A Randomized, Prospective, Single-center, Controlled, Single-blind Study to Evaluate the Impact of Standardization of Variable Embryo Transfer Conditions in a Medically Assisted Procreation Procedure in Humans on the Effectiveness of the Procedure, by Using: Standardization of Culture Conditions and Selection of Embryo for Transfer Through the Use of an Incubator With a Time-lapse Observation System and AI, an Embryopass-electronically Controlled Device for Controlled ET, and the Embryocase Device Maintaining Optimal Environmental Conditions for the Embryo Outside the Incubator During ET Time
Phase: NA
Conditions: Infertility (IVF Patients), Infertility, ART
Sponsor: Przychodnia Lekarska nOvum Katarzyna Kozioł, Piotr Lewandowski sp.k.

 
CONFIDENTIAL DOCUMENT 
PRZYCHODNIA LEKARSKA NOVUM 
PROTOCOL OF THE THERAPEUTIC EXPERIMENT "Standardization of 
variable conditions of embryo transfer into the uterine cavity in the procedure 
of medically assisted procreation in humans" 
EMBRYO PASSPORT/ EMBRYOCASE  A randomized, prospective, single-center, 
controlled, single-blind study to evaluate the impact of standardization of variable 
embryo transfer conditions in a medically assisted procreation procedure in humans 
on the effectiveness of the procedure, by using: standardization of culture 
conditions and selection of embryo for transfer through the use of an incubator with 
a time-lapse observation system and artificial intelligence, an Embryopass 
applicator -  electronically controlled device for controlled transfer, and the 
Embryocase case maintaining optimal environmental conditions for the embryo 
outside the incubator during the peri-transfer time. 
ACRONYM: EFECT 
Principal Investigator: Katarzyna Kozioł, MD  
Research team: Sylwia Trubacz, MSc, Ewa Stachowiak, PhD, Karolina Hardej, 
MSc, Karolina Kubiak, MSc, Karolina Leśniewska, Bartosz Sierakowski, MSc, Piotr 
Lewandowski, MD, Jan Lewandowski, MD, Dominika Puchta, MD, Iwona Sowińska-
Torz, MD, Janusz Wojewódzki, MD, Karolina Lao, MSc, Aleksandra Wiktorzak, 
MSc, Magda Molenda, MSc 
 
Przychodnia Lekarska nOvum 
2026-01-01 
 
 Therapeutic experiment - In accordance with the Act on the Professions of Doctor 
and Dentist (Journal of Laws of 2008 No. 136, item 857), a clinical trial is classified as 
a medical experiment. The Act distinguishes between two types of medical 
experiments - a therapeutic experiment and a research experiment, hence the term 
study or therapeutic experiment will be used interchangeably in the further part of the 
protocol. 
 

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1 
Table of contents 
 
1. ABSTRACT .......................................................................................................................3 
2. LIST OF TABLES ............................................................................................................ 11 
3. LIST OF DIAGRAMS ....................................................................................................... 11 
4. ABBREVIATIONS USED ................................................................................................. 11 
5. INTRODUCTION .............................................................................................................. 12 
5.1. Literature review ...................................................................................................................... 12 
5.2 Subject of the study ................................................................................................................. 17 
5.2.1 Embryopass – electronically controlled device for controlled embryo transfer ....... 17 
5.2.2 
Case EMBRYOCASE ................................................................................................ 20 
5.2.3 Innovative protocol for standardization of the embryo transfer procedure time-lapse 
(AI)/ Embryopass/Embryocase ................................................................................................. 21 
5.3 Justification for conducting the study .................................................................................... 21 
5.4 Risks and benefits .................................................................................................................... 22 
6. OBJECTIVES OF THE STUDY ........................................................................................ 23 
6.1 Effectiveness ............................................................................................................................ 23 
6.2 Safety ......................................................................................................................................... 24 
6.3 Usability ..................................................................................................................................... 24 
7. STUDY DESIGN .............................................................................................................. 25 
8. GROUP EXAMINED ........................................................................................................ 26 
8.1 Female patients ........................................................................................................................ 26 
8.1.1 Description of the population .......................................................................................... 26 
8.1.2 Number of patients ........................................................................................................... 28 
8.1.3. Study Region .................................................................................................................... 28 
8.2 Criteria for the selection of patients for the study................................................................ 28 
9. TEST PROCEDURES (METHODOLOGY) ....................................................................... 29 
9.1 Informed consent of patients to participate in the study .................................................... 29 
9.2 Blinding/Unblinding the Test................................................................................................... 29 
9.2.1 Emergency Blinding ......................................................................................................... 30 
9.3 Screening .................................................................................................................................. 30 
9.4 Synchronization of the endometrium with embryonic age ................................................. 31 
9.5 Defrosting embryos .................................................................................................................. 31 
9.6 Evaluation of embryos after thawing ..................................................................................... 32 
 

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9.7 Randomization .......................................................................................................................... 32 
9.8 Transfer visit ............................................................................................................................. 32 
9.9 βhCG Visit ................................................................................................................................. 36 
9.10 Visit – confirmation of clinical pregnancy ........................................................................... 36 
9.11 Termination of pregnancy ..................................................................................................... 37 
10. PARAMETERS TO BE ANALYSED IN THE STUDY ..................................................... 38 
10.1 Demographics ........................................................................................................................ 38 
10.2 Body Measurements ............................................................................................................. 38 
10.3 Medical history ....................................................................................................................... 38 
10.4 Cause of infertility .................................................................................................................. 38 
10.5 Evaluation of the menstrual cycle ....................................................................................... 39 
10.6 Obstetric Interview ................................................................................................................. 39 
10.7 Readiness to receive embryos after thawing .................................................................... 39 
10.8 Embryo Quality ....................................................................................................................... 39 
10.9 Transfer Procedure ................................................................................................................ 39 
10.10 Concomitant medications ................................................................................................... 39 
10.10.1 Permitted medications/therapies................................................................................ 39 
10.10.2 Prohibited medications/therapies ............................................................................... 40 
10.11 Endometrial thickness ......................................................................................................... 40 
10.12 Transfer Procedure ............................................................................................................. 40 
11. END OF THE STUDY ..................................................................................................... 40 
11.1 Study Completion................................................................................................................... 40 
11.2 Withdrawal of consent ........................................................................................................... 41 
11.3 Discontinuation ....................................................................................................................... 41 
11.4 Reasons for discontinuation of a clinical trial by a facility ................................................ 41 
12. PARAMETERS TO BE ANALYSED OUTSIDE THE STUDY ........................................ 42 
13. ADVERSE EVENTS ....................................................................................................... 42 
13.1 Definition ................................................................................................................................. 42 
13.2 Scope and method of collecting data on adverse events ................................................ 42 
14. SERIOUS ADVERSE EVENTS ...................................................................................... 43 
14.1 Definition ................................................................................................................................. 43 
14.2 Scope and method of collecting data on serious adverse events .................................. 43 
15. METHOD OF DATA COLLECTION AND PROCESSING .............................................. 44 
15.1 Source data ............................................................................................................................ 44 

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15.2 Electronic Database - eCRF ................................................................................................ 44 
16. DEVIATIONS FROM THE PROTOCOL ......................................................................... 44 
17. MONITORING ................................................................................................................ 44 
18. LEGAL AND ETHICAL REGULATIONS ....................................................................... 45 
19. REPORTING AND PUBLICATIONS .............................................................................. 45 
20. PROTECTION OF PERSONAL DATA ........................................................................... 45 
21. LITERATURE ................................................................................................................. 45 
22. ANNEXES ...................................................................................................................... 46 
 
1. ABSTRACT 
STUDY TITLE 
A randomized, prospective, single-center, controlled, single-blind study to evaluate 
the impact of standardization of variable embryo transfer conditions in a medically 
assisted procreation procedure in humans on the effectiveness of the procedure, by 
using: standardization of culture conditions and selection of embryo for transfer 
through the use of an incubator with a time-lapse observation system and artificial 
intelligence, an Embryopass applicator -  electronically controlled device for 
controlled transfer, and the Embryocase case maintaining optimal environmental 
conditions for the embryo outside the incubator during the peri-transfer time. 
ACRONYM: 
EFECT 
STUDY PRODUCT 
1. Embryocase case maintaining optimal environmental conditions for the 
embryo in which the embryo is placed in the peritransfer time outside the 
incubator (36.5oC – 37.5oC); 
2. Embryopass Applicator - an electronically controlled device for controlled 
embryo transfer; 
3. Protocol for standardization of embryo transfer conditions 
TL(AI)/EMBRYOCASE/EMBRYOPASS. 
STUDY PHASE 
NOT APPLICABLE 
RESEARCH CENTER 
Clinic Lekarska nOvum ul Bociania 13, 02-807 Warsaw, Poland 

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OBJECTIVES OF THE STUDY 
EFFECTIVENESS 
• PRIMARY PURPOSE 
The key objective of the study is to confirm the positive impact of 
standardization of the parameters of the embryo transfer procedure variables 
on its effectiveness 
1. Percentage of biochemical pregnancies  
The indicators confirming the achievement of the primary goal will be: 
a. confirmation of the positive impact of standardization of the environmental 
conditions in which the embryo is located outside the incubator during the 
peritransfer time will be an increase in the percentage of pregnancies (βhCG 
result indicating pregnancy 10-15 days after embryo transfer) in the group 
of patients in whom ET was performed with the help of the Embryocase 
case by 10% compared to the control group; 
b. confirmation of the effectiveness of the Embryopass applicator – achieving 
at least the same percentage of pregnancies (criteria as above) in the group 
of patients in whom ET was performed with the help of the Embryopass 
applicator in relation to the control group; 
c. confirmation of the effectiveness of standardization of variable conditions in 
the ET procedure (environmental changes and the human factor) will be an 
increase in the percentage of pregnancies (criteria mentioned above) in the 
group of patients in whom ET was performed with the help of the 
Embryocase case in combination with the Embryopass applicator compared 
to the control group by 15%. 
2. Percentage of clinical pregnancies in all groups of patients (visible 
gestational follicle at 25 - 35 days after ET). 
• SECONDARY PURPOSE 
The secondary objective of the study is: 
1. confirmation of the beneficial impact of standardization of 
parameters and conditions of the ET procedure on its effectiveness  
achieved thanks to the use of the Embryocase case and the Embryopass 
applicator – an electronically controlled device for controlled embryo 
transfer by: obtaining an increased percentage of implantation 

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(percentage of implanted embryos) – visible pregnancy follicle in 
ultrasound 25-35 days after ET in the group of patients in whom ET was 
performed with the help of the Embryocase case,  Embryopass applicator, 
and Embryocase in combination with Embryopass compared to a control 
group in which ET was performed according to the standard procedure 
adopted at the center (manually).  
• SECONDARY OBJECTIVE (AFTER COMPLETION OF THE STUDY) 
1. estimating the impact of using the Embryocase case and the 
Embryopass applicator separately and in combination on the 
percentage of live births – LBR (after completion of the study). 
SAFETY 
• Estimation of the safety profile of the use of the Embryocase case and the 
Embryopass applicator in the ET procedure (the rate of adverse events during 
transfer in the study group and control groups). 
USABILITY 
• Evaluation of the convenience of using the Embryocase case and the 
Embryopass applicator by an embryologist and a doctor (questionnaire - 
answer to 5 questions). 
• Evaluation of the repeatability of the standardization procedure - the time of 
embryo collection and the time of embryo administration Embryopass vs. 
manual transfer. 
 STUDY PLAN 
A randomized, prospective, single-center, controlled, single-blind study evaluating 
the impact of standardization of variable embryo transfer conditions in a medically 
assisted procreation procedure in humans on the effectiveness of the procedure, by 
using: standardization of culture conditions and selection of embryo for transfer by 
using an incubator with a time-lapse observation system and artificial intelligence, 
use of an applicator Embryopass - an electronically controlled device for controlled 
transfer, the use of the Embryocase case maintaining optimal environmental 
conditions for the embryo outside the incubator during the peritransfer time and the 
combination of all elements into one innovative embryo transfer protocol is to 
demonstrate an increase in the percentage of biochemical, clinical and implantation 
pregnancies in patients undergoing cryotransfer of the embryo at the blastocyst 

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stage, for whom this will be the first transfer, or the second if The previous one ended 
with pregnancy and the birth of a child.  
Patients who have frozen embryos at the blastocyst stage - at least 1 good quality, 
3BB (bl3.1.1) or more, have not had a fresh transfer due to contraindications, this 
will be their first transfer at all or the first after an effective previous one, embryo 
culture was carried out in the Time Lapse incubator with AI. Once included in the 
study, embryos will be thawed in the order consistent with the highest AI rating. 
Screening  of patients will take place within 60 days prior to randomisation. Study 
candidates will be assessed by the investigator at the screening visit for compliance 
with the study inclusion and study exclusion criteria. 
Preparation for the transfer of a thawed embryo will take place in the ovulatory 
cycle - natural or induced letrozole. Once ovulation is confirmed in an ultrasound 
and/or hormonal examination, a temporarily synchronized embryo thawing will be 
ordered.  
Randomization will take place on the day of CRIO-ET, i.e. on the 5th day after 
ovulation, counting the day of follicle rupture as day 0, confirmation of ovulation by 
the occurrence of the LH peak (LH peak day + 6 days), or by the administration of 
chorionic gonadotropin on the day of confirmation of the presence of the preovulatory 
follicle 17-22 mm, HCG drug (HCG administration day +7 days). Patients who meet 
all inclusion criteria and do not meet any of the exclusion criteria will be enrolled in 
the study (randomised). Randomization will be  randomized on a 1:1:1:1 basis, the 
same number of patients will be assigned to the control group and each of the three 
study groups. 
Embryo transfer of a thawed embryo (CRIO-ET) will be performed on day 5 after 
ovulation or LH+6, or HCG+7. Only one good quality embryo is allowed to be 
administered, as indicated by the AI. Key aspects of embryo transfer, both manually 
and with the use of the Embryocase case and the Embryopass applicator, will be 
standardized. Soft catheters (Cook symbol K-JETS-7019-ET) will be used for the 
transfer. Embryo transfer will be performed under ultrasound guidance, and the 
embryo will be placed 1.5-2 cm from the bottom of the uterus. The time from 
complete embryo acquisition to the catheter to the completion of the transfer must 
not exceed 2 minutes. During the transfer, the time of embryo collection and 
administration from the catheter to the uterine cavity will be subject to additional 

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evaluation and comparison – manually vs. with the Embryopass applicator. 
Immediately after embryo administration, the catheter will be withdrawn from the 
uterus and examined under a microscope. Once it is confirmed that the embryo has 
not been left in the catheter, the doctor will remove the speculum. After the transfer 
is complete, the patient will get up and leave the transfer room. 
Supplementation of the luteal phase In order to supplement the luteal phase, 
patients will use progesterone starting from the day of ovulation +1 until the visit (25 
- 35 days after ET) Duphaston orally 3x1 tabl. and 10 mg plus Cyclogest 2x400 mg 
globules vaginally according to the regimen used in the center. On the day of the 
appointment 25-35 days after CRIO-ET, your doctor will decide whether to continue 
using progesterone or exclude it.  
Confirmation of pregnancy will  occur at the βhCG visit 10-15 days after ET by 
determining the level of βhCG in the blood serum. In the absence of pregnancy 
(ꞵhCG ≤ 5.3 mIU/ml), the patient will stop taking progesterone and end the test, while 
in the case of confirmation of pregnancy, the patient will continue to take 
progesterone continuously until the clinical pregnancy is confirmed. 
Confirmation of clinical pregnancy  will  occur at the visit 25-35 days after ET in 
all patients who tested positive for βhCG. Confirmation of clinical pregnancy or its 
absence ends the examination. 
Termination data (GEU, miscarriage or childbirth) will be collected from patients in 
the form of a questionnaire that the patient can send to the center or provide the 
information contained in it by phone to one of the members of the study team after 
the patient completes the study. 
PLANNED NUMBER OF PATIENTS 
The total number of patients enrolled in the study (randomized) is expected to be 
160.  
Randomization will be based on a 1:1:1:1 basis. This means that 40 patients will be 
placed in the control group and each of the three groups of subjects. 
TL/AI control group – CRIO-ET manual 
research group 1 TL/AI – CRIO-ET manual + EMBRYOCASE 
study group 2 TL/AI – CRIO-ET using EMBRYOPASS 
research group 3 TL/AI – CRIO-ET using EMBRYOPASS + EMBRYOCASE 
CRITERIA FOR THE SELECTION OF PATIENTS FOR THE STUDY 

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INCLUSION CRITERIA: 
1. The patient and her partner gave written, informed consent to participate in 
the clinical trial. 
2. The patient underwent a medically assisted procreation procedure using 
IVF or ICSI in accordance with the applicable law, did not have a fresh 
transfer, has all frozen embryos in the blastocyst stage, of which at least 1 
is of good quality 
3. You and your partner are not currently taking part in or have not participated 
in any other clinical trial in the last 6 months. 
4. The patient's age on the day of screening ranges from ≥18 to ≤38 years. 
5. The patient's BMI on the day of screening ranges from ≥18 to < 30. 
6. Both partners have normal infectious tests performed 6 months before ET 
and bacteriological tests performed one month before ET.  
7. The patient has had IVF or ICSI embryo culture performed in an incubator 
with a Time Lapse monitoring system and an Artificial Intelligence system 
(or if not, the embryo will be placed in the EmbryoScope after thawing) and 
has not had a fresh transfer (all embryos after stimulation and puncture have 
been frozen), and after thawing she has at least 1 good quality blastocyst 
evaluated before freezing by an embryologist as a good quality blastocyst 
or bl class. 3.2.2. The embryos have also been evaluated by AI prior to 
freezing and will be thawed in the future in order of the highest AI-confirmed 
rating. 
8. The patient has a normal uterus and endometrium at least 7 mm on ET. 
9. The patient must be prepared for cryotransfer in the ovulatory cycle with 
natural or induced letrozole, and after ovulation in the current cycle, take a 
progesterone preparation at the doses specified above for luteal phase 
supplementation. 
10. On the day of transfer (5th day after ovulation), the patient must have at least 
one thawed, developed embryo of good quality – pre-frozen blastocyst 3.2.2 
thawed according to the highest AI rating. 
11. The patient must be qualified by the doctor for the procedure  
embryo transfer on day 5 after ovulation. 

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12. Embryo transfer was performed without general anesthesia or other 
procedures and/or additional antispasmodic drugs prior to transfer (e.g. 
oxytocin antagonist) with the exception of routine preparation (drotaverine 
1 table and 20 mg p.o. per hour prior to transfer). 
 
EXCLUSION CRITERIA: 
1. Failure to meet the inclusion criteria.  
2. The patient was found to have abnormalities in the anatomical structure of 
the uterus and reproductive tract, which, according to the researcher, could 
reduce the chances of getting pregnant. 
3. The patient was diagnosed with endometrial polyp(s). 
4. The patient was diagnosed with submucosal or intramural uterine fibroids. 
5. The patient was diagnosed with fallopian tube hydromas. 
6. The patient was diagnosed with ≥3 endometriosis.  
7. The patient or her partner is a carrier of a genetic defect that may have an 
impact on lowering fertility. 
8. The patient or her partner is currently or has been undergoing cancer 
treatment in the past, which may have had a negative impact on fertility. 
9. The patient has had 1 unsuccessful embryo transfer in the past, which 
means no clinical pregnancy. 
10. During the trial transfer in the preceding cycle, difficulties in entering the 
uterine cavity (the so-called difficult transfer) were found or if the patient had 
had an embryo transfer in the past and it was described as difficult, even if 
she became pregnant as a result. 
11. Embryos are formed from eggs after PBB (polar body biopsy) of oocytes 
have been examined or have undergone genetic testing of embryos. 
12. The embryos were formed from oocytes after cryopreservation. 
13. Semen was obtained for a procedure other than normal ejaculation 
(retrograde bladder ejaculation, epididymis biopsy, testicular biopsy, M-
TESE). 
14. The patient did not take progesterone for luteal phase supplementation. 
15. Inability to perform embryo transfer on day 5 after ovulation due to medical 
or random reasons. 

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16. The patient has indications for general anesthesia or pre-transfer 
antispasmodic procedure/medication (oxytocin receptor antagonist other 
than Drotaverine, or others that may affect implantation (intralipid, 
neupogen, and other significant in the investigator's judgment). 
17. The patient is to have an incision made in the AH areola before the ET 
procedure. 
18. The patient wants to have Embryoglue used for transfer. 
19. The patient takes heparin, Clexane, Acesan, Relanium drugs on and after 
embryo transfer. 
DATA ANALYTICS AND STATISTICS 
The data obtained in the study, which will be subjected to comparative analysis in 
the control group and each of the study groups: 
PRIMARY PURPOSE 
1. pregnancy rate - βhCG result indicating pregnancy 10-15 days after ET; 
2. percentage of clinical pregnancies - visible pregnancy follicle on ultrasound 
25-35 days after ET; 
SECONDARY PURPOSE 
1. implantation rate (percentage of implanted embryos) – visible pregnancy 
follicle on ultrasound 25-35 days after ET;  
SECONDARY OBJECTIVE (AFTER COMPLETION OF THE STUDY) 
1. Percentage of live births (LBR) in the control group and each of the study 
groups  
SAFETY 
Estimation of the safety profile of the use of the Embryocase case and the 
Embryopass applicator in the ET procedure (the rate of adverse events during 
transfer in the study group and control groups). 
STATISTICAL ANALYSIS 
Statistical analysis of the results will be carried out using the t-Student test for 
constant variables and the chi-square test for categorical variables. All data will be 
presented as mean ± standard deviation. A p value of < 0.05 will be considered 
statistically significant. It is possible to introduce additional statistical methods by the 
decision of the statistician. 
PLANNED USE OF RESULTS  

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After obtaining partial results and completing the study, its results will be presented 
during industry conferences in Poland and abroad in the field of infertility treatment, 
the key ones being: PTMRiE (Polish Society of Reproductive Medicine and 
Embryology) Congress, ESHRE Annual Meeting of the European Society of Human 
Reproduction and Embryology (ESHRE); It is planned to publish the results in an 
industry journal, as well as patent protection for EMBRYOCASE and the 
TL/EMBRYOPASS/ EMBRYOCASE protocol. Ultimately, the center plans to 
implement the inventions on the medical market in Poland and abroad, seeing 
numerous benefits for patients resulting from the standardization of the embryo 
transfer procedure, as well as for infertility treatment centers (description in the 
justification for conducting the study). 
2. LIST OF TABLES 
Table 1. Classification of embryos on day 3 according to PTMRiE. 
Table 2. Classification of embryos on day 5 according to PTMRiE. 
3. LIST OF DIAGRAMS 
Diagram 1 - study design 
Diagram 2 – diagram of the course of the visits covered by the study 
4. ABBREVIATIONS USED 
AE 
Adverse Event 
Adverse event 
AH 
Assisted hatching 
Incision of the transparent sheath of the 
embryo 
AI 
Artificial Intelligence 
Artificial Intelligence 
βhCG 
Β-human 
chorionic 
gonadotropin 
Human chorionic gonadotropin β subunit 
BMI 
Body Mass Index 
Body Mass Index 
CRIO-ET 
Cryotransfer 
Embryo transfer of a thawed embryo 
E2 
Estradiol 
Estradiol 
Embryocase Embryocase 
A 
case 
that 
maintains 
optimal 
environmental conditions for an embryo 
placed in a catheter outside the incubator 
during the peritransfer time (nOvum's own 
invention) 

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5. INTRODUCTION 
5.1. Literature review 
The treatment process using advanced assisted reproduction techniques is multi-stage 
and complex. It usually consists of the following stages: diagnosis and preparation of 
patients for the treatment process, controlled hormonal stimulation of the ovaries to 
obtain more eggs (oocytes) than in the natural cycle, acquisition and preparation of 
sperm, collection of oocytes (oocytes) through ovarian puncture, in vitro fertilization of 
egg cells, in vitro embryo culture, transfer of embryos into the uterine cavity, freezing 
of the remaining embryos for future use. Embryo transfer is an integral, final and 
perhaps decisive element of the entire process of in vitro fertilization treatment. The 
effectiveness of infertility treatment, determined at the level of 25-35% of pregnancies 
achieved after embryo transfer, has long aroused the interest of researchers who are 
Embryopass Embryopass 
Electronically 
controlled 
device 
for 
controlled embryo transfer - an invention of 
the nOvum clinic, constructed as part of the 
RPMA.01.02.00-14-5674/16 project. The 
applicator was tested on an animal model, 
obtaining a high 
pregnancy and birth rates. Industrial design 
reservation, patent, and CE1434-MDD-089 
certificate certifying compliance with the 
requirements 
for medical 
devices 
in 
accordance with EEC/93/42 Directive 
ET 
 
Embryo Transfer 
 
Embriotransfer 
 
ICSI 
Intra-Cytoplasmic 
Sperm Injection 
Docytoplasmic sperm injection 
IVF 
In vitro Fertilization 
The classic method of in vitro fertilization 
P4 
Progesterone 
Progesterone 
UAE 
Serious Adverse Event 
Serious adverse event 
TL 
Time Lapse   
Time-lapse imaging system 
Ultrasound 
Ultrasound Guide 
Visualization with ultrasound 

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looking for additional elements that can improve it and increase the effectiveness of in 
vitro fertilization treatment. The main cause of failures is considered to be spontaneous 
genetic errors occurring both in embryonic development in nature and in vitro, 
preventing the proper development of embryos and its final inhibition; these errors 
cannot be eliminated. The lack of pregnancy, despite the proper development of 
embryos, can also be caused by hormonally unprepared endometrium of the uterus or 
lack of synchronization of embryo development with endometrial development. 
Individualization of transfers, diagnostics of the so-called "implantation window" or 
performing transfers of thawed embryos in natural cycles are procedures that can 
increase the chance of success of the treatment process. Numerous studies conducted 
over the last decade see the reasons for the limited effectiveness of infertility treatment 
using the assisted reproduction method, among other things, in the transfer technique 
itself, and this stage of the procedure of infertility treatment using the assisted 
reproduction method has become the subject of particular interest of the nOvum 
medical clinic team. Success in the form of a pregnancy depends on the elimination of 
errors and the optimization of each of the stages of treatment. Embryo transfer is a 
stage of treatment that can still be improved and optimized, especially since it is 
estimated that about 30% of failures result from poor transfer technique. 
Description of the procedure of embryo transfer into the uterine cavity (embryo 
transfer) performed manually: 
Embryo transfer is a multi-stage and complex procedure. To perform it, special 
catheters (catheters) tightly connected to a syringe are used.  
The embryo transfer procedure can be divided into individual stages: 
• preparing the patient for embryo transfer through ultrasound examination and 
performing a trial transfer procedure (with an empty catheter without embryos) 
to verify that entry through the cervix into the uterine cavity is easy and to assess 
the length and direction of the uterine cavity as well as the cervix; 
• synchronization of the endometrium with the age of embryos;  
• preparation of the patient before the transfer, cleaning the cervical canal of 
cervical mucus to avoid possible blockage of the transfer catheter and 
preventing the delivery of embryos into the uterine cavity or the penetration of 
part of the cervical mucus into the cavity and disruption of the embryo 
implantation process; 

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• proper collection of embryos into the transfer catheter by the embryologist, 
which is an extremely important element of the entire procedure. There are 
several methods – you can collect embryos directly from drops from the medium 
or transfer them to a transfer dish from which they are taken into a catheter, but 
studies have not shown any differences in the percentage of pregnancies. The 
technique of collecting embryos into the catheter may also differ in the volume 
of fluid collected with the embryo; Scientific studies suggest that too much or 
too little fluid volume can negatively affect the transfer result, however, data on 
the volume of the medium are conflicting. Another issue is the collection of air 
bubbles (markers) into the catheter along with the medium (fluid in which the 
embryos are grown), which are to help move the embryos in the catheter, and 
the visualization of this process in ultrasound. However, even in this matter, no 
significant differences were found in the percentage of pregnancies. The 
researchers suggest that the density of the transfer medium, the choice of 
syringe type, the type of catheter, and the speed at which embryos are taken 
into the catheter may be key factors in the process of embryo uptake into the 
catheter; 
• insertion of a leading catheter into  the uterine cavity – involves inserting a 
transfer catheter through the internal cervical outlet into the uterine cavity just 
behind the internal outlet; 
• visualization of the embryo transfer process using an ultrasound machine – this 
is not an element necessary for the proper conduct of the procedure, but it is 
very helpful. It allows you to visualize the woman's reproductive organ, allows 
you to assess both possible anatomical obstacles and the right depth to which 
the catheter should be inserted into the uterine cavity without causing damage 
to the mucous membrane or stimulating it to excessive contraction. It allows you 
to visualize the entire transfer process - the movement of embryos marked with 
air bubbles from the catheter to the inside of the uterine cavity;  
• Proper embryo transfer - performed by a doctor with the assistance of an 
embryologist, consists in inserting a guide catheter, a catheter containing 
embryos suspended in the transfer medium, the so-called embryonic catheter, 
into the previously inserted uterine catheter. This is a key stage of the entire 
embryo transfer process – if performed incorrectly, it reduces the chances of 
success. After inserting the guide catheter, the operating doctor places the 

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embryonic catheter in it and gently moves it inside the uterus. After making sure 
during the visualization in the ultrasound examination that the embryonic 
catheter is located in the optimal place of the uterine cavity, the operator presses 
the plunger of the syringe connected to the embryonic catheter and carefully, 
by pressing on the plunger, initiates the movement of embryos from the catheter 
to the inside of the uterine cavity. Once the maximum resistance of the plunger 
has been reached and the last marking marker (air follicle) remains in the uterine 
cavity, the doctor retracts the catheters from the cavity. Retracting the 
embryonic catheter too abruptly or releasing pressure on the plunger can pull 
the embryos back into the catheter, while administering the embryos too 
abruptly can cause damage to the embryos. The catheter can be withdrawn 
from the uterus immediately after embryo administration or with a delay of 
approx. 30 seconds; research on this issue does not report significant 
differences in the number of clinical pregnancies achieved; 
• Checking the catheters – after the embryos are injected into the uterine cavity, 
the embryonic catheter is flushed using a transfer medium under a microscope 
to make sure that there are no embryos in it and that they remain in the uterine 
cavity. 
The most important stages of embryo transfer that have become the subject of interest 
of the research team of the nOvum Clinic and improvement are the variable elements 
of the procedure, which may affect its success: 
a) selection of embryos for transfer – the stage of the procedure depends on the 
experience of the embryologist, despite the introduction of embryo assessment 
standards, the embryo assessment by the embryologist remains subjective, 
b)  embryo collection into the catheter – a stage of the procedure depending on 
the training and experience of the embryologist and therefore burdened with 
variability, 
c) transfer of embryos placed in a catheter from the laboratory to the transfer room 
– at this stage, the embryos are affected by changing environmental conditions, 
which may affect their development and implantation, 
d) Administration of embryos from the catheter into the uterine cavity – another 
variable stage depending on the human factor, i.e. the experience and training 
of the doctor. 

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In recent years, scientific reports have been published on the conditions to which 
embryos in the catheter are subjected during transfer to the uterine cavity 
[1,3,4,5,6,7,8]. 
The above-mentioned reports and own experience confirming the unfavorable 
conditions that affect the embryos placed inside the catheter during the peritransfer 
time (the time the embryo remains in the catheter outside the incubator from being 
taken into the catheter to be administered into the uterine cavity) and during their 
transfer to the uterine cavity, such as: a sharp drop in temperature, shear stress, speed 
and pressure differences, prompted our team to work on standardizing the embryo 
transfer procedure.  
The first stage of work was a design on the design of an applicator that would 
allow for a controlled process of embryo acquisition into the transfer catheter, as well 
as the transfer of embryos into the uterine cavity at a constant, optimal speed and 
would eliminate the adverse conditions to which embryos are exposed during this 
procedure. An electronically controlled embryo transfer device will increase the safety 
and repeatability of the procedure and thus increase its effectiveness.  
Some mentions of the construction of a device to standardize the embryo transfer 
procedure appeared in the scientific publications of the team of researchers of the 
Department of Obstetrics and Gynaecology, VU University Medical Centre in 
Amsterdam, The Netherlands. The subject of particular interest of this group was the 
proper placement of embryos in the uterine cavity through the correct speed of their 
injection during the transfer procedure. The team's research resulted in the creation of 
the "PRET (the pump-regulated embryo transfer device)". This device connects directly 
to the transfer catheter. The "PRET device" works with the use of an automatic 
peristaltic pump capable of pumping small volumes of fluid and air. However, according 
to our current knowledge, this device has not entered the market, nor has a patent 
description of the device with such a name been found [2,7].  
The next stage of work on the standardization of the embryo transfer procedure 
concerns the peritransfer conditions in which the embryo is located outside the 
incubator during the peritransfer time, i.e. between its collection into the catheter by 
the embryologist in the embryology laboratory and its administration into the uterine 
cavity performed by the doctor in the transfer office. Once the embryo is placed in the 
catheter, the embryologist must transfer the catheter from the laboratory to the transfer 
room and hand it over to the doctor. Even a short time outside the incubator causes a 

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change in the environmental conditions in which the embryo placed in the catheter is 
located (a sharp drop in temperature), which has been described in the available 
pioneering publication (Nick Macklon, Olga Delikari, Giuseppina Lamanna, Alison 
Campbell, Simon Fishel, Zaloa Larreategui Laiseca, Marcos Ferrando Serrano, 
Charlotte Coat, Peter Svalander). Embryos are exposed to a significant drop in 
temperature during the embryo transfer procedure: a pilot study. Reprod Biomed 
Online. 2021 Aug; 43(2):193-195. doi: 10.1016/j.rbmo.2021.05.014. Epub 2021 May 
25 [8]. In this pilot study, the team of researchers showed a rapid drop in temperature 
in the catheter outside the incubator during the peritransfer time by up to 10◦C, which, 
given the current state of knowledge regarding the range of optimal and unfavorable 
temperatures for embryonic development, which has already been known, indicates 
that the embryo in the peritransfer period may be subjected to unfavorable and stress-
inducing environmental factors, which may result in impaired development - 
aneuploidy,  Mosiacism and reduced embryonic implantation potential (Munné, S., 
Alikani, M., Ribustello, L., Colls, P., Martínez-Ortiz, Pedro A. Referring Physician 
Group., McCulloh, D.H. Euploidy rates in donor egg cycles significantly differ between 
fertility centers. Human Reproduction 2017; 32: 743–749) [9]. 
In order to refer to the literature report in this regard and to gain new knowledge about 
the environmental conditions prevailing in the transfer catheter, and thus affecting the 
embryo placed in it in the peritransfer time, the nOvum team conducted their own 
experiment on the way between the embryology laboratory and the transfer room (a 
parameter planned for standardization), which confirmed the described temperature 
changes in the catheter. Maintaining optimal environmental conditions in which the 
embryo is located outside the incubator during the peritransfer time may therefore turn 
out to be crucial and is the subject of the study. The new knowledge gained will be 
used to develop a prototype of a device that minimizes environmental changes in the 
catheter by maintaining a constant and optimal temperature during the peritransfer 
time – the EMBRYOCASE case. 
5.2 Subject of the study 
5.2.1 Embryopass – electronically controlled device for controlled 
embryo transfer 
The subject of the study is an electronically controlled applicator enabling controlled 
embryo transfer into the uterine cavity, which is one of the most important elements of 
the medically assisted procreation procedure. The embryopass allows the transfer of 

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embryos into the uterine cavity in controlled conditions and increases the safety of the 
procedure. 
Features of the Embryopass applicator: 
✓ the cycle of taking the charge into the catheter, as well as its administration from 
the catheter into the uterine cavity, ensures repeatability of the procedure 
thanks to pre-programmed constant values of volume, time, speed; 
✓ the volume of the administered charge (i.e. the fluid with the administered 
embryo) is electronically controlled. After the injection of the entire volume of 
charge, it is impossible to retract the delivery system, which significantly 
increases the safety of the procedure of administering the embryo into the 
uterine cavity and eliminates the risk of retracting the embryo back into the 
catheter; 
✓ the ability to detect the phenomenon of occlusion (catheter obstruction). 
The Embryopass applicator - an electronically controlled device for controlled embryo 
transfer is adapted to UltraCruz 3 – Part Soft-Ject Disposable Syringes, 1 ml 
Tuberculin. The built-in power supply system is powered by an electronic 
microprocessor motion controller, which is controlled by a control system. The control 
system consists of buttons to control the process of charge picking and injection 
(air/medium/embryo) and an LED display.  A strain gauge force sensor that controls 
the phenomenon of occlusion is activated in the first phase of injection of the load into 
the uterine cavity. Exceeding the programmed force causes the injection to be stopped 
and the compression system returns to its initial conditions before the injection begins. 
The microprocessor motion controller built into the electronic applicator calculates the 
rotational speed of the drive system with high accuracy according to the programmed 
parameters of the transfer catheter charging and embryo transfer to the uterine cavity. 
The electronic microprocessor motion controller in the applicator also takes care of the 
precise measurement of time, speed and volume of the load/discharge, as well as 
displays the relevant information and messages using light signals of different colors 
and in different sequences, as well as controls the battery charge status. The 
Embryopass has a positioning of the correct attachment of the syringe plunger in the 
syringe attachment holder to protect against the syringe slipping out of the syringe 
attachment holder or accidental pushing out of the syringe plunger.  
The applicator for controlled embryo transfer was designed to work in the conditions 
prevailing in the embryology laboratory. The applicator does not come into direct 

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contact with biological material or the patient's body and does not need to be adapted 
to work in sterile conditions. It is a lightweight, easy-to-use device, enabling safe 
transfer conditions with constant, repeatable parameters.  
To perform the transfer procedure using the Embryopass device, you need to: 
• syringe connected to the catheter, flush the medium according to the procedure 
adopted, then press the plunger of the syringe, gently pushing out the medium so that 
the tip of the catheter is completely filled with the medium; 
• the syringe must be fixed in the syringe holder in such a way that the end of the 
syringe plunger is positioned inside the delivery system, the correct fitting of the syringe 
in the syringe holder is confirmed by a clicking sound; 
• Once you have inserted the syringe and made sure that it is inserted correctly, you 
can start working with the applicator. 
Embryo collection into a transfer catheter using the Embryopass applicator: 
• The procedure of embryo collection by an embryologist is multi-stage. Each of these 
steps is performed by pressing the appropriate button in the control system. The end 
of each stage is signaled by appropriate sequences and colors of light signals visible 
on the LED display located in the control system. 
Procedure for injecting embryos from a catheter into the inside of the uterine 
cavity:  
• It is a one-step procedure performed by a doctor. By pressing the appropriate button 
in the control system, the doctor starts this procedure. The end is signaled by an 
appropriate light signal visible on the LED display located in the control system. 
Occlusion detection: 
• 
the Embryopass applicator is equipped with a strain gauge force sensor used 
to detect occlusion (obstruction) of the catheter. If during the procedure of embryo 
delivery into the uterine cavity there is a catheter obstruction that prevents the embryo 
from being pushed out, the applicator detects occlusion (an increase in pressure in the 
catheter) and prevents further embryo administration. The applicator signals the 
detection of occlusion by means of a light signal visible on the LED display located in 
the control system. The discharge system is automatically retracted to the beginning 
of the load ejection phase, eliminating pressure in the catheter and preventing the load 
from being ejected. 
The electronically controlled device for controlled embryo transfer – Embryopass is an 
in-house invention of the nOvum clinic, constructed by the clinic as part of the 

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RPMA.01.02.00-14-5674/16 project. The applicator was tested on an animal model 
(sheep), obtaining a high percentage of pregnancies and births. The final result of the 
project is a prototype model of the EMBRYOPASS applicator, meeting the assumed 
design conditions and functionalities, launched and tested in laboratory and clinical 
conditions (animal model). Industrial design claim, patent, and CE1434-MDD-089 
certificate certifying compliance with the requirements for medical devices in 
accordance with the EEC/93/42 directive have been obtained. 
5.2.2  Case EMBRYOCASE 
In order to gain new knowledge about the environmental conditions prevailing in the 
transfer catheter, and thus affecting the embryo placed in it in the peritransfer time, on 
the way between the embryological laboratory and the transfer office (a parameter 
planned to be standardized in the innovative embryo transfer protocol) and to refer to 
the literature report in this area (Nick Macklon, Olga Delikari, Giuseppina Lamanna, 
Alison Campbell,  Simon Fishel, A Zaloa Larreategui Laiseca, Marcos Ferrando 
Serrano, Charlotte Coat, Peter Svalander "Embryos are exposed to a significant drop 
in temperature during the embryo transfer procedure: a pilot study" Reproductive 
BioMedicine Online Volume 43, Issue 2, August 2021, Pages 193-195 The nOvum 
clinic team conducted its own study in this area, the results of which are described in  
the paper "Protocol for the study of environmental changes in peritransfer time: 
documentation of temperature changes in the embryonic catheter in the 
peritransfer time defined as the time from the removal of the catheter from the 
incubator through the stage of embryo acquisition with the medium to the 
catheter, the path between the laboratory and the transfer room, to the time of 
insertion of the embryonic catheter into the uterine cavity during the embryo 
transfer procedure" (Appendix No. 2 to the study protocol). 
In a pilot study [8], a team of researchers showed a sharp drop in temperature in the 
catheter outside the incubator during the peritransfer time by up to 10◦C, which, given 
the current state of knowledge regarding the range of optimal and unfavorable 
temperatures for embryonic development, which has already been known, indicates 
that the embryo may be subjected to unfavorable and stress-inducing environmental 
factors in the peritransfer period, which may result in a reduced implantation potential 
of the embryo [9].  
The report presented in the publication [8] was verified by the research team of the 
nOvum Medical Clinic as part of its own research experiment. The new knowledge 

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gained will be used to develop a prototype device that minimizes the occurrence of 
environmental changes in the catheter by maintaining a constant and optimal 
temperature in the peritransfer time – Embryocase. The subject of the research – the 
EMBRYOCASE case, like the previously patented EMBRYOPASS applicator, is by 
definition a safe, easy to use, safe and reliable device. It will not have direct contact 
with the embryo or the woman's body. Such features and functionalities of the product 
make it possible to find the right niche for them in the medical market. The 
implementation of the invention will enable the standardization of the embryo transfer 
procedure, increase the effectiveness of assisted reproduction (ART) treatment, and 
increase the quality of patient service.  
5.2.3 Innovative protocol for standardization of the embryo transfer 
procedure time-lapse (AI)/ Embryopass/Embryocase 
Combining three innovative solutions into one optimal system: it is supposed to 
improve the effectiveness of infertility treatment:a) optimization of embryo selection 
through the use of a device for culture and monitoring equipped with an embryo culture 
system in an incubator with continuous monitoring of embryo development using 
cameras 
(time-lapse) 
and 
artificial 
intelligence 
b) implementation of an innovative, patented invention of the centre's own – the 
EMBRYOPASS applicator – into the embryo transfer (ET) procedure, c) development 
and implementation of a case stabilizing the conditions of the embryo's environment in 
the peri-transfer period Embryocase. 
5.3 Justification for conducting the study 
The market of products dedicated to assisted reproduction techniques lacks electronic 
devices to standardize the procedure of embryo transfer into the uterine cavity. On the 
other hand, the interest in this topic indicates a high awareness of the importance of 
the embryo transfer procedure into the uterine cavity in the community of researchers 
involved in the treatment of infertility. If the effectiveness of the Embryopass, 
Embryocase and TL(AI)/Embryopass/Embryocase protocol is supported by an 
increase in the rate of pregnancies during the embryo transfer procedure to the uterus, 
it will be a significant breakthrough in this field. The protocol for standardizing embryo 
transfer conditions, which the nOvum Clinic would like to implement, containing two 
inventions that eliminate the influence of external factors (human, environmental) on 
the success of the ET procedure, significantly exceeds the procedure used so far. It 

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will improve and increase the efficiency of the embryo transfer procedure used so far 
in everyday practice, which will be measured by the estimated percentage of 
pregnancies, as well as fill the existing gap in this area. This will bring great benefits to 
patients, shortening the time to pregnancy and will increase the safety of the embryo 
transfer procedure by optimizing the conditions to which embryos are subjected during 
the procedure.  
Both Embryopass, Embryocase and the innovative Time-Lapse (AI)/ EMBRYOPASS/ 
EMBRYOCASE standardization protocol for embryo transfer are solutions that have 
not yet been introduced on the market in Poland and abroad. An analysis of the range 
of products and services offered to patients by competing centres through the 
presented websites indicates that there are no service providers, manufacturers or 
entities in the country that use such a solution in clinical practice.  
The introduction of the Time-Lapse (AI)/ EMBRYOPASS/ EMBRYOCASE protocol 
also improves the activities related to the performance of the embryo transfer 
procedure in medically assisted procreation centers. A positive effect at the center level 
will be: automation of the procedure in the center, optimization of daily procedures, 
reduction of risk, increased productivity, reduction of costs, improvement of service 
quality, better patient service. 
5.4 Risks and benefits 
The benefits of using  the Embryopass applicator and the Embryocase in the embryo 
transfer procedure are, first of all, the possibility of standardizing the procedure, which 
may lead to an increase in the percentage of pregnancies and implantations obtained 
as a result of the assisted reproduction procedure. These benefits are possible to 
achieve through the use of the Embryopass applicator because: 
• 
the negative impact of factors affecting embryos during transfer to the uterine 
cavity has been eliminated thanks to a constant, optimal rate of embryo uptake 
into the transfer catheter, 
• 
the negative impact of factors affecting embryos during transfer to the uterine 
cavity has been eliminated thanks to a constant, optimal volume of charge taken 
into the transfer catheter, 
• 
the negative impact of factors affecting embryos during transfer was eliminated 
thanks to a constant, optimal injection rate of embryos from the transfer catheter 
into the uterine cavity, 

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• 
the negative impact of factors affecting embryos during transfer was eliminated by 
determining and programming the optimal duration of embryo injection from the 
transfer catheter into the uterine cavity, 
• 
the negative impact of the human factor on the quality of the embryo transfer 
procedure into the uterine cavity has been eliminated by eliminating pressure 
spikes in the catheter (the pressure force on the plunger is constant) both during 
the collection of the load into the catheter and during injection into the uterine 
cavity, 
• 
the safety of the embryo transfer procedure into the uterine cavity has been 
increased by introducing a system for detecting occlusion (obstruction) of the 
transfer catheter, 
• 
The safety of the embryo transfer procedure has been increased by eliminating the 
possibility of retracting the plunger and pulling the embryo back into the catheter, 
during or after its injection into the uterine cavity. 
The introduction of the Embryocase case into the Embryo Transfer procedure 
will eliminate the negative impact of environmental factors (rapid temperature drop) 
affecting the embryo placed in the transfer catheter outside the incubator during the 
peritransfer time. 
Risks of using Embryopass and Embryocase in the embryo transfer procedure: 
• 
The assumption of the test is to demonstrate the complete safety of the use of an 
electronic device for controlled embryo transfer during the procedure. The 
embryopass does not come into contact with the embryo or the patient's body, 
• 
The assumption of the test is to demonstrate the complete safety of using the 
Embryocase case maintaining the optimal temperature for embryos during the 
embryo transfer procedure. Embryocase has no contact with the embryo or the 
patient's body. 
6. OBJECTIVES OF THE STUDY 
6.1 Effectiveness 
In order to estimate the impact of standardization of ET conditions on its efficacy, data 
on the percentage of biochemical pregnancies, implantation and clinical pregnancies 
obtained (and after the study also live birth data) in the groups of patients in whom the 
embryo transfer procedure was performed using Embryopass, Embryocase and both 
devices together and compared with the results in the control group will be analyzed. 
Factors such as: 

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1. embryo class (including degree of expansion, germ node quality, trophoblast 
quality); 
2.  type of procedure.  
6.2 Safety 
The safety profile of the Embryopass applicator and the Embryocase will be 
presented as a percentage of adverse events. 
6.3 Usability 
The following will be evaluated: 
• convenience of using the Embryocase case and the Embryopass applicator 
by the embryologist and doctor, 
• repeatability of the procedure - the time of embryo collection into the catheter 
and the time of embryo delivery into the uterine cavity. 

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7. STUDY DESIGN 
Diagram 1 – study design 
                                                                                
 
 
 
Screening; patients for cryotransfer, 
without fresh transfer (freeze all) 
minimum 1 embryo frozen of good 
Preparation for cryotransfer in the 
ovulatory cycle: acceptable ovulation 
induction with letrozole 
Confirmation of clinical 
pregnancy; visible 
pregnancy follicle on 
ultrasound 25-35 days 
Data analysis and report 
 
Embryo thawing 
Pregnancy  
No pregnancy – 
withdrawal from 
progesterone  
Embryo transfer; 5 day after 
ovulation 
End of the study 
Randomization; 5 day after ovulation 
Presenting data at industry 
conferences 
Data publication  
Implementation of the invention on 
the medical market 
Determination of the level of βhCG in 
blood serum; 10-15 days after ET 

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8. GROUP EXAMINED 
8.1 Female patients 
The study will involve patients whose embryos have been created and subjected to 
cryopreservation at the "nOvum" Medical Clinic. Patients will be informed about the 
possibility of taking part in the study by the attending physician and additionally in the 
form of an internal announcement (registration, leaflets in the waiting room), on the 
website and, if necessary, on the Social Media of the nOvum Clinic. 
8.1.1 Description of the population 
The study population will consist of patients aged ≥18 to ≤38 years who have 
undergone a controlled ovarian stimulation and puncture procedure, and then the 
collected oocytes have been fertilized by IVF or ICSI. The embryos were cultured in 
an incubator with the Time-Lapse system, the embryos were evaluated by an 
embryologist and an Artificial Intelligence system, and then all were cryopserved. 
Currently, patients are preparing for their first cryotransfer. On the day of thawing, the 
patient will be randomized to be randomized to either a control group or one of three 
study groups. The embryos will be transferred to the uterine cavity on day 5 after 
ovulation. According to the randomized group procedure. 
The development of embryos before freezing in the following days of development will 
be subject to evaluation by an embryologist according to the criteria routinely used in 
the center (PTMRiE criteria; ESHRE – see Table 1, Table 2, and by artificial 
intelligence (according to the capabilities of AI in day 3 and day 5). Ratings will be 
compared.  
In the case of morphological assessment of blastocysts, TQ (top quality) embryos 
include blastocysts at the stage of development of min. 3 with an additional TE and 
ICM rating of at least 1 or 2. Other embryos that do not meet these criteria are referred 
to as weak – NTQ (non-top quality). NTQ (non top quality) embryos include embryos 
with a different number of cells than recommended on a given day of observation and 
a morphotic element rating scale of 3. 
All embryos will be frozen and described according to the AI assessment, on which the 
order of thawing will depend (the thawing of the embryos will occur in the order of the 
best rated by the AI). 
 
Table 1 

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Classification of embryos on day 3 according to PTMRiE  
In the description of an embryo at this stage of development, the symbol of the 
dividing embryo should be given: cl (cleavage), then the number of blastomeres and 
its quality class. 
Embryo 
Quality 
Class 
Morphology 
1- Good 
<10% fragmentation, blastomere size adequate to the number, no 
multinucleation, 
2- Medium 
10-25% fragmentation, the size of blastomeres adequate to the 
number, no multinucleation, 
3 – weak 
>25% fragmentation, blastomere size highly varied, present 
multinucleation, 
 
Table 2  
Classification of embryos on day 5 according to PTMRiE 
In the description of the embryo at this stage of development, the symbol of the 
embryo in the blastocyst stage should be given: bl, followed by the degree of 
expansion and its class of germ node and trophoblast. 
Degree of 
expansion 
Morphology 
1 
Early blastocyst. 
Blastocyst cavity less than half the volume of the embryo. 
2 
A blastocyst cavity greater than or equal to half the volume of the 
embryo. 
3 
A full blastocyst, the cavity of the blastocyst fills the embryo completely. 
4 
Expanding blastocyst, with a volume larger than the embryo at an 
earlier stage of development, the transparent sheath becomes thinner. 
5 
Blastocyst hatching. The trophoblast comes out of the envelope. 
 
6 
A hatched blastocyst. The embryo is entirely outside the envelope. 

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Germ 
node 
(ICM) 
The quality of the germ node. 
 
1 
Lots of cells, tightly packed. 
2 
Few cells, loosely grouped. 
3 
Very few cells. 
Trofoblast 
(TE) 
The quality of the trophoblast. 
 
1 
A lot of cells forming a tight shell. 
2 
Few cells forming a loose coating. 
3 
Very few large cells. 
 
8.1.2 Number of patients 
The total planned number of randomized patients is 160. In this pool, patients will be 
equally divided between the study group and the three control groups, Due to the risk 
of not being qualified for transfer on the 5th day after ovulation for various reasons 
(lack of a good quality embryo, lack of adequate endometrial width or other reasons 
important in the investigator's assessment in all patients), it is estimated that the 
percentage of the so-called " screen failure" i.e. patients who do not meet the criteria 
for inclusion in the study on the day of randomization will be about 20%, which is why 
the assumed number of patients who will undergo screening is 200. In addition, it is 
estimated that about 1% of patients will lose contact with the center, as a result of 
which it will not obtain complete data. 
8.1.3. Study Region 
Single-center study. Patients will be recruited in one center – the nOvum Medical Clinic 
at 13 Bociania Street in Warsaw. 
8.2 Criteria for the selection of patients for the study  
  
Described in Abstract 

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9. TEST PROCEDURES (METHODOLOGY) 
9.1 Informed consent of patients to participate in the study 
Before proceeding with any medical procedures, the patient and her partner must, after 
obtaining all information about the clinical trial from the investigator: sign  the 
"INFORMED CONSENT FORM - PATIENT" and the "INFORMED CONSENT FORM 
- PATIENT"  in the presence of the investigator.The informed consent document 
will include the patient's identification number in the clinical trial (the so-called 
screening number) – the next number from EEZ4412_001 to EEZ4412_200. If a 
patient withdraws consent to the study or is excluded from the study at any time, the 
identification number is not passed on to the next patient. 
The "Informed Consent Form"  must be signed by the Patient in duplicate. Each copy 
will bear the signature of the patient and the researcher, respectively. One copy of 
each of the consents will remain in the documentation of the examination at the 
"nOvum" Medical Clinic, the next will be handed over to the patient and her partner, 
respectively. 
Patients must be informed that their participation in the study is voluntary and they can 
withdraw their consent to participate in the clinical trial at any time. The withdrawal of 
consent must be made in writing in the presence of the investigator. 
From the moment of signing the informed consent until the end of the patient's 
participation in the clinical trial, all information about the patient covered by the subject 
of the study will be collected in the form of paper medical documentation, in electronic 
form in the electronic database of the nOvum Medical Clinic "bmedica2" and the 
database dedicated to clinical trials - eCRF 
9.2 Blinding/Unblinding the Test 
The study will be partially blinded. Patients will not be informed until the end of the 
study whether they will be placed in the control group or in one of the 3 groups of 
subjects. Staff participating in the study: doctors, embryologists and nurses, due to the 
specificity of performing the embryo transfer procedure to the uterus (no possibility of 
blinding), will know which group the patient has been assigned to, but they will 
undertake to maintain secrecy and not to provide each other with information orally 
during the procedure that could blind the patient. Information on how to perform the 
transfer (control group, one of the three groups of respondents) will be included in the 
electronic eCRF. During the transfer, the husband will not be able to be present, about 
which the patients will be informed at the screening stage.   Statisticians analyzing the 

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into the uterine cavity in the procedure of medically assisted procreation in humans" 
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results of the survey will be blinded. The results on the effectiveness of transfers in all 
groups will be the first to be statistically analysed. At this stage, blinded data will be 
provided to the statistics to guarantee the objectivity of the analysis. Blinding will occur 
after analyzing the efficacy and AEs and SAEs of all groups.  The test will be unblinded 
after the test report has been prepared. Patients will be informed by the investigator 
about their membership in groups only at their explicit request. 
9.2.1 Emergency Blinding 
Premature blinding for an individual patient may occur in the event of AE or SAE, the 
occurrence of which, in the opinion of the investigator, may be related to the use of 
Embryocase/ Embryopass. If it is necessary to unblind the patient, it is not required to 
exclude her from the examination. Each case of unblinding must be documented by 
the investigator in the study documentation, along with a description of the 
circumstances and arguments in favor of unblinding. 
9.3 Screening 
Screening for the study must be preceded by the signing of informed consent by the 
patient and her partner. Screening must be performed no more than 60 days prior to 
the estimated randomization. 
During screening, all of the information listed below must be collected: 
• initial eligibility criteria and non-emission;  
• Demographics: date of birth, race; 
• medical history: karyotypes or other genetic tests if performed, evaluation of 
laboratory tests normally required in an IVF/ICSI treatment center, cause and 
duration of infertility, concomitant diseases, oncological treatment (if any), 
partner/donor sperm test confirming the presence of sperm in the ejaculate 
from the day of embryo formation, assessment of the menstrual cycle (must be 
regular – i.e. in the doctor's description "ovulatory 21-35 days"),   obstetric 
history; 
• medications taken by both partners within 3 months before screening and 
currently; 
• gynecological ultrasound examination (performed within the last 3 months at 
most); 
• hormonal stimulation of the ovaries in the cycle in which the embryos were 
formed and the course of the in vitro fertilization procedure; 
• class, quality and procedures to which the embryos were subjected; 

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• A description of the previous transfer or trial transfer. 
During screening, all of the above procedures must be performed: 
• measurement of height, weight, BMI, 
• measurement of pressure, heart rate and temperature, 
• physical examination, 
• gynecological examination, 
• gynecological ultrasound examination (if the patient has not provided an 
examination performed in the last 3 months), 
• A trial transfer, if not done before the puncture, in the following days of 
monitoring after good bacteriology. 
Trial transfer procedure 
Preparing the patient for embryo transfer by performing a trial transfer 
procedure (with an empty catheter without embryos) in order to assess the 
length and direction of the uterine cavity and cervix, as well as diagnosing 
possible obstacles (a procedure performed in a cycle other than the one being 
tested, to prevent possible mechanical damage to the mucosa) will only be 
performed if there is no information in the medical records about how the 
previous transfer took place. 
9.4 Synchronization of the endometrium with embryonic age 
Endometrial synchronization will take place in the natural cycle if the cycles are 
ovulatory or induced by Letrozole. In order to supplement the luteal phase starting from 
the day of ovulation +1 until the visit 25 - 35 days after ET, the Patient will take the 
progesterone preparation vaginally and orally according to the routine regimen used in 
the nOvum clinic: Duphaston orally 3x1 tabl. 10 mg plus Cyclogest 2x400 mg globules 
vaginally. On the day of the appointment 25 - 35 days after CRIO-ET, your doctor will 
decide whether to continue using progesterone or turn it off.  
9.5 Defrosting embryos 
Doctor - The doctor's order to thaw the embryos and make an appointment for a 
transfer visit will take place in accordance with the routine practice adopted at the 
center. 
Embryologist - Embryo thawing will occur according to the highest rating indicated by 
AI: 
(a) on the day preceding CRIO-ET (for blastocysts with a degree of expansion rated 
as 3 before freezing); 

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b) on the day of CRIO-ET (in the case of blastocysts with a degree of expansion 
assessed at least 4, at least 2 hours before embryo transfer to the uterine cavity. 
Defrosting will be carried out in accordance with the routine procedure adopted at the 
"nOvum" Medical Clinic. 
9.6 Evaluation of embryos after thawing 
Evaluation of embryos after thawing will be performed by an embryologist and on its 
basis the embryo will be qualified for ET. 
9.7 Randomization 
Randomization will take place on the day of CRIO-ET, i.e. on the 5th day after 
ovulation, counting the day of follicle rupture as day 0, confirmation of ovulation by the 
occurrence of the LH peak (LH peak day + 6 days), or by the administration of chorionic 
gonadotropin on the day of confirmation of the presence of the preovulatory follicle 17-
22 mm, HCG drug (HCG administration day +7 days). 
Randomization will be randomized. Patients who meet all inclusion criteria and do not 
meet any of the exclusion criteria may be randomised. The patient's assignment to the 
control group or the study group will take place by drawing envelopes by an 
independent person (an administrative employee of the embryology laboratory), who 
is not part of the research team. 
The randomization number will be determined by a string of 6 characters: from 
EE_001 to EE_200. The numbers will be located in unmarked envelopes – each 
number will correspond to membership in a specific research group. The number will 
only be known to embryologists who are members of the research team. After 
randomly selecting the envelope, the administrative employee will open it and hand it 
over to the embryologist, who is a member of the research team. Both of them will sign 
the number drawn for the patient with the date of the draw. The number of numbers 
will be selected so that the same number of patients will be assigned to the control 
group and three groups of subjects. 
9.8 Transfer visit 
The transfer visit will be divided into two stages: 
Stage I: The following procedures will be performed prior to randomization to ensure 
that the patient is eligible for the study: 
• measurement of pressure, heart rate and temperature, 
• gynecological ultrasound, 

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• the medications taken by the patient will be evaluated, and they will receive 
further recommendations on the use of the medication, 
• AEs will be evaluated, 
• The doctor will communicate with the laboratory and confirm whether the 
embryo is eligible for transfer after thawing and whether the patient meets the 
criteria for inclusion in the study. 
Stage II: after randomisation, the patient enrolled in the clinical trial will undergo 
embryo transfer of a thawed embryo using a method consistent with the 
randomisation group in which she was placed. 
To perform the embryo transfer procedure, i.e. the administration of embryos into the 
uterine cavity, soft catheters will be used - Cook Medical Guardia™ Access Embryo 
Transfer Catheter K-JETS 7019, tightly connected to the UltraCruz 3 syringe – Part 
Soft-Ject Disposable Syringes, 1 ml Tuberculin. In the absence of the indicated 
medical devices on the market, the use of certified substitutes is allowed. In addition, 
in the test group, the catheter/syringe transfer kit will be accompanied by an 
Embryopass applicator, an Embryocase case or both devices at the same time. 
Common to the control group and all research groups will be the cultivation of embryos 
in the TLS system and the evaluation and selection of embryos for transfer by artificial 
intelligence (AI). 
The embryo transfer procedure will be divided into stages: 
a. Preparation of the patient prior to transfer, as described in section 5.1 – 
literature review  
In all groups, the control group and the three subjects, patients will be 
prepared for embryo transfer in the same way.  
b. The insertion of a catheter leading to the uterine cavity consists in inserting, 
with great delicacy, the catheter through the internal opening of the cervix into 
the interior of the uterine cavity just behind the internal outlet. 
After the catheter leading to the inside of the uterine cavity is placed, the nurse 
assisting the doctor will inform the embryologist that it is ready for transfer. The 
embryologist will then begin the procedure of collecting embryos into the 
catheter. 
In all groups, this stage of the embryo transfer procedure will look the 
same. 

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c.  Proper embryo acquisition into the transfer catheter. The embryos will be 
taken into the catheter directly from the medium (medium) intended for embryo 
transfer from the transfer dish, and the whole operation should not take more 
than 2 minutes, according to the scheme: air (marker) - medium with embryo-
air (marker)-medium.  
This step of the procedure will vary from group to group: 
in the control group (TL/AI – ET manual and study group no. 1 (TL/AI – 
ET manual + EMBRYOCASE) 
The embryologist will collect embryos into the transfer catheter in a manual 
manner, according to the above scheme adopted at the center. The time from 
the start of the 1st air bubble intake to the completion of the media intake will 
be measured by a stopwatch. 
in study groups 2 (TL/AI – ET using EMBRYOPASS) and 3 (TL/AI – ET 
using EMBRYOPASS + EMBRYOCASE),  the embryologist will collect 
embryos into the transfer catheter with the help of the Embryopass applicator, 
in accordance with its instructions for use. The embryologist will be trained in 
the use of the applicator by its designer, which will be confirmed by a training 
certificate (the Embryopass user manual will be available in the laboratory - 
attachment to the investigator's brochure).  The embryo acquisition time will 
also be measured. 
d. After collecting the embryos into the catheter, the embryologist will transfer the 
catheter to the transfer room without additional protection in the control group 
and study group 2, or after placing the catheter with the embryo in the 
Embryocase case (groups 1 and 3). 
e. Visualization of the embryo transfer process using an ultrasound machine 
allows you to visualize the entire process of embryo transfer from the catheter 
to the inside of the uterine cavity.  
In all groups, transfers will take place under ultrasound control. 
f. 
Administration of embryos into the uterine cavity (embryo transfer). The proper 
administration of embryos into the uterine cavity consists in the insertion by 
the doctor of a guide catheter, a catheter containing embryos suspended in 
the transfer medium, the so-called embryonic catheter, into the previously 
inserted into the uterine cavity. This is a key stage of the entire embryo transfer 
process. 

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This step of the procedure will vary from group to group: 
✓ In the control group and the 1 study group, the operating physician, after 
inserting the guide catheter, places the embryonic catheter in it and gently 
moves it inside the uterus. After making sure that the embryonic catheter is 
in the optimal place of the uterine cavity (1.5-2 cm from the bottom of the 
uterus), the operator presses the plunger of the syringe connected to the 
embryonic catheter with his finger and carefully causes the embryos to 
move from the catheter to the inside of the uterus by pressing on the 
plunger. Once the maximum resistance of the plunger has been reached 
and observing whether the last marking marker remains in the uterine 
cavity, the doctor retracts the catheters from the cavity. To measure the time 
it takes for the embryos to be placed in the uterine cavity, the doctor will 
inform the embryologist about the start and end of the procedure, and its 
duration will be measured with a stopwatch; 
✓ in study groups 2 and 3, the doctor will administer embryos from the transfer 
catheter into the uterine cavity using the Embryopass applicator, according 
to its instructions for use. The doctor will be trained in the operation of the 
applicator by its designer, which will be certified by a training certificate. 
Instead of pressing the plunger of the syringe, the doctor will press the 
appropriate button on the Embryopass applicator, which will trigger the 
movement of the syringe plunger. 
 As the time of embryo administration with the Embryopass applicator is a constant 
value, there is no need to control the time at this stage. The catheter will be withdrawn 
from the uterine cavity immediately after the embryos are administered.  
g. Checking the catheters. Once the embryos have been administered into the 
uterine cavity, the embryonic catheter will be flushed using a transfer medium 
under a microscope to make sure that the embryo remains in the uterine cavity. 
It is allowed to re-administer the embryo if it remains in the catheter. 
h. The course of the procedure and any adverse events that will occur during the 
embryo transfer procedure will be recorded in the documentation. 
i. 
Immediately after the transfer, the patient will get up from the chair and leave 
the transfer room. 

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9.9 βhCG Visit 
Confirmation of pregnancy will occur at the visit 10-15 days after ET. During this 
assessment visit, the following procedures will be carried out 
• measurement of pressure, heart rate and temperature; 
• determination of βhCG concentration in blood serum. A concentration ≤ 5.3 
mIU/ml will be considered negative (no pregnancy), and a result above this 
value will be considered positive (pregnancy). In the event of a doubtful βhCG 
result, subsequent determinations will be carried out in accordance with the 
routine practice of the center; 
• the medications you are taking will be evaluated and you will receive further 
recommendations on medication use. 
• AE/SAE will be evaluated. 
It is possible for the patient to carry out the pregnancy outside the research center at 
the place of residence, provided that medical data concerning individual stages of 
pregnancy development (βhCG, ultrasound, etc. tests will be made available to the 
doctor of the "nOvum" clinic in the form of documents, e.g. scans, photocopies or 
consulted with the doctor through any form of consultation, e.g. televisits, video 
consultation).  
In the absence of pregnancy, the patient ends the test and stops taking progesterone.  
9.10 Visit – confirmation of clinical pregnancy 
• measurement of pressure, heart rate and temperature; 
• physical examination; 
• examination in speculums; 
• ultrasound to assess the presence of a pregnancy follicle in the uterine cavity, 
25 – 35 days after ET; 
• the medications you are taking will be evaluated and you will receive further 
recommendations on medication use. 
• AE/SAE will be evaluated. 
It is possible for the patient to carry out the pregnancy outside the research center at 
the place of residence, provided that medical data concerning individual stages of 
pregnancy development (βhCG, ultrasound, etc. tests will be made available to the 
doctor of the "nOvum" clinic in the form of documents, e.g. scans, photocopies or 
consulted with the doctor through any form of consultation, e.g. televisits, video 
consultation).  

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The examination is completed. 
9.11 Termination of pregnancy 
• Data on the termination of pregnancy (data on childbirth, miscarriage or ectopic 
pregnancy) will be collected from patients using a questionnaire developed by the 
investigators. 
• The patient can send the questionnaire to the center or provide the information 
contained in it by phone to one of the members of the research team. 
• The questionnaire is attached as Annex No. 1 to the survey protocol. 
 
9.12 Diagram of procedures/visits 
 
        Type  
  
Appointments/Treatments 
 
 
 
 
 
 
Type  
Procedures 
Informed consent of patients to participate in 
the study. 
Screening 
Synchronization of the endometrium with the 
age of embryos. 
Embryo thawing 
Randomization. 
Embriotransfer 
βhCG Visit 
Visit – confirmation of clinical pregnancy. 
Termination of pregnancy 
Informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion Criteria 
 
X 
 
 
X 
 
 
 
 
Exclusion Criteria 
 
X 
 
 
X 
 
 
 
 
Gynecological examination 
 
X 
X 
 
 
 
 
 
 
Ultrasound examination 
 
X 
X 
 
 
X 
 
X 
 
Trial transfer 
 
X 
 
 
 
 
 
 
 
Ordering the tests required 
for CRYO-ET 
 
X 
X 
 
 
 
 
 
 
Medication regimen 
 
X 
X 
 
 
X 
X 
X 
X 
Embryo thawing order 
 
 
X 
 
 
 
 
 
 

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10. PARAMETERS TO BE ANALYSED IN THE STUDY 
10.1 Demographics 
Demographic information collected in the study: 
• Age 
• Race 
• Ethnicity 
The information collected from the patient will be recorded in the documentation. 
10.2 Body Measurements 
During the screening, body measurements will be evaluated: 
• Measuring body weight; 
• Height measurement 
• BMI. 
10.3 Medical history 
All relevant medical events will be described during screening, indicating whether they 
occurred in the past or are ongoing in the present. The information collected from the 
patient will be recorded in the documentation. 
10.4 Cause of infertility 
  During screening, the history of infertility will be described:  
• cause of infertility,  
• duration, 
• Treatment history (previous IVF attempts, if any. Patients who have already 
undergone in vitro fertilization (IVF) may be included in the study only if the 
previous transfer ended in pregnancy and childbirth and meet the other criteria). 
The information collected from the patient will be recorded in the documentation. 
Embryo thawing 
 
 
 
X 
 
 
 
 
 
Embryo culture after 
thawing 
 
 
 
X 
 
 
 
 
 
Embriotransfer 
 
 
 
 
 
X 
 
 
 
Serum ꞵhCG levels  
 
 
 
 
 
 
X 
 
 
AE 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SAE 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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10.5 Evaluation of the menstrual cycle 
During the screening, information about the patient's menstrual cycle will be collected: 
• Average cycle length 
• Cycle regularity 
The information collected from the patient will be recorded in the documentation. 
10.6 Obstetric Interview 
 During the screening, information about the patient's obstetric history will be collected: 
• number of biochemical and clinical pregnancies, 
•  miscarriages ≥ 2 consecutive should be a criterion for exclusion, 
• number of births. 
The information collected from the patient will be recorded in the documentation. 
10.7 Readiness to receive embryos after thawing 
• 
During the preparation of the patient for transfer, the width of the endometrium 
will be assessed during each stimulation visit in accordance with the routine 
practice of the center (ultrasound examination). The result of the measurement 
will be recorded in the documentation. 
• 
The patient's ovulation will also be evaluated. 
10.8 Embryo Quality 
• The quality of embryos and their development will be assessed in accordance 
with ESHRE and PTMRiE guidelines and by artificial intelligence. Observations 
will be recorded in the patient's medical records and electronic documentation of 
the examination. 
10.9 Transfer Procedure 
The course of the transfer and any difficulties related to the transfer will be recorded in 
the medical documentation. 
10.10 Concomitant medications 
10.10.1 Permitted medications/therapies 
• Letrozole 
• Progesterone (Duphaston, Cyclogest) to supplement the luteal phase, 
• Ovulation induction medications, if used, 
• other medicines/supplements that the investigator considers have no effect on 
fertility or the outcome of the embryo transfer procedure, 
• 
Bokmål 

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10.10.2 Prohibited medications/therapies 
• preparations other than hCG used for the purpose of liberation, which prevent 
the embryo transfer procedure from being performed, 
• drugs with proven harmful effects on fertility, 
• drugs used in oncological therapy with a proven harmful effect on fertility, 
• drugs that have a relaxing and antispasmodic effect on the uterus – atosiban, 
relanium scopolan (hyoscine butylbromide) or other hyoscine derivatives, 
• heparin drugs,  
• acetylsalicylic acid. 
10.11 Endometrial thickness 
When preparing the patient for CRIO-ET, endometrial width will be assessed at each 
visit according to the center's routine practice (ultrasound). The result of the 
measurement will be recorded in the documentation. A result below 7 mm on the day 
of ovulation will disqualify from embryo transfer. 
10.12 Transfer Procedure 
The course of the transfer and any difficulties related to the transfer will be recorded in 
the medical documentation. 
The data to be analysed are: 
• type of catheter,  
• the degree of difficulty of the transfer, 
•  ET time: Time of embryo collection into the catheter, time of administration by 
the doctor in the manual method, total ET time from collection to administration. 
11. END OF THE STUDY 
11.1 Study Completion 
It should be assumed that the patient has completed the clinical trial if: 
• She completed all scheduled procedures and visits in accordance with the 
protocol. 
• has not become pregnant as a result of a medically assisted procreation 
procedure (completion of the study occurs during a βhCG visit 10-15 days after 
ET), 
• positive blood serum βhCG result was found at the visit 10-15 days after ET, 
ends the study at the clinical pregnancy confirmation visit 25-35 days after ET, 

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• A 
questionnaire 
confirming 
the 
termination 
of 
pregnancy 
(childbirth/miscarriage) will allow you to achieve additional goals in the study. 
11.2 Withdrawal of consent 
The patient and her partner may withdraw their consent to participate in the clinical trial 
in writing at any time. If one of the partners withdraws consent to a clinical trial during 
the course of the trial, the trial is considered to have been discontinued. Patients do 
not need to provide reasons for withdrawing consent, but the investigator must 
accurately document the circumstances of the withdrawal of consent in the medical 
records. 
After the withdrawal of consent by the patient, no additional treatment data will be 
collected, but any medical data collected until the withdrawal of consent may be 
analysed, used for statistical purposes, scientific publications, etc. 
11.3 Discontinuation 
During the clinical trial, the patient may be excluded from participation in the study by 
the investigator due to: 
• failure to meet the inclusion or exclusion criteria at each stage of the study; 
• an adverse event that, in the opinion of the investigator, prevents the patient 
from further participation in the study, 
• withdrawal of consent by one or both partners, 
•  a material breach of the protocol – failure to comply with the rules of the 
protocol, as a result of which the test results could be falsified, 
• inability to contact the patient. 
In place of a patient excluded from the pre-randomisation trial, the centre may enrol 
another patient in the study, assigning her another screening number. 
If a patient has been excluded from a randomized trial, the center will not enroll another 
patient. 
11.4 Reasons for discontinuation of a clinical trial by a facility 
The reasons for the discontinuation of a clinical trial by the center may result from 
various factors. The Centre may decide to discontinue the examination in the event of: 
1. Patient safety issues: 
a. the occurrence of unexpected, serious side effects that outweigh the benefit 
of the treatment, 

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b. the occurrence of unacceptable risks, e.g. the discovery of new information 
that suggests that the risks associated with the therapy outweigh the 
potential benefits. 
2. Lack of treatment efficacy:  
a. periodic analyses will show that the subject of the study is not effective in 
achieving the assumed goals, 
b. The data will indicate that the continuation of the study will not bring positive 
clinical results. 
3. Ethical violations: the study may be terminated if ethical principles are violated. 
4. Organizational or financial problems: 
a. lack of sufficient financial resources to continue the study, 
b. too low a level of recruitment of participants, which makes it impossible to 
obtain representative data. 
12. PARAMETERS TO BE ANALYSED OUTSIDE THE STUDY 
After the study is completed, data on births will be collected. 
13. ADVERSE EVENTS 
13.1 Definition 
Adverse event – any medical event that deviates from the norm. 
An adverse event should be treated as: 
✓ abnormal laboratory test results, 
✓ symptoms and diseases that may exclude the patient from the clinical trial, 
✓ applicator dysfunctions found during its operation, 
✓ difficult transfer (criteria according to routine procedures of the center)  
13.2 Scope and method of collecting data on adverse events 
Adverse events will be reported in the medical history from the 1st stimulation visit to 
the study end visit.  Medical events that were noted during the screening visit will not 
be treated as adverse events, but medical history. 
When describing an adverse event, the investigator will note in the medical 
records: 
• the start and end dates of the adverse event, 
• diagnosis (name of the adverse event), 
• clinical significance, 
✓ CS- the event is medically significant, 
✓ NCS – no clinical significance, 

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• relationship with the subject under study, 
✓ Yes – the occurrence of an adverse event is related to the use of the 
study product 
✓ no - the occurrence of the adverse event is not related to the use of the 
study product 
• intensity, where:  
✓ weak – means no impact on the patient's daily activity, 
✓ medium – the patient feels discomfort affecting her daily activity, 
✓ serious – the adverse event significantly limits the patient's functioning or 
poses a threat to her life), 
• Actions taken in relation to the subject in relation to the occurrence of an 
adverse event 
✓ No action  
✓ resignation from the use of the test object 
• actions taken to correct the adverse event 
14. SERIOUS ADVERSE EVENTS 
14.1 Definition 
A serious adverse event is a sudden and unforeseen medical event:  
• resulting in the death of the patient, 
• posing a threat to the patient's life, 
• requiring hospitalization of the patient for more than 24 hours (excluding the 
patient's planned stay in hospital), 
• an adverse event (AE) whose intensity has been defined as "serious" and for 
which medical action must be taken to avoid hospitalization, threat to life or 
death of the patient. 
14.2 Scope and method of collecting data on serious adverse events 
Serious adverse events (SAEs) will be reported in the medical history starting at the 
1st stimulation visit.   
When describing an adverse event, the investigator will note in the medical 
records: 
• the start and end dates of the serious adverse event, 
• diagnosis (name of the adverse event), 
• clinical significance, 
✓  CS - the event is medically significant, 

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✓  NCS - no clinical significance , 
• relationship with the subject under study, 
✓ the occurrence of an adverse event is related to the use of the study 
product 
✓ the occurrence of an adverse event is not related to the use of the 
study product 
• Actions taken in relation to the subject in relation to the occurrence of an 
adverse event 
✓ No action  
✓ resignation from the use of the test object 
• actions taken to correct the adverse event, 
15. METHOD OF DATA COLLECTION AND PROCESSING 
15.1 Source data 
The source data will be medical documentation in the form of: patients' health and 
illness history, embryological protocols, electronic documentation in the bmedica 
system2. 
15.2 Electronic Database - eCRF 
The information collected in the medical records will be systematically entered into the 
eCRF system within 14 days of each visit. The database will be closed when all 
required data has been completed and any doubts and deficiencies have been 
clarified. 
16. DEVIATIONS FROM THE PROTOCOL 
Deviations from the protocol are prohibited. Any deviation from the protocol is treated 
as a protocol deviation. They must be documented and justified by the investigator in 
the medical records. 
17. MONITORING 
The planned therapeutic experiment will not be subject to external monitoring. This 
is the center's own study, non-commercial. The lack of external monitoring is justified 
as the entire research team has a solid GCP background and research procedures 
and ethical standards are properly implemented at the site, ensuring a high level of 
internal supervision and patient safety. 
Knowledge and experience of the research team at GCP: the entire research team 
has been trained and is fully aware of the principles of GCP, which are the international 
ethical and scientific standard for the conduct of clinical trials. Thanks to this, the team 

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into the uterine cavity in the procedure of medically assisted procreation in humans" 
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has adequate knowledge of the obligations that arise from the GCP, which minimizes 
the risk of errors and ethical violations. 
High quality of data and procedures: GCP principles ensure that a clinical trial is 
conducted appropriately and that the data obtained during the experiment is reliable, 
reliable and accurate. The team knows the rules for reporting and documenting results, 
which reduces the need for external monitoring. 
Responsibility of the research team: each member of the research team is aware of 
their role and responsibility in the experiment. All employees are trained to comply with 
ethical principles, which allows for effective risk management and ensures patient 
safety. 
Transparency and compliance with the study protocol: The study will be conducted in 
accordance with an approved protocol that precisely defines all procedures, including 
how data is collected and actions to ensure data integrity. In the event of any deviations 
or issues, the team will act in accordance with GCP policies, allowing for ongoing 
identification and resolution of issues without the need for formal monitoring. 
18. LEGAL AND ETHICAL REGULATIONS 
The research center applied to the Bioethics Committee for permission to conduct this 
study. 
19. REPORTING AND PUBLICATIONS 
It is planned to prepare a report on the results of the research and publish an article in 
the scientific press on the standardization of the embryo transfer procedure and the 
effectiveness of the Embryopass applicator, the Embryocase case and the TL(AI)/ 
Embryopass/ Embryocase protocol. 
 20. PROTECTION OF PERSONAL DATA 
The administrator of the Patients' personal data is the Medical Clinic "nOvum" 
Katarzyna Kozioł Piotr Lewandowski Sp. j., 13 Bociania Street, 02-807 Warsaw. 
The processing of Patients' personal data is carried out on the basis of Article 6(1)(a) 
and Article 9(2)(a) of Regulation (EU) 2016/679 of the European Parliament and of the 
Council of 27 April 2016 on the protection of natural persons with regard to the 
processing of personal data and on the free movement of such data, and repealing 
Directive 95/46/EC (GDPR) and on the basis of the provisions of applicable law. 
21. LITERATURE 
1.Marjan Omidi, et al. The effect of embryo catheter loading technique on the live birth 
rate  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC472460/. 

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into the uterine cavity in the procedure of medically assisted procreation in humans" 
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2.Groeneveld E, et al. Standardization of catheter load speed during embryo transfer: 
comparison of manual and pump-regulated embryo transfer. Reprod. Biomed Online. 
2012; 24:163–169 
3.Grygoruk C, et al. Pressure changes during embryo transfer. Fertil Steril 2011; 
95:538–41. 
4.Grygoruk C, et al. Inﬂuence of embryo transfer on blastocyst viability”. Fertil Steril 
2011; 95:1458–61. 
5.Grygoruk C, et al.. Influence of embryo transfer on embryo preimplantation 
development. Fertil Steril. 2012 Jun; 97(6):1417-21. 
6.Grygoruk C, ,et al. Fluid dynamics during embryo transfer. Fertil Steril 2011; 96:324–
7.4. 
7.Mirte R. et al. Gynecol Obstet Invest (2016); 81:394–404 DOI: 10.1159/000443954. 
Embryo Transfer with Controlled Injection Speed to Increase Pregnancy Rates: A 
Randomized Controlled Trial.  
8. Nick Macklon, Olga Delikari, Giuseppina Lamanna, Alison Campbell, Simon Fishel, 
Zaloa Larreategui Laiseca , Marcos Ferrando Serrano, Charlotte Coat, Peter 
Svalander. Embryos are exposed to a significant drop in temperature during the 
embryo transfer procedure: a pilot study. Reprod Biomed Online. 2021 Aug; 43(2):193-
195. doi: 10.1016/ j.rbmo.2021.05.014. Epub 2021 May 25. 
9. Munné, S., Alikani, M., Ribustello, L., Colls, P., Martínez-Ortiz, Pedro A. Referring 
Physician Group., McCulloh, D.H. Euploidy rates in donor egg cycles significantly differ 
between fertilty centers. Human Reproduction 2017; 32: 743–749.9. 
22. ANNEXES 
1. Patient Survey on Pregnancy and Childbirth 
2. "Protocol for the study of environmental changes in peritransfer time: 
documentation of temperature changes in the embryonic catheter in peritransfer 
time defined as the time from the removal of the catheter from the incubator 
through the stage of embryo acquisition with the medium to the catheter, the 
path between the laboratory and the transfer room, to the time of insertion of 
the embryonic catheter into the uterine cavity during the embryo transfer 
procedure"