A Prospective, Randomized, Open-label, Concurrent-controlled,Three-arm Study to Compare the Clinical Efficacy and Tolerability ofDifferent Follicle-stimulating Hormone (Endogen® HP, Sanzyme vsFostimon®, IBSA) and Human Chorionic Gonadotropin (Pubergen® HP,Sanzyme vs Pregnyl®, MSD Ltd.) Combinations in Women UndergoingIn Vitro Fertilization
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 162
- 试验地点
- 6
- 主要终点
- Total number of mature oocytes retrieved
研究概览
简要总结
A Prospective, Randomized, Open-label, Concurrent-controlled, Three-arm Study to Compare the Clinical Efficacy and Tolerability of Different Follicle-stimulating Hormone (Endogen® HP, Sanzyme vs Fostimon®, IBSA) and Human Chorionic Gonadotropin (Pubergen® HP, Sanzyme vs Pregnyl®, MSD Ltd.) Combinations in Women Undergoing In Vitro Fertilization.
Primary Objective:
To evaluate the clinical efficacy of different follicle-stimulating hormone (FSH) (Endogen® HP, Sanzyme vs Fostimon®, IBSA) and different human chorionic gonadotropin (hCG) (Pubergen® HP, Sanzyme vs Pregnyl®, MSD
Ltd.) combinations, when administered to female subjects undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF)
Secondary Objectives:
-
To evaluate additional efficacy of different FSH (Endogen® HP, Sanzyme vs Fostimon®, IBSA) and different hCG (Pubergen® HP, Sanzyme vs Pregnyl® HP, MSD Ltd.) combinations when administered to female subjects undergoing COS for IVF
-
To evaluate safety of different FSH (Endogen® HP, Sanzyme vs Fostimon®, IBSA) and different hCG (Pubergen® HP, Sanzyme vs Pregnyl® HP, MSD Ltd.) combinations when administered to female subjects undergoing COS for IVF.
This is a multicentre, prospective, randomized, open-label, concurrent-controlled, three-arm clinical study.
All the eligible female subjects will be randomized in a 1:1:1 ratio to the following study arms and will receive the following study products:
Arm 1:
-
FSH preparation of Endogen® HP, Sanzyme (for ovarian follicle stimulation) and
-
hCG preparation of Pubergen® HP, Sanzyme (for final oocyte maturation and trigger)
Arm 2:
-
FSH preparation of Fostimon®, IBSA (for ovarian follicle stimulation) and
-
hCG preparation of Pubergen® HP, Sanzyme (for final oocyte maturation and trigger)
Arm 3:
-
FSH preparation of Endogen® HP, Sanzyme (for ovarian follicle stimulation) and
-
hCG preparation of Pregnyl®, MSD Ltd. (for final oocyte maturationand trigger)
The purpose of this noninferiority study is to evaluate the clinical efficacy and general tolerability of different FSH and hCG combinations when administered to subjects undergoing COS for IVF. All enrolled subjects will undergo downregulation using a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen for COS. FSH will be given s.c. or i.m. (dose in the range of 150-225 IU) starting from day 2 to day 5 of the current menstrual cycle (C1) or an incremental dose not exceeding 600 IU per day (for the first 4 days) and then the dose of FSH will be optimally adjusted depending on the ovarian response monitored by serum E2 levels and transvaginal ultrasonography (TVUS) measurement. Approximately after 5 days of stimulation with FSH injection, GnRH antagonist (cetrorelix) will be administered subcutaneously (s.c.) following a flexible dose protocol i.e., dose according
to clinical judgement. Thus, each subject will receive cetrorelix injection. from Day 6 of the treatment cycle C1 along with FSH until the day of hCG administration. The FSH administration (plus GnRH antagonist) will be continued until at least two follicles ≥16 mm in diameter are observed on TVUS and serum E2 levels are appropriate as per clinical judgement for hCG trigger. Subjects fulfilling this criterion will be administered 5000 to 10000 IU of hCG
injection. After 34 to 36 hours of hCG injection, the mature oocytes will be retrieved, artificially fertilized, followed by Day 2 or Day 3 or Day 5 embryo transfer, and luteal phase support will be provided as per the site’s routine practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 21.00 Year(s) 至 37.00 Year(s)（—）
- 性别
- Female
入选标准
- •Subjects with all of the following criteria were considered for inclusion:
- •Women with unexplained infertility undergoing COS for their first or second cycle of IVF with or without intracytoplasmic sperm injection (ICSI), irrespective of the outcome of first IVF cycle with following characteristics:.
- •Age >21 and ≤37 years.
- •Ability to provide written informed consent voluntarily for study participation, along with consent by partner or spouse.
- •A BMI between 18.5 and 30 kg/m
- •Basal FSH, luteinizing hormone (LH), E2, progesterone (P4) and prolactin (PRL) levels within normal range in cycle 1 Day
- •Normal ovarian response: antral follicular count (AFC) ≥10 and anti-Müllerian hormone (AMH) level ≥1.0 ng/mL but ≤3.5 ng/mL.
- •Normal ovulatory cycles of 21 to 35 ±2 days inclusive.
- •TVUS documenting the presence of both ovaries, without evidence of abnormality (e.g., no endometrioma) and normal adnexa (e.g., no hydrosalpinx) within 6 months prior to randomization.
- •Normal or clinically insignificant haematology and blood chemistry values.
- •Husband or male partner, or donor with normal sperm motility and sperm count or with non-severe male factor infertility (defined as a semen concentrate 5 to 15×106 /mL or sperm with progressive motility (type a+b) 10% to 32%), including mild-to-moderate oligospermia, with or without asthenospermia.
排除标准
- •History of more than 2 unsuccessful induction cycles with FSH/ human menopausal gonadotropin (hMG) or hCG regimen or intolerability to these regimens requiring discontinuation.
- •History of ≥3 clinically confirmed miscarriages.
- •Persistent ovarian cysts more than 10 mm in size for >1 cycle or ovarian endometrioma.
- •Polycystic ovarian syndrome (PCOS).
- •Submucosal or intramural fibroids ≥5 cm or any other clinically relevant pathology, which could impair embryo implantation or pregnancy continuation.
- •Tumours and malformation of sexual organs incompatible with pregnancy.
- •Hydrosalpinx that has not been surgically removed or ligated.
- •Stage III or IV endometriosis (per revised American Society for Reproductive Medicine classification, 2012).
- •History of ectopic pregnancy.
- •Prior history of OHSS.
- •Hypersensitivity to study medication or its excipients.
- •Abnormal bleeding of undetermined origin.
- •Any significant systemic disease or endocrine disorders (pituitary, thyroid, adrenal, pancreas, liver, or kidney) or any active condition requiring treatment, which, according to the Investigator, might interfere with the study.
- •Metabolic disorders such as uncontrolled type I or type II diabetes mellitus.
- •Untreated hyperprolactinaemia.
- •Severe infections of the reproductive system such as tuberculosis and sexually transmitted diseases.
- •Receiving donor oocytes
- •Known history of human immunodeficiency virus (HIV), hepatitis B or C, or syphilis infection.
- •Use of the concomitant medication that might interfere with study evaluation
- •Pregnancy, lactation, or contraindication to pregnancy
- •Current or past (last 12 months) abuse of alcohol or drugs
- •Participation in a concurrent clinical trial or in another trial within the past 6 months.
结局指标
主要结局
Total number of mature oocytes retrieved
时间窗: 34 to 36 hours after hCG administration
次要结局
- - Total dose of FSH(- Number of days of FSH stimulation)