Delayed Embryo Transfer in Poor Responders

Antagonist and Short Protocols in Invitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) Cycles With Delayed Embryo Transfer in Poor Ovarian Response

Poor ovarian response indicates inadequate ovarian response to ovarian stimulation. In the current study the investigators will attempt to compare antagonist and short protocols regarding oocyte as well as embryo quantity and quality. Frozen embryo transfer will be performed in order to abolish iatrogenic effect of stimulation drugs on implantation. Still implantation and pregnancy rates are considered secondary outcomes.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Procedure: IVF/ICSI

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 12311
    • IVF centre, Obstetrics and Gynaecology Department, Cairo University Hospitals (Kasr EL Aini)
  • Giza, Egypt, 12411
    • Nile IVF center
  • Giza, Egypt, 12411
    • Kamal Shaeer center of infertility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient selection is based on the ESHRE consensus group 2011 definition of poor ovarian response (POR) (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 (AFC) <5-7 follicles or Antimullerian hormone (AMH) <0.5-1.1 ng/ml).

Two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal Ovarian reserve test (ORT). By definition, the term POR refers to the ovarian response and, therefore, one stimulated cycle is considered essential for the diagnosis of POR. However, patients over 40 years of age with an abnormal ORT may be classified as poor responders since both advanced age and an abnormal ORT may indicate reduced ovarian reserve and act as a surrogate of ovarian stimulation cycle. In this case, the patients should be more properly defined as expected PORs.

Exclusion Criteria:

• Women with endometriosis, endocrinal problems, uterine abnormalities as well as male azospermia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Antagonist; Antagonist protocol (fixed) for IVF/ICSI, with starting dose of human menopausal gonadotrophins (HMG) from 300-450 IU from day 1 of the cycle, antagonist start from day 6 stimulation. Follow-up by ultrasound and serum estradiol will be done. Triggering of ovulation using human chorionic gonadotrophin (HCG) 10000 IU I.M. when at least 2-3 follicles reach 17mm in diameter. Cryopreservation of all embryos at will be done. Frozen embryo transfer in the following cycle will be attempted using estradiol valerate (6mg) for endometrial preparation after pituitary down regulation using long acting GnRH analogue . A maximum of 3 good quality embryos will be transferred.	Procedure: IVF/ICSI; controlled ovarian hyperstimulation with various protocols, follow up till stimulated follicles measure from 18-20 mm, then ovum pickup followed by embryo transfer is done.
Active Comparator: Short; Short protocol for IVF/ICSI, gonadotrophin releasing hormone analogue (GnRHa) starts from day 1 of the cycle, HMG starts in a dose from 300-450 IU from day 3, Follow-up by ultrasound and serum estradiol will be done. Triggering of ovulation using human chorionic gonadotrophin (HCG) 10000 IU I.M. when at least 2-3 follicles reach 17mm in diameter. Cryopreservation of all embryos at will be done. Frozen embryo transfer in the following cycle will be attempted using estradiol valerate (6mg) for endometrial preparation after pituitary down regulation using long acting GnRH analogue . A maximum of 3 good quality embryos will be transferred.	Procedure: IVF/ICSI; controlled ovarian hyperstimulation with various protocols, follow up till stimulated follicles measure from 18-20 mm, then ovum pickup followed by embryo transfer is done.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Metaphase II (MII) oocytes	Number of MII oocytes collected from each patient on the day of ovum pickup (OPU)	9-14 days from stimulation
Number of good embryos	the number of good quality embryos obtained from each patient	3-5 days after ovum pickup

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	Pregnancy ending with a live birth	9 months
Early miscarriage rate	Pregnancy loss in the first 12 weeks gestation	3 months
Ongoing pregnancy rate	Pregnancy ongoing beyond 12 weeks gestation	3 months
chemical pregnancy rate	positive serum Beta HCG 14 days after embryo transfer	14 days after embryo transfer
clinical pregnancy rate	the detection of intrauterine gestational sac with positive pulsations	5 weeks after embryo transfer
Implantation rate	the ratio between the number of embryos transferred and the number of sacs	5 weeks after embryo transfer

Collaborators and Investigators

• Sponsor: Cairo University
• Collaborators: Nile Ivf Center, Cairo, Egypt; Kamal Shaeer center of infertility
• Investigators: Study Director: Iman K Shaeer, MD, Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: April 28, 2015
• First Submitted That Met QC Criteria: April 30, 2015
• First Posted (Estimate): May 1, 2015

Study Record Updates

• Last Update Posted (Actual): May 15, 2018
• Last Update Submitted That Met QC Criteria: May 12, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: 32015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No