Repeated Doses of GnRH Agonist as Oocyte Triggering in Antagonist Protocol for Patients With Polycystic Ovary Syndrome

NCT ID: NCT04600986

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-30
• Study Completion Date: 2022-09-30

Brief Summary

This is a prospective, randomized, proof-of-concept study, designed to compare the IVF results in patients diagnosed with polycystic ovarian syndrome (PCOS) defined as per the ESHRE/ASRM Rotterdam criteria (2003) undergoing in-vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) in antagonist protocol. Patients were randomized into two groups. Group A: single dose of GnRHa 0.2 mg, 35 h prior to oocyte retrieval, and Group B: 0.2 mg GnRHa 35 h prior to oocyte retrieval + a repeat dose of 0.1 mg 12 h following the 1st dose. 12 h post-trigger, luteinizing hormone (LH), progesterone (P4) values will be estimated.

Detailed Description

The aim of this study was to establish if a second dose of GnRHa repeated 12 h following the initial dose optimizes the cycle outcome in terms of oocyte maturity in women with PCOS of Asian origin.

The study was approved by the institutional review board and written, informed consent will be obtained from each participant. Infertile women with a diagnosis of PCOS, who undergo the IVF / ICSI cycle are assigned to two groups randomly. The random method is that the statistician will be provided a blocked randomization list for the number of patients,and whenever an eligible patient is referred, a sealed envelope will be delivered to the clinical physician. The random allocation is concealed from the physician performing the IVF/ICSI treatment cycle. All patients will receive antagonist controlled ovarian stimulation protocol with same starting dose of gonadotropin. On the day of trigger, serum E2, LH, and P4 concentrations will be measured. When three lead follicles achieved 17-mm diameter, in group A, the final oocyte maturation will be triggered with a single dose of 0.2 mg s.c triptorelin (decapeptyl), 35 h prior to oocyte retrieval in both the groups and in Group B, a repeat dose of 0.1 mg 12 h following the first dose. Post-trigger, LH, and progesterone levels will be measured 12 h following the first dose of GnRHa and ovum-pick up day. Transvaginal ultrasound-guided oocyte pickup (OPU) will be performed 35 h following the first dose under intravenous sedation with single-lumen oocyte retrieval needle. Post pickup on days 4 and 7, an assessment for symptoms and signs of OHSS and patients will be advised to present at any time within 2 weeks of GnRHa administration.

In all subjects, IVF or ICSI will be performed according to the standard operating procedure. The fertilization will be assessed 18 h following ICSI or IVF by the appearance of two pronuclei. All embryos will be cryopreserved by vitrification in the form of blastocyst. The frozen embryo transfer (FET) cycles will be performed following pretreatment with oral contraceptive pills in an artificial cycle with a daily dose of orally administered 6 mg of estradiol. When the endometrium evaluated by TVS was >8 mm with triple-layer morphology, it is considered mature. This will be followed by endometrial priming with 5 days of injectable progesterone for blastocysts. The transfer will be performed using Sure-Pro Ultra catheter. Luteal-phase supplementation will be continued with vaginal progesterone and estradiol for 14 days and when pregnancy will be achieved till 10 weeks of gestation..

The primary outcome will be the maturity rate of the oocytes (the ratio of MII oocytes to the total number of oocytes retrieved) and oocyte yield. The secondary outcomes are fertilization rate, number and quality of blastocyst embryos, OHSS occurrence, and post-trigger serum LH (IU/L), and P4 (ng/mL) levels. In addition, implantation and clinical pregnancy rates will be also evaluated. Data collection will be performed by using questionnaires to be filled as per the available records and laboratory results. Data analysis will be done through descriptive and perceptive statistical methods by using SPSS software version 20 for windows.

Conditions

Polycystic Ovary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

New oocyte triggering

The final oocyte maturation will be triggered with a single dose of 0.2 mg s.c triptorelin (decapeptyl) and in addition a repeat dose of 0.1 mg s.c triptorelin (decapeptyl) will prescribed 12 h following the first dose.

Group Type: EXPERIMENTAL

Repeated dose of GnRH agonist

Intervention Type: OTHER

0.2 mg triptorelin plus a repeat dose of 0.1 mg 12 hours following the first dose.

Routine oocyte trigering

The final oocyte maturation will be triggered with a single dose of 0.2 mg s.c triptorelin (decapeptyl), 35 h prior to oocyte retrieval.

Group Type: OTHER

Repeated dose of GnRH agonist

Intervention Type: OTHER

0.2 mg triptorelin plus a repeat dose of 0.1 mg 12 hours following the first dose.

Interventions

Repeated dose of GnRH agonist

0.2 mg triptorelin plus a repeat dose of 0.1 mg 12 hours following the first dose.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

All PCOS patients defined as per the ESHE/ASRM Rotterdam criteria undergoing ovarian stimulation for IVF/ICSI using GnRH antagonist protocol:

1. Anticipated high ovarian response (serum E2> 3000 on trigger day)

2. Body mass index (BMI) >18 and <35 kg/m2

3. Willingness to participate in the study

Exclusion Criteria

1. Severe male factor infertility

2. Patients with severe endometriosis

3. Donor cycles

4. Indication for preimplantation genetic diagnosis

5. Uterine abnormality or existing myoma greater than 5cm

6. couple's drug addiction

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Royan Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maryam Hafezi, MD.

Role: STUDY_DIRECTOR

Department of Endocrinology and Female Infertility, Royan Institute

Hoora Hashemi, MD.

Role: PRINCIPAL_INVESTIGATOR

Department of Endocrinology and Female Infertility, Royan Institute

Locations

Royan Institute

Tehran, , Iran

Countries

Iran

References

Hashemi SH, Hafezi M, Arabipoor A, Zareei M, Vesali S, Eftekhari-Yazdi P. Can We Harvest More Mature Oocytes by Repeating Gonadotropin-Releasing Hormone Agonist Doses in Polycystic Ovarian Syndrome Patients at Risk of OHSS in Antagonist Cycles? A Randomised Clinical Trial. Int J Fertil Steril. 2024 Jul 13;18(Suppl 1):48-54. doi: 10.22074/ijfs.2023.2008905.1513.

Reference Type: DERIVED

PMID: 39033370 (View on PubMed)

Other Identifiers

Female infertility (97000253)

Identifier Type: -

Identifier Source: org_study_id