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

• Sponsor: University of Illinois at Chicago (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01718444
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 2
• Duration (Months): 15
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome; Infertility	Drug: Progestin; Drug: Clomiphene Citrate	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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)
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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
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

Outcome Measures

Primary Outcome Measures

1. Live Birth [Within 36 weeks of a positive pregnancy test]

   Delivery of a viable infant after 24 weeks of pregnancy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Illinois at Chicago	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• University of Illinois at Chicago

Investigators

• Principal Investigator: Albert Asante, MD, MPH, University of Illinois at Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Albert Asante, MD MPH, Assistant Professor of Obstetrics-Gynecology, Consultant in Reproductive Endocrinology and Infertility, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT01718444
• Other Study ID Numbers: 2014-1070
• First Posted: Oct 31, 2012
• Last Update Posted: Sep 29, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by Albert Asante, MD MPH, Assistant Professor of Obstetrics-Gynecology, Consultant in Reproductive Endocrinology and Infertility, University of Illinois at Chicago: PCOS; Polycystic ovary syndrome; Infertility; Anovulation; Clomiphene citrate; Clomid; Progestin; Provera; Progesterone; Endometrial shedding
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Infertility; Syndrome; Medroxyprogesterone Acetate; Clomiphene; Enclomiphene; Zuclomiphene; Medroxyprogesterone; Progestins

Study Results

Participant Flow

Pre-assignment Detail	The study was terminated and data cannot be retrieved as the software where data has been stored has been upgraded. We have exhausted efforts to retrieve the data from this software and no study data are available.

Arm/Group Title	Group A (No PIES)	Group B (PIES Group)
Arm/Group Description	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 Clomiphene Citrate	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 Progestin Clomiphene Citrate
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group A (No PIES)	Group B (PIES Group)	Total
Arm/Group Description	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 Clomiphene Citrate	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 Progestin Clomiphene Citrate	Total of all reporting groups
Overall Participants	0	0	0
Age (years) []
Sex: Female, Male () []
Female
Male

Outcome Measures

1. Primary Outcome

Title	Live Birth
Description	Delivery of a viable infant after 24 weeks of pregnancy
Time Frame	Within 36 weeks of a positive pregnancy test

Outcome Measure Data

Analysis Population Description

The study was terminated and data cannot be retrieved as the software where data has been stored has been upgraded. We have exhausted efforts to retrieve the data from this software and no study data are available.

Arm/Group Title	Group A (No PIES)	Group B (PIES Group)
Arm/Group Description	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 Clomiphene Citrate	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 Progestin Clomiphene Citrate
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The study was terminated and data cannot be retrieved as the software where data has been stored has been upgraded. We have exhausted efforts to retrieve the data from this software and no study data are available.
Arm/Group Title	Group A (No PIES)		Group B (PIES Group)
Arm/Group Description	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 Clomiphene Citrate		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 Progestin Clomiphene Citrate
All Cause Mortality
	Group A (No PIES)		Group B (PIES Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Group A (No PIES)		Group B (PIES Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Group A (No PIES)		Group B (PIES Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

The study was terminated and data cannot be retrieved as the software where data has been stored has been upgraded. We have exhausted efforts to retrieve the data from this software and no study data are available.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.