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

Infertility Clinical Trial

Official title:

A Randomized Study to Analysis the Effectiveness of Estradiol Valerate Pretreatment in Antagonist Protocol for Poor Ovarian Response Patient

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03300518
• Other study ID #: MSD-MISP-ZX-01
• Status: Completed
• Phase: N/A
• Start date: November 15, 2017
• Est. completion date: August 18, 2021

Study information

• Verified date: January 2022
• Source: Reproductive & Genetic Hospital of CITIC-Xiangya
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 552
• Est. completion date: August 18, 2021
• Est. primary completion date: June 18, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Follitropin Beta;MSD
Patients will start stimulation with a daily s.c. injection of follitropin beta( 300IU Puregonon;MSD) menstrual cycle day 2 or 3.
• Ganirelix
A daily administration of ganirelix (0.25 mg Orgalutran; MSD) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.
• hCG
Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger
• estradiol valerate
Estradiol valerate (progynova,Schering) daily dose of 4 mg (2 mg twice a day) was given orally, started 7 days before the presumed onset of menses and administered up to 2 days of the next menstrual cycle

Locations

Country	Name	City	State
China	Reproductive & Genetic Hospital of Citic-Xiangya	Changsha	Hunan

Sponsors (2)

Lead Sponsor	Collaborator
Reproductive & Genetic Hospital of CITIC-Xiangya	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of oocytes retrieved by the IVG 36 hours after hCG administration	The total MII oocytes retrievedd	36 hours after hCG administration
Secondary	Clinical pregnancy rate	clinical pregnancy, defined as intrauterine pregnancy with a positive heartbeat at 6 weeks of gestation.Clinical pregnancy rate:Number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles, or embryo transfer cycles. When clinical pregnancy rates are given, the denominator must be specified.	6weeks
Secondary	ongoing pregnancy rate	ongoing pregnancy defined as an intact pregnancy at 12 weeks of gestation	12weeks
Secondary	Optimal number of embryo	According to the embryonic developmental rate and morphology, the high quality embryos were defined as the next day (D2) transplanted embryos reached 3 or 4 cells and the third day (D3) transplanted embryos reached 6 to 8 cells with morphological grade 1 or 2	1 week