Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle (NC).
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
研究概览
简要总结
To describe the peripheral serum levels of the anti-inflammatory cytokines IL-4 (Interleukin-4), IL-10 (Interleukin-10), TGF-ß1 (Transforming Growth Factor beta1), the pro-inflammatory cytokines IL-17 (Interleukin-17), IFγ (Interferon Gamma) and the immune mediator PIBF (Progesterone-Induced Blocking Factor) along a single frozen euploid blastocyst transfer in a natural cycle (NC) or Hormone Replacement Therapy (HRT).
详细描述
This a prospective, observational study including 40 infertile patients undergoing a "single embryo transfer" (SET). Blood samples will be drawn for Progesterone-Induced Blocking Factor (PIBF), interleukin 17 (IL-17), Interferon Gamma (IFγ), Interleukin 10 (IL-10), Interleukin 4 (IL-4) and Transforming Growth Factor beta 1 (TGF-ß1) measurement on the day of ovulation in the natural cycle (NC) or first day of progesterone in the Hormone Replacement Therapy (HRT) protocol, on the day of embryo transfer (ET) and 3 and 10 days later, coinciding with the early and late embryo invasion stages respectively. In case of pregnancy, an additional blood test for PIBF, IL-17, IFγ, IL-10, IL-4, TGF-ß1 and ßHCG (Beta-Human Chorionic Gonadotropin) will be performed at 5 weeks +/- 3 days. The study will be performed at ART Fertility Clinics and the estimated completion time will be 12 months.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women aged 18 years to 40 years
- •Having at least one good quality (grade A or B for inner mass cell and trophectoderm) day 5 or 6 chromosomally normal cryopreserved blastocyst available for transfer
- •Single embryo transfer in a natural cycle (NC) or an Hormone Replacement Therapy (HRT) protocol
- •Fresh ejaculate used for fertilization
排除标准
- •Body mass index lower than 18.5 or equal or higher than 29 kg/m2
- •Endometriosis or adenomyosis suspected by medical history (dysmenorrhea, dyspareunia, heavy or prolonged menstrual bleeding (> 8 days), chronic pelvic pain, catamenial rectal or bladder symptoms) or diagnosed by imaging (magnetic resonance imaging or ultrasonography)
- •Uterine abnormalities
- •Hydrosalpinx
- •Insulin resistance or diabetes mellitus diagnosed by HbA1c 5.7 %
- •Antiphospholipid syndrome
- •Polycystic ovarian syndrome according to Rotterdam criteria: presence of at least two of the following: irregular cycles (< 21 or > 35 days or < 8 cycles a year), biochemical or clinical hyperandrogenism, ovarian ultrasound morphology (> 20 follicles per ovary on transvaginal scan) or Anti-mullerian hormone > 5,98 ng/ml
- •History of recurrent miscarriage, defined as the loss of 2 or more pregnancies according to ESHRE guidelines
- •History of implantation failure, considered as the lack of pregnancy after the transfer of 2 good-quality (grade A or B for inner mass cell and trophectoderm (29)) euploid embryos
- •History or suspicion of Asherman syndrome
- •Autoimmune disease
- •Couple first degree consanguineous
研究组 & 干预措施
Hormone Replacement Therapy Protocol
Ultrasound monitoring of endometrial growth and exclude growing follicle
Oral Estradiol Valerate (Progyluton) 4 mg on cycle day 2 at 7 pm for 2 days. On 3rd day, increase dose to 6 mg. The dose may be increased based on endometrial thickness.
Once endometrial thickness is at least 7 mm and trilaminar, after 10-15 days of Estradiol Valerate administration, start Endometrin 100 mg at 1 pm and 9 pm. From 2nd day onwards increase to 3 times daily. Continue Progyluton & Endometrin until 12 weeks of pregnancy
ET on the 5th full day of Endometrin administration
Blood test to measure PIBF, IL-17, IFγ, IL-4, IL-10 and TGF-ß1 on the 1st day of Endometrin supplementation (before 1st administration), on the 4th day of Endometrin administration, on the day of ET and 3 and10 days after, 4 to 7 hours after the morning administration.
Blood test to measure beta human chorionic gonadotropin (ß-hCG) will be performed 3 and 10 days after ET and at 5 weeks +/- 3 days if pregnancy.
干预措施: Endometrin 100Mg Vaginal Insert (Drug)
Hormone Replacement Therapy Protocol
Ultrasound monitoring of endometrial growth and exclude growing follicle
Oral Estradiol Valerate (Progyluton) 4 mg on cycle day 2 at 7 pm for 2 days. On 3rd day, increase dose to 6 mg. The dose may be increased based on endometrial thickness.
Once endometrial thickness is at least 7 mm and trilaminar, after 10-15 days of Estradiol Valerate administration, start Endometrin 100 mg at 1 pm and 9 pm. From 2nd day onwards increase to 3 times daily. Continue Progyluton & Endometrin until 12 weeks of pregnancy
ET on the 5th full day of Endometrin administration
Blood test to measure PIBF, IL-17, IFγ, IL-4, IL-10 and TGF-ß1 on the 1st day of Endometrin supplementation (before 1st administration), on the 4th day of Endometrin administration, on the day of ET and 3 and10 days after, 4 to 7 hours after the morning administration.
Blood test to measure beta human chorionic gonadotropin (ß-hCG) will be performed 3 and 10 days after ET and at 5 weeks +/- 3 days if pregnancy.
干预措施: Estradiol Valerate (Drug)
结局指标
主要结局
Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
时间窗: 1 day
Blood levels of IL-4 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Blood levels of IL-10 (Interleukin 10) ten days after embryo transfer
时间窗: 10 days
Blood levels of IL-10 ten days after embryo transfer
Blood levels of IL-17 (Interleukin 17) ten days after embryo transfer
时间窗: 10 days
Blood levels of IL-17 ten days after embryo transfer
Blood levels of IL-10 (Interleukin 10) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
时间窗: 1 day
Blood levels of IL-10 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Blood levels of IFγ (Interferon gamma) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
时间窗: 1 day
Blood levels of IFγ on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Blood levels of IL-17 (Interleukin 17) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
时间窗: 1 day
Blood levels of IL-17 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
时间窗: 1 day
Blood levels of TGF-ß1 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Blood levels of IL-4 (Interleukin 4) on the day before embryo transfer
时间窗: 1 day
Blood levels of IL-4 on the day before embryo transfer
Blood levels of PIBF on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
时间窗: 1 day
Blood levels of PIBF on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day before embryo transfer
时间窗: 1 day
Blood levels of TGF-ß1 on the day before embryo transfer
Blood levels of IFγ (Interferon gamma) on the day before embryo transfer
时间窗: 1 day
Blood levels of IFγ on the day before embryo transfer
Blood levels of IL-10 (Interleukin 10) on the day before embryo transfer
时间窗: 1 day
Blood levels of IL-10 on the day before embryo transfer
Blood levels of IL-17 (Interleukin 17) on the day before embryo transfer
时间窗: 1 day
Blood levels of IL-17 on the day before embryo transfer
Blood levels of IL-4 (Interleukin 4) on the day of embryo transfer
时间窗: 1 day
Blood levels of IL-4 on the day of embryo transfer
Blood levels of IL-17 (Interleukin 17) on the day of embryo transfer
时间窗: 1 day
Blood levels of IL-17 on the day of embryo transfer
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day of embryo transfer
时间窗: 1 day
Blood levels of TGF-ß1 on the day of embryo transfer
Blood levels of IL-10 (Interleukin 10) three days after embryo transfer
时间窗: 3 days
Blood levels of IL-10 three days after embryo transfer
Blood levels of PIBF (Progesterone induced blocking factor) three days after embryo transfer
时间窗: 3 days
Blood levels of PIBF three days after embryo transfer
Blood levels of IL-4 (Interleukin 4) ten days after embryo transfer
时间窗: 10 days
Blood levels of IL-4 ten days after embryo transfer
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) ten days after embryo transfer
时间窗: 10 days
Blood levels of TGF-ß1 ten days after embryo transfer
Blood levels of IL-17 (Interleukin 17) in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of IL-17 in case of pregnancy at 5 weeks +/- 3 days
Blood levels of PIBF (Progesterone induced blocking factor) in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of PIBF in case of pregnancy at 5 weeks +/- 3 days
Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
时间窗: 1 day
Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Blood levels of progesterone on the day of embryo transfer
时间窗: 1 day
Blood levels of progesterone on the day of embryo transfer
Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) ten days after embryo transfer
时间窗: 10 days
Blood levels of ß-hCG ten days after embryo transfer
Blood levels of PIBF (Progesterone induced blocking factor) on the day before embryo transfer
时间窗: 1 day
Blood levels of PIBF on the day before embryo transfer
Blood levels of PIBF (Progesterone induced blocking factor) on the day of embryo transfer
时间窗: 1 day
Blood levels of PIBF on the day of embryo transfer
Blood levels of IL-4 (Interleukin 4) three days after embryo transfer
时间窗: 3 days
Blood levels of IL-4 three days after embryo transfer
Blood levels of IL-10 (Interleukin 10) on the day of embryo transfer
时间窗: 1 day
Blood levels of IL-10 on the day of embryo transfer
Blood levels of IFγ (Interferon gamma) on the day of embryo transfer
时间窗: 1 day
Blood levels of IFγ on the day of embryo transfer
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) three days after embryo transfer
时间窗: 3 days
Blood levels of TGF-ß1 three days after embryo transfer
Blood levels of IL-17 (Interleukin 17) three days after embryo transfer
时间窗: 3 days
Blood levels of IL-17 three days after embryo transfer
Blood levels of IFγ (Interferon gamma) three days after embryo transfer
时间窗: 3 days
Blood levels of IFγ three days after embryo transfer
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of TGF-ß1 in case of pregnancy at 5 weeks +/- 3 days
Blood levels of IFγ (Interferon gamma) in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of IFγ in case of pregnancy at 5 weeks +/- 3 days
Blood levels of progesterone on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
时间窗: 1 day
Blood levels of progesterone on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Blood levels of estradiol on the day before embryo transfer
时间窗: 1 day
Blood levels of estradiol on the day before embryo transfer
Blood levels of IFγ (Interferon gamma) ten days after embryo transfer
时间窗: 10 days
Blood levels of IFγ ten days after embryo transfer
Blood levels of PIBF (Progesterone induced blocking factor) ten days after embryo transfer
时间窗: 10 days
Blood levels of PIBF ten days after embryo transfer
Blood levels of estradiol on the day of embryo transfer
时间窗: 1 day
Blood levels of estradiol on the day of embryo transfer
Blood levels of estradiol three days after embryo transfer
时间窗: 3 days
Blood levels of estradiol three days after embryo transfer
Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days
Blood levels of IL-4 (Interleukin 4) in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of IL-4 in case of pregnancy at 5 weeks +/- 3 days
Blood levels of progesterone three days after embryo transfer
时间窗: 3 days
Blood levels of progesterone three days after embryo transfer
Blood levels of estradiol ten days after embryo transfer
时间窗: 10 days
Blood levels of estradiol ten days after embryo transfer
Blood levels of progesterone ten days after embryo transfer
时间窗: 10 days
Blood levels of progesterone ten days after embryo transfer
Blood levels of IL-10 (Interleukin 10) in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of IL-10 in case of pregnancy at 5 weeks +/- 3 days
Blood levels of progesterone on the day before embryo transfer
时间窗: 1 day
Blood levels of progesterone on the day before embryo transfer
Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days
Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) three days after embryo transfer
时间窗: 3 days
Blood levels of ß-hCG three days after embryo transfer
Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) in case of pregnancy at 5 weeks +/- 3 days
时间窗: 5 weeks
Blood levels of ß-hCG in case of pregnancy at 5 weeks +/- 3 days
次要结局
- Pregnancy rate(10 days)
- Clinical pregnancy rate(5 weeks and 3 days)
- Miscarriage rate(12 weeks)
研究者
Laura Marqueta Marques
Principal Investigator
ART Fertility Clinics LLC