Quickvue

The primary outcome of interest was live birth. Secondary outcomes included hCG pregnancy and pregnancy losses. hCG pregnancies were identified via (i) a positive result on a “real-time” urine pregnancy test (Quidel Quickvue, Quidel Corporation, San Diego, CA), sensitive to 25 mIU/ml hCG, conducted at home or any study visit during expected menses; and (ii) batched urine hCG testing performed after study completion on stored samples from the last 10 days of each woman’s first and second cycle (n=21 additional pregnancies detected).(11 (link)) Pregnancy losses were defined as a 1) positive urine hCG pregnancy test at home or the clinical site followed by absence of signs of clinical pregnancy at the study ultrasound; 2) positive hCG from batched augmented urine testing followed by the absence of a positive pregnancy test at home or in the clinic (11 (link)); or 3) loss after ultrasound confirmation. Live birth was defined as a live born infant as indicated on the medical record.

At enrollment, participants self-reported information on age, parity, race, marital status, household income, educational attainment, cigarette smoking and reproductive history, including prior pregnancies affected by preeclampsia. Weight and height were obtained at enrollment and used to calculate pre-pregnancy body mass index (BMI). Pregnancy status was assessed at the end of each menstrual cycle using at-home and in-clinic human chorionic gonadotropin (hCG) tests (Quidel Quickvue, Quidel Corporation, San Diego, CA, sensitive to 25 IU/ml hCG). Additional undetected pregnancies (n=21) were detected by laboratory measures of hCG in daily stored urine samples.¹⁶ Pregnancy losses were identified as absence of clinical signs of pregnancy following positive hCG test. Hypertension in pregnancy, birthweight, gestational age at delivery, gestational diabetes, preterm birth, and neonatal intensive care unit (NICU) admission were abstracted from medical records.

We assessed pregnancy at the end of each menstrual cycle with at-home and/or in-clinic human chorionic gonadotropin testing (Quidel Quickvue, Quidel Corporation, San Diego, CA, sensitive to 25 mIU/ml human chorionic gonadotropin). Additionally, β-human chorionic gonadotropin was assessed in stored first-morning urines collected during the last 10 days of the first two cycles and at all end of cycle visits to augment early pregnancy detection (catalogue no. 4221–16, Diagnostic Automation Inc, Calabasa, CA and catalogue no. R1S0011R, BioVendor, Asheville, NC). We assessed menstrual cycle-specific probability of pregnancy as time-to-pregnancy, the number of menstrual cycles from randomization to either positive pregnancy test or censoring. Pregnancy loss included both early losses and clinically recognized losses. Early losses were identified where a positive pregnancy test was followed by absence of clinical signs of pregnancy and clinical losses where a clinically confirmed pregnancy on ultrasound at approximately 6.5 weeks was followed by a participant- or clinician-observed loss.

The primary outcome in this analysis was pregnancy loss, subcategorized by timing of loss as clinical pregnancy loss or subclinical pregnancy loss. Pregnancies were confirmed by gestational sac on ultrasound, clinical recording of fetal heart tones, or a later-stage confirmatory sign. Clinically recognized pregnancy loss was defined as a pregnancy loss of a confirmed pregnancy occurring by 20 weeks’ gestation and included a small number of ectopic pregnancies that were observed (8 (link), 10 (link)).
Subclinical pregnancy losses were identified in two ways: first, a positive urine pregnancy test at the clinical site (Quidel Quickvue, Quidel Corporation, sensitive to 25 mIU/mL hCG) followed by the absence of signs of clinical pregnancy, with or without missed menses; second, using batched augmented urine hCG testing that was performed later in the laboratory on the last 10 days of each woman’s first and second cycle of study participation (using daily first-morning urine collected at home) and on spot urine samples collected at all postcycle visits. Overall pregnancy loss was defined as either clinically recognized loss or hCG detected loss (10 (link)).

Detection of an hCG pregnancy was defined as a positive result on a urine pregnancy test sensitive to hCG level of 25 mIU/ml (Quidel Quickvue, Quidel Corporation, San Diego, CA). These urine hCG pregnancy tests were conducted at home or at the clinic if a participant reported a missed menses. In addition to the urine hCG tests, free beta hCG was measured in daily first-morning urine collected at home from the last 10 days of each woman's first and second menstrual cycle of study participation, and on spot urine samples collected at study visits timed to coincide with day 2-4 of the expected next menstrual cycle to enable a more sensitive detection of very early pregnancy. Two laboratory assays for free beta hCG (initial test: catalogue no. RIS0011R, BioVendor, Asheville, NC, USA; confirmatory test: catalogue no. 4221-16, Diagnostic Automation Inc., Calabasas, CA, USA) were sequentially utilized to identify 21 additional pregnancies that were verified as very early positive tests for hCG detected pregnancy. An hCG detected loss was defined as the detection of an hCG pregnancy followed by the absence of signs of clinical pregnancy and ensuing menses.

We assessed fecundability, the per-cycle probability of pregnancy, as time to pregnancy (TTP), which was measured as the discrete number of menstrual cycles required to achieve human chorionic gonadotropin (hCG) pregnancy for up to six menstrual cycles of consecutive follow-up (42 ). Pregnancies were ascertained via positive urine hCG pregnancy tests (Quidel Quickvue, Quidel Corporation), conducted at home at the time of expected menses or in scheduled clinic visits at the time of expected menses during each cycle of follow-up. Free β-hCG was also measured to detect early pregnancies using batched augmented testing on daily first-morning urine collected over the first two cycles of follow-up and on spot urine samples from monthly clinic visits. This protocol was devised to enable more sensitive detection of pregnancy over follow-up. Samples were analyzed via sequential laboratory assays for free β-hCG (initial test: Catalog #: RIS0011R, BioVendor, Asheville, NC; confirmatory test: catalog #4221-16, Diagnostic Automation Inc., Calabasas, CA). Pregnancies lasting 6-7 weeks gestation were confirmed via ultrasound. Date of delivery and live birth were obtained by postpartum phone interview and medical chart abstraction.