AdenomyosisFET-ADENCT06239376
Artificial Cycle With or Without GnRH Agonist Pre-treatment for Frozen Embryo Transfer in Adenomyosis Patients
A study testing GnRHa+AI - AC and Artificial cycle in people with Adenomyosis and IVF, run by Mỹ Đức Hospital at 1 site in Vietnam.
Trial summary
This randomized clinical trial aims to assess the comparative effectiveness of two distinct endometrial preparation protocols for frozen embryo transfer (FET) among women with adenomyosis undergoing IVF/ICSI. Specifically, it seeks to address the following key questions: 1. Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- Adenomyosis, IVF, Frozen Embryo Transfer
- What is being tested?
- GnRHa+AI - AC and Artificial cycle
- 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
- 222 participants
- Where
- 1 siteVietnam
- Study dates
- 19 Feb 2024to 30 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Confirm diagnosis with adenomyosis by using transvaginal ultrasonography (MUSA consensus) and/or pelvic magnetic resonance imaging.
- Age between 18 - 42
- Undergo less or equal to three previous IVF cycles
- Indicate for frozen embryo transfer
- Agree to have not more than two day-3 embryo or one blastocyst (day-5 and day-6) transferred
- Not participating in any other study
Who cannot join
- Embryos from IVM cycle
- Having uterine or adnexal abnormalities (e.g., intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus; unremoved hydrosalpinx, endometrial polyp, submucosal leiomyoma, or leiomyoma with endometrial cavity distortion)
- Having contraindications for exogenous hormones administration: breast cancer, risks of venous thromboembolism
- Embryos from the oocyte donation cycle.
- Patients with a history of GnRH injection within three months, measured from the last GnRHa injection to the study screening date.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Vietnam1 site, 1 recruiting
- Recruiting
My Duc Hospital
Ho Chi Minh City, Ho Chi Minh City, 70000
Tuong M Ho, MSc, MD, +84 90 3633377, tuongho.ivfmd@gmail.com
About this study
Official title: The Effectiveness of the Two Different Endometrial Preparation Regimes for Frozen Embryo Transfer in Patients With Adenomyosis
This randomized clinical trial aims to assess the comparative effectiveness of two distinct endometrial preparation protocols for frozen embryo transfer (FET) among women with adenomyosis undergoing IVF/ICSI. Specifically, it seeks to address the following key questions:
- Does the protocol involving the combination of GnRH agonist and letrozole for down regulation with exogenous steroids (GnRHa+AI - AC) result in a higher live birth rate compared to the use of exogenous steroids alone (AC) in women with adenomyosis undergoing frozen embryo transfer?
- What are the common side effects of the GnRHa+AI - AC regimen?
Eligible participants will undergo screening before endometrial preparation for FET, following which they will be randomly assigned to one of two groups: GnRHa+AI - AC or AC. In the GnRHa+AI - AC group, participants will be pre-treated with GnRH agonist and letrozole two months before endometrial preparation. After this period, participants will return for endometrial preparation, and any side effects resulting from the down regulation will be evaluated. In contrast, the AC group will receive standard treatment.
Read the detailed description
- Adenomyosis is a benign gynecological disease in which the endometrial stroma invades the uterine myometrium. Adenomyosis affects approximately 10% of women of reproductive age. There are several hypothetical mechanisms in adenomyosis-associated infertility, including dysregulations of the myometrial architecture and function, chronic inflammation, presence of local oxygen, and altered endometrial function, which can cause implantation failure. The abnormal presence of endometrial tissue composed of glands and stroma impacts uterine smooth muscle's regular contractile function and peristalsis, resulting in menometrorrhagia, infertility, and adverse obstetric consequences. There is currently no consensus on the optimal protocol for endometrial preparation in this population, and a lack of data on this issue. Current protocols include routine protocols with or without the pre-treatment of GnRH agonist. However, it is still controversial whether GnRH agonist down-regulation can help patients with adenomyosis have better reproductive outcomes. To our knowledge, there have not been any randomized controlled trials to investigate the effectiveness of the protocols used for endometrial preparation in women with adenomyosis undergoing frozen embryo transfer.
- This will be a superiority-designed randomized clinical trial.
- This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Vietnam. Potentially eligible women 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 days 2nd - 4th 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 from all women by the investigator before enrollment.
- Women will be randomized (1:1) to either AC (artificial cycle) or GnRHa+AI - AC (Down-Regulation with GnRH agonist and Letrozole combined with artificial cycle) protocols using block randomization with a variable block size of 4, 6, using HOPE Epi with a computer-generated random list.
- Artificial cycle (AC): the endometrium will be prepared using oral estradiol valerate (Valiera; Abbott) 6 mg/day starting from the second or fourth day of the menstrual cycle (5). The endometrial thickness will be monitored from the tenth day of estradiol-priming onwards, and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day will be initiated when endometrial thickness reaches 7 mm or more and received oestradiol valerate for at least nine days.
Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Hormonal support will consist of oral estradiol valerate 4 mg/day and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day until the 7th week of gestation. Subsequently, progesterone alone (Cyclogest®; Actavis) at 400 mg twice times a day will be continued for luteal phase support until the 12th week of gestation.
- GnRH agonist + Letrozole - Artificial cycle protocol (GnRHa+AI - AC):
- Pre-treatment with GnRH agonist: GnRHa (Triptorelin - Diphereline®, Ipsen, France) will be injected at a dose of 3.75 mg on days 2nd - 4th of menstruation. In addition to GnRHa administration duration, the patients will be indicated letrozole 2.5 mg daily (Femara®, Novartis, Switzerland) to prevent the estradiol flare-up effect from the day of GnRH agonist injection. Repeat the same regimen for the second time 28 days after the first injection of GnRH agonist.
- After 55 days of Down Regulation with GnRH agonist, before starting the artificial cycle protocol for endometrial preparation, estradiol serum level will be tested before endometrial preparation.
- Endometrial preparation with AC protocol will be started 28 days after the second injection of GnRH agonist, as described previously
Frozen embryo transfer:
A maximum of 2 cleavage-stage embryos or 1 blastocyst will be thawed on the day of embryo transfer, three or five 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).
- Future babies' health evaluation and cost-effectiveness analysis will also be performed separately.
- Conditions
- Adenomyosis, IVF, Frozen Embryo Transfer
- Being tested
- GnRHa+AI - AC, Artificial cycle
- Medical subject headings
- Adenomyosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRHa+AI - ACProcedure or surgery
Also called DR-AC
Pre-treatment includes two doses of 3.75 mg GnRH agonist (Diphereline®, Ipsen, France) on days 2-4 of the menstrual cycle and 28 days later, along with daily 2.5 mg Letrozole (Femara®, Novartis, Switzerland) starting from the first agonist injection.
Endometrial preparation in an artificial cycle begins 28 days after the second agonist injection. Patients take 6 mg/day of oral estradiol valerate (Valiera; Abbott) at least 9 days before progesterone. Endometrial thickness is monitored starting on the 10th day. When it reaches ≥7 mm, 400 mg twice times a day of vaginal progesterone (Cyclogest®, Actavis, UK) is initiated. Embryo transfer aligns with progesterone initiation, taking the embryo's stage into account. Luteal phase support comprises oral estradiol valerate 4 mg/day and vaginal progesterone 400 mg twice times a day until the 7th week of gestational age (GA), followed by progesterone alone at 400 mg twice times a day up to the 12th week of GA.
Artificial cycleProcedure or surgery
Also called AC
The endometrium will be prepared using oral estradiol valerate (Valiera; Abbott) 6 mg/day starting from the 2nd to the 4th day of the menstrual cycle. The endometrial thickness will be monitored from day 10th onwards, and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must last for at least 9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Luteal phase support comprises estradiol 4 mg/day and vaginal progesterone 400 mg twice times a day until the 7th week of gestational age (GA), followed by progesterone alone at 400 mg twice times a day up to the 12th week of GA.
| Study group | Role | What they receive |
|---|---|---|
| GnRH agonist + Letrzole - Artificial Cycle | Active comparator | Pre-treatment includes two doses of 3.75 mg GnRH agonist (Diphereline®, Ipsen, France) on days 2-4 of the menstrual cycle and 28 days later, along with daily 2.5 mg Letrozole (Femara®, Novartis, Switzerland) starting from the first agonist injection.
Endometrial preparation in an artificial cycle begins 28 days after the second agonist injection. Patients will take 6 mg/day of oral estradiol valerate (Valiera; Abbott) at least 9 days before initiating progesterone. Endometrial thickness is monitored starting on the 10th day. When it reaches ≥7 mm, 400 mg twice times a day of vaginal progesterone (Cyclogest®, Actavis, UK) is initiated. Embryo transfer aligns with progesterone initiation, taking the embryo's stage into account. Luteal phase support comprises oral estradiol valerate 4 mg/day and vaginal progesterone 400 mg twice times a day until the 7th week of gestational age (GA), followed by progesterone alone at 400 mg twice times a day up to the 12th week of GA. Receives: Procedure: GnRHa+AI - AC |
| Artificial Cycle | Active comparator | The endometrium will be prepared using oral estradiol valerate (Valiera; Abbott) 6 mg/day starting from the 2nd to the 4th day of the menstrual cycle. The endometrial thickness will be monitored from day 10th onwards, and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must last for at least 9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Luteal phase support comprises oral estradiol valerate 4 mg/day and vaginal progesterone 400 mg twice times a day until the 7th week of gestational age (GA), followed by progesterone alone at 400 mg twice times a day up to the 12th week of GA. Receives: Procedure: Artificial cycle |
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 fertilization, after 22 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 500 grams or more can be used if gestational age is unknown
Measured: At 22 weeks of gestation
Secondary outcomes (26)
Cancellation rate
Cancellation due to: thin endometrium (thickness <7mm after ≥21 days using oral estradiol valerate), endometrial cavity fluid, functional cyst (homogeneous anechoic cyst with d ≥14 mm present after 10 days using estradiol valerate), or has side effects(Cluster headache, mood swing, abnormal uterine bleeding, nausea, vomit, VTE, stroke)
Measured: At 3 weeks from the start of artificial cycle
Hypoestrogenic side effects
Side effects include hot flushes, bone loss, vaginal dryness, decreased libido, unpredictable mood changes, and headache.
Measured: At 8 weeks from the start of the first dose of 3.75 mg GnRH agonist
Classification of adenomyosis
The classification of adenomyosis under ultrasound scan according to MUSA criteria
Measured: during ultrasound procedure
Differentiation of adenomyosis
The differentiation of adenomyosis under ultrasound scan according to MUSA criteria
Measured: during ultrasound procedure
Positive pregnancy test
Serum ß-hCG ≥25mIU/mL
Measured: At 2 weeks after embryo placement
Implantation rate
Implantation rate is explained as the number of gestational sacs per number of embryos transferred.
Measured: At 3 weeks after embryo placement
Clinical pregnancy
diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy at 6 weeks or more after the onset of the last menstrual period. In addition to intra-uterine pregnancy, it includes a clinically documented ectopic pregnancy.
Measured: At 5 weeks after embryo placement
Ectopic pregnancy
A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualisation, or histopathology
Measured: At 7 weeks of gestation
Ongoing pregnancy
Having at least one gestational sac on ultrasound at 12 weeks' gestation with heart beat activity
Measured: At 10 weeks after embryo placement
Miscarriage
The spontaneous loss of an intra-uterine pregnancy before 22 completed weeks of gestational age
Measured: before 22 completed weeks of gestational age
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
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
Gestational diabetes mellitus
GDM is diagnosed using a 75g oral glucose tolerance test
Measured: At 24 to 28 weeks of gestation
Hypertension in pregnancy
Pregnancy-induced hypertension, pre-eclampsia, eclampsia and HELLP syndrome
Measured: after 20 weeks of gestation or beyond
Major congenital abnormalities
Structural or functional disorders that occur during intra-uterine life and can be identified prenatally, at birth or later in life. Congenital anomalies can be caused by single gene defects, chromosomal disorders, multifactorial inheritance, environmental teratogens and micronutrient deficiencies. The time of identification should be reported. 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
Birth weight
Weight of singletons and twins
Measured: At the time of delivery
Low birth weight
Weight < 2500 gm at birth
Measured: At the time of delivery
Very low birth weight
Weight < 1500 gm at birth
Measured: At the time of delivery
High birth weight
Weight 4000 gm or 4500 gm at birth
Measured: At the time of delivery
Very high birth weight
Weight over than 4.500 g for women with diabetes, and a threshold of 5000 g for women without diabetes
Measured: At the time of delivery
Admission to NICU
The admittance of the newborn to NICU
Measured: At birth
Multiple pregnancy
≥2 gestational sac at early pregnancy ultrasound
Measured: At 6 to 8 weeks' gestation
Multiple delivery
Birth of more than one baby beyond 22 weeks
Measured: At 22 weeks' gestation
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
Neonatal mortality
Death of a live-born baby within 28 days of birth. This can be divided into early neonatal mortality, if death occurs in the first seven days after birth, and late neonatal if death occurs between eight and 28 days after delivery
Measured: within 28 days of birth
Direct costs to live birth
Total direct cost to have a live birth after embryo transfer. Direct cost include medical consultations, ovulation stimulation drugs, laboratory and embryology services, ultrasound scanning, medical procedures such as oocyte retrieval and embryo transfer, hospital charges, nursing and counselling services and administrative and overhead charges (Mark P. Connolly et al., 2010). Cost data will be collected for a supplementary analysis and will be reported in a separated paper.
Measured: At the time of delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2024
- Study start19 Feb 2024
- Primary completion15 Apr 2027 (estimated)
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for AdenomyosisStudies 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
- 222 participants (estimated)
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
- NCT06239376
- Sponsor's protocol ID
- 12/23/DD-BVMD
- Acronym
- FET-ADE
- Status last verified
- Jun 2026
- First submitted
- 18 Dec 2023
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020 Mar 26;382(13):1244-1256. doi: 10.1056/NEJMra1810764. No abstract available.
PubMed 32212520Szubert M, Kozirog E, Olszak O, Krygier-Kurz K, Kazmierczak J, Wilczynski J. Adenomyosis and Infertility-Review of Medical and Surgical Approaches. Int J Environ Res Public Health. 2021 Jan 30;18(3):1235. doi: 10.3390/ijerph18031235.
PubMed 33573117Antero MF, Ayhan A, Segars J, Shih IM. Pathology and Pathogenesis of Adenomyosis. Semin Reprod Med. 2020 May;38(2-03):108-118. doi: 10.1055/s-0040-1718922. Epub 2020 Oct 20.
PubMed 33080632Mumusoglu S, Polat M, Ozbek IY, Bozdag G, Papanikolaou EG, Esteves SC, Humaidan P, Yarali H. Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review. Front Endocrinol (Lausanne). 2021 Jul 9;12:688237. doi: 10.3389/fendo.2021.688237. eCollection 2021.
PubMed 34305815Zhang Y, Fu X, Gao S, Gao S, Gao S, Ma J, Chen ZJ. Preparation of the endometrium for frozen embryo transfer: an update on clinical practices. Reprod Biol Endocrinol. 2023 Jun 8;21(1):52. doi: 10.1186/s12958-023-01106-5.
PubMed 37291605Harmsen MJ, Van den Bosch T, de Leeuw RA, Dueholm M, Exacoustos C, Valentin L, Hehenkamp WJK, Groenman F, De Bruyn C, Rasmussen C, Lazzeri L, Jokubkiene L, Jurkovic D, Naftalin J, Tellum T, Bourne T, Timmerman D, Huirne JAF. Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure. Ultrasound Obstet Gynecol. 2022 Jul;60(1):118-131. doi: 10.1002/uog.24786.
PubMed 34587658
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of the Two Different Endometrial Preparation Regimes for Frozen Embryo Transfer in Patients With Adenomyosis
- ClinicalTrials.gov ID
- NCT06239376
- Acronym / sponsor ID
- FET-ADE / 12/23/DD-BVMD
- Conditions
- Adenomyosis, IVF, Frozen Embryo Transfer
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 222 participants (estimated)
- Lead sponsor
- Mỹ Đức HospitalUniversity, hospital or other
- Study start
- 19 Feb 2024 (actual)
- Primary completion
- 15 Apr 2027 (estimated)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 2 Feb 2024 (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.
This randomized clinical trial aims to assess the comparative effectiveness of two distinct endometrial preparation protocols for frozen embryo transfer (FET) among women with adenomyosis undergoing IVF/ICSI. Specifically, it seeks to address the following key questions:
- Does the protocol involving the combination of GnRH agonist and letrozole for down regulation with exogenous steroids (GnRHa+AI - AC) result in a higher live birth rate compared to the use of exogenous steroids alone (AC) in women with adenomyosis undergoing frozen embryo transfer?
- What are the common side effects of the GnRHa+AI - AC regimen?
Eligible participants will undergo screening before endometrial preparation for FET, following which they will be randomly assigned to one of two groups: GnRHa+AI - AC or AC. In the GnRHa+AI - AC group, participants will be pre-treated with GnRH agonist and letrozole two months before endometrial preparation. After this period, participants will return for endometrial preparation, and any side effects resulting from the down regulation will be evaluated. In contrast, the AC group will receive standard treatment.
Detailed description
- Adenomyosis is a benign gynecological disease in which the endometrial stroma invades the uterine myometrium. Adenomyosis affects approximately 10% of women of reproductive age. There are several hypothetical mechanisms in adenomyosis-associated infertility, including dysregulations of the myometrial architecture and function, chronic inflammation, presence of local oxygen, and altered endometrial function, which can cause implantation failure. The abnormal presence of endometrial tissue composed of glands and stroma impacts uterine smooth muscle's regular contractile function and peristalsis, resulting in menometrorrhagia, infertility, and adverse obstetric consequences. There is currently no consensus on the optimal protocol for endometrial preparation in this population, and a lack of data on this issue. Current protocols include routine protocols with or without the pre-treatment of GnRH agonist. However, it is still controversial whether GnRH agonist down-regulation can help patients with adenomyosis have better reproductive outcomes. To our knowledge, there have not been any randomized controlled trials to investigate the effectiveness of the protocols used for endometrial preparation in women with adenomyosis undergoing frozen embryo transfer.
- This will be a superiority-designed randomized clinical trial.
- This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Vietnam. Potentially eligible women 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 days 2nd - 4th 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 from all women by the investigator before enrollment.
- Women will be randomized (1:1) to either AC (artificial cycle) or GnRHa+AI - AC (Down-Regulation with GnRH agonist and Letrozole combined with artificial cycle) protocols using block randomization with a variable block size of 4, 6, using HOPE Epi with a computer-generated random list.
- Artificial cycle (AC): the endometrium will be prepared using oral estradiol valerate (Valiera; Abbott) 6 mg/day starting from the second or fourth day of the menstrual cycle (5). The endometrial thickness will be monitored from the tenth day of estradiol-priming onwards, and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day will be initiated when endometrial thickness reaches 7 mm or more and received oestradiol valerate for at least nine days.
Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Hormonal support will consist of oral estradiol valerate 4 mg/day and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day until the 7th week of gestation. Subsequently, progesterone alone (Cyclogest®; Actavis) at 400 mg twice times a day will be continued for luteal phase support until the 12th week of gestation.
- GnRH agonist + Letrozole - Artificial cycle protocol (GnRHa+AI - AC):
- Pre-treatment with GnRH agonist: GnRHa (Triptorelin - Diphereline®, Ipsen, France) will be injected at a dose of 3.75 mg on days 2nd - 4th of menstruation. In addition to GnRHa administration duration, the patients will be indicated letrozole 2.5 mg daily (Femara®, Novartis, Switzerland) to prevent the estradiol flare-up effect from the day of GnRH agonist injection. Repeat the same regimen for the second time 28 days after the first injection of GnRH agonist.
- After 55 days of Down Regulation with GnRH agonist, before starting the artificial cycle protocol for endometrial preparation, estradiol serum level will be tested before endometrial preparation.
- Endometrial preparation with AC protocol will be started 28 days after the second injection of GnRH agonist, as described previously
Frozen embryo transfer:
A maximum of 2 cleavage-stage embryos or 1 blastocyst will be thawed on the day of embryo transfer, three or five 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).
- Future babies' health evaluation and cost-effectiveness analysis will also be performed separately.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GnRH agonist + Letrzole - Artificial Cycle | Active comparator | Procedure: GnRHa+AI - ACPre-treatment includes two doses of 3.75 mg GnRH agonist (Diphereline®, Ipsen, France) on days 2-4 of the menstrual cycle and 28 days later, along with daily 2.5 mg Letrozole (Femara®, Novartis, Switzerland) starting from the first agonist injection. Endometrial preparation in an artificial cycle begins 28 days after the second agonist injection. Patients will take 6 mg/day of oral estradiol valerate (Valiera; Abbott) at least 9 days before initiating progesterone. Endometrial thickness is monitored starting on the 10th day. When it reaches ≥7 mm, 400 mg twice times a day of vaginal progesterone (Cyclogest®, Actavis, UK) is initiated. Embryo transfer aligns with progesterone initiation, taking the embryo's stage into account. Luteal phase support comprises oral estradiol valerate 4 mg/day and vaginal progesterone 400 mg twice times a day until the 7th week of gestational age (GA), followed by progesterone alone at 400 mg twice times a day up to the 12th week of GA. |
| Artificial Cycle | Active comparator | Procedure: Artificial cycleThe endometrium will be prepared using oral estradiol valerate (Valiera; Abbott) 6 mg/day starting from the 2nd to the 4th day of the menstrual cycle. The endometrial thickness will be monitored from day 10th onwards, and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must last for at least 9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Luteal phase support comprises oral estradiol valerate 4 mg/day and vaginal progesterone 400 mg twice times a day until the 7th week of gestational age (GA), followed by progesterone alone at 400 mg twice times a day up to the 12th week of GA. |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Confirm diagnosis with adenomyosis by using transvaginal ultrasonography (MUSA consensus) and/or pelvic magnetic resonance imaging.
- Age between 18 - 42
- Undergo less or equal to three previous IVF cycles
- Indicate for frozen embryo transfer
- Agree to have not more than two day-3 embryo or one blastocyst (day-5 and day-6) transferred
Key exclusion criteria (5 listed)
- Embryos from IVM cycle
- Having uterine or adnexal abnormalities (e.g., intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus; unremoved hydrosalpinx, endometrial polyp, submucosal leiomyoma, or leiomyoma with endometrial cavity distortion)
- Having contraindications for exogenous hormones administration: breast cancer, risks of venous thromboembolism
- Embryos from the oocyte donation cycle.
- Patients with a history of GnRH injection within three months, measured from the last GnRHa injection to the study screening date.
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 |
|---|---|---|
| GnRHa+AI - ACAlso: DR-ACPre-treatment includes two doses of 3.75 mg GnRH agonist (Diphereline®, Ipsen, France) on days 2-4 of the menstrual cycle and 28 days later, along with daily 2.5 mg Letrozole (Femara®, Novartis, Switzerland) starting from the first agonist injection. Endometrial preparation in an artificial cycle begins 28 days after the second agonist injection. Patients take 6 mg/day of oral estradiol valerate (Valiera; Abbott) at least 9 days before progesterone. Endometrial thickness is monitored starting on the 10th day. When it reaches ≥7 mm, 400 mg twice times a day of vaginal progesterone (Cyclogest®, Actavis, UK) is initiated. Embryo transfer aligns with progesterone initiation, taking the embryo's stage into account. Luteal phase support comprises oral estradiol valerate 4 mg/day and vaginal progesterone 400 mg twice times a day until the 7th week of gestational age (GA), followed by progesterone alone at 400 mg twice times a day up to the 12th week of GA. | Procedure or surgery | GnRH agonist + Letrzole - Artificial Cycle |
| Artificial cycleAlso: ACThe endometrium will be prepared using oral estradiol valerate (Valiera; Abbott) 6 mg/day starting from the 2nd to the 4th day of the menstrual cycle. The endometrial thickness will be monitored from day 10th onwards, and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day will be initiated when endometrial thickness reaches ≥7 mm. Estradiol exposure must last for at least 9 days before progesterone administration. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Luteal phase support comprises estradiol 4 mg/day and vaginal progesterone 400 mg twice times a day until the 7th week of gestational age (GA), followed by progesterone alone at 400 mg twice times a day up to the 12th week of GA. | Procedure or surgery | Artificial Cycle |
Primary outcome
Live birth rate after one frozen embryo transfer cycle
Time frame: At 22 weeks of gestation
Live birth is defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 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 500 grams or more can be used if gestational age is unknown
26 secondary outcomes
Cancellation rate
Time frame: At 3 weeks from the start of artificial cycle
Hypoestrogenic side effects
Time frame: At 8 weeks from the start of the first dose of 3.75 mg GnRH agonist
Classification of adenomyosis
Time frame: during ultrasound procedure
Differentiation of adenomyosis
Time frame: during ultrasound procedure
Positive pregnancy test
Time frame: At 2 weeks after embryo placement
Implantation rate
Time frame: At 3 weeks after embryo placement
Clinical pregnancy
Time frame: At 5 weeks after embryo placement
Ectopic pregnancy
Time frame: At 7 weeks of gestation
Ongoing pregnancy
Time frame: At 10 weeks after embryo placement
Miscarriage
Time frame: before 22 completed weeks of gestational age
Venous thromboembolism relating to medication
Time frame: From the start of treatment up to 10 weeks of gestation
Preterm delivery
Time frame: At 22, 28, 32 weeks and 37 weeks of gestation
Gestational diabetes mellitus
Time frame: At 24 to 28 weeks of gestation
Hypertension in pregnancy
Time frame: after 20 weeks of gestation or beyond
Major congenital abnormalities
Time frame: At birth
Birth weight
Time frame: At the time of delivery
Low birth weight
Time frame: At the time of delivery
Very low birth weight
Time frame: At the time of delivery
High birth weight
Time frame: At the time of delivery
Very high birth weight
Time frame: At the time of delivery
Admission to NICU
Time frame: At birth
Multiple pregnancy
Time frame: At 6 to 8 weeks' gestation
Multiple delivery
Time frame: At 22 weeks' gestation
Still birth
Time frame: At 20 weeks' gestation
Neonatal mortality
Time frame: within 28 days of birth
Direct costs to live birth
Time frame: At the time of delivery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Background: PubMed 32212520Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020 Mar 26;382(13):1244-1256. doi: 10.1056/NEJMra1810764. No abstract available.
- Background: PubMed 33573117Szubert M, Kozirog E, Olszak O, Krygier-Kurz K, Kazmierczak J, Wilczynski J. Adenomyosis and Infertility-Review of Medical and Surgical Approaches. Int J Environ Res Public Health. 2021 Jan 30;18(3):1235. doi: 10.3390/ijerph18031235.
- Background: PubMed 33080632Antero MF, Ayhan A, Segars J, Shih IM. Pathology and Pathogenesis of Adenomyosis. Semin Reprod Med. 2020 May;38(2-03):108-118. doi: 10.1055/s-0040-1718922. Epub 2020 Oct 20.
- Background: PubMed 34305815Mumusoglu S, Polat M, Ozbek IY, Bozdag G, Papanikolaou EG, Esteves SC, Humaidan P, Yarali H. Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review. Front Endocrinol (Lausanne). 2021 Jul 9;12:688237. doi: 10.3389/fendo.2021.688237. eCollection 2021.
- Background: PubMed 37291605Zhang Y, Fu X, Gao S, Gao S, Gao S, Ma J, Chen ZJ. Preparation of the endometrium for frozen embryo transfer: an update on clinical practices. Reprod Biol Endocrinol. 2023 Jun 8;21(1):52. doi: 10.1186/s12958-023-01106-5.
- Background: PubMed 34587658Harmsen MJ, Van den Bosch T, de Leeuw RA, Dueholm M, Exacoustos C, Valentin L, Hehenkamp WJK, Groenman F, De Bruyn C, Rasmussen C, Lazzeri L, Jokubkiene L, Jurkovic D, Naftalin J, Tellum T, Bourne T, Timmerman D, Huirne JAF. Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure. Ultrasound Obstet Gynecol. 2022 Jul;60(1):118-131. doi: 10.1002/uog.24786.
- 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.
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 GnRHa+AI - AC and Artificial cycle in people with Adenomyosis and IVF, 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 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: looking for participants now, as of the sponsor's last update on 1 Jul 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tien K Le, MD (+84962803875, bstien.lk@myduchospital.vn), or a site near the patient. 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 22 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 NCT06239376, which also lists 6 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 Jul 2026.