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This manuscript is the International Urogynecology Consultation (IUC) on pelvic organ prolapse (POP) chapter one, committee three, on the Pathophysiology of Pelvic Organ Prolapse assessing genetics, pregnancy, labor and delivery, age and menopause and animal models.An international group of urogynecologists and basic scientists performed comprehensive literature searches using pre-specified terms in selected biomedical databases to summarize the current knowledge on the pathophysiology of the development of POP, exploring specifically factors including (1) genetics, (2) pregnancy, labor and delivery, (3) age and menopause and (4) non-genetic animal models. This manuscript represents the summary of three systematic reviews with meta-analyses and one narrative review, to which a basic scientific comment on the current understanding of pathophysiologic mechanisms was added.The original searches revealed over 15,000 manuscripts and abstracts which were screened, resulting in 202 manuscripts that were ultimately used. In the area of genetics the DNA polymorphisms rs2228480 at the ESR1 gene, rs12589592 at the FBLN5 gene, rs1036819 at the PGR gene and rs1800215 at the COL1A1 gene are significantly associated to POP. In the area of pregnancy, labor and delivery, the analysis confirmed a strong etiologic link between vaginal birth and symptoms of POP, with the first vaginal delivery (OR: 2.65; 95% CI: 1.81-3.88) and forceps delivery (OR: 2.51; 95% CI: 1.24-3.83) being the main determinants. Regarding age and menopause, only age was identified as a risk factor (OR : 1.102; 95% CI: 1.02-1.19) but current data do not identify postmenopausal status as being statistically associated with POP. In several animal models, there are measurable effects of pregnancy, delivery and iatrogenic menopause on the structure/function of vaginal support components, though not on the development of POP.Genetics, vaginal birth and age all have a strong etiologic link to the development of POP, to which other factors may add or protect against the risk.

The provision of informed consent for antenatal and intrapartum care remains a contentious issue among healthcare professionals and has been the topic of controversies in the pages of this journal. Recently, the New South Wales (NSW) Department of Health has fundamentally changed the ground rules for the provision of maternity care within the state. In this opinion piece, we try to provide guidance to clinicians to help them deal with the medicolegal environment created by this document which is likely to affect practitioners not just in NSW.

Pregnancy and childbirth are considered risk factors for pelvic organ prolapse (POP). The long latency between obstetric events and morbidity hinders the establishment of cause-effect relationships. Recently, intermediate outcomes such as organ descent and levator avulsion (LA) have been identified. We aimed to assess the effect of obstetric events on symptoms and signs of POP and on LA. We systematically reviewed the literature by searching PubMed/MEDLINE, Embase and Cochrane Library. We included studies in women examining associations between obstetric events and symptoms and signs of POP and LA, assessed through questionnaires, clinical examination and pelvic floor imaging. Two reviewers evaluated the studies for eligibility and for methodological quality/susceptibility to bias. We extracted study results and clustered them by outcome: symptoms of POP (sPOP), clinical findings of POP (cPOP) and LA. When appropriate, we performed a random-effect meta-analysis and reported the summary odds ratios (OR) with 95% confidence intervals. Heterogeneity across studies was assessed using the I2 statistic. The first vaginal delivery was a risk factor for POP as measured by sPOP (OR: 2.65 [1.81–3.88]), cPOP (OR: 4.85 [2.15–10.94]) and in association with LA (OR: 41.6 [4.13– 419.41]). Forceps delivery was a risk factor for POP as measured by sPOP (OR: 2.51 [1.34–4.69]), cPOP (OR: 1.68 [1.21–2.34]) and in association with LA (OR: 5.92 [3.75–9.34]). Birth exclusively by caesarean was protective for sPOP (OR: 0.38 [0.29–0.51]) and for cPOP (OR: 0.29 [0.20–0.41]) and it did not confer any additional risk compared to nulliparity. This review confirms a strong aetiological link between vaginal birth and POP, with the first vaginal and forceps delivery being the main determinants.

Pregnancy and childbirth are considered risk factors for pelvic organ prolapse (POP). The long latency between obstetric events and morbidity hinders the establishment of cause-effect relationships. Recently, intermediate outcomes such as organ descent and levator avulsion (LA) have been identified. We aimed to assess the effect of obstetric events on symptoms and signs of POP and on LA.We systematically reviewed the literature by searching PubMed/MEDLINE, Embase and Cochrane Library. We included studies in women examining associations between obstetric events and symptoms and signs of POP and LA, assessed through questionnaires, clinical examination and pelvic floor imaging. Two reviewers evaluated the studies for eligibility and for methodological quality/susceptibility to bias. We extracted study results and clustered them by outcome: symptoms of POP (sPOP), clinical findings of POP (cPOP) and LA. When appropriate, we performed a random-effect meta-analysis and reported the summary odds ratios (OR) with 95% confidence intervals. Heterogeneity across studies was assessed using the IThe first vaginal delivery was a risk factor for POP as measured by sPOP (OR: 2.65 [1.81-3.88]), cPOP (OR: 4.85 [2.15-10.94]) and in association with LA (OR: 41.6 [4.13- 419.41]). Forceps delivery was a risk factor for POP as measured by sPOP (OR: 2.51 [1.34-4.69]), cPOP (OR: 1.68 [1.21-2.34]) and in association with LA (OR: 5.92 [3.75-9.34]). Birth exclusively by caesarean was protective for sPOP (OR: 0.38 [0.29-0.51]) and for cPOP (OR: 0.29 [0.20-0.41]) and it did not confer any additional risk compared to nulliparity.This review confirms a strong aetiological link between vaginal birth and POP, with the first vaginal and forceps delivery being the main determinants.

Telomeres are a specific base sequence of DNA, responsible for chromosome stability and DNA protection. We aimed to investigate the association between telomere systems and IVF outcomes according to patients' BMI. For all telomere characteristics, there was a distinct trend towards shorter telomeres and activation of telomere shortening compensatory mechanisms in the BMI group >25 kg/m2, reaching statistical significance for senescence only (r = 0.7, p value

ObjectiveMost patients with epithelial ovarian cancer will experience a recurrence; currently, there is no cure. In patients with platinum-sensitive disease (platinum-free interval >6 months), a combination similar to that used as frontline therapy (carboplatin and paclitaxel) is recommended. However, it is associated with a high incidence (20%) of neurotoxicity. This study evaluated the efficacy and toxicity of combination docetaxel/carboplatin therapy in patients with platinum-sensitive recurrent ovarian cancer.MethodsForty patients with recurrent, histologically proven ovarian, fallopian tube, or primary peritoneal cancer were enrolled in this phase 2 trial. The study protocol included combination therapy with docetaxel, 30 mg/m2, on days 1 and 8, and carboplatin, area under the curve 5, on day 1, every 21 days. Twenty received the classical paclitaxel/carboplatin regimen (control group), and another 20 received the modified docetaxel/carboplatin protocol (study group).ResultsMedian follow-up was 78 months for the study group and 62 months for the control group. The study group had a higher overall response rate compared to controls: 80% and 30%, respectively (P = 0.004; relative risk, 9.3; 95% confidence interval, 2.18–39.96). Complete response was achieved in 60% and 25%, respectively (P = 0.054). The study group patients showed a superior 2-year survival rate of 75% compared with the 35% of the controls (P = 0.011; relative risk, 5.57; 95% confidence interval, 1.47–21.56). Hematological and neurological toxicity rates did not differ between the groups (P = 0.451 and P = 0.605, respectively).ConclusionsPatients with recurrent ovarian cancer who received the modified docetaxel/carboplatin regimen had higher overall response and survival rates compared to those who had the paclitaxel/carboplatin regimen, with no difference in toxicity. Future larger studies should focus on strategies to compare this regimen to the current standard, with an emphasis on quality of life.

Telomeres are a specific base sequence of DNA, responsible for chromosome stability and DNA protection. We aimed to investigate the association between telomere systems and IVF outcomes according to patients' BMI. For all telomere characteristics, there was a distinct trend towards shorter telomeres and activation of telomere shortening compensatory mechanisms in the BMI group25

We investigated the physical characteristics and symptoms related to kneeling in a normal population. One hundred people were recruited at random. Of these, 27 subjects had knee pain and 73 were normal. Measurements were in kilograms with subjects on scales in three positions: standing, kneeling at 90 degrees and kneeling at full flexion. All 73 normal subjects could kneel at 90 degrees with an average of 94% of their body weight and at full flexion with an average of 51% of their body weight. The 27 subjects with knee pain were able to kneel at 90 degrees with an average of 97% of their body weight and in full flexion with an average of 50% of their body weight. Weight transmitted through the knees at full flexion is significantly less than when at 90 degrees whether subjects had pain or not. Future development of knee arthroplasty, when catering for kneeling might need to concentrate on achieving a better range of movement.

A 49-year-old Caucasian male with poorly controlled hypertension was admitted to St George’s Hospital in 1998 with a 6-week history of headaches and visual obscuration. He had an episode of left ventricular failure 8 months previously. A subsequent coronary and renal angiogram were normal. Hypertension was diagnosed 5 years previously and he was on treatment with amlodipine 10 mg od, methyldopa 250 mg tds, doxazosin 2 mg qds, labetalol 200 mg bd and furosemide 40 mg bd. His blood pressure (BP) was 160/90 mmHg on admission. Visual acuity was reduced in both eyes with bilateral papilloedema worse on the left than on the right. Magnetic resonance imaging (MRI) of his brain was normal. Diagnostic lumbar puncture (LP) revealed a high cerebrospinal fluid (CSF) opening pressure at 270 mmH2O (reference range 60–220 mmH2O). CSF of 4.5 ml was drained with a fall in CSF pressure to 165 mmH2O along with subjective improvement in headaches. On the basis of a normal MRI brain, bilateral papilloedema and high CSF pressure, he was diagnosed with idiopathic intracranial hypertension (IIH). His vision, however, did not improve and he underwent an optic nerve sheath fenestration to relieve the pressure on the left optic nerve. The patient was referred to the Blood Pressure Unit at St George’s Hospital in January 2003 with resistant hypertension with a BP of 210/100 mmHg. Initial investigations showed serum Na+ 139 mmol/l, serum K+ 3.5 mmol/l and bicarbonate 29 mmol/l. His plasma aldosterone concentration was 1476 pmol/l (normal range of 100–600 pmol/l) and his plasma renin activity (PRA) was suppressed at 0.1 ng/ml/h (normal upright range of 0.5–4.5 ng/ml/h) giving a plasma aldosterone concentration to PRA [aldosterone to renin (ARR)] ratio of 14760. Urinary catecholamines were normal. A computerized tomography (CT) scan of his …