Eight Weeks of Low Dose hCG Priming in Women With Diminished Ovarian Reserve Undergoing IVF/ICSI - a Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of oocytes retrieved
研究概览
简要总结
The aim of this randomized controlled trial is to further examine the possible effects of low dose human chorionic gonadotropin (hCG) priming for eight weeks in women with diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). The investigators want to retest the findings of our first study in an identical paired design (NCT04643925), as an increase of 1.5 in mean number of oocytes retrieved is clinically relevant. To incorporate the strengths of a randomized controlled trial design, women will be randomized after their first ICSI treatment to receive either hCG or placebo in a double-blinded design during an eight-week priming period preceding their second ICSI treatment. The primary outcome is the number of oocytes retrieved in the second ICSI treatment.
详细描述
This randomized, double-blinded, placebo-controlled trial investigates whether eight weeks of low-dose hCG (LH activity) can produce a local intra-ovarian androgen priming and stimulate theca cell androgen production and improve oocyte yield during IVF/ICSI in women with diminished ovarian reserve (DOR).
The study is conducted at four public fertility clinics in Denmark: The Fertility Clinic at Copenhagen University Hospital, Rigshospitalet, the Fertility Clinic at Odense University Hospital, the Fertility Clinic at Hvidovre Hospital and the Fertility Clinic at Herlev Hospital.
Eligible women with DOR fulfilling the inclusion criteria and none of the exclusion criteria and with an indication for IVF/ICSI are enrolled. Women can participate only once.
Participating women will undergo two identical ICSI cycles, ICSI I and ICSI II, separated by an eight-week priming period with either daily low dose hCG-injections (260 IU) or placebo-injections (NaCl) according to randomization. Eight weeks of hCG/placebo priming corresponds to two natural menstrual cycles. A freeze-all strategy is applied in the first ICSI treatment.
Both ICSI cycles follow a fixed GnRH-antagonist protocol with of 300 IU rFSH initiated from cd 2-3 and the GnRH antagonist (Ganirelix 0.25 mg) from stimulation day 5-6. The patients undergo routine transvaginal ultrasound scans on cd 2/3, and per standard clinical practice until the day of ovulation trigger. Ovulation trigger by 6500 IU hCG sc is planned at 10 pm according to standard clinical practice. Oocyte retrieval will be done ~36 hours after ovulation trigger. ICSI will be used as fertilization method.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 18-40 (both inclusive)
- •Regular menstrual cycle (23-35 days)
- •IVF/ICSI cycle at inclusion
- •AMH < 6.29 pmol/L (Elecsys® AMH assay)
排除标准
- •Uterine malformations or hydrosalpinx
- •Submucosal uterine myomas
- •Uterine polyps
- •Allergy to standard IVF/ICSI medication
- •Endometriosis stage III-IV
- •Preimplantation genetic testing
- •Testicular sperm aspiration/extraction
- •Ovarian enlargement or cysts (other than normally occurring corpora luteae)
- •Gynaecological haemorrhages of unknown aetiology
- •Known severe comorbidity*
- •i.e., Insulin dependent diabetes mellitus, non-insulin dependent diabetes mellitus, gastrointestinal, cardiovascular, thromboembolic (including active thromboembolic disorders), pulmonary, liver or kidney diseases, HIV or Hepatitis B/C, dysregulated thyroid disease, tumors of the hypothalamus or pituitary gland or ovarian, uterine, or mammary carcinoma.
研究组 & 干预措施
hCG Priming
Women in the experimental group will undergo the following treatment in order:
A standard IVF/ICSI cycle (ICSI I): A standard IVF/ICSI cycle in the fixed GnRH-antagonist protocol using a daily dose of 300 IU rFSH initiated from cd 2-3 and a GnRH antagonist (Ganirelix 0.25 mg) from stimulation day 5-6 followed by blastocyst culture and a freeze-all strategy.
Priming period: hCG priming 260 IU once daily for two menstrual cycles (approximately 8 weeks).
A standard IVF/ICSI cycle (ICSI I): A standard IVF/ICSI cycle in the fixed GnRH-antagonist protocol using a daily dose of 300 IU rFSH initiated from cd 2-3 and a GnRH antagonist (Ganirelix 0.25 mg) from stimulation day 5-6 followed by blastocyst culture and a single blastocyst transfer at day 5.
干预措施: Choriongonadotropin alfa (hCG) (Drug)
Placebo
Women in the placebo group will undergo the following treatment in order:
A standard IVF/ICSI cycle (ICSI I): A standard IVF/ICSI cycle in the fixed GnRH-antagonist protocol using a daily dose of 300 IU rFSH initiated from cd 2-3 and a GnRH antagonist (Ganirelix 0.25 mg) from stimulation day 5-6 followed by blastocyst culture and a freeze-all strategy.
Priming period: Placebo (isotone NaCl) injections once daily for two menstrual cycles (approximately 8 weeks).
A standard IVF/ICSI cycle (ICSI I): A standard IVF/ICSI cycle in the fixed GnRH-antagonist protocol using a daily dose of 300 IU rFSH initiated from cd 2-3 and a GnRH antagonist (Ganirelix 0.25 mg) from stimulation day 5-6 followed by blastocyst culture and a single blastocyst transfer at day 5.
干预措施: Isotonic NaCl (Placebo) (Drug)
结局指标
主要结局
Number of oocytes retrieved
时间窗: Through study completion, an average of 4 months
The number of oocytes retrieved in the ICSI II treatment performed after hCG priming/placebo
次要结局
- Number of mature oocytes(Through study completion, an average of 4 months)
研究者
Kristine Loessl
Associate professor, Ph.D., MD
Rigshospitalet, Denmark