Effectiveness of Estradiol Valerate Pretreatment in Antagonist Protocol for Poor Ovarian Response Patient

Reproductive & Genetic Hospital of CITIC-Xiangya

Status: Completed

Conditions: Infertility

Treatments: Drug: Ganirelix; Drug: Follitropin Beta;MSD; Drug: hCG; Drug: estradiol valerate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03300518

MSD-MISP-ZX-01

Details and patient eligibility

About

The purpose of study is to assess the efficacy of add-on estrogen pretreatment in GnRH antagonist protocol on oocyte retrieval as compared with GnRH antagonist protocol for patients with poor ovarian response Add-on estrogen pretreatment protocol is superior to none pretreatment GnRH antagonist protocol for the number of oocytes retrieval

Full description

Women of advanced maternal age seeking ART treatment are characterized as poor ovarian responders in the process of ovarian simulation. Poor response to ovarian stimulation causes high cycle cancellation rate and extremely low pregnancy rate.

More attention has been paid to the potential interest of steroid pretreatments in GnRH antagonist cycles; not only for scheduling the GnRH antagonist cycles, but also for synchronizing the follicular growth which may result in more oocytes retrieved. But available clinical results are controversial.

Previous studies have shown that utilizing the natural negative feedback of the hypothalamus-pituitary-ovary axis induced by estradiol valerate pretreatment effectively prevented inter-cycle increases in follicle-stimulating hormone, improved follicle synchronization, and resulted in a more coordinated follicular development, leading to the recovery of more mature oocytes. However none of the randomized controlled studies compared estradiol valerate pretreatment or not on treatment outcomes, ongoing pregnancy rate, directly on poor response patients using estradiol valerate pretreatment in GnRH antagonist protocol.

Enrollment: 552 patients

Sex: Female

Ages: 40 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:Bologna criteria

• At least two of the following three features must be present:

  1. Advanced maternal age (≥40 years) or any other risk factor for POR
  2. A previous POR (≤3 oocytes with a conventional stimulation protocol)
  3. An abnormal ovarian reserve test (i.e. antral follicle count < 5-7 follicles or AMH< 0.5 - 1.1 ng/mL)

Exclusion Criteria:

1. Age ≥45 years,
2. Patients who conducted PGD/PGS, and donor egg cycles were excluded.
3. Presence of unilateral ovary absence
4. Abnormal uterine deformity or structure.
5. Spontaneous abortion patients with three or more (including biochemical pregnancy abortion)
6. With other endocrine disease, ovulation disorders such as adrenal cortex function or thyroid dysfunction
7. Have assisted reproductive technology contraindications or pregnancy contraindication of patients

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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552 participants in 2 patient groups

pretreatment group

Other group

Description:

the pretreatment group underwent a modified treatment protocol with pretreatment with estogen administering during the cycle preceding the IVF/ICSI cycle. daily dose of 4 mg (2 mg twice a day) estradiol valerate was given orally in the middle luteal phase which is confirmed seven days after ovulation monitoring by the ultrasound up to 2 days of the next menstrual cycle.Recombinant FSH (Puregon) was initiated on menstrual cycle day 2- 3 at an initial dose of 300 IU/day.A daily administration of ganirelix (0.25 mg Orgalutran; Organon) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger.

Treatment:

Drug: estradiol valerate

Drug: hCG

Drug: Ganirelix

Drug: Follitropin Beta;MSD

control groups

Other group

Description:

In the control groups standard GnRH-antagonist protocol was applied.Recombinant FSH (Puregon) was initiated on menstrual cycle day 2- 3 at an initial dose of 300 IU/day.A daily administration of ganirelix (0.25 mg Orgalutran; Organon) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger.

Treatment:

Drug: hCG

Drug: Ganirelix

Drug: Follitropin Beta;MSD