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Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening

Authors:
  • The Reproductive Care Centre Mississauga ON L5N5S3

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22
Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018
Introduction
Preimplantation Genetic Screening (PGS) refers to
detection of chromosomal aneuploidy in the embryo
whereas Preimplantation Genetic Diagnosis (PGD)
refers to d      
the embryo that may transmit from parents to the
       
      
       

   
the repeated pregna
as a method for reducing miscarriage by selecting

      


    
    
later transfer of biopsied blastocysts is a practical
      
stage embryo      
implantation rate and low twinning and miscarriage
        
Archives of Reproductive Medicine and Sexual Health
Volume 1, Issue 1, 2018, PP: 22-30
Key Factors to Avoid Cancellation of Trophectoderm Biopsy
for Preimplantation Genetic Screening
Mur
id Javed
1
*, Othman Abdulrazzak
1
, Fatma Abdelraouf
1
, Tagwa Saad
1
, Sahar Be
ngawi1
Dana Alanzi2, Suleiman Najashi3, Hamad Sufyan3



*murid.javed@gmail.com
*Corresponding Author: Murid Javed, DVM, MSc (Hons), PhD, EMB, Laboratory Director, Thuriah Medical Center,
244 Makkah Road, PO Box 50246, Riyadh, 11523, KSA.
Abstract
This study analyzed 1103 cycles of assisted reproductive technology underdoing either intracytoplasmic sperm
injection (ICSI) only or ICSI with preimplantation genetic screening (ICSI+PGS). The primary objective was to

to the blastocyst stage. The trophectoderm biopsies were performed on day-5 or day-6 and the embryos were
      
     
                  
cancellation rate increased with increase in the age category. The key factors for ICSI+PGS cycle cancellation
were advanced female age and availability of <5 mature oocytes. Other reasons included poor oocyte quality,
increased abnormal fertilization and availability of no motile sperm. The study proposes to optimize ovarian
stimulation to retrieve about 15 oocytes per retrieval for a success ICSI+PGS cycle if trophectoderm biopsy is
to be performed. In advanced age or poor responders, multiple retrievals may be needed to obtain enough
blastocyst for PGS. The study highlights that counseling of patients undergoing ICSI+PGS should include not
only success rates with PGS, but also information on the factors that may result in cycle cancellation. Therefore,
prior to initiation of treatment it is essential to ensure that the patient has clearly understood the advantages
and disadvantages of PGS and is prepared for all possible cycle outcomes.
Keywords: Trophectoderm biopsy, aneuploidy, preimplantation, PGS, PGD, PGT, ICSI
23 Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018
Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening
     
      
      
     


       

biopsy compared with embryo selection based on
     

ed implantation rate in good progn
osis
patients but also reduced the multiple pregnancy rate
when one single euploid blastocyst was transferred
     
  
   
      
      
     
      

       
 


number of euploid blaststocysts as compared to a

      
     
       
  

        
 




       
an
     
n
      
      
       
       





A few other factors that   
num
ber of genetically normal embryos are the

he
authors suggested that there should be at least four

embryo in a PGD cycle for patients with single gene



ority of the studies on PGS report cli
nical

  
cancellation are not usually captured which may

       
immature o
 
cyst

opment and unsuitability of blastocysts fo
r
bi

atient
      
     
      
         
     

Materials and Methods
        
      

ge
      
re

    
     

Ovarian Stimulation
A
ll patients underwent gonadotropin rele
asing

  
    

    
r

       
      
furt

    
y
        
    
       
       
  

24
Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018
ICSI, Embryo Culture and Trophectoderm
Biopsy, Embryo Transfer

per st     
       




were then cultured in a new dish prepared with Global

The embryologists graded the blastocysts on the
   

trophectoderm according to Gardner’s grading scale
     

       
      
    

        
       
       
    

       

     
out of the breach
         

an
     

     
     
     

       
frozen embryo transfer and only euploid embryos

        
        

Statistical Analysis
       
     


   

Results
          

only a
       
        
    
      
reason
s are shown in Table 1
number 
tocyst
       
su
     
y poor
         

       

Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening
Age Group (yr.) 









Total

PGS cancel reasons



 



Abnormal fertilization
Table 1.
25 Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018
Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening

Poor quality oocytes 9



Total     
Percent
Cancelled
Cycles
       
group are shown in Fig 1   



     
       



(Fig 2
 

   


Fig 1. Percent cancellation of ICSI+PGS cases in different age groups (N=140)
Age Groups
Fig 2.

Age Groups
Percent
Cancelled
Cycles
26
Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018
        
Table 3       

  

       
their own oocytes and partner’s sperm and did not

Table 3. Pregnancy rates for ICSI only cycles after fresh
embryo transfer
Age
Group
#
Patients
# Embryos/
ET
% Positive/
ET
   
   
  
All ages  
Preg     
are shown in Table 4 
       
    
   
    

conclusi

Table 4. Pregnancy rates in ICSI+PGS group after transfer
of euploid embryos
Biopsy Day #
Patients
# Embryos/
ET
% Positive/
ET
   
  
Total  
Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening
The parameters of cases that succeeded in
trophectoderm biopsy and PGS are presented in
Table 2



Table 2. Parameters of successful PGS cycles resulting in blastocyst biopsy in different age groups (N = 140).
 







     
Range    
     
Range    
Number of blastocysts     
Range    
      
suggest that for ideal situations and for success in


     
       
     
Fig 3
Fig 3. Suggested scheme for success in ICSI+PGS cycles in ideal situations.
27 Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018
Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening
Discussion
T
     
ellation
      
cycle successful when at least one embryo reached
    
       
 
   
 
      

abnormal fertilization (Table 1    



cancelled (Fig 1
technology procedures is strongly dependent on
       
percentage of cycles with normal blastocysts increase
 

        
       


      Fig 3 


this number can’t be anticipated in poor responders
       
     
     

       
      
either about strategy of multiple cycles or the option
of transferring embryos without PGS followed by
      

about termination of pregnancy if prenatal testing
    

      
       
      

procedure and to decrease the miscarriage rate by not

There is scanty information in the literature on

studies report clinical outcomes

transfer and cycle cancellations at earlier stages are

     
    
      
on initiated    
because cycles inclusion in the SART database for

were initiated with the intent to perform PGT but were

is need to modify the database so that clinics are able



The SART he rates of PGT


       
      

      

     
      
         


      
     



         
cycles were cancelled (Fig 1   

maternal age due to chromosomally abnormal embryos


     
    
       

        


28
Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018
      

       
      
         
    
  
cycle of PGS is limited due to the high incidence of
       
       
       
      
         
      
      

W
       
e
       
Fig 2
         
     
age of 
in this group were older than those undergoing other

        

        
morphology blastocysts were selected for biopsy and
       Table 2 
     
      
         
  tocysts indicated that blastocyst
morphologic grading and particularly inner cell
        
poor quality euploid blastocysts resulted in higher
     
     
      
   
   
       



of the same quali
concept (Table 4  
      
     
faster or slower growing embryos showed a similar

        
    


       because
        



        
      
    
       
failed fertilization post egg insemination or in cases of


      






      
 

Conclusions
       

  
      

     
spec
ialists to opti   
e
genetic counselors to better counsel the couples and
the patients to get mentally prepared for all possible

References
    
an update on current technologies and ethical
consi
  
nd

Su
    
tion
Genetic Screening and Preimplantation Genetic
 stetrics and gynecology clinics of

Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening
29 Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018
Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening

analysis of preimplantation genetic screening and in
     
     



genetic screening is co
    




        
      
trophectoderm biopsy and preimplantation
     

       
Preimplantation Genetic Screning (PGS) with
    
      


     
 

     
     
   
     

       
       

   
research interna



screening technology on preimplantation genetic
screen
     
mized



        
   
    

         
       
      



 

     

Gar
      

T
     
ects
    




     

      
      

     



     

      
       
genetic diagnosis and preimplantation genetic
       
Assis
   
ting
      

       
 
    




        

      



30
Archives of Reproductive Medicine and Sexual Health V1 . I1 . 2018

for fresh blastocyst transfer when undergoing
   


   
         
fertilization and preimplantation genetic screening
   
patients with
     

  

      
of maternal age on the outcome of PGD for
aneuploidy screening in patients with recurrent
   

       

     
iation
between aneuploidy and the rate of blastocyst
     

  


     
mate
     



      

     
      
a
nd   
dicine

 

gra
    
uences
implan
tation and ongoing pregnancy ra


         
         
    
      
    

       

   
    
      
    

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trophectoderm biopsy and preimplantation
gen
etic screening (PGS) show incr
eased
aneuploidy rates but can lead 
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Key Factors to Avoid Cancellation of Trophectoderm Biopsy for Preimplantation Genetic Screening
Citation: Murid Javed, Othman Abdulrazzak, Fatma Abdelraouf, et al. Key Factors to Avoid Cancellation
of Trophectoderm Biopsy for Preimplantation Genetic Screening. Archives of Reproductive Medicine and Sexual
Health.
Copyright: Murid Javed, Othman Abdulrazzak, Fatma Abdelraouf, et al. This is an open access
article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
ResearchGate has not been able to resolve any citations for this publication.
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Objective: To determine whether the blastocyst development rate, as assessed by the day of trophectoderm biopsy (day 5 vs. day 6), affects the live birth rate (LBR) of similarly graded euploid blastocysts. Design: Retrospective cohort study. Setting: Academic medical center. Patient(s): Patients who underwent frozen-thawed single euploid blastocyst transfers from 2013 to 2016 were included. Blastocyst morphologic grading was performed on day 5 or day 6 before the biopsy, with embryos designated into the following groups: good (3-6AA, 3-6AB, and 3-6BA), average (2-6BB), and poor (2-6BC and 2-6CB). Intervention(s): Frozen-thawed embryo transfer. Main outcome measure(s): Implantation rate (IR) and LBR. Result(s): A total of 701 frozen-thawed single euploid blastocyst transfer cycles were included. Cycles in which day 5 blastocysts were transferred (n = 366) were associated with a significantly higher LBR than those in which day 6 blastocysts were transferred (n = 335; 60.4% vs. 44.8%). The odds ratio remained significant after controlling for all confounders, including the blastocyst grading. Furthermore, there was a significant difference in LBRs between good-quality, average-quality, and poor-quality blastocysts (67.8%, 53.4%, and 29.5%, respectively). Embryos reaching good-quality blastocysts on day 5 yielded significantly higher LBR (72.8% vs. 56.5%) and IR (77.7% vs. 58.7%) compared with those reaching similar quality blastocysts on day 6. Similarly, day 5 average-quality embryos conveyed a significantly higher IR compared with day 6 embryos of the same quality (64.4% vs. 53.4%). Conclusion(s): In addition to aneuploidy assessment, the speed of embryo development to the blastocyst stage and an evaluation of blastocyst morphology are critical to selecting the best embryo.
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Purpose The aim of this study was to report the results of IVF with trophectoderm biopsy and preimplantation genetic screening (PGS) following delayed intracytoplasmic sperm injection (ICSI). Methods Patients undergoing IVF with PGS and delayed ICSI were included in the study. Indications for delayed ICSI included absent or poor fertilization via standard insemination or more than 50 % immature oocytes, noted post-cumulus stripping for standard ICSI procedure. Delayed ICSI was performed the day after retrieval due to absent or poor fertilization. The immature oocytes were kept in extended culture, and if demonstrated maturity, ICSI was performed. Primary outcome included fertilization rate and blastocyst stage formation, defined by the number of blastocysts for biopsy. Secondary outcome included aneuploidy rate and pregnancy outcomes following single thawed euploid embryo transfers (STEET). Results Sixteen patients with delayed ICSI were included in the study. Twelve were due to poor fertilization and four secondary to immature oocytes. A total of 219 oocytes were retrieved; ten were frozen upon patient request, 168 had standard insemination, and 13 had routine ICSI on the day of retrieval. A total of 129 oocytes underwent delayed ICSI. Sixty-three (49 %) fertilized, 19 (14.7 %) reached blastocysts for biopsy; fivw of which were chromosomally normal (26.3 %). Three patients underwent STEET of a delayed ICSI embryo; all three resulted in live births, including one embryo biopsied on day 8 of development. Conclusion Fertilization failure or an excessive proportion of immature oocytes in an IVF cycle, necessitating delayed ICSI, showed equivalent fertilization and blast formation rates. With the implementation of trophectoderm biopsy and PGS, these embryos can lead to healthy live born babies.
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Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential.
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Objective: To determine the clinical value of preimplantation genetic diagnosis for aneuploidy screening (PGD-A) in women of advanced maternal age (AMA; between 38 and 41 years). Design: This was a multicenter, randomized trial with two arms: a PGD-A group with blastocyst transfer, and a control group with blastocyst transfer without PGD-A. Setting: Private reproductive centers. Patient(s): A total of 326 recruited patients fit the inclusion criteria, and 205 completed the study (100 in the PGD-A group and 105 in the control group). Intervention(s): Day-3 embryo biopsy, array comparative genomic hybridization, blastocyst transfer, and vitrification. Main outcome measure(s): Primary outcomes were delivery and live birth rates in the first transfer and cumulative outcome rates. Result(s): The PGD-A group exhibited significantly fewer ETs (68.0% vs. 90.5% for control) and lower miscarriage rates (2.7% vs. 39.0% for control). Delivery rate after the first transfer attempt was significantly higher in the PGD-A group per transfer (52.9% vs 24.2%) and per patient (36.0% vs. 21.9%). No significant differences were observed in the cumulative delivery rates per patient 6 months after closing the study. However, the mean number of ETs needed per live birth was lower in the PGD-A group compared with the control group (1.8 vs. 3.7), as was the time to pregnancy (7.7 vs. 14.9 weeks). Conclusion(s): Preimplantation genetic diagnosis for aneuploidy screening is superior compared with controls not only in clinical outcome at the first ET but also in dramatically decreasing miscarriage rates and shortening the time to pregnancy.
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The aim of reproductive medicine is to support the birth of healthy children. Advances in assisted reproductive technologies and genetic analysis have led to the introduction of preimplantation genetic diagnosis (PGD) for embryos. Indications for PGD have been a major topic in the fields of ethics and law. Concerns vary by nation, religion, population, and segment, and the continued rapid development of new technologies. In contrast to the ethical augment, technology has been developing at an excessively rapid speed. The most significant recent technological development provides the ability to perform whole genome amplification and sequencing of single embryonic cells by microarray or next-generation sequencing methods. As new affordable technologies are introduced, patients are presented with a growing variety of PGD options. Simultaneously, the ethical guidelines for the indications for testing and handling of genetic information must also rapidly correspond to the changes.
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To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). Decision analytic model comparing costs and clinical outcomes. Academic recurrent pregnancy loss programs. Women with unexplained RPL. IVF/PGS with 24-chromosome screening and expectant management. Cost per live birth. The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing 45,300perlivebirthcomparedwith45,300 per live birth compared with 418 per live birth with expectant management. In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.