HIV-1 and the Mycobacterium tuberculosis granuloma: A systematic review and meta-analysis.

Infection with HIV-1 greatly increases the risk of active tuberculosis (TB). Although hypotheses suggest HIV-1 disrupts Mycobacterium tuberculosis (Mtb) granuloma function, few studies have examined this directly. The objective of this study was to determine what evidence exists about the effect HIV-1 co-infection has upon Mtb granulomas. A systematic search of PubMed, Web of Science, and Medline up to 20 March 2015 was conducted, to identify studies comparing Mtb-infected tissue from HIV-1 infected and uninfected persons, or HIV-1 infected persons with stratified peripheral CD4 T cell (pCD4) counts. We summarized findings that focused on how HIV-1 changes granuloma formation, bacterial presence, cellular composition, and cytokine production. Nineteen studies with a combined sample size of 899 persons were included. Although studies frequently were limited by variable or inadequately described definitions of outcomes and analytical methods, HIV-1 was found to be associated with increased bacillary load within Mtb-infected tissue. Reductions in pCD4 counts within co-infected persons associated with both poorer granuloma formation and higher bacterial load. The high degree of heterogeneity among studies combined with experimental limitations made it difficult to conclusively support previously published and prevalent hypotheses about HIV-1/Mtb co-infection granulomas. To elucidate the validity of these hypotheses we have described areas that can be improved in future studies in order to clarify the influence HIV-1 co-infection has upon the Mtb granuloma.

Suicide: a personal reflection.

One of the authors of this paper, Carla Diedrich, had a personal experience of suicide in her family. She wants to both share the experience and allow the circumstances to be directive and informative for individuals who have had similar experiences with suicide and for those working in a clinical capacity. In this sense, the work belongs to Carla and her family and has been significant, almost cathartic, in helping her especially deal with this difficult set of personal circumstances.

A simple, inexpensive and effective artificial cycle with exogenous transdermal oestradiol and vaginal progesterone for the transfer of cryopreserved pronucleated human oocytes in women with normal cycles.

Supernumerary pronucleated stage oocytes (PN) are usually cryopreserved. PN are transferred in spontaneous, stimulated or artificial cycles. In this study, an artificial cycle with a transdermal therapeutic system was used for oestradiol release (Estraderm TTS 100) in combination with a targeted drug delivery system for vaginal progesterone release (Crinone 8%). Patients started transdermal 17beta-oestradiol treatment on cycle day 1. Only one clinical monitoring was necessary on day 14 for confirmation of satisfactory endometrial development and exclusion of ovulation by transvaginal ultrasound and endocrine determinations (oestradiol, progesterone and luteinizing hormone). Embryo transfer was performed on the third day of progesterone treatment (day 17). The first 25 cycles were recently completed in a prospective study; no cycles were cancelled due to ovulation or unsatisfactory endometrial development. In comparison with the previous protocol of embryo transfer in stimulated cycles in our clinic which required extensive ultrasound and endocrine monitoring, the pregnancy rate in these oestrogen- and progesterone-supplemented cycles was nearly twice as high (34.8%). Two pregnancies were even achieved with zygotes after micro-injection of frozen-thawed late spermatids extracted from testicular tissue (cryo-TESE). In these cycles, the Estraderm TTS 100/Crinone 8% protocol seems to be superior to stimulation protocols and even to other protocols reported so far for artificial cycles with exogenous oestradiol and progesterone treatment.

[The computed tomographic determination of intra-abdominal fat volume by single-layer measurement]. / Computertomographische Bestimmung des intraabdominellen Fettvolumens mittels Einschicht-Messung.

PURPOSE: Several studies emphasised the importance of the relationship between intra-abdominal and total body adipose tissue as a risk factor for the development of metabolic or cardiovascular diseases. Therefore, the aim of the present study was to examine whether a single-scan computed tomography is able to determine the whole intra-abdominal fat volume with high accuracy and reproducibility. MATERIALS AND METHODS: Regions of interests (ROIs) were drawn manually for measuring intra-abdominal fat in 51 unsuspicious abdominal CT. RESULTS: The sexual differentiation of adipose tissue already described in a lot of studies could be confirmed in this study. Fat still predominates in females in lower half of the body (gynecoid obesity). In men it predominates in the upper half (android obesity). Significant correlation concerning measuring the whole intra-abdominal fat volume could be found in L1-level in women (r = 0.992) and in L2-level in men (r = 0.992). Measurement of a single scan enables us to assess whole intra-abdominal fat volume due to a special formula. CONCLUSION: The determination of intra-abdominal fat measured by a single-scan computed tomography is a procedure associated with high accuracy and reproducibility.

Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages.

PURPOSE: The premature LH surge in ART programs seems to be avoided by daily administration of the GnRH-antagonist Cetrorelix during the midcycle phase in controlled ovarian hyperstimulation with hMG. The dosage necessary for sufficient suppression of the pituitary gland is not yet defined. METHODS: To elucidate this question three daily dosages (3, 1, 0.5 mg) were administered and the hormone profiles obtained as well as the number of oocytes retrieved, the fertilization rate, and the consumption of HMG were compared. RESULTS: No premature LH surge could be observed at any of the three dosages administered. Both gonadotropins were deeply suppressed. The fertilization rates of the oocytes obtained were 45.3% in the 3-mg group, 53.1% in the 1-mg group, and 67.7% in the 0.5-mg group. The average uses of hMG ampoules were 30 in the 3-mg group, 27 in the 1-mg group, and 26 in the 0.5-mg group. CONCLUSIONS: Cetrolix, 0.5 mg/day, administered during the midcycle phase of controlled ovarian hyperstimulation with hMG is enough to prevent completely the premature LH surge. Perhaps even lower dosages would be sufficient. Regarding fertilization rates and use of hMG, the lower dosage seems to be the most favorable.

Preserved pituitary response under ovarian stimulation with HMG and GnRH antagonists (Cetrorelix) in women with tubal infertility.

OBJECTIVE: To examine the pituitary response in patients undergoing short-term application of the GnRH antagonist Cetrorelix in the mid-cycle phase for hypophysial suppression of premature LH surges within an IVF-program. DESIGN: Twenty patients suffering from primary or secondary tubal infertility were stimulated with hMG from cycle day 2. From day 7 till ovulation induction Cetrorelix was administered in two different dose regimens (15 patients 3 mg s.c. daily; 5 patients 1 mg s.c. daily). Three hours before ovulation induction a GnRH test was performed using 25 micrograms of native GnRH and the pituitary response examined by measurement of the serum LH concentration after 30 min. RESULTS: Premature LH surges could be avoided in the 3-mg group and in the 1-mg group, respectively. Due to this, none of the cycles had to be cancelled. Oestradiol profiles and ultrasound demonstrated a satisfactory follicular maturation. All patients showed pronounced suppression of the serum LH levels before ovulation induction. The mean increase of serum LH due to the performed GnRH test was 10 mIU/ml for the 3-mg group, while the average maximum in the 1-mg group was about 32.5 mIU/ml. CONCLUSIONS: The pituitary response is preserved by the treatment with the GnRH antagonist Cetrorelix. The extent of suppression of the adenohypophysis, as expressed by the different reactions on GnRH test, can be modulated by the dosage administered. This should allow ovulation induction by GnRH or one of its agonists instead of hCG, which could be beneficial in patients at high risk of Ovarian Hyperstimulation Syndrome (OHSS) and those suffering from Polycystic Ovary Disease (PCOD).

Mini-swim-up: a new technique of sperm preparation for intracytoplasmic sperm injection.

PURPOSE: The male factor is nowadays one of the major problems in the treatment of infertility. New methods of assisted fertilization such as the intracytoplasmic sperm injection (ICSI) show better fertilization and pregnancy rates than classical IVF. METHOD: In this study, we present a new technique of sperm preparation: the "mini-swim-up." CONCLUSION: This technique, used in conjunction with the ICSI procedure, improves pregnancy and fertility rates in cases of severe oligoasthenoteratozoospermia.

[GnRH antagonists in gynecology: initial results within the scope of controlled ovarian hyperstimulation]. / Die GnRH-Antagonisten in der Gynäkologie: Erste Ergebnisse im Rahmen der kontrollierten ovariellen Hyperstimulation (COH).

OBJECTIVE: Applicability of the GnRH-antagonist Cetrorelix within controlled ovarian hyperstimulation (COH) to avoid the premature LH-surge should be examined. METHODS: 35 patients suffering from tubal infertility were stimulated for In Vitro Fertilization (IVF) by human menopausal gonadotrophins (HMG) and concomitant administration of Cetrorelix in different dosages (3 mg, 1 mg, 0,5 mg). RESULTS: No premature LH-surge could be observed. CONCLUSIONS: Short term administration of the GnGR-antagonists avoids the occurrence of a premature LH-surge.

Suppression of the endogenous luteinizing hormone surge by the gonadotrophin-releasing hormone antagonist Cetrorelix during ovarian stimulation.

Surges of luteinizing hormone (LH) that result in luteinization but occur prematurely with respect to the diameter of the leading follicle, prevent attempts to induce multiple follicular maturation for in-vitro fertilization (IVF) in a significant number of women. We examined the possibility of blocking premature LH surges by the administration of Cetrorelix, a potent antagonist of gonadotrophin-releasing hormone (GnRH), in a study including 20 patients, some of whom had previously shown premature LH surges. All patients were treated with human menopausal gonadotrophins (HMG) starting on day 2. From day 7 until the induction of ovulation by human chorionic gonadotrophin (HCG) the GnRH antagonist Cetrorelix was given daily. HCG was injected when the dominant follicle had reached a diameter of > or = 18 mm and oestradiol concentration was > 300 pg/ml for each follicle having a diameter of > 15 mm. Oocyte collection was performed 36 h later by transvaginal ultrasound puncture, followed by IVF and embryo transfer. The hormone profiles of these patients and the results of IVF and embryo transfer are comparable to those treated with GnRH agonists and HMG. However, less time and especially less HMG is needed in comparison to patients stimulated with a long agonist protocol. Hence, treatment with Cetrorelix proved to be much more comfortable for the patient. In this study we showed that combined treatment with gonadotrophins and the GnRH antagonist Cetrorelix is a promising method for ovarian stimulation in patients who frequently exhibit premature LH surges and therefore fail to complete treatment.

[Suppression of endogenous LH increase in ovarian stimulation with the GnRH antagonist Cetrorelix]. / Suppression des endogenen LH-Anstiegs bei der ovariellen Stimulation durch den GnRH-Antagonisten Cetrorelix.

Surges of LH in serum, which result in luteinization, but occur prematurely with respect to the diameter of the leading follicle, frustrate attemps to induce multiple follicular maturation for in-vitro fertilisation in a number of women. We examined the possibility of blocking premature LH-surges by the administration of Cetrorelix, a potent antagonist of gonadotrophin releasing hormone. Twenty patients, who had repeatedly shown premature LH surges, were treated with human menopausal gonadotrophins from the 2nd day onwards. From the 7th day until the induction of ovulation by HCG, the GNRH-antagonist Cetrorelix was given daily. HCG was injected when the dominant follicle had reached the diameter of at least 18 mm and oestradiol levels were above 300 pg for each follicle and more than 15 mm. Oocyte collection was performed 36 hours later by transvaginal ultrasound puncture, followed by IVF and embryo transfer. The hormone profiles of these patients and the results of in-vitro fertilisation and embryo transfer are discussed. It could be demonstrated in this study, that combined treatment with gonadotrophins and the GNRH-antagonist seems to be a promising method for ovarian stimulation in patients, who frequently exhibit premature LH discharges and therefore fail to complete treatment.

[Ovarian stimulation with various FSH/LH concentrations in an in vitro fertilization program]. / Ovarielle Stimulation mit verschiedenen FSH/LH-Konzentrationen in einem In-vitro-Fertilisationsprogramm.

Various stimulation regimes have been tried to induce multiple follicular development for in-vitro fertilisation and embryo transfer. Human menopausal gonadotrophins have been widely used to induce follicular growth. To evaluate the role of the FSH: LH-ratio and the importance of LH concentrations, the results of a randomised assessor-blind group comparative efficacy and safety study are described. The effects of preparations, comprising FSH: LH-ratio of 3:1 and FSH: LH-ratio of 1:1 respectively, in stimulation of the ovaries for in-vitro fertilisation in infertile women are compared. Patients under 38 years of age with regular menstrual cycle (27 +/- 3 days and 32 +/- 3 days) are included. Sperm parameters have to be in normal range, according to WHO criteria. Follicular and luteal hormone parameters, ultrasound measurements, oocyte quality, fertilisation, cleavage and pregnancy rates are reported. The outcome of in-vitro fertilisation after the administration of preparations containing different ratios of FSH:LH leads to comparable results. However, the rate of ovarian hyperstimulation syndrome and the abortion rate after embryo transfer seems to be lower in patients stimulated with FSH dominant gonadotrophins.

[Comparison of a long-acting and short-acting GnRH analog in combination with gonadotropins in in vitro fertilization under various indications]. / Vergleich eines langwirksamen und kurzwirksamen GnRH-Analogs in Kombination mit Gonadotropinen zur In-vitro-Fertilisierung unter verschiedenen Indikationsstellungen.

The occurrence of a premature luteinizing hormone (LH)-surge during gonadotropin stimulation for in-vitro fertilization leads to cancellation of the cycle. Moreover, insufficient follicular maturation is often caused by elevated basal gonadotropin levels. Therefore the gonadotropin releasing hormone (GnRH) agonist, D-TRP6-LHRH, was applied to patients exhibiting premature LH-surges, hyperandrogenemia or incipient premature menopause. 119 cycles were treated, using a long-acting versus a short-acting GnRH agonistic analogue. In protocol 1, patients received daily subcutaneous injections of 100-500 micrograms of a short-acting compound. In protocol 2, a long-acting bolus of 3.2 mg was given intramuscularly. Concomitant human gonadotropin (HMG) stimulation started in protocol 1 after clinical and biochemical evidence of pituitary suppression and in protocol 2 after a fixed suppression interval of 14 days. In protocol 1 higher estrogen levels were reached with more oocytes harvested. The pregnancy rate per transfer was increased from 3.5% to 18%, with most pregnancies occurring with protocol 2. The cancellation rate of 13.4% was mainly due to insufficient follicular development in patients, in whom premature menopause was suspected. Hyper-androgenemic patients with an elevated LH/FSH-ratio exhibited the best follicular recruitment with the highest pregnancy rate of 25% per transfer. Thus combined GnRH-agonist/gonadotropin stimulation offers a causal treatment for patients susceptible to premature LH-surges and for hyperandrogenemic patients.

Combined GnRH-agonist/gonadotrophin stimulation for in-vitro fertilization.

The occurrence of a premature luteinizing hormone (LH) surge during gonadotrophin stimulation for in-vitro fertilization leads to cancellation of the cycle. Moreover, insufficient follicular maturation is often caused by elevated basal gonadotrophin levels. Therefore, the gonadotrophin-releasing hormone (GnRH) agonist, D-Trp-6-LHRH, was applied to patients exhibiting premature LH surges, hyperandrogenaemia or incipient premature menopause. A total of 119 cycles were treated using a long-acting versus a short-acting GnRH agonistic analogue. In protocol 1, patients received daily s.c. injections of 100-500 micrograms of a short-acting compound. In protocol 2, a long-acting bolus of 3.2 mg was given i.m. Concomitant human gonadotrophin stimulation was started in protocol 1 after clinical and biochemical evidence of pituitary suppression and in protocol 2 after a fixed suppression interval of 14 days. In protocol 1, higher oestrogen levels were reached with more oocytes harvested. The pregnancy rate per transfer was increased from 3.5 to 18%, with most pregnancies occurring with protocol 1. The cancellation rate of 13.4% was mainly due to insufficient follicular development in patients in whom premature menopause was suspected. Hyperandrogenaemic patients with an elevated LH/FSH ratio exhibited the best follicular recruitment with the highest pregnancy rate of 25% per transfer. Thus, combined GnRH-agonist/gonadotrophin stimulation offers a causal treatment for patients susceptible to premature LH surges and for hyperandrogenaemic patients.

Ovarian stimulation using pure FSH in an in-vitro fertilization programme.

The therapeutic efficacy of stimulating ovarian follicular development by pure urinary FSH in an IVF programme was determined and compared with results of other therapeutic regimens. Forty-three patients selected for extracorporeal fertilization were treated with pure FSH after stimulation with clomiphene or HMG had proved to be unsuccessful. Treatment had to be discontinued in five patients before follicular puncture, and embryo transfer was performed in 32, of whom seven conceived. FSH stimulation evidently creates favourable conditions for in-vitro fertilization in patients with impaired follicular maturation following conventional stimulation with clomiphene or HMG. Levels of oestradiol, progesterone and androstenedione were measured in follicular fluid, and high progesterone concentrations were correlated with mature oocytes. The increased ratios of progesterone/androstenedione and progesterone/oestradiol in follicles containing mature oocytes are due to the onset of luteinization of mature follicles as a consequence of HCG administration.

[Ovarian stimulation with pure FSH in an in vitro fertilization program]. / Ovarielle Stimulation mit reinem FSH in einem In-vitro-Fertilisationsprogramm.

The therapeutic efficacy of stimulating ovarian follicular development by pure urinary FSH in an IVF programme was determined and compared with results of other therapeutic regimes. 43 patients selected for extracorporeal fertilization were treated with pure FSH after stimulation with clomiphene or HMG had proven not be successful. Only in 5 patients (12%) treatment had to be discontinued before follicular puncture. In 32 women an embryo transfer was performed, and 7 patients conceived. This result demonstrates that, applying pure FSH stimulation, favourable conditions can be created for an in-vitro fertilization in patients with impaired follicular maturation following conventional stimulation with clomiphene or HMG. On the strength of the values determined for progesterone and estradiol during the luteal phase one has to conclude that a normal corpus luteum function was achieved in all our patients following FSH-stimulation.