Open Label Pilot Study on Gene Expression Profiling of the Endometrial Tissue in Patients Undergoing Assisted Reproductive Technology [ART: In Vitro Fertilization (IVF)/ Intracytoplasmic Sperm Injection (ICSI)] With GONAL-f®
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Gene Expression of the Endometrium Following 1 Cycle With Gonal-f®
研究概览
简要总结
This is a Phase IV, pilot, open-label, national, multi-centric study planned to determine the gene expression profiles and histologic changes of the endometrial tissue before and after stimulation with Gonal-f®. Physicians are interested in identifying predictive genetic markers in assisted reproductive technologies (ART) in addition to the clinical predictive factors already known. Among those predictive factors, the state of the endometrium is considered as an important implantation determining factor for which pharmacogenomic research is of great interest.
The direct benefits of this study will be to know whether the endometrial gene expression profile is modified in response to stimulation treatment and have an impact or not on the endometrial tissue receptivity. The potential benefits of this study could be to assess the therapy optimization based on individual treatment response and gene expression profile compared to group treatment response in infertile women and prediction of response to therapy based on gene expression profiling before and after Gonal-f® stimulation in infertile women.
详细描述
This is a pilot open-label, national, multi-centre, Phase IV trial. This trial will be conducted with outpatients. Once subject has met all eligibility criteria, she will be treated with Gonal-f® prefilled pen and will receive on a randomization basis the GnRH agonist or antagonist. The follicle stimulating hormone (FSH) stimulation will start on day 2 of the menstrual cycle with a pre-defined fixed dose of 150 IU per day until follicles are recruited and developed. Dose adjustment will be allowed strictly in case of risk of ovarian hyperstimulation syndrome (OHSS). Ovulation triggering will be performed using a single injection of 250 mcg Ovitrelle®.
Ultrasound scans (US) will be performed concomitantly with hormonal assessment at each visit. Ovulation will be triggered as soon as there are at least 3 follicles > 16 mm, and with E2 > 1 mcg/L if agonist used. Oocyte retrieval, in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) and blastocyst transfer will be performed as per centre's standard practice. Vaginal progesterone will be administered in the luteal phase for all subjects (600 milligram per day [mg/d]).
Hormonal assessment and endometrial biopsy will be performed on:
- Day Luteinizing Hormone+7 ("LH+7") of the previous spontaneous cycle
- Day of Oocyte Retrieval (OR) of the stimulated cycle
- Day "OR+5 or 6" (biopsy performed only in subjects that did not have blastocyst(s) transfer).
Gene expression profiling will be carried out on ribonucleic acid (RNA) from endometrial tissue. As the main objective of this trial is to determine the gene expression profiles of endometrial tissue before and after controlled ovarian stimulation with Gonal-f®, a minimum of 2 endometrial samples per subject will be collected, 1 at day LH+7 of spontaneous cycle and 1 after the stimulation, on the day of OR.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Infertile female or infertile male. Infertile female means diverse infertility etiologies including tubal disease (excepting hydrosalpinx) and so called "unexplained infertility"
- •Suitable for ART: IVF undergoing first or second attempt, ICSI undergoing first attempt
- •18-35 years old, body mass index (BMI) less than or equal to 27 kilogram per square meter (kg/m^2), non smoking
- •Normal ovarian status (FSH less than or equal to 9.45 International Units per Liter [IU/L], E2 less than or equal to 40 picogram per milliliter [pg/mL], Anti-Mullerian Hormone [AMH] greater than or equal to 18 picomole/liter [pmol/L]; within normal laboratory range values, normal ovaries sonography and uterine echo doppler)
- •No history of active genito-urinary infection
- •Normal thyroid function (or adequate substitution for at least 3 months)
- •Negative cervical papanicolaou test within the last 12 months prior to study entry
- •No hormonal therapy, including gonadotropins and progesterone, for at least 2 months prior to the study
- •In couple with female infertility, male partner with normal sperm or moderate oligoasthenospermia in semen analysis and negative semen culture less than 6 months at the study entry
- •Willingness and ability to comply with the protocol for the duration of the study
- •Written informed consent prior to any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care
排除标准
- •Subjects with ongoing pregnancy, any pregnancy within 3 months prior to study entry, or any contraindication to pregnancy or carrying pregnancy to term
- •Subjects with uterine malformation, diethylstilbestrol syndrome, adenomyosis, synechia
- •Subjects with history of previous OHSS
- •Subjects with polycystic ovarian syndrome (PCOS) according to the revised Rotterdam Consensus 2003
- •Subjects with extra-uterine pregnancy during the previous 3 months
- •Subjects with recurrent miscarriages (early or late, more than 2)
- •Subjects having known infection with human immunodeficiency virus (HIV), hepatitis B or C virus, for subject or partner
- •Subjects with abnormal gynecological bleeding of undetermined origin
- •Subjects with history of major thromboembolic disease
- •Subjects with endometriosis
- •Subjects with presence or history of malignant tumors and related treatment
- •Subjects with clinically significant systemic disease or clinically significant abnormal hematology, chemistry, or urinalysis results at screening
- •Subjects with known allergy or hypersensitivity to Gonal-f® or Ovitrelle®
- •Subjects with any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years
- •Subjects who have participated within 3 months prior to study entry in another clinical trial
研究组 & 干预措施
Gonal-f® + Ovitrelle® + Long Agonist Protocol
干预措施: Gonal -f® [r-hFSH] (Drug)
Gonal-f® + Ovitrelle® + Long Agonist Protocol
干预措施: Ovitrelle® [r-hCG alfa] (Drug)
Gonal-f® + Ovitrelle® + Long Agonist Protocol
干预措施: Gonadotropin-releasing hormone (GnRH) Agonist (Drug)
Gonal-f® + Ovitrelle® + Multi-dose Antagonist Protocol
干预措施: Gonal -f® [r-hFSH] (Drug)
Gonal-f® + Ovitrelle® + Multi-dose Antagonist Protocol
干预措施: Ovitrelle® [r-hCG alfa] (Drug)
Gonal-f® + Ovitrelle® + Multi-dose Antagonist Protocol
干预措施: Gonadotropin-releasing hormone (GnRH) Antagonist (Drug)
结局指标
主要结局
Gene Expression of the Endometrium Following 1 Cycle With Gonal-f®
时间窗: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®
A list of genes based on gene expression profiling carried out on ribonucleic acid (RNA) extracted from endometrial tissue. The expression of messenger ribonucleic acid (mRNA) in endometrial tissue was measured by using microarrays such as the Affymetrix® GeneChip HG-U133 plus 2.0 array or equivalent.
Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f®
时间窗: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®
Participants with each histological pattern of endometrium were analyzed. Histological patterns included: Proliferative phase (described as the endometrial on the first two weeks after the menstruation \[or before ovulation\]), Early secretory phase (first step of the secretory phase, located at the Day 16-18 of the cycle) and Intermediate secretory phase (secretory phase located at the Day 20-22 of the cycle and describes endometrial closer to the implantation phase).
次要结局
- Gene Expression of the Endometrium in Participants With or Without Blastocyst Transfer(Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®)
- Gene Expression of the Endometrium Following 1 Cycle With Gonal-f® in Participants Having Undergone Agonist or Antagonist Protocol(Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®)
- Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f® and Having Undergone Agonist or Antagonist Protocol(Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®)
- Gene Expression in Participants Without Blastocyst Transfer(Day 5 or 6 (window of implantation) after Oocyte Retrieval)
- Number of Participants With a Specific Histological Pattern of the Endometrium in Participants Without Blastocyst Transfer(Day 5 or 6 (window of implantation) after Oocyte Retrieval)
- Gene Expression in Participants With Good or Poor Response to Gonal-f®(Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®)
- Number of Participants With a Specific Histological Pattern of the Endometrium in Participants With Good or Poor Response to Gonal-f®(Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®)