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Completed

NCT Number: NCT03428919

ICSI Versus Conventional IVF in Non-male Factor Couples

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.

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Key information

Conditions

Infertility Genital Diseases Urogenital Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Dang Q Vinh

Hochiminh City, Vietnam

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • In-vitro maturation (IVM) cycles
  • Using frozen semen
  • Poor fertilization in previous cycle (≤ 25%)

Treatment and study plan

ICSI

Procedure

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.

IVF

Procedure

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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. Fertilization rate per oocyte inseminated/injected

    Time frame: At 16-18 hours after injected or 17-19 hours after inseminated

    Fertilization is defined as the appearance of 2 PN

  2. Fertilization rate per oocyte retrieved

    Time frame: At 16-18 hours after injected or 17-19 hours after inseminated

    Fertilization is defined as the appearance of 2 PN

  3. Abnormal fertilization rate

    Time frame: At 16-18 hours after injected or 17-19 hours after inseminated

    Abnormal fertilization is defined as the appearance of 1PN or ≥3 PN

  4. Total fertilization failure rate

    Time frame: At 16-18 hours after injected or 17-19 hours after inseminated

    Total fertilization is defined as the absence of any zygotes with 2PN

  5. Number of embryos on day 3

    Time frame: 3 days after oocytes pick-up day in IVF/ICSI

    Number of embryos on day 3

  6. Number of good quality embryo on day 3

    Time frame: 3 days after oocytes pick-up day in IVF/ICSI

    Numbers of embryos on day 3 with good quality

  7. Number of embryo freezing on day 3

    Time frame: 3 days after oocytes pick-up day in IVF/ICSI

    Number of embryos freezing on day 3

  8. Positive pregnancy test

    Time frame: 14 days after embryo transfer

    Positive pregnancy test is defined as a serum human chorionic gonadotropin level greater than 25 mIU/mL after the completion of the first transfer

  9. Clinical pregnancy

    Time frame: At 7 weeks' gestation

    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

  10. Implantation rate

    Time frame: At 3 weeks after embryo transferred

    Implantation rate is defined as the number of gestational sacs per number of embryos transferred after the completion of the first transfer

  11. Ongoing pregnancy

    Time frame: At 12 weeks' gestation

    Ongoing pregnancy is defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond, after the completion of the first transfer

  12. 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 is defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond, after transfer of all embryos from the started treatment cycle.

  13. 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

    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).

  14. Time from randomization to ongoing pregnancy

    Time frame: 12 weeks of gestation after the completion of first transfer

    Time from randomization to ongoing pregnancy after the completion of the first transfer

  15. Ovarian hyperstimulation syndrome (OHSS)

    Time frame: At 10 days after hCG injection and 14 days after embryo transfer

    Symptoms of OHSS

  16. Ectopic pregnancy

    Time frame: At 12 weeks of gestation after the completion of the first transfer

    A pregnancy in which implantation takes place outside the uterine cavity after completion of the first transfer

  17. Ectopic pregnancy

    Time frame: At 12 weeks of gestation at 12 months after randomization.

    A pregnancy in which implantation takes place outside the uterine cavity after transfer of all embryos from the started treatment cycle.

  18. Miscarriage

    Time frame: At 24 weeks of gestation after the completion of the first transfer

    The loss of a clinical pregnancy at 24 weeks of gestation after the completion of the first transfer

  19. Miscarriage

    Time frame: At 24 weeks of gestation at 12 months after the randomization.

    The loss of a clinical pregnancy at 24 weeks of gestation after the completion transfer of all embryos from the started treatment cycle

  20. Multiple pregnancy

    Time frame: 7 weeks' gestation after the completion of the first transfer

    Multiple pregnancy is explained as two or more gestational sacs or positive heart beats by transvaginal sonography, after the completion of the first transfer

  21. Multiple pregnancy

    Time frame: 7 weeks' gestation at 12 months after randomization

    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

  22. Multiple delivery

    Time frame: At birth, after the completion of the first transfer

    Multiple delivery is defined as birth of more than one baby beyond 24 weeks, after the completion of the first transfer

  23. Multiple delivery

    Time frame: At birth at 12 months after randomization

    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

  24. Gestational diabetes mellitus

    Time frame: At 24 weeks of gestation after the completion of the first transfer

    Development of diabetes during pregnancy

  25. Gestational diabetes mellitus

    Time frame: At 24 weeks of gestation at 12 months after randomization

    Development of diabetes during pregnancy

  26. 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 will include pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia)

  27. Hypertensive disorders of pregnancy

    Time frame: From 20 weeks of gestation up to at birth at 12 months after randomization

    Hypertensive disorders of pregnancy will include pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia)

  28. Antepartum haemorrhage

    Time frame: From 20 weeks of gestation up to at birth, after the completion of the first transfer

    Including placenta previa, placenta accreta and unexplained

  29. Antepartum haemorrhage

    Time frame: From 20 weeks of gestation up to at birth, at 12 months after randomization

    Including placenta previa, placenta accreta and unexplained

  30. Gestational age at delivery

    Time frame: At birth, after the completion of the first transfer

    Gestational age at delivery

  31. Gestational age at delivery

    Time frame: At birth, at 12 months after randomization

    Gestational age at delivery

  32. Preterm delivery

    Time frame: At birth, after the completion of the first transfer

    Preterm delivery is defined as any delivery at <24, <28, <32, <37 completed weeks' gestation

  33. Preterm delivery

    Time frame: At birth, at 12 months after randomization

    Preterm delivery is defined as any delivery at <24, <28, <32, <37 completed weeks' gestation

  34. Spontaneous preterm birth

    Time frame: At birth, after the completion of the first transfer

    Spontaneous preterm birth is defined as delivery spontaneously at <24, <28, <32, <37 completed weeks

  35. Spontaneous preterm birth

    Time frame: At birth, at 12 months after randomization

    Spontaneous preterm birth is defined as delivery spontaneously at <24, <28, <32, <37 completed weeks

  36. Iatrogenic preterm birth

    Time frame: At birth, after the completion of the first transfer

    Iatrogenic preterm birth is defined as delivery non-spontaneously at <24, <28, <32, <37 completed weeks

  37. Iatrogenic preterm birth

    Time frame: At birth, at 12 months after randomization

    Iatrogenic preterm birth is defined as delivery non-spontaneously at <24, <28, <32, <37 completed weeks

  38. Birth weight

    Time frame: At birth, after the completion of the first transfer

    Weight of newborn

  39. Birth weight

    Time frame: At birth, at 12 months after randomization

    Weight of newborn

  40. Low birth weight

    Time frame: At birth, after the completion of the first transfer

    Low birth weight is defined as <2500 gm

  41. Low birth weight

    Time frame: At birth, at 12 months after randomization

    Low birth weight is defined as <2500 gm

  42. Very low birth weight

    Time frame: At birth, after the completion of the first transfer

    Very low birth weight is defined as <1500 gm

  43. Very low birth weight

    Time frame: At birth, at 12 months after randomization

    Very low birth weight is defined as <1500 gm

  44. High birth weight

    Time frame: At birth, after the completion of the first transfer

    High birth weight is defined as >4000 gm

  45. High birth weight

    Time frame: At birth, at 12 months after randomization

    High birth weight is defined as >4000 gm

  46. Very high birth weight

    Time frame: At birth, after the completion of the first transfer

    Very high birth weight is defined as >4500 gm

  47. Very high birth weight

    Time frame: At birth, at 12 months after randomization

    Very high birth weight is defined as >4500 gm

  48. Large for gestational age

    Time frame: At birth, after the completion of the first transfer

    Large for gestational age is defined as birth weight >90th percentile

  49. Large for gestational age

    Time frame: At birth, at 12 months after randomization

    Large for gestational age is defined as birth weight >90th percentile

  50. Small for gestational age

    Time frame: At birth, after the completion of the first transfer

    Small for gestational age is defined as birth weight <10th percentile

  51. Small for gestational age

    Time frame: At birth, at 12 months after randomization

    Small for gestational age is defined as birth weight <10th percentile

  52. Congenital anomaly diagnosed at birth

    Time frame: At birth, after the completion of the first transfer

    Any congenital anomaly will be included

  53. Congenital anomaly diagnosed at birth

    Time frame: At birth, at 12 months after randomization

    Any congenital anomaly will be included

  54. Admission to NICU

    Time frame: 7 days after delivery after the completion of the first transfer

    The admittance of the newborn to NICU

  55. Admission to NICU

    Time frame: 7 days after delivery, at 12 months after randomization

    The admittance of the newborn to NICU

  56. Genetic and epigenetic analysis of newborn

    Time frame: 1 day (Prior to the initiation of IVF/IVM) and 1 day ( at the time of delivery)

    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.

  57. Cost-effectiveness

    Time frame: Two year after randomization

    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.

Sponsors and collaborators

Lead sponsor

Mỹ Đức Hospital

Other

Collaborators

  • An Sinh Hospital

Registry information

Official study title

The Effectiveness of Intracytoplasmic Sperm Injection Versus Conventional in Vitro Fertilization in Couples With Non-male Factor Infertility: a Randomized Controlled Trial

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Feb 12, 2018
Registry last updated
Oct 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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