Quantitative differences in TGF-β family members measured in small antral follicle fluids from women with or without PCO

CONTEXT: Members of the Transforming-Growth-Factor-β (TGF-β) family have been implicated in aberrant follicle development in women with polycystic ovaries (PCO). OBJECTIVE: Are there quantitative differences in the concentrations of TGF-β family members in fluid from small antral follicles (hSAF) from women with or without PCO? DESIGN SETTING: & Follicle fluids (FF) were collected from 4-11 mm hSAF obtained from women undergoing ovarian tissue cryopreservation for fertility preservation. PATIENTS: FFs from 16 women with PCO (FF=93) and 33 women without PCO (FF=92). MAIN OUTCOME MEASURES: Intrafollicular concentrations of Growth-Differentiation-Factor-9 (GDF9), Anti-Müllerian-Hormone (AMH), inhibin-A and -B, total inhibin, activin-A, -B and -AB, follistatin, follistatin-like-3, estradiol, and testosterone. RESULTS: Activin-B concentrations are reported for the first time in hSAF and concentrations were 10 times higher than activin-A and -AB. Activin-B showed significant associations to other growth factors. Concentrations of inhibin-A and -B were significantly lower in FF from women with PCO, especially in hSAF below 8 mm in diameter. AMH concentrations did not differ between the groups in hSAF below 8 mm, however, AMH remained high in hSAF above 8 mm in PCO but decreased in non-PCO women. Estradiol was significantly lower in FF from women with PCO and showed significant associations with AMH. Concentrations of GDF9 are reported for the first time showing significantly higher concentrations in PCO FF of follicles above 6 mm. CONCLUSIONS: Altered concentrations of TGF-β family members in hSAF from women with PCO highlight altered growth factor signaling as a potential mechanism for follicle growth arrest

Management of major obstetric hemorrhage prior to peripartum hysterectomy and outcomes across nine European countries

Introduction Peripartum hysterectomy is applied as a surgical intervention of last resort for major obstetric hemorrhage. It is performed in an emergency setting except for women with a strong suspicion of placenta accreta spectrum (PAS), where it may be anticipated before cesarean section. The aim of this study was to compare management strategies in the case of obstetric hemorrhage leading to hysterectomy, between nine European countries participating in the International Network of Obstetric Survey Systems (INOSS), and to describe pooled maternal and neonatal outcomes following peripartum hysterectomy. Material and methods We merged data from nine nationwide or multi-regional obstetric surveillance studies performed in Belgium, Denmark, Finland, France, Italy, the Netherlands, Slovakia, Sweden and the UK collected between 2004 and 2016. Hysterectomies performed from 22 gestational weeks up to 48 h postpartum due to obstetric hemorrhage were included. Stratifying women with and without PAS, procedures performed in the management of obstetric hemorrhage prior to hysterectomy between countries were counted and compared. Prevalence of maternal mortality, complications after hysterectomy and neonatal adverse events (stillbirth or neonatal mortality) were calculated. Results A total of 1302 women with peripartum hysterectomy were included. In women without PAS who had major obstetric hemorrhage leading to hysterectomy, uterotonics administration was lowest in Slovakia (48/73, 66%) and highest in Denmark (25/27, 93%), intrauterine balloon use was lowest in Slovakia (1/72, 1%) and highest in Denmark (11/27, 41%), and interventional radiology varied between 0/27 in Denmark and Slovakia to 11/59 (79%) in Belgium. In women with PAS, uterotonics administration was lowest in Finland (5/16, 31%) and highest in the UK (84/103, 82%), intrauterine balloon use varied between 0/14 in Belgium and Slovakia to 29/103 (28%) in the UK. Interventional radiology was lowest in Denmark (0/16) and highest in Finland (9/15, 60%). Maternal mortality occurred in 14/1226 (1%), the most common complications were hematologic (95/1202, 8%) and respiratory (81/1101, 7%). Adverse neonatal events were observed in 79/1259 (6%) births. Conclusions Management of obstetric hemorrhage in women who eventually underwent peripartum hysterectomy varied greatly between these nine European countries. This potentially life-saving procedure is associated with substantial adverse maternal and neonatal outcome.</p

Lessons learnt from anonymized review of cases of peripartum hysterectomy by international experts: A qualitative pilot study

Severe obstetric complications are not extensively studied and individual cases are used too little and inappropriately in quality improvement activities, due to limited numbers and prioritization of quantitative research. Nordic and European experts performed a qualitative pilot study using anonymized cases of peripartum hysterectomy. It was feasible to anonymize narratives and we learned lessons in the form of themes for improved clinical care and future research. Therefore, we plan a Nordic anonymized review of the care of women who have undergone peripartum hysterectomy based on narratives. The qualitative outcomes of clinically relevant themes for quality improvement and research will add value to the quantitative analyses from the Nordic medical birth registries. In the longer term, we believe that qualitative audits should be essential part of the process of continuing improvement in maternity care. This article is protected by copyright. All rights reserved

Epidemiological analysis of peripartum hysterectomy across 9 European countries

Introduction Peripartum hysterectomy is a surgical procedure performed for severe obstetric complications such as major obstetric hemorrhage. The prevalence of peripartum hysterectomy in high‐resource settings is relatively low. Hence, international comparisons and studying indications and associations with mode of birth rely on the use of national obstetric survey data. Objectives were to calculate the prevalence and indications of peripartum hysterectomy and its association with national cesarean section rates and mode of birth in nine European countries. Material and methods We performed a descriptive, multinational, population‐based study among women who underwent peripartum hysterectomy. Data were collected from national or multiregional databases from nine countries participating in the International Network of Obstetric Survey Systems. We included hysterectomies performed from 22 gestational weeks up to 48 hours postpartum for obstetric hemorrhage, as this was the most restrictive, overlapping case definition between all countries. Main outcomes were prevalence and indications of peripartum hysterectomy. Additionally, we compared prevalence of peripartum hysterectomy between women giving birth vaginally and by cesarean section, and between women giving birth with and without previous cesarean section. Finally, we calculated correlation between prevalence of peripartum hysterectomy and national cesarean section rates, as well as national rates of women giving birth after a previous cesarean section. Results A total of 1302 peripartum hysterectomies were performed in 2 498 013 births, leading to a prevalence of 5.2 per 10 000 births ranging from 2.6 in Denmark to 10.7 in Italy. Main indications were uterine atony (35.3%) and abnormally invasive placenta (34.8%). Relative risk of hysterectomy after cesarean section compared with vaginal birth was 9.1 (95% CI 8.0‐10.4). Relative risk for hysterectomy for birth after previous cesarean section compared with birth without previous cesarean section was 10.6 (95% CI 9.4‐12.1). A strong correlation was observed between national cesarean section rate and prevalence of peripartum hysterectomy (ρ = 0.67, P < .05). Conclusions Prevalence of peripartum hysterectomy may vary considerably between high‐income countries. Uterine atony and abnormally invasive placenta are the commonest indications for hysterectomy. Birth by cesarean section and birth after previous cesarean section are associated with nine‐fold increased risk of peripartum hysterectomy