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

ART Fertility Clinics LLC

Status: Enrolling

Conditions: Infertility, Female

Treatments: Drug: Estradiol Valerate; Drug: Endometrin 100Mg Vaginal Insert

Study type: Observational

Funder types: Other

Identifiers

NCT05473273

2206-ABU-004-LMM

Details and patient eligibility

About

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).

Full 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.

Enrollment: 40 estimated patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

40 participants in 2 patient groups

Natural Cycle Protocol

Description:

Ultrasound monitoring to monitor follicular and endometrial growth. Serial measurements of serum Lutenizing Hormone (LH), estradiol (E2), and progesterone (P4) to identify ovulation. Minimal endometrial thickness of 7 mm is required. No progesterone supplementation. Embryo transfer (ET) will be scheduled 5 days after the day of ovulation (120 hours of P4 exposure). Blood samples will be drawn to measure PIBF, IL-17, IFγ, 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, between 9 and 12 am. A 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 in case of pregnancy, between 9 and 12 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 between 9 and 12 am..

Hormone Replacement Therapy Protocol

Description:

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.

Treatment:

Drug: Endometrin 100Mg Vaginal Insert

Drug: Estradiol Valerate