Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Effects of Aspirin in Gestation and Reproduction: A Multi-center, Controlled, Double-blind Randomized Trial.
Brief Summary: The primary objective of the study is to help elucidate the effects of low-dose aspirin in combination with folic acid on the incidence of live births and spontaneous abortions among a group of women who become pregnant compared to a control group.


Options:
A: Inclusion Criteria:

* Women experiencing one or two pregnancy losses at any point in gestation in the past that were not elective termination(s). At least one of these losses must be well documented by one of the following:

  * Sonogram demonstrating anembryonic loss, embryonic loss or fetal death.
  * Histologic confirmation of products of conception that were spontaneously passed per vagina or surgically obtained.
  * Hospital records of fetus delivery.
  * 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 3 days.
  * Home pregnancy tests without hCG confirmation from a healthcare provider (either serum or urine) will not be accepted.
* No more than 5 pregnancies in total including the pregnancy loss(es).\*
* Up to two prior pregnancies that did not end in a loss.\*

  \*Women may have up to two pregnancies beyond 20 weeks that were not losses, two spontaneous pregnancy losses at any time in the past, and up to one therapeutic or elective termination (two therapeutic or elective terminations if no other pregnancies). Ectopic and molar pregnancies would, for the purpose of enrollment, be considered in the same category as therapeutic termination pregnancies. Women with more than two live births or those with more than two losses, regardless of the week of gestation of the loss, are excluded.
* Presence of intact tubes (both), ovaries (both), and uterus.
* Between 18 and 40 years of age at time of baseline visit.
* Regular menstrual periods between 21 - 42 days in length (within the last 12 months). Regular menstrual periods are defined as no more than an 8-day difference between the woman's shortest and longest cycle.
* No more than one missed menses in the past 12 months (other than those missed due to pregnancy or breastfeeding).
* Actively trying to conceive with a male partner and not using contraception by the baseline visit.
* Not currently pregnant at the baseline or randomization visits.
* Ability and willingness to give informed consent.
* Willingness to be randomized and to take daily study pills for 6 months to a possible 15 months

Exclusions Criteria:

* Known allergies to aspirin or non-steroidal anti-inflammatory agents.
* Clinical indication for anticoagulant therapy. These include prior or current thrombosis, antiphospholipid syndrome (APS) or known major thrombophilia.
* Clinical indication for chronic use of NSAIDs such as rheumatoid arthritis.
* Indication for additional folic acid supplementation, such as prior infant with neural tube defect (NTD), seizure disorder.
* Medical contraindication to aspirin therapy. These include uncontrolled asthma, nasal polyps, bleeding disorders, or history of gastrointestinal ulcer.
* Presence of major medical disorders (regardless of severity). These include diabetes, hypertension, systemic lupus erythematosus (SLE), untreated or active cancer (any cancer in remission or non-melanoma skin cancer is not included in the exclusion criteria), liver disease, renal disease, rheumatoid arthritis, cardiac disease, pulmonary disease other than mild asthma, neurologic disease requiring medical treatment, uncontrolled hypothyroidism, uncontrolled seizure disorder. Untreated vitamin B12 deficiency, severe anemia (Hct \< 30%), hemophilia, gout, nasal polyps, among others.
* Currently undergoing/planned use of assisted reproductive techniques during trial (IVF; IUI; Clomid).
* History of infertility or sub-fertility. This includes any of the following:

  * No conception after ≥ 1 year of unprotected intercourse and actively trying to conceive.
  * Any prior medical treatment for infertility.
  * Prior treatment for known pelvic inflammatory disease.
  * Known male infertility or sperm abnormality (current partner).
  * Known tubal occlusion, anovulation, uterine abnormality, or endometriosis stage III or IV.
  * History of polycystic ovarian syndrome.
* Presence of unstable mental disorder. These include bipolar illness, schizophrenia, uncontrolled depression, uncontrolled anxiety disorder.
* Known current or recent alcohol abuse or illicit drug use.
* Current diagnosis of sexually transmitted infection (STI) (temporary exclusion)
B: Inclusion Criteria:

* Single pregnancy, 5th to 8th week of gestation
* Documented foetal heart activity in US
* History of recurrent pregnancy loss, defined as:

  * 2 or more early (\< 12 weeks of gestation) pregnancy losses or
  * 1 or more late (\> 12 weeks of gestation) pregnancy loss
* at least 18 years of age
* Written informed consent of the patient

Exclusion Criteria:

* Previous pregnancy losses caused by foetal structural or chromosomal anomalies
* Uterine anomalies
* Maternal infection which caused previous pregnancy loss
* Risk group II or III according to ETHIG I risk stratification (clinical need for heparin prophylaxis)
* Acute thromboembolic event (need of heparin therapy)
* Known hypersensitivity to any of the trial drugs or its ingredients (i.e. thrombocytopenia type II caused by allergic reaction to heparin)
* Antiphospholipid antibody syndrome
* Diabetes mellitus
* Ongoing nicotine or drug or alcohol abuse
* Known HIV infection
* Expected low compliance (e.g. by travel distance to trial site)
* Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial
C: Inclusion Criteria:

1. All women with recurrent first-trimester miscarriage and all women with one or more second-trimester miscarriage who screened before pregnancy for antiphospholipid antibodies.
2. To diagnose antiphospholipid syndrome it is mandatory that the woman has two positive tests at least 12 weeks apart for either lupus anticoagulant or anticardiolipin antibodies of immunoglobulin G and/or immunoglobulin M class present in a medium or high titre over 40 g/l or ml/l,or above the 99th percentile).

In the detection of lupus anticoagulant, the dilute Russell's viper venom time test together with a platelet neutralisation procedure is more sensitive and specific than either the activated partial thromboplastin time test or the kaolin clotting time test. Anticardiolipin antibodies are detected using a standardised enzyme linked immunosorbent assay.

Exclusion Criteria:

1. Age above forty years old .
2. Intrauterine abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram, or hysteroscopy).
3. Fibroids distorting uterine cavity .
4. Abnormal parental karyotype .
5. Other identifiable causes of recurrent miscarriages (tests initiated only if clinically indicated) e.g., diabetes, thyroid disease and systemic lupus erythematosus (SLE).
D: Inclusion Criteria:

* Couple has a history of unexplained secondary recurrent miscarriage.
* Most recent pregnancy occurred within one year of discontinuing contraception.

Exclusion Criteria:

* Maternal IgA deficiency
* Maternal history of immunoglobulin hypersensitivity.
* Maternal contraindication to pregnancy.
* Evidence of active hepatitis or immunocompromised state in either partner.
* Concomitant use of medication(s) for treatment of recurrent miscarriage, such as but not limited to progesterone, clomiphene citrate, acetylsalicylic acid, heparin, glucocorticoids or hCG injections.

Answer: A