Tubal Patency
Conditions
Keywords
hysterosalpingography, DMPA, combined oral contraceptive, tubal patency
Brief summary
The investigators' research group is working to develop a highly effective, low cost non-surgical method of permanent contraception for women. To support this goal, we need to know more about the normal fallopian tube (tube that passes the egg from the ovary into the womb). The purpose of this study is to learn about how menstrual cycles and hormonal contraceptives affect tubal patency. Normally there is an opening between the tube and uterus to permit the flow of fluid and cells. If this opening is blocked, this can result in infertility. Tubal patency is when a woman's fallopian tubes are not blocked. Tubal patency is determined by an x-ray test called a hystero-(uterus)salpingo-(fallopian tube)graphy (HSG). HSG is a standard radiological imaging study that is used to determine if the fallopian tubes are open and free of disease. It is commonly done in women with an infertility diagnosis. The investigators usually do this test in the first 10 days of the menstrual cycle. Sometimes the tubes will appear to be blocked on the HSG when they are actually open. The timing of the HSG study during the menstrual cycle, or the use of hormonal contraception may make a difference in whether the tubes appear blocked on the HSG when they are actually patent. The results of the HSG test provide a good model for how our nonsurgical permanent contraception method might work. The investigators think that if the tubes are not patent, that our treatment will not work as well. Therefore, in this study we want to learn if menstrual cycle timing or current hormonal contraception use will affect the patency of the tubes as assessed by the HSG. The investigators want to examine the same women to see if tubal patency is changes during the menstrual cycle and during the use of a birth control pill and the birth control shot.
Interventions
combined oral contraceptive pill will be dosed continuously for 30 days without cycle interruption
DRUGDepoProvera
injectable hormonal contraceptive
Sponsors
Bill and Melinda Gates Foundation
Jeffrey Jensen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
i. Women between 18 and 40 years old ii. In good health, with regular menstrual cycles that occur 24 - 37 days iii. No current use of hormonal contraception or an intrauterine device and having had at least one complete menstrual cycle since having stopped hormonal contraception before starting the treatment. iv. Have a negative urine pregnancy test at the admission visit. v. Have a negative chlamydia test at the admission visit. vi. Not be at risk for pregnancy. They will be consistently using a non-hormonal contraception method, have a surgically sterile male partner with a vasectomy, be abstinent, or be in a same-sex relationship from the screening visit through the first study cycle. After starting the combined OC (see Visit 4 below), use of a non-hormonal method is no longer required. vii. In the opinion of the investigator, willing and able to follow all study requirements, including use of the approved study medications (doxycycline, oral contraceptive and DMPA). viii. Understand and sign an IRB approved inform consent form prior to screening activities. ix. Will have diastolic blood pressure (BP) ≤85 mm Hg and systolic BP ≤145 mm Hg after 5 minutes in sitting position. x. Agree not to participate in any other clinical trials during the course of this study.
Exclusion criteria
* i. Women with menstrual cycle length of less than 24 or more than 37 days; or with spontaneous irregular menstrual cycle length with intra-individual variations of more than 5 days ii. Currently pregnant as confirmed by positive high-sensitivity urine pregnancy test iii. Women planning pregnancy within their months of study participation iv. Currently breast-feeding or within 30 days of discontinuing breast feeding v. Current use of a hormonal IUD, or other hormonal contraception (including oral contraceptives, contraceptive vaginal rings, contraceptive patches, or contraceptive implants) within 30 days prior to screening. NOTE: Discontinuation of hormonal contraception or removal of implanted hormonal contraceptives must have been for personal reasons unrelated to the purpose of enrollment in this study. vi. Undiagnosed abnormal genital bleeding vii. Known hypersensitivity to radio-opaque contrast, doxycycline, levonorgestrel, ethinyl estradiol or depo-medroxyprogesterone acetate. The active ingredients in the approved medications used in the study. viii. Anomalies in the clinical exam or history done at screening visit recognized as clinically significant by the investigator. ix. Unable to pass a uterine sound at the screening examination. x. A positive test for chlamydia at screening, or a history of a positive test within the last 6 months. xi. A clinically significant Pap test abnormality, as managed by current local or national guidelines that would require treatment over the next 6 months. xii. Invasive cancer (past history of any carcinoma or sarcoma, except non-melanoma skin cancer) xiii. Body mass index (BMI) \>35. xiv. Current use of a non-hormone containing (copper) intrauterine device (IUD). NOTE: Removal of an IUD must have been for personal reasons unrelated to the purpose of enrollment in this study. xv. Smoking if \> age 35. xvi. Personal history of venous or arterial thrombosis or embolism, or family history in a first-degree relative \<55 years of age suggesting familial defect in blood coagulation system, which in the opinion of the principal investigator, suggests use of a hormonal contraceptive could pose a significant risk. xvii. Cerebrovascular or cardiovascular disease. xviii. History of retinal vascular lesions, unexplained partial or complete loss of vision. xix. Headaches with focal neurological symptoms. xx. History of cholestatic jaundice of pregnancy or jaundice with prior steroid use. xxi. Use of liver enzyme inducers on a regular basis. xxii. History of involuntary infertility, pelvic inflammatory disease (not followed by a normal pregnancy), or known gynecologic conditions or surgery that could affect tubal patency (e.g. tubal adhesions, endometriosis, hydrosalpinx, salpingectomy, hysterectomy, oophorectomy). xxiii. History of a prior HSG showing tubal occlusion on one or both sides.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bilateral Tubal Patency as Assessed by HSG-follicular | follicular phase HSG | Assessment of patency at follicular phase exam |
| Number of Participants With Bilateral Tubal Patency as Assessed by HSG - Luteal | luteal phase HSG | Assessment of patency at luteal phase exam |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bilateral Tubal Patency as Assessed by HSG - OC HSG | HSG on OC | HSG during OC treatment |
| Number of Participants With Bilateral Tubal Patency as Assessed by HSG - DMPA HSG | HSG on DMPA | HSG during DMPA treatment |
| Number of Participants With Bilateral Tubal Patency as Assessed by HSG -- Post DMPA Add Back COC HSG | HSG on OC after DMPA | — |
Countries
United States
Participant flow
Recruitment details
14 subjects were screened, and 11 signed consent and enrolled. One dropped out prior to the first HSG, and10 completed the 2 natural cycle HSG, 9 completed the COC HSG, 7 the DMPA HSG, and one a final post DMPA HSG after restarting COCs
Participants by arm
| Arm | Count |
|---|---|
| HSG Studies Women will be given combined oral contraceptives and Depo-medroxyprogesterone acetate (DepoProvera®).
2 HSG studies will be done prior to hormonal treatment, 1 after the pill treatment, and depending on whether the tubes appear patent, 1 more after the depoProvera treatment, and a final HSG after another 2 weeks on the pill.
Combined oral contraceptive: combined oral contraceptive pill will be dosed continuously for 30 days without cycle interruption
DepoProvera: injectable hormonal contraceptive | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | HSG Studies |
|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 5 |
| Nulligravid | 6 Participants |
| One or more births | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 11 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Number of Participants With Bilateral Tubal Patency as Assessed by HSG-follicular
Assessment of patency at follicular phase exam
Time frame: follicular phase HSG
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG-follicular | bilateral patent | 9 Participants |
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG-follicular | blocked | 1 Participants |
Comparison: McNemar paired. Hypothesis is no change in tubal patency status. All subjects know to have bilateral patency in one of the exams during natural cyclep-value: 0.4795McNemar
Primary
Number of Participants With Bilateral Tubal Patency as Assessed by HSG - Luteal
Assessment of patency at luteal phase exam
Time frame: luteal phase HSG
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG - Luteal | bilateral tubal patency | 10 Participants |
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG - Luteal | blocked | 0 Participants |
Other Pre-specified
Number of Participants With Bilateral Tubal Patency as Assessed by HSG - DMPA HSG
HSG during DMPA treatment
Time frame: HSG on DMPA
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG - DMPA HSG | bilateral patubal patency | 6 Participants |
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG - DMPA HSG | blocked | 1 Participants |
Other Pre-specified
Number of Participants With Bilateral Tubal Patency as Assessed by HSG - OC HSG
HSG during OC treatment
Time frame: HSG on OC
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG - OC HSG | bilateral tubal patency | 7 Participants |
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG - OC HSG | blocked | 2 Participants |
Other Pre-specified
Number of Participants With Bilateral Tubal Patency as Assessed by HSG -- Post DMPA Add Back COC HSG
Time frame: HSG on OC after DMPA
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG -- Post DMPA Add Back COC HSG | bilateral patent | 1 Participants |
| Follicular Phase HSG | Number of Participants With Bilateral Tubal Patency as Assessed by HSG -- Post DMPA Add Back COC HSG | blocked | 0 Participants |