Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle
Study Details
Study Description
Brief Summary
To describe the peripheral serum levels of the anti-inflammatory cytokines IL-4 (Interleukin-4), IL-10 (Interleukin-10), TGF-ß1 (Transforming growth factor ß1), 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 (SET) in a NC or HRT (Hormones Replacement Therapy).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
This a prospective, observational study including 40 infertile patients undergoing a SET. Blood samples will be drawn for PIBF, IL-17, IFγ, IL-10, IL-4 and TGF-ß1 measurement on the day of ovulation in the NC or first day of progesterone in the 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 will be performed at 5 weeks + 0 days. The study will be performed at ART Fertility Clinics and the estimated completion time will be 12 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Natural Cycle Protocol Ultrasound monitoring to monitor follicular and endometrial growth. Serial measurements of serum LH, E2, and P4 levels to determine timing of ovulation. A minimal endometrial thickness of 7 mm is required. No progesterone supplementation. ET will be scheduled 5 days after the day of ovulation, approximately after 120 hours of P4 exposure. Blood samples will be drawn to measure PIBF, IL-17, IFy, IL-10, IL-4 and TGF-ß1 on day of ovulation (P4 rise), on the day before ET, on the day of ET and 3 and 10 days later, always at 9 am. A blood test to measure ß-hCG will be performed 3, 10 days and 5 weeks +/- 3 days after ET, always at 9 am. In case of pregnancy, a blood test to measure PIBF, IL-17, IFγ, IL-10, IL-4 and TGF-ß1 will be performed at 5 weeks +/- 3 days at 9 am. |
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| HRT Cycle Protocol Ultrasound monitoring of endometrial growth & exclude presence of a growing follicle Oral Estradiol Valerate (Progyluton) 4mg on cycle day 2 at 7pm for 2 days. On 3rd day, increase dose to 6mg. The dose may be increased based on endometrial thickness. Once endometrial thickness is atleast 7 mm trilaminar, after 10-15 days of E2 administration, start 1st dose Endometrin 100mg at 1pm & 9pm. From 2nd day onwards, dose to increase to 3x daily. Check P4 levels before Endometrin. Continue Progyluton & Endometrin until 12weeks of pregnancy ET on the 5th full day of P4 administration Blood test to check PIBF, IL-17, IFγ, IL-4, IL-10 & TGF-ß1 on the 1st day of P4 supplementation (before the 1st administration), on the 4th day of P4 administration, on the day of ET & 3, 10 days later at 9am Blood test ß-hCG on 3, 10 days & 5 weeks +/- 3 days after ET at 9am |
Drug: Endometrin 100Mg Vaginal Insert
Endometrin will start once endometrial thickness is equal or higher to 7 mm with a trilaminar appearance, after at least 10 days and always less than 16 days of estradiol administration. First day of supplementation a dose of 100mg will be administered at of at 1.pm and 9 pm. From the second day and onwards administration will be increased to three times daily, at 6 am, 2 pm and 10 pm
Drug: Estradiol Valerate
Estradiol valerate dose will be reduced to 4mg daily at 7 pm during the first two days of vaginal natural micronized progesterone supplementation and increased afterwards to 6 mg daily (2 mg at 10 am and 4 mg at 7 pm).
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Outcome Measures
Primary Outcome Measures
- Blood levels of IL-4 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [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 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [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 IL-17 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [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 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [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 IFγ on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [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 PIBF on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [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 IL-4 on the day before embryo transfer [1 day]
Blood levels of IL-4 on the day before embryo transfer
- Blood levels of IL-10 on the day before embryo transfer [1 day]
Blood levels of IL-10 on the day before embryo transfer
- Blood levels of IL-17 on the day before embryo transfer [1 day]
Blood levels of IL-17 on the day before embryo transfer
- Blood levels of TGF-ß1 on the day before embryo transfer [1 day]
Blood levels of TGF-ß1 on the day before embryo transfer
- Blood levels of IFγ on the day before embryo transfer [1 day]
Blood levels of IFγ on the day before embryo transfer
- Blood levels of PIBF on the day before embryo transfer [1 day]
Blood levels of PIBF on the day before embryo transfer
- Blood levels of IL-4 on the day of embryo transfer [1 day]
Blood levels of IL-4 on the day of embryo transfer
- Blood levels of IL-10 on the day of embryo transfer [1 day]
Blood levels of IL-10 on the day of embryo transfer
- Blood levels of IL-17 on the day of embryo transfer [1 day]
Blood levels of IL-17 on the day of embryo transfer
- Blood levels of TGF-ß1 on the day of embryo transfer [1 day]
Blood levels of TGF-ß1 on the day of embryo transfer
- Blood levels of IFγ on the day of embryo transfer [1 day]
Blood levels of IFγ on the day of embryo transfer
- Blood levels of PIBF on the day of embryo transfer [1 day]
Blood levels of PIBF on the day of embryo transfer
- Blood levels of IL-4 three days after embryo transfer [3 days]
Blood levels of IL-4 three days after embryo transfer
- Blood levels of IL-10 three days after embryo transfer [3 days]
Blood levels of IL-10 three days after embryo transfer
- Blood levels of IL-17 three days after embryo transfer [3 days]
Blood levels of IL-17 three days after embryo transfer
- Blood levels of TGF-ß1 three days after embryo transfer [3 days]
Blood levels of TGF-ß1 three days after embryo transfer
- Blood levels of IFγ three days after embryo transfer [3 days]
Blood levels of IFγ three days after embryo transfer
- Blood levels of PIBF three days after embryo transfer [3 days]
Blood levels of PIBF three days after embryo transfer
- Blood levels of IL-4 ten days after embryo transfer [10 days]
Blood levels of IL-4 ten days after embryo transfer
- Blood levels of IL-10 ten days after embryo transfer [10 days]
Blood levels of IL-10 ten days after embryo transfer
- Blood levels of IL-17 ten days after embryo transfer [10 days]
Blood levels of IL-17 ten days after embryo transfer
- Blood levels of TGF-ß1 ten days after embryo transfer [10 days]
Blood levels of TGF-ß1 ten days after embryo transfer
- Blood levels of IFγ ten days after embryo transfer [10 days]
Blood levels of IFγ ten days after embryo transfer
- Blood levels of PIBF ten days after embryo transfer [10 days]
Blood levels of PIBF ten days after embryo transfer
- Blood levels of IL-4 in case of pregnancy at 5 weeks [5 weeks]
Blood levels of IL-4 in case of pregnancy at 5 weeks
- Blood levels of IL-10 in case of pregnancy at 5 weeks [5 weeks]
Blood levels of IL-10 in case of pregnancy at 5 weeks
- Blood levels of IL-17 in case of pregnancy at 5 weeks [5 weeks]
Blood levels of IL-17 in case of pregnancy at 5 weeks
- Blood levels of TGF-ß1 in case of pregnancy at 5 weeks [5 weeks]
Blood levels of TGF-ß1 in case of pregnancy at 5 weeks
- Blood levels of IFγ in case of pregnancy at 5 weeks [5 weeks]
Blood levels of IFγ in case of pregnancy at 5 weeks
- Blood levels of PIBF in case of pregnancy at 5 weeks [5 weeks]
Blood levels of PIBF in case of pregnancy at 5 weeks
- Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [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 on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [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 [1 day]
Blood levels of estradiol on the day before embryo transfer
- Blood levels of progesterone on the day before embryo transfer [1 day]
Blood levels of progesterone on the day before embryo transfer
- Blood levels of estradiol on the day of embryo transfer [1 day]
Blood levels of estradiol on the day of embryo transfer
- Blood levels of progesterone on the day of embryo transfer [1 day]
Blood levels of progesterone on the day of embryo transfer
- Blood levels of estradiol three days after embryo transfer [3 days]
Blood levels of estradiol three days after embryo transfer
- Blood levels of progesterone three days after embryo transfer [3 days]
Blood levels of progesterone three days after embryo transfer
- Blood levels of estradiol ten days after embryo transfer [10 days]
Blood levels of estradiol ten days after embryo transfer
- Blood levels of progesterone ten days after embryo transfer [10 days]
Blood levels of progesterone ten days after embryo transfer
- Blood levels of estradiol in case of pregnancy at 5 weeks [5 weeks]
Blood levels of estradiol in case of pregnancy at 5 weeks
- Blood levels of progesterone in case of pregnancy at 5 weeks [5 weeks]
Blood levels of progesterone in case of pregnancy at 5 weeks
- Blood levels of ß-hCG three days after embryo transfer [3 days]
Blood levels of ß-hCG three days after embryo transfer
- Blood levels of ß-hCG ten days after embryo transfer [10 days]
Blood levels of ß-hCG ten days after embryo transfer
- Blood levels of ß-hCG in case of pregnancy 5 weeks after embryo transfer [5 weeks]
Blood levels of ß-hCG in case of pregnancy 5 weeks after embryo transfer
Secondary Outcome Measures
- Pregnancy rate [10 days]
Number of patients with a ß-hCG > 5 IU out of the number of patients who underwent an embryo transfer
- Clinical pregnancy rate [5 weeks and 3 days]
Number of patients with an ultrasonographic visible sac out of the number of patients who underwent an embryo transfer
- Miscarriage rate [12 weeks]
Number of patients with a pregnancy loss out of the number of patients who had a ß-hCG > 5 IU after embryo transfer
Eligibility Criteria
Criteria
Inclusion Criteria:
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Women aged 18 years to 40 years
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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
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Single embryo transfer in a NC or an HRT protocol
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Fresh ejaculate used for fertilization
Exclusion Criteria:
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BMI lower than 18.5 or equal or higher than 29 kg/m2
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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 (MRI or ultrasonography)
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Uterine abnormalities
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Hydrosalpinx
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Insulin resistance or diabetes mellitus diagnosed by HbA1c 5.7 %
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Antiphospholipid syndrome
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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 AMH > 6.25 ng/ml
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History of recurrent miscarriage, defined as the loss of 2 or more pregnancies according to ESHRE guidelines
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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
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History or suspicion of Asherman syndrome
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Autoimmune disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ART Fertility Clinics LLC | Abu Dhabi | United Arab Emirates | 60202 |
Sponsors and Collaborators
- ART Fertility Clinics LLC
Investigators
- Principal Investigator: LAURA MARQUETA MARQUES, Consultant, ART Fertility Clinics LLC
Study Documents (Full-Text)
None provided.More Information
Publications
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