The clinical significance of the retrieval of a low number of oocytes following mild ovarian stimulation for IVF: a meta-analysis.

BACKGROUND: Milder ovarian stimulation protocols for in vitro fertilization (IVF) are being developed to minimize adverse effects. Mild stimulation regimens result in a decreased number of oocytes at retrieval. After conventional ovarian stimulation for IVF, a low number of oocytes are believed to represent poor ovarian reserve resulting in reduced success rates. Recent studies suggest that a similar response following mild stimulation is associated with better outcomes. METHODS: This review investigates whether the retrieval of a low number of oocytes following mild ovarian stimulation is associated with impaired implantation rates. Three randomized controlled trials comparing the efficacy of the mild ovarian stimulation regimen (involving midfollicular phase initiation of FSH and GnRH co-treatment) for IVF with a conventional long GnRH agonist co-treatment stimulation protocol could be identified by means of a systematic literature search. RESULTS: These studies comprised a total of 592 first treatment cycles. Individual patient data analysis showed that the mild stimulation protocol results in a significant reduction of retrieved oocytes compared with conventional ovarian stimulation (median 6 versus 9, respectively, P < 0.001). Optimal embryo implantation rates were observed with 5 oocytes retrieved following mild stimulation (31%) versus 10 oocytes following conventional stimulation (29%) (P = 0.045). CONCLUSIONS: The optimal number of retrieved oocytes depends on the ovarian stimulation regimen. After mild ovarian stimulation, a modest number of oocytes is associated with optimal implantation rates and does not reflect a poor ovarian response. Therefore, the fear of reducing the number of oocytes retrieved following mild ovarian stimulation appears to be unjustified.

LH suppression following different low doses of the GnRH antagonist ganirelix in polycystic ovary syndrome.

Elevated LH concentration is a common feature in polycystic ovary syndrome (PCOS). This study was designed to establish whether elevated LH levels in PCOS might be suppressed to normal range values by the administration of different low doses of GnRH antagonist, which subsequently might reverse the anovulatory status of these patients. Twenty-four PCOS patients with elevated endogenous LH concentrations were randomized into 3 different dose groups, receiving either 0.125 mg (Group A), 0.250 mg (Group B) or 0.500 mg (Group C) ganirelix sc daily for 7 subsequent days. During the first day of treatment, LH and FSH levels were assessed at 20 min intervals, during 8 h. Thereafter LH, FSH, androgens, estradiol (E2) and inhibins were assessed daily and frequent ultrasound scans were performed for 7 days to record follicle development. Repeated GnRH antagonist administration induced a significant suppression of LH (and to a lesser extent of FSH) serum levels, which was comparable between the different doses. Six hours after ganirelix administration, endogenous LH was suppressed by 49, 69 and 75%, and endogenous FSH was suppressed by 23, 19 and 25%, respectively. The decrease in serum LH and FSH levels was transient and lasted for 12 h, after which serum levels returned to baseline levels at 24 h after drug administration. Androgen levels were not significantly suppressed using this regimen. E2 levels decreased significantly (p < 0.001) and suppression was most pronounced in Group C. Spontaneous follicle development or ovulations were not recorded during the course of treatment. In conclusion, the present study demonstrates that the GnRH antagonist ganirelix is capable of normalising elevated LH levels in PCOS patients, in doses similar to the ones previously shown to prevent a premature LH rise during ovarian hyperstimulation for in vitro fertilization (IVF). In addition, the transient suppression of elevated endogenous LH levels per se does not re-establish normal follicle development in PCOS. However, follicle development may be insufficiently supported by the accompanied subtle suppression of endogenous FSH. Similarly, a transient decline in E2 levels does not effectively restore normal pituitary ovarian feedback. Moreover, these results support the contention of a limited role of LH in the pathogenesis of PCOS.

Low-dose exogenous FSH initiated during the early, mid or late follicular phase can induce multiple dominant follicle development.

This prospective, randomized trial in normo-ovulatory women was designed to test whether administration of low-dose exogenous FSH initiated during the early, mid to late follicular phase can induce multiple dominant follicle development. Forty normal weight women (age 19-35 years, cycle length 25-32 days) participated. A fixed dose (75 IU/day) of recombinant FSH was started on either cycle day 3 (n = 13), 5 (n = 13) or 7 (n = 14) until the induction of ovulation with human chorionic gonadotrophin. Frequent transvaginal ultrasound scans and blood sampling were performed. Multifollicular growth occurred in all groups (overall in 60%), although day 7 starters showed less multifollicular growth. Age, cycle length and initial FSH and inhibin B concentrations were similar between subjects with single or multiple follicle development. However, for all women the lower the body mass index (BMI), the more follicles emerged (r = -0.44, P = 0.007). If multifollicular growth occurred, the length of the luteal phase was reduced (P = 0.002) and midluteal serum concentrations of LH (P = 0.03) and FSH (P = 0.004) were decreased and oestradiol (P = 0.002) and inhibin A (P = 0.01) were increased. In conclusion, interference with decremental serum FSH concentrations by administration of low dose FSH starting on cycle day 3, 5 or as late as day 7, is capable of disrupting single dominant follicle selection. The role of BMI in determining ovarian response suggests that differences in pharmacokinetics of exogenous FSH are involved. Multifollicular growth per se has a distinct effect on luteal phase characteristics. These observations may be relevant for the design of mild ovarian stimulation protocols.

Spinal epidural abscess following blunt pelvic trauma.

A 17-year-old patient with pre-existing grade II spondylolisthesis of L5/S1 sustained a partial disruption of the left sacroiliac joint with haematoma of the iliac muscle after a fall. The haematoma probably led to occlusion of the left ureter, resulting in a urinary tract infection. After initial conservative treatment the patient developed fever and radicular pain of the left leg. Magnetic resonance imaging (MRI) revealed a left-sided epidural abscess at L5/S1, which had probably spread from the infected iliac haematoma along the injured sacroiliac joint. Prompt surgical drainage and antibiotic coverage with cefuroxime and flucloxacillin led to rapid clinical improvement. Staphylococcus aureus was identified as the pathogen. At follow-up 6 months postoperatively all symptoms had resolved, while MRI still revealed residual osseous oedema of the sacroiliac joint. The haematoma of the iliac muscle resolved without surgical intervention.

Vertebral remodeling in eosinophilic granuloma of the spine. A long-term follow-up.

STUDY DESIGN: In this study, 14 conservatively treated patients were reviewed who had eosinophilic granuloma of the spine, which had been diagnosed on the basis of histologic study of the vertebral lesion or of specimens from other sites in patients with multiple involvement. The remodeling of the vertebral body was studied in an average follow-up of 5.6 years. OBJECTIVES: To analyze the remodeling process of the involved growing vertebral body in Langerhans Cell Histiocytosis after conservative treatment and to assess the sagittal and frontal profile of the spine at the end of growth. Fourteen patients, aged between 1.2 and 11.3 years, with spinal involvement of a Langerhans' cell histiocytosis were treated in the department of orthopedics between 1980 and 1990. All patients had immobilization of the affected region by a custom-made brace. Six patients with symptomatic lesions had radiotherapy and four patients with disseminated disease were treated with chemotherapy. Clinical and radiologic examinations were made at regular intervals to evaluate the development of the vertebrae during the remodeling process. SUMMARY OF BACKGROUND DATA: In the 14 patients, both sexes were affected equally. The disease was located in the cervical spine in two patients and in thoracic and lumbar vertebrae in seven patients each. Two patients had two vertebral lesions. METHODS: The radiologic evolution of the 16 vertebral lesions was evaluated using follow-up standardized lateral radiographs. The reconstitution of the vertebral height in the presence of vertebra plana was calculated by measuring the ventral distance between the superior and inferior margins of the vertebral body in relation to the adjacent uninvolved vertebra. RESULTS: The measurements showed a growth rate of 1.5-6 (average, 3) in vertebrae with vertebra plana and a growth rate of 1.1-2.7 (average, 1.4) in the unaffected vertebra. The reconstitution of the vertebral height was between 18.2% and 63.8% of the adjacent vertebrae before and between 72.2% and 97% after skeletal maturity. CONCLUSIONS: The results demonstrate that conservative orthopedic treatment with immobilization in a brace is sufficient to allow for optimal vertebral remodeling. Partial to nearly complete reconstitution of vertebral height was seen in all cases. Thus, operative treatment with curettage of the lesion and bone grafting including multisegmental fusion with instrumentation is not necessary. In instances with neurologic impairment, rarely seen in adults, surgical decompression and short fusion of the spine is necessary. Nevertheless, complete staging and biopsy are mandatory for an accurate diagnosis.

Indication for lumbosacral fusion and reduction in spondylolisthesis.

The indication for operative treatment in spondylolisthesis results from pain, progressive sliding and, in up to 60 % of the patients with progressive dislocation, from radicular malfunction. The posterolateral fusion in situ is a safe procedure, but the deformation remains and in spondyloptosis plastic deformation of the fusion mass can lead to further dislocation. With the external fixator as an instrument for reduction and the internal fixator for stabilization the reduction of even serious spondyloptosis and the recovery of a normal spine alignement and posture is possible, with an acceptable neurological risk. Therefore a concept of treatment is suggested, which as a rule is aiming at the anatomical reduction of the dislocated vertrebra beside stabilization and nerveroot decompression. Depending on the extent of the slip, reduction and stabilization is to be performed in one, two or three stages. An anterior or posterior fusion is sufficient in grade I dislocation. In grade II-V a combined posterior and anterior surgical proceedure is recommended.

[Differential indications for lumbosacral fusion and reposition operation in spondylolisthesis]. / Differentialindikation zur lumbosakralen Fusions- und Repositionsoperation beim Wirbelgleiten.

The indication for operative treatment in spondylolisthesis results from pain, progressive sliding and, in up to 60% of the patients with progressive dislocation, from radicular malfunction. The posterolateral fusion in situ is a safe procedure, but the deformation remains and in spondyloptosis plastic deformation of the fusion mass can lead to further dislocation. With the external fixator as an instrument for reduction and the internal fixator for stabilization the reduction of even serious spondyloptosis and the recovery of a normal spine alignement and posture is possible, with an acceptable neurological risk. Therefore a concept of treatment is suggested, which as a rule is aiming at the anatomical reduction of the dislocated vertrebra beside stabilization and nerveroot decompression. Depending on the extent of the slip, reduction and stabilization is to be performed in one, two or three stages. An anterior or posterior fusion is sufficient in grade I dislocation. In grade II-V a combined posterior and anterior surgical proceedure is recommended.

[Reconstruction of the tibial plateau fracture with arthroscopic monitoring without arthrotomy]. / Reconstructie van de tibiaplateaufractuur onder artroscopische controle zonder artrotomie.

In the period from October 1986 to November 1988 in the Medisch Spectrum Twente of Enschede, 25 patients were treated for a tibial plateau fracture by means of arthroscopic surgery. The mean hospital stay was 18 days. Active movement of the leg was prescribed from the fifth day. The results were very good in 23 and poor in 2 patients. Complications such as wound infections and skin necrosis were not seen. Additional meniscal lesions could be diagnosed and treated better using this surgical technique. In addition, the limited incisions and consequently the avoidance of extensive arthrotomy allowed faster rehabilitation and a higher probability of healing the chondral tissue.

Induction of stilbene synthase by Botrytis cinerea in cultured grapevine cells.

The interaction between Botrytis cinerea Pers. and grapevine (Vitis vinifera L.) was studied in a model system of reduced complexity. Cultured plant cells and fragments of fungal cell wall were used to simulate some of the processes taking place upon infection of grapevine with B. cinerea. A soluble glucan elicitor was prepared from the fungal cell wall by acid hydrolysis. Like the insoluble wall preparation, the soluble fragment derived from the cell wall acted upon plant cells in eliciting stilbene formation. In grapevine cells, the interaction with the fungus led to a dramatic shut-off general protein synthesis and to the selective formation of a small set of proteins involved in induced resistance. The proteins synthesized de novo with highest rates were stilbene synthase (StiSy) and L-phenylalanine ammonia-lyase (PAL). Stilbene synthase was purified to apparent homogeneity and its molecular properties were characterized. The enzyme is a homodimer with subunit Mr 43 000 and pl = 5.4. Although there were indications of the presence of isoenzymes, these were not distinguished by charge differences. In size, the grapevine StiSy shows microheterogeneity and differs from the appreciably larger enzyme prepared from peanut. Prior to induction by fungal attack, virtually no stilbenes are formed in the plant cell. Upon induction of the pathway leading to the stilbene resveratrol, StiSy activity determines the ratelimiting step in the metabolic sequence. The highly induced grapevine cells produce and secrete resveratrol and derivatives which are known to be fungistatic.

Selective low-dose thrombolysis in patients with an axillary-subclavian vein thrombosis.

The treatment of axillary-subclavian vein thrombosis is still controversial. Development of a post-phlebitic syndrome in patients treated conservatively occurs in many patients. Therefore more aggressive treatment is advocated. We report six patients treated with selective low-dose streptokinase infusion with excellent short-term results. Major complications did not occur. Recanalisation was observed in all patients. Long-term results are not yet available.

Carcinoma of the thyroglossal duct.

Based on the case histories of six patients with carcinoma of the thyroglossal duct, the literature on the origin and treatment of this disease was reviewed. As to the treatment of papillary adenocarcinoma there is some controversy, although in most cases treatment is limited to local excision as described by Sistrunk, provided that tumor growth is restricted to the cyst. The prognosis of this carcinoma seems favorable. Squamous cell carcinoma of the thyroglossal duct is rare; there is no uniform advice as to its treatment, and the prognosis is poor.

Two patients with recurrent pneumonias in one lung.

Case histories are described of two young patients, both known to have recurrent infections of one pulmonary lobe. Further investigations (especially aortography) disclosed the cause in both to be an intrapulmonary sequestration. Surgical intervention made both patients symptom-free. The aetiology, clinical and investigational findings as well as therapy are discussed. The need for further investigations in patients with recurring infections of one pulmonary lobe is stressed.

Is streptokinase useful in the treatment of deep vein thrombosis?

Because of its fibrinolytic action, streptokinase is believed to reduce the severity of the postthrombotic syndrome in patients with deep vein thrombosis. A prospective and a retrospective study have been undertaken in an attempt to determine when this therapy is useful for patients with deep vein thrombosis. The prospective study included 15 patients with deep vein thrombosis: 5 were treated in the hospital with streptokinase and heparin and 5 only with heparin, 5 were treated at home with only phenprocoumon. All the patients received oral anticoagulant therapy for at least 6 months. Three to four months after the acute episode, phlebography and venous pressure measurements were carried out. Streptokinase appeared to give the best results but with more side-effects. In the retrospective study, 51 patients who had had deep vein thrombosis in 1969 were reexamined 31-47 months later. It was found that more than 50% of the patients with a thrombosis in the femoral and/or iliac vein developed a severe postthrombotic syndrome, in contrast to only 9% of those with a thrombosis in the popliteal vein or lower. It is recommended, on the basis of both the prospective and the retrospective study, that patients with a thrombosis in the femoral and/or iliac vein should be treated with either heparin or streptokinase during the early stage. It is probable that streptokinase will significantly decrease the frequency and severity of the postthrombotic syndrome in these patients in particular, although this has not yet been proven.