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
Trial ID: NCT07396181
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: NA
Start date: 2026-01-01
Completion date: 2027-10
Sponsor: Przychodnia Lekarska nOvum Katarzyna Kozioł, Piotr Lewandowski sp.k.
Collaborators: Fundusze Europejskie dla Mazowsza 2021-2027 (FEMA.01.01-IP.01-04WN/24)
Conditions: Infertility (IVF Patients); Infertility; ART
Interventions: Embryocase; Embryopass; Embryocase+Embryopass; Manual cryo transfer without using any devices
Locations: Przychodnia Lekarska nOvum Katarzyna Kozioł, Piotr Lewandowski sp.k.
Countries: Poland
Enrollment: 200
Age range: 18 Years - 38 Years
Sex: FEMALE

Summary:
The EFECT study is a clinical trial designed to determine whether improving the consistency of embryo transfer procedures can increase pregnancy success in patients undergoing frozen embryo transfer (cryoET). While laboratory techniques for fertilization, embryo culture, and selection have advanced significantly, the process of transferring embryos to the uterus remains variable and depends on small procedural differences, such as temperature changes, mechanical forces, timing, and individual operator techniques. These variations may affect embryo survival and implantation, ultimately influencing pregnancy outcomes.

This study tests whether using specialized devices to standardize key aspects of embryo transfer-specifically temperature stability during transport and controlled, precise embryo aspiration and expulsion speed, optimal fluid volume, programmed injection time, elimination of pressure fluctuations and plunger backflow, prevention of embryo re-aspiration and detection of transfer catherer oclusion-can improve pregnancy rates. All embryos in the study are cultured using time-lapse monitoring and selected using artificial intelligence-supported grading, ensuring uniform quality for all participants. The study compares standard manual embryo transfer with transfer using one or both of the devices: Embryocase, which maintains a stable temperature during transport, and Embryopass, which standardizes the procedure and eliminates human factor.

A total of 160 participants are randomly assigned to one of four groups: manual transfer without device support, manual transfer with Embryocase, transfer with Embryopass, or transfer with both devices. Participants and outcome assessors are blinded to group assignment, while the staff performing the transfer are aware due to the nature of the devices. All participants receive standard luteal phase support with progesterone following routine clinical practice.

The study's main goal is to evaluate whether these procedural improvements lead to higher rates of biochemical pregnancy (positive pregnancy test) and clinical pregnancy (confirmed by ultrasound). Secondary outcomes include implantation rate, live birth rate, device safety, and ease of use as reported by staff. Pregnancy outcomes, including delivery, pregnancy loss, or ectopic pregnancy, are followed until the end of pregnancy.

By investigating the impact of procedural standardization, this study aims to determine whether technological improvements during embryo transfer can increase the effectiveness of assisted reproductive treatments. If successful, the results could support the broader adoption of standardized, device-assisted embryo transfer protocols in fertility clinics, helping more patients achieve successful pregnancies.

Eligibility criteria:
Inclusion Criteria:

* The patient and her partner gave written, informed consent to participate in the clinical trial.
* 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
* You and your partner are not currently taking part in or have not participated in any other clinical trial in the last 6 months.
* The patient's age on the day of screening ranges from ≥18 to ≤38 years.
* The patient's BMI on the day of screening ranges from ≥18 to \< 30.
* Both partners have normal infectious tests performed 6 months before ET and bacteriological tests performed one month before ET.
* 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.
* The patient has a normal uterus and endometrium at least 7 mm on ET.
* 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.
* 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.
* The patient must be qualified by the doctor for the procedure embryo transfer on day 5 after ovulation.
* 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:

* Failure to meet the inclusion criteria.
* 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.
* The patient was diagnosed with endometrial polyp(s).
* The patient was diagnosed with submucosal or intramural uterine fibroids.
* The patient was diagnosed with fallopian tube hydromas.
* The patient was diagnosed with ≥3 endometriosis.
* The patient or her partner is a carrier of a genetic defect that may have an impact on lowering fertility.
* 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.
* The patient has had 1 unsuccessful embryo transfer in the past, which means no clinical pregnancy.
* 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.
* Embryos are formed from eggs after PBB (polar body biopsy) of oocytes have been examined or have undergone genetic testing of embryos.
* The embryos were formed from oocytes after cryopreservation.
* Semen was obtained for a procedure other than normal ejaculation (retrograde bladder ejaculation, epididymis biopsy, testicular biopsy, M-TESE).
* The patient did not take progesterone for luteal phase supplementation.
* Inability to perform embryo transfer on day 5 after ovulation due to medical or random reasons.
* 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).
* The patient is to have an incision made in the AH areola before the ET procedure.
* The patient wants to have Embryoglue used for transfer.
* The patient takes heparin, Clexane, Acesan, Relanium drugs on and after embryo transfer.

Outcomes:
Percentage of biochemical pregnancies; Percentage of clinical pregnancies in all groups of patients