InfertilityNCT05481684
The Importance of Embryo Transfer Day Progesterone Value in Natural Cycle Frozen Embryo Transfers and the Evaluation of the Effect of Rescue Therapy on Pregnancy Outcomes in Patients With Low Progesterone Levels
A study testing Normal Progesterone group and Low Progesterone group in people with Infertility and IVF, run by Bezmialem Vakif University at 3 sites in Turkey (Türkiye).
Trial summary
Thanks to recent advances in clinical practice and laboratory, embryo cryopreservation has become the first-line procedure in assisted reproductive technology. Improved laboratory techniques have increased the number of available embryos derived from an in vitro fertilization (IVF) or intracytoplasmic sperm injection… Read more about this study
- Who is it for?
- Ages 20 to 42 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility, IVF, Progesterone
- What is being tested?
- Normal Progesterone group and Low Progesterone group
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 3 sitesTurkey (Türkiye)
- Study dates
- 8 Aug 2022to 1 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 42 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women between the ages of 20-42 who applied to the infertility clinic
- BMI<30
Who cannot join
- Severe male factor (Sperm count <5 ml/ml, progressively motile sperm count <10%)
- Intrauterine structural anomalies not corrected by surgery
- Hydrosalpenx if not underwent surgery
- Refusal to participate in the study
- cycle cancelation
Trial locations and contacts
3 sites in 1 country.
Turkey (Türkiye)3 sites, 3 recruiting
- Recruiting
Acıbadem Ataşehir Hospital
Istanbul
Cem Demirel, PhD, +905309556505, cem.demirel@acibadem.com
- Recruiting
Bezmialem Foundation University
Istanbul
Pınar Özcan
- Recruiting
Novaart IVF and Women's Health Center
Istanbul
Mehmet Erdem, PhD, +905442204024, iletisim@novaarttupbebek.com
About this study
Official title: The Importance of Embryo Transfer Day Progesterone Value in Natural Cycle Frozen Embryo Transfers and the Evaluation of the Effect of Rescue Therapy on Pregnancy Outcomes in Patients With Low Progesterone Levels: A Multicentric Randomized Controlled Study.
Thanks to recent advances in clinical practice and laboratory, embryo cryopreservation has become the first-line procedure in assisted reproductive technology. Improved laboratory techniques have increased the number of available embryos derived from an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle. Implementation of a single embryo transfer policy to improve vitrification, improve postwarm embryo survival rates, and reduce multiple pregnancies without reducing cumulative birth rates has contributed to an increase in the number of frozen-warms (1,2) Embryo freezing; It is becoming an adopted practice for an increasing number of indications, including prevention of ovarian hyperstimulation syndrome, preimplantation genetic testing (PGT), late follicular phase progesterone elevation, and embryo-endometrial asynchrony. In our study, we are investigating the effect of pre-transfer serum progesterone levels on pregnancy outcomes in patients who underwent frozen-thawed embryo transfer.Supplementary progesterone preparations can be used to prevent luteal phase defect and to provide progesterone support in cycle preparations for frozen-thawed embryo transfer(3). The aim in this study is to show the effect of serum progesterone level on the pregnancy results on the day of embryo transfer in natural cycles.
Read the detailed description
The patients to be included in the study are the patients followed in the IVF centers of two different hospitals.Patients between the ages of 20-42 and having a BMI of <30, who are scheduled for IVF due to tubal factor, infertility of unknown cause, mild male factor, and anovulation will be included in the study. An antagonist (Cetrotide; Serono, Geneva, Switzerland) protocol will be used for controlled ovarian hyperstimulation, and recombinant follicle-stimulating hormone (recFSH) (Gonal F; Serono, Geneva, Switzerland) and Human Menopausal Gonadotropin (HMG) (Merional; Switzerland) will be used for stimulation. The dose of gonadotropin to be administered to patients is in the range of 150 to 450 IU per day and will be determined according to the age of each patient, serum FSH and E2 levels in the early follicular phase, and the number of antral follicles determined by ultrasound in the early follicular phase. Adjustment of the gonadotropin dose during the treatment will be adjusted by serial ultrasound measurements of the follicle diameters developed during the treatment and serum E2 levels. The patient's eggs will be collected at 34-36 hours. Fertilization check will be done the next day. During 3-5 days of embryo culture, embryo quality will be determined according to the D.Gardner criteria (1999). Embryos will be frozen on the 3rd or 5th day and transferred to a planned frozen cycle within the next month. In the frozen cycle, basal ultrasonography is performed on the 3rd day of the menstrual cycle and if there is no follicle over 10 mm, the patient will be called for a control on the 10th day of the cycle if the endometrial thickness is less than 5 mm. In the follow-ups after the 10th day, daily LH monitoring will be performed with the dominant follicle reaching 15 m in diameter. When the LH level increases 1.8 times, it will be considered as LH surge. Serum progesterone level will be checked on embrio transfer day. The patients with serum progesterone value below 10 on the day of embryo transfer will be divided into two groups, and the first group will be given vaginal progesterone (Lutinus 2*1) as rescue therapy, and the second group will be given subcutaneous progesterone (prolutex 1*1) as rescue therapy. Rescue treatment will not be applied to those whose serum progesterone level is 10 and above on the ET day. At the time of presumed LH surge, E2 (estradiol), P4 (progesterone), LH will be checked and the endometrial thickness in the uterus will be measured.
If the patient's endometrium is suitable, embryo transfer will be performed and a blood pregnancy test will be performed 10-12 days later. The research is planned to last for a year, starting in August 2022 and ending in August 2023. Patient data will be evaluated as prospective data analysis.
- Conditions
- Infertility, IVF, Progesterone
- Being tested
- Normal Progesterone group, Low Progesterone group
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal Progesterone groupOther
No progesterone supplementation
Low Progesterone groupOther
Progesterone level <10 ng/mL on ET day. If serum progesterone levels were <10 ng/ml at ET day, vaginal pills (Lutinus 2*1) or SC progesterone daily (Prolutex) was given to patients and ET was performed on the same day. Progesterone supplementation was discontinued if there was no pregnancy. Progesterone supplementation at the same dose was continued until 10 gestational weeks for viable pregnancies.
| Study group | Role | What they receive |
|---|---|---|
| Normal Progesterone group | Experimental | Progesterone level ≥ 10 ng/mL on ET day. Receives: Other: Normal Progesterone group |
| Low Progesterone group | Active comparator | Progesterone level <10 ng/mL on ET day. Grup a Rescue vaginal progesterone, Grup b Rescue subcutan progesterone Receives: Other: Low Progesterone group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rates
fetal heartbeat by transvaginal ultrasound
Measured: average of 1 year
Secondary outcomes (2)
Ongoing pregnancy rate
Pregnancies that continue until the 12th week of pregnancy
Measured: average of 15 month
Miscarriage
any clinical pregnancy lost before pregnancy week 12
Measured: average of 15 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2022
- Study start8 Aug 2022
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Bezmialem Vakif UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bezmialem Vakif University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- pınar özcan, PhD, Principal investigator, Bezmialem Foundation UniversityCem Demirel, PhD, Study chair, Acıbadem Ataşehir HospitalMehmet Erdem, PhD, Study chair, Novaart IVF and Women's Health Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05481684
- Sponsor's protocol ID
- 26.07.2022-E.71262
- Status last verified
- Aug 2023
- First submitted
- 28 Jul 2022
- Last updated
- 1 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, Vanderpoel S, Racowsky C. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017 Mar 1;23(2):139-155. doi: 10.1093/humupd/dmw038.
PubMed 27827818Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008 Jul;90(1):186-93. doi: 10.1016/j.fertnstert.2007.06.010. Epub 2007 Nov 5.
PubMed 17980870Groenewoud ER, Cohlen BJ, Macklon NS. Programming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles. Fertil Steril. 2018 May;109(5):768-774. doi: 10.1016/j.fertnstert.2018.02.135.
PubMed 29778369
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Importance of Embryo Transfer Day Progesterone Value in Natural Cycle Frozen Embryo Transfers and the Evaluation of the Effect of Rescue Therapy on Pregnancy Outcomes in Patients With Low Progesterone Levels: A Multicentric Randomized Controlled Study.
- ClinicalTrials.gov ID
- NCT05481684
- Acronym / sponsor ID
- 26.07.2022-E.71262
- Conditions
- Infertility, IVF, Progesterone
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Bezmialem Vakif UniversityUniversity, hospital or other
- Study start
- 8 Aug 2022 (actual)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 1 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Thanks to recent advances in clinical practice and laboratory, embryo cryopreservation has become the first-line procedure in assisted reproductive technology. Improved laboratory techniques have increased the number of available embryos derived from an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle. Implementation of a single embryo transfer policy to improve vitrification, improve postwarm embryo survival rates, and reduce multiple pregnancies without reducing cumulative birth rates has contributed to an increase in the number of frozen-warms (1,2) Embryo freezing; It is becoming an adopted practice for an increasing number of indications, including prevention of ovarian hyperstimulation syndrome, preimplantation genetic testing (PGT), late follicular phase progesterone elevation, and embryo-endometrial asynchrony. In our study, we are investigating the effect of pre-transfer serum progesterone levels on pregnancy outcomes in patients who underwent frozen-thawed embryo transfer.Supplementary progesterone preparations can be used to prevent luteal phase defect and to provide progesterone support in cycle preparations for frozen-thawed embryo transfer(3). The aim in this study is to show the effect of serum progesterone level on the pregnancy results on the day of embryo transfer in natural cycles.
Detailed description
The patients to be included in the study are the patients followed in the IVF centers of two different hospitals.Patients between the ages of 20-42 and having a BMI of <30, who are scheduled for IVF due to tubal factor, infertility of unknown cause, mild male factor, and anovulation will be included in the study. An antagonist (Cetrotide; Serono, Geneva, Switzerland) protocol will be used for controlled ovarian hyperstimulation, and recombinant follicle-stimulating hormone (recFSH) (Gonal F; Serono, Geneva, Switzerland) and Human Menopausal Gonadotropin (HMG) (Merional; Switzerland) will be used for stimulation. The dose of gonadotropin to be administered to patients is in the range of 150 to 450 IU per day and will be determined according to the age of each patient, serum FSH and E2 levels in the early follicular phase, and the number of antral follicles determined by ultrasound in the early follicular phase. Adjustment of the gonadotropin dose during the treatment will be adjusted by serial ultrasound measurements of the follicle diameters developed during the treatment and serum E2 levels. The patient's eggs will be collected at 34-36 hours. Fertilization check will be done the next day. During 3-5 days of embryo culture, embryo quality will be determined according to the D.Gardner criteria (1999). Embryos will be frozen on the 3rd or 5th day and transferred to a planned frozen cycle within the next month. In the frozen cycle, basal ultrasonography is performed on the 3rd day of the menstrual cycle and if there is no follicle over 10 mm, the patient will be called for a control on the 10th day of the cycle if the endometrial thickness is less than 5 mm. In the follow-ups after the 10th day, daily LH monitoring will be performed with the dominant follicle reaching 15 m in diameter. When the LH level increases 1.8 times, it will be considered as LH surge. Serum progesterone level will be checked on embrio transfer day. The patients with serum progesterone value below 10 on the day of embryo transfer will be divided into two groups, and the first group will be given vaginal progesterone (Lutinus 2*1) as rescue therapy, and the second group will be given subcutaneous progesterone (prolutex 1*1) as rescue therapy. Rescue treatment will not be applied to those whose serum progesterone level is 10 and above on the ET day. At the time of presumed LH surge, E2 (estradiol), P4 (progesterone), LH will be checked and the endometrial thickness in the uterus will be measured.
If the patient's endometrium is suitable, embryo transfer will be performed and a blood pregnancy test will be performed 10-12 days later. The research is planned to last for a year, starting in August 2022 and ending in August 2023. Patient data will be evaluated as prospective data analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal Progesterone group | Experimental | Other: Normal Progesterone groupProgesterone level ≥ 10 ng/mL on ET day. |
| Low Progesterone group | Active comparator | Other: Low Progesterone groupProgesterone level <10 ng/mL on ET day. Grup a Rescue vaginal progesterone, Grup b Rescue subcutan progesterone |
Who may qualify
- Ages
- 20 to 42 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Women between the ages of 20-42 who applied to the infertility clinic
- BMI<30
Key exclusion criteria (5 listed)
- Severe male factor (Sperm count <5 ml/ml, progressively motile sperm count <10%)
- Intrauterine structural anomalies not corrected by surgery
- Hydrosalpenx if not underwent surgery
- Refusal to participate in the study
- cycle cancelation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Normal Progesterone groupNo progesterone supplementation | Other | Normal Progesterone group |
| Low Progesterone groupProgesterone level <10 ng/mL on ET day. If serum progesterone levels were <10 ng/ml at ET day, vaginal pills (Lutinus 2*1) or SC progesterone daily (Prolutex) was given to patients and ET was performed on the same day. Progesterone supplementation was discontinued if there was no pregnancy. Progesterone supplementation at the same dose was continued until 10 gestational weeks for viable pregnancies. | Other | Low Progesterone group |
Primary outcome
Clinical pregnancy rates
Time frame: average of 1 year
fetal heartbeat by transvaginal ultrasound
2 secondary outcomes
Ongoing pregnancy rate
Time frame: average of 15 month
Miscarriage
Time frame: average of 15 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
- Results publication: PubMed 27827818Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, Vanderpoel S, Racowsky C. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017 Mar 1;23(2):139-155. doi: 10.1093/humupd/dmw038.
- Results publication: PubMed 17980870Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008 Jul;90(1):186-93. doi: 10.1016/j.fertnstert.2007.06.010. Epub 2007 Nov 5.
- Results publication: PubMed 29778369Groenewoud ER, Cohlen BJ, Macklon NS. Programming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles. Fertil Steril. 2018 May;109(5):768-774. doi: 10.1016/j.fertnstert.2018.02.135.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
pınar özcan, PhD principal investigator
Bezmialem Foundation University
Cem Demirel, PhD study chair
Acıbadem Ataşehir Hospital
Mehmet Erdem, PhD study chair
Novaart IVF and Women's Health Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Normal Progesterone group and Low Progesterone group in people with Infertility and IVF, run by Bezmialem Vakif University at 3 sites in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact pınar özcan, PhD (+905414031625, pinarozcan@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical pregnancy rates (time frame: average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05481684, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2023.