| CTRI Number |
CTRI/2025/03/082363 [Registered on: 17/03/2025] Trial Registered Prospectively |
| Last Modified On: |
13/03/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Comparison of efficacy of coadministration of oral ovulation induction drugs to conventional ovarian stimulation protocol in infertile women with diminished ovarian reserve undergoing IVF or ICSI cycles |
|
Scientific Title of Study
|
Efficacy of coadministration of clomiphene citrate and letrozole to conventional GnRH antagonist protocol in expected poor responders undergoing IVF or ICSI cycles A Randomized Controlled Trial |
| Trial Acronym |
Nil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Reeta Mahey |
| Designation |
Professor |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Department of Obstetrics and Gynaecology, AIIMS
New Delhi
DELHI
110029
India |
| Phone |
9818447845 |
| Fax |
|
| Email |
drreetamahey@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Reeta Mahey |
| Designation |
Professor |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Department of Obstetrics and Gynaecology, AIIMS
New Delhi
DELHI
110029
India |
| Phone |
9818447845 |
| Fax |
|
| Email |
drreetamahey@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Nishtha Jaiswal |
| Designation |
DM resident- Reproductive Medicine |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Department of Obstetrics and Gynaecology, AIIMS
New Delhi
DELHI
110029
India |
| Phone |
8744042192 |
| Fax |
|
| Email |
nishtha.amu@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India - 110029 |
|
|
Primary Sponsor
|
| Name |
All India Institute of Medical Sciences |
| Address |
Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East, New Delhi, Delhi 110029 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Nishtha Jaiswal |
All India Institute of Medical Sciences |
IVF Lab, Service floor, Mother and Child Block, Department of Obstetrics and Gynaecology, Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East
New Delhi
DELHI |
8744042192
nishtha.amu@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| AIIMS Institutional Ethics Committee for Post Graduate Research |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: N979||Female infertility, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Clomiphene citrate plus Letrozole group |
In this group, patients will receive oral tablet Clomiphene citrate (100 mg) and tablet Letrozole (5 mg) from day 2 to day 6 of menses along with Injection Gonadotropin (dose 300 IU in POSEIDON group 3 and 375 IU in POSEIDON group 4) from day 2 of menses during one month of ovarian stimulation cycle |
| Comparator Agent |
GnRH Antagonist |
In the control group (antagonist cycle), Injection Gonadotropin will be started on day 2 of the menses during one month of ovarian stimulation cycle (dose of gonadotropin will be depending on the age of patient, BMI (body mass index), AMH, antral follicle count (AFC) and/or ovarian response in previous cycles) |
|
|
Inclusion Criteria
|
| Age From |
22.00 Year(s) |
| Age To |
40.00 Year(s) |
| Gender |
Female |
| Details |
BMI of less than 35kg/m2, unexplained infertility, tubal factor, mild male infertility, willing to participate in study |
|
| ExclusionCriteria |
| Details |
Women with diagnosed PCOS, Endometrioma of size more than 3 cm, fibroid or adenomyoma distorting the endometrial cavity, severe male factor infertility (oligoasthenoteratozoospermia) |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Number of Grade 1 oocytes (Expanded cumulus, very radiant corona, distinct zona pellucida, clear ooplasm, expanded well aggregated membrana granulosa cells) |
once during IVF or ICSI Cycle |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Total dose of gonadotropins required
Duration of stimulation
Peak estradiol & progesterone on the day of trigger
Number of oocytes retrieved
Number of mature oocytes retrieved
Mature oocyte output rate (MOOR)
Number of follicles more than 14 mm on the day of trigger
Follicular output rate (FORT)
Endometrial thickness on the day of trigger
Fertilization rate
Cleavage rate
Blastulation rate
Cycle cancellation rate
Clinical pregnancy rate per embryo transfer
Cumulative clinical pregnancy rate
|
During IVF or ICSI cycle- Ovum pick up and Embryo transfer |
|
|
Target Sample Size
|
Total Sample Size="212"
Sample Size from India="212"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
15/04/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
GnRH antagonist protocol is a conventional ovarian stimulation protocol in IVF. In expected poor responders (POSEIDON group 3 and 4), usually higher amount of gonadotropin is required along with prolonged duration of stimulation in order to achieve the target follicular stimulation. Few studies have been done lately on effect of addition of aromatase inhibitors (letrozole) and/or clomiphene citrate (CC) to gonadotropins (Gn) in women undergoing IVF/ICSI cycles. The addition of these oral drugs have shown comparable or non-inferior results in terms of oocyte yield in expected poor responders, along with decreasing the overall cost of the cycle. But most of the studies have used either Let or CC. The data on combined addition of CC and Let is sparse. Only one retrospective study on combined addition of CC+ Let to Gn found on literature review.The rationale for protocols using combination of oral agents such as CC and/or Let with relatively low-dose gonadotropins is: - To reduce cost of IVF cycle
- To reduce time required for controlled ovarian stimulation
- To combat side-effects of high dose of Gn on endometrium
CC and Let both stimulate GnRH secretion by decreasing the negative feedback effect of estrogen. CC depletes central estrogen receptors whereas Let decreases estrogen production directly and increases androgen levels in the ovary. The increase of intraovarian androgen by Let also prevents follicular atresia during the preantral-early antral transition phase, and stimulates granulosa cell mitosis and proliferation, thereby facilitating follicular growth and enhanced quality of oocyte. These different mechanisms of both oral agents may result in an additive effect to improve the IVF outcomes in expected poor responders. |