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1.  On-Site Array CGH Applications in Clinical In Vitro Fertilization: Reproductive Outcomes and Impact on Cryopreservation of Non-transferred Human Embryos 
Background: IVF pregnancy rates have trended upward although gains have been accompanied by unwelcome increases in pre-term delivery and multiple gestation. These adverse outcomes happen because multiple embryos are typically transferred during IVF. Integrating newer molecular cytogenetic techniques with IVF can optimize selection of a single embryo for transfer. Methods: The SurePlex DNA amplification system (BlueGnome Ltd; Cambridge, UK) was used on-site for whole genome amplification of human blastocyst trophectoderm (TE) cells obtained by biopsy. IVF patients (initial cycle, age <35, no prior miscarriage, normal karyotype) were prospectively randomized into two groups: In Group 1, embryos were selected on the basis of morphology and comprehensive chromosomal screening via array comparative genomic hybridization (aCGH) from d5 TE biopsy, while Group 2 embryos were assessed by morphology only. All patients underwent a single fresh blastocyst transfer on d6. For embryos in the aCGH group, only one euploid blastocyst was selected for transfer and surplus euploid blastocysts were vitrified. In the non-aCGH (control) group, a single blastocyst was selected for fresh transfer based on appearance only, with vitrification of any surplus blastocysts with satisfactory morphology. Results: Aneuploidy was identified in 191/425 of Group 1 balstocysts (44.9%). Control embryos (n=389) were assessed by microscopy only. A higher clinical pregnancy rate was observed in Group 1 patients compared to the control group (70.9 vs. 45.8%; p = 0.017). Only 64 (28.3%) surplus euploid embryos were frozen in Group 1 while 157 (40.4%) blastocysts were cryopreserved for Group 2 (p=0.017). Conclusion: These data underscore the intrinsic imprecision of IVF when conventional morphology is used alone to select embryos for transfer. Embryos evaluated with aCGH implant with greater efficiency and achieve clinical pregnancy more often than those selected without aCGH. Patients should be advised that aCGH screening may reduce the number of surplus embryos for cryopreservation.
PMCID: PMC3635430
2.  Selection of euploid blastocysts for cryopreservation with array comparative genomic hybridization (aCGH) results in increased implantation rates in subsequent frozen and thawed embryo transfer cycles 
In assisted reproductive treatments, embryos remaining after fresh embryo transfer are usually selected for cryopreservation based on traditional morphology assessment. Our previous report has demonstrated that array comparative genomic hybridization (aCGH) screening for IVF patients with good prognosis significantly improves clinical and ongoing pregnancy rates in fresh embryo transfer cycles. The current study further investigates the efficiency of applying aCGH in the selection of euploid embryos for cryopreservation as related to pregnancy and implantation outcomes in subsequent frozen embryo transfer (FET) cycles.
First-time IVF patients with good prognosis undergoing fresh single embryo transfer and having at least one remaining blastocyst for cryopreservation were prospectively randomized into two groups: 1) Group A patients had embryos assessed by morphology first and then by aCGH screening of trophectoderm cells and 2) Group B patients had embryos evaluated by morphology alone. All patients had at least one blastocyst available for cryopreservation after fresh embryo transfer. There were 15 patients in Group A and 23 patients in Group B who failed to conceive after fresh embryo transfer and completed the FET cycles. Blastocyst survival and implantation rates were compared between the two groups.
There were no significant differences in blastocyst survival rates between Group A and Group B (90.9% vs. 91.3%, respectively; p >0.05). However, a significantly higher implantation rate was observed in the morphology assessment plus aCGH screening group compared to the morphology assessment alone group (65.0% vs. 33.3%, respectively; p = 0.038). There was no miscarriage observed in Group A while a 16.7% miscarriage rate was recorded in Group B (0% vs. 16.7%, respectively; p >0.05).
While aCGH screening has been recently applied to select euploid blastocysts for fresh transfer in young, low-risk IVF patients, this is the first prospective study on the impact of aCGH specifically on blastocyst survival and implantation outcomes in the subsequent FET cycles of IVF patients with good prognosis. The present study demonstrates that aCGH screening of blastocysts prior to cryopreservation significantly improves implantation rates and may reduce the risk of miscarriage in subsequent FET cycles. Further randomized clinical studies with a larger sample size are needed to validate these preliminary findings.
PMCID: PMC3766007  PMID: 23937723
aCGH; Trophectoderm biopsy; Cryopreservation; Implantation
3.  Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study 
Single embryo transfer (SET) remains underutilized as a strategy to reduce multiple gestation risk in IVF, and its overall lower pregnancy rate underscores the need for improved techniques to select one embryo for fresh transfer. This study explored use of comprehensive chromosomal screening by array CGH (aCGH) to provide this advantage and improve pregnancy rate from SET.
First-time IVF patients with a good prognosis (age <35, no prior miscarriage) and normal karyotype seeking elective SET were prospectively randomized into two groups: In Group A, embryos were selected on the basis of morphology and comprehensive chromosomal screening via aCGH (from d5 trophectoderm biopsy) while Group B embryos were assessed by morphology only. All patients had a single fresh blastocyst transferred on d6. Laboratory parameters and clinical pregnancy rates were compared between the two groups.
For patients in Group A (n = 55), 425 blastocysts were biopsied and analyzed via aCGH (7.7 blastocysts/patient). Aneuploidy was detected in 191/425 (44.9%) of blastocysts in this group. For patients in Group B (n = 48), 389 blastocysts were microscopically examined (8.1 blastocysts/patient). Clinical pregnancy rate was significantly higher in the morphology + aCGH group compared to the morphology-only group (70.9 and 45.8%, respectively; p = 0.017); ongoing pregnancy rate for Groups A and B were 69.1 vs. 41.7%, respectively (p = 0.009). There were no twin pregnancies.
Although aCGH followed by frozen embryo transfer has been used to screen at risk embryos (e.g., known parental chromosomal translocation or history of recurrent pregnancy loss), this is the first description of aCGH fully integrated with a clinical IVF program to select single blastocysts for fresh SET in good prognosis patients. The observed aneuploidy rate (44.9%) among biopsied blastocysts highlights the inherent imprecision of SET when conventional morphology is used alone. Embryos randomized to the aCGH group implanted with greater efficiency, resulted in clinical pregnancy more often, and yielded a lower miscarriage rate than those selected without aCGH. Additional studies are needed to verify our pilot data and confirm a role for on-site, rapid aCGH for IVF patients contemplating fresh SET.
PMCID: PMC3403960  PMID: 22551456
4.  Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study 
BMC Medical Genomics  2015;8:30.
Recent advances in next-generation sequencing (NGS) have provided new methods for preimplantation genetic screening (PGS) of human embryos from in vitro fertilization (IVF) cycles. However, there is still limited information about clinical applications of NGS in IVF and PGS (IVF-PGS) treatments. The present study aimed to investigate the effects of NGS screening on clinical pregnancy and implantation outcomes for PGS patients in comparison to array comparative genomic hybridization (aCGH) screening.
This study was performed in two phases. Phase I study evaluated the accuracy of NGS for aneuploidy screening in comparison to aCGH. Whole-genome amplification (WGA) products (n = 164) derived from previous IVF-PGS cycles (n = 38) were retrospectively analyzed with NGS. The NGS results were then compared with those of aCGH. Phase II study further compared clinical pregnancy and implantation outcomes between NGS and aCGH for IVF-PGS patients. A total of 172 patients at mean age 35.2 ± 3.5 years were randomized into two groups: 1) NGS (Group A): patients (n = 86) had embryos screened with NGS and 2) aCGH (Group B): patients (n = 86) had embryos screened with aCGH. For both groups, blastocysts were vitrified after trophectoderm biopsy. One to two euploid blastocysts were thawed and transferred to individual patients primarily based on the PGS results. Ongoing pregnancy and implantation rates were compared between the two study groups.
NGS detected all types of aneuploidies of human blastocysts accurately and provided a 100 % 24-chromosome diagnosis consistency with the highly validated aCGH method. Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05). The observed implantation rates were also comparable between the NGS and aCGH groups (70.5 % vs. 66.2 %, respectively, p >0.05).
While NGS screening has been recently introduced to assist IVF patients, this is the first randomized clinical study on the efficiency of NGS for preimplantation genetic screening in comparison to aCGH. With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.
PMCID: PMC4477308  PMID: 26100406
NGS; aCGH; PGS; Aneuploidy screening; Ongoing pregnancy; Implantation
5.  AB095. Comparison pregnancy of day 6 fresh blastocyst and day 5 frozen-thawed blastocyst transfer following array comparative genome hybridization (aCGH) 
Annals of Translational Medicine  2015;3(Suppl 2):AB095.
Advances in assisted reproductive technologies (ART) have benefitted many infertile couples. However while many modern technologies were applied in ART, pregnancy rates remained lower than expected. Some studies have suggested that successful embryo implantation depends on many factors including genetic anomalies such as aneuploidy. While pre-implantation genetic screening (PGS) using fluorescent in situ hybridization (FISH) was introduced around 20 years ago to screen for aneuploidy in selected subsets of chromosomes, it failed to improve pregnancy rates and reduce miscarriage rates. FISH had technical limitations, some inaccuracies, and could only screen up to 8-11 chromosomes. Recent more modern technology, array comparative genome hybridization (aCGH), has been shown to significantly improve pregnancy rates and decrease miscarriage rates by allowing the detection of aneuploidy in all 23 pairs of chromosomes, and allowing the transfer of euploid embryos. Couples have an ovarian stimulation, eggs are collected and fertilized using intracytoplasmic sperm injection (ICSI), and any normally fertilized embryos are cultured to the blastocyst stage. Suitable blastocysts are biopsied on either day 5 or day 6 of embryo culture with the assistance of a near-infra-red laser, and the removed cells amplified in a whole genome amplification (WGA), fluorescently labelled, hybridized and scanned using the BlueGnome (Illumina) 24Sure CGH microarray system. Advances in aCGH means the total process from biopsy to result can be done overnight, allowing for a suitable embryo from a day 5 biopsy to have potential fresh embryo transfer on day 6 of culture. Alternatively, following biopsy, embryos can be frozen immediately and euploid embryos transferred in a subsequent frozen-thaw cycle. We retrospectively compared pregnancy outcomes of good quality blastocysts biopsied and analysed using aCGH following by fresh embryo transfer on day 6 (n=50) versus frozen embryo transfer of embryos biopsied and frozen on day 5 (n=61). The average age of patients having a fresh embryo transfer on day 6 is 32±3.2 and having frozen embryo transfer is 30±3.7 years old. The results showed that pregnancy rates were not significantly different between frozen embryo transfer and fresh embryo transfer (59% vs. 52% respectively, P value >0.05). Nevertheless, as well as indicating that not only is frozen embryo transfer as good as or better than fresh embryo transfer, frozen embryo transfer can also have advantages in in-vitro fertilization in allowing optimal embryo transfer planning for couples.
PMCID: PMC4563383
Array comparative genome hybridization (aCGH); in vitro fertilization, fresh blastocyst transfer; frozen-thawed blastocyst transfer
6.  Reduction of multiple pregnancies in the advanced maternal age population after implementation of an elective single embryo transfer policy coupled with enhanced embryo selection: pre- and post-intervention study 
Human Reproduction (Oxford, England)  2015;30(9):2097-2106.
Is an elective single-embryo transfer (eSET) policy an efficient approach for women aged >35 years when embryo selection is enhanced via blastocyst culture and preimplantation genetic screening (PGS)?
Elective SET coupled with enhanced embryo selection using PGS in women older than 35 years reduced the multiple pregnancy rates while maintaining the cumulative success rate of the IVF programme.
Multiple pregnancies mean an increased risk of premature birth and perinatal death and occur mainly in older patients when multiple embryos are transferred to increase the chance of pregnancy. A SET policy is usually recommended in cases of good prognosis patients, but no general consensus has been reached for SET application in the advanced maternal age (AMA) population, defined as women older than 35 years. Our objective was to evaluate the results in terms of efficacy, efficiency and safety of an eSET policy coupled with increased application of blastocyst culture and PGS for this population of patients in our IVF programme.
In January 2013, a multidisciplinary intervention involving optimization of embryo selection procedure and introduction of an eSET policy in an AMA population of women was implemented. This is a retrospective 4-year (January 2010–December 2013) pre- and post-intervention analysis, including 1161 and 499 patients in the pre- and post-intervention period, respectively. The primary outcome measures were the cumulative delivery rate (DR) per oocyte retrieval cycle and multiple DR.
Surplus oocytes and/or embryos were vitrified during the entire study period. In the post-intervention period, all couples with good quality embryos and less than two previous implantation failures were offered eSET. Embryo selection was enhanced by blastocyst culture and PGS (blastocyst stage biopsy and 24-chromosomal screening). Elective SET was also applied in cryopreservation cycles.
Patient and cycle characteristics were similar in the pre- and post-intervention groups [mean (SD) female age: 39.6 ± 2.1 and 39.4 ± 2.2 years; range 36–44] as assessed by logistic regression. A total of 1609 versus 574 oocyte retrievals, 937 versus 350 embryo warming and 138 versus 27 oocyte warming cycles were performed in the pre- and post-intervention periods, respectively, resulting in 1854 and 508 embryo transfers, respectively. In the post-intervention period, 289 cycles were blastocyst stage with (n = 182) or without PGS (n = 107). A mean (SD) number of 2.9 ± 1.1 (range 1–4) and 1.4 ± 0.8 (range 1–3) embryos were transferred pre- and post-intervention, respectively (P < 0.01) and similar cumulative clinical pregnancy rates per transfer and per cycle were obtained: 26.8, 30.9% and 29.7, 26.3%, respectively. The total DR per oocyte retrieval cycle (21.0 and 20.4% pre- and post-intervention, respectively) defined as efficacy was not affected by the intervention [odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.7–1.1; P = 0.23]. However, a significantly increased live birth rate per transferred embryo (defined as efficiency) was observed in the post-intervention group 17.0 versus 10.6% (P < 0.01). Multiple DRs decreased from 21.0 in the preintervention to 6.8% in the post-intervention group (OR = 0.3. 95% CI = 0.1–0.7; P < 0.01).
In this study, the suitability of SET was assessed in individual women on the basis of both clinical and embryological prognostic factors and was not standardized. For the described eSET strategy coupled with an enhanced embryo selection policy, an optimized culture system, cryopreservation and aneuploidy screening programme is necessary.
Owing to the increased maternal morbidity and perinatal complications related to multiple pregnancies, it is recommended to extend the eSET policy to the AMA population. As shown in this study, enhanced embryo selection procedures might allow a reduction in the number of embryos transferred and the number of transfers to be performed without affecting the total efficacy of the treatment but increasing efficiency and safety.
PMCID: PMC4542718  PMID: 26150408
elective single embryo transfer; advanced maternal age; comprehensive chromosome screening; vitrification; preimplantation genetic screening
7.  Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates 
To compare single nucleotide polymorphism (SNP) and comparative genomic hybridization (aCGH) microarray platforms to evaluate embryos for parental translocation imbalances and aneuploidy.
A retrospective review of preimplantation genetic diagnosis and screening (PGD/PGS) results of 498 embryos from 63 couples undergoing 75 in vitro fertilization cycles due to parental carriers of a reciprocal translocation.
There was no significant difference between SNP and aCGH microarrays when comparing the prevalence of embryos that were euploid with no translocation imbalance, euploidy with a parental translocation imbalance or aneuploid with or without the parental chromosome imbalance. The clinical pregnancy rates were also equivalent for SNP (60 %) versus aCGH (65 %) microarrays. Of 498 diagnosed embryos, 45 % (226/498) were chromosomally normal without translocation errors or aneuploidy, 22 % (112/498) were euploid but had a parentally derived unbalanced chromosomal segregant, 8 % (42/498) harbored both a translocation imbalance and aneuploidy and 24 % (118/498) of embryos were genetically balanced for the parental reciprocal translocation but were aneuploid for other chromosomes. The overall clinical pregnancy rate per IVF cycle following SNP or aCGH microarray analysis was 61 % and was higher if the biopsy was done on blastocysts (65 %) versus cleavage stage embryos (59 %), although not statistically significant.
SNP or aCGH microarray technologies demonstrate equivalent clinical findings that maximize the pregnancy potential in patients with known parental reciprocal chromosomal translocations.
PMCID: PMC4096875  PMID: 24771116
Translocation; PGD; PGS; Microarray; IVF; Reciprocal
8.  Increasing Live Birth Rate by Preimplantation Genetic Screening of Pooled Polar Bodies Using Array Comparative Genomic Hybridization 
PLoS ONE  2015;10(5):e0128317.
Meiotic errors during oocyte maturation are considered the major contributors to embryonic aneuploidy and failures in human IVF treatment. Various technologies have been developed to screen polar bodies, blastomeres and trophectoderm cells for chromosomal aberrations. Array-CGH analysis using bacterial artificial chromosome (BAC) arrays is widely applied for preimplantation genetic diagnosis (PGD) using single cells. Recently, an increase in the pregnancy rate has been demonstrated using array-CGH to evaluate trophectoderm cells. However, in some countries, the analysis of embryonic cells is restricted by law. Therefore, we used BAC array-CGH to assess the impact of polar body analysis on the live birth rate. A disadvantage of polar body aneuploidy screening is the necessity of the analysis of both the first and second polar bodies, resulting in increases in costs for the patient and complex data interpretation. Aneuploidy screening results may sometimes be ambiguous if the first and second polar bodies show reciprocal chromosomal aberrations. To overcome this disadvantage, we tested a strategy involving the pooling of DNA from both polar bodies before DNA amplification. We retrospectively studied 351 patients, of whom 111 underwent polar body array-CGH before embryo transfer. In the group receiving pooled polar body array-CGH (aCGH) analysis, 110 embryos were transferred, and 29 babies were born, corresponding to live birth rates of 26.4% per embryo and 35.7% per patient. In contrast, in the control group, the IVF treatment was performed without preimplantation genetic screening (PGS). For this group, 403 embryos were transferred, and 60 babies were born, resulting in live birth rates of 14.9% per embryo and 22.7% per patient. In conclusion, our data show that in the aCGH group, the use of aneuploidy screening resulted in a significantly higher live birth rate compared with the control group, supporting the benefit of PGS for IVF couples in addition to the suitability and effectiveness of our polar body pooling strategy.
PMCID: PMC4449032  PMID: 26024488
9.  Comparing thaw survival, implantation and live birth rates from cryopreserved zygotes, embryos and blastocysts 
Most in vitro fertilization (IVF) programs employ embryo cryopreservation to enhance pregnancies from a single ovarian stimulation. More embryos are created, some of which are not transferred to the uterus immediately, generating a need for improved cryopreservation protocols. One protocol may involve growing embryos to a further stage of development, allowing only embryos with proven developmental capabilities to be cryopreserved. Here we examined thaw survival, implantation and live birth rates of embryos cryopreserved at different stages.
We examined thaw survival, implantation and live birth rates of embryos cryopreserved at the zygote, day 3 (D3) embryos or blastocyst stage.
This is a retrospective study from a single academic IVF program.
A retrospective study of all patients who had frozen embryos transferred to their uteri from year 2002 to 2008 at a single academic IVF program was conducted.
Analysis of variance followed by Fisher's Exact Test was performed to compare the survival after thaw, implantation and live birth rates between the three groups.
One thousand nine hundred and ninety-one zygotes, 2880 D3 embryos and 503 blastocysts were frozen using a slow freeze technique, thawed and transferred. Significantly more D3 embryos and blastocysts survived the thawing process compared to zygotes and significantly higher implantation rate per number of thawed blastocysts was achieved than that for zygotes. Live birth rates were similar between the three groups.
Growing embryos to blastocyst stage prior to cryopreservation is associated with fewer frozen embryos but does not appear compromise patients’ chance of achieving pregnancy
PMCID: PMC3136065  PMID: 21772736
Blastocyst; embryo cryopreservation; frozen embryo transfer; implantation; in vitro fertilization; slow-freeze; zygote
10.  Comparative Genomic Hybridization Selection of Blastocysts for Repeated Implantation Failure Treatment: A Pilot Study 
BioMed Research International  2014;2014:457913.
The aim of this study is to determine if the use of preimplantation genetic screening (PGS) by array comparative genomic hybridization (array CGH) and transfer of a single euploid blastocyst in patients with repeated implantation failure (RIF) can improve clinical results. Three patient groups are compared: 43 couples with RIF for whom embryos were selected by array CGH (group RIF-PGS), 33 couples with the same history for whom array CGH was not performed (group RIF NO PGS), and 45 good prognosis infertile couples with array CGH selected embryos (group NO RIF PGS). A single euploid blastocyst was transferred in groups RIF-PGS and NO RIF PGS. Array CGH was not performed in group RIF NO PGS in which 1-2 blastocysts were transferred. One monoembryonic sac with heartbeat was found in 28 patients of group RIF PGS and 31 patients of group NO RIF PGS showing similar clinical pregnancy and implantation rates (68.3% and 70.5%, resp.). In contrast, an embryonic sac with heartbeat was only detected in 7 (21.2%) patients of group RIF NO PGS. In conclusion, PGS by array CGH with single euploid blastocyst transfer appears to be a successful strategy for patients with multiple failed IVF attempts.
PMCID: PMC3980987  PMID: 24779011
11.  Selection of competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing for patients undergoing preimplantation genetic screening: a prospective study with sibling oocytes 
BMC Medical Genomics  2014;7:38.
Recent advances in time-lapse monitoring in IVF treatment have provided new morphokinetic markers for embryonic competence. However, there is still very limited information about the relationship between morphokinetic parameters, chromosomal compositions and implantation potential. Accordingly, this study aimed at investigating the effects of selecting competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing on pregnancy and implantation outcomes for patients undergoing preimplantation genetic screening (PGS).
A total of 1163 metaphase II (MII) oocytes were retrieved from 138 PGS patients at a mean age of 36.6 ± 2.4 years. These sibling MII oocytes were then randomized into two groups after ICSI: 1) Group A, oocytes (n = 582) were cultured in the time-lapse system and 2) Group B, oocytes (n = 581) were cultured in the conventional incubator. For both groups, whole genomic amplification and array CGH testing were performed after trophectoderm biopsy on day 5. One to two euploid blastocysts within the most predictive morphokinetic parameters (Group A) or with the best morphological grade available (Group B) were selected for transfer to individual patients on day 6. Ongoing pregnancy and implantation rates were compared between the two groups.
There were significant differences in clinical pregnancy rates between Group A and Group B (71.1% vs. 45.9%, respectively, p = 0.037). The observed implantation rate per embryo transfer significantly increased in Group A compared to Group B (66.2% vs. 42.4%, respectively, p = 0.011). Moreover, a significant increase in ongoing pregnancy rates was also observed in Group A compared to Group B (68.9% vs. 40.5%. respectively, p = 0.019). However, there was no significant difference in miscarriage rate between the time-lapse system and the conventional incubator (3.1% vs. 11.8%, respectively, p = 0.273).
This is the first prospective investigation using sibling oocytes to evaluate the efficiency of selecting competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing for PGS patients. Our data clearly demonstrate that the combination of these two advanced technologies to select competent blastocysts for transfer results in improved implantation and ongoing pregnancy rates for PGS patients.
PMCID: PMC4077552  PMID: 24954518
Time-lapse monitoring; Array CGH; PGS; Ploidy; Implantation; Miscarriage
12.  An update of preimplantation genetic diagnosis in gene diseases, chromosomal translocation, and aneuploidy screening 
Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence in-situ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium.
PMCID: PMC3283069  PMID: 22384431
Array Comparative Genomic Hybridization; Preimplantation Genetic Diagnosis; Preimplantation Genetic Screening; Single Nucleotide Polymorphisms Array; Vitrification; Whole Genome Amplification; Human
13.  Ovarian hyperstimulation syndrome and prophylactic human embryo cryopreservation: analysis of reproductive outcome following thawed embryo transfer 
To review utilisation of elective embryo cryopreservation in the expectant management of patients at risk for developing ovarian hyperstimulation syndrome (OHSS), and report on reproductive outcome following transfer of thawed embryos.
Materials and methods
Medical records were reviewed for patients undergoing IVF from 2000–2008 to identify cases at risk for OHSS where cryopreservation was electively performed on all embryos at the 2 pn stage. Patient age, total number of oocytes retrieved, number of 2 pn embryos cryopreserved, interval between retrieval and thaw/transfer, number (and developmental stage) of embryos transferred (ET), and delivery rate after IVF were recorded for all patients.
From a total of 2892 IVF cycles undertaken during the study period, 51 IVF cases (1.8%) were noted where follicle number exceeded 20 and pelvic fluid collection was present. Elective embryo freeze was performed as OHSS prophylaxis in each instance. Mean (± SD) age of these patients was 32 ± 3.8 yrs. Average number of oocytes retrieved in this group was 23 ± 8.7, which after fertilisation yielded an average of 14 ± 5.7 embryos cryopreserved per patient. Thaw and ET was performed an average of 115 ± 65 d (range 30–377 d) after oocyte retrieval with a mean of 2 ± 0.6 embryos transferred. Grow-out to blastocyst stage was achieved in 88.2% of cases. Delivery/livebirth rate was 33.3% per initiated cycle and 43.6% per transfer. Non-transferred blastocysts remained in cryostorage for 24 of 51 patients (46.1%) after ET, with an average of 3 ± 3 blastocysts refrozen per patient.
OHSS prophylaxis was used in 1.8% of IVF cycles at this institution; no serious OHSS complications were encountered during the study period. Management based on elective 2 pn embryo cryopreservation with subsequent thaw and grow-out to blastocyst stage for transfer did not appear to compromise embryo viability or overall reproductive outcome. For these patients, immediate elective embryo cryopreservation and delay of ET by as little as 30 d allowed for satisfactory conclusion of the IVF sequence, yielding a livebirth-delivery rate (per ET) >40%.
PMCID: PMC2585559  PMID: 19014420
14.  Assessment of aneuploidy formation in human blastocysts resulting from cryopreserved donor eggs 
Increased embryo implantation rates were reported after transfer of euploid embryos selected by preimplantation genetic screening (PGS). Egg cryopreservation by vitrification has become one of the most important assisted human reproduction technologies. Although reports indicate that development and implantation of human embryos derived from frozen donor eggs are comparative to fresh eggs, it is still unknown whether egg vitrification increases chromosomal abnormalities in eggs, which in turn causes formation of embryonic aneuploidy. Therefore, in this study, we evaluated the aneuploidy formation in the blastocysts derived from frozen donor eggs and also evaluated the efficiency of egg vitrification as an advanced technology for egg cryopreservation.
In this study, donated human eggs from young women were cryopreserved by vitrification and PGS was performed in the resulted blastocysts by DNA microarray. A total of 764 frozen eggs from 75 egg thawing cycles were warmed and 38 blastocysts were biopsied for PGS before embryo transfer. A 97.1% of egg survival rate was obtained and 59.1% of embryos developed to blastocyst stage. After biopsy and PGS, it was found that 84.2% of blastocysts were euploid and 15.8% were aneuploid. Aneuploidy rates varied among donors. Transfers of blastocysts without PGS resulted in higher clinical pregnancy and implantation rates as compared with transfer of blastocysts with PGS.
Although the overall aneuploidy rate was low in the blastocysts derived from frozen donor eggs, high aneuploidy rates were observed in the embryos resulting from some donated eggs. Clinical pregnancy rate was not improved by PGS of embryos resulting from donor eggs, indicating that PGS may not be necessary for embryos derived from donor eggs in most cases.
Electronic supplementary material
The online version of this article (doi:10.1186/s13039-015-0117-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4339107  PMID: 25713597
Aneuploidy; Egg freezing; Donor eggs; Implantation
15.  Live birth following serial vitrification of embryos and PGD for fragile X syndrome in a patient with the premutation and decreased ovarian reserve 
To present a live birth resulting from serial vitrification of embryos and pre-implantation genetic diagnosis (PGD).
A 31-year-old with primary infertility, fragile-X premutation, and decreased ovarian reserve (DOR) (baseline FSH level 33 IU/L), presented after failing to stimulate to follicle diameters >10 mm with three cycles of invitro fertilization (IVF). After counseling, the couple opted for serial in-vitro maturation (IVM), embryo vitrification, and genetic testing using array comparative genomic hybridization (aCGH) and PGD. Embryos were vitrified 2 days after intra-cytoplasmic sperm injection (ICSI). Thawed embryos were biopsied on day-three and transferred on day-five.
The couple underwent 20 cycles of assisted reproductive technology. A total of 23 in-vivo mature and five immature oocytes were retrieved, of which one matured in-vitro. Of 24 embryos, 17/24 (71 %) developed to day two and 11/24 (46 %) survived to blastocyst stage with a biopsy result available. Four blastocysts had normal PGD and aCGH results. Both single embryo transfers resulted in a successful implantation, one a blighted ovum and the other in a live birth.
Young patients with DOR have potential for live birth as long as oocytes can be obtained and embryos created. Serial vitrification may be the mechanism of choice in these patients when PGD is needed.
PMCID: PMC3879937  PMID: 24062195
In-vitro maturation (IVM); Embryo vitrification; Diminished Ovarian Reserve (DOR); Fragile X Syndrome (FXS); Preimplantation Genetic Diagnosis (PGD); Array Comparative Genomic Hybridization (aCGH)
16.  A greater number of euploid blastocysts in a given cohort predicts excellent outcomes in single embryo transfer cycles 
This multicentered retrospective study analyzed whether the quantity of euploid blastocysts in a given cohort after comprehensive chromosomal screening can be used to identify candidates for single embryo transfer.
Blastocysts from 437 patients underwent trophectoderm biopsy followed by array comparative genomic hybridization. Embryos were then selected for single or double embryo transfer. The number of euploid blastocysts produced and transferred for each patient was recorded, as was clinical pregnancy rate and multiple gestation rate.
In patients with ≤3 euploid blastocysts, clinical pregnancy rate was higher in double, compared to single embryo transfers. However, in patients with ≥4 euploid blastocysts, clinical pregnancy rate was not reduced with single embryo transfer was performed, whereas the multiple gestation rate was greatly reduced.
Size of the euploid embryo cohort is a marker for success in single embryo transfer cycles. Patients who produce at least four euploid blastocysts are outstanding candidates for single embryo transer.
PMCID: PMC4048376  PMID: 24659020
Single embryo transfer (SET); Preimplantation Genetic Screening (PGS); Trophectoderm biopsy; Array comparative genomic hybridization (array-CGH); Assisted reproductive technology (ART)
17.  AB094. Efficacy of combined preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) cycles—early results 
Annals of Translational Medicine  2015;3(Suppl 2):AB094.
Preimplantation genetic diagnosis (PGD) using PCR allows couples where one or both carry a hereditary single gene disorder to avoid having a child with that disorder. It can also be an effective therapeutic tool in curing an existing affected sibling through tissue matched cord blood stem cell transplant. However early preimplantation embryos have significant levels of chromosomal aneuploidy increasing with maternal age. Recent PGS technologies such as comparative genome hybridization (CGH) allow screening of all 24 chromosomes in the early embryo, allowing selective single embryo transfer (eSET) with significantly increased IVF implantation rates and significantly decreased miscarriage rates. We discuss early results on the efficacy of using PGD-PCR in combination with PGS-CGH (combined cycle) in couples who present for PGD for hereditary single gene disorders. PGD-PCR patients have a family specific test established, with the test components multiplexed and checked for reliability on single maternal cumulus cells. Patients having combined cycle had the individual test components checked on existing whole genome amplification (WGA) products and, if unreliable, reverted back to a standard PGD-PCR test/cycle only. Couples had an ovarian stimulation cycle, harvested eggs were fertilized using intracytoplasmic sperm injection (ICSI), and resultant normally fertilized embryos cultured to day 5 and day 6 blastocyst stage. Suitable blastocysts were biopsied with assistance of a near-infra-red laser. The 1-6 cells obtained had their DNA extracted and either PCR amplified using the established multiplexed PGD-PCR test (PGD-PCR cycle) or WGA amplified (combined cycle). From 2007-2014, 109 couples presented for PGD-PCR for 16 different familial single gene disorders, predominantly beta-thalassemia (61/109) or alpha-thalassemia (25/109). In 2012 we introduced PGS-CGH for 24 chromosome screening of infertility couples, and soon after offered PGD-PCR patients the option of a combined PGS-CGH and PGD-PCR cycle; to date 19 patients had requested the combined cycle. For PGD-PCR only, 97 patients had 154 cycles with 85 embryo transfers (114 embryos). 57/85 (67%) were clinically pregnant with an implantation rate of 50%. For requested combined cycles, 5/19 patients (all alpha-thalassemia) failed the WGA check and reverted to PGD-PCR test/cycle only. 11/14 had 14 cycles with 8/14 cycles freeze-all (with no transfers to date) and 4 embryo transfers (5 embryos). 4/4 (100%) were clinically pregnant with an implantation rate of 80%. Early results, while low numbers, indicate offering patients presenting with a hereditary single gene disorder the option of having all 24 chromosomes screened prior to implantation may significantly increase their chance of a healthy pregnancy.
PMCID: PMC4563550
Preimplantation genetic diagnosis (PGD); preimplantation genetic screening (PGS); array comparative genome hybridization (aCGH)
18.  Vitrification of mouse embryos at 2-cell, 4-cell and 8-cell stages by cryotop method 
The objective of this study was to investigate the effects of vitrification on the preimplantation developmental competence of mouse 2-cell, 4-cell and 8-cell stage embryos.
Mouse 2-cell, 4-cell and 8-cell stage embryos were cryopreserved using the cryotop vitrification method and subsequently warmed on a later date. The embryos were then assessed by their morphology, blastocyst formation and hatching rates. Additionally, trophectoderm (TE) and inner cell mass (ICM) cell numbers were compared in hatched blastocysts from the control and experimental groups.
Vitrified embryos at the 2-cell, 4-cell and 8-cell stages appeared morphologically normal after warming. The overall survival rate of vitrified embryos at various stages after warming was 96.7% and there were no significant differences among 2-cell stage (96.0%), 4-cell stage (96.8%) and 8-cell stage (97.1%) embryos (P > 0.05). The blastocyst formation rate (69.4%) and hatching rate (52.6%) of vitrified 2-cell embryos were significantly lower than that from the control group and vitrified 8-cell embryos (P < 0.05). In the vitrified 4-cell embryo group, the blastocyst formation rate (90.3%) was similar to the 8-cell group (91.2%), but the hatching rate (60.0%) was significantly lower than that of the non-vitrified control ( 84.1%) and vitrified 8-cell embryo (78.4%) groups (P < 0.05). When further development to the fully hatched blastocyst stage was compared, hatched blastocysts derived from vitrified 2-cell, 4-cell and 8-cell embryos had significantly lower cell counts both in the ICM and TE, as compared to fresh blastocysts (P < 0.05). Among the vitrified 2-cell, 4-cell and 8-cell embryo groups, there were no significant differences in the cell counts of ICM and TE (P > 0.05).
Although cryotop vitrification was suitable for the cryopreservation of mouse embryos from the 2-cell stage, 4-cell stage and 8-cell stage without significant loss of survival, vitrification had an adverse effect on the development of 2-cell embryos. Mouse embryos at the 8-cell stage had the best tolerance for vitrification and would yield the highest level of post-vitrification developmental competence among early cleavage stage embryos. Nevertheless, it is unclear how these findings can be extrapolated to human embryos.
PMCID: PMC2799565  PMID: 19967554
Vitrification; Cleavage; Embryos; Development; Cryopreservation; Mouse
19.  New Tools for Embryo Selection: Comprehensive Chromosome Screening by Array Comparative Genomic Hybridization 
BioMed Research International  2014;2014:517125.
The objective of this study was to evaluate the usefulness of comprehensive chromosome screening (CCS) using array comparative genomic hybridization (aCGH). The study included 1420 CCS cycles for recurrent miscarriage (n = 203); repetitive implantation failure (n = 188); severe male factor (n = 116); previous trisomic pregnancy (n = 33); and advanced maternal age (n = 880). CCS was performed in cycles with fresh oocytes and embryos (n = 774); mixed cycles with fresh and vitrified oocytes (n = 320); mixed cycles with fresh and vitrified day-2 embryos (n = 235); and mixed cycles with fresh and vitrified day-3 embryos (n = 91). Day-3 embryo biopsy was performed and analyzed by aCGH followed by day-5 embryo transfer. Consistent implantation (range: 40.5–54.2%) and pregnancy rates per transfer (range: 46.0–62.9%) were obtained for all the indications and independently of the origin of the oocytes or embryos. However, a lower delivery rate per cycle was achieved in women aged over 40 years (18.1%) due to the higher percentage of aneuploid embryos (85.3%) and lower number of cycles with at least one euploid embryo available per transfer (40.3%). We concluded that aneuploidy is one of the major factors which affect embryo implantation.
PMCID: PMC4022197  PMID: 24877108
20.  Comparison of clinical outcomes between fresh embryo transfers and frozen-thawed embryo transfers 
Background: Advances in embryo culture technology and cryopreservation have led to a shift in in vitro fertilization (IVF) from early fresh or frozen-thawed cleavage embryo transfer to fresh or frozen-thawed blastocyst stage transfer.
Objective: To compare the clinical outcomes of fresh embryo transfers and frozen-thawed embryo transfers.
Materials and Methods: In this retrospective case control study, patients undergoing IVF cycles from January 2012 to December 2012 were enrolled in Assisted Reproduction of Wuhan Union Hospital were enrolled. A total of 1891 cycle contains 1150 fresh embryo transfers and 741 frozen-thawed embryo transfers were studied. All data were transferred directly to SPSS 18 and analyzed.
Results: Clinical pregnancy rates of fresh cleavage-stage embryo transfers compared with fresh blastocyst transfers, frozen-thawed cleavage-stage embryo transfers, post thaw cleavage-stage extended blastocyst culture transfers and frozen-thawed blastocyst transfers were 52.7%, 35.88%, 35.29%, 47.75%, 59.8% in patients under 35 years of ages and 41.24%, 26.92%, 11.32%, 46.15%, 55.8% in patients older than 35 years old, respectively. The multiple pregnancy rates, abortion rates and ectopic pregnancy rates did not differ significantly among the five groups.
Conclusion: The clinical pregnancy rates were not different significantly between fresh cleavage-stage embryo transfers and fresh blastocyst transfers. But the clinical pregnancy rate of frozen-thawed blastocyst transfer was the highest among fresh/frozen-thawed embryo transfers.
PMCID: PMC4111889  PMID: 25071849
In vitro fertilization; Embryo transfer; Clinical outcome; Ectopic pregnancy; Endometrial receptivity
21.  Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials 
Objective To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth and multiple live birth after fresh and frozen embryo transfers.
Design One stage meta-analysis of individual patient data.
Data sources A systematic review of English and non-English articles from Medline, Embase, and the Cochrane Central Register of Controlled Trials (up to 2008). Additional studies were identified by contact with clinical experts and searches of bibliographies of all relevant primary articles. Search terms included embryo transfer, randomised controlled trial, controlled clinical trial, single embryo transfer, and double embryo transfer.
Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2 or 3) elective single versus double embryo transfer after fresh or frozen in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included. Trials were included if the intervention differed only in terms of the intended number of embryos to be transferred. Trials that involved only blastocyst (day five) transfers were excluded.
Results Individual patient data were received for every patient recruited to all eight eligible trials (n=1367). A total of 683 and 684 women randomised to the single and double embryo transfer arms, respectively, were included in the analysis. Baseline characteristics in the two groups were comparable. The overall live birth rate in a fresh IVF cycle was lower after single (181/683, 27%) than double embryo transfer (285/683, 42%) (adjusted odds ratio 0.50, 95% confidence interval 0.39 to 0.63), as was the multiple birth rate (3/181 (2%) v 84/285 (29%)) (0.04, 0.01 to 0.12). An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer (132/350 (38%) v 149/353 (42%) (0.85, 0.62 to 1.15), with a minimal cumulative risk of multiple birth (1/132 (1%) v 47/149 (32%)). The odds of a term singleton birth (that is, over 37 weeks) after elective single embryo transfer was almost five times higher than the odds after double embryo transfer (4.93, 2.98 to 8.18).
Conclusions Elective single embryo transfer results in a higher chance of delivering a term singleton live birth compared with double embryo transfer. Although this strategy yields a lower pregnancy rate than a double embryo transfer in a fresh IVF cycle, this difference is almost completely overcome by an additional frozen single embryo transfer cycle. The multiple pregnancy rate after elective single embryo transfer is comparable with that observed in spontaneous pregnancies.
PMCID: PMC3006495  PMID: 21177530
22.  Blastocyst Morphology Holds Clues Concerning The Chromosomal Status of The Embryo  
Embryo morphology has been proposed as an alternative marker of chro- mosomal status. The objective of this retrospective cohort study was to investigate the association between the chromosomal status on day 3 of embryo development and blas- tocyst morphology.
Materials and Methods
A total of 596 embryos obtained from 106 cycles of intra- cytoplasmic sperm injection (ICSI) followed by preimplantation genetic aneuploidy screening (PGS) were included in this retrospective study. We evaluated the relation- ship between blastocyst morphological features and embryonic chromosomal altera- tion.
Of the 564 embryos with fluorescent in situ hybridization (FISH) results, 200 reached the blastocyst stage on day 5 of development. There was a significantly high- er proportion of euploid embryos in those that achieved the blastocyst stage (59.0%) compared to embryos that did not develop to blastocysts (41.2%) on day 5 (P<0.001). Regarding blastocyst morphology, we observed that all embryos that had an abnormal inner cell mass (ICM) were aneuploid. Embryos with morphologically normal ICM had a significantly higher euploidy rate (62.1%, P<0.001). As regards to the trophectoderm (TE) morphology, an increased rate of euploidy was observed in embryos that had nor- mal TE (65.8%) compared to embryos with abnormal TE (37.5%, P<0.001). Finally, we observed a two-fold increase in the euploidy rate in high-quality blastocysts with both high-quality ICM and TE (70.4%) compared to that found in low-quality blastocysts (31.0%, P<0.001).
Chromosomal abnormalities do not impair embryo development as ane- uploidy is frequently observed in embryos that reach the blastocyst stage. A high-quality blastocyst does not represent euploidy of chromosomes 13, 14, 15, 16, 18, 21, 22, X and Y. However, aneuploidy is associated with abnormalities in the ICM morphology. Further studies are necessary to confirm whether or not the transfer of blastocysts with low-quality ICM should be avoided.
PMCID: PMC4518490  PMID: 26246880
Aneuploidy; Dysmorphism; In Vitro Fertilization; Preimplantation Genetic Screening
23.  Live birth after fresh embryo transfer vs elective embryo cryopreservation/frozen embryo transfer in women with polycystic ovary syndrome undergoing IVF (FreFro-PCOS): study protocol for a multicenter, prospective, randomized controlled clinical trial 
Trials  2014;15:154.
Polycystic ovary syndrome (PCOS) patients are at increased risk of pregnancy complications, which may impair pregnancy outcome. Transfer of fresh embryos after superovulation may lead to abnormal implantation and placentation and further increase risk for pregnancy loss and complications. Some preliminary data suggest that elective embryo cryopreservation followed by frozen–thawed embryo transfer into a hormonally primed endometrium could result in a higher clinical pregnancy rate than that achieved by fresh embryo transfer.
This study is a multicenter, prospective, randomized controlled clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be enrolled and randomized into two parallel groups. Participants in group A will undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants in group B will undergo elective embryo cryopreservation after oocyte retrieval and frozen–thawed embryo transfer in programmed cycles. The primary outcome is the live birth rate. Our study is powered at 80 to detect an absolute difference of 10 at the significance level of 0.01 based on a two-sided test.
We hypothesize that elective embryo cryopreservation and frozen–thawed embryo transfer will reduce the incidence of pregnancy complications and increase the live birth rate in PCOS patients who need IVF to achieve pregnancy.
Trial registration Identifier: NCT01841528
PMCID: PMC4022358  PMID: 24885793
Frozen–thawed embryo transfer; In vitro fertilization; Live birth; Polycystic ovarian syndrome
24.  Cryopreservation of Embryos, Blastocysts, and Pregnancy Rates of Blastocysts Derived from Frozen-Thawed Embryos and Frozen-Thawed Blastocysts 
Purpose: To evaluate the development of cryopreserved embryos when thawed and subsequently cultured to the blastocyst stage in comparison to transferring cryopreserved blastocysts.
Methods: In this retrospective clinical study, we have evaluated 170 cycles in patients undergoing IVF treatment for infertility. Cryopreserved embryos were thawed and were subsequently cultured and transferred at the blastocyst stage. Cryopreserved blastocysts (Day 6) were thawed and transferred immediately.
Results: Five hundred and sixty embryos and 444 blastocysts have been thawed. In the embryos group, the survival rate was 89% while in the blastocyst group the survival rate was 56%. In the embryos group the blastocyst development rate was 24.5%. The implantation rate in the embryos group was 20.6% per group blastocyst transferred compared to 5.3% in the blastocyst group.
Conclusions: The ability of cryopreserved embryos to develop to blastocysts and their implantation potential does not seem to be greatly affected by the cryopreservation procedure.
PMCID: PMC3455699  PMID: 11804424
blastocyst; cryopreservation; embryos; implantation rate; pregnancy rate
25.  Polar body based aneuploidy screening is poorly predictive of embryo ploidy and reproductive potential 
Polar body (polar body) biopsy represents one possible solution to performing comprehensive chromosome screening (CCS). This study adds to what is known about the predictive value of polar body based testing for the genetic status of the resulting embryo, but more importantly, provides the first evaluation of the predictive value for actual clinical outcomes after embryo transfer.
SNP array was performed on first polar body, second polar body, and either a blastomere or trophectoderm biopsy, or the entire arrested embryo. Concordance of the polar body-based prediction with the observed diagnoses in the embryos was assessed. In addition, the predictive value of the polar body -based diagnosis for the specific clinical outcome of transferred embryos was evaluated through the use of DNA fingerprinting to track individual embryos.
There were 459 embryos analyzed from 96 patients with a mean maternal age of 35.3. The polar body-based predictive value for the embryo based diagnosis was 70.3 %. The blastocyst implantation predictive value of a euploid trophectoderm was higher than from euploid polar bodies (51 % versus 40 %). The cleavage stage embryo implantation predictive value of a euploid blastomere was also higher than from euploid polar bodies (31 % versus 22 %).
Polar body based aneuploidy screening results were less predictive of actual clinical outcomes than direct embryo assessment and may not be adequate to improve sustained implantation rates. In nearly one-third of cases the polar body based analysis failed to predict the ploidy of the embryo. This imprecision may hinder efforts for polar body based CCS to improve IVF clinical outcomes.
PMCID: PMC4156943  PMID: 25106935
Preimplantation genetic screening (PGS); Polar bodies; Aneuploidy; Blastocyst; SNP array

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