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

Fundación IVI

Status: Enrolling

Conditions: Endometrial Receptivity

Treatments: Procedure: Hormonal Replacement Therapy programmed artificial cycle; Procedure: Endometrial receptivity reference group; Procedure: Controlled Ovarian Stimulation + Luteal Phase Support; Procedure: Natural Cycle (NC)

Study type: Observational

Funder types: Other

Identifiers

NCT06280560

2109-FIVI-087-FD

PI23/00860 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

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.

Enrollment: 60 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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 design

60 participants in 4 patient groups

Natural Cycle (NC)

Description:

No hormonal stimulation

Treatment:

Procedure: Natural Cycle (NC)

Controlled Ovarian Stimulation (COS) + Luteal Phase Support (LPS)

Description:

Hormonal fresh transfer protocol

Treatment:

Procedure: Controlled Ovarian Stimulation + Luteal Phase Support

HRT programmed artificial cycle

Description:

Delayed hormonal transfer protocol

Treatment:

Procedure: Hormonal Replacement Therapy programmed artificial cycle

Endometrial receptivity reference group

Description:

No hormonal stimulation

Treatment:

Procedure: Endometrial receptivity reference group