Gestational hormone trajectories and early pregnancy failure: a reassessment.

BACKGROUND: Studies have commonly assessed the endocrinolgical status of women once miscarriage is threatened or suspected; few studies have explored the antecedent hormonal environment or used a longitudinal strategy. Using refined statistical techniques, we sought to re-evaluate whether gestational hormone trajectories in early pregnancy can identify future miscarriage in asymptomatic pregnancies. METHODS: This prospective cohort study followed 105 women over-conception; 72 had normal term pregnancy outcomes while 33 experienced early pregnancy failure between 35 and 115 days of gestation. Participants attended a pre-conception and antenatal clinic at Newcastle University, United Kingdom (UK). Evaluation methods included ultrasound, clinical assessments of pregnancy progress and serial measurements of gestational hormones by radioimmunoassays. Linear mixed-effects regression analysis examined hormone relationships with pregnancy outcomes. RESULTS: Detailed longitudinal illustration of gestational hormones, antecedent to miscarriage indications, revealed early pathophysiological trends. In particular, oestradiol showed as marked a deviation from normal as progesterone before miscarriage was evident, reflecting a deficiency in the ovarian response to rising human chorionic gonadotrophin (hCG) levels. Regression analysis provided equations for gestational hormone slopes that significantly differentiated asymptomatic women with subsequent early pregnancy failure, compared to women with normal term pregnancies. Both progesterone and oestradiol displayed negative mean slopes in pregnancies destined for failure; in this group, both human placental lactogen (hPL) and hCG revealed mean positive trajectories that imitated normal pregnancies but at slower rates of increase. CONCLUSIONS: Oestradiol, progesterone and hCG trajectories, from 50 days of gestation, have good potential for revealing pathophysiology and for identifying which asymptomatic pregnancies are destined for subsequent failure. In asymptomatic patients where there is concern about viability and ultrasound diagnosis is ambiguous, a combined hormonal profile could contribute to guiding patient care decisions.

Treatment Decisions at the Time of Miscarriage Diagnosis.

OBJECTIVE: To describe the factors patients and physicians prioritize during first-trimester miscarriage management and assess what drives satisfaction with care. METHODS: We conducted a mixed-methods study of clinically stable women seeking surgical, medical, or expectant miscarriage treatment. Women with first-trimester fetal demise or anembryonic gestation (N=55) completed demographic and psychosocial surveys. Using purposive sampling, 45 (82%) completed in-depth interviews. Fifteen obstetricians were interviewed. Participants described factors that informed their counseling (physicians) or decision-making (patients). Content analysis used an integrated approach with inductively and deductively derived codes. Patient-derived themes were stratified by treatment choice. Associations between variables and treatment choices were analyzed. RESULTS: Thirty-four women (62%) received surgical management, 19 (35%) received medical, and two (4%) received expectant. Physicians expected that women with prior pregnancies have strong management preferences, and indeed, multigravid patients were less likely to change their initial treatment choice after counseling than primigravid patients (12% compared with 42%, odds ratio [OR] 0.18, 95% confidence interval [CI] 0.04-0.81, P=.03). Physicians favored patient-centered decisions and patients chose the treatment that they thought would least affect other responsibilities. Those ultimately receiving surgical management had a higher monthly income (adjusted OR 1.30, 95% CI 1.04-1.63, P=.023) and more social support (adjusted OR 2.45, 95% CI 1.07-5.61, P=.035) than the medical group. The surgical group cited loss acceptance, a favorable perception of surgery, and a desire to expedite the miscarriage as decisive factors. The medical group endorsed control over, and timed completion of, the miscarriage in a more intimate setting, an aversion to surgery or anesthesia, and a perception of improved fertility preservation as decisive factors. Regardless of treatment choice, satisfaction with treatment was linked to a supportive clinical team and expeditious resolution. CONCLUSION: Prior pregnancy experiences, obligations, and sociodemographic factors influence miscarriage management decision-making. Structured counseling, especially for primigravid patients, could improve both the physician and the patient experience with miscarriage care.

Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes.

BACKGROUND: Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. OBJECTIVE: This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. STUDY DESIGN: A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. RESULTS: In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P < .001, P = .011, P < .001, and P = .035, respectively). Women had similar initial human chorionic gonadotropin levels in either protocol but the mean rate of decline of human chorionic gonadotropin from day 0 (day of administration of first dose of methotrexate) to day 7 was significantly more rapid in women who received the single-dose protocol compared to those treated with the 2-dose protocol (mean change -31.3% vs -10.4%, P = .037, adjusted for propensity score and site). The 2 protocols had no significant differences in success rate or time to resolution. CONCLUSION: In a racially and geographically diverse group of women, the single- and double-dose methotrexate protocols had comparable outcomes. The more rapid human chorionic gonadotropin initial decline in the single-dose group suggested these patients were probably at lower risk for ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication.

Abnormal relaxin secretion during pregnancy in women with type 1 diabetes.

To test the hypothesis that relaxin may play a role in the fetal abnormalities associated with pregnancy in type 1 diabetic women, we previously compared gestational relaxin concentrations in diabetic and clinically normal women using a porcine relaxin radioimmunoassay (RIA): Serum immunoactive relaxin was significantly (P < 0.001) elevated in the diabetic women. To confirm and extend this work in a larger group of subjects, we have now used an enzyme-linked immunosorbent assay (ELISA) specific for human H2 relaxin (the normal human gene product) to determine immunoactive serum relaxin concentrations in serial samples from 61 Type 1 diabetic and 21 normal pregnant women. Samples from 22 of the diabetic and nine of the normal women were also directly compared in the porcine relaxin RIA. ELISA-determined serum relaxin was higher (P < 0.001) at 24 and 36 weeks of pregnancy in type 1 diabetic women than in controls, confirming previous findings. However, the geometric mean increase in immunoactive relaxin concentration in identical samples from pregnant diabetic women over that of controls was significantly greater with the RIA than with the ELISA (271% vs 44%; P < 0.001). To investigate this discrepancy, the specificity and epitope selectivity of the RIA and the ELISA were compared using several synthetic polypeptides, including human relaxins H1 and H2, and relaxin and insulin derivatives. Both assays showed great specificity, but the porcine RIA selectively identified the epitopes of the receptor-binding domain of the relaxin B chain and cross-reacted strongly with H1 and H2 relaxins. In contrast, only the H2 peptide was detected by the ELISA antiserum. Therefore, the marked discrepancy between the RIA and the ELISA could be due to the presence in the diabetic samples of another relaxin-like molecule in addition to the normal H2 relaxin. The biological consequences of elevated serum relaxin in diabetic pregnancy remain to be elucidated.