Use of High Cost Monitoring During Letrozole Ovulation Induction

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT01279200
• Collaborator: Blue Cross Blue Shield of Michigan Foundation (Other)
• Enrollment: 21
• Location: 1
• Arms: 2
• Duration (Months): 26
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate monitoring methods during ovulation induction cycles with letrozole and their effect on pregnancy rates. Monitoring ovulation induction cycles with letrozole can be done with a variety of methods, the two most commonly utilized are home-based urinary LH kits (or ovulation predictor kits) and office-based midcycle follicular ultrasound. Letrozole coupled with follicular monitoring by ultrasound may add extra cost per cycle with no improvement in fecundability (pregnancy rates per cycle).

Condition or Disease	Intervention/Treatment	Phase
Infertility	Other: Midcycle ultrasound + hCG injection; Other: Urinary LH kits	Phase 4

Detailed Description

The study will be a randomized controlled trial of adult women with primary and secondary infertility seen at the University of Michigan Health System undergoing ovulation induction (OI) with letrozole as part of their standard clinical care. Patients who are undergoing OI with letrozole as per standard clinical care will be randomized to urinary luteinizing hormone (LH) ovulation predictor kit use versus mid-cycle ultrasound with administration of hCG when appropriate for timing of intercourse or intrauterine insemination. Patients who have been prescribed letrozole as per routine clinical care will be approached to determine willingness to participate in this study. Study period involves up to three ovulation induction cycles or until pregnancy occurs.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Use of High Cost Monitoring During Letrozole Ovulation Induction and Effect on Pregnancy Rates - A Pilot Study
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Urinary LH Kits Patients randomized to this arm will monitor ovulation with home-based urinary LH kits (Ovulation Predictor Kits, OPK's).	Other: Urinary LH kits; Subjects randomized to monitoring with LH kits at home will keep a monthly calendar documenting when LH testing begins, day LH surge occurs and day(s) of intercourse/insemination.; Other Names: ClearBlue Easy
Active Comparator: Midcycle ultrasound + hCG injection Patients randomized to this arm will undergo ovulation monitoring with midcycle ultrasound and receive hCG injection if evidence of a mature size follicle.	Other: Midcycle ultrasound + hCG injection; Mid-cycle ultrasound with administration of hCG (single dose of standardized pre-filled injection, 250 mcg, at time of ultrasound) when appropriate.; Other Names: Ovidrel

Outcome Measures

Primary Outcome Measures

1. Pregnancy Success Rate [3 menstrual/treatment cycles (approximately 28-33 days each)]

   Percentage of women in each arm who became pregnant within the study time frame.

Secondary Outcome Measures

1. Time to Conception, Measured in Cycles [3 menstrual/treatment cycles, or upon conception, whichever comes first]

   Cycles means treatment/menstrual cycles, approximately 28-33 days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 39 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women ages 21-39 undergoing letrozole ovulation induction (as part of routine clinical care) at a single academic-infertility center.

• Normal uterus and evidence of at least tubal patency on one side (as assessed by saline-infusion sonography or hysterosalpingogram per clinical care).

Exclusion Criteria:

• Current pregnancy

• Nursing mothers

• Prior hypersensitivity to hCG preparations

• Primary ovarian failure or menopausal levels of FSH (>12 mIU/mL)

• Patients with abnormal uterine bleeding of undetermined origin or ovarian cyst of undetermined origin, sex-hormone dependent tumors, documented bilateral tubal obstruction, uncorrected uterine anomalies,

• Previous letrozole or gonadotropin use and/or previous treatment with in vitro fertilization

• Other uncorrected medical condition that would be a contraindication to attempting elective ovulation induction (e.g., uncontrolled diabetes, intracranial lesion, thyroid or adrenal disease).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Reproductive Medicine, University of Michigan	Ann Arbor	Michigan	United States	48108

Sponsors and Collaborators

• University of Michigan
• Blue Cross Blue Shield of Michigan Foundation

Investigators

• Principal Investigator: Senait Fisseha, MD, JD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Deaton JL, Clark RR, Pittaway DE, Herbst P, Bauguess P. Clomiphene citrate ovulation induction in combination with a timed intrauterine insemination: the value of urinary luteinizing hormone versus human chorionic gonadotropin timing. Fertil Steril. 1997 Jul;68(1):43-7.
• Lewis V, Queenan J Jr, Hoeger K, Stevens J, Guzick DS. Clomiphene citrate monitoring for intrauterine insemination timing: a randomized trial. Fertil Steril. 2006 Feb;85(2):401-6.
• Mitwally MF, Abdel-Razeq S, Casper RF. Human chorionic gonadotropin administration is associated with high pregnancy rates during ovarian stimulation and timed intercourse or intrauterine insemination. Reprod Biol Endocrinol. 2004 Jul 7;2:55.
• Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril. 2001 Feb;75(2):305-9.
• Pritts EA. Letrozole for ovulation induction and controlled ovarian hyperstimulation. Curr Opin Obstet Gynecol. 2010 Aug;22(4):289-94. doi: 10.1097/GCO.0b013e32833beebf. Review.
• Smith YR, Randolph JF Jr, Christman GM, Ansbacher R, Howe DM, Hurd WW. Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction. Fertil Steril. 1998 Jul;70(1):165-8.
• Zreik TG, García-Velasco JA, Habboosh MS, Olive DL, Arici A. Prospective, randomized, crossover study to evaluate the benefit of human chorionic gonadotropin-timed versus urinary luteinizing hormone-timed intrauterine inseminations in clomiphene citrate-stimulated treatment cycles. Fertil Steril. 1999 Jun;71(6):1070-4.

• Responsible Party: Senait Fisseha, MD, JD, Medical Director, University of Michigan
• ClinicalTrials.gov Identifier: NCT01279200
• Other Study ID Numbers: HUM00041349; 1726.PIRAP
• First Posted: Jan 19, 2011
• Last Update Posted: Jan 6, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Senait Fisseha, MD, JD, Medical Director, University of Michigan: letrozole; ovulation monitoring; pregnancy rate
• Additional relevant MeSH terms: Infertility

Study Results

Participant Flow

Arm/Group Title	Urinary LH Kits	Midcycle Ultrasound + hCG Injection
Arm/Group Description	Patients randomized to this arm will monitor ovulation with home-based urinary LH kits (Ovulation Predictor Kits, OPK's). Urinary LH kits: Subjects randomized to monitoring with LH kits at home will keep a monthly calendar documenting when LH testing begins, day LH surge occurs and day(s) of intercourse/insemination.	Patients randomized to this arm will undergo ovulation monitoring with midcycle ultrasound and receive hCG injection if evidence of a mature size follicle. Midcycle ultrasound + hCG injection: Mid-cycle ultrasound with administration of hCG (single dose of standardized pre-filled injection, 250 mcg, at time of ultrasound) when appropriate.
Period Title: Overall Study
STARTED	10	11
COMPLETED	8	4
NOT COMPLETED	2	7

Baseline Characteristics

Arm/Group Title	Urinary LH Kits	Midcycle Ultrasound + hCG Injection	Total
Arm/Group Description	Patients randomized to this arm will monitor ovulation with home-based urinary LH kits (Ovulation Predictor Kits, OPK's). Urinary LH kits: Subjects randomized to monitoring with LH kits at home will keep a monthly calendar documenting when LH testing begins, day LH surge occurs and day(s) of intercourse/insemination.	Patients randomized to this arm will undergo ovulation monitoring with midcycle ultrasound and receive hCG injection if evidence of a mature size follicle. Midcycle ultrasound + hCG injection: Mid-cycle ultrasound with administration of hCG (single dose of standardized pre-filled injection, 250 mcg, at time of ultrasound) when appropriate.	Total of all reporting groups
Overall Participants	10	11	21
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	28.7	29.8	29.3
Sex: Female, Male (Count of Participants)
Female	10 100%	11 100%	21 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 10%	2 18.2%	3 14.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	9 90%	9 81.8%	18 85.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Gravidity: number of previous pregnancies (pregnancies) [Mean (Full Range) ]
Mean (Full Range) [pregnancies]	.7	1.1	.9
Diagnosis of ovulatory dysfunction (participants) [Number]
prior diagnosis of ovulatory dysfunction	4 40%	3 27.3%	7 33.3%
no prior diagnosis of ovulatory dysfunction	6 60%	8 72.7%	14 66.7%

Outcome Measures

1. Secondary Outcome

Title	Time to Conception, Measured in Cycles
Description	Cycles means treatment/menstrual cycles, approximately 28-33 days.
Time Frame	3 menstrual/treatment cycles, or upon conception, whichever comes first

Outcome Measure Data

Analysis Population Description

Numbers of participants analyzed changes from 8 with kits and 4 with ultrasound (enrolled) because time to conception can be measured only for those who conceived, so the 6 and 1 participants analyzed here are those who were successful in getting pregnant.

Arm/Group Title	Urinary LH Kits	Midcycle Ultrasound + hCG Injection
Arm/Group Description	Patients randomized to this arm will monitor ovulation with home-based urinary LH kits (Ovulation Predictor Kits, OPK's). Urinary LH kits: Subjects randomized to monitoring with LH kits at home will keep a monthly calendar documenting when LH testing begins, day LH surge occurs and day(s) of intercourse/insemination.	Patients randomized to this arm will undergo ovulation monitoring with midcycle ultrasound and receive hCG injection if evidence of a mature size follicle. Midcycle ultrasound + hCG injection: Mid-cycle ultrasound with administration of hCG (single dose of standardized pre-filled injection, 250 mcg, at time of ultrasound) when appropriate.
Measure Participants	6	1
Mean (Full Range) [menstrual cycles]	1.83	1

2. Primary Outcome

Title	Pregnancy Success Rate
Description	Percentage of women in each arm who became pregnant within the study time frame.
Time Frame	3 menstrual/treatment cycles (approximately 28-33 days each)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Urinary LH Kits	Midcycle Ultrasound + hCG Injection
Arm/Group Description	Patients randomized to this arm will monitor ovulation with home-based urinary LH kits (Ovulation Predictor Kits, OPK's). Urinary LH kits: Subjects randomized to monitoring with LH kits at home will keep a monthly calendar documenting when LH testing begins, day LH surge occurs and day(s) of intercourse/insemination.	Patients randomized to this arm will undergo ovulation monitoring with midcycle ultrasound and receive hCG injection if evidence of a mature size follicle. Midcycle ultrasound + hCG injection: Mid-cycle ultrasound with administration of hCG (single dose of standardized pre-filled injection, 250 mcg, at time of ultrasound) when appropriate.
Measure Participants	8	4
Number [percentage of participants]	75 750%	25 227.3%

Adverse Events

Time Frame	End of Cycle 1, Cycle 2 and Cycle 3; OB ultrasound (if applicable); and at the End of Study visit.
Adverse Event Reporting Description	Phone call (group A) or in-person assessment (group B).
Arm/Group Title	Urinary LH Kits		Midcycle Ultrasound + hCG Injection
Arm/Group Description	Patients randomized to this arm will monitor ovulation with home-based urinary LH kits (Ovulation Predictor Kits, OPK's). Urinary LH kits: Subjects randomized to monitoring with LH kits at home will keep a monthly calendar documenting when LH testing begins, day LH surge occurs and day(s) of intercourse/insemination.		Patients randomized to this arm will undergo ovulation monitoring with midcycle ultrasound and receive hCG injection if evidence of a mature size follicle. Midcycle ultrasound + hCG injection: Mid-cycle ultrasound with administration of hCG (single dose of standardized pre-filled injection, 250 mcg, at time of ultrasound) when appropriate.
All Cause Mortality
	Urinary LH Kits		Midcycle Ultrasound + hCG Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Urinary LH Kits		Midcycle Ultrasound + hCG Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Urinary LH Kits		Midcycle Ultrasound + hCG Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		0/11 (0%)
Musculoskeletal and connective tissue disorders
Side effects	1/10 (10%)	1	0/11 (0%)	0

Limitations/Caveats

The original intent was to study 400 women, but due to recruiting and time restraints, final enrollment was only 21. Therefore, statistical analyses of the results were eliminated, as well as some additional outcome measures originally planned for.

More Information

Certain Agreements

All Principal Investigators ARE 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.