Infertility, FemaleNCT05473273
Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle.
An observational study of Infertility, Female, run by ART Fertility Clinics LLC at 1 site in United Arab Emirates.
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… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility, Female
- What is being tested?
- Endometrin 100Mg Vaginal Insert and Estradiol Valerate
- Type of treatment
- Pill or oral medicine
- How many people
- 40 participants
- Where
- 1 siteUnited Arab Emirates
- Study dates
- 24 Apr 2023to 30 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Infertile women undergoing a single frozen embryo transfer
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Arab Emirates1 site, 1 recruiting
- Recruiting
ART Fertility Clinics LLC
Abu Dhabi, Abu Dhabi Emirate, 60202
Barbara Lawrenz, PhD, +97102 652 8000, suzan.samir@artfertilityclinics.com
Laura Marqueta Marques
About this study
Official title: Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle (NC).
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).
Read the 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.
- Conditions
- Infertility, Female
- Being tested
- Endometrin 100Mg Vaginal Insert, Estradiol Valerate
- Keywords
- infertilty, ivf, progesterone, estradiol, cytokines, immunology, Pharmacological effect of drugs, hormones
- Medical subject headings
- Infertility, Female, Long Qt Syndrome 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endometrin 100Mg Vaginal InsertDrug
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 ValerateDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Natural Cycle Protocol | 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 | 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. Receives: Drug: Endometrin 100Mg Vaginal Insert; Drug: Estradiol Valerate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Blood levels of IL-10 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Measured: 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)
Blood levels of IL-17 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Measured: 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)
Blood levels of TGF-ß1 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Measured: 1 day
Blood levels of IFγ (Interferon gamma) 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)
Measured: 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 PIBF on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Measured: 1 day
Blood levels of IL-4 (Interleukin 4) on the day before embryo transfer
Blood levels of IL-4 on the day before embryo transfer
Measured: 1 day
Blood levels of IL-10 (Interleukin 10) on the day before embryo transfer
Blood levels of IL-10 on the day before embryo transfer
Measured: 1 day
Blood levels of IL-17 (Interleukin 17) on the day before embryo transfer
Blood levels of IL-17 on the day before embryo transfer
Measured: 1 day
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
Measured: 1 day
Blood levels of IFγ (Interferon gamma) on the day before embryo transfer
Blood levels of IFγ on the day before embryo transfer
Measured: 1 day
Blood levels of PIBF (Progesterone induced blocking factor) on the day before embryo transfer
Blood levels of PIBF on the day before embryo transfer
Measured: 1 day
Blood levels of IL-4 (Interleukin 4) on the day of embryo transfer
Blood levels of IL-4 on the day of embryo transfer
Measured: 1 day
Blood levels of IL-10 (Interleukin 10) on the day of embryo transfer
Blood levels of IL-10 on the day of embryo transfer
Measured: 1 day
Blood levels of IL-17 (Interleukin 17) on the day of embryo transfer
Blood levels of IL-17 on the day of embryo transfer
Measured: 1 day
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
Measured: 1 day
Blood levels of IFγ (Interferon gamma) on the day of embryo transfer
Blood levels of IFγ on the day of embryo transfer
Measured: 1 day
Blood levels of PIBF (Progesterone induced blocking factor) on the day of embryo transfer
Blood levels of PIBF on the day of embryo transfer
Measured: 1 day
Blood levels of IL-4 (Interleukin 4) three days after embryo transfer
Blood levels of IL-4 three days after embryo transfer
Measured: 3 days
Blood levels of IL-10 (Interleukin 10) three days after embryo transfer
Blood levels of IL-10 three days after embryo transfer
Measured: 3 days
Blood levels of IL-17 (Interleukin 17) three days after embryo transfer
Blood levels of IL-17 three days after embryo transfer
Measured: 3 days
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) three days after embryo transfer
Blood levels of TGF-ß1 three days after embryo transfer
Measured: 3 days
Blood levels of IFγ (Interferon gamma) three days after embryo transfer
Blood levels of IFγ three days after embryo transfer
Measured: 3 days
Blood levels of PIBF (Progesterone induced blocking factor) three days after embryo transfer
Blood levels of PIBF three days after embryo transfer
Measured: 3 days
Blood levels of IL-4 (Interleukin 4) ten days after embryo transfer
Blood levels of IL-4 ten days after embryo transfer
Measured: 10 days
Blood levels of IL-10 (Interleukin 10) ten days after embryo transfer
Blood levels of IL-10 ten days after embryo transfer
Measured: 10 days
Blood levels of IL-17 (Interleukin 17) ten days after embryo transfer
Blood levels of IL-17 ten days after embryo transfer
Measured: 10 days
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) ten days after embryo transfer
Blood levels of TGF-ß1 ten days after embryo transfer
Measured: 10 days
Blood levels of IFγ (Interferon gamma) ten days after embryo transfer
Blood levels of IFγ ten days after embryo transfer
Measured: 10 days
Blood levels of PIBF (Progesterone induced blocking factor) ten days after embryo transfer
Blood levels of PIBF ten days after embryo transfer
Measured: 10 days
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
Measured: 5 weeks
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
Measured: 5 weeks
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
Measured: 5 weeks
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
Measured: 5 weeks
Blood levels of IFγ (Interferon gamma) in case of pregnancy at 5 weeks +/- 3 days
Blood levels of IFγ in case of pregnancy at 5 weeks +/- 3 days
Measured: 5 weeks
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
Measured: 5 weeks
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)
Measured: 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 progesterone on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Measured: 1 day
Blood levels of estradiol on the day before embryo transfer
Blood levels of estradiol on the day before embryo transfer
Measured: 1 day
Blood levels of progesterone on the day before embryo transfer
Blood levels of progesterone on the day before embryo transfer
Measured: 1 day
Blood levels of estradiol on the day of embryo transfer
Blood levels of estradiol on the day of embryo transfer
Measured: 1 day
Blood levels of progesterone on the day of embryo transfer
Blood levels of progesterone on the day of embryo transfer
Measured: 1 day
Blood levels of estradiol three days after embryo transfer
Blood levels of estradiol three days after embryo transfer
Measured: 3 days
Blood levels of progesterone three days after embryo transfer
Blood levels of progesterone three days after embryo transfer
Measured: 3 days
Blood levels of estradiol ten days after embryo transfer
Blood levels of estradiol ten days after embryo transfer
Measured: 10 days
Blood levels of progesterone ten days after embryo transfer
Blood levels of progesterone ten days after embryo transfer
Measured: 10 days
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
Measured: 5 weeks
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
Measured: 5 weeks
Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) three days after embryo transfer
Blood levels of ß-hCG three days after embryo transfer
Measured: 3 days
Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) ten days after embryo transfer
Blood levels of ß-hCG ten days after embryo transfer
Measured: 10 days
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
Measured: 5 weeks
Secondary outcomes (3)
Pregnancy rate
Number of patients with a ß-hCG > 5 IU out of the number of patients who underwent an embryo transfer.
Measured: 10 days
Clinical pregnancy rate
Number of patients with an ultrasonographic visible sac out of the number of patients who underwent an embryo transfer
Measured: 5 weeks and 3 days
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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2022
- Study start24 Apr 2023
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (33)Papers the sponsor has linked to this study.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ART Fertility Clinics LLC
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Laura Marqueta Marques, ART Fertility Clinics LLC
- Investigators
- LAURA MARQUETA MARQUES, Consultant, Principal investigator, ART Fertility Clinics LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05473273
- Sponsor's protocol ID
- 2206-ABU-004-LMM
- Status last verified
- Jan 2026
- First submitted
- 22 Jul 2022
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 34512661DeJong CS, Maurice NJ, McCartney SA, Prlic M. Human Tissue-Resident Memory T Cells in the Maternal-Fetal Interface. Lost Soldiers or Special Forces? Cells. 2020 Dec 16;9(12):2699. doi: 10.3390/cells9122699.
PubMed 33339211Diaz-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.
PubMed 33528013Lucas ES, Vrljicak P, Muter J, Diniz-da-Costa MM, Brighton PJ, Kong CS, Lipecki J, Fishwick KJ, Odendaal J, Ewington LJ, Quenby S, Ott S, Brosens JJ. Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Commun Biol. 2020 Jan 21;3(1):37. doi: 10.1038/s42003-020-0763-1.
PubMed 31965050Lash GE, Robson SC, Bulmer JN. Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta. 2010 Mar;31 Suppl:S87-92. doi: 10.1016/j.placenta.2009.12.022. Epub 2010 Jan 12.
PubMed 20061017Liu 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.
PubMed 34054831Robertson SA, Moldenhauer LM. Immunological determinants of implantation success. Int J Dev Biol. 2014;58(2-4):205-17. doi: 10.1387/ijdb.140096sr.
PubMed 25023687Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol. 2017 Aug;17(8):469-482. doi: 10.1038/nri.2017.64. Epub 2017 Jun 19.
PubMed 28627518Piccinni MP, Raghupathy R, Saito S, Szekeres-Bartho J. Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction. Front Immunol. 2021 Jul 28;12:717808. doi: 10.3389/fimmu.2021.717808. eCollection 2021.
PubMed 34394125AbdulHussain G, Azizieh F, Makhseed M, Raghupathy R. Effects of Progesterone, Dydrogesterone and Estrogen on the Production of Th1/Th2/Th17 Cytokines by Lymphocytes from Women with Recurrent Spontaneous Miscarriage. J Reprod Immunol. 2020 Aug;140:103132. doi: 10.1016/j.jri.2020.103132. Epub 2020 Apr 17.
PubMed 32380371Salem ML. Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):97-104. doi: 10.2174/1568010043483944.
PubMed 15032646Szekeres-Bartho J. The Role of Progesterone in Feto-Maternal Immunological Cross Talk. Med Princ Pract. 2018;27(4):301-307. doi: 10.1159/000491576. Epub 2018 Jun 27.
PubMed 29949797Wang W, Sung N, Gilman-Sachs A, Kwak-Kim J. T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells. Front Immunol. 2020 Aug 18;11:2025. doi: 10.3389/fimmu.2020.02025. eCollection 2020.
PubMed 32973809Raghupathy R, Szekeres-Bartho J. Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy. Int J Mol Sci. 2022 Jan 25;23(3):1333. doi: 10.3390/ijms23031333.
PubMed 35163255Zhao Y, Zhang T, Guo X, Wong CK, Chen X, Chan YL, Wang CC, Laird S, Li TC. Successful implantation is associated with a transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy. Fertil Steril. 2021 Apr;115(4):1044-1053. doi: 10.1016/j.fertnstert.2020.10.031. Epub 2020 Nov 30.
PubMed 33272613
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle (NC).
- ClinicalTrials.gov ID
- NCT05473273
- Acronym / sponsor ID
- 2206-ABU-004-LMM
- Conditions
- Infertility, Female
- Keywords
- infertilty, ivf, progesterone, estradiol, cytokines, immunology, Pharmacological effect of drugs, hormones
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- ART Fertility Clinics LLCUniversity, hospital or other
- Study start
- 24 Apr 2023 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 25 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Natural Cycle Protocol | – | –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 | – | Drug: Endometrin 100Mg Vaginal Insert, Drug: Estradiol ValerateUltrasound 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Infertile women undergoing a single frozen embryo transfer
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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 %
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endometrin 100Mg Vaginal InsertEndometrin 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 | Hormone Replacement Therapy Protocol |
| Estradiol ValerateEstradiol 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). | Drug | Hormone Replacement Therapy Protocol |
Primary outcome
Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Time frame: 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 (Interleukin 10) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Time frame: 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 (Interleukin 17) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Time frame: 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 (Transforming Growth Factor beta1) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Time frame: 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 (Interferon gamma) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Time frame: 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)
Time frame: 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 (Interleukin 4) on the day before embryo transfer
Time frame: 1 day
Blood levels of IL-4 on the day before embryo transfer
Blood levels of IL-10 (Interleukin 10) on the day before embryo transfer
Time frame: 1 day
Blood levels of IL-10 on the day before embryo transfer
Blood levels of IL-17 (Interleukin 17) on the day before embryo transfer
Time frame: 1 day
Blood levels of IL-17 on the day before embryo transfer
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day before embryo transfer
Time frame: 1 day
Blood levels of TGF-ß1 on the day before embryo transfer
Blood levels of IFγ (Interferon gamma) on the day before embryo transfer
Time frame: 1 day
Blood levels of IFγ on the day before embryo transfer
Blood levels of PIBF (Progesterone induced blocking factor) on the day before embryo transfer
Time frame: 1 day
Blood levels of PIBF on the day before embryo transfer
Blood levels of IL-4 (Interleukin 4) on the day of embryo transfer
Time frame: 1 day
Blood levels of IL-4 on the day of embryo transfer
Blood levels of IL-10 (Interleukin 10) on the day of embryo transfer
Time frame: 1 day
Blood levels of IL-10 on the day of embryo transfer
Blood levels of IL-17 (Interleukin 17) on the day of embryo transfer
Time frame: 1 day
Blood levels of IL-17 on the day of embryo transfer
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day of embryo transfer
Time frame: 1 day
Blood levels of TGF-ß1 on the day of embryo transfer
Blood levels of IFγ (Interferon gamma) on the day of embryo transfer
Time frame: 1 day
Blood levels of IFγ on the day of embryo transfer
Blood levels of PIBF (Progesterone induced blocking factor) on the day of embryo transfer
Time frame: 1 day
Blood levels of PIBF on the day of embryo transfer
Blood levels of IL-4 (Interleukin 4) three days after embryo transfer
Time frame: 3 days
Blood levels of IL-4 three days after embryo transfer
Blood levels of IL-10 (Interleukin 10) three days after embryo transfer
Time frame: 3 days
Blood levels of IL-10 three days after embryo transfer
Blood levels of IL-17 (Interleukin 17) three days after embryo transfer
Time frame: 3 days
Blood levels of IL-17 three days after embryo transfer
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) three days after embryo transfer
Time frame: 3 days
Blood levels of TGF-ß1 three days after embryo transfer
Blood levels of IFγ (Interferon gamma) three days after embryo transfer
Time frame: 3 days
Blood levels of IFγ three days after embryo transfer
Blood levels of PIBF (Progesterone induced blocking factor) three days after embryo transfer
Time frame: 3 days
Blood levels of PIBF three days after embryo transfer
Blood levels of IL-4 (Interleukin 4) ten days after embryo transfer
Time frame: 10 days
Blood levels of IL-4 ten days after embryo transfer
Blood levels of IL-10 (Interleukin 10) ten days after embryo transfer
Time frame: 10 days
Blood levels of IL-10 ten days after embryo transfer
Blood levels of IL-17 (Interleukin 17) ten days after embryo transfer
Time frame: 10 days
Blood levels of IL-17 ten days after embryo transfer
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) ten days after embryo transfer
Time frame: 10 days
Blood levels of TGF-ß1 ten days after embryo transfer
Blood levels of IFγ (Interferon gamma) ten days after embryo transfer
Time frame: 10 days
Blood levels of IFγ ten days after embryo transfer
Blood levels of PIBF (Progesterone induced blocking factor) ten days after embryo transfer
Time frame: 10 days
Blood levels of PIBF ten days after embryo transfer
Blood levels of IL-4 (Interleukin 4) in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of IL-4 in case of pregnancy at 5 weeks +/- 3 days
Blood levels of IL-10 (Interleukin 10) in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of IL-10 in case of pregnancy at 5 weeks +/- 3 days
Blood levels of IL-17 (Interleukin 17) in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of IL-17 in case of pregnancy at 5 weeks +/- 3 days
Blood levels of TGF-ß1 (Transforming Growth Factor beta1) in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of TGF-ß1 in case of pregnancy at 5 weeks +/- 3 days
Blood levels of IFγ (Interferon gamma) in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of IFγ in case of pregnancy at 5 weeks +/- 3 days
Blood levels of PIBF (Progesterone induced blocking factor) in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of PIBF in case of pregnancy at 5 weeks +/- 3 days
Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)
Time frame: 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)
Time frame: 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
Time frame: 1 day
Blood levels of estradiol on the day before embryo transfer
Blood levels of progesterone on the day before embryo transfer
Time frame: 1 day
Blood levels of progesterone on the day before embryo transfer
Blood levels of estradiol on the day of embryo transfer
Time frame: 1 day
Blood levels of estradiol on the day of embryo transfer
Blood levels of progesterone on the day of embryo transfer
Time frame: 1 day
Blood levels of progesterone on the day of embryo transfer
Blood levels of estradiol three days after embryo transfer
Time frame: 3 days
Blood levels of estradiol three days after embryo transfer
Blood levels of progesterone three days after embryo transfer
Time frame: 3 days
Blood levels of progesterone three days after embryo transfer
Blood levels of estradiol ten days after embryo transfer
Time frame: 10 days
Blood levels of estradiol ten days after embryo transfer
Blood levels of progesterone ten days after embryo transfer
Time frame: 10 days
Blood levels of progesterone ten days after embryo transfer
Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days
Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days
Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) three days after embryo transfer
Time frame: 3 days
Blood levels of ß-hCG three days after embryo transfer
Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) ten days after embryo transfer
Time frame: 10 days
Blood levels of ß-hCG ten days after embryo transfer
Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) in case of pregnancy at 5 weeks +/- 3 days
Time frame: 5 weeks
Blood levels of ß-hCG in case of pregnancy at 5 weeks +/- 3 days
3 secondary outcomes
Pregnancy rate
Time frame: 10 days
Clinical pregnancy rate
Time frame: 5 weeks and 3 days
Miscarriage rate
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Background: PubMed 34512661Zhang 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.
- Background: PubMed 33339211DeJong CS, Maurice NJ, McCartney SA, Prlic M. Human Tissue-Resident Memory T Cells in the Maternal-Fetal Interface. Lost Soldiers or Special Forces? Cells. 2020 Dec 16;9(12):2699. doi: 10.3390/cells9122699.
- Background: PubMed 33528013Diaz-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.
- Background: PubMed 31965050Lucas ES, Vrljicak P, Muter J, Diniz-da-Costa MM, Brighton PJ, Kong CS, Lipecki J, Fishwick KJ, Odendaal J, Ewington LJ, Quenby S, Ott S, Brosens JJ. Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Commun Biol. 2020 Jan 21;3(1):37. doi: 10.1038/s42003-020-0763-1.
- Background: PubMed 20061017Lash GE, Robson SC, Bulmer JN. Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta. 2010 Mar;31 Suppl:S87-92. doi: 10.1016/j.placenta.2009.12.022. Epub 2010 Jan 12.
- Background: PubMed 34054831Liu 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.
- Background: PubMed 25023687Robertson SA, Moldenhauer LM. Immunological determinants of implantation success. Int J Dev Biol. 2014;58(2-4):205-17. doi: 10.1387/ijdb.140096sr.
- Background: PubMed 28627518Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol. 2017 Aug;17(8):469-482. doi: 10.1038/nri.2017.64. Epub 2017 Jun 19.
- Background: PubMed 34394125Piccinni MP, Raghupathy R, Saito S, Szekeres-Bartho J. Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction. Front Immunol. 2021 Jul 28;12:717808. doi: 10.3389/fimmu.2021.717808. eCollection 2021.
- Background: PubMed 32380371AbdulHussain G, Azizieh F, Makhseed M, Raghupathy R. Effects of Progesterone, Dydrogesterone and Estrogen on the Production of Th1/Th2/Th17 Cytokines by Lymphocytes from Women with Recurrent Spontaneous Miscarriage. J Reprod Immunol. 2020 Aug;140:103132. doi: 10.1016/j.jri.2020.103132. Epub 2020 Apr 17.
- Background: PubMed 15032646Salem ML. Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):97-104. doi: 10.2174/1568010043483944.
- Background: PubMed 29949797Szekeres-Bartho J. The Role of Progesterone in Feto-Maternal Immunological Cross Talk. Med Princ Pract. 2018;27(4):301-307. doi: 10.1159/000491576. Epub 2018 Jun 27.
- Individual participant dataSharing planned: Undecided
Related trials for Infertility, Female
Recruiting
Endometriosis Transcriptomic Cell Atlas
Endometriosis, Infertility
RecruitingPhase 1
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Anovulatory Infertility
RecruitingPhase 2
A Study to Investigate Mibavademab in Adult Women With Functional Hypothalamic Amenorrhea
Functional Hypothalamic Amenorrhea, FHA
Not yet recruitingPhase 2
PRECISION-E2: Teverelix in Women With Endometriosis - Pharmacodynamics, Safety and Precision Medicine Correlates
Endometriosis Pelvic, Endometriosis Ovaries
Recruiting
Clinical Impact of Uterine Repair During Cesarean Section With Barbed Suture on the Incidence of Isthmocele
Isthmocele, Cesarean Scar Defect
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
LAURA MARQUETA MARQUES, Consultant principal investigator
ART Fertility Clinics LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infertility, Female, run by ART Fertility Clinics LLC at 1 site in United Arab Emirates.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Arab Emirates. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact BARBARA LAWRENZ, PhD (97126528000 ext. 1108, barbara.lawrenz@artfertilityclinics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT) (time frame: 1 day). The study lists 51 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05473273, which also lists 33 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.