Edward Christian Healy, M.B.A., M.D.

https://www.hopkinsmedicine.org/profiles/results/directory/profile/2290046/edward-healy

Both agonist analogues and antagonists have been developed medicine 5513 order dulcolax uk, of which the agonists have been in established clinical practice for much longer medications 5 rights buy cheap dulcolax 5mg online. The intranasal route tends to be less costly treatment for pink eye purchase cheap dulcolax, while depot administration improves compliance symptoms 5 weeks into pregnancy purchase dulcolax without prescription. When three months of treatment was compared with six months medicine 44-527 cheap 5mg dulcolax amex, clinical response was similar medicine 377 buy dulcolax 5mg fast delivery, with the exception of deep dyspareunia, for which improvement was significantly greater after six months [A]. In women needing longer-term treatment, hormonal add-back therapy can be used with the object of reducing or preventing bone loss and minimizing other unwanted side effects. All were effective in relieving pain while reducing side effects and maintaining bone density during treatment and up to 6 and 12 months after discontinuation of treatment. No Yes 200 g bd Yes Yes Data from British National Formulary indicating whether each preparation is licensed for treatment of endometrosis. Because operative laparoscopy is associated with a significant risk of major complications and potential litigation [C],8 such interventions are in urgent need of critical review. To date, there have been only two randomized doubleblind controlled trials of surgery compared with expectant management for relief of endometriosis-associated pain. In a follow up of the original study at one year,21 which included second-look laparoscopy in women who remained symptomatic, 90 per cent of those who initially responded remained well, but only 29 per cent of the control women showed signs of disease progression. The second study22 compared full excisional surgery with a diagnostic procedure, followed by a second-look laparoscopy after six months. Eighty per cent of the surgically treated group compared with 32 per cent of the control group reported symptomatic improvement. Disease progression was seen in 45 per cent of the control group, with static disease in 33 per cent and an improvement in 22 per cent. These important but small-scale studies, carried out in nationally recognized laparoscopic surgery centres, support the use of conservative laparoscopic surgery for the relief of pain in endometriosis [A], but more data are needed from larger studies to establish the duration of benefit and how this is influenced by the severity of the disease. No serious surgical complications were reported, but these results may not be reproducible in a more general context, in terms of both efficacy and safety [E]. The studies highlight the variability of disease progression and also the placebo response associated with surgical intervention. Several studies evaluating the role of laparoscopic uterine nerve ablation alone or as an adjunct to laparoscopic surgical treatment for pain in endometriosis have failed to show any benefit of this procedure [A]. Where issues of safety arise, laparotomy still has a role in the conservative management of advanced disease [C],24 both for pain management and for enhancement of fertility. Surgical management of endometriomas the relationship between the presence of endometriomas and pain symptoms is unclear, but their presence in association with pain or infertility is usually regarded as an indication for laparoscopic surgical intervention. Endometriomas do not resolve during medical suppression, although, if small, they may reduce in size and become asymptomatic. Simple drainage of an endometrioma is followed by rapid recurrence, even if it is fenestrated and irrigated [A]. Laparoscopic excision is therefore the surgical treatment of choice in endometriomas [A]. Medical adjuncts to surgery There is no evidence to support the use of medical adjuncts prior to conservative surgery for endometriosis [A], although they may be valuable in the control of symptoms. Drugs which suppress ovarian activity are frequently used following conservative surgery of endometriosis. There are no randomized studies comparing medical and surgical therapies, in terms of either short-term efficacy or long-term recurrence. Management of pain in endometriosis is supported by two evidence-based guidelines and six systematic reviews based on a large number of randomized, controlled trials. Surgical management of pain in endometriosis is based on two evidence-based guidelines, two small randomized, controlled trials and a systematic review of the use of pelvic denervation. There have been no randomized studies comparing medical with surgical management in the relief of endometriosisassociated pain. Definitive surgery In women with symptomatic endometriosis who have completed childbearing, hysterectomy offers a long-term cure, but only if combined with bilateral oophorectomy [C]. One was a very small study comparing tibolone with continuous transdermal oestradiol in combination with cyclical progestogen. The other was a larger study comparing transdermal oestradiol and cyclical progesterone with no treatment. There was a small incidence of symptom recurrence in all treatment groups, but not in the placebo group. Where appropriate, surgical ablative therapy should be carried out at the time of the initial laparoscopy [E]. Transvaginal ultrasound is useful in identifying endometriomas, but lacks specificity [A]. Hormonal suppression of ovulation is effective in the management of pain associated with endometriosis [A]. Because of a high risk of recurrence, medical treatment may need to be intermittent or long term [A]. Levonorgestrel-releasing intrauterine systems may have a role in long-term pain control [B], but further evaluation is required. Laparoscopic surgery is effective in the treatment of pain secondary to endometriosis in experienced hands [B]. There is insufficient evidence to recommend surgical pelvic nerve interruption for the relief of pain associated with endometriosis [A]. The role of post-operative medical therapy as an adjunct to surgery is uncertain [A]. Operative laparoscopy carries a significant risk, and cases of advanced disease should be referred to specialist centres for laparoscopic surgery [E]. If fertility is no longer an issue, hysterectomy with bilateral oophorectomy may provide a cure, but disease excision may be incomplete [C]. Comparison of a levonorgestrel-releasing intrauterine system versus expectant management after conservative surgery for fendometriosis: a pilot study. Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot study. Gonadotrophin-hormone releasing hormone analogues for the treatment of endometriosis; long term follow up. Prospective randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild and moderate endometriosis. Follow-up report on a randomized, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal to moderate endometriosis. Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. Laparoscopy versus laparotomy in conservative surgical management for severe endometriosis. A gonadotropin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis. However, recent studies based on imaging techniques (see below) have cast doubt on this distinction. Studies based on findings at hysterectomy have yielded varied conclusions about the correlation between symptomatology and the presence of adenomyosis. Some have related the severity of dysmenorrhoea to the extent of adenomyosis and its depth of invasion into the myometrium,7,8 but others have failed to find any relationship between its presence and individual symptoms2 or the main indication for the hysterectomy. Most published information on adenomyosis is based on studies of hysterectomy specimens. This is because, until recently, the diagnosis has only been possible in retrospect. Recent advances in imaging have facilitated its diagnosis and led to greater opportunities for clinical trials of medical and conservative management. To date, such studies have been very limited and consequently the literature on adenomyosis remains small, as is the evidence base for its management. Among women Management 589 undergoing hysterectomy, the incidence of adenomyosis is increased with increasing parity3,4 and with a history of miscarriage3 or induced abortion. Various sonographic appearances have been described15 including: Surgical management the presence or absence of adenomyosis may influence the choice of surgical treatment for women with menstrual disorders. There is some evidence that the presence of deep lesions of adenomyosis is associated with failure of endometrial ablation,17,21 with both regeneration of the endometrium and glandular activity within the myometrium [D]. However, further studies comparing the results of imaging before and after such procedures are needed to distinguish between pre-existing and iatrogenic lesions. It is not known whether second generation ablation techniques have any advantage over first generation methods in this regard. Where preservation of fertility is desired, management options are even less clear. There have been a few preliminary reports of laparoscopic or microsurgical excision or coagulation12 of adenomyosis with variable results. Both techniques, even when used in combination, may lack accuracy for the evaluation of very large uteri with a volume greater than 400 mL. Its prevalence in the population is unclear and its role as a contributing factor to menstrual disorders is not well understood. Medical therapies that have proven value in management of painful heavy menstruation and endometriosis have not been adequately assessed in adenomyosis but are likely to be beneficial [E]. Endometrial ablation and local excision of endometriosis may have a greater failure rate in the presence of adenomyosis [D]. Hysterectomy is an effective treatment for menstrual symptoms attributed to adenomyosis [D]. Preliminary data suggest that uterine artery embolization has a limited role in the management of adenomyosis [D]. Adenomyosis at hysterectomy: a study on frequency distribution and patient characteristics. Adenomyosis at hysterectomy: prevalence and relationship to operative findings and reproductive and menstrual factors. Relationship between the degree of dysmenorrhoea and histologic findings in adenomyosis. Diagnostic accuracy of transvaginal sonography for the diagnosis of adenomyosis: systematic review and metaanalysis. Ultrasonography compared with magnetic resonance imaging for the diagnosis of adenomyosis: correlation with histopathology. Depth of endometrial penetration in adenomyosis helps determine outcome of rollerball ablation. Treatment of adenomyosis-associated menorrhagia with a levonorgestrelreleasing intrauterine device. Persistence of dysmenorrhoea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Early results of magnetic resonance-guided focused ultrasound surgery of adenomyosis: analysis of 20 cases. However, a substantial number of women are sufficiently distressed by their symptoms to seek medical help and a minority are severely incapacitated by them. Prospective methods of symptom assessment are now well established and there is an expanding literature of randomized, controlled trials covering various approaches to management, including several systematic reviews. These symptoms occur during the luteal phase of the cycle and are relieved with the onset of menstruation or soon afterwards. Symptoms occur with a variable degree of severity from mild (no interference with personal or professional life) to severe in which symptoms are so disruptive that the individual is unable to function socially or professionally. There may also be premenstrual exacerbation of underlying psychiatric or medical disorders. However, it is evident that cyclical symptoms contribute significantly to menstrual cycle morbidity. This may be abnormal metabolism of progesterone to its metabolites allopregnenalone and pregnenalone, neuroactive steroids with differential effects on anxiety-related symptoms. Allopregnenalone has anxiolytic actions, whereas pregnenalone may promote anxiety. There was a significant relationship between menstrual and premenstrual magnification and previous psychiatric disorders, marital breakdown and increased parity. This emphasizes the importance of critical appraisal of the evidence base before recommending specific therapies. Complementary and alternative therapies these approaches are popular with patients and, given the high level of placebo response, are likely to be perceived as effective without the potential disadvantage of side effects associated with conventional medications. There have been three systematic reviews of trials of such therapies: one covering a wide range of approaches,10 one addressing dietary supplements11 and one on the use of vitamin B6. Beneficial effects were reported with calcium, calcium combined with vitamin D, magnesium, vitamin E and isoflavones. Despite these positive results, the reviewers felt that weaknesses in methodology limited their recommendations of the value of such interventions [E]. Similarly, studies of nutritional supplements containing high doses of vitamins and other micronutrients have yielded inconclusive results. Referral for specialist help will depend on the severity of the problem, the experience of individual general practitioners and the expectations of the women involved. Most women referred for specialist help will be experiencing disruption of family or professional life and have a history of previous treatment failures. Similarly, reports of benefit from the use of Chinese herbal medicine16 are limited by the lack of standard formulations. Ginko biloba and pollen extract have both been shown to be beneficial in small-scale studies, although further data would be needed to support their use. Most commonly studied were fluoxetine (n = 14) and sertraline (n = 11), followed by citalopram (n = 3), paroxetine (n = 9), clomipramine (n = 2) and fluvoxamine (n = 1).

This is compounded by the fact that pregnant women also have an altered hormonal response to hypoglycaemia and reduced awareness medications neuropathy 5 mg dulcolax otc. One study of 84 women found that 71 per cent of women suffered a hypoglycaemic episode requiring assistance medications you can take during pregnancy discount dulcolax 5 mg with amex, and that this peaked at between 10 and 15 weeks medicine bow order dulcolax online now. Alternatives include a glucose gel (two tubes of HypoStop/Glucogel) which can be rubbed on the inside of the cheek symptoms 9 weeks pregnancy safe dulcolax 5 mg. This should be followed by a slower releasing carbohydrate such as bread or a sandwich medications drugs prescription drugs discount dulcolax 5mg fast delivery. For these reasons medications while breastfeeding cheap dulcolax 5 mg with visa, it is recommended that patients carry information identifying them as having diabetes. If after 10 minutes the blood glucose remains less than 5 mmol/L, the treatment should be repeated. Insulin doses with the next meal should not be withheld but may require modification. This can be caused by failure to appreciate the increasing insulin requirements in pregnancy, missed insulin doses, concurrent illness such as infection, steroid therapy and stress. Treatment should involve the diabetic teams, treatment of the precipitating cause and will usually require intravenous insulin via a sliding scale. Severe hyperglycaemia requiring intensive treatment is defined as persistent premeal blood glucose values of greater than 12 mmol/L on two consecutive occasions, or a random level of more than 15 mmol/L. Betablockers should be avoided as antihypertensives due to their possible adverse effects of glucose metabolism. Diabetic nephropathy is considered as a continuous spectrum from microalbuminuria, proteinuria and impaired renal function to end stage renal disease in which there is increasing serum urea and creatinine. Overall, with the exception of women with pre-existing renal failure, nephropathy does not deteriorate with pregnancy. However, there is an increased risk of growth restriction, pre-eclampsia and preterm birth. Although low dose aspirin and uterine artery Doppler assessments have been used in other high risk pregnancies, there is currently no specific evidence to support their use in women with these diabetic complications. This can be achieved by increasing subcutaneous doses, or by the use of intravenous insulin via a sliding scale. Diabetes should not be considered a contraindication to the use of antenatal steroids. Although caudal regression (sacral agenesis) is the most well known associated abnormality (200-fold increased risk), the prevalence is low. Thus, all women with diabetes should have a detailed fetal anatomy scan at 20 weeks, which should include the four chamber cardiac view and the outflow tracts. Monitoring strategies the longer the duration of the diabetes, the higher the chance of a patient having pre-existing vasculopathy, renal dysfunction, neuropathy and diabetic retinopathy. The presence of these complications increases the risks of pre-eclampsia and fetal growth restriction. Pregnancy is associated with progression of pre-existing retinopathy, and this is more likely with increased severity of the pre-existing disease, duration of diabetes, poor glycaemic control and rapid improvements in control [C]. Furthermore, interpretation must consider the effects of diabetes on the monitoring. Therefore, patterns of change may be a better indicator of deterioration in fetal well-being. Growth velocity and, in particular, crossing centiles are of use in identifying the development of macrosomia and growth restriction. Higher rates of caesarean sections and shoulder dystocia have also been described in large cohorts in other populations. There is now some evidence to suggest that induction of labour at 38 weeks may reduce the risks of shoulder dystocia in macrosomic infants of women with diabetes. More recently, data have suggested that short term control of maternal blood glucose, i. Thus, current guidance is that maternal blood glucose should be kept between 4 and 7 mmol/L during labour and delivery. Blood glucose should be tested hourly and women not maintaining their blood glucose within this range should be commenced on an intravenous insulin and dextrose infusion via a sliding scale. Sliding scales should be developed together with local Diabetologists, but an example is given in Table 6. This may be considered at the onset of labour for women with type 1 diabetes, particularly if their oral intake is reduced. Care should be taken with the use of sliding scales, and the intravenous infusions regularly checked (preferably hourly), as severe clinical incidents and death have occurred when infusions have become blocked or run too fast. General anaesthesia also increases risks of hypoglycaemia and reduces awareness, thus these women should have blood glucose monitoring every 30 minutes until fully conscious. Since women with other co-morbidities, such as autonomic neuropathy or obesity, face additional risks, these women should be offered an anaesthetic review during the third trimester. Antenatal complications: maternal Postpartum care Intrapartum care Good control of maternal blood glucose during labour in women with diabetes is important due to the association between hyperglycaemia and neonatal hypoglycaemia. Some infants produce high levels of insulin antenatally in response to high levels of glucose crossing the placenta. After delivery, there is withdrawal of the maternal glucose but With delivery of the placenta, insulin requirements dramatically decrease, thus all women will require a reduction in insulin dose, even when managed with the insulin sliding scale. Consultant diabetologist involvement is very important at this time, and especially when the patient is converted back to subcutaneous insulin. Advice varies regarding the subcutaneous insulin dose following 56 Diabetes mellitus Table 6. Some suggest changing insulin regimes to the pre-pregnancy dosing, others suggest a halving of insulin doses. Hypoglycaemia is a major risk for women with type 1 diabetes at this time, especially in overweight or obese women who experience a large increase in their insulin requirements during pregnancy. Women who have undergone caesarean section will require continuation of the sliding scale until normal eating is resumed. Women with type 2 diabetes can change from insulin back to their oral hypoglycaemic agents. Breastfeeding Small cohort studies have demonstrated that breastfeeding increases the frequency of hypoglycaemia in insulin-dependent diabetics [C]. Current guidance is that drugs avoided in the antenatal period should also be avoided during breastfeeding. Treat hypoglycaemia with three glucose tablets, 60 mL lucozade or 150 mL of intravenous 10 per cent dextrose. Setting up the insulin sliding scale should always be done in consultation with the consultant physician. Some patients required higher or lower insulin infusion rates, especially if they are receiving high dose of insulin (>60 units/day). The rate of the insulin pump is adjusted based on hourly blood glucose measurements Contraception and follow up Women with pre-existing diabetes should be referred back to their routine diabetic care team, usually following a 6 week postnatal review. Contraceptive choices should be discussed with individual women, with careful consideration of their risk factors. Complications of diabetes 57 In particular, caution should be taken in women with risk factors for vascular disease. Women should also be made aware of the importance of preconception care when planning future pregnancies. Good glycaemic control pre-conception and in the first 8 weeks reduces the risk of congenital abnormalities (HbA1c of 6. Pregnant women with diabetes should be managed in a joint obstetric/diabetic clinic involving the input of obstetricians, diabetologists, dieticians, specialist nurses and midwives. Post-prandial bood glucose levels, rather than levels of HbA1c, should be used to monitor glycaemic control in the second and third trimesters as these are associated with a better outcome. Women with diabetes should be offered monitoring of fetal growth and well-being, although there is no good evidence that these monitoring strategies reduce the risks of stillbirth and macrosomia. Women with macrosomia should have the risks and benefits of different modes of delivery discussed with them. Maternal blood glucose should be kept between 4 and 7 mmol/L during labour and delivery to reduce the risks of neonatal hypoglycaemia. Health Survey for England 2006: the Information Centre, Joint Health Surveys Unit, National Centre for Social Research, Department of Epidemiology and Public Health at the Royal Free and University College Medical School, 2008. Management of diabetes and its complications from pre-conception to the postnatal period. Macrosomia despite good glycaemic control in Type I diabetic pregnancy; results of a nationwide study in the Netherlands. Preprandial versus postprandial blood glucose monitoring in type 1 diabetic pregnancy: a randomized controlled clinical trial. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin-dependent diabetes mellitus. Hypoglycemia: the price of intensive insulin therapy for pregnant women with insulin-dependent diabetes mellitus. Insulin-requiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management. Induction of labor at 38 to 39 weeks of gestation reduces the incidence of shoulder dystocia in gestational diabetic patients class A2. Theoretical skills Understand the epidemiology, aetiology, pathophysiology, clinical characteristics, prognostic features and management of women with heart disease. Palpitations, extrasystoles and ejection systolic murmurs are common in pregnancy but rarely represent underlying pathology. This chapter covers the most important conditions relevant to pregnancy, including pulmonary hypertension, aortic dissection, ischaemic heart disease, mitral stenosis and mechanical heart valves. Peripartum cardiomyopathy is included as it is specific to the pregnant or postpartum state. These are mostly diagnosed before pregnancy and are usually either haemodynamically insignificant or corrected. Acquired causes of cardiac disease include ischaemic heart disease, rheumatic heart disease, cardiomyopathies, and aneurysms and dissection of the aorta or its branches. Most pregnancy-associated deaths can be attributed to thromboembolism, hypovolaemia or pre-eclampsia. Experiences symptoms even at rest Management Women with pulmonary hypertension should be advised to avoid pregnancy or, in the event of unplanned pregnancy, to have a therapeutic termination [D]. Bosentan) and sildenafil should be continued in pregnancy, not withstanding the possible fetal risks associated with the former. In addition, women with previous cardiac events including transient ischaemic attacks, arrhythmia, pulmonary oedema or heart failure, and those with left-sided lesions. During pregnancy, women with heart disease require multidisciplinary team care,2 with regular antenatal visits and judicious monitoring to avoid or treat expediently any anaemia, infection or hypertension. There should be early involvement of obstetric anaesthetists and a carefully documented plan for delivery. All the literature supports a high risk of maternal death sufficient to make this condition one of the absolute contraindications to pregnancy. There is no evidence that monitoring the pulmonary artery pressure prepartum or intrapartum improves outcome. Progressive aortic root dilatation and an aortic root dimension >4 cm are associated with increased risk [D]. Pulmonary hypertension from any cause is dangerous and maternal mortality is 40 per cent [D],4 although this may be decreasing. Recommendations include monthly echocardiograms, beta-blockers for those with hypertension or aortic root dilatation, vaginal delivery for those with stable aortic root measurements, but elective caesarean section with epidural if there is an enlarged or dilating aortic root [D]. The literature supports a higher risk of pulmonary oedema in severe mitral stenosis. The literature supports a higher risk of aortic rupture and maternal death if the aortic root is >4 cm. The problem for women with metal heart valve replacements is that they require life-long anticoagulation, and this must be continued in pregnancy because of the increased risk of thrombosis. Warfarin is associated with warfarin embryopathy12 and increased risks of miscarriage, stillbirth and fetal intracerebral haemorrhage. Mitral stenosis is the most common rheumatic heart disease and is important in pregnancy because women may deteriorate secondary to tachycardia, arrhythmias or the increased cardiac output. The commonest complication is pulmonary oedema secondary to increased left atrial pressure and precipitated by increased heart rate or increased volume (such as occurs during the third stage of labour) [C]. Betablockers decrease heart rate and the risk of pulmonary oedema [D],10 but if medical therapy fails or for those with severe mitral stenosis, balloon mitral valvotomy may be safely and successfully used in pregnancy [D].

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By the sixth week treatment for shingles buy dulcolax 5 mg online, the indifferent stage is completed symptoms 2 weeks after conception dulcolax 5 mg cheap, leaving the indifferent gonads consisting of germ cells and supporting cells derived from the coelomic epithelium and the mesenchyme of the gonadal ridge treatment irritable bowel syndrome discount dulcolax 5 mg without prescription. The genetic material in the two haploid gametes combines to produce a diploid zygote symptoms pregnancy buy line dulcolax. In mammals symptoms 3 days dpo order dulcolax online now, the fusion of the gametes occurs within the female reproductive tract 3 medications that cannot be crushed buy cheap dulcolax 5 mg online, and is followed by implantation and the development of the fetus in the uterus. Gametes are produced in the gonads, which also have endocrine functions that are essential for successful reproduction. It is important to explore the embryology, anatomy and some physiological aspects of the ovary and testis in order to understand conception and infertility. Follicular development, maturation and ovulation 599 maximal oogonial content of the gonads. From this point onwards, the germ cell content will irretrievably decrease and will be exhausted approximately 50 years later. The germ cells undergo mitosis to produce the oogonia that enter the first meiotic division and arrest in the prophase to become oocytes. The completion of the first meiotic division occurs just before ovulation, and the second meiotic division takes place at sperm penetration. As a result of the two meiotic divisions, a single haploid ovum is produced and the excess genetic material is extruded as one polar body at the completion of each meiotic division. There is a continuous loss of germ cells during all these events, as a result of several mechanisms: (1) follicular growth, atresia and regression during meiosis; (2) the follicles, which fail to become enveloped by granulosa cells, undergo atresia; (3) some germ cells migrate to the surface of the gonads and become incorporated into the surface epithelium or become eliminated into the peritoneal cavity. Once all the oocytes are incorporated into follicles (shortly after birth), the loss of oocytes will only take place as a result of follicular growth and atresia. At the onset of puberty, the germ cell mass, incorporated into primordial follicles, is usually reduced to approximately 300 000 follicles. This enormous attrition of primordial follicles forms part of the process of natural selection, by which only a tiny number of randomly selected germ cells pass through the reproductive cycle and form a new individual. As the dominant follicle grows, it produces oestrogens, predominantly oestradiol, and inhibins, predominantly inhibin B. Ovulation results in the physical release of the oocyte, allowing it to enter the Fallopian tube, with potential for fertilization. The follicle then becomes blood filled and develops into the corpus luteum, the source of progesterone and inhibin A in the second half (luteal phase) of the cycle. For this regular periodic process to occur, accurate communication between the ovary and the pituitary gland is essential. However, sex steroid production in the male is a continuous, non-episodic process, which is independent of the development of gametes. The early embryonic stages of testicular development also follow those of the ovary, starting from the indifferent gonad stage. The absence of these two factors leads to the development of the female phenotype. Differentiation of the testis leads to the production of the spermatic cords, which include the Sertoli cells and primordial germ cells that later become the spermatogonia. The former is responsible for maintaining the high local androgen environment necessary for spermatogenesis. The Leydig cells develop from the mesenchymal cells surrounding the spermatic cords. They produce testosterone, the secretion of which increases with the increase in the number of Leydig cells. These cells become responsive to gonadotrophins at puberty, leading to the production of testosterone and the initiation of spermatogenesis. The spermatogonia divide mitotically to produce primary spermatocytes, which then divide meiotically to produce the haploid secondary spermatocytes. Secondary spermatocytes undergo a maturation process to produce the spermatid, then the mature spermatozoon. The Sertoli cells influence the process of spermatogenesis and are directed by genes on the Y chromosome. Approximately 74 days are required to produce a mature spermatozoon, of which about 50 days are spent in the seminiferous tubules. The mechanism determining which primordial follicles and how many will be released into the pool of growing follicles in each menstrual cycle is not known. The number of primordial follicles released from quiescence to enter the pool of growing follicles each cycle seems to be proportional to the size of the residual pool. Therefore, the reduction of the primordial follicle pool by total or partial unilateral oophorectomy, or towards the end of reproductive life, may result in a smaller cohort of growing follicles. This is known as the pre-antral stage, which starts to occur towards the end of the luteal phase of the preceding cycle. Therefore, the fate of each pre-antral follicle in the developing pool depends on its ability to convert an androgen microenvironment to an oestrogen microenvironment. This requires the development of aromatase within the granulosa cells that line the follicle. Once one follicle acquires sufficient aromatase to produce and secrete significant quantities of oestradiol, the remainder of the cohort stop growing and gradually become atretic. The granulosa cell layer is separated from the stromal cells by a basement membrane called the basal lamina (lamina basalis). The surrounding stromal cells differentiate into concentric layers designated as the theca interna (closest to the basal lamina) and the theca externa (the outer portion). The intrafollicular fluid contains oestrogens and a variety of peptide growth factors, which provide the oocytes and the surrounding granulosa cells with an endocrine-rich environment essential for maturation and eventually ovulation. Oestradiol and inhibin B are produced in increasing amounts by the rapidly growing lead follicle in the cohort. The oocyte resumes its first meiotic division, leading to the production and extrusion of the first polar body, and enters the second meiotic division, which will be completed on fusion of the sperm with the oocyte later on. Furthermore, progesterone enhances the activity of proteolytic enzymes and prostaglandins to digest the follicular wall, leading to the rupture of the follicle and the release of the oocyte. Fertilization the oocyte released at the time of ovulation is surrounded by granulosa cells known as the cumulus oophorus, which is separated from the actual oocyte by a layer of glycoprotein known as the zona pellucida. Although several million sperm are deposited in the vagina, only about 200 will come in contact with the oocyte. For the sperm to bind with the zona pellucida, a receptor is required, the selection of a dominant follicle In primates and humans, usually one follicle proceeds to ovulation and the rest of the cohort is destined for Acknowledgement 601 which is species specific. The zona pellucida not only contains the receptors for the sperm, but also has a mechanism by which it prevents more than one sperm from entering the oocyte (polyspermy). This process requires preparation of both the endometrium and the embryo for a successful implantation to take place. Sufficient cell division needs to take place to produce the inner cell mass essential for the formation of the blastocyst. The embryo usually reaches the blastocyst stage by day 5 post-fertilization, with a prominent inner cell mass and trophoectoderm. The two structures expand and hatch through the zona pellucida from day 7 onwards. This prevents the onset of menstruation and allows the early pregnancy to continue. At the time of hatching, the trophoblast cells begin to differentiate into cytotrophoblasts and syncytiotrophoblasts. The expression of adhesion molecules in the trophoblast may be responsible for the initial attachment of embryo to the uterus. The embryo gradually develops its self-regulatory paracrine system and establishes a communication system with the endometrium. This leads to interaction with the uterine epithelium and decidua during apposition and invasion by the trophoblast. At the onset of puberty, the size of the primordial follicles pool is approximately 300 000 follicles. The zona pellucida precludes more than one sperm entering the oocyte through a mechanism known as the zona reaction. The embryo usually reaches the blastocyst stage by day 5 post-fertilization with a prominent inner cell mass and trophectoderm. Inhibition of oogenesis in the human fetal ovary: ultrasound structural and squash preparation study. The dependence of folliculogenesis and corpus luteum function on pulsatile gonadotrophin secretion in cycling women using a gonadotrophin-releasing hormone antagonist as a probe. Temporal relationships of oestrogen, progesterone, and luteinizing hormone levels to ovulation in women and infrahuman primates. Endometrial preparation After ovulation, oestradiol and progesterone from the corpus luteum alter the molecular structure of the endometrium from proliferative to secretory. The individual components of the endometrium continue to grow, leading to tortuosity of the glands and coiling of the spiral arterioles. Intracytoplasmic glycogen vacuoles appear and transudation of plasma occurs, contributing to endometrial secretion. At this point, the endometrial cells are rich in glycogen and Reproductive medicine Chapter 52 Fertility and conception 52. Furthermore, if the female partner is 35 years of age or older, the investigations should not be delayed, given the rapid decline of female fecundity after this age. Worldwide, more than 70 million couples suffer from infertility, the majority being residents of the developing countries. The recent advances in infertility treatment and the access of patients to such information have led to early presentation of these patients and their request for treatment. The cumulative spontaneous pregnancy rate for a couple is approximately 57 per cent after three months, 72 per cent after six months, 85 per cent after one year and 93 per cent after two years [D]. However, if the physician For pregnancy to occur, there must be fertile sperm and egg, a means of bringing them together and a receptive endometrium to allow the resulting embryo to implant. It has been estimated that in 35 per cent of cases a male factor is the reason for infertility [C]. In the remaining 65 per cent of cases, a female factor is identified in 50 per cent of couples and no cause will be identified in the remainder [C]. The most common causes of infertility in the female are ovulatory and tubal factors. Endometriosis in its moderate to severe forms has also been linked to infertility, despite a lack of clear understanding of the connection between the two Causes of infertility 603 phenomena [C]. Although failure of implantation will cause infertility, it is difficult to determine whether the embryo or the endometrium is at fault in such cases. The effect of age on female fertility is not a new concept, with a gradual decline in female fertility and an increase in the miscarriage rate being observed many years before the menopause [D]. As discussed earlier, women enter the reproductive age at puberty with a pool of primordial follicles of a predetermined number. The size of this pool and the rate of follicular depletion are the deciding factors in the timing of the menopause. Female fertility declines after the age of 35 and declines more rapidly after the age of 40 [C]. The rate of follicular loss is inversely proportional to the size of the primordial pool, i. Delaying starting a family to the later years of reproductive life also increases the risk of developing endometriosis and the risk of miscarriage. The pituitary can also be damaged by cranial irradiation or surgically at the time of hypophysectomy for a pituitary tumour. This is seen in hypothalamic dysfunction, commonly secondary to excessive exercise, psychological stress or anorexia nervosa. Hypergonadotrophic hypogonadism this occurs as a result of failure of the ovary to respond to gonadotrophic stimulation by the pituitary gland. Hypergonadotrophic hypogonadism classically results from premature ovarian failure with exhaustion of the ovarian follicle pool. A variant of the condition, resistant ovary syndrome, describes the occurrence of elevated levels of serum gonadotrophins in the presence of a good reserve of follicles.

The choice of incision and closure should be individualized to the characteristics of the woman and the circumstances demanding operative intervention treatment 30th october best 5mg dulcolax. The transverse incision has the advantages of improved cosmetic results symptoms exhaustion buy dulcolax 5 mg otc, decreased inter-operative and postoperative analgesic requirements and thus less pulmonary compromise and superior wound strength postpartum treatment xanthelasma cheap dulcolax 5 mg on-line. Haeri demonstrated no difference between the two incisions when comparing overall operative time symptoms 6 days past ovulation cheap dulcolax 5 mg line, post-operative haemoglobins of <10 g/dL medications hard on liver buy dulcolax amex, or post-operative febrile morbidity [D] symptoms 2 year molars cheap 5 mg dulcolax. The Pfannenstiel incision the skin and subcutaneous tissues are incised using a transverse curvilinear incision at a level of two fingerbreadths above the symphysis pubis, extending from and to points lateral to the lateral margins of the abdominal rectus muscles. The subcutaneous tissues are separated by blunt dissection and the rectus sheath is incised transversely along the middle 2 cm. This incision is then extended with scissors or blunt dissection before the fascial sheath is separated from the underlying muscle. Separation is performed cephalad to permit adequate exposure of the peritoneum in a longitudinal plane and perforating blood vessels should be cauterized to minimize the risks of development of subrectus haematomas. The recti are separated from each other, the peritoneum incised and the abdominal cavity entered. It is the policy in many units for a catheter to remain in situ peri-operatively and for a defined period thereafter the Cohen incision this incision is similar to the Pfannenstiel incision, but permits a more rapid and bloodless entry into the peritoneal cavity. A straight transverse incision is made between 406 Caesarean section two points inferior and medial to the anterior superior iliac spine, the subcutaneous tissues are divided in the midline for 3 cm and the central rectus sheath is similarly divided. By blunt dissection and vertical traction, the subfascial space is opened, the peritoneum exposed and the abdominal cavity entered high above the bladder. Entry with this technique into the abdominal cavity is often not suitable for repeat caesarean sections, where scarring may distort the underlying fascial planes. The lower midline incision is made from the lower border of the umbilicus to the symphysis pubis, and may be extended caudally towards the xiphisternum if required. Sharp dissection to the level of the anterior rectus sheath is performed, which is then freed of subcutaneous fat in the midline. The rectus sheath is then incised, taking care to avoid damage to any underlying bowel, and extended inferiorly to the vesical peritoneal reflection and superiorly to the upper limit of the abdominal incision. Uterine incisions As with the skin incision, the nature of the uterine incision is determined by the clinical situation. A low transverse uterine incision is used in more than 95 per cent of caesarean deliveries due to ease of repair, reduced blood loss and lower incidence of dehiscence or rupture in subsequent pregnancies when compared with the alternative incisions. However, these include a lower uterine segment containing fibroids or a lower segment covered with dense adhesions, both of which may make entry difficult. Such obstruction may be associated with heavy bleeding or may distort the anatomy to such an extent that the lower segment approach is not safe. The uterus is palpated to identify the size and presenting part of the fetus and to determine the direction and degree of rotation of the uterus. A Doynes or similar retractor blade is inserted inferiorly and the loose reflection of vesico-uterine serosa overlying the uterus picked up with toothed forceps, opened with scissors and divided laterally. Such an incision should be adequate to allow delivery of the fetus without extension into the broad ligament or uterine vessels. If necessary, cutting the incision upward unilaterally (J-incision) or bilaterally (U-shape) will avoid such an extension and provide extra room. Damage to the uterine vessels or broad ligament, when it occurs, is associated with an increase in maternal morbidity (especially blood loss) and prolonged hospitalization. If a midline extension is required, the T-incision, in future pregnancies vaginal delivery will be contraindicated because of an increased risk of uterine rupture [C]. This entry is vertical on the uterus in the sagittal plane, is extended to the level of entry of the round ligaments, but is not taken onto the fundus (unlike a true classical section). If cephalic, the head is flexed and delivered by elevation though the uterine incision, either manually or with forceps. Some authors advise confirmation of a patent cervical canal to ensure a patent passage for the drainage of lochia, although this is not necessary in labouring women. Repair of the incision may be performed with the uterus in situ or following exteriorization. Exteriorization is not Complications 407 routinely necessary, but enhances visualization of the lower segment and thus facilitates surgical repair; especially when there have been lateral extensions to the incision margins. One trial reported a decrease in the haematocrit fall with exteriorization compared with intraperitoneal procedures, whereas another did not. The main problems with exteriorization are increases in maternal pain, vagal-induced vomiting and the incidence of venous air emboli, although the incidence of infectious morbidity is not altered. There is currently not enough information to adequately evaluate the routine use of exteriorization of the uterus for repair of the uterine incision. Peritoneal closure is unnecessary and may result in a higher incidence of adhesion formation than would otherwise occur [A]. Abdominal closure Closure is performed in the anatomical planes with highstrength, low-reactivity materials such as polyglycolic acid or polyglactin (Dexon and Vicryl). Interlocking of the sutures should be avoided as this can devascularize the tissues and delay the healing process. Here, repair should be effected with a running continuous suture of polyglycolic acid, large-bore monofilament polypropylene or nylon, which have delayed/prolonged absorption characteristics. The most common involve surgical staples, subcuticular stitches or tension sutures (interrupted or continuous/polyglycolic acid, large-bore monofilament polypropylene or nylon). However, lower transverse abdominal skin incisions closed with a subcuticular stitch result in less post-operative discomfort and are more cosmetically appealing at the 6-week post-operative visit when compared to incisions closed with staples. Closure should be performed in either single or double layers with continuous or interrupted sutures. The initial suture should be placed just lateral to the incision angle, and the closure continued to a point just lateral to the angle on the opposite side. If a second layer is used, an inverting suture or horizontal suture should overlap the myometrium. There are only two reported randomized, controlled trials comparing single-layer versus two-layer closure. A single-layer closure is associated with reduced operating time, with no statistically significant differences in the use of extra haemostatic sutures, incidence of endometritis, decrease in post-operative haematocrit or use of blood transfusion [B]. There have recently been some concerns regarding singlelayer closure, as one widely reported observational study of scar dehiscence in subsequent labours showed a higher incidence than previously reported. One possible aetiological factor that has been suggested is the move to single-layer closure during the period studied. The effectiveness and safety of single layer closure of the uterine incision is therefore uncertain and, except within a research context, the uterine incision should be sutured with two layers. However, vertical lacerations into the vagina or lateral extensions into the broad ligament may be associated with substantial blood loss and the potential for ureteric damage. To minimize bleeding from the perforated myometrial vessels in such cases, the needle must be positioned just distal to the apex of the laceration and, once inserted, should not be withdrawn. The management is dependent on the site of the injury, and is best conducted in conjunction with a general surgeon. Small bowel damage is repaired using a two-layer closure with 2-0 Vicryl or equivalent. Large First stage of labour 408 Caesarean section bowel damage is managed likewise, but in addition a temporary defunctioning colostomy may be required. Post-repair peritoneal lavage is mandatory, as is a treatment course with broad-spectrum antibiotics, for example a cephalosporin and metronidazole. Pre-operative catheterization in association with careful operative technique should reduce the likelihood of damage occurring. If damage to the bladder is suspected, transurethral instillation of methylene blue-coloured saline will help to delineate the extent of the defect. When such an injury is observed, a repair with 2-0 Vicryl as a single continuous or interrupted layer is appropriate. Damage to the ureters is uncommon, as reflection of the bladder displaces them rostrally, but if suspected, the ureters should be investigated and repaired in conjunction with a urological surgeon. This complication may be due to the operative procedure as a consequence of damage to the uterine vessels, or may be incidental as a consequence of uterine atony or placenta praevia. There are many manoeuvres that may be employed to manage such cases, which range from bimanual compression, infusions of oxytocin and administration of 15-methyl prostaglandin F2 to conservative surgical procedures such as uterine compression sutures, to the more radical, but lifesaving, hysterectomy. In patients with an anticipated high risk of haemorrhage, for example known cases of placenta praevia, at least four units of blood should be routinely cross-matched, and must be available in theatre before the procedure is commenced. A combined approach to the management of such patients, with the anaesthetists, haematologists and obstetricians working together, will result in the best standard of care. This operation, while a major undertaking, should not be left too late as the risk of operative complications, maternal morbidity and mortality increase with increasing haemorrhage. Although postpartum haemorrhage is relatively common (occurring after about 1 per cent of deliveries), life-threatening haemorrhage requiring immediate treatment affects only 1 in 1000 deliveries. It is important to note that the Confidential Enquiries continue to cite delays in performing definitive surgery, for example a hysterectomy, as an avoidable cause of maternal mortality. This complication alone accounts for 30 per cent of emergency caesarean hysterectomies. It is also important to counsel such patients accordingly, and to gain consent preoperatively for caesarean hysterectomy when appropriate. The incidence of post-operative wound infection has been quoted to be between 1 and 9 per cent. The following factors are associated with an increased risk of postoperative infection: It should be remembered that the pelvic tissues in the pregnant woman are lax, with increased vascularity. They are therefore prone to bleed more freely than in the nonpregnant state, and extra care must be taken to ensure the pedicles are correctly ligated. Identification of the lower margin of the cervix may be exceedingly difficult, and a subtotal procedure may need to be considered. This should include the categorization of the degree of urgency of the procedure and critical timings, i. The type of suture material used, the procedure and any complications must be recorded. The surgeon should include a note that the cavity of the uterus was checked and empty and that ovaries and tubes were inspected. The blood loss must be noted and for all emergency procedures the cord gas results should be recorded. Clear post-operative instructions should include a note on suture removal (or not) and, if there are any specific instructions, these must be clearly recorded and communicated to the midwife caring for the woman. Labour, its duration and the presence of ruptured membranes appear to be the most important factors, with obesity playing a particularly important role in the occurrence of wound infections. The most important source of microorganisms responsible for post-caesarean section infection is the genital tract, particularly if the membranes are ruptured preoperatively. Even in the presence of intact membranes, microbial invasion of the intrauterine cavity is common, especially with preterm labour. These complications include fever, wound infection, endometritis, bacteraemia, other serious infection (including pelvic abscess, septic shock, necrotizing fasciitis and septic pelvic vein thrombophlebitis) and urinary tract infection. Such sequelae are an important and substantial cause of maternal morbidity and are often associated with a significant increase in the length of the hospital stay. It should be remembered that fever can occur after any operative procedure, and a low-grade fever following a caesarean delivery may not necessarily be a marker of infection. Other common causes that enter the differential Escherichia coli and other aerobic Gram-negative rods; group B Streptococcus; other Streptococcus species; Enterococcus faecalis; Staphylococcus aureus; coagulase-negative staphylococci; anaerobes (including Peptostreptococcus species and Bacteroides species); Gardnerella vaginalis and genital mycoplasmas. Although Ureaplasma urealyticum is commonly isolated from the upper genital tract and infected wounds, it is unclear whether it is a pathogen in this setting. Wound infections caused by Staphylococcus aureus and coagulase-negative staphylococci arise from contamination of the wound with the endogenous flora of the skin at the time of surgery. The general principles for the prevention of any surgical infection include careful surgical technique, skin antisepsis and antimicrobial prophylaxis. Without prophylaxis, the incidence of endometritis is reported to range from 20 to 85 per cent and the rates of wound infection and serious infectious complications may be as high as 25 per cent. The reduction in the risk of endometritis with antibiotics appears to be similar across a spectrum of patient groups: First stage of labour 410 Caesarean section Table 31. The common regimens have been subjected to a number of trials and have been summarized by meta-analysis [A]. Almost all trials included endometritis, febrile morbidity, wound infection and urinary tract infection as outcome measures. In only three trials were antibiotics given pre-operatively, making comparison of the timing of the first dose impossible. The analysis examined types of antibiotic prophylaxis, single-dose versus multiple-dose regimens and method of administration (systemic versus peritoneal lavage). The drug regimens compared included comparisons of different types of cephalosporins, extended spectrum penicillins, ampicillin and ampicillin plus gentamicin. The most recent large randomized, controlled trial (not included in the meta-analysis) suggested again that prophylactic antibiotics might be unnecessary [B]. Prophylactic antibiotics did not decrease febrile morbidity, wound infection, endometritis, urinary tract infection and pneumonia.

Occlusive devices are available in a range of sizes and initially need to be fitted by trained personnel georges marvellous medicine purchase dulcolax 5 mg. They require a high degree of motivation for successful use medicine grand rounds buy discount dulcolax 5mg on-line, which is the strength of the latex condoms is considerably reduced by oil-based lubricants and vaginal preparations medicine number lookup purchase dulcolax overnight. The patch and the ring are no different from the pill in terms of mechanism of action treatment 5 alpha reductase deficiency purchase dulcolax 5 mg on-line, safety and efficacy treatment rosacea discount dulcolax 5mg online. This risk is further increased with smoking and hypertension and in migraine sufferers symptoms indigestion cheap dulcolax 5 mg on line. The vaginal and cervical mucus becomes scanty and viscous and inhibits sperm transport. Cancer Breast cancer Non-contraceptive benefits Combined hormonal contraceptives decrease menstrual pain and blood loss. There is a decrease in the incidence of functional ovarian cysts, benign ovarian tumours, benign breast disease, pelvic inflammatory disease and acne. There is a possible protective effect against rheumatoid arthritis, thyroid disease and duodenal ulceration. Combined oral contraceptive formulations are either fixed dose or phasic, when the dose of the oestrogen and progestogen changes during the cycle. Drosperinone acts like a natural Combined hormonal contraception 543 progestogen and displays progestogenic, antiandrogenic and antimineralocorticoid activities. Studies have shown that it has less effect on the haemostatic parameters and lipid profile than Microgynon 30 and Logynon. It may therefore prove useful for women over 35 and those with uncomplicated diabetes. The following guidelines should be followed if one pill is missed for more than 12 hours. Reducing the pillfree interval has been shown to decrease mood changes, headaches, menstrual loss and pelvic pain. Other combined hormonal contraceptives Evra patch Twenty microgrammes of ethinyl oestradiol and 150 g of norelgestromin are released per 24 hours. It is the first transdermal contraceptive applied once weekly for 3 weeks followed by a patch-free week (3 weeks on, 1 week off). It has been reported that contraceptive efficacy is reduced in women weighing over 90 kg. Nuva ring the Nuva ring is a flexible, latex-free ring made of plastic and ethylene vinyl acetate which releases 120 g of etonogestrel and 15 g of ethinyl oestrdiol daily. It is placed vaginally once every 3 weeks and following a 1 week ring-free interval, a new ring is inserted. However, women have reported more vaginal symptoms of vaginitis, leucorrhoea, foreign body sensation, coital problems and expulsion. Past history of breast cancer and no evidence of recurrence for five years; carriers of known gene mutations associated with breast cancer. Two in ten women are amenorrhoeic, whereas four in ten have regular bleeding and another four in ten have irregular bleeding. An inflammatory reaction within the endometrium can also have an anti-implantation effect. Copper is toxic to the ovum and the sperm and the copper content of the cervical mucus inhibits sperm penetration as well. They can be safely used by women who suffer from migraines (with or without aura). The woman is therefore advised to abstain, use condoms or start another method 7 days before removal [C]. Antibiotic prophylaxis for the prevention of infective endocarditis is not recommended in women undergoing intrauterine insertion or removal. Management If perforation is suspected at the time of insertion, the procedure should be stopped and vital signs (blood pressure and pulse rate) and level of discomfort monitored until they are stable. An ultrasound scan and/or plain abdominal x-ray should be organized to locate the device if it has been left in situ. Management In a woman with an intrauterine contraceptive in situ and the signs and symptoms are suggestive of pelvic infection, then appropriate antibiotics should be commenced. Where possible, triple swabs should be taken prior to commencing antibiotic therapy. The intrauterine method can be removed if symptoms fail to improve after commencement of antibiotics for 72 hours. The removal should be carried out at an appropriate time (see above under insertion and removal prerequisites). There may even be a need to give emergency hormonal contraception following the removal. The woman should be followed up to ensure resolution of symptoms, counselling for safer sex and partner notification. Vasovagal syncope the incidence of vasovagal syncope at intrauterine contraception insertions is between 0. Management If there are no signs or symptoms suggestive of pelvic infection, then there is no need to remove the device. If symptoms of infection develop, then the woman should be advised to seek medical advice. Medication Perforation the risk of uterine perforation associated with intrauterine contraception is up to two per 1000 insertions [B]. Women should be informed about signs and symptoms of uterine perforation and infection. Reproductive medicine Lost threads Management Women should be advised to use another method until it is confirmed that the device is in situ. The cervical canal can be explored with a thread retriever or a Spencer Wells forceps to 548 Contraception, sterilization and termination of pregnancy bring the threads down if they are in the canal. If this is not successful then an ultrasound scan of the pelvis should be organized. If the intrauterine device is not located on ultrasound, then a plain x-ray of the abdomen should be arranged to identify an extrauterine location. If radiological investigations fail to reveal the device it then is presumed to have been expelled. The device should be removed (provided the threads are visible at the external os) if a woman gets pregnant with a coil/Mirena in situ. It provides endometrial protection from the stimulatory effects of oestrogens and is used along with oestrogen therapy in the management of menopausal symptoms [B]. Sometimes, giving the injection 2 weeks earlier helps with the bleeding, but this is not evidence based. A third of the women are amenorrhoeic at three months and 70 per cent by 12 months of use [B]. A re-evaluation of the risks and benefits of treatment for all women should be carried out every two years in those who wish to continue use [E]. For women with significant lifestyle and/or medical risk factors for osteoporosis, other methods of contraception should be considered. Thickening of the cervical mucus prevents sperm penetration into the upper reproductive tract. It also brings about changes in the endometrium making the environment unfavourable for implantation. The interaction of any enzyme-inducing medication, for example certain anticonvulsants, antiretroviral therapy, rifampicin or rifabutin, is likely to reduce the effectiveness of the implant, therefore consistent use of condoms is recommended. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. They include prolonged bleeding, irregular bleeding, oligomenorrhoea and amenorrhoea. There is no need to decrease the time intervals between injections for women on enzyme inducing drugs. When these have been excluded, bleeding problems can be treated with mefenamic acid or ethinylestradiol (alone or as an oral contraceptive), provided there are no contraindications to oestrogen therapy [C]. Weight gain Weight gain has been reported in various studies ranging from 3 to 12 per cent. It is licensed for three years [C] and is available in a preloaded disposable introducer. There is no evidence of a causal association between the use of an implant and headache [C]. Discontinuation Discontinuation rates of up to 43 per cent within three years have been reported [C]. Emergency contraception 551 Complications with removal Complications with removal are low, in the region of 1 per cent. Endocarditis Prophylactic antibiotics to prevent endocarditis are not needed for insertion and removal of implants [E]. It alters cervical mucus, impairs sperm transport, inhibits ovulation and implantation. However, it can also be given between 73 and 120 hours outside product licence, but there is limited evidence of efficacy [E]. Women who are on liver enzyme-inducing drugs should be advised to take double the dose, i. Interaction with enzyme inducing medication decreases the contraceptive effectiveness of the implant. However, ulipristal acetate appears to be more efficacious compared to levonorgestrel in women who are categorized as overweight or obese. Ulipristal is not recommended in those with severe hepatic impairment, nor in women with severe asthma. As it is not known whether ulipristal is excreted in breast milk, breastfeeding women are advised not to breastfeed for 36 hours after treatment. The most commonly reported side effects are abdominal pain and menstrual disorders, for example irregular vaginal bleeding, premenstrual syndrome and uterine cramps. Use of ulipristal with antacids, proton pump inhibitors and H2 receptor antagonists, or any other drugs that increase gastric pH, may reduce absorption of ulipristal and decrease efficacy. Ulipristal binds to progesterone receptors and so may reduce the efficacy of progestogen-containing contraceptives. Ulipristal is not recommended to be used more than once per cycle as the safety and efficacy of repeated exposure has not been assessed. If hormonal contraception is continued after administering ulipristal, barrier contraception should be used until the next period or withdrawal bleed. Counselling and written information regarding the procedure, its risks, benefits and failure rates should be provided to the client. Discussion and information should also be given regarding other methods, especially the longacting reversible methods of contraception. There have been no studies Sterilization 553 Both men and women should be informed that reversal operations are rarely provided by the National Health Service. The procedure can be carried out under a local anaesthetic and is safer than female sterilization. Following the procedure, men should be advised to use effective contraception until two consecutive semen samples 4 weeks apart confirm azoospermia. It involves using absorbable sutures to tie the base of a loop of the Fallopian tube near the mid-portion and cutting off the top of the loop. A modified Pomeroy procedure rather than Filshie clip application may be preferable for postpartum sterilization performed by mini-laparotomy or at the time of caesarean section, as this leads to lower failure rates [B]. Mechanical occlusion of the tubes by either Filshie clips or rings should be the method of choice for laparoscopic tubal occlusion [A]. Diathermy should not be used as the primary method of tubal occlusion because it increases the risk of subsequent ectopic pregnancy and is less easy to reverse than mechanical occlusive methods [C]. Risks Failure rate Essure method Micro-inserts made from nickel-titanium and stainless steel are inserted hysteroscopically through the cornual ends of both tubes. These generate fibrosis around the devices and the tubes are occluded by three months of the procedures. Some departments carry out a hysterosalpingogram at three months to confirm full occlusion of the tubes. It is an irreversible procedure and the failure rates quoted are the same as for the other methods of tubal occlusion. Therefore, men should be informed that pregnancies can occur several years after vasectomy. Early failures can occur because the wrong structure has been occluded (leaving one or both vasa intact) or because the vas is partially occluded (if ligatures or clips are applied too loosely). Although the vasa may have been occluded bilaterally, if there are any more vasa, spermatozoa can still be released. Early recanalization is recognized by post-vasectomy sperm counts which may at first be azoospermic or reduced, but then rapidly increase again. Late recanalization presents with a pregnancy several months or years after two consecutive azoospermic samples. Chronic testicular pain this is probably due to distension and granuloma formation in the epididymis and vas deferens following the operation [B].

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