Infertility
Conditions
Keywords
Infertility, Intrauterine insemination, Luteinizing hormone surge
Brief summary
The aim of this study is to assess the impact of the timing of intrauterine insemination (IUI) in relation to the natural surge of luteinizing hormone (LH), as detected by home ovulation predictor kits, on pregnancy rates per treatment cycle. The study will take place at the offices of Midwest Fertility Specialists and include patients who have been independently recommended by their primary physician to undergo ovulation induction with clomiphene citrate (CC) or letrozole and IUI as therapy for infertility.
Detailed description
Intrauterine insemination is a procedure that is performed in the physician's office. During the procedure the sperm from the male partner are placed directly into the female partner's uterus around the time of ovulation (release of oocyte or egg). Ovulation predictor kits, available over the counter at pharmacies, test for the presence of luteinizing hormone in the urine. When the test result is a positive, it means the hormone is present in the urine. This is a sign of ovulation. Physicians typically choose to perform intrauterine insemination either the day of a positive ovulation test or the day after a positive ovulation test. The purpose of this study is to determine if the day when intrauterine insemination is performed influences the chance of becoming pregnant.
Interventions
PROCEDUREIntrauterine Insemination
Intrauterine insemination is either performed on the day the home ovulation predictor kit first turns positive or the day after the first positive.
DRUGClomiphene
Patient is to take clomiphene citrate during cycle days 3-7.
DRUGLetrozole
Patient is to take letrozole during cycle days 3-7.
Sponsors
Midwest Fertility Specialists
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 39 Years
Healthy volunteers
No
Inclusion criteria
* All couples consisting of male and female partner undergoing CC or letrozole cycle plus IUI at a single infertility center (Midwest Fertility Specialists) * The female partner must be aged 21-39 * Infertile couples include those with a diagnosis(s) of unexplained infertility, mild male factor, ovulatory dysfunction, or anovulation * Evidence of a normal uterus and at least unilateral tubal patency on saline infusion sonogram or hysterosalpingogram within the last 2 years * Semen analysis for male partner must have minimal sperm concentration of 10 million per milliliter
Exclusion criteria
* Recurrent miscarriages * Nursing mothers * Diagnoses of primary ovarian failure, diminishing ovarian reserve (as indicated by blood follicle stimulating hormone \>10 milliInternationalUnits/mL and/or anti-mullerian hormone level \<0.5), abnormal uterine bleeding of undetermined origin, ovarian cyst of undetermined origin, stage IV endometriosis, or sex-hormone dependent tumors * Documented bilateral tubal obstruction or other uncorrected uterine anomalies (e.g. uterine septum) * Previous gonadotropin use and/or previous treatment with in vitro fertilization * Abnormal semen analysis (sperm concentration less than 10 million per mL) or ejaculatory dysfunction in male partner * Other uncorrected medical condition in female partner 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 |
|---|---|
| Number of Pregnancies Achieved Per Menstrual Cycle. | Up to 3 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pregnancy Rate Per Female Partner Age | Up to cycle day 35 | Pregnancy rate will be compared between patients \<35 and \>35 at time of study entry. |
| Per Cycle Pregnancy Rate Based on Infertility Diagnosis | Up to cycle day 35 | — |
| Pregnancy Rate Per Semen Morphology Score | Up to cycle day 35 | Comparison of pregnancy rate based on semen morphology of \<4% vs \>4% normal morphology scores. |
| Pregnancy Rate Per Body Mass Index Category | Up to cycle day 35 | — |
Countries
United States
Participant flow
Recruitment details
Patients recruited from two clinical offices from 1/2014 until 9/2015.
Participants by arm
| Arm | Count |
|---|---|
| Insemination Day Of Positive OPK This group takes either clomiphene or letrozole on cycle days 3-7 and then receives intrauterine insemination on the day the home ovulation predictor kit first turns positive.
Intrauterine Insemination: Intrauterine insemination is either performed on the day the home ovulation predictor kit first turns positive or the day after the first positive.
Clomiphene: Patient is to take clomiphene citrate during cycle days 3-7.
Letrozole: Patient is to take letrozole during cycle days 3-7. | 7 |
| Insemination Day After Positive OPK This group takes either clomiphene or letrozole on cycle days 3-7 and then receives intrauterine insemination on the day after the home ovulation predictor kit first turns positive.
Intrauterine Insemination: Intrauterine insemination is either performed on the day the home ovulation predictor kit first turns positive or the day after the first positive.
Clomiphene: Patient is to take clomiphene citrate during cycle days 3-7.
Letrozole: Patient is to take letrozole during cycle days 3-7. | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Insemination Day Of Positive OPK | Insemination Day After Positive OPK | Total |
|---|---|---|---|
| Age, Continuous | 30.4 years STANDARD_DEVIATION 5.9 | 29.6 years STANDARD_DEVIATION 3.05 | 30.1 years STANDARD_DEVIATION 4.8 |
| Anti-mullerian Hormone | 3.1 ng/ml STANDARD_DEVIATION 2.2 | 5.8 ng/ml STANDARD_DEVIATION 0 | 5.2 ng/ml STANDARD_DEVIATION 2.3 |
| Body Mass Index | 30 kg/m^2 STANDARD_DEVIATION 8.9 | 25 kg/m^2 STANDARD_DEVIATION 4 | 27.9 kg/m^2 STANDARD_DEVIATION 7.5 |
| Day 3 Follicle Stimulating Hormone | 7.6 mIU/ml STANDARD_DEVIATION 1.7 | 6.2 mIU/ml STANDARD_DEVIATION 1.9 | 6.9 mIU/ml STANDARD_DEVIATION 1.8 |
| Mid-luteal progesterone | 21.1 ng/ml STANDARD_DEVIATION 16.4 | 12.1 ng/ml STANDARD_DEVIATION 4.3 | 18.6 ng/ml STANDARD_DEVIATION 13.7 |
| Region of Enrollment United States | 7 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sperm Concentration | 32.6 million sperm/ml STANDARD_DEVIATION 13.9 | 71.2 million sperm/ml STANDARD_DEVIATION 39.2 | 39.4 million sperm/ml STANDARD_DEVIATION 30.9 |
| Sperm morphology | 5.6 Percent normal STANDARD_DEVIATION 2.3 | 8.5 Percent normal STANDARD_DEVIATION 2.4 | 6.2 Percent normal STANDARD_DEVIATION 2.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 7 | 0 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Number of Pregnancies Achieved Per Menstrual Cycle.
Time frame: Up to 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insemination Day Of Positive OPK | Number of Pregnancies Achieved Per Menstrual Cycle. | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Number of Pregnancies Achieved Per Menstrual Cycle. | 0 pregnancies per cycle |
Other Pre-specified
Per Cycle Pregnancy Rate Based on Infertility Diagnosis
Time frame: Up to cycle day 35
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insemination Day Of Positive OPK | Per Cycle Pregnancy Rate Based on Infertility Diagnosis | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Per Cycle Pregnancy Rate Based on Infertility Diagnosis | 0 pregnancies per cycle |
Other Pre-specified
Pregnancy Rate Per Body Mass Index Category
Time frame: Up to cycle day 35
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insemination Day Of Positive OPK | Pregnancy Rate Per Body Mass Index Category | Body mass index normal | 0 pregnancies per cycle |
| Insemination Day Of Positive OPK | Pregnancy Rate Per Body Mass Index Category | Body mass index overweight | 0 pregnancies per cycle |
| Insemination Day Of Positive OPK | Pregnancy Rate Per Body Mass Index Category | Body mass index obese | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Pregnancy Rate Per Body Mass Index Category | Body mass index obese | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Pregnancy Rate Per Body Mass Index Category | Body mass index normal | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Pregnancy Rate Per Body Mass Index Category | Body mass index overweight | 0 pregnancies per cycle |
Other Pre-specified
Pregnancy Rate Per Female Partner Age
Pregnancy rate will be compared between patients \<35 and \>35 at time of study entry.
Time frame: Up to cycle day 35
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insemination Day Of Positive OPK | Pregnancy Rate Per Female Partner Age | Female age < 35 | 0 pregnancies per cycle |
| Insemination Day Of Positive OPK | Pregnancy Rate Per Female Partner Age | Female age > 35 | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Pregnancy Rate Per Female Partner Age | Female age < 35 | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Pregnancy Rate Per Female Partner Age | Female age > 35 | 0 pregnancies per cycle |
Other Pre-specified
Pregnancy Rate Per Semen Morphology Score
Comparison of pregnancy rate based on semen morphology of \<4% vs \>4% normal morphology scores.
Time frame: Up to cycle day 35
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insemination Day Of Positive OPK | Pregnancy Rate Per Semen Morphology Score | Semen morphology > 4% | 0 pregnancies per cycle |
| Insemination Day Of Positive OPK | Pregnancy Rate Per Semen Morphology Score | Semen morphology < 4% | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Pregnancy Rate Per Semen Morphology Score | Semen morphology < 4% | 0 pregnancies per cycle |
| Insemination Day After Positive OPK | Pregnancy Rate Per Semen Morphology Score | Semen morphology > 4% | 0 pregnancies per cycle |