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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by University of Illinois at Chicago
Sponsor:
Information provided by (Responsible Party):
Albert Asante, University of Illinois at Chicago
ClinicalTrials.gov Identifier:
NCT01718444
First received: October 19, 2012
Last updated: March 3, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention
Polycystic Ovary Syndrome
Infertility
Drug: Progestin
Drug: Clomiphene Citrate

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by University of Illinois at Chicago:

Primary Outcome Measures:
  • Live birth [ Time Frame: Within 36 weeks of a positive pregnancy test ] [ Designated as safety issue: No ]
    Delivery of a viable infant after 24 weeks of pregnancy


Secondary Outcome Measures:
  • Time to first ovulation [ Time Frame: Within 3 months of start of CC ] [ Designated as safety issue: No ]
  • Time to clinical pregnancy [ Time Frame: Within 6 months of start of CC ] [ Designated as safety issue: No ]
  • Clinical pregnancy rate [ Time Frame: Within 3 weeks of a positive pregnancy test ] [ Designated as safety issue: No ]
  • Miscarriage rate [ Time Frame: Within 20 weeks of pregnancy ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: March 2015
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A (No PIES)

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
Other Names:
  • Clomid
  • Clomiphene citrate
Active Comparator: Group B (PIES Group)

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
Other Names:
  • Provera
  • Medroxyprogesterone acetate
Drug: Clomiphene Citrate
Other Names:
  • Clomid
  • Clomiphene citrate

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718444

Contacts
Contact: Albert Asante, MD, MPH 312-355-4983 alasante@uic.edu
Contact: Eve Hardin, RN 312-355-2740 ehardin@uic.edu

Locations
United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Albert Asante, MD, MPH    312-355-4983    alasante@uic.edu   
Principal Investigator: Albert Asante, MD, MPH         
Sub-Investigator: Musa Zamah, MD, PhD         
Sub-Investigator: Mary Stephenson, MD, MSc         
Sub-Investigator: Humberto Scoccia, MD         
Sponsors and Collaborators
University of Illinois at Chicago
Investigators
Principal Investigator: Albert Asante, MD, MPH University of Illinois at Chicago
  More Information

No publications provided

Responsible Party: Albert Asante, Assistant Professor of Obstetrics-Gynecology, Consultant in Reproductive Endocrinology and Infertility, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT01718444     History of Changes
Other Study ID Numbers: 12-006213
Study First Received: October 19, 2012
Last Updated: March 3, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Illinois at Chicago:
PCOS
Polycystic ovary syndrome
Infertility
Anovulation
Clomiphene citrate
Clomid
Progestin
Provera
Progesterone
Endometrial shedding

Additional relevant MeSH terms:
Infertility
Polycystic Ovary Syndrome
Adnexal Diseases
Cysts
Endocrine System Diseases
Genital Diseases, Female
Genital Diseases, Male
Gonadal Disorders
Neoplasms
Ovarian Cysts
Ovarian Diseases
Citric Acid
Clomiphene
Enclomiphene
Medroxyprogesterone
Medroxyprogesterone Acetate
Progestins
Zuclomiphene
Anticoagulants
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Chelating Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Estrogen Antagonists
Estrogen Receptor Modulators
Fertility Agents

ClinicalTrials.gov processed this record on August 31, 2015