Prevalence of High BloodPressure: An estimated 1.8 million people in Sweden, or 27% of the adult population (aged 20 or older), have high blood pressure (hypertension). The condition is just as common among women as men. Of the 1.8 million Swedish adults with elevated blood pressure: 60% have mild hypertension (140–159/90–99 mm Hg). 30% have moderate hypertension (160–179/100–109 mm Hg). 10% have severe hypertension (≥180/≥110 mm Hg). Studies in Sweden find that the number of patients who reach the treatment goal of blood pressure below 140/90 mm Hg rarely exceeds 20–30% of those who have been prescribed blood pressure lowering drugs. Risk Factor for Cardiovascular Disease: Elevated blood pressure is a risk factor for coronary heart disease, stroke and other cardiovascular disease, including heart failure (Evidence Grade 1). High blood pressure is also a risk factor for dementia (Evidence Grade 3). An increase of 20 mm Hg in systolic pressure or 10 mm Hg in diastolic pressure above 115/75 mm Hg doubles the risk of death from cardiovascular disease (Evidence Grade 1). The increase is independent of other risk factors for cardiovascular disease, and it is similar for women and men (Evidence Grade 1). Women have a lower absolute risk of cardiovascular disease than men (Evidence Grade 1). However, blood pressure lowering treatment reduces relative risk equally in women and men (Evidence Grade 1). Guidelines in Different Countries: The guidelines released in various countries over the past few years for the management of hypertension are largely in agreement. The guidelines are basically the same for women and men. All guidelines: Stress the importance of reaching the treatment goal of blood pressure below 140/90 mm Hg – below 130/80 mm Hg for patients with diabetes and/or renal disease. Emphasise the need to consider the patients total risk of cardiovascular disease rather than treating high blood pressure in isolation. Recommend a low-dose thiazide diuretic as the first-line therapy or as one of several first-line therapies. Lifestyle Changes as the Basis of Successful Treatment: With or without concurrently lowering blood pressure, a number of lifestyle changes – including physical activity, weight loss, dietary modifications, stress management, smoking cessation and the avoidance of excessive alcohol consumption – can minimise the risk factors for cardiovascular disease (Evidence Grade 1). Lifestyle measures can reduce the need for drug therapy and should form the basis for treating people with high blood pressure (hypertensives) (Evidence Grade 1). Smoking cessation measures should also be a priority for hypertensives and can generate major treatment benefits (Evidence Grade 1). Pharmacological Treatment: Blood pressure lowering treatment reduces the risk of stroke, myocardial infarction and premature death in hypertensives of both sexes (Evidence Grade 1). The various groups of blood pressure lowering drugs – thiazide diuretics, angiotensin converting enzyme (ACE) inhibitors, calcium antagonists, angiotensin receptor blockers (ARBs) and beta blockers – ordinarily used in Sweden are equally effective (reduction of approximately 10/5 mm Hg) when administered separately (Evidence Grade 1). Since the efficacy of different types of drugs can vary for a particular individual, switching to or adding one or more medications may be required in order to lower blood pressure sufficiently. For people with uncomplicated hypertension, all the major drug groups – thiazide diuretics, ACE inhibitors, calcium antagon- ists and ARBs – are equally effective in minimising the risk of cardiovascular disease (Evidence Grade 1). Beta blockers reduce the risk of stroke to a lesser extent (Evidence Grade 1). That is partly due to poorer reduction in blood pressure (Evidence Grade 2). Following stroke, blood pressure lowering drugs reduce the risk of myocardial infarction (Evidence Grade 3) and stroke recurrence (Evidence Grade 1). Treatment is equally effective with or without concurrent hypertension. At least half of all patients with type 2 diabetes also have hypertension. The effect of hypertension treatment on the absolute risk of cardiovascular disease morbidity and mortality is greater with concurrent diabetes (Evidence Grade 1). In people with type 2 diabetes, the impact on relative risk is also greater (Evidence Grade 1). Patients whose treatment is based on drugs (ACE inhibitors and ARBs) that directly affect the renin-angiotensin-aldosterone system are less likely to develop type 2 diabetes than those whose treatment is based on a thiazide diuretic combined with a beta blocker or on a calcium antagonist (Evidence Grade 2). In patients with high risk (multiple risk factors) of cardiovascular disease and concurrent type 2 diabetes mellitus, blockade of the renin–angiotensin–aldosterone system may reduce the risk beyond the impact of simply lowering blood pressure (ACE inhibitors – Evidence Grade 2, ARBs – Evidence Grade 3). Blood pressure lowering treatment counteracts clinically relevant deterioration of renal function (Evidence Grade 1). No difference with regard to the long-term effect on renal function has been shown among the various groups of blood pressure lowering drugs in patients who have mild to moderate hypertension without other concurrent kidney complications. This report did not review treatment of patients with diabetes and impaired renal function. Hypertension leads to thickening of the heart muscle. Blood pressure lowering treatment reduces left ventricular mass (Evidence Grade 1). Such a reduction is associated with a lower risk of cardiovascular disease (Evidence Grade 2). Economic Aspects: Sales of blood pressure lowering drugs for the indication of hypertension more than doubled from 70 defined daily doses (DDSs) per 1 000 Swedes in 1992 to 155 in 2002. Costs for drug treatment of hypertension totalled SEK 1,656 million in 2002. Since satisfactory treatment of everyone with hypertension would involve both a larger number of patients and more medications per person, total drug costs would rise (Evidence Grade 2). Choice of medication has a major impact on both drug costs and cost effectiveness. Prescribing the least expensive equiva- lent medication whenever possible would reduce drug costs and improve cost effectiveness compared with current pre- scription patterns (Evidence Grade 2). Treatment of uncomplicated hypertension with the least expensive equivalent drug entails cost savings for older women, as well as middle-aged and older men. Improving the treatment of patients with moderate to high risk is more cost-effective than treating more people with low risk (Evidence Grade 2). Ethical aspects: The ethical dilemma of treating an apparently healthy person with drugs for what is likely to be a long period of time should be weighed against the risks associated with withholding treatment that may prevent serious disease. Principles of Evidence Grading Quality refers to the scientific quality of a particular study and its ability to reliably answer a specific question. Evidence Grade refers to the total scientific evidence for a conclusion, i.e., how many high-quality studies support the conclusion. Evidence Grade 1 A conclusion assigned Evidence Grade 1 is supported by at least two studies with high quality among the total scientific evidence. If some studies are at variance with the conclusion, the evidence grade may be lower. Evidence Grade 2 A conclusion assigned Evidence Grade 2 is supported by at least one study with high quality and two studies with moderate quality among the total scientific evidence. If some studies are at variance with the conclusion, the evidence grade may be lower. Evidence Grade 3 A conclusion assigned Evidence Grade 3 is supported by at least two studies with moderate quality among the total scientific evidence. If some studies are at variance with the conclusion, the evidence grade may be lower.

Equine pituitary gonadotropins (eLH, eFSH, eCG) are heterodimeric glycoprotein hormones with alpha (α) and beta (β) subunits. It is responsible for maintenance of pregnancy in mares during early gestation and fairly valuable for inducing superovulation in animals other than equines. The alpha subunit is common, while beta subunit is species-specific in all glycoprotein hormones. In the present investigation, molecular cloning and in silico characterization including homology modeling and molecular docking analysis of the equine chorionic gonadotropin (eCG) alpha subunit was carried out for gaining structural and functional insights into the eCG alpha subunit and its possible interaction with ganirelix, a gonadotropin-releasing hormone (GnRH) antagonist. The equine chorionic gonadotropin (eCG) alpha subunit expressed in pituitary gland was selected, amplified from total RNA, cloned and sequenced. The in silico analyses were made for homology modelling, structural details, epitope identification and chromosomal localization. Molecular docking studies of eCG alpha were undertaken with a drug ganirelix which is used to control ovulation and has antagonistic activity against GnRH. The protein sequence corresponding to selected open reading frame (ORF) was 99-100% similar with domesticated horse, Przewalski's horse, and 92-93% with Burchell's zebra and donkey. Molecular docking studies revealed the possible interaction of eCG alpha with ganirelix. The possible drug-macromolecule interactions were visualized between eCG alpha and ganirelix. The study will provide structural insight into unique sites and an alternate route of gonadotropin suppression applicable to assisted reproductive technologies.

In in vitro fertilization (IVF) cycles, some patients show a high rate of immature oocytes retrieved after controlled ovarian stimulation. In vitro oocyte maturation is an experimental technique, with poorer results than conventional IVF. For this reason, improving in vivo maturation could meliorate the reproductive outcome of these patients. We performed a retrospective, not interventional, study analyzing the difference in the number and percentage of mature oocytes retrieved in patients with more than 50% immature oocytes in a previous IVF cycle triggered with human chorionic gonadotropin (hCG) compared to the number and rate of mature oocytes retrieved in subsequent cycles, triggered with both gonadotropin-releasing hormone agonist (GnRH-a) and hCG. The number of mature oocytes retrieved with a dual trigger was significantly higher than that for hCG alone: 5.3 ± 3.6 (4.4-6.1) versus 2.4 ± 2.2 (2-2.9). The proportion of mature oocytes showed the same tendency (79.6% vs 43.6%). The implantation, clinical, and ongoing pregnancy rates were 17.3%, 26.9%, and 15.3%, respectively, for the hCG trigger and 30.8%, 43.6%, and 31.6%, respectively, for the dual trigger. In patients with a low percentage of retrieved mature oocytes, who were triggered with a combination of GnRH-a and hCG, the number and percentage of retrieved mature oocytes improved. The dual trigger also seemed to meliorate gestational outcomes after IVF.

Ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone agonist (GnRH-a) trigger is rare. Here, we report a case of severe OHSS after combined GnRH-a and low-dose human chorionic gonadotropin (hCG) trigger in a patient with a single kidney. The patient is a 32-year-old women with a two-year history of infertility. The patient's history was significant for a single kidney, that is, she had donated a kidney to a family member three years ago. The patient underwent controlled ovarian stimulation (COS) for in vitro fertilization (IVF) and received a combined 2 mg GnRH-a and 1500 IU hCG ovulatory trigger. Estradiol (E2) levels on the day of and after the trigger were 3800 pg/mL and 4001 pg/mL, respectively. Four days after the trigger, the patient began experiencing nausea, abdominal distention and dyspnea, and her blood testing revealed hemoconcentration (hemoglobin: 16.9 g/dL; hematocrit: 51.0%) and an elevated creatinine level (1.16 mg/dL). Fresh embryo transfer was deferred. The patient was admitted to the hospital for fluid monitoring and prophylactic anticoagulation. Following inpatient management, her hemoglobin, hematocrit and creatinine levels normalized. The current report highlights that the systemic effects of OHSS can be accentuated in patients with preexisting renal disease or a single kidney.

No significant differences in outcomes have been found between protocols of endometrial preparation for frozen embryo transfer (FET), though gonadotropin releasing hormone (GnRH) antagonists may have detrimental effects on the endometrium. We conducted a retrospective cohort noninferiority study at a single academic center of women receiving multiple doses of mid-cycle GnRH antagonist (GAnt) to those receiving GnRH agonist (GAg) to determine if there are detrimental effects of GnRH antagonists. 1047 FET cycles were identified, detailed data was available in 840 cycles: 610 GAg and 230 GAnt cycles. Patients undergoing GAnt cycles were older (40 ± 6.6 versus 37 ± 5.1 years, p < 0.0001), more often used donor oocyte (36% versus 18.6%, p < 0.0001), and more often exhibited diminished ovarian reserve (49.1% versus 36.2%, p = 0.0009). Clinical pregnancy rates (CPRs) per transfer and implantation rates (IRs) were similar for GAnt and GAg cycles. There was a trend for higher pregnancy and IRs with GAg cycles in younger women (CPR 38.8% versus 26.7%, p = 0.16; IR 36% versus 23.3%, p = 0.07). Stratifying by diagnosis, CPR and IR were similar in GAnt and GAg cycles. A GAnt protocol of endometrial preparation for FET is not inferior to a GAg protocol regardless of patient age, use of donor oocyte, or infertility diagnosis.

Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle?

A retrospective, cohort study of high-risk patients undergoing IVF treatment was performed to assess if there is a difference in clinical pregnancy rate, live birth rate and the incidence of ovarian hyperstimulation syndrome, when a GnRH agonist (GnRHa) trigger with intensive luteal support is compared to human chorionic gonadotropin (hCG) with standard luteal support. The control group consisted of 382 high-risk patients having a GnRH antagonist protocol with 194 receiving an hCG trigger. All patients had ≥18 follicles ≥11mm or serum oestradiol >18,000pmol/l on the day of trigger. Patients had a single or double embryo transfer at cleavage or blastocyst stage. Logistic regression was used to adjust for differences between the groups. An intention-to-treat analysis of all cycles was performed. No statistically significant differences were observed in terms of positive pregnancy test, clinical pregnancy rate and live birth rate. Only one patient (0.3%) was hospitalized with severe OHSS in the GnRHa group, compared to 26 patients (13%) in the hCG group. In conclusion, GnRHa trigger is associated with similar pregnancy rates with hCG trigger and a significant reduction in hospitalization for severe OHSS after an intention to treat analysis was performed.

Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH (rFSH)?