Evaluation of Different Luteal Phase Support Methods in Patients With Poor Ovarian Response

Comparison of Different Methods for Luteal Phase Support in IVF / ICSI Cycles With Antagonist Protocol in Women With Poor Ovarian Response

This study is a randomized clinical trial to investigate the efficacy of different luteal phase support methods in patients with poor ovarian response undergoing IVF and intracytoplasmic sperm injection (ICSI) cycles.

The study protocol is approved by the Ethics Committee (Institutional Review Board) of Royan institute. The study is conducted according to the Declaration of Helsinki for medical research. All participants provide informed consent after counseling for infertility treatments and routine IVF/ICSI programs.

Study Overview

• Status: Unknown
• Conditions: Infertility
• Intervention / Treatment: Drug: Choriomon® injection; Drug: Choriomon® injection+Endometrin ®; Drug: Endometrin ® vaginal tablets

Detailed Description

All the patients who diagnose as poor ovarian responders (POR) based on the Bologna criteria are eligible for participation in this study. In order to define the poor response in IVF, at least two of the following three features must be present: (i) advanced maternal age or any other risk factor for POR; (ii) a previous POR; and (iii) an abnormal ovarian reserve test (ORT). 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 ORT.

The ovarian stimulation is performed with antagonist protocol with E2 priming for all eligible patients. All women receive estrogen priming (E2 tablet) starting a week after LH surge until menses. Controlled ovarian stimulation is started on day 2 of menstrual cycle with 225 IU recombinant FSH (Gonal-F®; Serono Laboratories Ltd., Geneva, Switzerland) and 75 IU hMG (Menopur®; Ferring). The doses of gonadotropins were adjusted as ovarian response in the ultrasound monitoring. Gonadotropin releasing hormone (GnRH) antagonist (Cetrorelix acetate 0.25 mg; Cetrotide ®, USAN) is administrated to prevent premature ovulation when the lead follicle measured ≥ 12 mm and was continued until the hCG trigger. Final oocyte triggering will be done with 10000 IU of hCG (Choriomon®; IBSA). If there were or more dominant follicles, oocytes retrieval will be done under transvaginal ultrasound guidance 32-34 hours after hCG administration. Intracytoplasmic sperm injection will be performed for all metaphase II oocytes. Embryo transfer will be done under ultrasound guidance on day 3 for all patients.

On the day of oocyte pickup, patients are allocated randomly (by the blocked randomization method) into three groups to receive three different luteal support protocols and they remained on the same allocation throughout the study. Group 1, subjects receive 1,500 IU of hCG IM on the embryos transfer (ET) day, as well as 4 days after the embryos transfer. Group 2: patients will receive 1,500 IU of hCG IM on the ET day, as well as 3 and 6 days after the transfer along with Endometrin ® vaginal tablets (Ferring Pharmaceuticals Ltd., Germany) 100 mg twice daily. Group 3, patients will receive only Endometrin ® vaginal tablets (Ferring Pharmaceuticals Ltd., Germany) 100 mg twice daily for luteal support from the day of oocyte pickup to the day of the pregnancy test. The vaginal progesterone is continued in all patients who become pregnant in all three groups until the 12th week of pregnancy. The serum ß-hCG level is checked 2 weeks after ET to confirm positive pregnancy test. Clinical pregnancies are detected with the confirmation of positive fetal heart activities by transvaginal sonography. The implantation rate is considered as the proportion of number of observed intrauterine gestational sac to number of transferred embryos. Multiple pregnancies are defined as two or more gestational sacs in the uterine cavity. Miscarriage is defined as a loss of a clinical pregnancy before the 12th week of gestation.

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Recruiting
    • Royan Institute
    • Contact: Nasser Aghdami, MD,PhD; Phone Number: 516 (+98)2123562000; Email: nasser.aghdami@royaninstitute.org
    • Contact: Leila Arab, MD; Phone Number: 414 (+98)2123562000; Email: Leara91@gmail.com
    • Sub-Investigator: Shabnam Khodabakhshi, B.S.c
    • Sub-Investigator: Zahra Zolfaghary, M.S.c

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 52 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Diagnosis of poor ovarian response (POR), according to Bologna criteria:

the patients have at least two of the following criteria:

• age over 40 years;
• a history of ovarian surgery;
• previous treatment using conventional protocols that yielded less than three oocytes;
• antral follicle count of less than 5 on menstrual cycle day 2-3; and basal serum FSH concentration between 10 and 19 IU/l or serum anti-Müllerian hormone level less than 1 ng/ml.

Exclusion Criteria:

1- Female age over 45 years old 2- Ovarian failure including basal FSH above 20 IU/l or no antral follicle by ultrasound examination 3- Severe male factor (Azoospermia) 4- Endometriosis diagnosis and the presence of hydrosalpinges 5- Uterine factor (polyps, myoma and previous myomectomy, …) 6- Patients with cardiovascular disease and/or uncontrolled systemic or endocrine diseases 7- Patients with repeated implantation failures and repeated miscarriages. 8- Female smokers

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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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Choriomon®; subjects receive 1,500 IU of hCG (Choriomon®; IBSA) intramuscular (IM) on the embryos transfer (ET) day, as well as 4 days after the embryos transfer for luteal support	Drug: Choriomon® injection; Intramuscular injection of 1,500 IU of hCG (Choriomon®; IBSA) on the embryos transfer (ET) day, as well as 4 days after the embryos transfer for luteal support
Experimental: Choriomon®+Endometrin ®; patients will receive 1,500 IU of hCG (Choriomon®; IBSA) (IM) on the ET day, as well as 3 and 6 days after the transfer along with Endometrin ® vaginal tablets (Ferring Pharmaceuticals Ltd., Germany) 100 mg twice daily for luteal support from the day of oocyte pickup to the day of the pregnancy test.	Drug: Choriomon® injection+Endometrin ®; Intramuscular injection of 1,500 IU of hCG (Choriomon®; IBSA) on the ET day, as well as 3 and 6 days after the transfer along with Endometrin ® vaginal tablets (Ferring Pharmaceuticals Ltd., Germany) 100 mg twice daily for luteal support from the day of oocyte pickup to the day of the pregnancy test.
Experimental: Endometrin ®; patients will receive only Endometrin ® vaginal tablets (Ferring Pharmaceuticals Ltd., Germany) 100 mg twice daily for luteal support from the day of oocyte pickup to the day of the pregnancy test.	Drug: Endometrin ® vaginal tablets; Endometrin ® vaginal tablets (Ferring Pharmaceuticals Ltd., Germany) 100 mg twice daily for luteal support from the day of oocyte pickup to the day of the pregnancy test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	Evaluation the clinical pregnancy rate at least 4 weeks after embryo transfer.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	Evaluation the implantation rate at least 4 weeks after embryo transfer	4 weeks
chemical pregnancy rates	Evaluation of chemical pregnancy rates 2 weeks after embryo transfer	2 weeks
miscarriage rate	Evaluation of miscarriage rate 12 weeks after embryo transfer.	12 weeks

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Chair: Hamid Gourabi, p, Head of Royan Institute; Study Director: Tahere Madani, MD, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.; Principal Investigator: Fariba Ramezani, MD, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.; Principal Investigator: Arezoo Arabipour, M.S.c, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): November 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: June 13, 2016
• First Posted (Estimate): June 14, 2016

Study Record Updates

• Last Update Posted (Actual): December 27, 2018
• Last Update Submitted That Met QC Criteria: December 26, 2018
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: Royan-Emb-024