IVFMONARTNCT04804020
Natural Cycle vs. Modified Natural Cycle vs. Artificial Cycle Protocol for Endometrial Preparation.
A study testing NC, mNC and AC in people with IVF and Frozen Embryo Transfer, run by Mỹ Đức Hospital at 1 site in Vietnam.
Trial summary
Fresh embryo transfer is a routine procedure in vitro fertilization (IVF) treatment. Since the first live birth after an IVF-FET (frozen embryo transfer), recent years have seen a dramatic rise in the number of FET cycles. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- IVF, Frozen Embryo Transfer
- What is being tested?
- NC, mNC and AC
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,428 participants
- Where
- 1 siteVietnam
- Study dates
- 22 Mar 2021to 31 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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Aged of 18 to 45
- Having menstrual cycle duration of 24 to 38 days
- Undergoing no more than 3 previous IVF/ICSI - FET cycles
- Planning a frozen-thawed embryo transfer
- Agreeing to have no more than 2 day 3 and 1 day 5 embryos transferred
- Not participating in another IVF study at the same time
Who cannot join
- Menopausal/ Anovulatory women
- Having contraindication for exogenous hormones administration: breast cancer, risks of venous thromboembolism
- Having embryos from in vitro Maturation or oocyte donation or PGT (pre-implantation genetics testings) cycles
- Having uterine abnormalities (e.g., adenomyosis, intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus; unremoved hydrosalpinx, endometrial polyp)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effectiveness and Safety of the Three Endometrial Preparation Protocols for Frozen Embryo Transfer Natural Cycle, Modified Natural Cycle and Artificial Cycle: a Randomized Controlled Trial
Fresh embryo transfer is a routine procedure in vitro fertilization (IVF) treatment. Since the first live birth after an IVF-FET (frozen embryo transfer), recent years have seen a dramatic rise in the number of FET cycles. Three endometrial preparation protocols for frozen-thawed embryo transfer, including artificial, natural, modified natural protocol, have been studied and applied to maximize treatment outcomes. However, those methods are being applied empirically as their efficacy and safety are yet to be determined. The objective of this study is to compare the effectiveness and safety of those protocols.
Read the detailed description
This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Viet Nam. Women who are potentially eligible will be provided information about the trial as long as their stimulation cycles are initiated. Screening for eligibility will be performed by treating physicians on day 2 of the menstrual cycle in the subsequent frozen embryo transfer cycles. Patients will be provided a copy of the informed consent documents. Written informed consent will be obtained by the investigator from all women before the enrolment. Women will be randomized (1:1:1) to AC (artificial cycle) or NC (natural cycle), or mNC (modified natural cycle) protocols using block randomization with a variable block size of 6 or 9 by an independent study coordinator via telephone, using a computer-generated random list (block size of 6, or 9).
Artificial protocol The endometrium is prepared using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day, ranging from the second or fourth menstruation day. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Utrogestan®; Besins) 800 mg/day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must be lasting for ≥9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. In cases where a dominant follicle emerged, serum LH and progesterone will be determined to rule out luteinization. If LH concentrations are <13 IU and progesterone levels <15 nmol/l, luteinization will deem not to have occurred, and FET was performed.
Natural protocol The first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patient's uterus or adnexa. The second ultrasound will be performed on the sixth day of the cycle. Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter to a level of 20 IU/l or more detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages.
modified Natural protocol The first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patient's uterus or adnexa. A second ultrasound scan will be performed on the sixth day of the cycle; if there is at least one follicle with a diameter of ≥12 mm, an ultrasound scan will be performed daily. When the dominant follicle's mean diameter is ≥16 mm, human chorionic gonadotropin - hCG (Ovitrelle® 250 μg; Merck, Kenilworth, NJ, USA) will be injected to trigger ovulation. Embryo transfer will be scheduled by the time of the hCG injection and embryo stages.
Serum progesterone level was also evaluated using the electrochemiluminescence immunoassay (Elecssys Progesterone III, Cobas®, Roche diagnosis, Germany) with a CV of 5.2%.
Serum progesterone was measured at 3 time points:
- 1st sample: On day 2 to day 4 of the cycle, before starting the endometrial preparation regime
- 2nd sample:
- For AC protocol: Before administration of vaginal progesterone
- For mNC protocol: Before hCG administration
- For NC protocol: When an LH surge initiation was recorded, i.e., serum LH measured 20 IU/L or more
- 3rd sample: On the day of frozen embryo transfer at 8 a.m. Cycle cancellation
- Artificial protocol: When the endometrial thickness is below 7mm after a duration of estradiol administration of ≥21 days or the emergence of a dominant follicle.
- Natural cycle protocol: When there is no development of follicle, or no dominant follicle (≥14 mm), or no onset of LH surge observed after a duration of ≥21 days or unexpected spontaneous ovulation appears.
- modified Natural cycle protocol: When there is no developing follicle (>16mm) observed after a duration of ≥21 days or pre-hCG unexpected spontaneous ovulation appears.
- Both protocols: When there is no embryo surviving after thawing.
Frozen embryo transfer:
A maximum of 2 day-3 and one day-5 embryos will be thawed on the day of embryo transfer, three days after the start of progesterone. Two hours after thawing, surviving embryos will be transferred into the uterus under ultrasound guidance using a soft uterine catheter (Gynétics®, Belgium).
A series of progesterone levels evaluation will be performed at three times: (1) at the start of the cycle, (2) Before the time the embryo transfer is scheduled, (3) On the day of embryo transfer.
The blood sample at the start of the cycle will be stored for further epigenetics analysis.
Future babies' health will also be performed separately.
- Conditions
- IVF, Frozen Embryo Transfer
- Being tested
- NC, mNC, AC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NCProcedure or surgery
The first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patients' uterus or adnexa. The second ultrasound will be performed on the sixth day of the cycle. Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter9 to a level of 20 IU/l or more10 detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages.
mNCProcedure or surgery
The first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to patients' uterus or adnexa. A second ultrasound scan will be performed on the sixth day of the cycle; if there is at least one follicle with a diameter of ≥12 mm, an ultrasound scan will be performed daily. When the dominant follicle's mean diameter is ≥16 mm, human chorionic gonadotropin (Ovitrelle® 250 μg; Merck, Kenilworth, NJ, USA) will be injected to trigger ovulation. Embryo transfer will be scheduled by the time of the hCG injection and embryo stages.
ACProcedure or surgery
The endometrium is prepared using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day, ranging from the second or fourth menstruation day. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Utrogestan®; Besins) 800 mg/day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must be lasting for ≥9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages.
| Study group | Role | What they receive |
|---|---|---|
| NC (Natural cycle) | Active comparator | Performing the first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patients' uterus or adnexa. The second ultrasound will be performed on the sixth day of the cycle. Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter to a level of 20 IU/l or more detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages. Receives: Procedure: NC |
| mMC (modified Natural cycle) | Active comparator | Performing the first ultrasound scan on the second to the fourth day of the menstrual cycle to identify any problem related to patients' uterus or adnexa. A second ultrasound scan will be performed on the sixth day of the cycle; if there is at least one follicle with a diameter of ≥12 mm, an ultrasound scan will be performed daily. When the dominant follicle's mean diameter is ≥16 mm, human chorionic gonadotropin (Ovitrelle® 250 μg; Merck, Kenilworth, NJ, USA) will be injected to trigger ovulation. Embryo transfer will be scheduled by the time of the hCG injection and embryo stages. Receives: Procedure: mNC |
| AC (Artificial cycle) | Active comparator | Preparing the endometrium by using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day, ranging from the second or fourth menstruation day. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Utrogestan®; Besins) 800 mg/day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must be lasting for ≥9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Receives: Procedure: AC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate after one frozen embryo transfer cycle
Live birth is defined as the complete expulsion or extraction from a woman of a product of fertilisation, after 24 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 350 grams or more can be used if gestational age is unknown (twins are a single count).
Measured: At 24 weeks of gestation
Secondary outcomes (22)
Positive pregnancy test
Serum ß-hCG ≥25mIU/mL
Measured: At 2 weeks after embryo placement
Clinical pregnancy
Having at least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity
Measured: At 5 weeks after embryo placement
Ongoing pregnancy
Having at least 1 gestational sac on ultrasound at 12 weeks' gestation with heart beat activity
Measured: At 10 weeks after embryo placement
Implantation
Implantation rate is explained as the number of gestational sacs per number of embryos transferred.
Measured: At 3 weeks after embryo placement
Ectopic pregnancy
A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualisation, or histopathology
Measured: At 12 weeks of gestation
Miscarriage
The spontaneous loss of an intra-uterine pregnancy prior to or at 20 completed weeks of gestational age
Measured: At 20 weeks of gestation
Preterm delivery
Multiple definitions, defined as delivery at <24, <28, <32, <37 completed weeks
Measured: At 22, 28, 32 weeks and 37 weeks of gestation
Endometrial preparation cycles cancelation
Cycle cancelling due to:
- Artificial protocol: When the endometrial thickness is below 7mm after a duration of estradiol administration of ≥21 days or the emergence of a dominant follicle.
- Natural cycle protocol: When there is no development of follicle, or no dominant follicle (≥14 mm), or no onset of LH surge observed after a duration of ≥21 days or unexpected spontaneous ovulation appears.
- modified Natural cycle protocol: When there is no developing follicle (>16mm) observed after a duration of ≥21 days or pre-hCG unexpected spontaneous ovulation appears.
- Both protocols: When there is no embryo surviving after thawing.
- Fluid in uterine cavity
- Side effects of taking exogenous hormones: severe migraine/headache, mood swings, vaginal bleeding, nausea; venous thromboembolism, stroke.
- Patient preferences
Measured: At 3 weeks from the start of treatment cycle
Gestational diabetes mellitus
using a 75g oral glucose tolerance test
Measured: At 24 to 28 weeks of gestation
Hypertensive disorders of pregnancy
Pregnancy-induced hypertension, pre-eclampsia and eclampsia
Measured: At 20 weeks of gestation or beyond
Birth weight
Weight of singletons and twins
Measured: At the time of delivery
Low birth weight
Weight < 2500 gm at birth
Measured: At birth
Very low birth weight
Weight < 1500 gm at birth
Measured: At birth
High birth weight
Weight >4000 gm at birth
Measured: At birth
Very high birth weight
Weight >4500 gm at birth
Measured: At birth
Major congenital abnormalities
Structural, functional, and genetic anomalies, that occur during pregnancy, and identified antenatally, at birth, or later in life, and require surgical repair of a defect, or are visually evident, or are life-threatening, or cause death. Any congenital anomaly will be included as followed definition of congenital abnormalities in Surveillance of Congenital Anomalies by Division of Birth Defects and Developmental Disabilities, NCBDDD, Centers for Disease Control and Prevention (2020).
Measured: At birth
Admission to NICU
The admittance of the newborn to NICU
Measured: At birth
Venous thromboembolism relating to medication
Venous thromboembolism is diagnosed after clinical examination, ultrasound scan and blood test
Measured: From the start of treatment up to 10 weeks of gestation
Multiple pregnancy
≥1 gestational sac at early pregnancy ultrasound
Measured: At 6 to 8 weeks' gestation
Multiple delivery
Birth of more than one baby beyond 24 weeks
Measured: At 24 weeks' gestation
Cost-effectiveness
Including direct and indirect costs; costs related to complications treatment. Cost data will be collected for a supplementary analysis and will be reported in a separated paper.
Measured: Two year after randomization
Still birth
The death of a fetus prior to the complete expulsion or extraction from its mother after 20 completed weeks of gestational age. The death is determined by the fact that, after such separation, the fetus does not breathe or show any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles.
Measured: At 20 weeks' gestation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2021
- Study start22 Mar 2021
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for IVFStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,428 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mỹ Đức Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lan N Vuong, MD, PhD, Principal investigator, University of Medicine and Pharmacy at Ho Chi Minh City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04804020
- Sponsor's protocol ID
- 187/HĐĐĐ-ĐHYD
- Acronym
- MONART
- Status last verified
- Jul 2024
- First submitted
- 11 Mar 2021
- Last updated
- 29 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ho VNA, Pham TD, Nguyen NT, Wang R, Norman RJ, Mol BW, Ho TM, Vuong LN. Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial. Lancet. 2024 Jul 20;404(10449):266-275. doi: 10.1016/S0140-6736(24)00756-6. Epub 2024 Jun 26.
PubMed 38944045
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness and Safety of the Three Endometrial Preparation Protocols for Frozen Embryo Transfer Natural Cycle, Modified Natural Cycle and Artificial Cycle: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04804020
- Acronym / sponsor ID
- MONART / 187/HĐĐĐ-ĐHYD
- Conditions
- IVF, Frozen Embryo Transfer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,428 participants (actual)
- Lead sponsor
- Mỹ Đức HospitalUniversity, hospital or other
- Collaborators
- University of Medicine and Pharmacy at Ho Chi Minh City
- Study start
- 22 Mar 2021 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 18 Mar 2021 (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.
Fresh embryo transfer is a routine procedure in vitro fertilization (IVF) treatment. Since the first live birth after an IVF-FET (frozen embryo transfer), recent years have seen a dramatic rise in the number of FET cycles. Three endometrial preparation protocols for frozen-thawed embryo transfer, including artificial, natural, modified natural protocol, have been studied and applied to maximize treatment outcomes. However, those methods are being applied empirically as their efficacy and safety are yet to be determined. The objective of this study is to compare the effectiveness and safety of those protocols.
Detailed description
This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Viet Nam. Women who are potentially eligible will be provided information about the trial as long as their stimulation cycles are initiated. Screening for eligibility will be performed by treating physicians on day 2 of the menstrual cycle in the subsequent frozen embryo transfer cycles. Patients will be provided a copy of the informed consent documents. Written informed consent will be obtained by the investigator from all women before the enrolment. Women will be randomized (1:1:1) to AC (artificial cycle) or NC (natural cycle), or mNC (modified natural cycle) protocols using block randomization with a variable block size of 6 or 9 by an independent study coordinator via telephone, using a computer-generated random list (block size of 6, or 9).
Artificial protocol The endometrium is prepared using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day, ranging from the second or fourth menstruation day. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Utrogestan®; Besins) 800 mg/day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must be lasting for ≥9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. In cases where a dominant follicle emerged, serum LH and progesterone will be determined to rule out luteinization. If LH concentrations are <13 IU and progesterone levels <15 nmol/l, luteinization will deem not to have occurred, and FET was performed.
Natural protocol The first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patient's uterus or adnexa. The second ultrasound will be performed on the sixth day of the cycle. Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter to a level of 20 IU/l or more detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages.
modified Natural protocol The first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patient's uterus or adnexa. A second ultrasound scan will be performed on the sixth day of the cycle; if there is at least one follicle with a diameter of ≥12 mm, an ultrasound scan will be performed daily. When the dominant follicle's mean diameter is ≥16 mm, human chorionic gonadotropin - hCG (Ovitrelle® 250 μg; Merck, Kenilworth, NJ, USA) will be injected to trigger ovulation. Embryo transfer will be scheduled by the time of the hCG injection and embryo stages.
Serum progesterone level was also evaluated using the electrochemiluminescence immunoassay (Elecssys Progesterone III, Cobas®, Roche diagnosis, Germany) with a CV of 5.2%.
Serum progesterone was measured at 3 time points:
- 1st sample: On day 2 to day 4 of the cycle, before starting the endometrial preparation regime
- 2nd sample:
- For AC protocol: Before administration of vaginal progesterone
- For mNC protocol: Before hCG administration
- For NC protocol: When an LH surge initiation was recorded, i.e., serum LH measured 20 IU/L or more
- 3rd sample: On the day of frozen embryo transfer at 8 a.m. Cycle cancellation
- Artificial protocol: When the endometrial thickness is below 7mm after a duration of estradiol administration of ≥21 days or the emergence of a dominant follicle.
- Natural cycle protocol: When there is no development of follicle, or no dominant follicle (≥14 mm), or no onset of LH surge observed after a duration of ≥21 days or unexpected spontaneous ovulation appears.
- modified Natural cycle protocol: When there is no developing follicle (>16mm) observed after a duration of ≥21 days or pre-hCG unexpected spontaneous ovulation appears.
- Both protocols: When there is no embryo surviving after thawing.
Frozen embryo transfer:
A maximum of 2 day-3 and one day-5 embryos will be thawed on the day of embryo transfer, three days after the start of progesterone. Two hours after thawing, surviving embryos will be transferred into the uterus under ultrasound guidance using a soft uterine catheter (Gynétics®, Belgium).
A series of progesterone levels evaluation will be performed at three times: (1) at the start of the cycle, (2) Before the time the embryo transfer is scheduled, (3) On the day of embryo transfer.
The blood sample at the start of the cycle will be stored for further epigenetics analysis.
Future babies' health will also be performed separately.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NC (Natural cycle) | Active comparator | Procedure: NCPerforming the first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patients' uterus or adnexa. The second ultrasound will be performed on the sixth day of the cycle. Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter to a level of 20 IU/l or more detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages. |
| mMC (modified Natural cycle) | Active comparator | Procedure: mNCPerforming the first ultrasound scan on the second to the fourth day of the menstrual cycle to identify any problem related to patients' uterus or adnexa. A second ultrasound scan will be performed on the sixth day of the cycle; if there is at least one follicle with a diameter of ≥12 mm, an ultrasound scan will be performed daily. When the dominant follicle's mean diameter is ≥16 mm, human chorionic gonadotropin (Ovitrelle® 250 μg; Merck, Kenilworth, NJ, USA) will be injected to trigger ovulation. Embryo transfer will be scheduled by the time of the hCG injection and embryo stages. |
| AC (Artificial cycle) | Active comparator | Procedure: ACPreparing the endometrium by using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day, ranging from the second or fourth menstruation day. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Utrogestan®; Besins) 800 mg/day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must be lasting for ≥9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Aged of 18 to 45
- Having menstrual cycle duration of 24 to 38 days
- Undergoing no more than 3 previous IVF/ICSI - FET cycles
- Planning a frozen-thawed embryo transfer
- Agreeing to have no more than 2 day 3 and 1 day 5 embryos transferred
Key exclusion criteria (4 listed)
- Menopausal/ Anovulatory women
- Having contraindication for exogenous hormones administration: breast cancer, risks of venous thromboembolism
- Having embryos from in vitro Maturation or oocyte donation or PGT (pre-implantation genetics testings) cycles
- Having uterine abnormalities (e.g., adenomyosis, intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus; unremoved hydrosalpinx, endometrial polyp)
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 |
|---|---|---|
| NCThe first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to the patients' uterus or adnexa. The second ultrasound will be performed on the sixth day of the cycle. Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter9 to a level of 20 IU/l or more10 detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages. | Procedure or surgery | NC (Natural cycle) |
| mNCThe first ultrasound scan will be performed on the second to the fourth day of the menstrual cycle to identify any problem related to patients' uterus or adnexa. A second ultrasound scan will be performed on the sixth day of the cycle; if there is at least one follicle with a diameter of ≥12 mm, an ultrasound scan will be performed daily. When the dominant follicle's mean diameter is ≥16 mm, human chorionic gonadotropin (Ovitrelle® 250 μg; Merck, Kenilworth, NJ, USA) will be injected to trigger ovulation. Embryo transfer will be scheduled by the time of the hCG injection and embryo stages. | Procedure or surgery | mMC (modified Natural cycle) |
| ACThe endometrium is prepared using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day, ranging from the second or fourth menstruation day. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Utrogestan®; Besins) 800 mg/day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must be lasting for ≥9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. | Procedure or surgery | AC (Artificial cycle) |
Primary outcome
Live birth rate after one frozen embryo transfer cycle
Time frame: At 24 weeks of gestation
Live birth is defined as the complete expulsion or extraction from a woman of a product of fertilisation, after 24 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 350 grams or more can be used if gestational age is unknown (twins are a single count).
22 secondary outcomes
Positive pregnancy test
Time frame: At 2 weeks after embryo placement
Clinical pregnancy
Time frame: At 5 weeks after embryo placement
Ongoing pregnancy
Time frame: At 10 weeks after embryo placement
Implantation
Time frame: At 3 weeks after embryo placement
Ectopic pregnancy
Time frame: At 12 weeks of gestation
Miscarriage
Time frame: At 20 weeks of gestation
Preterm delivery
Time frame: At 22, 28, 32 weeks and 37 weeks of gestation
Endometrial preparation cycles cancelation
Time frame: At 3 weeks from the start of treatment cycle
Gestational diabetes mellitus
Time frame: At 24 to 28 weeks of gestation
Hypertensive disorders of pregnancy
Time frame: At 20 weeks of gestation or beyond
Birth weight
Time frame: At the time of delivery
Low birth weight
Time frame: At birth
Very low birth weight
Time frame: At birth
High birth weight
Time frame: At birth
Very high birth weight
Time frame: At birth
Major congenital abnormalities
Time frame: At birth
Admission to NICU
Time frame: At birth
Venous thromboembolism relating to medication
Time frame: From the start of treatment up to 10 weeks of gestation
Multiple pregnancy
Time frame: At 6 to 8 weeks' gestation
Multiple delivery
Time frame: At 24 weeks' gestation
Cost-effectiveness
Time frame: Two year after randomization
Still birth
Time frame: At 20 weeks' gestation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2024.
- Derived from this study: PubMed 38944045Ho VNA, Pham TD, Nguyen NT, Wang R, Norman RJ, Mol BW, Ho TM, Vuong LN. Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial. Lancet. 2024 Jul 20;404(10449):266-275. doi: 10.1016/S0140-6736(24)00756-6. Epub 2024 Jun 26.
- Individual participant dataSharing planned: No
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Trigger Timing in Ovarian Stimulations
IVF Outcome
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.
Lan N Vuong, MD, PhD principal investigator
University of Medicine and Pharmacy at Ho Chi Minh City
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NC, mNC and AC in people with IVF and Frozen Embryo Transfer, run by Mỹ Đức Hospital at 1 site in Vietnam.
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 6 inclusion and 4 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: finished, as of the sponsor's last update on 29 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Vietnam. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate after one frozen embryo transfer cycle (time frame: At 24 weeks of gestation). 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 NCT04804020, which also lists 1 linked publication.
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 29 Jul 2024.