Successful pregnancy rates amongst patients undergoing ovarian tissue cryopreservation for non-malignant indications: A systematic review and meta-analysis.

BACKGROUND: Ovarian tissue cryopreservation (OTC) is a fertility preservation method that has been clinically applied for almost 30 years. Studies specifically evaluating patients presenting with non-malignant indications for OTC and their subsequent pregnancy rates are limited. OBJECTIVE: To summarise the evidence on the rates of successful pregnancy amongst women who have undergone OTC for non-malignant indications. METHODS: A systematic review with meta-analysis (PROSPERO registration CRD42022307925) was conducted to investigate the pregnancy outcomes of patients who have undergone ovarian tissue cryopreservation for non-malignant indications. Articles published in EMBASE and Ovid MEDLINE before October 2022 were screened for inclusion based on the following criteria: original human studies pertaining to OTC with a defined non-malignant cohort and pregnancy outcomes. The successful pregnancy rates were pooled with a random-effects model of double-arcsine transformed proportions. Sensitivity analysis involved pooling the results of studies with a low risk of bias after being assessed with NIH tools. RESULTS: The database search retrieved 3,225 results, of which 16 were included in the meta-analysis. The pooled successful pregnancy rate was 23.52 % (16 studies, 95 % CI 6.48 to 44.79 %). When subgroup analysis of study types was performed, the successful pregnancy rate was higher amongst case series (47.02 %, 9 studies, 95 % CI 6.98 to 89.00 %) than cohort studies (14.64 %, 7 studies, 95 % CI 3.59 to 29.78 %). Sensitivity analysis limited to studies at low risk of bias revealed a similar pooled successful pregnancy rate of 23.35 % (12 studies, 95 % CI 2.50 to 51.96 %). CONCLUSIONS: Approximately one quarter of women who underwent OTC for non-malignant indications had a successful pregnancy. These findings are clinically important for fertility preservation counselling by providing greater evidence for more informed care.

[Do temporomandibular disorders really exist?].

Temporomandibular Disorders (TMD) is a collective term embracing a number of clinical problems that involve the muscles of mastication, the temporomandibular joint (TMJ) and associated structures or both. This group of disorders has been identified as the chief cause of pain, which is not of dental origin, in the orofacial area, and is defined as a subgroup in the category of musculoskeletal disorders. These disorders impair the quality of life of those suffering from them due to the extent of the pain and the chronic nature of its symptoms. It is known that chronic pain causes the development of psychological disturbances (anxiety, depression, etc.). The most common symptoms of TMD are the pain that usually appears as the result of mandibular activity (speaking or chewing), and is usually located in the masticulatory muscles, in the preauricular area and the temporomandibular joint (TMJ). Additional common symptoms are: a. restriction in jaw movement; b. asymmetry in jaw movement; c. noises from the joint. Patients suffering from TMD are likely to exhibit additional symptoms: hypertrophy of the muscles of mastication (an adaptive and asymptomatic phenomenon), abnormal occlusar erosion due to nighttime or daytime bruxism, or teeth grinding. Most functional temporomandibular disorders have similar signs and symptoms. As a result, diagnosis of the various disorders presents a serious problem. Functional temporomandibular disorders are often accompanied by mental symptoms such as depression, anxiety and/or somatization on various levels. One of today's accepted methods of classification also refers to the mental aspect and thus enables, for the first time, a suitable scientific comparison of the epidemiological, diagnostic and treatment data in the various studies. This method, initiated by Dworkin and LeResche (1992) is known as Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The purpose of this method is to classify every subgroup of TMD according to agreed upon, clear and measurable diagnostic criteria, both from the physical (AXIS I) and the mental (AXIS II) aspect. The method includes a scale which grades the extent of severity, damage and limitations caused by the illness, in a manner which now can make scientific comparisons between the various studies and between the population of patients and the general population. Temporomandibular disorders are very common and affect between 30%-50% of the population, and appear to be more prevalent among women than among men. Studies conducted on youth revealed significant relationships between oral parafunctions (especially chewing gum and "jaw playing"), and functional temporomandibular disorders. The significance of this finding is in the need to warn young people of the possible risks of engaging in intensive oral practices. The high prevalence of signs and symptoms among the Israeli population obligates us, in our opinion, to change the physical examination for identification of these disorders, to a routine procedure in all dental clinics in Israel.

Systemic chemotherapy for a primary germ cell tumor of the brain: a pharmacokinetic study.

Systemic administration of most chemotherapeutic agents has been assumed to be ineffective in the treatment of primary and metastatic brain tumors because these agents fail to cross the intact blood-brain barrier. However, agents which fail to penetrate the intact blood-brain barrier may penetrate it under conditions which include the presence of tumor in the central nervous system (CNS) and prior CNS irradiation. This paper reports the results of pharmacokinetic studies of bleomycin, cisplatin, and vinblastine in the CNS of a patient with a primary germ cell tumor of the brain who had received prior radiotherapy. Significant concentrations of bleomycin and cisplatin, but not of vinblastine, were reached in the cerebrospinal fluid (CSF) of the patient following iv administration. The area under the bleomycin CSF concentration times time curve was 25% of the area under the bleomycin plasma concentration times time curve. The areas under two cisplatin CSF curves were 50% and 155% of the areas under the corresponding free cisplatin plasma curves. Moreover, an objective response of the tumor to the chemotherapy was documented. This study provides evidence that, under certain circumstances, significant concentrations of cisplatin and bleomycin may be obtained in human CSF following systemic administration and that it may be possible to treat primary or metastatic CNS tumors with agents effective against systemic tumor of the same histologic type.

Determination of platinum in serum and ultrafiltrate by flameless atomic absorption spectrophotometry.

A graphite furnace atomic absorption spectrophotometric assay, capable of accurately determining nanogram amounts of platinum in serum and ultrafiltrate, was developed. A sample serum or ultrafiltrate was acidified with nitric acid and heated to destroy the protein-platinum bond. A measured excess of ammonium 1-pyrrolidinedithiocarbamate was added, and the platinum complex was extracted into isopropylacetone. The extract was injected into the graphite furnace. The sample was dried, charred, and atomized using optimal conditions. The resulting absorbance was used to determine the platinum content.

Anthracycline assay by high-pressure liquid chromatography.

A general method of analysis of anthracycline concentrations was developed. Drug is extracted from plasma with organic solvent and separated from metabolites by high-pressure liquid chromatography on an aminocyanosilica column. Detection and quantitation are by the endogenous fluorescence of compounds having an intact tetracyclic ring structure. Limits of sensitivity are 5, 1, and 5 ng/ml of plasma for doxorubicin, carubicin, and marcellomycin, respectively. The assay can be used for studying the aldo-keto reductase and reductive glycosidase reactions with anthracyclines as the substrates and for the evaluation of the clinical pharmacology or pharmacodynamics of various doxorubicin analogs.

Pharmacokinetics of carminomycin in dogs and humans. Preliminary report.

Carminomycin was administered to four dogs and two human patients as a single intravenous dose. Plasma samples were obtained and assayed for carminomycin and carminomycinol by high pressure liquid chromatography with fluorescence detection. The plasma disappearance of carminomycin could be described by a three-compartment open model. Distribution was rapid and the apparent volume of distribution was greater than 100 l/m2 in both species. The terminal half-life of drug was 86 h in dogs and 20 h in humans. In both dogs and humans carminomycinol concentrations rapidly surpassed carminomycin levels, and terminal half-lives were longer than for the parent compound in the two species. Since carminomycinol has antitumor activity and host toxicity, this metabolite may play an important role in the efficacy and toxicity of carminomycin therapy.

Colonic cancer and associated diverticulitis.

In a total group of 385 cases of colonic cancer, there was evidence of associated diverticulitis in 42 cases. Of these, 92% of the patients were over 60 years of age. In 45% of the cases the coexisting lesions were located in the sigmoid colon. It is suggested that cancer of the colon contributes to the development of diverticulosis and diverticulitis; this is confirmed by the finding of 52.8% of the total group of diverticulosis (98 cases) complicated by diverticulitis. Signs of diverticulitis may mask the presence of cancer, and the diagnosis of associated lesions is sometimes difficult. The patient's history and repeated radiographic studies play an important role in the detection of associated cancer. The final diagnosis is confirmed by pathologic examination.