Progestin-induced Endometrial Shedding in PCOS (The PIES in PCOS Study)

Study Overview
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Brief Summary
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Progestin-induced endometrial shedding (PIES) followed by clomiphene citrate is fertility treatment of choice in anovulatory women with polycystic ovary syndrome (PCOS). However, some preliminary data suggest that skipping PIES could result in a higher live birth rate. The investigators are performing the first randomized controlled trial to find out if skipping the use of progestin during fertility treatment of anovulatory PCOS women is associated with improved pregnancy and live birth rates compared to the traditional approach of using progestin prior to use of clomiphene citrate.

Detailed Description
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This is a prospective randomized trial of clomiphene citrate (CC) preceded by progestin-induced endometrial shedding (PIES) vs CC without PIES in the treatment of infertility in patients with PCOS, for up to 5 treatment cycles. Participants will be randomized to receive either progestin followed by CC starting on day 3 of the induced menses, or CC without induced menses. Study participants will be monitored at regular 2 to 4 wks intervals for response to medication using ultrasound and hormonal parameters. The maximum dose of CC will not exceed 750 mg/cycle. Treatment will not exceed 5 ovulatory cycles. Participants who are resistant to 150 mg of CC will exit the study. 170 anovulatory PCOS women actively seeking pregnancy, aged 18 through 40 years will be enrolled and randomized in a 1:1 treatment ratio into the two study arms. Anovulation will be the only infertility factor in all patients.

Official Title
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Optimizing Fertility Treatment in Women With Polycystic Ovary Syndrome (PCOS) - A Randomized Controlled Trial: The Role of Progestin-induced Endometrial Shedding in PCOS (PIES in PCOS)

Conditions
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Polycystic Ovary Syndrome, Infertility

Intervention / Treatment
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* Drug: Progestin
* Drug: Clomiphene Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Women aged 18 - 40, desiring pregnancy Established diagnosis of PCOS confirmed by the Rotterdam criteria Oligo or anovulatory, with menstrual cycles > 35 days apart or less than 9 menstrual cycles per year Normal vaginal ultrasound with endometrial stripe < 12 mm Normal thyroid stimulating hormone (TSH) within past one year Normal prolactin (PRL) within past one year For women with previous successful Clomid treatment, a washout period of at least 2 months is required Exclusion Regular menstrual cycles occurring less than 35 days apart Evidence of other infertility factors such as endometriosis, tubal factor or male infertility Prior unsuccessful Clomiphene citrate ovulation cycles Abnormal vaginal ultrasound findings such as endometrial polyps, submucous myomas, synechiae Uterine anomaly such as unicornuate or bicornuate uterus Presence of hydrosalpinx Evidence of active endocrinopathy, such as thyroid disorder or hyperprolactinemia Partner with abnormal semen analysis (count < 15 million sperm /ml)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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 |
| --- | --- |
| Experimental: Group A (No PIES)<br>Subjects randomized to this group will receive clomiphene citrate (CC) without using progestin throughout their treatment course. CC 50 mg oral for 5 days (Days 3-7) If no ovulation, CC 100 mg for 5 days (Days 12-16) If no ovulation, CC 150 mg for 5 days (Day 21-25) Exit study if no response to 150 mg CC, or if no pregnancy after 5 ovulatory cycles | Drug: Clomiphene Citrate<br> <br> * Other names: Clomid;|
| Active Comparator: Group B (PIES Group)<br>Women randomized to this group will receive progestin to induce endometrial shedding before starting any doses of clomiphene citrate (CC) Progestin 10 mg oral for 10 days to induce endometrial shedding (PIES) CC 50 mg oral for 5 days (Day 3-7) If no ovulation, progestin 10 mg for 10 days to induce endometrial shedding (starting on CD28) and CC 100 mg x 5 days, starting on day 3 of induced menses If no ovulation, progestin 10 mg for 10 days to induce endometrial shedding, and CC 150 mg for 5 days Exit study if no response to 150 mg CC, or if no pregnancy after 5 ovulatory cycles | Drug: Progestin<br> <br> * Other names: Medroxyprogesterone acetate;Drug: Clomiphene Citrate<br> <br> * Other names: Clomid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live Birth | Delivery of a viable infant after 24 weeks of pregnancy | Within 36 weeks of a positive pregnancy test | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, Polycystic ovary syndrome, Infertility, Anovulation, Clomiphene citrate, Clomid, Progestin, Provera, Progesterone, Endometrial shedding