Relationship Between Plasma Concentration of Hydroxyprogesterone Caproate (17-OHPC) and Preterm Birth

1. Randomized Clinical Trial Eligibility Criteria: Inclusion Criteria: * pregnant with a prior preterm birth 16 0/7-35 6/7 weeks from spontaneous labor or preterm premature rupture of membranes(PPROM), * current gestational age \<22 weeks, * pregnant with one baby * age between 18-45 years * able to give consent and undergo study procedures Exclusion Criteria: * plans for cerclage at enrollment, plan for progesterone treatment other than study medications at enrollment * known fetal anomaly or chromosomal anomaly that could affect gestational age at delivery * malformation of the uterus or known cervical length \<2.5cm * participation in another trial that may affect gestational age at delivery * planned delivery where outcome data cannot be collected * medical or obstetrical complication that may affect gestational age at delivery, such as active ulcerative colitis, liver tumors, liver disease/failure, renal disease/failure, undiagnosed vaginal bleeding unrelated to pregnancy, or hypertension requiring 2 or more agents * Current or history of thrombosis or thromboembolic disorders * known or suspected breast cancer, other hormone-sensitive cancer, or a history of these conditions * moderately severe depression (PHQ-9 score ≥ 15, EPDS score of \>13, or suicidal ideation) 2. Ancillary Cohort Eligibility Criteria: Inclusion Criteria: * Pregnant female with documented prior birth between 16 0/7- 35 6/7 week gestation from spontaneous preterm labor or preterm premature rupture of membranes * Receiving 250 mg 17-OHPC weekly- must be compliant with that treatment based on interview and reviewing the medical record * Gestational age (GA) \<26 weeks, based on study determined GA * Singleton gestation * Age between 18 - 45 years * Able to give informed consent and undergo study procedures Exclusion Criteria: * Inclusion in the RCT of 250 vs 500 mg OPRC study * Cerclage in place * Plan for progesterone treatment other than study medication * Known major fetal anomaly or chromosomal anomalies that might affect gestational age at delivery * Malformation of uterus (uterine didelphus, septate uterus or bicornuate uterus) or known cervical length \<2.5 cm * Participation in another trial that may affect gestational age at delivery * Planned delivery at other institution where pregnancy outcome data cannot be obtained * Medical or obstetrical complication that might affect gestational age at delivery, such as active ulcerative colitis, liver tumors, liver disease/failure, renal disease/failure, undiagnosed vaginal bleeding unrelated to pregnancy, or hypertension requiring 2 or more agents * Current or history of thrombosis or thromboembolic disorder. * Known or suspected breast cancer, other hormone-sensitive cancer, or a history of these conditions. * Moderately severe depression (PHQ-9 score ≥15, EPDS score of \>13, or suicidal ideation)- based on criteria in the RCT