Pre-implantation Genetic Testing for Monogenic Disease: Single Center Experience
Conditions: Genetic Disease, Aneuploidy
Sponsor: Istituto Clinico Humanitas

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
1 
 
Pre-implantation genetic testing for monogenic diseases: single 
center study 
 
 
 
Product Identifier: NA 
 
 
Protocol Code: GIN2/OSS_001/2023 
 
 
Version No. (29/06/2023): 1 
 
 
Sponsor (Institution): Humanitas Research Hospital 
 
 
Coordinating Investigator: Paolo Emanuele Levi Setti, MD 
 
 
 
Confidentiality Statement 
The information contained in this document, especially unpublished data, is provided to you in confidence 
as an investigator, potential investigator, or consultant. It is understood that this information will not be 
disclosed to others than the applicable Competent Ethics Committee(s) and Regulatory Authority(ies) 
without written authorization from Istituto Clinico Humanitas except to the extent necessary to obtain 
informed consent from those who will participate in the study. 
 
 
 
 
 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
2 
CONTACT ADDRESSES 
 
 
  
 
Coordinating Investigator:  
Name: Paolo Emanuele Levi Setti 
e-mail: paolo.levi_setti@hunimed.eu 
Study Research Coordinator: 
Name: Federico Cirillo 
e-mail: federico.cirillo@humanitas.it 
Statistician: 
Name: Emanuela Morenghi 
Phone: +39 3387146364 
e-mail: emanuela.morenghi@humanitas.it 
Data Manager 
 
Name: Sabrina Segura 
Phone: +39 3479948417 
e-mail: sabrina.segura@st.hunimed.eu 
 
Contract Research Organization: 
NA 
 
Central Laboratory 
 
NA 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
3 
COORDINATING INVESTIGATOR 
I have approved this Protocol entitled “Pre-implantation genetic testing for monogenic disease: single 
center experience.” and I agree to conduct the study as detailed herein and according to the current version 
of the World Medical Association Declaration of Helsinki, Good Clinical Practice guideline and applicable 
regulatory requirements. I will provide all study personnel under my supervision with all information needed 
to perform the study and I will inform them about their responsibilities and obligations. 
 
 
Printed name 
Paolo Emanuele Levi Setti 
Role 
Coordinating investigator 
Department 
Department of Gynecology, Division of Gynecology and Reproductive Medicine, 
Humanitas Fertility Center 
Signature 
 
 
Date 
29/06/2023 
 
STATISTICIAN 
I have approved this Protocol entitled “Pre-implantation genetic testing for monogenic disease: single 
center experience.” 
 
 
Printed name 
Emanuela Morenghi 
Signature 
Date 
29/06/2023 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
4 
CENTRE SIGNATURE – PRINCIPAL INVESTIGATOR 
 
I have read this Protocol Amendment relevant to the study entitled “Pre-implantation genetic testing for 
monogenic disease: single center experience.” and I agree to conduct the study as detailed herein and in 
compliance with guidelines for Good Clinical Practice and applicable regulatory requirements. I will provide 
all study personnel under my supervision with all information provided by the Coordinating 
Investigator/Sponsor and I will inform them about their responsibilities and obligations. 
 
 
Printed name 
Paolo Emanuele Levi Setti 
Role 
Principal investigator 
Department 
Department of Gynaecology, Division of Gynaecology and Reproductive 
Medicine, Humanitas Fertility Center 
Signature 
Date 
29/06/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
5 
 
INDEX 
 
1. 
SUMMARY .................................................................................................................................. 6 
2. 
STUDY FLOW-CHART ................................................................................................................... 9 
3. BACKGROUND ................................................................................................................................ 9 
4. STUDY OBJECTIVES ....................................................................................................................... 11 
3.1. 
Endpoints .............................................................................................................................. 11 
4. 
STUDY POPULATION ................................................................................................................. 11 
4.1. 
Inclusion criteria .................................................................................................................... 12 
4.2. 
Exclusion criteria ................................................................................................................... 12 
No group will be excluded from this study. ....................................................................................... 12 
4.3. 
Recruitment .................................................................................................................. 12 
5. 
STUDY ASSESSMENT ................................................................................................................. 12 
6. 
STATISTICAL CONSIDERATIONS .................................................................................................. 13 
6.1. 
Sample size ........................................................................................................................... 13 
6.2. 
Analysis ................................................................................................................................ 13 
7. 
QUALITY ASSURANCE AND CONTROL......................................................................................... 13 
7.1. 
Data handling and record keeping / archiving ........................................................................ 13 
7.2. 
Case Report Forms ................................................................................................................ 13 
7.3. 
Source documents ................................................................................................................. 13 
8. 
CONFIDENTIALITY OF PATIENT RECORDS ................................................................................... 13 
9. 
ETHICAL CONSIDERATIONS ........................................................................................................ 14 
10. 
INFORMED CONSENT ............................................................................................................. 14 
11. 
DATA OWNERSHIP................................................................................................................. 14 
12. 
PUBLICATION POLICY............................................................................................................. 14 
13. 
FUNDING AND SUPPORT ....................................................................................................... 14 
14. 
REFERENCES .......................................................................................................................... 15 
 
 
 
 
 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
6 
1. SUMMARY   
Study Title 
“Pre-implantation genetic testing for monogenic disease: single 
center experience.”  
Study code  
GIN2/OSS_001/2023 Acronym: 
PGT-M experience 
Version and Date 
Version No.1 (29/06/2023) 
Sponsor (Institution) 
Humanitas Research Hospital,  
Vía Alessandro Manzoni, 56, 20089 Rozzano MI 
Coordinating Investigator 
Paolo Emanuele Levi Setti, MD 
Product Name 
NA 
Study indication  
Efficacy of pre-implantation genetic testing for monogenic diseases in 
a single center scenario.  
Background and rationale 
From the early 1990s, preimplantation genetic diagnosis (PGD) and 
embryo biopsy became available: over the years, with the evolution of 
the technique, PGT-M has revolutionized the landscape of clinical 
genetics by decreasing the risk of transmitting a serious genetic 
disorder to patients offspring and allowing to potentially eliminate the 
disease from the population. With the term PGD, we include three 
different tests: pre-implantation genetic testing for monogenic disease 
(PGT-M), Pre-implantation genetic testing for aneuploidy (GT-A), and 
Pre-implantation for structural rearrangements (PGT-SR). PGT-M is 
used in patients who have or are carriers of a congenital disease that 
can be passed down to their offspring. Pre-implantation genetic testing 
for aneuploidy (PGT-A) is a procedure that screens embryos before 
transfer to reduce the risk of aneuploidy and chromosomal 
abnormalities. Pre-implantation for structural rearrangements (PGT-
SR) is an option for patients with an inversion, reciprocal 
translocation, or Robertsonian translocation.  
These approaches, when combined with in vitro fertilization (IVF), 
enable us to differentiate between affected and unaffected embryos. To 
achieve these biopsy results, many IVF laboratories perform 
trophectoderm cell biopsies (TE), which is the development of 
embryos up to the blastocyst stage, which occurs 5-7 days after 
fertilization. Prior to trophectoderm cell biopsies (TE), biopsies were 
performed on polar bodies or cleavage embryos.  

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
7 
It is still open to debate the disadvantage discussed in the scientific 
literature that affects the technique's efficacy due to the presence of 
mosaic embryos and whether it should be paired with PGT for 
aneuploidy (PGT-A) for more concrete results. 
 Study Objectives 
The primary objective of this retrospective observational single-center 
study is to describe the efficacy of PGT-M in a real-life setting. 
Efficacy will be evaluated in terms of live birth rate (LBR), simple and 
cumulative live birth rate (CLBR) per couple, and abortion rate (AR). 
Furthermore, investigators will consider how many cycles the 
participants need to undergo to achieve a viable blastocyst.  
 
The secondary objective is to evaluate the incidence of aneuploidy in 
tested embryos, in order to understand the need for PGTA in addition 
to PGTM. 
 
Study Endpoints/Outcomes 
For the evaluation of the study objectives, all patients that underwent 
PGTM from 2016 to 2022 will be included in the study.  
The results obtained from the PGT-M will be calculated as:  
 
Live birth rate (LBR): defined as the “the number of deliveries that 
resulted in at least one live birth, divided by the number of cycles.” 
Embryology and Alpha Scientists in Reproductive Medicine. 
Electronic address [1]  
Cumulative live birth (CLBR) per couple: defined as the “delivery 
of at least one live-born infant (>24 weeks of gestation) in the fresh or 
in the subsequent frozen-thawed cycles in relation to the number of 
oocytes retrieved per couple.” Polyzos, Drakopoulos [2] 
Abortion rate (AR): is defined as the “spontaneous demise of a 
pregnancy before the foetus reaches viability. The term therefore 
includes all pregnancy losses (PLs) from the time of conception until 
24 weeks of gestation.” Group, Vlaisavljevic [3] 
 
Aneuploid embryo rate: “the most common genetic abnormality 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
8 
resulting 
in 
embryonic 
demise, 
pregnancy 
loss, 
and 
congenital birth defects. At the preimplantation stage, ∼50% of the 
IVF-derived embryos have chromosomal abnormalities that are 
incompatible with implantation or normal fetal development.”  Hindi 
E. Stohl [4] 
 
Study design 
Monocentric retrospective observational study 
Product/Intervention 
PGT-M is an option for all patients, fertile and infertile, who are at risk 
of transmitting a monogenic disease to their offspring. PGT-A is only 
performed on unaffected embryos that have undergone PGT-M; 
therefore, investigators do not know the percentage of aneuploidy in 
affected embryos. 
Eligibility Criteria 
 
Patients fertile or infertile that have undergone preimplantation 
genetic testing for monogenic diseases (PGTM). 
No exclusion criteria will be considered.  
Study Procedures   
The information collected for the database will be retrieved from the 
Fertility Center internal web-based registry where data about 
pregnancy follow up are noted. The study database includes all PGTM 
cycles performed between 2016-2022 at the Humanitas Fertility 
Center.  
Number of patients (planned) 
All 76 patients who underwent PGTM testing in the Fertility Center 
starting from the beginning of 2016 and going through the end of 2022 
will be included in the study.  
Investigational Sites (planned)  
University affiliated 3rd level Fertility Center  
Sample size and statistical 
consideration 
Data will be described as number and percentage, if categorical, or 
mean and standard deviation, if continuous and approximately 
Gaussian, or with median and range.  
Study timetable 
• 
7 years of inclusion 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 
9 
GCP Statement: 
 
This study will be conducted in compliance with the protocol, the 
current version of the Declaration of Helsinki and applicable 
guidelines as well as all national legal and regulatory requirements.  
 
2. STUDY FLOW-CHART 
 
3. BACKGROUND  
 
 
Handyside et al. were the first to publish research on pre-implantation genetic testing for cystic fibrosis in 
1992. The study aimed to take cells from a cleavage-stage embryo and use DNA amplification to look for the 
cystic fibrosis mutation. A total of 13 embryos were biopsied from the three patients. Only one of the four 
suitable for transfer resulted in a pregnancy and the subsequent birth of a healthy baby. According to the 
study, couples have a high chance that their pregnancy will be unaffected by cystic fibrosis. As a result, pre-
implantation diagnosis was considered clinically accurate, despite it taking several years to confirm its 
accuracy.[5] 
 
A 2005 study published by McArthur et al. aimed to compare trophectoderm biopsies with their previously 
published experience with day-3 cleavage-stage embryos. They found that blastocysts have a lower 
percentage of chromosomal monosomies than cleavage-stage embryos. Meanwhile, performing a biopsy in 
the cleavage stage can arrest further development by reducing the inner cell mass, which is not the case for 
trophectoderm biopsies. Concluding that trophectoderm biopsies are a practical addition to IVF and great 
progress for PGD practices. [6] 
 
A review done by Harper et al. in 2017 explained the advantages and disadvantages of the different biopsy 
methods for pre-implantation genetic screening (PGS) and pre-implantation genetic diagnosis (PGD). Three 
stages are available for biopsy: polar bodies from oocytes, blastomeres from cleavage-stage embryos, and 
trophectoderm cells from blastocysts. The polar body is the earliest stage that can be biopsied but is limited 
by the fact that only maternal errors can be tested. The second stage is cleavage embryos, which until 
recently lost their popularity since these cells are more mosaic and the number of cells biopsied is limited. 
The majority of pre-implantation is now done at the blastocyst stage, which is already a method of selection 
as only good-quality embryos reach the blastocyst stage. The advantages of a trophectoderm biopsy are that 
the cells are less mosaic and more abundant to analyze, making the results more accurate. This review agrees 
with the outcomes of the study above: that trophectoderm biopsies are the best technique for pre-
implantation genetic testing.[7] 
 
In 2018, a study done by Zanetti et al. described the cases of PGT-M in fertile couples in a Brazilian IVF 
center and compared their results to those reported by the European Society of Human Reproduction and 
Embryology (ESHRE) Consortium PGD XIV–XV. They mentioned the prevalence of trophectoderm 
biopsies and how they have become a highly viable option due to the excellent survival rates in embryo 
culture. They obtained a 22.1% implantation rate, a 26.8% pregnancy rate, and a 7.1% miscarriage rate. 
These results were comparable with ESHRE consortium cycles. They conclude that PGT-M is a very 
feasible option for families affected by monogenic disease. [8] 
 
Procedures 
Blastocysts trophectoderm biopsy 
PGTM analysis  
567 embryos  
 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 10 
 
Goldman et al. published a study in 2016 with the goal of understanding the benefits of concurrent testing 
for both monogenic disorders and aneuploidy in a population of patients undergoing blastocyst culture, 
trophectoderm biopsy, and single gene testing, with and without aneuploidy screening.There are two goals: 
first, to quantify the incidence of aneuploidy in a population of patients undergoing trophectoderm biopsy 
and PGD for a single gene disorder, to better understand the benefits of dual-testing and the potential risk of 
not performing concomitant aneuploidy screening, and second, to determine the risk of not performing 
concomitant aneuploidy screening. Most patients (53.2%) had at least one blastocyst that was unaffected by 
monogenic disease but were affected by aneuploidy. Without screening, these unaffected but aneuploid 
embryos would have been transferred, leading to implantation failure, pregnancy loss, or a pregnancy 
affected by chromosomal aneuploidy. Therefore, the obstetrical outcomes, such as the live birth rate, were 
higher and the abortion rate was lower for those who underwent concomitant aneuploidy screening. When 
performed together with PGD, aneuploidy screening offers useful information for selecting embryos and 
significantly improves the rate of single embryo transfer. This study concluded that a significant increase in 
single embryo transfer rates between the dual-screening group and the monogenic disease-tested group 
shows that concurrent screening significantly benefits embryo selection. [9] 
 
 
 
 
 
A retrospective case-control study done by Shen et al.  had the objective of determining the application 
value of next-generation sequencing (NGS)-based pre-implantation genetic testing for aneuploidies (PGT-
A). They performed NGS-based aneuploidy screening on multiple displacement amplification (MDA) 
products of embryonic trophectoderm biopsy samples that were frozen after PGT-M with known transfer 
outcomes. A total of 76 embryos, which resulted in live birth after transfer, showed that if the patients had 
PGT-A during their PGT-M cycle, 17.1% of the embryos would have been wasted due to being diagnosed as 
affected. It can then be understood that Shen et al. along with their data, believe that PGT-A might cause 
more harm than benefit for patients undergoing IVF. [10] 
 
In a review published in 2022, Scriven et al. explored the potential harmful effect of combining PGT-M 
with PGT-A. The most recent ESHRE PGT Consortium data were incorporated. Combining testing for 
unrelated sporadic chromosomal abnormalities (PGT-A) and excluding embryos with chromosomally 
abnormal results from transfer offers the opportunity to reduce the risk of miscarriage and the number of 
embryo transfers, but it also risks excluding healthy embryos from transfer due to abnormal test results that 
do not reflect the embryo's true potential. The data was divided into two categories in the review: high-
success clinics and typical-success clinics. The clinic success groups are subjective and are based on the 
number of live births per embryo transplanted (high success is 60% PGT-MA vs. 50% PGT-M) and typical 
success is 45.6% PGT-MA (38.0% compared. PGT-M). Both success groups had identical miscarriage rates 
per clinical pregnancy. The PGT-MA live birth rate per embryo transplanted is higher (45.6% vs. 38.0%), 
demonstrating that testing for unrelated chromosomal gain or loss can help determine if an embryo is viable. 
All scenarios reveal that PGT-A reduces the chance of miscarriage just slightly at the expense of healthy live 
births. This study concludes that PGT-M without PGT-A is preferable for achieving an undamaged live 
birth. [11] 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 11 
 
3. Rationale  
From the early 1990s, preimplantation genetic diagnosis (PGD) and embryo biopsy became available: over 
the years, with the evolution of the technique, PGT-M has revolutionized the landscape of clinical genetics 
by decreasing the risk of transmitting a serious genetic disorder to patients offspring and allowing to 
potentially eliminate the disease from the population. With the term PGD we include three different tests: 
pre-implantation genetic testing for monogenic disease (PGT-M), Pre-implantation genetic testing for 
aneuploidy (PGT-A) and Pre-implantation for structural rearrangements (PGT-SR). PGT-M is used in 
patients who have or are carriers of a congenital disease that can be passed down to their offspring. Pre-
implantation genetic testing for aneuploidy (PGT-A) is a procedure that screens embryos before transfer to 
reduce the risk of aneuploidy and chromosomal abnormalities. Pre-implantation for structural 
rearrangements (PGT-SR) is an option for patients with an inversion, reciprocal translocation, or 
Robertsonian translocation.  
These approaches, when combined with in vitro fertilization (IVF), enable us to differentiate between 
affected and unaffected embryos. To achieve these biopsy results, many IVF laboratories perform 
trophectoderm cell biopsies (TE), which is the development of embryos up to the blastocyst stage, which 
occurs 5-7 days after fertilization. Prior to trophectoderm cell biopsies (TE), biopsies were performed on 
polar bodies or cleavage embryos.  
It is still open to debate the disadvantage discussed in the scientific literature that affects the technique's 
efficacy due to the presence of mosaic embryos and whether it should be paired with PGT for aneuploidy 
(PGT-A) for more concrete results. 
 
 
4. STUDY OBJECTIVES 
 
The primary objective of this retrospective observational single-center study is to describe the efficacy of 
PGT-M in a real-life setting. Efficacy will be evaluated in terms of live birth rate (LBR), simple and 
cumulative live birth rate (CLBR) per couple, and abortion rate (AR). Furthermore, investigators will 
consider how many cycles the participants need to undergo to achieve a viable blastocyst.  
 
The secondary objective is to evaluate the incidence of aneuploidy in tested embryos, in order to understand 
the need for PGTA in addition to PGTM. 
 
3.1. Endpoints  
For the evaluation of the study objectives, all patients that underwent PGTM from 2016 to 2022 will be 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 12 
included in the study.  
The results obtained from the PGT-M will be calculated as:  
 
Live birth rate (LBR): defined as the “the number of deliveries that resulted in at least one live birth, 
divided by the number of cycles.” 
 Embryology and Alpha Scientists in Reproductive Medicine. Electronic address [1]  
Cumulative live birth (CLBR) per couple: defined as the “delivery of at least one live-born infant (>24 
weeks of gestation) in the fresh or in the subsequent frozen-thawed cycles in relation to the number of 
oocytes retrieved per couple.” Polyzos, Drakopoulos [2] 
 
Abortion rate (AR): is defined as the “spontaneous demise of a pregnancy before the foetus reaches 
viability. The term therefore includes all pregnancy losses (PLs) from the time of conception until 24 weeks 
of gestation.” Group, Vlaisavljevic [3] 
 
Aneuploid embryo rate: “the most common genetic abnormality resulting in embryonic demise, pregnancy 
loss, and congenital birth defects. At the preimplantation stage, ∼50% of the IVF-derived embryos 
have chromosomal abnormalities that are incompatible with implantation or normal fetal development.” 
Hindi E. Stohl [4] 
4. STUDY POPULATION 
4.1. Inclusion criteria  
The study will include all fertile or infertile patients undergoing PGT analysis for monogenic 
diseases.  
 
4.2. Exclusion criteria 
No group will be excluded from this study.  
 
4.3.  Recruitment 
The study sample will include retrospectively all patients who have undergone PGTM, matching the 
inclusion and exclusion criteria cited above. Data of children included in the study are retrieved from the 
database of Reproductive Medicine Unit (Fertility Center) in which their mothers information about the 
IVF cycle and results of PTGM are recorded.  
 
5. STUDY ASSESSMENT  
The study is not associated with any adverse effects or risks. 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 13 
 
 
 
6. STATISTICAL CONSIDERATIONS  
6.1. Sample size 
For the purpose of the study all the children born from single thawed embryos in Fertility Center from the 
beginning to 2016, will be included in the study, and the sample is 567.  
 
6.2. Analysis 
Data will be described as number and percentage, if categorical, or mean and standard deviation, if 
continuous and approximately Gaussian, or with median and range, otherwise. Adherence to Gaussian 
distribution will be checked with Shapiro Wilks test.  
 
 
7. QUALITY ASSURANCE AND CONTROL  
7.1. Data handling and record keeping /archiving 
The investigator must keep the documents on file for at least 7 years after completion or discontinuation of 
the study. After that period, the documents may be destroyed, subject to local regulations. Before proceeding 
to documents’ destruction, sites must inform the Coordinating Investigator/delegate in writing.  
Should the investigator wish to assign the study records to another party or move them to another location, 
the Coordinating Investigator/delegate must be notified in advance.  
 
7.2. Case Report Forms  
Data will be collected and included in a Microsoft Excel sheet. For each patient negative or affirmative 
answer will be registered for each of the 567 cycles. The investigator at each site will ensure the 
accuracy, completeness, and timeliness of the data. The data will be collected anonymously, and 
patients will be identified in the database with successive numbers. Participants will not be identified 
in the CRF by name or initials and birth date and appropriate coded identification will be used. 
 
7.3. Source documents  
Source data must be available at the site to document the existence of the study participants. Source data 
include the original documents relating to the study, as well as the medical treatment and medical history of 
the participant. 
 
8. CONFIDENTIALITY OF PATIENT RECORDS 
The investigator assures that patients’ anonymity should be maintained and that their identities are protected 
from unauthorized parties. Particular attention should be paid whenever patient data are supplied to third 
parties and may be autonomously processed.  
The investigator should keep in a confidential way a patient identification log recording both patient code 
and name. The investigator should also maintain patients’ written consent forms, in strict confidence (i.e., 
not for submission to the Coordinating Investigator).  
Any investigator and/or research staff member who has a conflict of interest with this study (such as patent 
ownership, royalties, or financial gain greater than the minimum allowable by their institution) must fully 
disclose the nature of the conflict of interest.  

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 14 
   
9. ETHICAL CONSIDERATIONS 
The responsible investigator ensures that this study is conducted in agreement with this protocol, the Good 
Clinical Practice, the current version of Declaration of Helsinki and the applicable regulations. 
The protocol and any amendments are subject to review and approval by the competent Independent Ethics 
Committee(s) (“IEC”). 
 
10. INFORMED CONSENT 
Documented informed consent to access patients’ information after fertility treatment for research purposes 
has been obtained before fertility treatment. Informed consent signed by the patient allows the staff of 
Fertility Center to recontact telephonically patients to collect further information about pregnancy evolution 
and follow up. The written informed consent form has been signed and personally dated by the patient or by 
the patient’s legally acceptable representative, and by a medical doctor employed in the Fertility Center.  
Moreover, during recruitment, all patients will be informed of the aims of the study. Verbal consent will be 
collected to gather information about the children considered; the patient is free to deny consent to answer all 
or any question. Participation is voluntary and does not prejudice the patient’s subsequent care.  
Patients will be informed as to the strict confidentiality of collected data.  
 
11. DATA OWNERSHIP 
Istituto Clinico Humanitas is the owner of the data resulting from the study. All centers and investigators 
participating in the study should be made aware of such circumstances and not disseminate information or 
data without the prior written consent by Istituto Clinico Humanitas. 
 
12. PUBLICATION POLICY 
After completion of the study, the Coordinating Investigator prepares a draft manuscript containing results of 
the study based on the statistical analysis. The manuscript is delivered to the co-authors for comments and 
then sent to a scientific journal for publication. 
All publications, abstracts, presentations, manuscripts, and slides - issued by the Investigators of the 
collaborative sites and including data from the present study- should be submitted to and reviewed by the 
Coordinator Investigator at least 3 (three) weeks in advance the planned date for the submission to the 
scientific journal.  
 
13. FUNDING AND SUPPORT 
NA 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 15 
 
 
 
 
 
15. REFERENCES 
 
1. 
Embryology, E.S.I.G.o. and c.b.g.i. Alpha Scientists in Reproductive Medicine. Electronic address, 
The Vienna consensus: report of an expert meeting on the development of ART laboratory 
performance indicators. Reprod Biomed Online, 2017. 35(5): p. 494-510. 
2. 
Polyzos, N.P., et al., Cumulative live birth rates according to the number of oocytes retrieved after 
the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter 
multinational analysis including approximately 15,000 women. Fertil Steril, 2018. 110(4): p. 661-
670 e1. 
3. 
Group, E.C.P.W., et al., The Maribor consensus: report of an expert meeting on the development of 
performance indicators for clinical practice in ART. Hum Reprod Open, 2021. 2021(3): p. hoab022. 
4. 
Hindi E. Stohl, L.D.P., 147 - Introduction to Aneuploidy,, in Obstetric Imaging: Fetal Diagnosis and 
Care (Second Edition),, M.E.D.A. Joshua A. Copel, Helen Feltovich, Eduard Gratacós, Deborah 
Krakow, Anthony O. Odibo, Lawrence D. Platt, Boris Tutschek,, Editor. 2018, Elsevier. p. 596-598. 
5. 
Handyside, A.H., et al., Birth of a normal girl after in vitro fertilization and preimplantation 
diagnostic testing for cystic fibrosis. N Engl J Med, 1992. 327(13): p. 905-9. 
6. 
McArthur, S.J., et al., Pregnancies and live births after trophectoderm biopsy and preimplantation 
genetic testing of human blastocysts. Fertil Steril, 2005. 84(6): p. 1628-36. 
7. 
Harper, J.C., Preimplantation genetic screening. J Med Screen, 2018. 25(1): p. 1-5. 
8. 
Zanetti, B.F., et al., Preimplantation genetic testing for monogenic diseases: a Brazilian IVF centre 
experience. JBRA Assist Reprod, 2019. 23(2): p. 99-105. 
9. 
Goldman, K.N., et al., Preimplantation Genetic Diagnosis (PGD) for Monogenic Disorders: the 
Value of Concurrent Aneuploidy Screening. J Genet Couns, 2016. 25(6): p. 1327-1337. 
10. 
Shen, X., et al., Evaluating the application value of NGS-based PGT-A by screening cryopreserved 
MDA products of embryos from PGT-M cycles with known transfer outcomes. J Assist Reprod 
Genet, 2022. 39(6): p. 1323-1331. 
11. 
Scriven, P.N., Combining PGT-A with PGT-M risks trying to do too much. J Assist Reprod Genet, 
2022. 39(9): p. 2015-2018. 
 
 
 
 
 
 
 
 
 
 

 
 
GIN2/OSS_001/2023 
Effective date: 
29/06/2023 
Version no: 01 
 
 16