Clinical trial NCT02798653: Evaluation of Different Luteal Phase Support Methods in Patients With Poor Ovarian Response
Official title: Comparison of Different Methods for Luteal Phase Support in IVF / ICSI Cycles With Antagonist Protocol in Women With Poor Ovarian Response
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Infertility
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
First posted: 2016-06-14
Enrollment: 210
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 52
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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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Primary outcomes:
measure: Clinical pregnancy rate
timeFrame: 4 weeks
Secondary outcomes:
measure: Implantation rate
timeFrame: 4 weeks
measure: chemical pregnancy rates
timeFrame: 2 weeks
measure: miscarriage rate
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
affiliation: Head of Royan Institute
name: Hamid Gourabi, p
role: STUDY_CHAIR
affiliation: Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
name: Tahere Madani, MD
role: STUDY_DIRECTOR
affiliation: Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
name: Fariba Ramezani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
name: Arezoo Arabipour, M.S.c
role: PRINCIPAL_INVESTIGATOR
References: