Infertility
Conditions
Keywords
letrozole, ovulation monitoring, pregnancy rate
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).
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.
Interventions
OTHERMidcycle 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.
OTHERUrinary 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.
Sponsors
Blue Cross Blue Shield of Michigan Foundation
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 39 Years
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Urinary LH Kits 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. | 10 |
| 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.
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. | 11 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Inconvenience of ultrasound visit | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Patient withdrawal due to high cost | 0 | 1 |
| Overall Study | ultrasound screening failure | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Urinary LH Kits | Midcycle Ultrasound + hCG Injection | Total |
|---|---|---|---|
| Age, Continuous | 28.7 years | 29.8 years | 29.3 years |
| Diagnosis of ovulatory dysfunction no prior diagnosis of ovulatory dysfunction | 6 participants | 8 participants | 14 participants |
| Diagnosis of ovulatory dysfunction prior diagnosis of ovulatory dysfunction | 4 participants | 3 participants | 7 participants |
| Gravidity: number of previous pregnancies | .7 pregnancies | 1.1 pregnancies | .9 pregnancies |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 10 | 0 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 |
Outcome results
Primary
Pregnancy Success Rate
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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Urinary LH Kits | Pregnancy Success Rate | 75 percentage of participants |
| Midcycle Ultrasound + hCG Injection | Pregnancy Success Rate | 25 percentage of participants |
Secondary
Time to Conception, Measured in Cycles
Cycles means treatment/menstrual cycles, approximately 28-33 days.
Time frame: 3 menstrual/treatment cycles, or upon conception, whichever comes first
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Urinary LH Kits | Time to Conception, Measured in Cycles | 1.83 menstrual cycles |
| Midcycle Ultrasound + hCG Injection | Time to Conception, Measured in Cycles | 1 menstrual cycles |