Delayed Embryo Transfer in Poor Responders

Study Overview
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Brief Summary
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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.

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

Conditions
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Infertility

Intervention / Treatment
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* Procedure: IVF/ICSI


Participation Criteria
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Eligibility Criteria
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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: Advanced maternal age (≥40 years) or any other risk factor for POR; A previous POR (≤3 oocytes with a conventional stimulation protocol); 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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antagonist<br>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<br>* 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.<br>|
| Active Comparator: Short<br>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<br>* 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.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Early miscarriage rate | Pregnancy loss in the first 12 weeks gestation | 3 months | 
| Ongoing pregnancy rate | Pregnancy ongoing beyond 12 weeks gestation | 3 months | 
| Live birth rate | Pregnancy ending with a live birth | 9 months |