Hyaluronan-enriched Embryo Transfer Medium for Frozen-thawed Embryo Transfer
Condition: In Vitro Fertilization; Subfertility
MeSH terms: Infertility
Study type: Interventional

Summary: 
      This is a randomized-controlled trial evaluating the effect of the use of hyaluronan
      (HA)-enriched embryo transfer medium on the live birth rate in women undergoing frozen-thawed
      embryo transfer. For half of the women, hyaluronan-enriched medium will be used as embryo
      transfer medium. For the other half of women, a control will be used.
    

Detailed description: 
      Women being scheduled for FET will be assessed for eligibility. Eligible women will be
      recruited for the study and each woman will only be included in the study with one FET cycle.
      Informed written consent will be obtained. Their baseline characteristics will be collected.

      Women with regular ovulatory cycles will undergo the standard procedures of blood taking to
      identify the day of luteinizing hormone (LH) surge. Women with irregular cycles will either
      receive clomiphene or letrozole followed by detection of the LH surge, or undergo hormone
      replacement therapy (HRT) cycle with oral oestradiol 6 mg daily for 14 days for endometrial
      priming followed by the addition of vaginal micronized progesterone 100 mg three times daily.
      HRT cycle may also be used for scheduling purposes.

      Embryo transfer will be performed 3 or 4 days (for cleavage-stage embryos) or 6 or 7 days
      (for blastocysts) after the LH surge. For women in HRT cycles, FET will be scheduled on the
      4th or 5th day (for cleavage-stage embryos) or the 7th or 8th day (for blastocysts) of
      starting vaginal progesterone. They will continue oral oestradiol and vaginal progesterone
      after FET up to 12 weeks of gestation.

      Randomization:

      One day before scheduled FET, recruited women will be randomized into one of the following
      two groups: (1) HA group and (2) control group according to a computer-generated
      randomization list prepared by a designated research nurse.

      One the day of FET, frozen embryos or blastocysts will be thawed and incubated for at least
      10 minutes in embryo transfer medium. For women allocated to the HA group, EmbryoGlue
      (Vitrolife) will be used as embryo transfer medium, while in the control group the usual
      medium used in the study center will used. The main difference between the two media is that
      EmbryoGlue contains a higher concentration of HA.

      The rest of the embryo transfer procedure will be the same as the usual practice.

      Blinding:

      The patient and the physicians performing the FET and involved in her care will not know the
      group allocation. Only the embryologist will know the group allocation, but they will not be
      involved in the patient care, the FET procedure and subsequent assessment.

      Follow-up and data collection:

      A urine pregnancy test is performed 18 days after the LH surge or starting vaginal
      progesterone. If the pregnancy test is positive, transvaginal ultrasound will be performed 2
      weeks later to locate the pregnancy and fetal viability. Subsequent management will be the
      same as other women with early pregnancy. They will be referred for antenatal care when the
      pregnancy is on-going at 8 weeks.

      Follow-up:

      Written consent regarding retrieval of pregnancy and delivery data from both public and
      private sectors will be sought from the patient at the time of study. The obstetric outcomes
      will be traced from the electric patient record system if the patients deliver in Hospital
      Authority hospitals. A pre-formatted letter with replying address available will be given to
      the patient at the end of the study period and is to be filled by the private obstetrician
      and returned to us after delivery. If no reply letter is received 2-3 months after the
      expected date of confinement of the patient, a letter including patient's authorization will
      be sent to the corresponding private obstetrician to retrieve the information of the
      pregnancy outcomes. The outcome of the pregnancy (delivery, miscarriage), number of babies
      born, birth weights and obstetrics complications will be recorded.
    

Intervention name(s): EmbryoGlue (Vitrolife); Control medium
Intervention type(s): Other; Other
Intervention description(s): A hyaluronan-enriched embryo transfer medium; The usual embryo transfer medium used in the study centres.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment