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

Infertility, Female Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05473273
• Other study ID #: 2206-ABU-004-LMM
• Status: Recruiting
• Start date: April 24, 2023
• Est. completion date: January 30, 2024

Study information

• Verified date: July 2023
• Source: ART Fertility Clinics LLC
• Contact: BARBARA LAWRENZ, PhD
• Phone: 97126528000
• Email: barbara.lawrenz[@]artfertilityclinics.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Infertility
• Infertility, Female

Intervention

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
• 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).

Locations

Country	Name	City	State
United Arab Emirates	ART Fertility Clinics LLC	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (33)

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* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of IL-4 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of IL-10 (Interleukin 10) 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
Primary	Blood levels of IL-17 (Interleukin 17) 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
Primary	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)	Blood levels of TGF-ß1 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of IF? (Interferon gamma) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of IF? on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of PIBF 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
Primary	Blood levels of IL-4 (Interleukin 4) on the day before embryo transfer	Blood levels of IL-4 on the day before embryo transfer	1 day
Primary	Blood levels of IL-10 (Interleukin 10) on the day before embryo transfer	Blood levels of IL-10 on the day before embryo transfer	1 day
Primary	Blood levels of IL-17 (Interleukin 17) on the day before embryo transfer	Blood levels of IL-17 on the day before embryo transfer	1 day
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day before embryo transfer	Blood levels of TGF-ß1 on the day before embryo transfer	1 day
Primary	Blood levels of IF? (Interferon gamma) on the day before embryo transfer	Blood levels of IF? on the day before embryo transfer	1 day
Primary	Blood levels of PIBF (Progesterone induced blocking factor) on the day before embryo transfer	Blood levels of PIBF on the day before embryo transfer	1 day
Primary	Blood levels of IL-4 (Interleukin 4) on the day of embryo transfer	Blood levels of IL-4 on the day of embryo transfer	1 day
Primary	Blood levels of IL-10 (Interleukin 10) on the day of embryo transfer	Blood levels of IL-10 on the day of embryo transfer	1 day
Primary	Blood levels of IL-17 (Interleukin 17) on the day of embryo transfer	Blood levels of IL-17 on the day of embryo transfer	1 day
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day of embryo transfer	Blood levels of TGF-ß1 on the day of embryo transfer	1 day
Primary	Blood levels of IF? (Interferon gamma) on the day of embryo transfer	Blood levels of IF? on the day of embryo transfer	1 day
Primary	Blood levels of PIBF (Progesterone induced blocking factor) on the day of embryo transfer	Blood levels of PIBF on the day of embryo transfer	1 day
Primary	Blood levels of IL-4 (Interleukin 4) three days after embryo transfer	Blood levels of IL-4 three days after embryo transfer	3 days
Primary	Blood levels of IL-10 (Interleukin 10) three days after embryo transfer	Blood levels of IL-10 three days after embryo transfer	3 days
Primary	Blood levels of IL-17 (Interleukin 17) three days after embryo transfer	Blood levels of IL-17 three days after embryo transfer	3 days
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) three days after embryo transfer	Blood levels of TGF-ß1 three days after embryo transfer	3 days
Primary	Blood levels of IF? (Interferon gamma) three days after embryo transfer	Blood levels of IF? three days after embryo transfer	3 days
Primary	Blood levels of PIBF (Progesterone induced blocking factor) three days after embryo transfer	Blood levels of PIBF three days after embryo transfer	3 days
Primary	Blood levels of IL-4 (Interleukin 4) ten days after embryo transfer	Blood levels of IL-4 ten days after embryo transfer	10 days
Primary	Blood levels of IL-10 (Interleukin 10) ten days after embryo transfer	Blood levels of IL-10 ten days after embryo transfer	10 days
Primary	Blood levels of IL-17 (Interleukin 17) ten days after embryo transfer	Blood levels of IL-17 ten days after embryo transfer	10 days
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) ten days after embryo transfer	Blood levels of TGF-ß1 ten days after embryo transfer	10 days
Primary	Blood levels of IF? (Interferon gamma) ten days after embryo transfer	Blood levels of IF? ten days after embryo transfer	10 days
Primary	Blood levels of PIBF (Progesterone induced blocking factor) ten days after embryo transfer	Blood levels of PIBF ten days after embryo transfer	10 days
Primary	Blood levels of IL-4 (Interleukin 4) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of IL-4 in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of IL-10 (Interleukin 10) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of IL-10 in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of IL-17 (Interleukin 17) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of IL-17 in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of TGF-ß1 in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of IF? (Interferon gamma) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of IF? in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of PIBF (Progesterone induced blocking factor) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of PIBF in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of progesterone 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
Primary	Blood levels of estradiol on the day before embryo transfer	Blood levels of estradiol on the day before embryo transfer	1 day
Primary	Blood levels of progesterone on the day before embryo transfer	Blood levels of progesterone on the day before embryo transfer	1 day
Primary	Blood levels of estradiol on the day of embryo transfer	Blood levels of estradiol on the day of embryo transfer	1 day
Primary	Blood levels of progesterone on the day of embryo transfer	Blood levels of progesterone on the day of embryo transfer	1 day
Primary	Blood levels of estradiol three days after embryo transfer	Blood levels of estradiol three days after embryo transfer	3 days
Primary	Blood levels of progesterone three days after embryo transfer	Blood levels of progesterone three days after embryo transfer	3 days
Primary	Blood levels of estradiol ten days after embryo transfer	Blood levels of estradiol ten days after embryo transfer	10 days
Primary	Blood levels of progesterone ten days after embryo transfer	Blood levels of progesterone ten days after embryo transfer	10 days
Primary	Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days	Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days	Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) three days after embryo transfer	Blood levels of ß-hCG three days after embryo transfer	3 days
Primary	Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) ten days after embryo transfer	Blood levels of ß-hCG ten days after embryo transfer	10 days
Primary	Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of ß-hCG in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Secondary	Pregnancy rate	Number of patients with a ß-hCG > 5 IU out of the number of patients who underwent an embryo transfer.	10 days
Secondary	Clinical pregnancy rate	Number of patients with an ultrasonographic visible sac out of the number of patients who underwent an embryo transfer	5 weeks and 3 days
Secondary	Miscarriage rate	Number of patients with a pregnancy loss out of the number of patients who had a ß-hCG > 5 IU after embryo transfer	12 weeks