RCT of Low-dose Clomiphene vs. High Dose Gonadotropin Protocol for IVF Poor Responders

Study Overview
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Brief Summary
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The purpose of this study is compare two commonly-used medication protocols ( low-dose clomiphene citrate and high dose gonadotropin protocols) for the treatment of patients with diminished ovarian reserve (decreased number of eggs remaining in the ovary) undergoing IVF. This research is being done because we do not know if these two medication protocols are equally likely to help a woman become pregnant.

Detailed Description
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The objective of this protocol is to prospectively evaluate whether a clomid-based, low dose gonadotropin protocol (225 IU) would be non-inferior in terms of mature oocyte yield (eggs that are ready to be fertilized) as compared to a high-dose protocol. Patients meeting the criteria for poor ovarian response will be consented and randomized to either a stimulation protocol involving pretreatment with a 0.1mg estradiol patch in the luteal phase starting 10 days after the LH surge (the hormone released by the brain to cause ovulation to occur, which is detectable in urine) followed by oral clomiphene citrate 100mg on days 2-6 of the menstrual cycle and 225 international units of gonadotropins starting on day 5, or to the control group involving the same pretreatment with 0.1mg luteal estradiol patches starting 10 days after the LH surge, with high dose gonadotropins (600IU) alone, starting on day 2 of the cycle. After randomization, patients will undergo routine IVF procedures, monitoring, blood draws, cancellation criteria, oocyte retrieval, and embryo transfer as non-study participants.

Official Title
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Randomized Prospective Controlled Non-inferiority Trial of Low-dose Clomiphene Based Antagonist Protocol vs. High Dose Gonadotropin/Antagonist Protocol for IVF Poor Responders

Conditions
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Infertility

Intervention / Treatment
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* Drug: Low-dose Clomiphene
* Drug: High dose gonadotropins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients age 18-42 undergoing IVF AFC <7 (see definition above) and AMH (see definition above) <0.5 and/or prior poor IVF response Exclusion Criteria: BMI (body mass index) >30 PGD (preimplantation genetic diagnosis, in which embryos are biopsied to rule out chromosomal abnormalities) Age >42 Fragile X carriers (a condition associated with premature ovarian aging) TESE (Testicular sperm extraction) Asherman's syndrome (uterine scarring which can affect implantation and pregnancy) Untreated hydrosalpinx (accumulated fluid in the fallopian tube which may be toxic to embryos) >6 prior attempted cycles

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 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: High dose gonadotropins<br>High dose gonadotropins protocol compared to Low-dose Clomiphene | Drug: High dose gonadotropins<br>* Pretreatment with a 0.1mg estradiol patch in the luteal phase starting 10 days after the LH surge followed high dose gonadotropins (eg. Follistim. Menopur) 600IU starting on day 2 of the cycle<br>* Other names: Gonal F or Follistim;|
| Experimental: Low-dose Clomiphene<br>clomid-based, low dose gonadotropin protocol compared to High dose gonadotropins | Drug: Low-dose Clomiphene<br>* Pretreatment with a 0.1mg estradiol patch in the luteal phase starting 10 days after the LH surge followed by clomiphene citrate 100mgon days 2-6 of the menstrual cycle with 225 international units of gonadotropins (eg Follistim , Menopur) starting on day 5<br>* Other names: clomiphene citrate with low dose gonadotropins;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of mature oocytes retrieved | To evaluate the number of mature oocytes retrieved in two different IVF protocols for poor responders | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of embryos transferred | To evaluate the number of embryos transferred | 1year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF, poor responder, low ovarian reserve, ART, ovarian stimulation, IVF protocols