Atonic Postpartum Hemorrhage: Blood Loss, Risk Factors, and Third Stage Management.

OBJECTIVE: Atonic postpartum hemorrhage rates have increased in many industrialized countries in recent years. We examined the blood loss, risk factors, and management of the third stage of labour associated with atonic postpartum hemorrhage. METHODS: We carried out a case-control study of patients in eight tertiary care hospitals in Canada between January 2011 and December 2013. Cases were defined as women with a diagnosis of atonic postpartum hemorrhage, and controls (without postpartum hemorrhage) were matched with cases by hospital and date of delivery. Estimated blood loss, risk factors, and management of the third stage labour were compared between cases and controls. Conditional logistic regression was used to adjust for confounding. RESULTS: The study included 383 cases and 383 controls. Cases had significantly higher mean estimated blood loss than controls. However, 16.7% of cases who delivered vaginally and 34.1% of cases who delivered by Caesarean section (CS) had a blood loss of < 500 mL and < 1000 mL, respectively; 8.2% of controls who delivered vaginally and 6.7% of controls who delivered by CS had blood loss consistent with a diagnosis of postpartum hemorrhage. Factors associated with atonic postpartum hemorrhage included known protective factors (e.g., delivery by CS) and risk factors (e.g., nulliparity, vaginal birth after CS). Uterotonic use was more common in cases than in controls (97.6% vs. 92.9%, P < 0.001). Delayed cord clamping was only used among those who delivered vaginally (7.7% cases vs. 14.6% controls, P = 0.06). CONCLUSION: There is substantial misclassification in the diagnosis of atonic postpartum hemorrhage, and this could potentially explain the observed temporal increase in postpartum hemorrhage rates.

Recombinant human luteinizing hormone to trigger ovulation: randomized, controlled, dose-finding pilot study in ovulation induction.

OBJECTIVE: To evaluate recombinant human luteinizing hormone (r-hLH) versus urine-derived human chorionic gonadotropin (u-hCG) to trigger ovulation in women (aged 20-40 years) with WHO Group II anovulatory infertility undergoing ovulation induction (OI) with recombinant human follicle-stimulating hormone (r-hFSH) (150 IU/day starting dose). STUDY DESIGN: For this Phase II, open-label, dose-finding pilot study, patients were randomized to doses of 825, 2,750, 5,500, 11,000, or 22,000 IU r-hLH or u-hCG (5,000 IU). Primary endpoints were ovulation and ratio of ruptured follicles/follicle > or = 15 mm (day of r-hLH/ u-hCG administration). Secondary endpoints included monofollicular ovulation and clinical pregnancy rates. RESULTS: All 67 randomized patients completed treatment. All patients in the r-hLH 2,750 (13/13), 5,500 (12/ 12), 11,000 IU (13/13), and u-hCG 5,000 IU (12/ 12) groups ovulated; 3/5 patients in the r-hLH 825 IU and 2/12 in the r-hLH 22,000 IU group failed to ovulate (p = 0.105 between evaluable groups). The mean ratio of ruptured follicles/ follicle > or = 15 mm was 1.1 (p = 0.675 between groups). The monofollicular ovulation rate was 15/60 (25%). Two cases of ovarian hyperstimulation syndrome were reported. CONCLUSION: This open-label, pilot study (conducted in 1999-2001) suggests that the minimal effective dose of r-hLH to trigger ovulation in women with WHO Group II anovulatory infertility undergoing OI with r-hFSH (150 IU starting dose) was 2,750 IU.

Effects of oral contraceptives administered at defined stages of ovarian follicular development.

OBJECTIVE: To elucidate the effects of initiating oral contraceptives (OC) at defined stages of ovarian follicle development. DESIGN: Prospective longitudinal study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Forty-five healthy women between the ages of 18 and 35 years, randomized to initiate OC when a follicle diameter of 10, 14, or 18 mm was first detected. INTERVENTION(S): The OC administration at defined stages of dominant follicle development. MAIN OUTCOME MEASURE(S): Fates of all dominant follicles and serum concentrations of E(2)-17beta, LH, and P before and after initiating OC. RESULT(S): No ovulations (0/16) were observed when OC use was initiated at a follicle diameter of 10 mm, 4/14 (29%) follicles ovulated when OC were initiated at 14 mm, and 14/15 (93%) ovulated when OC were initiated at 18 mm. When ovulation did not occur, follicles regressed or became anovulatory cysts. Peak LH and E(2) levels were lowest in the 10-mm group, moderate in the 14-mm group, and greatest in the 18-mm group. Peak endocrine levels in all treatment groups were lower than the historic reference group. CONCLUSION(S): Follicular development, ovulation, and endocrine concentrations were not suppressed effectively when OC were initiated at late stages of dominant follicle development.

Ovarian follicular dynamics during conventional vs. continuous oral contraceptive use.

OBJECTIVES: The purpose of this study was to characterize ovarian follicular and endometrial development during conventional vs. continuous oral contraceptive (OC) dosing regimens, to explore follicular development during the hormone-free interval (HFI) and to examine follicular development following OC discontinuation. STUDY METHODS: A randomized clinical trial involving 36 clinically normal healthy women between the ages of 18 and 35 years (24.4 +/- 3.9, SEM). Transvaginal ultrasonography and blood sampling were done to ascertain ovarian function. RESULTS: Fewer follicles > 4 mm developed during continuous vs. conventional OC use (p = .006). No dominant follicles developed during continuous OC use vs. eight dominant follicles (16.1 +/- 3.3 mm) during the conventional OC regimen. Two of eight (25%) dominant follicles ovulated. All dominant follicles began development during the HFI. Following discontinuation of OC use, ovulation took approximately 5 days longer when compared to natural cycles. CONCLUSION: Continuous OC regimens more effectively prevent dominant follicle development and breakthrough ovulation. The slight delay in time to ovulation following OC discontinuation and natural cycles could be attributed to suppression of follicle wave activity.

Ultrasound image attributes of human ovarian dominant follicles during natural and oral contraceptive cycles.

BACKGROUND: Computer-assisted analyses were used to examine ultrasound image attributes of human dominant ovarian follicles that developed during natural and oral contraceptive (OC) cycles. We hypothesized that image attributes of natural cycle follicles would quantitatively differ from those in OC cycles and that OC cycle follicles would possess image attributes indicative of atresia. METHODS: Dominant ovarian follicles of 18 clinically normal women were compared using transvaginal ultrasonography for the 7 days before ovulation during a natural cycle (n = 9) or the 7 days before peak estradiol in women using OC (n = 11). Follicles were analyzed using region and line techniques designed to compare the image attributes numerical pixel value (NPV), pixel heterogeneity (PH) and area under the curve (AUC). RESULTS: NPV was higher in OC cycle follicles with region analysis and tended to be higher with line analysis (p = 0.005 and p = 0.06, respectively). No differences were observed in two other image attributes (AUC and PH), measured with either technique, between natural and OC cycle follicles. CONCLUSION: The increased NPV value of OC cycle follicles and lack of differences in PH and AUC values between natural cycle and OC cycle follicles did not support the hypothesis that OC cycle follicles would show ultrasonographically detectable signs of atresia. Image attributes observed in OC cycle follicles were not clearly indicative of atresia nor were they large enough to preclude preovulatory physiologic status in OC cycle follicles.

Magnetic resonance diffusion imaging of ovarian masses: a first experience with 12 cases.

OBJECTIVE: The objective of the study was to determine the feasibility of using apparent diffusion coefficient (ADC) measurement for the differential diagnosis of malignancy in ovarian masses. MATERIALS AND METHODS: Twelve cases involving ovarian masses were imaged using spin echo diffusion magnetic resonance imaging (MRI). Five cases involved malignant ovarian masses, on the basis of postoperative histologic examination, and the rest involved benign masses. The ovarian masses were imaged in vivo (10 cases) before surgery and ex vivo (8 cases) after surgical resection. Diffusion-weighted data were corrected for motion using the phase data from unweighted data in nine cases. Multifactorial analysis of variance was used to evaluate the effects of malignancy, location (in vivo versus ex vivo), and motion correction on the measurement of ADC intensity and texture. RESULTS: Motion correction caused an undesirable spatial smoothing of the ADC maps and a significant interaction (p=0.047) was found between location and motion correction. ADC value (p=0.028) and texture (p=0.001) differences were found between malignant and nonmalignant ovarian masses. CONCLUSION: Measurement of ADC intensity and texture has the potential to differentially diagnose malignancy in individual ovarian masses if the problem of image motion artifact can be eliminated through the use of faster imaging sequences.

Curriculum reform for reproductive health.

A new model of reproductive health care delivery is unfolding, driven by emerging health issues, expanding technology and increasing public expectations. Additional imperatives in service provision for women's health compel reforms to undergraduate medical education using reproductive health as the basis for restructuring curriculum contents. These developments provide an opportunity for implementing the recommendations from various international conferences through continuing professional development and an evidence-based approach to clinical decision-making. A three-pronged approach based on reproductive health, problem-based learning and evidence-based medicine, has much potential for improving subsequent clinical practice and the overall reproductive health of the community. Appropriate changes to existing curricula will facilitate integration of the principles of reproductive health and the new philosophy of doctor-patient relationship into clinical supervision and training of students.