Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle.

Официальное название

Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle (NC).

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат 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
• Препарат 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).

Первичные конечные точки

• Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [Срок оценки: 1 day]
• Blood levels of IL-10 (Interleukin 10) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [Срок оценки: 1 day]
• Blood levels of IL-17 (Interleukin 17) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [Срок оценки: 1 day]
• 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) [Срок оценки: 1 day]
• Blood levels of IFγ (Interferon gamma) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [Срок оценки: 1 day]
• Blood levels of PIBF on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) [Срок оценки: 1 day]
• Blood levels of IL-4 (Interleukin 4) on the day before embryo transfer [Срок оценки: 1 day]
• Blood levels of IL-10 (Interleukin 10) on the day before embryo transfer [Срок оценки: 1 day]
• Blood levels of IL-17 (Interleukin 17) on the day before embryo transfer [Срок оценки: 1 day]
• Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day before embryo transfer [Срок оценки: 1 day]

Вторичные конечные точки (3)

• Pregnancy rate [Срок оценки: 10 days]
• Clinical pregnancy rate [Срок оценки: 5 weeks and 3 days]
• Miscarriage rate [Срок оценки: 12 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

ОАЭ · 1 центр

• ART Fertility Clinics LLC — Abu Dhabi

Публикации

• Zhang X, Wei H. Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications. Front Immunol. 2021 Aug 26;12:728291. doi: 10.3389/fimmu.2021.728291. eCollection 2021. PMID 34512661
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• Diaz-Hernandez I, Alecsandru D, Garcia-Velasco JA, Dominguez F. Uterine natural killer cells: from foe to friend in reproduction. Hum Reprod Update. 2021 Jun 22;27(4):720-746. doi: 10.1093/humupd/dmaa062. PMID 33528013
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• Liu Y, Gao S, Zhao Y, Wang H, Pan Q, Shao Q. Decidual Natural Killer Cells: A Good Nanny at the Maternal-Fetal Interface During Early Pregnancy. Front Immunol. 2021 May 12;12:663660. doi: 10.3389/fimmu.2021.663660. eCollection 2021. PMID 34054831
• Robertson SA, Moldenhauer LM. Immunological determinants of implantation success. Int J Dev Biol. 2014;58(2-4):205-17. doi: 10.1387/ijdb.140096sr. PMID 25023687
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Идентификаторы

NCT: NCT05473273 · 2206-ABU-004-LMM

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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