Evidence around early induction of labor in women of advanced maternal age and those using assisted reproductive technology.

Worldwide, there has been a trend toward later motherhood. Concurrently, the incidence of subfertility has been on the rise, necessitating conception using assisted reproductive technologies (ARTs). These pregnancies are considered high risk due to fetal complications such as antepartum stillbirth and growth restriction and maternal complications such as increase in maternal morbidity and mortality. Early induction of labor can help to mitigate these risks. However, this has to be balanced against the iatrogenic harms of earlier delivery to both the baby, including respiratory distress and NICU stay, and the mother who might experience longer labor and other complications such as uterine hyperstimulation. Induction of labor at 39 weeks is the optimal timing for preventing antepartum stillbirth and avoiding iatrogenic harm. Delivery by elective cesarean section is not advocated as its benefits in these patients are unclear compared with the short- and long-term complications of a major abdominal surgery.

Evaluating the influence of progesterone concentration and time of exposure on in vitro endometrial decidualisation.

This study aimed to evaluate the influence of progesterone (concentration and time of exposure) on endometrial decidualisation using an in vitro model cell line: Human Endometrial Stromal Cells (HESCs). HESCs exposed to progesterone (1 and 10 µM) had higher percentages of decidualised cells and higher expression of the decidual marker (Insulin Like Growth Factor Binding Protein 1 (IGFBP1)) compared with those exposed to (0.1 µM). Among those HESCs cultured with 1 µM progesterone for 11 days, the highest rate of morphological differentiation (40-50%) occurred between days 7-9 and IGFBP1 peaked on day 7. The cell-cycle pathway was significantly down-regulated in HESCs exposed to at least 1 µM progesterone regardless of the incubation period. We conclude that exposure to high progesterone concentration for 7-9 days is essential to maximise the process of decidualisation.

Pharmacological interventions for treating intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build-up of bile acids in the maternal blood. It has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been largely empiric. As ICP is an uncommon condition (incidence less than 2% a year), many trials have been small. Synthesis, including recent larger trials, will provide more evidence to guide clinical practice. This review is an update of a review first published in 2001 and last updated in 2013. OBJECTIVES: To assess the effects of pharmacological interventions to treat women with intrahepatic cholestasis of pregnancy, on maternal, fetal and neonatal outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials, including cluster-randomised trials and trials published in abstract form only, that compared any drug with placebo or no treatment, or two drug intervention strategies, for women with a clinical diagnosis of intrahepatic cholestasis of pregnancy. DATA COLLECTION AND ANALYSIS: The review authors independently assessed trials for eligibility and risks of bias. We independently extracted data and checked these for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 26 trials involving 2007 women. They were mostly at unclear to high risk of bias. They assessed nine different pharmacological interventions, resulting in 14 different comparisons. We judged two placebo-controlled trials of ursodeoxycholic acid (UDCA) in 715 women to be at low risk of bias. The ten different pharmacological interventions were: agents believed to detoxify bile acids (UCDA) and S-adenosylmethionine (SAMe); agents used to bind bile acids in the intestine (activated charcoal, guar gum, cholestyramine); Chinese herbal medicines (yinchenghao decoction (YCHD), salvia, Yiganling and Danxioling pill (DXLP)), and agents aimed to reduce bile acid production (dexamethasone) Compared with placebo, UDCA probably results in a small improvement in pruritus score measured on a 100 mm visual analogue scale (VAS) (mean difference (MD) -7.64 points, 95% confidence interval (CI) -9.69 to -5.60 points; 2 trials, 715 women; GRADE moderate certainty), where a score of zero indicates no itch and a score of 100 indicates severe itching. The evidence for fetal distress and stillbirth were uncertain, due to serious limitations in study design and imprecision (risk ratio (RR) 0.70, 95% CI 0.35 to 1.40; 6 trials, 944 women; RR 0.33, 95% CI 0.08 to 1.37; 6 trials, 955 women; GRADE very low certainty). We found very few differences for the other comparisons included in this review. There is insufficient evidence to indicate if SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with intrahepatic cholestasis of pregnancy. AUTHORS' CONCLUSIONS: When compared with placebo, UDCA administered to women with ICP probably shows a reduction in pruritus. However the size of the effect is small and for most pregnant women and clinicians, the reduction may fall below the minimum clinically worthwhile effect. The evidence was unclear for other adverse fetal outcomes, due to very low-certainty evidence. There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, YCHD, DXLP, Salvia, Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy. There are no trials of the efficacy of topical emollients. Further high-quality trials of other interventions are needed in order to identify effective treatments for maternal itching and preventing adverse perinatal outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA).

The risks of a range of maternal pregnancy choices, expressed as "baby micromorts" (risk of death per million births).

OBJECTIVE: To present the risks of baby death from various maternal choices on a common scale. DESIGN: Review of published data. METHODS: Mortality calculated as the attributable risk per activity, expressed in "baby micromorts", the number of one in a million chances of the baby dying. RESULTS: Amniocentesis and chorionic villous sampling carry procedure related risks of 9142 (-600 to 19,000) and 37,902 (23,302 to 52,502) micromorts respectively. Smoking carries a risk of 0.21 micromorts per cigarette or 300 micromorts for a woman smoking 5/day throughout pregnancy. Drinking a unit of alcohol in the first trimester carries a risk of 400 micromorts via miscarriage or 19,200 micromorts for a woman drinking 4 units/week in the first trimester. The risk per unit due to stillbirth is only about 19 or 3,710 micromorts when drinking 5 units/week throughout pregnancy. Cocaine use carries a risk of about 45 micromorts per single use; 3,630 micromorts using cocaine twice/week during pregnancy. For low risk women in the UK, planned first birth at home carries an additional 843 (-200 to 2620) micromorts compared with in hospital, and planned vaginal breech birth an additional 5870 (-4400 to 18,500), compared with planned caesarean. The risk of delaying conception by a year varies by age group. For women aged 35-39 the risk increases by 220 (-430 to 870) micromorts each year versus 600 (-800 to 2000) micromorts for women aged over 40. Compared with the above, the risk from the mother eating a serving of unpasteurised cheese, is negligible at 0.00026 micromorts. CONCLUSIONS: This way of expressing risk may help put choices which pregnant women make into perspective, although it needs evaluating in well conducted experimental studies.

Do surgical techniques used in groin lymphadenectomy for vulval cancer affect morbidity rates?

OBJECTIVE: To determine the complication rates associated with differing surgical techniques for groin node dissection for vulval cancer. MATERIALS AND METHODS: We performed a retrospective case note review of patients undergoing groin node dissection for vulval cancer between 2001 and 2009 at Nottingham University Hospitals NHS Trust. RESULTS: Notes for 56 patients undergoing a total of 98 groin node dissections were examined. Sixty-four percent of the patients had at least one complication from surgery. The use of suction drains was not associated with an increase in complications. However, when drains were used, a short duration of use was associated with high rates of wound breakdown and a long duration of use was associated with higher rates of lymphedema. The use of staples for skin closure was associated with an increased risk of lymphocysts and chronic lymphedema. The greater the number of nodes collected at lymphadenectomy, the higher the risk of lymphocysts and lymphedema. CONCLUSIONS: We recommend the use of subcuticular suture for wound closure. Patients who undergo lymphadenectomy with a node count per groin of more than 7 should be closely monitored for lymphedema and referred promptly to specialist services. The prolonged use of suction drainage may increase the risk of lymphedema.

Levonorgestrel intra-uterine system as a treatment option for complex endometrial hyperplasia.

OBJECTIVE: The objective of this study was to evaluate the potential treatment of atypical and non-atypical endometrial hyperplasia with the levonorgestrel intrauterine system (LNG-IUS). STUDY DESIGN: A prospective observational study was undertaken at Queen's Medical Centre's menstrual disorder clinic between 2001 and 2008. Women presenting with abnormal perimenopausal and postmenopausal bleeding, underwent an endometrial biopsy followed by the insertion of a levonorgestrel intrauterine system (LNG-IUS). The study population comprised of 51 patients. The histology of 32 patients (Group A) showed complex hyperplasia without atypia, and in 19 patients (Group B), biopsy revealed atypical endometrial hyperplasia. These patients chose to be managed conservatively with repeat sampling of the endometrium. RESULTS: Group A: 28 (87.5%) patients out of 32 had regression of their endometrial hyperplasia within the first 12 months of follow-up. Three of the patients achieved regression by 24 months increasing regression rate to 96.8% and the remaining one had a hysterectomy due to a rare side effect. Group B: 16 (84.2%) of 19 patients had regression of the atypical hyperplasia after treatment with the intrauterine system within 12 months of treatment. One patient achieved regression of the hyperplasia by 24 months and two patients went on to have surgical management due to persistent atypia and severe atypia respectively. CONCLUSION: This study contribute further evidence that illustrates that levonorgestrel intrauterine systems have a potential role in patients requiring non-operative management although close follow-up is essential.

A neglected shelf pessary resulting in a urethrovaginal fistula.

Vaginal pessaries are safe, simple and effective treatment for pelvic organ prolapse. However, they must be fitted and followed-up correctly as serious complications can arise when pessaries are neglected. In this case report, we present the first reported case of a urethrovaginal fistula due to a neglected shelf pessary.