Clinical trial NCT05473273: Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle.
Official title: Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle (NC).
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Infertility, Female
Keywords: infertilty
ivf
progesterone
estradiol
cytokines
immunology
Pharmacological effect of drugs
hormones
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2022-07-25
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Infertile women undergoing a single frozen embryo transfer

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 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
timeFrame: 1 day
measure: Blood levels of IL-10 (Interleukin 10) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
timeFrame: 1 day
measure: Blood levels of IL-17 (Interleukin 17) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
timeFrame: 1 day
measure: 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)
timeFrame: 1 day
measure: Blood levels of IFγ (Interferon gamma) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
timeFrame: 1 day
measure: Blood levels of PIBF on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
timeFrame: 1 day
measure: Blood levels of IL-4 (Interleukin 4) on the day before embryo transfer
timeFrame: 1 day
measure: Blood levels of IL-10 (Interleukin 10) on the day before embryo transfer
timeFrame: 1 day
measure: Blood levels of IL-17 (Interleukin 17) on the day before embryo transfer
timeFrame: 1 day
measure: Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day before embryo transfer
timeFrame: 1 day
measure: Blood levels of IFγ (Interferon gamma) on the day before embryo transfer
timeFrame: 1 day
measure: Blood levels of PIBF (Progesterone induced blocking factor) on the day before embryo transfer
timeFrame: 1 day
measure: Blood levels of IL-4 (Interleukin 4) on the day of embryo transfer
timeFrame: 1 day
measure: Blood levels of IL-10 (Interleukin 10) on the day of embryo transfer
timeFrame: 1 day
measure: Blood levels of IL-17 (Interleukin 17) on the day of embryo transfer
timeFrame: 1 day
measure: Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day of embryo transfer
timeFrame: 1 day
measure: Blood levels of IFγ (Interferon gamma) on the day of embryo transfer
timeFrame: 1 day
measure: Blood levels of PIBF (Progesterone induced blocking factor) on the day of embryo transfer
timeFrame: 1 day
measure: Blood levels of IL-4 (Interleukin 4) three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of IL-10 (Interleukin 10) three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of IL-17 (Interleukin 17) three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of TGF-ß1 (Transforming Growth Factor beta1) three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of IFγ (Interferon gamma) three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of PIBF (Progesterone induced blocking factor) three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of IL-4 (Interleukin 4) ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of IL-10 (Interleukin 10) ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of IL-17 (Interleukin 17) ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of TGF-ß1 (Transforming Growth Factor beta1) ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of IFγ (Interferon gamma) ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of PIBF (Progesterone induced blocking factor) ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of IL-4 (Interleukin 4) in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
measure: Blood levels of IL-10 (Interleukin 10) in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
measure: Blood levels of IL-17 (Interleukin 17) in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
measure: Blood levels of TGF-ß1 (Transforming Growth Factor beta1) in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
measure: Blood levels of IFγ (Interferon gamma) in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
measure: Blood levels of PIBF (Progesterone induced blocking factor) in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
measure: Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
timeFrame: 1 day
measure: Blood levels of progesterone on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
timeFrame: 1 day
measure: Blood levels of estradiol on the day before embryo transfer
timeFrame: 1 day
measure: Blood levels of progesterone on the day before embryo transfer
timeFrame: 1 day
measure: Blood levels of estradiol on the day of embryo transfer
timeFrame: 1 day
measure: Blood levels of progesterone on the day of embryo transfer
timeFrame: 1 day
measure: Blood levels of estradiol three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of progesterone three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of estradiol ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of progesterone ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
measure: Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
measure: Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) three days after embryo transfer
timeFrame: 3 days
measure: Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) ten days after embryo transfer
timeFrame: 10 days
measure: Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) in case of pregnancy at 5 weeks +/- 3 days
timeFrame: 5 weeks
Secondary outcomes:
measure: Pregnancy rate
timeFrame: 10 days
measure: Clinical pregnancy rate
timeFrame: 5 weeks and 3 days
measure: Miscarriage rate
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: ART Fertility Clinics LLC
Study officials:
affiliation: ART Fertility Clinics LLC
name: LAURA MARQUETA MARQUES, Consultant
role: PRINCIPAL_INVESTIGATOR
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