Clinical trial NCT03071172: Clinical Study of Recombinant Human Follitropin for Injection Assisted in COH Assisted IVF-ET
Official title: Clinical Study of Recombinant Human Follitropin for Injection Assisted in Controlled Ovarian Hyperstimulation Assisted IVF-ET
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Ovarian Hyperstimulation Syndrome
Lead sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking University Third Hospital
name: The First Affiliated Hospital with Nanjing Medical University
name: Women's Hospital School Of Medicine Zhejiang University
name: Xiangya Hospital of Central South University
name: Sixth Affiliated Hospital, Sun Yat-sen University
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: The First Affiliated Hospital of Anhui Medical University
First posted: 2017-03-06
Enrollment: 252
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study was to evaluate the efficacy and safety of domestic recombinant human follicle stimulating hormone (rhFSH) stimulating ovarian to promote follicular development before assisted reproductive technology, which was non-inferiority than that of the imported rhFSH.


Eligibility criteria: Inclusion Criteria:

* Age is more than 20 years old and less than 39 years old, married.
* Applicable for ART controlled ovarian hyperstimulation, such as IVF/ET, ICSI, GIFT, ZIFT and so on.
* Regular menstrual cycle (25-35 days).
* 18kg/m2≤BMI\<30kg/m2.
* The level of basic serum FSH \<10IU / L in the 2nd-5th days of the menstrual cycle, the luteinizing hormone, estradiol and progesterone levels were normal.
* The screening period or recent three months of vaginal ultrasound examination showed that the shape of bilateral ovarian and uterine size were normal and 5 ≤ number of basal antral follicle in unilateral ovarian \<10, and follicular diameter \<10 mm.
* The in vitro fertilization and embryo transfer (IVF/ET) and (or) intracytoplasmic sperm injection (ICSI) technology were less than three times used prior to the reproductive treatment (provide copies of previous cases).
* Volunteer to participate and sign informed consent.

Exclusion Criteria:

* There are high risk of ovarian hyperstimulation syndrome (OHSS), such as the subject who has high response to gonadotropin in the previous ovarian hyperstimulation cycle, polycystic ovary syndrome (PCOS), the subject who has severe OHSS cancellation cycle.
* Affect the outcome of pregnancy-related diseases (any one): untreated hydrosalpinx, untreated uterine polyps, untreated uterine infection, stage Ⅲ \~ IV endometriosis, ovarian cyst\> 4cm , uterine fibroids diameter\> 4cm, pelvic benign tumor\> 4cm, pituitary tumors and malignant tumors of tissues and organs.
* The subject has abnormal uterine bleeding.
* Affect pregnancy-related endocrine and metabolic diseases (any one): hyperprolactinemia, thyroid disease (including hyperthyroidism, hypothyroidism), hyperandrogenism, adrenal dysfunction (including adrenal hyperfunction, adrenal cortical dysfunction).
* The subject has severe liver and kidney dysfunction, which the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are 2.5 times higher than the upper limit of normal value, and serum creatinine (Cr) and urea nitrogen (BUN) are 2 times higher than the upper limit of normal value.
* Severe heart disease, unstable angina pectoris, heart failure grade Ⅲ above, acute myocardial infarction and/or old myocardial infarction, hypertension diagnosed according to the 2010 edition of the Chinese Hypertension Prevention Guidelines.
* The subject who have contraindications or allergic history for gonadotropin-releasing hormone agonists (GnRH-a), rFSH/human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG), progesterone drugs.
* Positive HIV or syphilis.
* The subject has alcoholism, smoking, drug abuse, bad drug abuse habits.
* At least one of the spouses has received sperm donor or egg donor or PGD (genetic diagnosis before embryo transfer) and PGS (Preimplantation of embryos before genetic screening)。
* The subject received clomiphene or gonadotropin therapy within 1 month before screening。
* The subject was participated in last three months or are participating in other clinical research。
* Patients with positive serum pregnancy test.
* The investigators considered the subject inappropriate to be enrolled in this study.

Primary outcomes:
measure: The total number of oocytes obtained during the start-up period
timeFrame: On the days of ovum picking up (hCG trigger 36-38h)
Secondary outcomes:
measure: The number of follicle-1
timeFrame: on the day of hCG day
measure: The number of follicle-2
timeFrame: on the fifth day of rhFSH ovarian stimulation
measure: Number of 2PN oocytes
timeFrame: Collected on the day of embryo transfer day after three days of ovum picking up.
measure: Number of metaphase II oocytes
timeFrame: Collected on the day of embryo transfer day after three days of ovum picking up, which only collected during ICSI cycle.
measure: Number of transferred embryos
timeFrame: Collected on the day of embryo transfer day after three days of ovum picking up.
measure: Number of high quality embryos
timeFrame: Collected on the day of embryo transfer day after three days of ovum picking up.
measure: Fresh cycle embryo implantation
timeFrame: Collected on the day of embryo transfer day after three days of ovum picking up.
measure: rhFSH administered days and vials; administered total dose of rhFSH (IU)
timeFrame: Collected on the day of hCG day.
measure: Serum E2 level
timeFrame: Collected on the day of hCG day.
measure: High quality embryos rate
timeFrame: Collected on the day of embryo transfer day after three days of ovum picking up.
measure: Fertilization rate
timeFrame: Collected on the day of embryo transfer day after three days of ovum picking up.
measure: Fresh cycle embryo implantation rate
timeFrame: Collected between 28-35 days after embryo transfer.
measure: Biochemical pregnancy rate
timeFrame: Collected between 14-16 days after embryo transfer.
measure: Clinical pregnancy rate
timeFrame: Collected between 28-35 days after embryo transfer.
measure: Continuous pregnancy rate
timeFrame: Collected after 12 weeks of embryo transfer.
measure: The number of follicle-3
timeFrame: on the day of hCG day
measure: The number of follicle-4
timeFrame: on the day of hCG day
measure: Endometrium thickness (mm)
timeFrame: on the day of hCG
Other outcomes:
Locations:
city: Hefei
country: China
facility: The first Affiliated Hospital of Anhui Medical University
state: Anhui
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Hangzhou
country: China
facility: Women's Hospital School of Medicine Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: Peking University Third Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
Study officials:
affiliation: Peking University Third Hospital
name: Rong Li, Doctor
role: PRINCIPAL_INVESTIGATOR
References: