Stuart Campbell Ray, M.D.

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0005222/stuart-ray

Natural course and pathogenesis of transient focal neurologic symptoms during pregnancy diabetes insipidus genetic testing generic glimepiride 2 mg buy on line. The second European evidencedbased consensus on reproduction and pregnancy in inflammatory bowel disease diabetes symptoms hindi purchase glimepiride 1 mg overnight delivery. Effects of prenatal exposure to cancer treatment on neurocognitive development: a review brittle diabetes in dogs cheap 1 mg glimepiride free shipping. Complications need to be considered seriously diabetes type 2 treatment guidelines 2014 purchase glimepiride on line, as the potential problems may not be minor: obesity has been shown to increase the risk of morbidity and mortality [1] blood sugar calculator order glimepiride 4 mg on-line. While the immediate risks may be evident to any clinician in practice, what may not be appreciated are the subtle risks of obesity in pregnancy, how even mild obesity may affect progress in labour, the relative malnutrition of vitamins and minerals, maternal malabsorption and consequent malnutrition as a result of bariatric surgery, as well as the effects of maternal obesity on both fetal programming and longterm risk of cardiovascular disease and the increased risk of childhood obesity. Adipose tissue is an endocrine organ, synthesizing and secreting a variety of hormones and inflammatory markers, including cytokines, leptin and adiponectin. It is well recognized that obesity is increasing in prevalence in both the developed and developing world. While all obstetricians appreciate that routine antenatal care needs to be modified in order to provide optimal care to overweight, obese and morbidly obese women, this chapter aims to review the uptodate evidence that will guide those adaptations. Contraception, fertility and conception In adolescence, several studies have shown that obese teenagers may have a higher number of sexual partners, older partners and less use of contraception [4]. This is a worrying pattern that does not continue into adulthood, but does lead to concerns regarding pregnancy risk in a vulnerable group. For those not wishing to conceive, obesity may be a significant factor when considering contraceptive options. The following points should be noted when discussing with obese women the most effective contraception. Safety of contraception should also be discussed at length, including the risk of thromboembolism with some forms of contraception. Concerns regarding weight gain are reassuring for adult women, with mean weight gain of less than 2 kg. In contrast, adolescents showed increased weight gain, with obese adolescents having more weight gain than normal weight adolescents. Combined oral contraceptives: data are conflicting but overall there is no significant reduction in efficacy in obese women. Transdermal combined contraception: body weight over 90 kg is a significant risk factor for failure. The copper intrauterine device is considered the most effective form of emergency contraception in all women, irrespective of body weight. Tubal ligation: no difference in efficacy, though obesity confers additional risks of surgery (access, infection, risk with anaesthesia). Additional benefits may include improvement in menstrual irregularities and reduction in risk of endometrial carcinoma. Given the possible complications of obesity in pregnancy the ethics of providing subfertility treatment to obese women may be hotly debated, with some centres advocating that couples undergo weight loss prior to commencing any treatment. This is also an opportunity for prepregnancy consultation, which will be outlined in more detail in the next section. Weight loss has been shown to increase conceptions, pregnancy and live births; in contrast, women desiring fertility treatment may be concerned regarding nonmodifiable factors such as age. Temporarily withholding fertility care may feel patriarchal, but may be an incentive to motivate women and their partners to achieve change. Even a weight loss of 10% of body weight can increase the rate of fertility, between 77 and 88%. When undergoing fertility treatment, women who are obese face additional challenges, including: It is now well recognized that there is a reduction in fecundity in obese women. Median time to conception in obese women is 5 months, compared with 3 months for normalweight women. Various theories suggesting a causative mechanism have been proposed, including the following [5]. Increased hyperinsulinaemia, resulting in stimulation of ovarian androgen production and hypersecretion of lutenizining hormone. Transdermal combined contraception is a notable exception, with a reduction in efficacy in obese women. The success of fertility treatment is reduced in obese women when compared with normalweight women. This aims not just to inform the woman and her partner of the possible risks of pregnancy but also to modify behaviour and medical care in order to best prepare her for a pregnancy. Obesity, given the significant risks of maternal and fetal morbidity, should be regarded similarly. Indeed, this may be a more productive consultation, as the risk factor is modifiable in a way that cardiac disease and autoimmune disease may not be. Women who present for prepregnancy consultations selfselect to inform themselves and make decisions. Empowering women to make changes can influence not just their health but also the risks of obesity to their pregnancies and their children. Most of the studies reviewing the effects of lifestyle intervention focus on pregnancy itself, but expert opinion suggests that prepregnancy interventions hold considerable potential to improve maternal metabolic health. Opportunities for these consultations include general practice review visits, gynaecological reviews and fertility consultations as well as specialist obstetrics visits with multidisciplinary input. Unlike other longterm diseases, obesity is modifiable, with even small differences in weight significantly reducing the risks to both mother and child. Nutritional support needs to be tailored both to the patient and the type of surgery she had; an appropriately trained dietitian should ideally provide this. As an example, women who have undergone bariatric surgery may require supplemental calcium, iron, vitamin B12, vitamin A, folic acid, iodine and vitamin K [6]. It is advised that pregnancy should be avoided for 1 year after bariatric surgery because of the rapid weight loss and because malabsorption may increase the rate of intrauterine growth restriction, neural tube defects, neonatal hypoglycaemia and low birthweight. Concerns have been raised regarding mechanical complications during pregnancy as a result of pregnancyrelated vomiting, increased intraabdominal pressure and repositioning of the abdominal organs to facilitate fetal and uterine growth. Band migration, band leakage, dehydration, herniation and rotation as well as electrolyte disturbances have been described [5]. Some women may choose to undergo tubal ligation concurrently to bariatric surgery. Screening and general advice Screening for obesityrelated comorbidities (such as type 2 diabetes, chronic hypertension, sleep apnoea, proteinuria, nonalcoholic fatty liver disease and cardiac disease) would be valuable. Specific comorbidities such as ischaemic heart disease may be a relative contraindication to pregnancy. Women should be advised not to smoke cigarettes as this is an additional modifiable risk factor for morbidity and mortality. Such an assessment could include family history, waist circumference, blood pressure, glycaemic control. Special bariatric equipment may be required, for example blood pressure should be measured with an appropriately sized cuff in order to most accurately measure a baseline and assess risk. Because of the relative malnutrition associated with obesity ­ where the maternal diet may comprise mostly of carbohydrates and fat, high in calories, with minimal minerals and vitamins ­ it is generally recommended that obese and overweight women should take a higher dose of folic acid than normalweight women. A dose of 4­5 mg, similar to that for women with diabetes, 210 Maternal Medicine epilepsy or a family history of neural tube defects, should be encouraged. At all times care and communication should be conducted sensitively and respectfully. Prepregnancy consultation presents an opportunity to screen for obesityrelated comorbidities such as diabetes, hypertension, cardiac disease and sleep apnoea. Because of sensitivities regarding the personal nature of weight and selfimage, clinicians may shy away from the challenge of counselling women of the risks of obesity. Some may believe that little can be gained from it as the pregnancy has already started and significant weight loss will not be achievable. It is important that this advice is repeated, and from multiple angles from different clinicians. An honest discussion means that all members of the team caring for a pregnant woman with obesity approach the pregnancy openly and give the woman information on what may happen in her pregnancy. Similar to the prepregnancy consultation, the first booking visit can be an opportunity to screen for pre existing disease in order to be able to accurately discuss prognosis. Blood pressure should be measured with an appropriately sized cuff to establish pregnancy baseline. Pregnant obese women have been shown to have a diet high in saturated fats and inadequate in carbohydrates, calcium, iron, folate and vitamin D [7]. If not already started, consideration should be given to prescribing highdose folic acid in order to reduce the risk of neural tube defects (it is obviously best to commence this before conception). Depending on the location, consideration can also be given to supplementation with vitamin D. This will depend on maternal exposure to sunlight of appropriate wavelength and clothing. It is also recommended that obese pregnant women lower their intake of processed highfat foods and confectionary, with a concomitant increase in complex carbohydrates (wholegrain rice, pasta, bread and cereals) in order to be able to improve macronutrient intake by diet. Women who have lost weight since a previous pregnancy or a prepregnancy consultation should be congratulated: even a small loss of weight can reduce the morbidity associated with a pregnancy affected by obesity. Advice regarding gestational weight gain can be gently but assertively given; the Institute of Medicine recommends a total weight gain in pregnancy of 5­8 kg in obese women [8] (Table 16. This is not just for the pregnancy but also for longterm health, since the strongest predictor of weight retention at 1 year post partum is weight gain in pregnancy. Obesity and Pregnancy 211 Provided there are no obstetric or medical contraindications, obese women should be encouraged to exercise during and after pregnancy, just as with normalweight women. Selfreporting shows that onethird of obese pregnant women are compliant with exercise in pregnancy guidelines; this may be reviewed with caution as a consistent finding is that obese women will overreport activity and under report dietary intake [7]. Dedicated clinics There is no current evidence that one model of antenatal care is superior to any other for obese pregnant women. In contrast, however, a dedicated clinic may not only send a message that obesity is being taken seriously by all members of the multidisciplinary team, but also allow for a package of care to be provided that is consistent to all participants. Pregnancy following bariatric treatment Women who have undergone bariatric surgery prior to pregnancy have specific needs to maximize the health of the pregnancy. There are several case reports of internal bowel rotation during pregnancy following gastric bariatric surgery. Women presenting with severe upper abdominal pain should have urgent surgical assessment as they may require emergency laparotomy and bowel excision. Some of these case reports have also described emergency caesarean delivery at the time of laparotomy; others have described preterm delivery or intrauterine demise in the postoperative period in pregnancies at gestations of very early viability. Consideration should be given to screening earlier in women with significant risk factors, such as morbid obesity, as discussed in the sections on booking visit and prepregnancy consultations. Hypertension and hypertensive disorders Obesity is a risk factor for essential hypertension, pregnancyinduced hypertension and preeclampsia. This is why it is crucially important to accurately measure blood pressure at both booking visits (to establish baseline) and at subsequent visits in order to screen for both pregnancyinduced hypertension and preeclampsia. Stages in the pathogenesis of preeclampsia (cytotrophoblast migration, placental ischaemia, release of placental factors into the maternal circulation, maternal endothelial and vascular dysfunction) are increased as a result of obesityrelated metabolic factors [9]. Antenatal anaesthetic consultation should be considered due to the potential difficulties with venous access and regional or general anaesthesia. In addition, the risk of recurrent miscarriage and intrauterine death is also increased. Given the difficulty of adequate visualization in obesity, it is suggested that a transvaginal probe should be used to scan in early pregnancy in obese women, especially when making the diagnosis of miscarriage. Fetal anomalies Obesity confers an increased risk of fetal anomalies, in particular an increased rate of neural tube defects and congenital heart disease. This may be due to a difference in oocyte quality, increased need for artificial reproductive technologies, relative malnutrition or other yet unidentified factors. Ultrasound assessment Balanced against the increased risks of congenital abnormalities is the difficulty in obtaining highquality ultrasound assessment in obese women, with a substantial number of incomplete anatomical assessments. It is disappointing that the rate of complete anatomy ultrasound was not higher, but this reflects the difficulty of assessing fetal anatomy in obese pregnant women [10]. Growth assessment Because of the difficulty of assessing fetal growth trajectories by measuring symphysis­fundal height in the obese woman, and the risk of either macrosomia or intrauterine growth restriction, a formal ultrasound assessment of fetal growth in the third trimester is recommended. Intrauterine death Obese and morbidly obese women are at increased risk of intrauterine death compared with normalweight women. The threshold for investigation should be reduced in obese and morbidly obese women, for example women presenting with reduced fetal movements or with complications in labour. This was despite the fact that 40% of women undergoing induction of labour required an intrapartum caesarean section. Similarly, the risks of neonatal morbidity were equally distributed between the groups [12]. On closer reading, the risks of maternal and neonatal morbidity were highest in those with unsuccessful induction of labour and emergency caesarean section. A composite maternal morbidity score showed a 45% morbidity rate in women with an emergency caesarean birth, compared with 24% in those undergoing elective caesarean birth and 18% in those having a vaginal delivery following induction of labour. Neonatal morbidity followed a similar pattern: 21% with emergency caesarean section, 10% with planned caesarean and 8% following a vaginal delivery after induction. That vaginal delivery is an appropriate aim, which means correct selection of women and careful management of labour induction. Regarding options for induction and augmentation of labour, there are few published studies comparing efficacy of methods in obese women [11]. Even for obese women who are not morbidly obese, equipment such as longer spinal needles, longer speculums, large blood pressure cuffs and specialized surgical equipment are required to provide safe care [12]. Communication Highquality communication is a key part of the working of any multidisciplinary team caring for patients, and no less so on the labour ward. Both the consultant obstetrician and anaesthetist should be informed when obese women, at least class 3, present in labour. The remainder of the anaesthetic and obstetric teams, as well as the clinical midwife manager, also need to be aware of obese women in labour due to the increased risk of morbidity, and so early intravenous access and epidural/ spinal/combined analgesia should be sited. Dinoprostone tampon: obese women are twice as likely to require a second cervical ripening agent compared with nonobese women, and had labour lasting 5 hours longer.

Detection of endometrial pathology using saline infusion sonography versus gel instillation sonography: a prospective cohort study diabete zuccheri glimepiride 4 mg otc. Diagnostic accuracy of saline infusion sonography in the evaluation of uterine cavity abnormalities prior to assisted reproductive techniques: a systematic review and metaanalyses treatment diabetes mellitus cheap glimepiride amex. An evaluation of sonohysterography and diagnostic hysteroscopy for the assessment of intrauterine pathology diabetic diet 101 discount 1 mg glimepiride with visa. Hysterosalpingo contrast sonography (HyCoSy) and its future role within the investigation of infertility in Europe diabetes ii medications 4 mg glimepiride order with mastercard. Transvaginal sonographic tubal patency testing using air and saline solution as contrast media in a routine infertility clinic setting diabetic diet meal plan cheap glimepiride 1 mg buy online. First experiences with hysterosalpingofoam sonography (HyFoSy) for office tubal patency testing. Can hysterosalpingocontrast sonography replace hysterosalpingography in confirming tubal blockage after hysteroscopic sterilization and in the evaluation of the uterus and tubes in infertile patients Ultrasound guided trucut biopsy in the management of advanced abdominopelvic tumors. Transvaginal ultrasoundguided aspiration for treatment of tubo ovarian abscess: a study of 302 cases. Can the endometrial thickness as measured by transvaginal sonography be used to exclude polyps or hyperplasia in premenopausal patients with abnormal uterine bleeding The pedicle artery sign based on sonography with color Doppler imaging can replace secondstage tests in women with abnormal vaginal bleeding. Comparison of transvaginal ultrasonography and saline infusion sonography for the detection of intracavitary abnormalities in premenopausal women. Evaluation of the uterine cavity with magnetic resonance imaging, transvaginal sonography, hysterosonographic examination, and diagnostic hysteroscopy. Grayscale ultrasound morphology in the presence or absence of intrauterine fluid and vascularity as assessed by color Doppler for discrimination between benign and malignant endometrium in women with postmenopausal bleeding. The characteristic ultrasound features of specific types of ovarian pathology (review). Centralisation of services for gynaecological cancers: a Cochrane systematic review. Ultrasound experience substantially impacts on diagnostic performance and confidence when adnexal masses are classified using pattern recognition. Subjective assessment versus ultrasound models to diagnose ovarian cancer: a systematic review and metaanalysis. Presurgical diagnosis of adnexal tumours using mathematical 48 49 50 51 52 53 54 55 56 57 58 59 models and scoring systems: a systematic review and metaanalysis. Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: a multicenter study by the International Ovarian Tumor Analysis Group. Predicting the risk of malignancy in adnexal masses based on the Simple Rules from the International Ovarian Tumor Analysis group. Ultrasound in preoperative assessment of pelvis and abdominal spread in patients with ovarian cancer: a prospective study. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta analysis. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in the rectosigmoid: systematic review and metaanalysis. Diagnostic accuracy of physical examination, transvaginal sonography, rectal endoscopic sonography, and magnetic resonance imaging to diagnose deep infiltrating endometriosis. A simplified ultrasound based 72 73 74 75 76 77 78 79 80 81 82 83 84 85 infertility investigation protocol and its implications for patient management. Ultrasound assessment of the polycystic ovary: international consensus definitions. The cohort of antral follicles measuring 2­6 mm reflects the quantitative status of ovarian reserve as assessed by serum levels of antiMullerian hormone and response to controlled ovarian stimulation. Automated follicle tracking improves measurement reliability in patients undergoing ovarian stimulation. Assessing first trimester growth: the influence of ethnic background and maternal age. Evidence of early firsttrimester growth restriction in pregnancies that subsequently end in miscarriage. The optimal timing of an ultrasound scan to assess the location and viability of an early pregnancy. Defining safe criteria to diagnose miscarriage: prospective observational multicentre study. The diagnostic effectiveness of an initial transvaginal scan in detecting ectopic pregnancy. Why are some ectopic pregnancies characterized as pregnancies of unknown location at the initial transvaginal ultrasound examination Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies. The clinical 93 94 95 96 performance of the M4 decision support model to triage women with a pregnancy of unknown location as at low or high risk of complications. Human chorionic gonadotrophin and progesterone levels in pregnancies of unknown location. Rationalizing the management of pregnancies of unknown location: temporal and external validation of a risk prediction model on 1962 pregnancies. These minimally invasive approaches enhance recovery from the insult of surgery by avoiding large sur gical incisions, allowing more rapid discharge from hos pital and a quicker return to normal functioning. In previous editions of this textbook, hysteroscopy and laparoscopy were often considered novel interventions, restricted to diagnosis for most practitioners and with therapeutic interventions essentially the preserve of those with a particular interest in minimal access sur gery. This paradigm shift has arisen primarily as a result of the enthusiasm of surgeons, the expectations of patients and advances in technology. The latter factor is of key importance as visualization, surgical instrumentation and energy modalities have hugely improved the safety and feasibility of endoscopic surgery. Operative hysteros copy has benefited from the development of new tech nologies such as bipolar electrosurgery to resect uterine pathologies and tissue removal systems to simultaneously cut and aspirate tissue (overcoming issues over compro mised visualization from collected debris and its removal). Advances in instrumentation have not only impacted on the feasibility, safety and effectiveness of existing hystero scopic procedures, they have also allowed new proce dures to be introduced such as hysteroscopic sterilization and global semiautomated endometrial destruction for the treatment of heavy menstrual bleeding. Moreover, the miniaturization and portability of equipment now facili tate ambulatory or outpatient/officebased intervention in traditional hospital or contemporary community based settings. Ambulatory gynaecology avoids the costs and morbidity of hospital admission, providing safe, acceptable and convenient treatment to women. In operative laparoscopy, advanced bipolar and ultra sonic instruments have facilitated haemostasis and tissue dissection. Laparoscopic instruments are now smaller and have greater degrees of articulation that facilitate singleport laparoscopy and natural orifice transluminal endoscopic surgery. The enhanced visualization, instru mentation and ergonomics associated with robotic sur gery are manifest in many centres but at present the costs are prohibitive for more generalized adoption in the absence of data supporting enhanced effectiveness. The scientific evidence supporting the adoption of minimal access surgery is expanding, with the publica tion of diagnostic studies examining the accuracy of endoscopic tests, observational series/registries scruti nizing complications of endoscopic interventions and randomized controlled trials evaluating effectiveness of interventions. However, as pointed out by a previous author of this chapter, it is worth reminding readers, and especially the new cadre of gynaecologists in training, that laparoscopic surgery was first developed by gynae cologists not general surgeons. Indeed, it was Semm, a gynaecologist, who carried out the first laparoscopic appendicectomy in 1983 [1]. Light sources have evolved from the initial platinum wire loop to fibreoptics and the rodlens system. Illumination is now usually achieved using an incandescent bulb and heat generated is in the form of infrared light. A condensing lens concentrates light from the bulb into a narrow beam at the cable input and the light is then transmitted to the laparoscope via a gel or fibre cable. Highdefinition cameras require a higher performance light source because they have reduced sensitivity given the smaller pixel size. Camera and monitor system the camera system consists of three key components: the camera head, the camera control unit and the monitor to visualize the image. The image is captured as a digital signal from a distal mounted lens and transmitted through a rodlens system to an ocular mounted lens which mag nifies it and the image is visualized on a monitor. Current threechip cameras consist of a goal lens, a prism assembly and three sensors for acquiring the pri mary colours, providing more natural colour reproduc tion than earlier technologies. Video laparoscopes are now also available where the chips are built into the end of the optic, capturing the image at the tip of the laparo scope and improving image quality and accuracy. Three dimensional imaging provides greater depth perception [2], although the technology has yet to achieve wide spread popularity. A video cable transmits the digital image data between the camera head, camera control unit, and monitor. Flat screens in high definition have superseded earlier monitors and provide a much supe rior image. Narrowband imaging is a recent innovation, which uses a specific narrow wavelength to change the normal colour contrasts of the laparoscopic image. Energy modalities Electrosurgery, often referred to as diathermy, has been used in surgery for over 100 years and has become an integral component of both hysteroscopic and laparo scopic surgery. Laparoscopic energy modalities are essential for dissection, ligation and haemostasis [3]. Monopolar, bipolar, ultrasonic and advanced bipolar energy sources are currently used. Ambulatory Gynaecology, Hysteroscopy and Laparoscopy 521 depends on electrical arcing between the electrode and tissue resulting in vaporization and cell explosion, whereas coagulation is achieved with the electrode in contact with tissue causing heating and coagulation. Monopolar electrosurgery delivers an electrical current via one active electrode that disperses through the patient to an attached passive return electrode. The advantages of monopolar diathermy include the ability to chose pure or mix/blend currents so that cutting and dissection can be achieved while providing haemostasis and coagulation. Disadvantages include (i) unintentional thermal injury due to thermal spread and unintentional visceral contact with active or heated electrodes, (ii) direct or capacitive coupling and (iii) improper place ment of the return electrode or contact with volatile sub stances such as cleaning fluids. Bipolar electrosurgery differs from monopolar in that the current travels only between the two active prongs of the electrodes. Therefore, the energy travels only through the target tissue and not through the patient. Both electrodes are of equal size, producing similar temperature changes at both ends, allowing for targeted desiccation at lower temperatures. The advantages of bipo lar electrosurgery include a virtually eliminated chance of alternate site burns or direct and capacitative coupling. As no return electrode is required, the risk of a dispersive electrode burn is eradicated. Advanced bipolar electrosurgery refers to devices that have been developed to more precisely manage delivery of bipolar electrical energy, providing consistent and rapid tissue and blood vessel sealing. This blade is deployed to provide bloodless cutting after very effective desiccation of the tissue. Ultrasonic energy can also be used to dissect, cut and coagulate tissue, avoiding the potential dangers associ ated with electrical currents. Mechanical energy is generated from rapid vibrations of a blade or shears at the tip of the instrument, causing water to evap orate from the tissues at a low temperature. The other mechanism it uses is stretching of the tissue by the blade edge, causing friction and generating heat, cut ting the tissue. The advantage of the ultrasonic scalpels compared with electrosurgery is the reduction in tissue charring, desiccation and spread of thermal energy, low ering the risk of inadvertent injury to other structures. Devices are now also available that combine both advanced bipolar electrosurgery with ultrasonic energy. Advanced bipolar devices and ultrasonic energy appear to provide more rapid and bloodless operating compared with conventional electrosurgery. Ultrasonic energy is used to dissect and desiccate tissue studies have not demonstrated a significant difference in complication rate between devices but this may be due to a relatively low complication rate in gynaecological pro cedures [4,5]. However, there is a need for properly designed and powered comparative studies to guide sur geons regarding the most effective and safe modes of energy to use for specific operations. Laser energy in minimal access gynaecological surgery has diminished with the advent of the newer, easier to use and cheaper energy modalities described here. Photo and video documentation the universal use of video cameras at endoscopic sur gery lends itself to recording still images, short excerpts of procedures or even whole procedures. Photographs are clinical records that can be discussed with the patient as well as colleagues if a second opinion is sought. Video recordings are excellent for teaching, and can also be 522 Basic Science used for research, to measure performance and to assess new instruments and techniques. Review of recordings can also help with the understanding of operative com plications and are increasingly useful with regard to complaints and negligence claims. Equipment for hysteroscopy Direct imaging within the uterine cavity utilizing hyster oscopy requires an endoscope, outer sheath(s) for pas sage of distension media, a light lead and camera relaying to a monitor. The majority of gynaecologists use rigid hysteroscopes because the image tends to be superior, the equipment is more robust and it can be sterilized. Moreover, operative procedures can be undertaken using rigid hysteroscopes whereas flexible hysteroscopes are restricted to diagnosis. Rigid hysteroscopes generally have a Hopkins rodlens optical system whereas flexible and very narrow rigid hystero scopes contain optical fibres. The distal lens can be straight or oblique, the most frequently used being 0° and 30° angles of view. Oblique lenses have the advantage of a wider field of view, ena bling diagnosis and facilitating operative procedures as instrumentation can be visualized under higher magnifi cation. Diagnostic procedures can be performed using a single outer sheath fitted around the optic to allow irri gation of fluid or gas distension media thereby achieving uterine distension. Continuous flow permits simultane ous irrigation/suction and tends to be used for surgery where removal of blood and tissue debris is necessary to maintain visualization within the uterine cavity. To achieve continuous flow, operative hysteroscopes have both inflow and outflow channels (inner sheath for inflow, outer sheath for outflow) in addition to a working channel which can accommodate miniature ancillary instruments. Uterine distension the uterine cavity is a potential space and has to be dis tended at relatively high pressure to afford a panoramic view. The choice of fluid distension media for operative hysteroscopy depends on the type of instrumentation; physiological media, namely normal saline, should be preferred when using mechanical instruments. Resectoscopic electro surgery traditionally required the use of electrolytefree solutions such as glycine, sorbitol or mannitol because they employed monopolar electrical circuits. Bipolar electrosurgery using miniature electrodes or conven tionally sized resectoscopes are now widely available and these necessitate the use of electrolytecontaining fluid distension media, i.

A metaanalysis of studies that reported umbilical artery Doppler parameters in pregnancies defined as having a high risk of fetal growth restriction during the third tri mester found that absent or reversed enddiastolic flow was associated with a significant increase in risk of peri natal mortality [58] diabetes mellitus y embarazo pdf discount glimepiride 2 mg. In many centres diabetes type 1 information 2 mg glimepiride order, umbilical artery Doppler parameters are now reported as a matter of routine during a thirdtrimester scan diabetes symptoms kids causes glimepiride 4 mg with amex, but it is important to interpret the findings in the context of the literature diabetes mellitus obesity order cheap glimepiride, as other studies have shown that this is not a useful marker for fetal wellbeing in lowrisk patient cohorts late in the third trimester [59] diabetes symptoms swollen ankles glimepiride 1 mg purchase with visa. In this example there is forward flow in diastole, a normal finding in the third trimester of pregnancy. Later in the third trimester, where the pathology underlying growth failure and ultimately stillbirth is more likely to be due to placental failure rather than pla cental insufficiency, other Doppler indices become more important in defining fetal welfare. As yet, there are few data that have demonstrated that either routine screening with a cerebroplacental ratio or application to specific highrisk groups. The ultrasound assessment of fetal growth, amniotic fluid index and haemodynamics has, to a large extent, replaced the more formal process of assessing fetal wellbeing by scoring the biophysical profile. Each component of the test is scored two points (if normal) or zero points (if abnormal). Scores below 10 lead to further intensive surveillance or induction of labour depending on the level of the score and the gestation of the pregnancy. Whilst the biophysical profile provides a clear structured method of assessing fetal wellbeing, it fails to include all parameters that may be of importance (biometry and Doppler) and does not adequately weight the various components of the test in relation to their likely associa tion with pathology. The score has, on occasion, been modified and applied in various high or lowrisk cir cumstances with various ongoing management strategies [68,69]. Predicting fetal macrosomia, risk of failure to progress and shoulder dystocia in labour Fetal macrosomia also poses a significant risk of adverse pregnancy outcome in the third trimester of pregnancy. Macrosomia is associated with stillbirth and birth injury (shoulder dystocia, brachial plexus injury and limb frac ture) as well as increased rates of operative delivery and perineal trauma [71]. Postnatally, macrosomic infants have higher rates of admission to the neonatal unit and are more likely to develop hypoglycaemia and hyperbili rubinaemia [72]. Macrosomic infants have increased rates of diabetes, metabolic syndrome and cardiovascu lar disease later in childhood and in adult life [73]. Across the world, changes in lifestyle and diet are contributing to increasing rates of gestational diabetes and hypergly caemia in pregnancy and we face a global epidemic of macrosomia and its sequelae [74]. Macrosomia has traditionally been defined using a fixed birthweight cutoff (commonly 4000 or 4500 g) independent of gesta tional age of delivery. These thresholds are based on the finding of increased rates of morbidity above these lim its, although the reality is that these are continuous variables and it would likely be better to describe risks based on algorithms that define centiles in relation to , rather than being independent of, gestational age, although this adds complexity to categorization [75]. Many macrosomic infants are born to women who have diabetes in pregnancy and it has been suggested that stillbirth results from metabolic acidosis in these cases [76]. Interestingly, others have suggested that death might occur if the fetal cell mass exceeds pla cental ability for tissue oxygenation, and it has been proposed that maternal cardiac failure may contribute to fetal death in this circumstance [77]. Clinicians have a poor history for accurate estimation of fetal weight in the later part of the third trimester. The heterogeneity of the literature, using different charts and cutoffs to define macrosomia, make it difficult to determine absolute sensitivity of ultrasound and studies have reported detection rates of 15­79% [79]. Researchers have com pared different algorithms for estimation of fetal weight and prediction of macrosomia which have shown sig nificant variation in findings. Predicting risk purely through ultrasound assessment using standard biomet ric parameters appears unlikely to be useful in defining a macrosomic cohort in routine practice [80]. There is also evidence that different algorithms should be applied to diabetic and nondiabetic populations [81]. Risk assessment may be improved by acknowledging differing maternal characteristics and using a Bayesian multivariate approach to screening [82]. It is not clear whether screening should then be limited to highrisk cohorts (perhaps defined through maternal characteris tics and/or medical history), through a contingent process based on findings of screening tests performed at an early stage of pregnancy, or to the whole population [83]. Opinion regarding the management of macrosomic fetuses at term has typically been divided, with few prospective data to inform clinical practice. Some have argued that induction of labour may prevent maternal and neonatal morbidity associated with delivery of an overgrown infant whilst others have maintained that the process of induction carries its own inherent risks. There are now four randomized controlled trials that, in meta analysis, appear to show that induction of labour may be beneficial and result in reduction in rates of neonatal birth injury (brachial plexus injury and limb fracture) [84]. Some of the trials in this metaanalysis are relatively small and did not report all outcome measures. These are also relatively uncommon outcomes, so 60 inductions need to be performed to prevent one adverse outcome. When this is coupled to the fact that we do not yet have a validated and strongly predictive screening test, it is dif ficult to advocate a process of routine screening and intervention without further research in this field [85]. In addition to developing algorithms that identify the macrosomic fetus, some groups have focused on the development of algorithms that will predict the likely success of induction of labour or the spontaneous onset of labour. These algorithms variously include maternal demographic factors with ultrasound estimates of fetal size and/or fetal Doppler, cervical length and/or mobility of the pelvic floor [86­89]. There is currently no consen sus on the factors that should be included in such a predictive model and no prospective validation or dem onstration of improved maternal and perinatal outcomes through application of such a test [90]. Conclusion Ultrasound is a diverse tool that has many applications in the third trimester. In many settings, a thirdtrimester scan is not currently part of a routine antenatal screen ing strategy and there are limited data to support routine populationbased screening. Ultrasound is often best applied as one component of multivariate risk assessment and this is the subject of much ongoing research, with applications as diverse as the prevention of stillbirth, shoulder dystocia or mater nal perineal trauma. Given the current medicolegal environment, it is likely that these methods of risk assessment will become an integral part of management of the third trimester as they will allow clinicians to have better informed conversations about risk with their patients. Predictive tools (ultrasound and biochemical testing) for preterm birth improve the chances of preventing or ameliorating outcomes of early birth. Ultrasound assessment allows early recognition of invasive placentation and appropriate management at delivery improves maternal outcomes. Further research is needed to determine whether routine thirdtrimester ultrasound surveillance reduces the prevalence of stillbirth. Prediction and prevention of earlyonset preeclampsia: impact of aspirin after firsttrimester screening. Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index. Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor. Cervical length at 23 weeks of gestation: relation to demographic characteristics and previous obstetric history. A comparison 14 15 16 17 18 19 20 21 22 23 24 25 of vaginal ultrasound and digital examination in predicting preterm delivery in women with threatened preterm labour: a cohort study. The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women. Is the third trimester repeat ultrasound scan for placental localisation needed if the placenta is low lying but clear of the os at the midtrimester morphology scan Transvaginal ultrasonography for all placentas that appear to be lowlying or over the internal cervical os. Transvaginal sonographic assessment of cervical length and wedging for predicting outcome of labor induction at term: a systematic review and metaanalysis. Predictive model for risk of cesarean section in pregnant women after induction of labor. Transabdominal ultrasonography as a screening test for secondtrimester placenta previa. Sonographic measurement of lower uterine segment thickness to predict uterine rupture during a trial of labor in women with previous Cesarean section: a metaanalysis. Update on the diagnosis and classification of fetal growth restriction and proposal of a stagebased management protocol. The sequence of changes in Doppler and biophysical parameters as severe fetal growth restriction worsens. Antecedents of cerebral palsy and perinatal death in term and late preterm singletons. A new approach to developing birth weight reference charts: a retrospective observational study. Customised versus populationbased growth charts as a screening tool for detecting small for gestational age infants in lowrisk pregnant women. Gestational age at delivery and special educational need: retrospective cohort study of 407,503 schoolchildren. Effectiveness of detection of intrauterine growth retardation by abdominal palpation as screening test in a low risk population: an observational study. Value of a single early third trimester fetal biometry for the prediction of birth weight deviations in a low risk population. Using unconditional and conditional standard deviation scores of fetal abdominal area measurements in the prediction of intrauterine growth restriction. A kick from within: fetal movement counting and the cancelled progress in antenatal care. Predicting poor perinatal outcome in women who present with decreased fetal movements. Clinical Practice Guideline for the Management of Women who Report Decreased Fetal Movements. Predictors of poor perinatal outcome following maternal perception of reduced fetal movements: a prospective cohort study. Induction of labor as compared with serial antenatal monitoring in postterm pregnancy: a randomized controlled trial. Association and prediction of amniotic fluid measurements for adverse pregnancy outcome: systematic review and metaanalysis. Doppler ultrasonography in highrisk pregnancies: systematic review with meta analysis. Cerebral blood perfusion and neurobehavioral performance in fullterm smallforgestationalage fetuses. MoralesRoselló J, Khalil A, Morlando M, Papageorghiou A, Bhide A, Thilaganathan B. Changes in fetal Doppler indices as a marker of failure to reach growth potential at term. The association between a low cerebroumbilical ratio at 30­34 weeks gestation, increased intrapartum operative intervention and adverse perinatal outcomes. Clinical utility of third trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in smallforgestationalage fetuses. Longitudinal changes in uterine, umbilical and fetal cerebral Doppler indices in lateonset smallforgestational age fetuses. Fetal biophysical profile scoring: a prospective study in 1,184 highrisk patients. Comparison of modified biophysical profile and Doppler ultrasound in predicting the perinatal outcome at or over 36 weeks of gestation. Ultrasonographic weight estimation in large for gestational age fetuses: a comparison of 17 sonographic formulas and four models algorithms. Sonographic estimation of fetal weight in macrosomic fetuses: diabetic versus nondiabetic pregnancies. Predicting risk for largeforgestational age neonates at term: a populationbased Bayesian theorem study. Performance of the ultrasound examination in the early and late third trimester for the prediction of birth weight deviations. Clinical and ultrasound parameters to predict the risk of cesarean delivery after induction of labor. Cervical condition and fetal cerebral Doppler as determinants of adverse perinatal outcome after labor induction for lateonset smallfor gestationalage fetuses. Prior to this the fetus relies on placental trans fer of maternal thyroid hormones. There is no relationship between maternal and fetal thyroid hormone levels, confirming that development of the fetal pituitary­thyroid axis is independent of the mother. Disruption of normal thyroid function, if unrecognized and untreated, can therefore have significant longterm sequelae. Thyroid dysfunction in the fetus can result from a primary prob lem affecting the fetus. More commonly it occurs second ary to maternal thyroid disease and/or its treatment. The presence of fetal goitre indicates thyroid dysfunc tion, provided other differential diagnoses of a fetal neck mass, such as cystic hygroma, cervical teratoma and hae mangioma, have been excluded. The serious adverse consequences of fetal hyperthyroidism are miscarriage and intrauterine death, and of hypothy roidism neonatal cretinism. High concentrations of antibodies identify a pregnancy at risk of fetal hyperthyroidism. A large fetal goitre can cause hyperextension of the fetal neck resulting in malpresentation. Oesophageal compression may result in polyhydramnios with its associated risk of preterm labour. There may be tachycardia or bradycar dia and in severe cases complete heart block. Fetal hypo thyroidism is often unrecognized and should be consid ered in all women with a history of thyroid disease and/or antithyroid medication. Management Ultrasound can detect fetal goitre, which is the earliest ultrasound feature of fetal thyroid dysfunction and appears before fetal tachycardia. Fetal goitre is defined as a thyroid circumference equal to or greater than the 95th centile for gestational age and normative fetal thyroid measurements have been defined [4]. Colour flow Doppler may help differentiate between a hyperthyroid and a hypothyroid goitre. Hyperthyroidism is associated with a signal throughout the gland, whereas a signal con fined to the periphery of the gland is suggestive of hypo thyroidism [5,6].

A standardized scoring system diabetes signs eyes glimepiride 4 mg line, such as the modified Ferriman­Gallwey score diabetic diet 2000 calories per day purchase 1 mg glimepiride with mastercard, may be used to evaluate the degree of hirsutism before and during treatments diabetes definition by ada trusted glimepiride 2 mg. Many women attend having already tried cosmetic techniques and so it may be difficult to obtain a baseline assessment diabetes mellitus journal glimepiride 4 mg order mastercard. Drug therapies may take 6­9 months or longer before any improvement in hirsutism is perceived diabetic diet for weight loss trusted glimepiride 4 mg. The chart is used both to provide an initial score, with a scale of 0­3 at each of 12 points, depending on severity, and for the monitoring of progress with therapy. Electrolysis is timeconsuming, painful and expen sive, and should be performed by an expert practitioner. Laser and photothermolysis techniques are more expensive but may have a longer duration of effect. Repeated treatments are required for a nearpermanent effect because only hair follicles in the growing phase are obliterated at each treatment. Hair growth occurs in three cycles, so 6­9 months of regular treatments are typical. It works by inhibiting the enzyme ornithine decarboxylase in hair follicles and may be a useful therapy for those who wish to avoid hormonal treatments, but may also be used in conjunction with hormonal therapy. Eflornithine may cause some thin ning of the skin and so highfactor sun block is recom mended when exposed to the sun. Medical regimens should stop further progression of hirsutism and decrease the rate of hair growth. Adequate contraception is important in women of reproductive age as transplacental passage of antiandrogens may disturb the genital development of a male fetus. Firstline therapy has traditionally been the preparation Dianette, which contains ethinylestradiol (30 µg) in combination with cyproterone acetate (2 mg). The addition of higher doses of the synthetic progestogen cyproterone acetate (50­ 100 mg) do not appear to confer additional benefit. Cyproterone acetate can rarely be associated with liver damage, and liver function should be checked after 6 months and then annually. Once symp tom control has been obtained, it is advisable to switch to a combined oral contraceptive pill containing a lower dose of ethinylestradiol because of concerns about the increased risk of thromboembolism with Dianette [5]. In women in whom the combined oral contraceptive pill is contraindicated, spironolactone, a weak diuretic with antiandrogenic properties, may be used at a daily dose of 25­100 mg. Strategies to induce ovulation include weight loss, oral antioestrogens (principally clomifene citrate or tamoxifen), parenteral gonadotrophin therapy and laparoscopic ovarian surgery. Clomifene is the tradi tional firstline therapy and can be continued for 6­12 cycles of treatment if the patient is ovulating with normal endocrinology. Aromatase inhibitors, such as letrozole, may also stimulate ovulation and appear to be associated with a lower risk of multiple pregnancy; however, they are not currently licensed for the treat ment of infertility. Improvements in lifestyle, with a combination of exercise and diet to achieve weight reduction, are important for improving the prospects of both spon taneous and druginduced ovulation. Ovulation can be induced with the antioestrogen clomifene citrate (50­100 mg) taken from days 2­6 of a natural or artificially induced bleed. While clomifene is successful in inducing ovulation in over 80% of women, pregnancy only occurs in about 40%. Clomifene citrate should only be prescribed in a setting where ultra sound monitoring is available (and performed) in order to minimize the 10% risk of multiple pregnancy and to ensure that ovulation is taking place [14]. A daily dose of more than 100 mg rarely confers any benefit and can cause thickening of the cervical mucus, which can impede passage of sperm through the cervix. Once an ovulatory dose has been reached, the cumulative conception rate continues to increase for up to 10­12 cycles [14]. The therapeutic options for patients with anovula tory infertility who are resistant to antioestrogens are either parenteral gonadotrophin therapy or laparo scopic ovarian diathermy. Because the polycystic ovary is very sensitive to stimulation by exogenous hor mones, it is extremely important to start with very low doses of gonadotrophins and follicular development must be carefully monitored by ultrasound scans. The advent of transvaginal ultrasonography has enabled the multiple pregnancy rate to be reduced to less than 5% because of its higher resolution and clearer view of the developing follicles. Cumulative conception and livebirth rates after 6 months may be 62% and 54%, respectively, and after 12 months 73% and 62%, respec tively [16]. Close monitoring should enable treatment to be suspended if more than two mature follicles develop, as the risk of multiple pregnancy increases. This occurs if too many follicles (>10 mm) are stimulated and results in abdominal dis tension, discomfort, nausea, vomiting and sometimes difficulty in breathing. While patients with weightrelated amenorrhoea conceive readily after ovulation induction, we now believe that their management should be weight gain before conception (see text). Cumulative conception and live birth rates after the treatment of anovulatory infertility. Hospitalization is sometimes necessary in order for intravenous fluids and heparin to be given to prevent dehydration and thromboembolism. Pregnancy rates are higher with 6 months of gonado trophin therapy compared with 6 months after laparo scopic ovarian diathermy [17]. The ascites and pleural and pericardial effusions exacerbate this serious condition and the resultant haemoconcen tration can lead to thromboembolism. The situation worsens if a pregnancy has resulted from the treatment as human chorionic gonadotrophin from the placenta A number of pharmacological agents have been used to amplify the physiological effect of weight loss, notably metformin. This biguanide inhibits the production of hepatic glucose and enhances the sensitivity of periph eral tissue to insulin, thereby decreasing insulin secretion. All subjects had an individualized assessment by a dietitian in order to set a realistic goal that could be sustained with an average reduction of energy intake of 500 kcal/ day. As a result, both the metformintreated and pla cebo groups managed to lose weight, but the amount of weight reduction did not differ between the two groups. An increase in menstrual cyclicity was observed in those who lost weight but again did not differ between the two arms of the study, reinforcing the key role of weight reduction. Diagnosis is made by the presence of two of the following three criteria: (i) oligo ovulation and/or anovulation, (ii) hyperandrogenism (clinical and/or biochemical) or (iii) polycystic ovaries, with the exclusion of other aetiologies of menstrual irregularity and androgen excess. Dietary advice and exercise are essential components of a weightreduction programme. Menstrual cycle control may be achieved by using cyclical oral contraceptives or progestogens. Ovulation induction may be difficult and require progression through various treatments, which should be monitored carefully to prevent multiple pregnancy. Hyperandrogenism is usually managed with Dianette, which contains ethinylestradiol in combination with cyproterone acetate, or Yasmin, which contains drospirenone. The recent Cochrane review has also concluded that there is no benefit of met formin in achieving an increased rate of live birth either alone or in combination, and so the use of metformin is only recommended when there is impaired glucose tol erance or type 2 diabetes [21]. Polycystic ovary syndrome Premature ovarian insufficiency Hyperprolactinaemia Weightrelated amenorrhoea Hypogonadotrophic hypogonadism Hypopituitarism Exerciserelated amenorrhoea 37% 24% 17% 10% 6% 4% 3% Secondary amenorrhoea Cessation of menstruation for six consecutive months in a woman who has previously had regular periods is the usual criterion for investigation. However, some authori ties consider 3 or 4 months of amenorrhoea to be patho logical, but this is a debate between the definition of amenorrhoea and oligomenorrhoea. Women with sec ondary amenorrhoea must have a patent lower genital tract, an endometrium that is responsive to ovarian hor mone stimulation and ovaries that have responded to pituitary gonadotrophins. Secondary amenorrhoea is best classified according to its aetiological site of origin and can be subdivided into disorders of the hypothalamic­pituitary­ovarian­uter ine axis and generalized systemic disease. The frequency with which these conditions present, on the other hand, can be seen in Table 47. This may be the result of an overvigorous endometrial curettage affecting the basalis layer of the endometrium or adhesions that may follow an episode of endometritis. It is thought that oestrogen deficiency increases the risk of adhesion formation in breast feeding women who require a puerperal curettage for retained placental tissue. Typically, amenorrhoea is not absolute, and it may be possible to induce a with drawal bleed using a combined oestrogen/progestogen preparation. Alternatively, hysteroscopic inspec tion of the uterine cavity will confirm the diagnosis and enable treatment by adhesiolysis. The adhesions bridge the anterior and posterior walls of the uterine cavity 646 Menstruation and are usually avascular, although may contain vessels, muscle and even endometrium. Following surgery, high dose oral oestrogens are initially prescribed followed by a 3month course of cyclical progesterone/oestrogens. Some clinicians insert a Foley catheter into the uterine cavity for 7­10 days postoperatively or an intrauterine contraceptive device for 2­3 months in order to prevent recurrence of adhesions. Cervical stenosis Cervical stenosis is an occasional cause of secondary amenorrhoea. It was relatively common following a tra ditional cone biopsy for the treatment of cervical intraep ithelial neoplasia. However, modern procedures, such as laser or loop diathermy, have less postoperative cervical complications. It still occasionally occurs following curettage of the uterus which inadvertently damages the endocervix. Treatment for cervical stenosis consists of careful cervical dilatation, usually under ultrasound guidance. Premature ovarian insufficiency Ovarian failure by definition is the cessation of periods accompanied by a raised gonadotrophin level prior to the age of 40 years [23]. The exact incidence of this condition is unknown as many cases go unrecognized, but estimates vary between 1 and 5% of the female population. Ovarian failure occurring before puberty is usually due to a chromosomal abnormality or a childhood malig nancy that required chemotherapy or radiotherapy. It is therefore important to consider other autoim mune disorders and screen for autoantibodies to the thy roid gland, gastric mucosa parietal cells and adrenal gland if there is any clinical indication. This occult ovarian failure, or resistant ovary syndrome, is associated with the pres ence of primordial follicles on ovarian biopsy (which incidentally is not a procedure that should be performed to make the diagnosis). Pregnancies are sometimes achieved, although the ovaries are usually resistant to exogenous gonadotrophins as they are to endogenous hormones. An alternative approach is the surgical removal of a whole ovary and transplantation of cryopreserved ovar ian tissue once the cancer treatment is completed. Live births have been achieved by all these methods, although the technology for oocyte cryopreservation is less effi cient than for embryo cryopreservation and ovarian this sue freezing is still in its infancy [23]. It may be particularly difficult for a young woman to accept the need to take oestrogen preparations that are clearly labelled as being intended for older postmenopausal women while at the same time having to come to terms with the inability to conceive naturally. The short and longterm consequences of ovarian failure and oestrogen deficiency are similar to those occurring in the fifth and sixth decade. Younger women with premature loss of ovarian func tion have an increased risk of osteoporosis. The degree of bone loss was correlated with the duration of the amen orrhoea and the severity of the oestrogen deficiency rather than the underlying diagnosis, and was worse in patients with primary amenorrhoea than in those with secondary amenorrhoea. However, it is not certain if the radiological improvement seen will actually reduce the risk of fracture, as remineralization is not equivalent to the restrengthening of bone. Oestrogens have been shown to have beneficial effects on cardiovascular status in women. Pituitary causes of secondary amenorrhoea Hyperprolactinaemia is the commonest pituitary cause of amenorrhoea. There are many causes of a mildly ele vated serum prolactin concentration, including stress, and a recent physical or breast examination. In women with amenorrhoea associated with hyper prolactinaemia, the main symptoms are usually those of oestrogen deficiency. Galactorrhoea may be found in up to onethird of patients with hyper prolactinaemia, although its appearance is correlated neither with prolactin levels nor with the presence of a tumour. The management of hyperprolactinaemia centres around the use of a dopamine agonist, of which bro mocriptine and cabergoline are the most widely used. Of course, if the hyperprolactinaemia is drug induced, stop ping the relevant preparation should be commended. However, this may not be appropriate if the cause is a psychotropic medication, for example a phenothiazine being used to treat schizophrenia. In these cases it is rea sonable to continue the drug and prescribe a lowdose combined oral contraceptive preparation in order to counteract the symptoms of oestrogen deficiency. Serum prolactin concentrations must then be carefully moni tored to ensure that they do not rise further. Most patients show a fall in prolactin levels within a few days of commencing bromocriptine therapy and a reduction in tumour volume within 6 weeks. Side effects can be troublesome (nausea, vomiting, headache, postural hypotension) and are minimized by commencing the therapy at night for the first 3 days of treatment and taking the tablets in the middle of a mouthful of food. The longeracting preparation cabergoline appears to have fewer side effects and is more commonly used these days. Bromocriptine and cabergoline have been associated with pulmonary, retroperitoneal and pericar dial fibrotic reactions and so echocardiography is recom mended before starting treatment in order to exclude valvulopathy and this should be repeated after 3­6 months and then annually, although young patients are less at risk than older patients who may be prescribed 648 Menstruation (a) (b) (c) (d). The normal pituitary gland is hyperintense (bright) while the tumour is seen as a 4mm area of nonenhancement (grey) in the right lobe of the pituitary, encroaching up to the right cavernous sinus. There is suprasellar extension with compression of the optic chiasm (small arrows). The tumour signal intensity on the T1 image and only part of the periphery of the tumour enhances. The carotid arteries have a low signal intensity (black arrows) due to the rapid flow within them and are deviated laterally and superiorly by the mass (C), which arises out of the pituitary fossa (P). The maintenance dose should be the lowest that reduces prolactin to normal levels and is often lower than that needed to initiate a response (Table 47. Surgery, in the form of transsphenoidal adenectomy, is reserved for cases of drug resistance and failure to shrink a macroadenoma or if there are intolerable side effects of the drugs (the most common indication). Operative treatment is also required if there is suprasellar extension of the tumour that has not regressed during treatment with bromocriptine and a pregnancy is desired.

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