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

NCT ID: NCT03300518

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 552 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-15
• Study Completion Date: 2021-08-18

Brief 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

Detailed 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.

Conditions

Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

pretreatment group

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.

Group Type: OTHER

Follitropin Beta;MSD

Intervention Type: DRUG

Patients will start stimulation with a daily s.c. injection of follitropin beta( 300IU Puregonon;MSD) menstrual cycle day 2 or 3.

Ganirelix

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

control groups

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.

Group Type: OTHER

Follitropin Beta;MSD

Intervention Type: DRUG

Patients will start stimulation with a daily s.c. injection of follitropin beta( 300IU Puregonon;MSD) menstrual cycle day 2 or 3.

Ganirelix

Intervention Type: DRUG

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

Intervention Type: DRUG

Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Puregon; Orgalutran; Ovidrel; progynova

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Reproductive & Genetic Hospital of CITIC-Xiangya

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fei Gong, Doctor

Role: STUDY_DIRECTOR

Reproductive & Genetic Hospital of CITIC-Xiangya

Locations

Reproductive & Genetic Hospital of Citic-Xiangya

Changsha, Hunan, China

Countries

China

References

Zhang S, Tang Y, Wang X, Zong Y, Li X, Cai S, Ma H, Guo H, Song J, Lin G, Lu G, Gong F. Estrogen valerate pretreatment with the antagonist protocol does not increase oocyte retrieval in patients with low ovarian response: a randomized controlled trial. Hum Reprod. 2022 Jun 30;37(7):1431-1439. doi: 10.1093/humrep/deac081.

Reference Type: DERIVED

PMID: 35460400 (View on PubMed)

Other Identifiers

MSD-MISP-ZX-01

Identifier Type: -

Identifier Source: org_study_id