Clinical trial NCT04064840: GnRH Agonist for Dual Trigger in IVF and for Luteal Phase Support in FET
Official title: Gonadotrophin Releasing Hormone Agonist for Dual Trigger in in Vitro Fertilization and for Luteal Phase Support in Frozen-thawed Embryo Transfer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Subfertility
Keywords: subfertility
IVF
FET
dual trigger
luteal phase support
Gonadotrophin releasing hormone agonist
live birth rate
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2019-08-22
Enrollment: 784
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this study are to compare the efficacy of the dual trigger group vs the hCG trigger group on the live birth rate in women undergoing IVF and the efficacy of the agonist in LP group vs the placebo group on the live birth rate in women undergoing FET.

Detailed description: Trial design:

A randomised, double-blinded and placebo controlled trial will be performed in IVF cycles and another randomised, double-blinded and placebo controlled trial will be performed in FET cycles.

Treatment of subjects:

IVF Women being scheduled for IVF at Department of Obstetrics \& Gynaecology of Kwong Wah Hospital and Queen Mary Hospital will be assessed for eligibility. Eligible women will be recruited for the study and each woman will only be included in the study. Informed written consent will be obtained after counseling.

All techniques of IVF including ovarian stimulation, harvesting of oocytes, insemination with specially prepared sperm and embryo culture in the laboratory will be according to local protocols. Women will receive ovarian stimulation using antagonist protocol. Ultrasound scanning will be arranged on day 2-3 of menses for the antral follicle counts and to exclude the presence of ovarian cyst. Oestradiol and progesterone concentration will be checked and if they are basal, ovarian stimulation with gonadotropin injections will be given. GnRH antagonist will be started on day 6 of ovarian stimulation. Regular ultrasound monitoring will be performed to monitor the growth of follicles. Adjustment of the gonadotropin dosage is corresponding to the number and size of follicles.

Randomization When three follicles reach 18 mm in diameter, recruited women will be randomized according to a computer-generated randomization list prepared by a designated research nurse into one of the following: (1) the dual trigger: recombinant hCG 0.25mg and decapeptyl 0.2mg subcutaneously and (2) the hCG trigger: recombinant hCG 0.25mg subcutaneously and normal saline.

Transvaginal ultrasound-guided egg retrieval will be scheduled 36 hours after the dual or hCG trigger. Intracytoplasmic sperm injection will be performed if necessary, depending on the semen quality of the husbands. A maximum of 2 embryos or blastocysts will be replaced 2 days or 5 days after egg retrieval according to the standard protocol under transabdominal ultrasound guidance.

Two days after egg retrieval, each woman will receive vaginal progesterone (Endometrin 100mg bd) for two weeks for the luteal phase support.

FET 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.

Women with regular ovulatory cycles will undergo the standard procedures of blood taking to identify the day of luteinizing hormone (LH) surge, which is defined as an elevation of the LH to 2 times the level of the average of the previous 3 days and the absolute level of the LH surge is greater than 20 IU/L. Transvaginal ultrasound will be done to measure the endometrial thickness on the day after the LH surge. A maximum of two early cleavage embryos or two blastocysts will be transferred 3 days or 6 days after the LH surge respectively.

Randomization On the day of FET, recruited women will be randomized into one of the following two groups: (1) decapeptyl 0.1 mg subcutaneously and (2) normal saline as control group according to a computer-generated randomization list prepared by a designated research nurse.

The rest of the embryo transfer procedure will be the same as our usual practice.

Blinding The women and the physicians will not know the group allocation. Only the research nurse will know the group allocation, but they will not be involved in the patient care.

Follow-up and data collection A urine pregnancy test is performed 18 days after the dual or hCG trigger in IVF cycles or the LH surge in FET cycles. If the pregnancy test is positive, transvaginal ultrasound will be performed 2 weeks later to locate the pregnancy and foetal 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 8-10 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.

Eligibility criteria: IVF

Inclusion criteria:

- Women aged \<43 years at the time of IVF treatment

Exclusion criteria:

* Preimplantation genetic diagnosis treatment
* Use of donor oocytes or donor embryos
* Hydrosalpinx shown on pelvic scanning and not surgically treated
* Women at risk of OHSS

FET

Inclusion criteria:

* Women aged \<43 years at the time of IVF treatment
* Replacing early cleavage embryos or blastocysts after thawing
* FET in natural cycles

Exclusion criteria:

* Frozen early cleavage embryos thawed and cultured to blastocysts prior to transfer as requested by the patient
* Preimplantation genetic diagnosis treatment
* Use of donor oocytes or donor embryos
* Hydrosalpinx shown on pelvic scanning and not surgically treated

Primary outcomes:
measure: Live birth rate
timeFrame: after 22 weeks
Secondary outcomes:
measure: Pregnancy
timeFrame: 18 days after the dual or hCG trigger in IVF cycles or the LH surge in FET cycles
measure: Clinical pregnancy
timeFrame: 6 weeks
measure: Biochemical pregnancy
timeFrame: before 6 weeks
measure: Ongoing pregnancy
timeFrame: 8 weeks
measure: Implantation rate
timeFrame: 1 day
measure: Adverse events
timeFrame: 8 weeks
measure: Neonatal outcome
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Department of Obstetrics and Gynaecology
state: Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Ernest HY Ng, MD
role: PRINCIPAL_INVESTIGATOR
References: