Clinical trial NCT04522479: Prolonged Protocol of Early Follicular or Mid Luteal Phase
Official title: Comparison of Efficacy and Safety of Controlled Hyperstimulation of Prolonged Protocol in Early Follicular or Mid Luteal Phase: a Single Center, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: IVF
Keywords: prolonged protocol
In vitro fertilization (IVF)
Intracytoplasmic sperm injection (ICSI)
single blastocyst transfer
Lead sponsor: Second Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
First posted: 2020-08-21
Enrollment: 1150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The early follicular and mid luteal prolonged regimens were randomly enrolled in a ratio of 1 to 1
Primary purpose: TREATMENT

Brief summary: Due to the injection of gonadotropin releasing hormone agonist (GnRH-a) before controlled ovarian hyperstimulation (COH), the scheme of prolonged early follicular period protocol has obvious advantages in achieving ideal egg number, increasing endometrial receptivity to embryo transfer, inhibiting endogenous luteinizing hormone (LH) peak and reducing cycle cancellation rate. The full dose of long acting GnRH-a was also applied before COH in the mid luteal Hypergrowth program, and the mechanism of its lowering tone was similar. But whether the clinical and perinatal outcome of early follicular hyperlengthening is as effective as that of mid luteal hyperlengthening has not been reported at home and abroad. Moreover, there is a lack of prospective randomized controlled studies.

Detailed description: One injection of 3.75mg GnRHa was injected on the 1st-3rd or 21st-23rd day of menstruation. The level of estradiol (E2), progesterone (P), luteinizing hormone (LH) in peripheral blood and the number of follicles in bilateral ovarian internal sinuses were monitored on the 32nd-38th day after pituitary hyporegulation.Gonadotropin (Gn) will be given after pituitary desensitization. When the diameter of at least two follicles ≥ 18mm or more than three follicles ≥ 17mm, the trigger of human chorionic gonadotropin (hCG) will be given and oocyte will be retrieved. The selective fresh single blastocyst transplantation will be carried out on the 4th-6th day after oocyte retrieval. HCG test at 12nd day after transplatation. Follow-up investigation will given during the pregnancy and perinatal period.

Eligibility criteria: Inclusion Criteria:

1. Tubal factor infertility;
2. polycystic ovary (PCO) or polycystic ovary syndrome (PCOS) patients;
3. Patients of mild to moderate endometriosis；
4. Oligoasthenospermia in male；
5. More than 5 antral follicle count (AFC) on both ovaries；
6. Unexplained infertility: there is a history of no contraception and pregnancy for more than 1 year, no clear cause of infertility such as ovulation, fallopian tube, endometrium and male factors is found, or the above factors return to normal after treatment.

Exclusion Criteria:

1. History of adverse pregnancy and childbirth；
2. Unilateral ovariectomy；
3. Uterine malformation, intrauterine adhesion, submucous myoma；
4. Chromosomal abnormality of both husband and wife；
5. Patients with contraindications of assisted reproductive technology or pregnancy: such as uncontrolled diabetes mellitus, undiagnosed liver and kidney dysfunction, history of deep vein thrombosis, history of pulmonary embolism, history of cerebrovascular accident, uncontrolled hypertension, heart disease, suspected cervical cancer, endometrial cancer, breast cancer or previous history, undetermined vaginal bleeding;
6. Unable to be regularly follow up；
7. Participating in other clinical trials；
8. No fresh single blastocyst transfer.

Primary outcomes:
measure: live birth rate
timeFrame: live birth of more than 28 pregnancy weeks
Secondary outcomes:
measure: clinical pregnancy rate
timeFrame: fetal heart beat confirmed by transvaginal ultrasound 26-35 days after embryo transplantation
measure: good quality blastocyst rate
timeFrame: The ratio of good quality blastocysts above 4BB degree 4-6 days after oocyte collection
measure: Incidence rate of early on-set severe ovarian hyperstimulation syndrome (OHSS)
timeFrame: Severe ovarian hyperstimulation syndrome according to Golan standard within 7 days after ovum removal
measure: Early misscarage rate
timeFrame: Abortion before 12 pregnancy weeks
measure: Perinatal complications
timeFrame: Incidence rate of mother and child complications from pregnancy to postpartum in 42 days
Other outcomes:
Locations:
city: Wenzhou
country: China
facility: The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: The 2nd Affiliated Hospital of Wenzhou Medical University
name: Yingfen Ying
role: PRINCIPAL_INVESTIGATOR
References: