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Endometrial ReceptivityHormoSenoRecNCT06280560

Impact of IVF Hormonal Therapy on Endometrial Receptivity and Endometrial Senescent Cell Pathological Accumulation

An observational study of Endometrial Receptivity, run by Fundación IVI at 1 site in Spain.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Both controlled ovarian stimulation (COS) and frozen embryo transfer has become an integral part of in vitro fertilization (IVF) treatment. Fresh embryo transfer is usually performed by providing Luteal Phase Support (LPS) with progesterone after COS. Read more about this study

Who is it for?
Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
Endometrial Receptivity
What is being tested?
Hormonal Replacement Therapy programmed artificial cycle, Natural Cycle (NC) and Endometrial receptivity reference group
How many people
60 participants
Where
1 siteSpain
Study dates
1 Feb 2024to 30 Dec 2026
How long will I take part?
2 Months
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 45 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Study population: The study population will consist in 45 women undergoing IVF treatment for fertility problems and who, as indicated by their clinical practice, will be subjected to one of the following hormonal protocols (fifteen participants per group) (Natural Cycle, Controled Ovarian Stimulation + Luteal Phase Support, Hormone Replacement Therapy). Additionally, as an endometrial receptivity reference group, we will recruit a population of 15 women with proven fertility belonging to the oocyte donation program in an endometrial cycle without hormonal stimulation (natural cycle). The 60 participants will be recruited at the IVI-RMA Valencia clinic (Valencia).

Study group (subfertile IVF patients).

  • Inclusion Criteria: Women aged 18-45 years, BMI ≥ 18.5- 30.
  • Exclusion criteria: Women presenting any uterine disease that affects the endometrial cavity, or with a thin or irregular endometrium, altered karyotypes, thrombophilias, or uncorrected systemic or endocrine diseases will be excluded.

Endometrial receptivity reference group (oocyte donors).

  • Inclusion criteria: women aged between 18 and 35 years, BMI ≥ 18.5- 25.
  • Exclusion criteria: Any cases of DIU presence, hormonal contraceptives at least during the last three months, altered karyotypes, thrombophilias, or uncorrected systemic or endocrine diseases will be excluded.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Francisco Domínguez Hernández, PhD contact

+34963903305

francisco.dominguez@ivirma.com

Roberto González Martín, PhD contact

+34963903305

roberto.gonzalez@ivirma.com

Spain1 site, 1 recruiting

  • IVI-RMA Valencia Clinic

    Valencia, Valencia, 46015

    Laura Caracena, PhD, 651791000, Laura.Caracena@ivirma.com

    Recruiting

Other trials in Spain

About this study

Official title: Impact of Controlled Ovarian Stimulation and Luteal Phase Support on Endometrial Receptivity and Endometrial Senescent Cell Pathological Accumulation: Pilot Study

Both controlled ovarian stimulation (COS) and frozen embryo transfer has become an integral part of in vitro fertilization (IVF) treatment. Fresh embryo transfer is usually performed by providing Luteal Phase Support (LPS) with progesterone after COS. Frozen embryo transfer (FET) is usually performed in artificial cycles with hormone replacement treatment (HRT), in which exogenous progesterone is administered, although it can also be performed in a Natural Cycle (without hormone supplementation) (NC). There is evidence that the supraphysiologic levels of estradiol and progesterone during COS+LPS and HRT could lead to morphologic and biochemical endometrial modifications, altering endometrial receptivity and lowering implantation and pregnancy rates.

We hypothesize that the supraphysiologic hormone levels required for both COS+LPS, and HRT may be inducing alterations in endometrial composition and function, specifically the chronic accumulation of senescent cells; either due to an excessive hormonal induction, a lack of clearance due to a deficit of uNKs, or a combination of both, ultimately affecting both endometrial receptivity and decidualization, worsening IVF outcomes.

Read more

The in vitro clearance of endometrial senescent cells by selective induction of apoptosis has been found to enhance the decidualization capacity of the rest of Endometrial Stromal Cells (EnSC), which could represent in a future adjuvant strategy to reduce the potentially deleterious effects of supraphysiologic hormone levels and improve reproductive outcomes in IVF patients.

The results derived from this project would have a direct impact on clinical practice. First, the results would allow us to evaluate, based on experimental data, potential endometrial side effects of stimulation protocols commonly used in IVF treatments. In addition, in the case of finding a pathological accumulation of senescent cells affecting endometrial receptivity, we will be able to in vitro evaluate the effectiveness of adjuvant senolytic (drugs designed to specifically remove senescent cells) compounds to in vitro improve the expression of endometrial receptivity markers, as a first step to demonstrate the effectiveness of their use in improving the reproductive outcomes of IVF patients.

Being tested
Controlled Ovarian Stimulation + Luteal Phase Support, Hormonal Replacement Therapy programmed artificial cycle, Natural Cycle (NC), Endometrial receptivity reference group
Keywords
Controled Ovarian Stimulation, Luteal Phase Support, Endometrial Receptivity, Organoid, Senescence, Senolytic, Single Cell Sequencing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Controlled Ovarian Stimulation + Luteal Phase SupportProcedure or surgery

    Short COS protocol with GnRH antagonist followed by progesterone supplementation. Will be initiated after a negative vaginal ultrasonographic scans to define ovarian quiescence, on days 1 and 2 of the menstrual period. For ovarian stimulation, 150-225 UI /day of FSHrec (GONAL F) will be administered along or in combination with 75 UI/day of HMG (Menopur). From day 6 onwards, HMG/FSHrec will be administered on an individual basis according to the serum E2 levels and transvaginal ovarian ultrasound scans and GnRH antagonist (Orgalutran) 0.25 mg /day is introduced as soon as a follicle of 14 mms diameter has achieved. hCGrec (6500 IU, Ovitrelle) will be administered when 7 or 8 follicles with a maximum diameter of >17-18 mms will observed. 400 mg of micronized vaginal progesterone will be administered (200 mg twice a day vaginal route), during 5 days. An endometrial biopsy and a blood sample will be obtained 7 days after hCG administration (hCH+7)

  • Hormonal Replacement Therapy programmed artificial cycleProcedure or surgery

    6 mg of oestradiol orally administered starting the first day of the menstrual period, followed by an endometrial scan 10-days later, and when a 7 mms triple line endometrium has seen by vaginal ultrasound scan, 800 mg of micronized vaginal progesterone (400 mg twice a day vaginal route), during five days, will be added to the oestrogen therapy. An endometrial biopsy and a blood sample will be obtained on day 5 of progesterone administration (P+5)

  • Natural Cycle (NC)Procedure or surgery

    No hormonal stimulation. From day 6 of the menstrual period, follicular growth will be evaluated. As soon as a follicle reaches 17mm in diameter, ovulation test strips will be provided to assess LH levels in the first morning urine. The participant will report the positive and will be scheduled for sampling seven days later. An endometrial biopsy and a blood sample will be obtained 7 days after LH peak (LH+7)

  • Endometrial receptivity reference groupProcedure or surgery

    Recruited among women belonging to the oocyte donation program and will follow the procedures described above for the Natural Cycle group. No hormonal stimulation. From day 6 of the menstrual period, follicular growth will be evaluated. As soon as a follicle reaches 17mm in diameter, ovulation test strips will be provided to assess LH levels in the first morning urine. The participant will report the positive and will be scheduled for sampling seven days later. An endometrial biopsy and a blood sample will be obtained 7 days after LH peak (LH+7)

Study groups in NCT06280560
Study groupRoleWhat they receive
Natural Cycle (NC)No hormonal stimulation
Receives: Procedure: Natural Cycle (NC)
Controlled Ovarian Stimulation (COS) + Luteal Phase Support (LPS)Hormonal fresh transfer protocol
Receives: Procedure: Controlled Ovarian Stimulation + Luteal Phase Support
HRT programmed artificial cycleDelayed hormonal transfer protocol
Receives: Procedure: Hormonal Replacement Therapy programmed artificial cycle
Endometrial receptivity reference groupNo hormonal stimulation
Receives: Procedure: Endometrial receptivity reference group

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Endometrial receptivity

    To evaluate in vitro (on cells) endometrial receptivity markers such as prolactin, Prolactin, IGFBP1, FOXO1, HOXA-10, CLU, SCAS5, DIO, VEGF, TGFβ, CD34, CD31, CD44, MMPs, IL-15, IL-11, IL-6, LIF, Glycodelin, β-catenin, ALCAM, IGF-1R, c-KIT, SMAD3, etc

    Measured: through study completion, an average of 2 years

Secondary outcomes (1)

  1. Senescent Cell Pathological Accumulation

    To evaluate in vitro (on cells) the presence of senescence markers such as lipofuscin granules (SentraGor or Sudan Black B), NF-kB, p-16, p-21, p38, P-p38, p53, cGAS, STRING, γH2AX, carbonyl proteins, etc

    Measured: through study completion, an average of 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2024
  2. Study start1 Feb 2024
  3. Primary completion30 Dec 2026 (estimated)
  4. Study completion30 Dec 2026 (estimated)

Resources

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
Case-control
Time perspective
Prospective
Enrolment
60 participants (estimated)
Target duration
2 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT06280560
Sponsor's protocol ID
2109-FIVI-087-FD
Other IDs
PI23/00860
Acronym
HormoSenoRec
Status last verified
Sep 2026
First submitted
15 Feb 2024
Last updated
4 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Anonymized results from Single Cell Sequencing will be uploaded to public databases belonging to Gene Expression Omnibus-NCBI for free access by researchers.

Publications

  • Aplin JD, Stevens A. Use of 'omics for endometrial timing: the cycle moves on. Hum Reprod. 2022 Apr 1;37(4):644-650. doi: 10.1093/humrep/deac022.

    PubMed 35147196

  • Birch J, Gil J. Senescence and the SASP: many therapeutic avenues. Genes Dev. 2020 Dec 1;34(23-24):1565-1576. doi: 10.1101/gad.343129.120.

    PubMed 33262144

  • Boretto M, Cox B, Noben M, Hendriks N, Fassbender A, Roose H, Amant F, Timmerman D, Tomassetti C, Vanhie A, Meuleman C, Ferrante M, Vankelecom H. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development. 2017 May 15;144(10):1775-1786. doi: 10.1242/dev.148478. Epub 2017 Apr 25.

    PubMed 28442471

  • Boretto M, Maenhoudt N, Luo X, Hennes A, Boeckx B, Bui B, Heremans R, Perneel L, Kobayashi H, Van Zundert I, Brems H, Cox B, Ferrante M, Uji-I H, Koh KP, D'Hooghe T, Vanhie A, Vergote I, Meuleman C, Tomassetti C, Lambrechts D, Vriens J, Timmerman D, Vankelecom H. Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening. Nat Cell Biol. 2019 Aug;21(8):1041-1051. doi: 10.1038/s41556-019-0360-z. Epub 2019 Aug 1.

    PubMed 31371824

  • Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update. 2003 Nov-Dec;9(6):515-22. doi: 10.1093/humupd/dmg045.

    PubMed 14714588

  • Brighton PJ, Maruyama Y, Fishwick K, Vrljicak P, Tewary S, Fujihara R, Muter J, Lucas ES, Yamada T, Woods L, Lucciola R, Hou Lee Y, Takeda S, Ott S, Hemberger M, Quenby S, Brosens JJ. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. Elife. 2017 Dec 11;6:e31274. doi: 10.7554/eLife.31274.

    PubMed 29227245

  • Burton GJ, Jauniaux E, Charnock-Jones DS. Human early placental development: potential roles of the endometrial glands. Placenta. 2007 Apr;28 Suppl A:S64-9. doi: 10.1016/j.placenta.2007.01.007. Epub 2007 Mar 8.

    PubMed 17349689

  • Burton GJ, Redman CW, Roberts JM, Moffett A. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019 Jul 15;366:l2381. doi: 10.1136/bmj.l2381.

    PubMed 31307997

  • Check JH, Wilson C, Choe JK, Amui J, Brasile D. Evidence that high serum progesterone (P) levels on day of human chorionic gonadotropin (hCG) injection have no adverse effect on the embryo itself as determined by pregnancy outcome following embryo transfer using donated eggs. Clin Exp Obstet Gynecol. 2010;37(3):179-80.

    PubMed 21077517

  • Cindrova-Davies T, Fogarty NME, Jones CJP, Kingdom J, Burton GJ. Evidence of oxidative stress-induced senescence in mature, post-mature and pathological human placentas. Placenta. 2018 Aug;68:15-22. doi: 10.1016/j.placenta.2018.06.307. Epub 2018 Jun 19.

    PubMed 30055665

  • Clevers H. Modeling Development and Disease with Organoids. Cell. 2016 Jun 16;165(7):1586-1597. doi: 10.1016/j.cell.2016.05.082.

    PubMed 27315476

  • Cox LS, Redman C. The role of cellular senescence in ageing of the placenta. Placenta. 2017 Apr;52:139-145. doi: 10.1016/j.placenta.2017.01.116. Epub 2017 Jan 16.

    PubMed 28131318

  • Deane JA, Cousins FL, Gargett CE. Endometrial organoids: in vitro models for endometrial research and personalized medicine. Biol Reprod. 2017 Jan 1;97(6):781-783. doi: 10.1093/biolre/iox139. No abstract available.

    PubMed 29106468

  • Deryabin P, Griukova A, Nikolsky N, Borodkina A. The link between endometrial stromal cell senescence and decidualization in female fertility: the art of balance. Cell Mol Life Sci. 2020 Apr;77(7):1357-1370. doi: 10.1007/s00018-019-03374-0. Epub 2019 Nov 15.

    PubMed 31728580

  • Deryabin PI, Borodkina AV. Stromal cell senescence contributes to impaired endometrial decidualization and defective interaction with trophoblast cells. Hum Reprod. 2022 Jun 30;37(7):1505-1524. doi: 10.1093/humrep/deac112.

    PubMed 35604371

Questions about this trial

What is this clinical trial studying?

An observational study of Endometrial Receptivity, run by Fundación IVI at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 4 Sep 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 Spain. 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 Francisco Domínguez Hernández, PhD (+34963903305, francisco.dominguez@ivirma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Endometrial receptivity (time frame: through study completion, an average of 2 years). 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 NCT06280560, which also lists 61 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 4 Sep 2026.

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