What are the factors affecting IVF success in women with hypogonadotropic hypogonadism?

OBJECTIVE: This study aimed to investigate in vitro fertilization (IVF) outcomes in women with hypogonadotropic hypogonadism (HH) and unexplained infertility and investigate factors affecting the pregnancy rate among HH patients. MATERIALS AND METHODS: This retrospective cohort study was conducted at Zeynep Kamil Maternity and Children's Diseases Training and Research Hospital, Turkey, a tertiary care referral center. The medical records of 143 women who underwent IVF treatment at this hospital between 2015 and 2020 were reviewed. Sixty-three had hypogonadotropic hypogonadism (HH) and 74 had unexplained infertility. Demographics, hormonal profile, IVF cycle characteristics, and pregnancy rates were recorded. The factors affecting the ongoing pregnancy rates were evaluated among HH patients. RESULTS: Anti-Mullerian hormone (AMH) levels were lower among women with HH compared to those with unexplained infertility (1.64±1.2 vs. 3.0±2.13). IVF cycle characteristics and ongoing pregnancy outcome (20.28% vs. 22.97%) were similar between the groups; however, the total dose of human menopausal gonadotrophin (HMG) used (5127.74±1845.8 vs. 2035.71±1387.45) was higher in the HH group. Increased estradiol level (2596.35±1085 vs. 1869.9±1203.4), endometrial thickness (10.82±1.74 vs. 8.43±2.33), higher number of total oocytes retrieved (12.14±4.34 vs. 8.43±5.44) were correlated with higher ongoing pregnancy rates among the HH group. CONCLUSIONS: IVF success rates were similar between the HH and unexplained infertility groups. Although AMH level was not a prognostic factor for IVF success, higher doses of HMG were needed to achieve pregnancy in the HH group. The factors affecting the ongoing pregnancy rates in the HH group were higher estradiol level, increased endometrial thickness, and a higher number of oocytes retrieved.

Fatigue resistance of all-ceramic fixed partial dentures - Fatigue tests and finite element analysis.

OBJECTIVE: To estimate the fatigue resistance of a new translucent zirconia material in comparison to lithium disilicate for 3-unit fixed partial dentures (FPDs). METHODS: Eighteen 3-unit FPDs (replacement of first upper molar) with a connector size of 4mm×4mm were dry milled with a five-axis milling machine (Zenotec Select, Wieland, Germany) using discs made of a new translucent zirconia material (IPS e.max ZirCAD MT, Ivoclar Vivadent). Another 9 FPDs with a reduced connector size (3mm×4mm) were milled. The zirconia FPDs were sintered at 1500°C. For a comparison, 9 FPDs were made of IPS e.max Press, using the same dimensions. These IPS e.max Press FPDs were ground from a wax disc (Wieland), invested and pressed at 920°C. All FPDs were glazed twice. The FPDs were adhesively luted to PMMA dies with Multilink Automix. Dynamic cyclic loading was carried out on the molar pontic using Dyna-Mess testing machines (Stolberg, Germany) with 2×106 cycles at 2Hz in water (37°C). Two specimens per group and load were subjected to decreasing load levels (at least 4) until the two specimens no longer showed any failures. Another third specimen was subjected to this load to confirm the result. All the specimens were evaluated under a stereo microscope (20× magnification). The number of cycles reached before observing a failure, and their dependence on the load and on the material, were modeled, using a Weibull model. This made it possible to estimate the fatigue resistance as the maximum load for which one would observe less than 1% failure after 2×106 cycles. In addition to the experimental study, Finite Element Modeling (FEM) simulations were conducted to predict the force to failure for IPS e.max ZirCAD MT and IPS e.max Press with a reduced cross-section of the connectors. RESULTS: The failure mode of the zirconia FPDs was mostly the fracture of the distal connector, whereas the failure mode of the lithium disilicate FPDs observed to be the fracture of the connectors or multiple cracks of the pontic. The fatigue resistance with 1% fracture probability was estimated to be 488N for the IPS e.max ZirCAD MT FPDs (453N for repeated test), 365N for IPS e.max ZirCAD MT FPDs with reduced connector size and 286N for the e.max Press FPDs. All three IPS e.max ZirCAD groups statistically performed significantly better than IPS e.max Press (p<0.001). On the other hand, no significant difference could be established between the two IPS e.max ZirCAD MT3 groups with a 4mm×4mm connector size (p>0.05). The allowable maximum principal stress (σmax) which did not lead to failure during fatigue testing for IPS e.max ZirCAD MT3 was calculated between 208MPa and 223MPa for FPDs with 4mm×4mm connectors for 2×106 cycles. This value could also be verified for the FPDs of the same material with 3mm×4mm connectors. On the other hand fatigue strength in terms of σmax at 2×106 cycles of IPS e.max Press was calculated to be between 78 and 90MPa. SIGNIFICANCE: The fatigue resistance of the translucent zirconia 3-unit FPDs was about 60-70% higher than that of the lithium disilicate 3-unit FPDs, which may justify their use for molar replacements, provided that a minimal connector size of 4mm×4mm is observed. Even with a limited number of specimens (n=9) per group it was possible to statistically differentiate between the tested groups.

Using a chewing simulator for fatigue testing of metal ceramic crowns.

OBJECTIVE: Dynamic loading is a more important predictor for the clinical longevity of ceramic crowns than static loading. However, dynamic loading machines are costly and mostly have only one test station. The SD Mechatronik Chewing Simulator (formerly Willytec) may be a cost-effective alternative to evaluate the fatigue resistance of metal ceramic crowns. METHOD: Four metal ceramic materials were tested on lower first molar crowns: GC InitiaI, Creation (Willy Geller), IPS InLine (Ivoclar Vivadent) and the new low-fusion IPS Style Ceram (Ivoclar Vivadent). The ceramic material was manually layered on frames made of the nickel-chromium alloy 4all (Ivoclar Vivadent) by using a silicone mould. The crowns were adhesively luted to PMMA dies. Dynamic loading was carried out with a SD Mechatronik Chewing Simulator using additional bars with weights. A steel antagonist (Ø 4mm) with 40mm/s downward speed hit the disto-buccal cusp of the crown with minimal impulse while sliding for a distance of 0.7mm. The starting load was 250N. The forces at each load level had been verified with a 3D force sensor (Kistler). Four crowns per group and load were submitted to four decreasing load levels for 200,000 cycles with a resulting simulation frequency of 0.9Hz and simultaneous thermocycling (5°C/55°C) until all four crowns no longer showed chippings. Statistical analyses had been carried out using an exponential, a Weibull and a lognormal model. The fatigue resistance was defined as the maximal load for which one would observe less than 1% failure after 200,000 cycles. In addition to the fatigue testing of the molar crowns, simulations of finite element method (FEM) were conducted in order to investigate the influence of the mismatch of the thermal expansion coefficient (CTE) between the PMMA die and the molar crown on the fatigue resistance. RESULTS: The 3D-force measurements revealed that the summarised forces were very similar to the force of the dead weights that were put on the bars. The failure modes consisted of cracks and small and big chippings. Chi-square test and Gamma revealed no statistically significant differences between the four test materials in relation to the failure mode. At 250N all materials showed chippings within the ceramic or down to the metal frame, while at lower loads there were differences. The estimated fatigue resistance was 68N for GC Initial, 88N for Creation, 96N for IPS Style Ceram, and 105N for IPS InLine, when using a Weibull model and considering all possible events. Furthermore, FEM simulations revealed that the maximum values of the maximum principal stress were 90 MPa for the thermocycling and 225 MPa for the external load. CONCLUSION: The SD Mechatronik Chewing Simulator is an adequate and cost-effective tool to test layered PFM crowns for fatigue resistance. The test method and the chewing simulator can be used for ceramic on metal, ceramic on zirconia and monolithic ceramic materials.

Perinatal outcomes of sonographically detected nuchal cord in southeastern Turkey.

PURPOSE: To investigate the outcomes of pregnancies with a sonographically detected nuchal cord (NC) from a single center in south-eastern Turkey. MATERIALS AND METHODS: A retrospective study was carried out at Maternity and Child Health Hospital Diyarbakir, Turkey, between 2011 and 2013. A-total of 477 pregnancies with sonographically detected NC during the second and third trimesteri of gestation (20-40 weeks) were included. The control group consisted of 1,043 randomly selected pregnancies without NC matched for gestational age at the time of ultrasound examination. Outcome variables, including maternal age, parity, gestational age at delivery, mnode of delivery, intrapartum fetal heart abnormalities, meconium-stained amniotic fluid, birth weight, and one- and five-minute Apgar scores, were compared between the two groups. RESULTS: There were no statistically significant differences in any of the outcome variables between patients with sonographically detected NC and controls. CONCLUSIONS: The presence of NC indicates a need for increased care but is not associated with adverse perinatal outcomes.

Protective effect of curcumin on ovarian reserve in a rat ischemia model: an experimental study.

PURPOSE OF INVESTIGATION: To determine the protective effect of curcumin on ovarian reserve in a rat ischemia model. MATERIALS AND METHODS: Thirty female Albino rats were randomly divided into two groups by time of unilateral, left ovary ischemia/reperfusion (group 1: two-hour ischemia / two-hour reperfusion; group 2: four-hour ischemia / four-hour reperfusion). Each group was subdivided into three subgroups, sham, control, and curcumin (intraperitoneal curcumin (200 mg/kg) simultaneously with reperfusion). Histological grading of ischemic indices of paraffin-embedded ovarian tissue using hematoxylin and eosin (H&E), and anti-Mulerian hormone (AMH) levels by enzyme-linked immunosorbent assay (ELISA), were measured 40 days later. RESULTS: No difference was found between groups 1 and 2 or among subgroups within either group for right and left ovary grades. AMH levels were significantly higher in the curcumin subgroup compared to sham and control within group 2 and in group 2 versus group 1 curcumin subgroups. CONCLUSION: Curcumin maintains and protects ovarian functions in an ischemia-reperfusion rat model.

The efficacy and safety of either infliximab or adalimumab in 362 patients with anti-TNF-α naïve Crohn's disease.

BACKGROUND: TNFα antagonists, including infliximab (IFX) and adalimumab (ADA), have revolutionised treatment for Crohn's disease. Studies comparing efficacy in patients with Crohn's disease naïve to TNFα antagonists are lacking. METHODS: Consecutive TNFα antagonist-naïve patients with luminal or perianal Crohn's disease from four tertiary centres in Austria were assessed prospectively for induction and maintenance efficacy, and safety, of either IFX or ADA. RESULTS: In a total of 362 patients, 251 (69.3%) started IFX and 111 (30.7%) started ADA. At baseline, the median Harvey-Bradshaw Index (HBI) score was 8 (range 5-29) and 8 (5-36), and the median C-reactive protein (CRP) was 1.07 (interquartile range (IQR) 1.36) mg/dL and 1.16 (IQR 1.23) mg/dL for IFX and ADA, respectively. At week 12, there was no difference between IFX and ADA among patients with luminal Crohn's disease in clinical remission (IFX 128/204; 62.7% vs. ADA 68/107; 63.6%, P = 0.47), clinical response (IFX 154/204; 75.5% vs. ADA 82/107; 76.6%, P = 0.82) and steroid-free remission (IFX 110/204; 53.9% vs. ADA 61/107; 57%, P = 0.60). At 12 months, there were similar numbers of patients treated with IFX and ADA who maintained clinical remission (IFX 77/154; 50.4% vs. ADA 47/82; 57.3%, P = 0.48) and steroid-free remission (IFX 68/154; 44.3% vs. ADA 44/82; 53.7%, P = 0.16). Baseline CRP >0.7 mg/dL (OR 0.24; 95% CI 0.07-0.77, P = 0.01) was the only predictor of clinical remission at 12 months in patients who did not have escalation of anti-TNFα therapy. CONCLUSION: IFX and ADA appear comparable in clinical outcomes for patients with Crohn's disease who are naïve to TNFα antagonists.

Clitoral and labial sizes in women with PCOS.

The aim of this study was to examine the external genital features in Turkish women with polycystic ovary syndrome (PCOS). Thirty-two newly diagnosed PCOS cases and 35 healthy women were included the study. All women underwent a thorough gynaecological examination. Clitoral length, and labia minora length and width were recorded. The groups were compared for features of external genital structures. Clitoral and labial lengths were significantly higher in PCOS group. There was a strong correlation between clitoral length and modified Ferriman-Gallwey score. The most effective predictor of PCOS was found to be clitoral length. Clitoral length alone predicted 99.9% of PCOS patients. There were some subclinical genital changes in women with PCOS. These changes in PCOS patients may be a sign of hyperandrogenism and might have diagnostic value in indistinct cases.

[Probiotics for the prevention of antibiotic-induced diarrhea]. / Probiotika in der Prävention der Antibiotika-induzierten Diarrhö.

Between 5 and 49% of patients treated with antibiotics suffer from diarrhoea. Principally all microbial agents can cause diarrhoea, especially oral agents like cephalosporines, clindamycin, broad-spectrum penicillins, and quinolones of the 3  rd and 4th generation. Manifestations of antibiotic-associated diarrhoea range from mild self-limiting forms to severe life-threatening courses. The potentially most severe form of antibiotic-associated diarrhoea is caused by Clostridium diffcile accounting for approx. 25  % of antibiotic-associated diarrhoea. In the past two decades a broad spectrum of different probiotic strains has been evaluated for the primary prevention of antibiotic-associated diarrhoea in children and adults. Based on their efficacy and clinical data, different levels of evidence and recommendations are emerging on the preventive use of probiotics in antibiotic-associated diarrhoea.

Retesting for latent tuberculosis in patients with inflammatory bowel disease treated with TNF-α inhibitors.

BACKGROUND: Patients treated with TNF-α inhibitors (TNFi) are at high risk of reactivation of latent tuberculosis (LTB). Prospective studies on monitoring of TB reactivation and/or infection in this risk group are lacking. AIM: To test the conversion and reversion rate of screening tests for latent TB serial tuberculin skin test (TST) and interferon-γ release assay (IGRA) under ongoing TNFi therapy. METHODS: We retested consecutive patients with IBD receiving TNFi therapy for a minimum of 5 months for LTB using IGRA and TST. A detailed patient history and concomitant therapy were recorded for each subject. RESULTS: After a median of 34.9 weeks (20.7­177.7), IGRA was retested in 184/227 patients (81.1%; Crohn's disease n = 139, ulcerative colitis n = 45) still under index TNFi. TST was available in 144/184 subjects (78.2%). The majority of patients were TNFi naïve (147/184, 79.9%). In a subgroup of patients who received isoniazid due to diagnosis of latent TB at baseline (n = 32), 6/13 patients (46.2%) with baseline positive IGRA and 3/22 patients (13.6%) with baseline positive TST reverted to negative at retesting. In patients without diagnosis of LTB at baseline no permanent IGRA conversion was observed, but there were 6/144 (4.2%) TST conversions from negative to positive. No single case of TB reactivation or infection was recorded during the observation period. CONCLUSIONS: During treatment TNF-α inhibitors conversion was observed for tuberculin skin test, but not interferon-γ release assay. As compared with tuberculin skin test, interferon-γ release assay reverted in nearly half of isoniazid-treated patients for latent tuberculosis. However, the fact that patients in whom the interferon-γ release assay test result remained positive did not develop active tuberculosis during follow-up questions the utility of interferon-γ release assay as a monitoring tool during chemoprevention.

The impact of intestinal resection on serum levels of anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn's disease.

BACKGROUND: Antibodies to Saccharomyces cerevisiae (ASCA) are highly prevalent in sera of patients with Crohn's disease and have been proposed to identify subgroups of patients with a disabling disease course. AIM: To investigate the impact of intestinal resection on serum levels of ASCA in patients with Crohn's disease and the predictive value of ASCA levels on surgical recurrence. METHODS: Sera from 60 patients who underwent 'curative' intestinal resection due to stricturing and/or penetrating complications were collected preoperatively and during post-operative follow-up (week 2, months 4, 8 and 11 ± 1). Measurement of ASCA IgG and IgA isotypes were performed using ELISA. Re-operation rate was associated with ASCA status and serum levels. RESULTS: At baseline 44/60 (73%) of patients were rated as positive for ASCA IgG, 45/60 (75%) for ASCA IgA and 52/60 (87%) as positive for at least one of both. ASCA serum levels remained stable during first year from resection. After a median of 106 months 10 of 40 (25%) patients with long-term follow-up underwent one or more intestinal re-operations. Neither ASCA positivity nor absolute ASCA serum levels were predictive of surgical recurrence. CONCLUSIONS: Serum ASCA levels remain stable after curative intestinal resection in Crohn's disease. This indicates the persistence of both stimulus and immunological mechanism operative in the production of ASCA even after complete surgical resection of macroscopically inflamed intestinal tissue. After intestinal resection, neither ASCA positivity nor ASCA serum levels predict the risk of surgical recurrence during long-term follow-up.

Recurrence of ovarian cyst after sclerotherapy.

AIM: The aim of this paper was to evaluate correlation between cyst recurrence and some cyst characteristics after sclerotherapy of non-neoplastic ovarian cyst with alcohol-erythromycin combination. METHODS: Fifty two cases of simple ovarian cysts were subjected to sclerotherapy with alcohol and erythromycin. Two patients were excluded due to suspicious cytologic result. All patients were followed-up monthly with color Doppler ultrasonography for over 12 months. Failure of procedure was considered if recurrent cyst diameter exceeds 5 centimeters detected by ultrasound. Cyst size, volume and color of aspirate, steroid hormone, and tumor marker levels of the cyst fluid were correlated to the recurrence rate. RESULTS: The fluid of cyst was serous in 32 cases and dark chocolate-colored in twenty cases. Cytological analyses of thirty cysts were acellular sediment, twenty were suitable with endometrioma and two were reported as suspicious. At 12-month follow-up, 12 cyst recurrences was detected. There was no difference in aspirated cyst volume, cyst size and FSH and LH content of recurrent and resolved cyst. The cyst wall thickness of recurrent cyst was higher than that of resolved cyst (P<0.001). The mean estradiol and progesterone concentrations of resolved cysts were significantly higher than that of recurrent cysts on the other hand, the mean CA125 levels in recurrent cysts (347.9±204.4) was significantly higher as compared to the mean CA125 concentrations of resolved cyst (16.75±22.45). CONCLUSION: Aspiration and sclerotherapy with alcohol and erythromycin yielded a relatively high recurrence rate in cyst with a bloody aspirate and high CA125 levels in cyst fluid.

[Human cloning. The biological fundamentals and an ethical-legal assessment]. / La clonación humana. Fundamentos biológicos y valoración ético-jurídica.

Following a description of the cloning process and how this might be used in humans, the authors examine the possibility of human cloning in the light of recognised ethical principles. They also address the question of whether current national and international laws are sufficient to prevent such practices.

The role of law in the patient-physician relationship.

Free or bound decision, individual responsibility or professional ethical control, conduct according to conscience or to legal directives: these buzzword dyads indicate just a few of the issues with which a physician sees himself confronted in his decision-making. And indeed not only in cases of extraordinary procedures, such as reanimation and transplantation, sterilization and fertilization, abortion and perinatology, psychosurgery and sex-change operations, experiments on human subjects and gene manipulation; but also in the day-to-day routine of patient referral or non-referral, or of continuation or termination of treatment, a physician faces the dilemma of whether or not he may take advantage of opportunities that present themselves. These problems could be summed up under the rubric of the justifications and limits of 'medical discretion'. This, however, is certainly wide open to misunderstandings because, in this way, the doctor appears to usurp an exemption for himself which ethicists and legal experts do not believe they can grant him unconditionally. In order to elucidate this problem, two issues are subject to closer analysis. First, the widespread prejudice that medical conduct is determined largely by impartial medical facts for which the establishment of norms is fundamentally elusive: this issue will be disputed on the basis of problems determining the concept and criteria of death and the appropriate termination of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The legal status of the embryo in comparative perspective.

Almost all decisions with regard to allowing or forbidding research with and on the embryo as well as any other diagnostic invasion into the embryo depend on what kind and range of protection human life in this early stage of its development is or should be entitled to. This question is commonly referred to as that of the 'moral status' of the embryo or-with special regard to legal provisions and sanctions-as its 'legal status'. The answer to this fundamental question, however, is much debated and highly controversial, both nationally and internationally. Therefore professional and legal regulations range from the rather permissive (as in the new English Human Fertilization and Embryology Act of 1990) on the one hand to the total prohibition of embryo research or certain reproductive procedures on the other (as has recently been enacted by the German Embryo Protection Act of 1990). Thus, trying to reach consensus with regard to an embryo's legal/ethical right to protection is made all the more difficult because such an opinion is often, consciously or unconsciously, prejudiced by the desire to give researchers either more or less freedom of action, depending on one's point of view: Those who wish to see diagnostic or other experimental procedures with embryos facilitated, are inclined to deny their human quality from the very start. They base their arguments on the lack of individual personality in the preinidation phase of development, or simply on the fact that in many countries abortion is not illegal at that stage. Those who, on the contrary, find abortion as well as embryo research indefensible, believe their position well-founded by assuming that the embryo, from the time of fertilization, has the individuality and personality of a human being and thus is entitled to its own basic legal rights. Since to me neither of these extreme positions seems to be particularly cogent, I will try in this article to show the reasons for and consequences of adopting a middle course which neither leaves the embryo at free disposition nor bars any kind of diagnostic or other scientific invasion.

[Law and freedom in medical decisions from the viewpoint of the law]. / Gesetz und Freiheit bei ärztlichen Entscheidungen aus der Sicht des Rechts.

Modern medicine has given doctors more and more possibilities for "manipulative" intervention in natural processes. However, even in the context of daily medical routine of beginning, continuing or terminating treatment, the doctor is repeatedly faced with the dilemma of whether to make use of the opportunities open to him. Contrary to the widely-held view that such decisions are of a purely empirico-medical nature, it becomes apparent with reference, for example, to the definition of death and the discontinuation of treatment that these decisions also have a normative-evaluative character. In relation to the postulate of the widest possible "medical discretion" emphasis is attached to the necessity for a legal framework for four functions of the law as regards the relationship between doctor and patient: protection--avoidance of abuse--presentation of guidelines--stabilisation of confidence. In conclusion the question of medical freedom in relation to active euthanasia is considered.

[Current legal problems of sterilization]. / Aktuelle Rechtsprobleme der Sterilisation.

PIP: Voluntary sterilization has not yet acquired comprehensive legal formulation. Thus there is a legal vacuum which physicians have attempted to fill by relying on their internal professional regulations. These provide for sterilization on an indication; however, an offense against this rule is not punishable in the courts. There is a prohibition, in particular, against so-called "courtesy sterilization," but this is of little significance today when so many social indications for sterilization can be found. But in general these professional regulations provide no useful assistance in deciding when a sterilization is permitted. In criminal law sterilization done by free will is not punishable nor is any indication required. The law deals in detail with the meaning and definition of the "free will" of the person being sterilized. This involves: capacity to have a free will, what to do about persons lacking that capacity (especially minors), and necessity to ensure that that woman understands all the consequences of sterilization. The civil courts have much more to do with sterilization than the criminal ones. One ground for suit is that the sterilization was "contrary to accepted morality," although the courts will generally hold that the woman herself cannot assert this claim. Another ground is lack of consent by the woman. Another ground is improper performance by the physician, i.e., malpractice. Thus the physician has to fear most the charges of no valid consent or malpractice. Questions of insurance law are also pertinent, since an insured person can be compensated for sterilization only if the procedure is legal.^ieng