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Treatment should recommence in the next cycle at a lower dose than in the previous cycle. Females undergoing controlled ovarian stimulation for multiple follicular development prior to in-vitro fertilization or other assisted reproductive technologies. A commonly used protocol for superovulation involves the administration of 150-225 IU of Merional daily commencing on days 2 or 3 of the cycle and continued until sufficient follicular development has been achieved as assessed by monitoring serum oestrogen concentrations and/or ultrasound examination with the dose adjusted according to the patient’s response but usually not higher than 450 IU daily, buy trenbolone 100 mg injectable steroids trenbolone acetate. Adequate follicular development is usually achieved by the tenth day of treatment (range 5-20 days). A single injection of 5,000 IU-10,000 IU of hCG should be administered 24-48 hours after the last injection to induce follicular maturation. Pituitary down-regulation in order to suppress the endogenous LH surge and to control tonic levels of LH is now commonly achieved by administration of a gonadotrophin releasing hormone (GnRH) agonist. In a commonly used protocol the administration of Merional-is started approximately two weeks after the start of agonist treatment, both being continued until adequate follicular development has been achieved. For example, following two weeks of pituitary down-regulation with an agonist, 150-225 IU Merional are administered for seven days; the dose is then adjusted according to the patient’s ovarian response. Experience with ART indicates that in general the treatment success rate remains stable during the first four attempts and gradually declines thereafter. Females with anovulation resulting from severe LH and FSH deficiency In these women (hypogonadotrophic hypogonadism) the objective of Merional treatment is to develop a single mature Graafian follicle from which the oocyte will be released following the administration of hCG. As these women are amenorrhoeic and have low endogenous oestrogen secretion treatment may commence at any time. The treatment should be adjusted to the individual patient’s response as assessed by measuring follicle size by ultrasound and/or oestrogen secretion. A commonly used regimen commences at 75-150 IU of Merional-and is increased according to the patient’s response. Should an increased dose of Merional-be deemed appropriate, dose adaptation should preferably be made after 7-14 day intervals and preferably by 150 IU increments. It may be acceptable to extend the duration of stimulation in any one cycle up to 5 weeks. When an ideal response is obtained a single injection of 5,000 IU-10,000 IU of hCG should be administered 24-48 hrs after the last Merional injection. The patient should be recommended to have coitus on the hCG injection day and the following day. Alternatively intrauterine insemination (IUI) may be performed. Luteal support may be considered since lack of substances with luteotrophic activity (LH/hCG) after ovulation may lead to a premature loss of the corpus luteum. In the event of an excessive response treatment should be suspended and hCG withheld (see section 4. Treatment should recommence in the next cycle at a lower dose than in the previous cycle. There is no relevant use of Merional in the paediatric population in the indications (anovulatory Infertility, females undergoing controlled ovarian stimulation for multiple follicular development prior to assisted reproductive technologies and males with hypogonadotrophic hypogonadism). Merional is intended for intramuscular and subcutaneous administration. The powder should be reconstituted immediately prior to use with the solvent provided. In order to avoid injection of large volumes up to 5 vials of Merional 150 IU may be dissolved in one ml of solvent.
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OHSS is a medical event distinct from uncomplicated ovarian enlargement. It is a syndrome that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and an increase in vascular permeability, pleural and rarely in pericardial cavities. The following symptoms may be observed in severe cases of OHSS: abdominal pain, abdominal distensions, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhoea. Clinical examination may reveal hypovolaemia, haemoconcentation, electrolyte imbalances, ascites, haemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress and thromboembolic events. Excessive ovarian response to gonadotrophin treatment seldom gives rise to OHSS unless hCG is administered to trigger ovulation. Therefore in cases of OHSS it is prudent to withhold hCG and to advise the patient to refrain from coitus or to use barrier methods for at least four days. OHSS may progress rapidly (within 24 hours to several days) to become a serious medical event, therefore patients should be followed for at least two weeks after hCG administration. To minimize the risk of OHSS or of multiple pregnancy, ultrasound scans as well as oestradiol measurements are recommended. In anovulation the risk of OHSS and multiple pregnancy is increased by a serum oestradiol >900 pg/ml (3300pmol/L) and more than 3 follicles of 14 mm or more in diameter. In ART there is an increased risk of OHSS with a serum oestradiol > 3000 pg/ml (11000 pmol/L) and 20 or more follicles of 12 mm or more in diameter. When the oestradiol level is > 5500 pg/ml (20200 pmol/L) and where there are 40 or more follicles in total, it may be necessary to withhold hCG administration. Adherence to recommended Merional dosage, regimen of administration and careful monitoring of therapy will minimise the incidence of ovarian hyperstimulation and multiple pregnancy (see sections 4. In ART, aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation. OHSS may be more severe and more protracted if pregnancy occurs. Most often OHSS occurs after hormonal treatment has been discontinued and reaches its maximum at about 7-10 days following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If severe OHSS occurs, gonadotrophin treatment should be stopped if still ongoing, the patient hospitalised and specific therapy for OHSS started. This syndrome occurs with higher incidence in patients with polycystic ovarian disease. Multiple pregnancy, especially high order, carries an increased risk of adverse maternal and perinatal outcomes. 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