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Follicular Synchronization in PCOS Patients Undergoing ICSI

Primary Purpose

Polycystic Ovarian Syndrome

Status
Completed
Phase
Phase 4
Locations
Egypt
Study Type
Interventional
Intervention
letrozole 2.5mg (Femara; Novartis Pharma Services, Basel, Switzerland)
Sponsored by
Mansoura University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovarian Syndrome

Eligibility Criteria

20 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • 1. Ages ≥20 and <40 years old 2. Women having the diagnosis of polycystic ovarian syndrome according to Rotterdam criteria (15) 3. Women who have at least one of the following indications for IVF or ICSI:

    1. Resistance to slandered ovulation induction and life style modification
    2. Tubal factors: unilateral or bilateral tubal obstruction, unilateral or bilateral salpingectomy or tubal ligation
    3. Male factors: oligoasthenozoospermia or obstructive azoospermia

Exclusion Criteria:

  • 1. Women with unexplained infertility. 2. women with poor ovarian reserve according to Bologna criteria (16). 3. Couples with known chromosomal abnormalities. 4. Women who refuse to participate in this study.

Sites / Locations

  • Faculty of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

• Study group

• Control group

Arm Description

It contains 100 patients will undergo ovarian stimulation with letrozole 2.5mg twice daily (Femara; Novartis Pharma Services, Basel, Switzerland) for 5 days starting from the first day of menstruation in combination with low dose step up stimulation with recombinant FSH starting in the third day of menstruation.

It contains 100 patients will undergo ovarian stimulation with low dose step up stimulation with recombinant FSH starting in the third day of menstruation

Outcomes

Primary Outcome Measures

the number of asynchronized follicles in both groups
• Asynchronization will considered when there is a difference of at least 2 mm between the dominant follicle and other follicles

Secondary Outcome Measures

Full Information

First Posted
August 23, 2019
Last Updated
April 5, 2022
Sponsor
Mansoura University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04069117
Brief Title
Follicular Synchronization in PCOS Patients Undergoing ICSI
Official Title
Follicular Synchronization in Polycystic Ovarian Syndrome Patients Undergoing Intracytoplasmatic Sperm Injection With Letrozole /Antagonist Protocol: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
February 20, 2022 (Actual)
Study Completion Date
February 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mansoura University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

Brief Summary
The use of GnRH antagonist protocol nowadays is the slandered protocol of controlled ovarian stimulation in patients with poly cystic ovarian syndrome (PCOS) because it decreases the incidence of OHSS(1, 2). However, this protocol may lead to asynchronous growth of follicles with an early dominant follicle specially in PCOS patients(3). In most of cases this phenomenon will affect the IVF outcomes(2, 4) Aromatase inhibitors (AIs) nowadays is recommended to be used for ovulation induction in patients with PCOS (5, 6).It has fewer side effects, and a shorter half-life than clomiphene citrate(CC), and no effect ON the endometrial receptivity. It is used in treating patients with chronic anovulation, unexplained infertility and poor ovarian reserve(7). It acts through decreasing estrogen levels and allows follicle stimulating hormone (FSH) release from the hypothalamus (8, 9). It could be used alone or with combination with human menopausal gonadotropin (HMG) specially in patients with CC resistant(10-13). It also improves the ovarian response to FSH when they are used in combination and it decreases the risk of OHSS (14). This study aims to evaluate the effect of uses of letrozole in combination with HMG during ovarian stimulation in patients having PCOS undergoing IVF/ICSI on the follicular growth pattern, synchronized growth of follicles, maturity of oocyte and the quality of embryos.
Detailed Description
Participants in this study will be group of subfertile women undergoing IVF/ ICSI trial and having polycystic ovarian syndrome Inclusion criteria Ages ≥20 and <40 years old Women having the diagnosis of polycystic ovarian syndrome according to Rotterdam criteria (15) Women who have at least one of the following indications for IVF or ICSI: Resistance to slandered ovulation induction and life style modification Tubal factors: unilateral or bilateral tubal obstruction, unilateral or bilateral salpingectomy or tubal ligation Male factors: oligoasthenozoospermia or obstructive azoospermia Exclusion criteria 1. Women with unexplained infertility. 2. women with poor ovarian reserve according to Bologna criteria (16). 3. Couples with known chromosomal abnormalities. 4. Women who refuse to participate in this study. Methods patients will be randomly assigned into two groups (100 patients in each group): letrozole group (study group) and non letrozole group (control group). Treatment assignment will be blinded to patients, physicians, and nursing staff. All patients will receive combined oral pills before stimulation. letrozole 2.5mg twice daily (Femara; Novartis Pharma Services, Basel, Switzerland) will be given for 5 days starting from the second day of menstruation in combination with low dose step up stimulation with recombinant FSH in the study group. Allocated patients will be randomized into either of two groups.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovarian Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
randomized controlled trial
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
double blinded clinical trial
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
• Study group
Arm Type
Active Comparator
Arm Description
It contains 100 patients will undergo ovarian stimulation with letrozole 2.5mg twice daily (Femara; Novartis Pharma Services, Basel, Switzerland) for 5 days starting from the first day of menstruation in combination with low dose step up stimulation with recombinant FSH starting in the third day of menstruation.
Arm Title
• Control group
Arm Type
No Intervention
Arm Description
It contains 100 patients will undergo ovarian stimulation with low dose step up stimulation with recombinant FSH starting in the third day of menstruation
Intervention Type
Drug
Intervention Name(s)
letrozole 2.5mg (Femara; Novartis Pharma Services, Basel, Switzerland)
Other Intervention Name(s)
letroz 2.5mg (Sun Pharmaceuticals Industries Ltd.,India)
Intervention Description
letrozole /antagonist protocol
Primary Outcome Measure Information:
Title
the number of asynchronized follicles in both groups
Description
• Asynchronization will considered when there is a difference of at least 2 mm between the dominant follicle and other follicles
Time Frame
30 min

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
subfertile women undergoing IVF/ ICSI trial and having polycystic ovarian syndrome
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Ages ≥20 and <40 years old 2. Women having the diagnosis of polycystic ovarian syndrome according to Rotterdam criteria (15) 3. Women who have at least one of the following indications for IVF or ICSI: Resistance to slandered ovulation induction and life style modification Tubal factors: unilateral or bilateral tubal obstruction, unilateral or bilateral salpingectomy or tubal ligation Male factors: oligoasthenozoospermia or obstructive azoospermia Exclusion Criteria: 1. Women with unexplained infertility. 2. women with poor ovarian reserve according to Bologna criteria (16). 3. Couples with known chromosomal abnormalities. 4. Women who refuse to participate in this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohamed E Taman, MD
Organizational Affiliation
Faculty of Medicine - Mansoura University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Faculty of Medicine
City
Mansoura
State/Province
Dakahlia
ZIP/Postal Code
050
Country
Egypt

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27126581
Citation
Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016 Apr 29;4(4):CD001750. doi: 10.1002/14651858.CD001750.pub4.
Results Reference
background
PubMed Identifier
30052961
Citation
Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 Sep 1;33(9):1602-1618. doi: 10.1093/humrep/dey256. Erratum In: Hum Reprod. 2019 Feb 1;34(2):388.
Results Reference
background
PubMed Identifier
28119448
Citation
Wang R, Mol BW. The Rotterdam criteria for polycystic ovary syndrome: evidence-based criteria? Hum Reprod. 2017 Feb;32(2):261-264. doi: 10.1093/humrep/dew287. Epub 2016 Nov 9.
Results Reference
background
PubMed Identifier
25008235
Citation
Ferraretti AP, Gianaroli L. The Bologna criteria for the definition of poor ovarian responders: is there a need for revision? Hum Reprod. 2014 Sep;29(9):1842-5. doi: 10.1093/humrep/deu139. Epub 2014 Jul 9.
Results Reference
background
PubMed Identifier
29797697
Citation
Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018 May 24;5(5):CD010287. doi: 10.1002/14651858.CD010287.pub3.
Results Reference
background
PubMed Identifier
28277124
Citation
Zhao Y, Ruan X, Mueck AO. Letrozole combined with low dose highly purified HMG for ovulation induction in clomiphene citrate-resistant infertile Chinese women with polycystic ovary syndrome: a prospective study. Gynecol Endocrinol. 2017 Jun;33(6):462-466. doi: 10.1080/09513590.2017.1292241. Epub 2017 Feb 28.
Results Reference
background
PubMed Identifier
28143834
Citation
Wang R, Kim BV, van Wely M, Johnson NP, Costello MF, Zhang H, Ng EH, Legro RS, Bhattacharya S, Norman RJ, Mol BW. Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis. BMJ. 2017 Jan 31;356:j138. doi: 10.1136/bmj.j138. Erratum In: BMJ. 2022 Oct 24;379:o2436.
Results Reference
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Follicular Synchronization in PCOS Patients Undergoing ICSI

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