Status:Active, not recruiting
Keywords:Miscarriage
, Pregnancy
IRB Number:00021732
Specialty:Maternal-Fetal Medicine
Sub Specialty:
Human reproduction is a remarkable but inefficient process. Maximally fertile couples have only an approximately 30 percent chance of conception in a given menstrual cycle, and average monthly fecundity is 20%. Successful conception does not guarantee a live birth. Estimates of miscarriages and early pregnancy loss vary and range between about 15 to 31%. Available data suggest that low dose aspirin (LDA) has the potential to favorably impact on several aspects of reproduction including conception, implantation, early pregnancy loss, late fetal death, preeclampsia, small for gestational age fetus, placental insufficiency and preterm birth. LDA is an ideal therapy; it is apparently safe, widely available, has few maternal side effects, and is inexpensive. It is unclear which patients would benefit from LDA. Prior studies have focused on narrow aspects of the effect of LDA such as IVF outcome or the development of preeclampsia. Reproduction is unique in that each stage is inextricably linked. Better blood flow at the time of conception and implantation may ultimately lead to improved placental function, and a reduced risk of preeclampsia, SGA, and preterm birth.
Unanswered questions about LDA and pregnancy can best be answered through a comprehensive, carefully designed, prospective randomized clinical trial. Observational epidemiological studies of endpoints such as these are often limited in their ability to properly evaluate implantation and early pregnancy loss as this requires a very careful daily monitoring of hormonal levels based on collection of daily samples of first morning urine, necessitating both a very committed population and a well designed system to help women to comply with this demanding regimen.
Women who have experienced a miscarriage in the last year and desiring another pregnancy will be enrolled. They will be randomized to one of two groups: 1) folic acid and low-dose aspirin or 2) folic acid and placebo. This will be taken daily for at least two months or throughout a pregnancy if she is successful at getting pregnant. Blood and urine samples (most urine samples collected at home) will be collected at various points during the study. Outcome data, maternal blood, cord blood, and placental samples will be collected. If a woman experiences a miscarriage, products of conception will be evaluated.
Principle Investigator: Bob Silver
Principle Department: Obstetrics And Gynecology (Dept)
Co Investigator:
Name:Laurie Lesher
Phone:801-581-4128
Email:laurie.lesher@hsc.utah.edu
Inclusion Criteria:
1. Women experiencing one or two pregnancy losses. At least one loss must be well documented by one of the following:
a. Sonogram demonstrating anembryonic loss, embryonic loss or fetal death.
b. Histologic confirmation of products of conception that were spontaneously passed per vagina or surgically obtained.
c. Late menses and positive serum hCG or positive urine hCG documented by hospital or clinic records. Followed by either a negative hospital/clinic pregnancy test or a decline in urinary hCG level over three days.*
2. No more than two prior pregnancies greater than 20 weeks gestation.**
3. No more than two pregnancy losses
4. No more than five total pregnancies, including the pregnancy losses.
5. Presence of intact tubes (both), ovaries(both), and uterus.
6. Between 18 and 40 years of age at time of baseline visit.
7. Regular menstrual periods between 21 – 42 days in length (within the last 12 months). Regular menstrual periods are defined as no more than an eight day difference between a women’s shortest and longest cycle.
8. No more than one missed menses in the past 12 months (other than those missed due to the previous pregnancy or breastfeeding).
9. Actively trying to conceive with a male partner and not using contraception.
10. Not currently pregnant at the baseline or randomization visits.
11. Ability and willingness to give informed consent.
12. Willingness to be randomized and to take daily study pills for six months and a possible 15 months.
13. Willingness to be randomized and to take daily study pills for six months and a possible 15 months.
*See protocol for more information.
** See protocol for more information.
Exclusion Criteria:
1. Known allergies to aspirin or non-steroidal anti-inflammatory agents.
2. Clinical indication for anticoagulant therapy. These include prior or current thrombosis, antiphospholipid syndrome (APS) or known major thrombophilia.
3. Clinical indication for chronic use of NSAIDs such as rheumatoid arthritis.
4. Indication for additional folic acid supplementation, such as prior infant with neural tube defect (NTD) or seizure disorder.
5. Medical contraindication to aspirin therapy. These include uncontrolled asthma, nasal polyps, bleeding disorders, or history of gastrointestinal ulcer.
6. Presence of major medical disorders (regardless of severity). These include diabetes, hypertension, systemic lupus erythematosus (SLE), untreated or active cancer, any prior history of cancer, liver disease, renal disease, rheumatoid arthritis, cardiac disease, pulmonary disease other than mild asthma, neurologic disease requiring medical treatment, hyperthyroidism, hypothyroidism, seizure disorder requiring use of anticonvulsant medications, Untreated vitamin B12 deficiency, severe anemia (Hct < 30%), hemophilia, gout, nasal polyps, among others.
7. Currently undergoing/planned use of assisted reproductive techniques during trial (IVF; IUI; Clomid)
8. History of infertility or sub-fertility. This includes any of the following:
8a. No conception after ≥ 1 year of unprotected intercourse and actively trying to conceive.
8b. Any prior medical treatment for infertility.
8c. Prior treatment for known pelvic inflammatory disease.
8d. Known male infertility or sperm abnormality (current partner), tubal occlusion, anovulation, uterine abnormality, or endometriosis.
8e. History of polycystic ovarian syndrome.
9. Presence of unstable mental disorder. These include bipolar illness, schizophrenia, uncontrolled depression, uncontrolled anxiety disorder.
10. Known current or recent alcohol abuse or illicit drug use.
11. Current diagnosis of sexually transmitted infection (STI) (temporary exclusion).
