsy and deferred (frozen-thawed) embryo transfer were established. Fewer embryos were biopsied and a higher euploidy rate was observed in the trophectoderm biopsy group. No differences in implantation (50.3% vs. 61.4%) and clinical pregnancy rate per transfer (56.1% vs. 65.3%) were found. Although the mean number of euploid embryos per cycle did not diffe...
Journal of Assisted Reproduction and Genetics, 2017
Purpose The purpose of this study was to investigate the chromosomal constitution and the develop... more Purpose The purpose of this study was to investigate the chromosomal constitution and the developmental potential of intracytoplasmic sperm injection (ICSI) deriving embryos displaying a single pronucleus at the zygote stage. Methods Eighty-eight embryos from single pronucleus (1PN) t w o p o l a r b o d i e s (2 P B) I C S I z y g o t e s f r o m 6 4 preimplantational genetic screening (PGS) cycles (October 2012-December 2014), were retrospectively analyzed. Zygotes were cultured in a time-lapse incubator. Embryo biopsy was performed on day 3 and genetic analysis approached by array comparative genomic hybridization. Results Chromosomal analysis revealed that 17% (15/88) of embryos derived from 1PN 2PB zygotes were diagnosed as euploid. After blastomere biopsy at day 3, the blastocyst rate at day 5 was 3.4% (3/88). Only 2.3% (2/88) euploid blastocysts were obtained. In two couples and after counseling and patient agreement, the transfer of a euploid blastocyst from a 1PN 2PB ICSI zygote was performed resulting in the birth of a healthy child. Conclusions These results open the possibility to consider embryos coming from 1PN 2PB ICSI zygotes for transfer when no other embryos from 2PN 2PB ICSI zygotes are available and if a PGS diagnosis of euploidy is obtained. Confirmation of biparental inheritance is strongly recommended.
Folia Clinica En Obstetricia Y Ginecologia, 2006
Medicina Reproductiva y Embriología Clínica, 2015
Abstract Introduction The purpose of this study is to analyze the correlation between the occurre... more Abstract Introduction The purpose of this study is to analyze the correlation between the occurrence of early cleavage and chromosome constitution of embryos from preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). Material and methods A total of 595 embryos from 96 cycles were included in this retrospective study. Results When clinical pregnancy rates per transfer were compared, statistically significant differences were observed between patients that had at least one early cleavage (ECpos) embryo and patients no EC (ECneg) (35.7% vs. 6.7%; p p p p p Discussion Early cleavage has shown to correlate with embryo quality, with the capacity to develop up to blastocyst stage, as well as with euploid chromosome constitution.
Reproductive BioMedicine Online, 2008
and newborn babies. Statistical analysis of the chosen variables was performed using analysis of ... more and newborn babies. Statistical analysis of the chosen variables was performed using analysis of variance (ANOVA) for those variables with normal distribution and the Kruskal-Wallis test for the remainder (significance P < 0.05). Results: Male carriers of sexual chromosome alterations present significantly lower sperm concentration, motility and morphology than males in the other groups. The least affected group regarding sperm morphology are those with chromosomal inversions. The highest fertilization rate was observed in the group of males with reciprocal translocations. The most affected group was the miscarriage patients in whom reciprocal translocations, inversions and marker chromosomes were found. Those with Robertsonian translocations and polymorphisms (groups 6 and 7) were less affected. The difference between the group with reciprocal translocations compared with the polymorphism groups was significant. For the other parameters we did not find significant differences. Conclusion: Numerical and structural alterations that affect the sexual chromosomes disturb the different seminal parameters more than other chromosomal anomalies. The highest miscarriage rate is observed in carriers of reciprocal translocations. The clinical pregnancy and live birth rates do not differ between groups; therefore, treatment by ART and PGD when required, appears to be the best reproductive option for male carriers of chromosomal alterations.
She also has a BSc in Cellular Biology (2003) from the Universitat Autònoma de Barcelona. She has... more She also has a BSc in Cellular Biology (2003) from the Universitat Autònoma de Barcelona. She has been working at the IVF laboratory at Institut Universitari Dexeus since 1999. She is an active member of the Association for the Study of Reproductive Biology and the Spanish Society of Fertility. Her main interest is focused on oocyte maturation in vitro, and oocyte and early embryo morphology.
PloS one, 2014
Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation ... more Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH) and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array...