InfertilityNCT03428919
ICSI Versus Conventional IVF in Non-male Factor Couples
A study testing ICSI and IVF in people with Infertility, run by Mỹ Đức Hospital at 1 site in Vietnam.
Trial summary
Conventionally, ICSI was initially developed and has been shown to be an effective treatment for male factor infertility. It is increasingly being used for patients without a male factor diagnosis, despite the lack of clinical evidence to support its use. Moreover, ICSI is an invasive and expensive procedure. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Infertility
- What is being tested?
- ICSI and IVF
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,064 participants
- Where
- 1 siteVietnam
- Study dates
- 16 Mar 2018to 12 Aug 2020
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Having ≤ 2 IVF/ICSI cycles
- Total sperm count and motility are normal (WHO, 2010)
- Antagonist protocol
- Agree to have ≤ 2 embryos transferred
- Not participating in another IVF study at the same time
Who cannot join
- In-vitro maturation (IVM) cycles
- Using frozen semen
- Poor fertilization in previous cycle (≤ 25%)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effectiveness of Intracytoplasmic Sperm Injection Versus Conventional in Vitro Fertilization in Couples With Non-male Factor Infertility: a Randomized Controlled Trial
Conventionally, ICSI was initially developed and has been shown to be an effective treatment for male factor infertility. It is increasingly being used for patients without a male factor diagnosis, despite the lack of clinical evidence to support its use. Moreover, ICSI is an invasive and expensive procedure. This multi-center, randomized, controlled, parallel-group trial will be conducted to compare the effectiveness of ICSI versus conventional IVF in infertile couples scheduled for IVF treatment, in whom the male partner has normal sperm.
Read the detailed description
All patients undergoing IVF/ICSI will be treated with a GnRH antagonist protocol. Recombinant FSH (Puregon, MSD) will be given on day 2 or day 3 of menstrual cycle for 5 days. The starting dose is individualized for each patient based on the following criteria: AMH <0.7 ng/mL, dose 300 IU/day; AMH 0.7-2.1 ng/mL, dose 200 IU/day; AMH >2.1 ng/mL, dose 150 IU/day. After that, investigators can titrate the dose based on their clinical judgment. Follicular development will be monitored by ultrasound scanning and measurement of estradiol and progesterone levels, starting on day 5 of stimulation. Scanning and hormonal measurement will be repeated every 2 to 3 days, depending on the size of follicles. An antagonist is routinely used on day 5 until the day of triggering. Criteria for triggering, by hCG (Ovitrelle 250 mg, Merck, Germany) will be the presence of at least three leading follicles of 17 mm. In women with excessive follicular response (≥15 follicles ≥12 mm), 0,2 mg Triptorelin (Diphereline, Ipsen Beaufour, France) will be used when there are at least two leading follicles of 17 mm. Oocyte retrieval will be performed 36 hours after triggering.
Randomization and allocation of participants to study groups will be performed on the day of egg pick up, after having obtained the semen from the husband. Eligible participants that have provided informed consent will be randomised to either ICSI or conventional IVF.
In ICSI group, insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. OCCs will be stripped by using hyaluronidase. Only matured oocytes will be inseminated.
In conventional IVF group, insemination will be performed by conventional IVF. Two hours after retrieval, collected OCCs will be inseminated for another 2 hours, at a concentration of 100,000 motile sperm/ml. Inseminated OCCs will be cultured overnight in culture medium.
In both groups, fertilization check will be performed under inverted microscope at period of 16-18 hours after insemination. On day 3, embryo evaluation will be performed at fixed time point 66±2 hours after fertilization, using the Istanbul consensus. Embryo transfer will be performed on day 3 under ultrasound guidance. A maximum of 2 embryos will be transferred into the uterus. The remaining grade 1 and 2 embryos will be frozen. Luteal-phase support will be done with estradiol (Valiera 2mg) 8mg/day and vaginal progesterone 800mg/day (Cyclogest 400mg) until 7th week of gestation.
If there are contra-indications for fresh embryo transfer, a freeze-all strategy will be applied, using Cryotech technique. Indications for freeze-all include: risk of ovarian hyperstimulation syndrome (OHSS), premature progesterone rise (≥1.5 ng/ml), thin endometrium (<7 mm), fluid in cavity on day of embryo transfer, endometrial polyp, hydrosalpinx that have not removed before oocyte retrieval.
In the next cycle, endometrium will be prepared by using estradiol (Valiera 2 mg, 8 mg/day) orally, starting from day 2-3 of menstrual cycle. When the endometrium thickness reaches 8 mm or more, patients will start using progesterone vaginally (Cyclogest 400 mg, 800 mg/day). Embryo transfer will be performed 3 days after using progesterone. On the day of embryo transfer, embryos will be thawed. In the frozen/thawed cycle, the best embryos will be utilized first, as in fresh transfer. Two hours after thawing, a maximum of 2 surviving embryos will be transferred into the uterus under ultrasound guidance. Luteal phase support will be provided with estradiol (Valiera 2mg) 8mg/day and vaginal progesterone 800 mg/day (Cyclogest 400 mg) until the seventh week of gestation.
In both groups, clinicians who perform embryo transfer, either fresh or frozen cycles, will be blinded to the intervention.
A serum hCG will be measured 2 weeks after embryo transferred, and if positive, an ultrasound scan of the uterus will be performed at gestational weeks 7 and 12. At 11 - 12 weeks of gestation, participants will be referred to the Outpatient clininc, O\&G Department, My Duc hospital or An Sinh hospital for prenatal care until giving birth.
- Conditions
- Infertility
- Being tested
- ICSI, IVF
- Keywords
- ICSI, Conventional IVF, Non-male factor
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICSIProcedure or surgery
In ICSI group, insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. OCCs will be stripped by using hyaluronidase. Only matured oocytes will be inseminated.
IVFProcedure or surgery
In IVF group, insemination will be performed by conventional IVF. Two hours after retrieval, collected OCCs will be inseminated for another 2 hours, at a concentration of 100,000 motile sperm/ml. Inseminated OCCs will be cultured overnight in culture medium.
| Study group | Role | What they receive |
|---|---|---|
| Intracytoplasmic Sperm Injection (ICSI) | Active comparator | All patients will be treated with a GnRH antagonist protocol. hCG (Ovitrelle 250 mg) will be used in the presence of at least three leading follicles of 17 mm. In women with ≥15 follicles ≥12 mm, 0,2 mg Triptorelin (Diphereline) will be used when there is at least two leading follicles of 17 mm. Oocyte retrieval will be performed 36 hours after triggering.
Insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. OCCs will be stripped by using hyaluronidase. Only matured oocytes will be inseminated.
Fertilization check will be performed at period of 16-18 hours after insemination. Embryo transfer will be performed on day 3 under ultrasound guidance. A maximum of 2 embryos will be transferred into the uterus. The remaining grade 1 and 2 embryos will be frozen. Receives: Procedure: ICSI |
| In Vitro Fertilization (IVF) | Active comparator | All patients will be treated with a GnRH antagonist protocol. hCG (Ovitrelle 250 mg) will be used in the presence of at least three leading follicles of 17 mm. In women with ≥15 follicles ≥12 mm, 0,2 mg Triptorelin (Diphereline) will be used when there is at least two leading follicles of 17 mm. Oocyte retrieval will be performed 36 hours after triggering.
Insemination will be performed by conventional IVF. Two hours after retrieval, collected OCCs will be inseminated for another 2 hours (100,000 motile sperm/ml). Inseminated OCCs will be cultured overnight in culture medium.
Fertilization check will be performed at period of 16-18 hours after insemination. Embryo transfer will be performed on day 3. A maximum of 2 embryos will be transferred. The remaining grade 1-2 embryos will be frozen. Receives: Procedure: IVF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ongoing pregnancy resulting in live birth after the first embryo transfer of the started treatment cycle.
Live birth is defined as the birth of at least one newborn after 24 weeks' gestation that exhibits any sign of life (twin will be a single count).
For the timing of this occur, ongoing pregnancy will be used, conditional on the fact that this ongoing pregnancy results in live birth.
Measured: At 12 weeks of gestation
Secondary outcomes (57)
Fertilization rate per oocyte inseminated/injected
Fertilization is defined as the appearance of 2 PN
Measured: At 16-18 hours after injected or 17-19 hours after inseminated
Fertilization rate per oocyte retrieved
Fertilization is defined as the appearance of 2 PN
Measured: At 16-18 hours after injected or 17-19 hours after inseminated
Abnormal fertilization rate
Abnormal fertilization is defined as the appearance of 1PN or ≥3 PN
Measured: At 16-18 hours after injected or 17-19 hours after inseminated
Total fertilization failure rate
Total fertilization is defined as the absence of any zygotes with 2PN
Measured: At 16-18 hours after injected or 17-19 hours after inseminated
Number of embryos on day 3
Number of embryos on day 3
Measured: 3 days after oocytes pick-up day in IVF/ICSI
Number of good quality embryo on day 3
Numbers of embryos on day 3 with good quality
Measured: 3 days after oocytes pick-up day in IVF/ICSI
Number of embryo freezing on day 3
Number of embryos freezing on day 3
Measured: 3 days after oocytes pick-up day in IVF/ICSI
Positive pregnancy test
Positive pregnancy test is defined as a serum human chorionic gonadotropin level greater than 25 mIU/mL after the completion of the first transfer
Measured: 14 days after embryo transfer
Clinical pregnancy
Clinical pregnancy is defined as the presence of at least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity, after the completion of the first transfer
Measured: At 7 weeks' gestation
Implantation rate
Implantation rate is defined as the number of gestational sacs per number of embryos transferred after the completion of the first transfer
Measured: At 3 weeks after embryo transferred
Ongoing pregnancy
Ongoing pregnancy is defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond, after the completion of the first transfer
Measured: At 12 weeks' gestation
Cumulative ongoing pregnancy
Ongoing pregnancy is defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond, after transfer of all embryos from the started treatment cycle.
Measured: At 12 weeks' gestation at 12 months after randomization. After 12 months, most patients doing IVF have finished all their frozen embryos; therefore, we consider this time point for analyzing the cumulative ongoing pregnancy rate.
Ongoing pregnancy resulting in live birth obtained from all embryos from the first started treatment cycle
Live birth is defined as the birth of at least one newborn after 24 weeks' gestation that exhibits any sign of life (twin will be a single count).
Measured: 12 weeks of gestation at 12 months after randomization
Time from randomization to ongoing pregnancy
Time from randomization to ongoing pregnancy after the completion of the first transfer
Measured: 12 weeks of gestation after the completion of first transfer
Ovarian hyperstimulation syndrome (OHSS)
Symptoms of OHSS
Measured: At 10 days after hCG injection and 14 days after embryo transfer
Ectopic pregnancy
A pregnancy in which implantation takes place outside the uterine cavity after completion of the first transfer
Measured: At 12 weeks of gestation after the completion of the first transfer
Ectopic pregnancy
A pregnancy in which implantation takes place outside the uterine cavity after transfer of all embryos from the started treatment cycle.
Measured: At 12 weeks of gestation at 12 months after randomization.
Miscarriage
The loss of a clinical pregnancy at 24 weeks of gestation after the completion of the first transfer
Measured: At 24 weeks of gestation after the completion of the first transfer
Miscarriage
The loss of a clinical pregnancy at 24 weeks of gestation after the completion transfer of all embryos from the started treatment cycle
Measured: At 24 weeks of gestation at 12 months after the randomization.
Multiple pregnancy
Multiple pregnancy is explained as two or more gestational sacs or positive heart beats by transvaginal sonography, after the completion of the first transfer
Measured: 7 weeks' gestation after the completion of the first transfer
Multiple pregnancy
Multiple pregnancy is explained as two or more gestational sacs or positive heart beats by transvaginal sonography, after the completion transfer of all embryos from the started treatment cycle
Measured: 7 weeks' gestation at 12 months after randomization
Multiple delivery
Multiple delivery is defined as birth of more than one baby beyond 24 weeks, after the completion of the first transfer
Measured: At birth, after the completion of the first transfer
Multiple delivery
Multiple delivery is defined as birth of more than one baby beyond 24 weeks, after the completion transfer of all embryos from the started treatment cycle
Measured: At birth at 12 months after randomization
Gestational diabetes mellitus
Development of diabetes during pregnancy
Measured: At 24 weeks of gestation after the completion of the first transfer
Gestational diabetes mellitus
Development of diabetes during pregnancy
Measured: At 24 weeks of gestation at 12 months after randomization
Hypertensive disorders of pregnancy
Hypertensive disorders of pregnancy will include pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia)
Measured: From 20 weeks of gestation up to at birth after the completion of the first transfer
Hypertensive disorders of pregnancy
Hypertensive disorders of pregnancy will include pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia)
Measured: From 20 weeks of gestation up to at birth at 12 months after randomization
Antepartum haemorrhage
Including placenta previa, placenta accreta and unexplained
Measured: From 20 weeks of gestation up to at birth, after the completion of the first transfer
Antepartum haemorrhage
Including placenta previa, placenta accreta and unexplained
Measured: From 20 weeks of gestation up to at birth, at 12 months after randomization
Gestational age at delivery
Gestational age at delivery
Measured: At birth, after the completion of the first transfer
Gestational age at delivery
Gestational age at delivery
Measured: At birth, at 12 months after randomization
Preterm delivery
Preterm delivery is defined as any delivery at <24, <28, <32, <37 completed weeks' gestation
Measured: At birth, after the completion of the first transfer
Preterm delivery
Preterm delivery is defined as any delivery at <24, <28, <32, <37 completed weeks' gestation
Measured: At birth, at 12 months after randomization
Spontaneous preterm birth
Spontaneous preterm birth is defined as delivery spontaneously at <24, <28, <32, <37 completed weeks
Measured: At birth, after the completion of the first transfer
Spontaneous preterm birth
Spontaneous preterm birth is defined as delivery spontaneously at <24, <28, <32, <37 completed weeks
Measured: At birth, at 12 months after randomization
Iatrogenic preterm birth
Iatrogenic preterm birth is defined as delivery non-spontaneously at <24, <28, <32, <37 completed weeks
Measured: At birth, after the completion of the first transfer
Iatrogenic preterm birth
Iatrogenic preterm birth is defined as delivery non-spontaneously at <24, <28, <32, <37 completed weeks
Measured: At birth, at 12 months after randomization
Birth weight
Weight of newborn
Measured: At birth, after the completion of the first transfer
Birth weight
Weight of newborn
Measured: At birth, at 12 months after randomization
Low birth weight
Low birth weight is defined as <2500 gm
Measured: At birth, after the completion of the first transfer
Low birth weight
Low birth weight is defined as <2500 gm
Measured: At birth, at 12 months after randomization
Very low birth weight
Very low birth weight is defined as <1500 gm
Measured: At birth, after the completion of the first transfer
Very low birth weight
Very low birth weight is defined as <1500 gm
Measured: At birth, at 12 months after randomization
High birth weight
High birth weight is defined as >4000 gm
Measured: At birth, after the completion of the first transfer
High birth weight
High birth weight is defined as >4000 gm
Measured: At birth, at 12 months after randomization
Very high birth weight
Very high birth weight is defined as >4500 gm
Measured: At birth, after the completion of the first transfer
Very high birth weight
Very high birth weight is defined as >4500 gm
Measured: At birth, at 12 months after randomization
Large for gestational age
Large for gestational age is defined as birth weight >90th percentile
Measured: At birth, after the completion of the first transfer
Large for gestational age
Large for gestational age is defined as birth weight >90th percentile
Measured: At birth, at 12 months after randomization
Small for gestational age
Small for gestational age is defined as birth weight <10th percentile
Measured: At birth, after the completion of the first transfer
Small for gestational age
Small for gestational age is defined as birth weight <10th percentile
Measured: At birth, at 12 months after randomization
Congenital anomaly diagnosed at birth
Any congenital anomaly will be included
Measured: At birth, after the completion of the first transfer
Congenital anomaly diagnosed at birth
Any congenital anomaly will be included
Measured: At birth, at 12 months after randomization
Admission to NICU
The admittance of the newborn to NICU
Measured: 7 days after delivery after the completion of the first transfer
Admission to NICU
The admittance of the newborn to NICU
Measured: 7 days after delivery, at 12 months after randomization
Genetic and epigenetic analysis of newborn
Maternal whole blood; newborn's materials including cord blood, neonatal buccal smear, and placental tissue will be collected. Data will be collected for a supplementary analysis and will be reported in a separated paper.
Measured: 1 day (Prior to the initiation of IVF/IVM) and 1 day ( at the time of delivery)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2018
- Study start16 Mar 2018
- Primary completion1 Aug 2020
- Study completion12 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies 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
- 1,064 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mỹ Đức Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- An Sinh Hospital
- Responsible party
- Sponsor
- Investigators
- Lan N Vuong, PhD, Principal investigator, University of Medicine and Pharmacy at Ho Chi Minh City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03428919
- Sponsor's protocol ID
- CS/MD/17/12
- Other IDs
- CS/AS/17/10
- Status last verified
- Oct 2020
- First submitted
- 2 Feb 2018
- Last updated
- 9 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pham TD, Dang VQ, Ho VNA, Tran CT, Nguyen DTP, Vuong LN, Ho TM, Mol BW, Wang R. Intracytoplasmic sperm injection versus conventional in vitro fertilization in infertile couples with normal total sperm count and motility: does sperm morphology matter? Hum Reprod. 2025 Jan 1;40(1):23-29. doi: 10.1093/humrep/deae252.
PubMed 39547931Nguyen NA, Nguyen NT, Tran VTT, Vo TTM, Uong TS, Nguyen HT, Nguyen NT, Nguyen DL, Pham TD, Nguyen DTN, Ho TM, Vuong LN. Developmental outcomes of children born through ICSI versus conventional IVF (cIVF) in couples with non-male factor infertility. Hum Reprod. 2024 Jun 5:deae120. doi: 10.1093/humrep/deae120. Online ahead of print.
PubMed 38840410Dang VQ, Vuong LN, Luu TM, Pham TD, Ho TM, Ha AN, Truong BT, Phan AK, Nguyen DP, Pham TN, Pham QT, Wang R, Norman RJ, Mol BW. Intracytoplasmic sperm injection versus conventional in-vitro fertilisation in couples with infertility in whom the male partner has normal total sperm count and motility: an open-label, randomised controlled trial. Lancet. 2021 Apr 24;397(10284):1554-1563. doi: 10.1016/S0140-6736(21)00535-3.
PubMed 33894833Dang VQ, Vuong LN, Ho TM, Ha AN, Nguyen QN, Truong BT, Pham QT, Wang R, Norman RJ, Mol BW. The effectiveness of ICSI versus conventional IVF in couples with non-male factor infertility: study protocol for a randomised controlled trial. Hum Reprod Open. 2019 Mar 27;2019(2):hoz006. doi: 10.1093/hropen/hoz006. eCollection 2019.
PubMed 30937394
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Intracytoplasmic Sperm Injection Versus Conventional in Vitro Fertilization in Couples With Non-male Factor Infertility: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03428919
- Acronym / sponsor ID
- CS/MD/17/12
- Conditions
- Infertility
- Keywords
- ICSI, Conventional IVF, Non-male factor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,064 participants (actual)
- Lead sponsor
- Mỹ Đức HospitalUniversity, hospital or other
- Collaborators
- An Sinh Hospital
- Study start
- 16 Mar 2018 (actual)
- Primary completion
- 1 Aug 2020 (actual)
- Study completion
- 12 Aug 2020 (actual)
- First posted
- 12 Feb 2018 (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.
Conventionally, ICSI was initially developed and has been shown to be an effective treatment for male factor infertility. It is increasingly being used for patients without a male factor diagnosis, despite the lack of clinical evidence to support its use. Moreover, ICSI is an invasive and expensive procedure. This multi-center, randomized, controlled, parallel-group trial will be conducted to compare the effectiveness of ICSI versus conventional IVF in infertile couples scheduled for IVF treatment, in whom the male partner has normal sperm.
Detailed description
All patients undergoing IVF/ICSI will be treated with a GnRH antagonist protocol. Recombinant FSH (Puregon, MSD) will be given on day 2 or day 3 of menstrual cycle for 5 days. The starting dose is individualized for each patient based on the following criteria: AMH <0.7 ng/mL, dose 300 IU/day; AMH 0.7-2.1 ng/mL, dose 200 IU/day; AMH >2.1 ng/mL, dose 150 IU/day. After that, investigators can titrate the dose based on their clinical judgment. Follicular development will be monitored by ultrasound scanning and measurement of estradiol and progesterone levels, starting on day 5 of stimulation. Scanning and hormonal measurement will be repeated every 2 to 3 days, depending on the size of follicles. An antagonist is routinely used on day 5 until the day of triggering. Criteria for triggering, by hCG (Ovitrelle 250 mg, Merck, Germany) will be the presence of at least three leading follicles of 17 mm. In women with excessive follicular response (≥15 follicles ≥12 mm), 0,2 mg Triptorelin (Diphereline, Ipsen Beaufour, France) will be used when there are at least two leading follicles of 17 mm. Oocyte retrieval will be performed 36 hours after triggering.
Randomization and allocation of participants to study groups will be performed on the day of egg pick up, after having obtained the semen from the husband. Eligible participants that have provided informed consent will be randomised to either ICSI or conventional IVF.
In ICSI group, insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. OCCs will be stripped by using hyaluronidase. Only matured oocytes will be inseminated.
In conventional IVF group, insemination will be performed by conventional IVF. Two hours after retrieval, collected OCCs will be inseminated for another 2 hours, at a concentration of 100,000 motile sperm/ml. Inseminated OCCs will be cultured overnight in culture medium.
In both groups, fertilization check will be performed under inverted microscope at period of 16-18 hours after insemination. On day 3, embryo evaluation will be performed at fixed time point 66±2 hours after fertilization, using the Istanbul consensus. Embryo transfer will be performed on day 3 under ultrasound guidance. A maximum of 2 embryos will be transferred into the uterus. The remaining grade 1 and 2 embryos will be frozen. Luteal-phase support will be done with estradiol (Valiera 2mg) 8mg/day and vaginal progesterone 800mg/day (Cyclogest 400mg) until 7th week of gestation.
If there are contra-indications for fresh embryo transfer, a freeze-all strategy will be applied, using Cryotech technique. Indications for freeze-all include: risk of ovarian hyperstimulation syndrome (OHSS), premature progesterone rise (≥1.5 ng/ml), thin endometrium (<7 mm), fluid in cavity on day of embryo transfer, endometrial polyp, hydrosalpinx that have not removed before oocyte retrieval.
In the next cycle, endometrium will be prepared by using estradiol (Valiera 2 mg, 8 mg/day) orally, starting from day 2-3 of menstrual cycle. When the endometrium thickness reaches 8 mm or more, patients will start using progesterone vaginally (Cyclogest 400 mg, 800 mg/day). Embryo transfer will be performed 3 days after using progesterone. On the day of embryo transfer, embryos will be thawed. In the frozen/thawed cycle, the best embryos will be utilized first, as in fresh transfer. Two hours after thawing, a maximum of 2 surviving embryos will be transferred into the uterus under ultrasound guidance. Luteal phase support will be provided with estradiol (Valiera 2mg) 8mg/day and vaginal progesterone 800 mg/day (Cyclogest 400 mg) until the seventh week of gestation.
In both groups, clinicians who perform embryo transfer, either fresh or frozen cycles, will be blinded to the intervention.
A serum hCG will be measured 2 weeks after embryo transferred, and if positive, an ultrasound scan of the uterus will be performed at gestational weeks 7 and 12. At 11 - 12 weeks of gestation, participants will be referred to the Outpatient clininc, O\&G Department, My Duc hospital or An Sinh hospital for prenatal care until giving birth.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intracytoplasmic Sperm Injection (ICSI) | Active comparator | Procedure: ICSIAll patients will be treated with a GnRH antagonist protocol. hCG (Ovitrelle 250 mg) will be used in the presence of at least three leading follicles of 17 mm. In women with ≥15 follicles ≥12 mm, 0,2 mg Triptorelin (Diphereline) will be used when there is at least two leading follicles of 17 mm. Oocyte retrieval will be performed 36 hours after triggering. Insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. OCCs will be stripped by using hyaluronidase. Only matured oocytes will be inseminated. Fertilization check will be performed at period of 16-18 hours after insemination. Embryo transfer will be performed on day 3 under ultrasound guidance. A maximum of 2 embryos will be transferred into the uterus. The remaining grade 1 and 2 embryos will be frozen. |
| In Vitro Fertilization (IVF) | Active comparator | Procedure: IVFAll patients will be treated with a GnRH antagonist protocol. hCG (Ovitrelle 250 mg) will be used in the presence of at least three leading follicles of 17 mm. In women with ≥15 follicles ≥12 mm, 0,2 mg Triptorelin (Diphereline) will be used when there is at least two leading follicles of 17 mm. Oocyte retrieval will be performed 36 hours after triggering. Insemination will be performed by conventional IVF. Two hours after retrieval, collected OCCs will be inseminated for another 2 hours (100,000 motile sperm/ml). Inseminated OCCs will be cultured overnight in culture medium. Fertilization check will be performed at period of 16-18 hours after insemination. Embryo transfer will be performed on day 3. A maximum of 2 embryos will be transferred. The remaining grade 1-2 embryos will be frozen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Having ≤ 2 IVF/ICSI cycles
- Total sperm count and motility are normal (WHO, 2010)
- Antagonist protocol
- Agree to have ≤ 2 embryos transferred
- Not participating in another IVF study at the same time
Key exclusion criteria (3 listed)
- In-vitro maturation (IVM) cycles
- Using frozen semen
- Poor fertilization in previous cycle (≤ 25%)
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 |
|---|---|---|
| ICSIIn ICSI group, insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. OCCs will be stripped by using hyaluronidase. Only matured oocytes will be inseminated. | Procedure or surgery | Intracytoplasmic Sperm Injection (ICSI) |
| IVFIn IVF group, insemination will be performed by conventional IVF. Two hours after retrieval, collected OCCs will be inseminated for another 2 hours, at a concentration of 100,000 motile sperm/ml. Inseminated OCCs will be cultured overnight in culture medium. | Procedure or surgery | In Vitro Fertilization (IVF) |
Primary outcome
Ongoing pregnancy resulting in live birth after the first embryo transfer of the started treatment cycle.
Time frame: At 12 weeks of gestation
Live birth is defined as the birth of at least one newborn after 24 weeks' gestation that exhibits any sign of life (twin will be a single count). For the timing of this occur, ongoing pregnancy will be used, conditional on the fact that this ongoing pregnancy results in live birth.
57 secondary outcomes
Fertilization rate per oocyte inseminated/injected
Time frame: At 16-18 hours after injected or 17-19 hours after inseminated
Fertilization rate per oocyte retrieved
Time frame: At 16-18 hours after injected or 17-19 hours after inseminated
Abnormal fertilization rate
Time frame: At 16-18 hours after injected or 17-19 hours after inseminated
Total fertilization failure rate
Time frame: At 16-18 hours after injected or 17-19 hours after inseminated
Number of embryos on day 3
Time frame: 3 days after oocytes pick-up day in IVF/ICSI
Number of good quality embryo on day 3
Time frame: 3 days after oocytes pick-up day in IVF/ICSI
Number of embryo freezing on day 3
Time frame: 3 days after oocytes pick-up day in IVF/ICSI
Positive pregnancy test
Time frame: 14 days after embryo transfer
Clinical pregnancy
Time frame: At 7 weeks' gestation
Implantation rate
Time frame: At 3 weeks after embryo transferred
Ongoing pregnancy
Time frame: At 12 weeks' gestation
Cumulative ongoing pregnancy
Time frame: At 12 weeks' gestation at 12 months after randomization. After 12 months, most patients doing IVF have finished all their frozen embryos; therefore, we consider this time point for analyzing the cumulative ongoing pregnancy rate.
Ongoing pregnancy resulting in live birth obtained from all embryos from the first started treatment cycle
Time frame: 12 weeks of gestation at 12 months after randomization
Time from randomization to ongoing pregnancy
Time frame: 12 weeks of gestation after the completion of first transfer
Ovarian hyperstimulation syndrome (OHSS)
Time frame: At 10 days after hCG injection and 14 days after embryo transfer
Ectopic pregnancy
Time frame: At 12 weeks of gestation after the completion of the first transfer
Ectopic pregnancy
Time frame: At 12 weeks of gestation at 12 months after randomization.
Miscarriage
Time frame: At 24 weeks of gestation after the completion of the first transfer
Miscarriage
Time frame: At 24 weeks of gestation at 12 months after the randomization.
Multiple pregnancy
Time frame: 7 weeks' gestation after the completion of the first transfer
Multiple pregnancy
Time frame: 7 weeks' gestation at 12 months after randomization
Multiple delivery
Time frame: At birth, after the completion of the first transfer
Multiple delivery
Time frame: At birth at 12 months after randomization
Gestational diabetes mellitus
Time frame: At 24 weeks of gestation after the completion of the first transfer
Gestational diabetes mellitus
Time frame: At 24 weeks of gestation at 12 months after randomization
Hypertensive disorders of pregnancy
Time frame: From 20 weeks of gestation up to at birth after the completion of the first transfer
Hypertensive disorders of pregnancy
Time frame: From 20 weeks of gestation up to at birth at 12 months after randomization
Antepartum haemorrhage
Time frame: From 20 weeks of gestation up to at birth, after the completion of the first transfer
Antepartum haemorrhage
Time frame: From 20 weeks of gestation up to at birth, at 12 months after randomization
Gestational age at delivery
Time frame: At birth, after the completion of the first transfer
Gestational age at delivery
Time frame: At birth, at 12 months after randomization
Preterm delivery
Time frame: At birth, after the completion of the first transfer
Preterm delivery
Time frame: At birth, at 12 months after randomization
Spontaneous preterm birth
Time frame: At birth, after the completion of the first transfer
Spontaneous preterm birth
Time frame: At birth, at 12 months after randomization
Iatrogenic preterm birth
Time frame: At birth, after the completion of the first transfer
Iatrogenic preterm birth
Time frame: At birth, at 12 months after randomization
Birth weight
Time frame: At birth, after the completion of the first transfer
Birth weight
Time frame: At birth, at 12 months after randomization
Low birth weight
Time frame: At birth, after the completion of the first transfer
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 9 Oct 2020.
- Derived from this study: PubMed 39547931Pham TD, Dang VQ, Ho VNA, Tran CT, Nguyen DTP, Vuong LN, Ho TM, Mol BW, Wang R. Intracytoplasmic sperm injection versus conventional in vitro fertilization in infertile couples with normal total sperm count and motility: does sperm morphology matter? Hum Reprod. 2025 Jan 1;40(1):23-29. doi: 10.1093/humrep/deae252.
- Derived from this study: PubMed 38840410Nguyen NA, Nguyen NT, Tran VTT, Vo TTM, Uong TS, Nguyen HT, Nguyen NT, Nguyen DL, Pham TD, Nguyen DTN, Ho TM, Vuong LN. Developmental outcomes of children born through ICSI versus conventional IVF (cIVF) in couples with non-male factor infertility. Hum Reprod. 2024 Jun 5:deae120. doi: 10.1093/humrep/deae120. Online ahead of print.
- Derived from this study: PubMed 33894833Dang VQ, Vuong LN, Luu TM, Pham TD, Ho TM, Ha AN, Truong BT, Phan AK, Nguyen DP, Pham TN, Pham QT, Wang R, Norman RJ, Mol BW. Intracytoplasmic sperm injection versus conventional in-vitro fertilisation in couples with infertility in whom the male partner has normal total sperm count and motility: an open-label, randomised controlled trial. Lancet. 2021 Apr 24;397(10284):1554-1563. doi: 10.1016/S0140-6736(21)00535-3.
- Derived from this study: PubMed 30937394Dang VQ, Vuong LN, Ho TM, Ha AN, Nguyen QN, Truong BT, Pham QT, Wang R, Norman RJ, Mol BW. The effectiveness of ICSI versus conventional IVF in couples with non-male factor infertility: study protocol for a randomised controlled trial. Hum Reprod Open. 2019 Mar 27;2019(2):hoz006. doi: 10.1093/hropen/hoz006. eCollection 2019.
- Individual participant dataSharing planned: No
Related trials for Infertility
RecruitingPhase 3
A Study to Compare the Efficacy and Safety of Follitropin Alfa/Lutropin Alfa Versus hMG in Japanese Participants With LH and FSH Deficiency Undergoing ART (HINATA)
Infertility
Active, not recruitingObservational study
Fresh Versus Vitrified-Warmed Donor Oocytes: Embryological and Clinical Outcomes
Infertility, Donor Oocyte Assisted Reproduction
RecruitingObservational study
Safety and Efficacy of Corifollitropin Alfa N02 Injection in Elderly Women Undergoing Assisted Reproductive Technology (ART)
Infertility
Active, not recruiting
Automation of the In Vitro Fertilization Laboratory
Infertility, ART
Not yet recruiting
Implementing IVM for Fertility Treatment in Clinical Practice
Infertility
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, 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 ICSI and IVF in people with Infertility, 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 5 inclusion and 3 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 9 Oct 2020. 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?
Ongoing pregnancy resulting in live birth after the first embryo transfer of the started treatment cycle. (time frame: At 12 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 NCT03428919, which also lists 4 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 9 Oct 2020.