• Introduction: Differences in the mode of action between recombinant FSH (rFSH) preparations and urinary derived FSH (uFSH) or hMG preparations have been reported in cycles down-regulated by GnRH-agonists. The aim of our study was to determine, if these differences also exist in cycles down-regulated by GnRH-antagonists. Methods: GnRH-antagonist cycles performed between 2009 – 2012 were divided into two groups: 1. 203 cycles stimulated with Follitropin alfa plus 443 cycles stimulated with Follitropin beta (rFSH), and 2. 405 cycles stimulated with Urofollitropin (uFSH). Cetrorelix or Ganirelix were used as GnRH-antagonists. All patients received 75 IU hMG additionally from day 6 of stimulation onwards up to the day of hCG administration. Initially, a logistic regression analysis was conducted to find the most significant parameters predicting hCG-positive pregnancy for 2471 IVF cycles. The results demonstrated that the predictors age of patients (p<0,001) and number of cycles ever performed (p=0,003) made negative contributions and number of oocytes retrieved (p=0,076) and number of embryos transferred (p<0,001) made positive contributions to prediction. Taking this into consideration, comparable groups could be created by including only first-ever IVF cycles with more than 10 oocytes retrieved and 2 embryos transferred. Thus, the final sample for comparison included 98 patients in the rFSH-group and 27 patients in the uFSH group. Results: There were no differences in basic personal data and gonadotropin consumption between the groups. Stimulation with rFSH resulted in a higher yield of oocytes compared to uFSH (15,6 vs. 14,4 m.n.), however, the results of the following reproductive outcome parameters were all in favour of uFSH when rFSH and uFSH were compared: oocyte maturation rate (76.5% vs. 79.0 %), fertilization rate (53,6% vs. 58,6%), embryo score 4 rate (25,7% vs. 31,1%), hCG-positive pregnancy rate (43,9% vs. 59,3%), clinical pregnancy rate (33,7% vs. 44,4%), embryo-cryopreservation rate (19,3% vs. 30,5%) and abortion rate (14,0% vs. 12,5%). Conclusion: These results seem to support the concept that uFSH produces fewer oocytes than rFSH, but the oocytes produced by uFSH are, on an average, of better quality than those produced by rFSH. Basic studies have shown that different FSH isoforms with different elimination kinetics in the two gonadotropin preparations could be responsible for this different effects. Our preliminary results, based on a retrospective study, have to be confirmed, however, by well designed prospective randomized studies. * corresponding author. E-mail address: peter.kemeter@wunschbaby.at 

BACKGROUND:

Arch Gynecol Obstet. 2013 Nov;288(5):1081-6. 2013 May 7.

Grimm C(1), Brammen L, Sliutz G, Weigert M, Sevelda P, Pils S, Reinthaller A, Polterauer S.

PURPOSE: The extent of conization seems to influence the risk of preterm birth. The aim of this study was to compare the cone volume after surgical resection with large loop excision of the transformation zone (LLETZ) and cold knife conization (CKC).

METHODS: The present retrospective multi-center study comprises 804 consecutive women, who underwent LLETZ (n = 412) or CKC (n = 392) between 2004 and 2009. Univariate and multivariable analyses were performed to compare cone volumes removed by LLETZ and CKC and identify independent risk factors for large cone volume.

RESULTS: The median resected cone volume after LLETZ was significantly smaller [1.6 cm(3) (0.8-2.9)] than after CKC [2.1 cm(3) (1.4-3.5)] (<0.0001). Complete resection rates were comparable in both groups. Conization method, cone depth, and institution type were independent risk factors for removal of a large cone volume.

CONCLUSION: CKC removes larger cone volumes than LLETZ without the advantage of higher complete resection rates.

Exp Ther Med. 2011 Sep;2(5):991-995. Epub 2011 Jun 30.

Tempfer C(1), Froese G, Buerkle B, Polterauer S, Grimm C, Concin N, Hofstetter G, Weigert M, Oehler MK.

Women with endometrial cancer often undergo hysteroscopy during their diagnostic work-up. Whether or not the duration of hysteroscopy affects the rate of positive peritoneal cells and the duration of recurrence-free survival is unknown. In a retrospective multi-centre study, the records of 552 patients with endometrial cancer were investigated. Duration of hysteroscopy was correlated with clinicopathological parameters and patient survival data. The mean [standard deviation (SD)] duration of hysteroscopy was 18.2 (10.5) min in the study population and 17.9 (10.1) min and 17.9 (10.2) min in patients with positive (n=109) and negative peritoneal cytology (n=443), respectively (p=0.9). There were no statistically significant correlations between duration of hysteroscopy and positive peritoneal cytology (p=0.6; rho=-0.028), FIGO stage (p=0.2; rho=-0.080), lymph node involvement (p=0.2; rho=0.106) and patient age (p=0.5; rho=0.033). Longer duration of hysteroscopy (>15 min) was not associated with
positive peritoneal cytology (yes vs. no, p=0.8), advanced tumour stage (FIGO I vs. II, III and IV, p=0.3), lymph node involvement (yes vs. no, p=0.1) and patient age (≤65 vs. >65 years, p=0.4). In a multivariate analysis, FIGO stage [p<0.0001; hazard ratio (HR)=5.1, 95% confidence interval (CI) 2.5-10.2], lymph node involvement (p=0.02; HR=3.2, 95% CI 1.2-8.8) and patient age (p=0.003; HR=2.4, 95% CI 1.3-4.2), but not duration of hysteroscopy (p=0.4; HR=1.2, 95% CI 0.7-2.2), were associated with recurrence-free survival. We conclude that longer duration of hysteroscopy does not increase the risk of positive peritoneal cytology and it is not an adverse prognostic factor for recurrence-free survival in patients with endometrial cancer.

N Engl J Med. 2009 Feb 12;360(7):679-91. doi: 10.1056/NEJMoa0806285.

Gnant M(1), Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rücklinger E, Greil R; ABCSG-12 Trial Investigators, Marth C.

Collaborators: Taucher S, Bachleitner-Hofmann T, Schoppmann S, Rudas M, PluschnigU, Hussian D, Sevelda U, Bartsch R, Locker G, Wenzel C, Dadak C, Obwegeser R, Kubista E, Asseryanis E, Möslinger-Gehmayr R, Hanzal E, Sam C, Mayer P, Moik M,Rass C, Reitsamer R, Russ G, Bauernhofer T, Kasparek AK, Wagner P, Langsenlehner U, Krippl P, Balic M, Andritsch E, Schaberl-Moser R, Lileg B, Weitzer W, Hofmann ,Mischinger HJ, Ploner F, Smola M, Stöger H, Depisch D, Lenauer A, Haider K,Payrits T, Greul R, Hochreiner G, Wahl G, Tschmelitsch J, Reichenauer A, Wette V, Selim U, Artner S, Matzinger H, Galid A, Baumann J, Medl M, Schmidbauer U,Wunderlich M, Hofbauer F, Lang M, Horvath W, Luisser I, Fandl G, Prager M, Klug E, Kier P, Renner K, Pichler M, Weigert M, Sevelda F, Sevelda P, Denison U,Peters-Engl C, Veneziano N, Kocher R, Stangl F, Winter R, Sandbichler P, Schennach W, Mühlthaler M, Anderl P, Mitterdorfer B, Draxler U, Volgger B,Helfgott R, Schmidhammer C, Heck D, Kugler F, Aufschnaiter M, Michlmayr G, Schildberger R, Haid A, Köberle-Wührer R, Döller W, Melbinger E, Berger J,Lenzhofer R, Zeilmann W, Medek B, Schäfer S, Stephan H, Schmid FX, Ludwig H, Sagaster P, Reiner G, Semmler D, Kretschmer A, Trapl H, Tichatschek R, Magg P,Bosse C, Weissinger G, Labuda B, Hartmann B, Bernhaus A, Lechner P, Zeh B, Beer B, Simma W, Pichler-Gebhard B, Schiller L, Wilthoner K, Haslbauer F, Thaler J,Trommet V, Pillichshammer S, Baldinger C, Oppitz P, Kühr T, Wimmer L, Koplmüller R, Tausch C, Wenzl-Eybl SA, Haberfellner H, Függer R, Havlicek W, HinterbuchingerC, Aschauer W, Grenzfurtner G, Omann J, Urbania A, Holzmüller K, Hofmann H, Radl C, Neunteufel W, Poyssl C, Bischofberger K, Marth C, Widschwendtner M, Bergant A,Zeimet A, Müller H, Volgger B, Ramoni A, Spechtenhauser B, Felgel-Farnholz C, Alicke S, Matthä K, Bachmann A, Hartner E, Seewann HL, Keckstein J, Tuttlies F,Pacher D, Unterrieder K, Jonat W, Eiermann W, Seitz J, Sanchez M, Hanusch C, Lorch R, Jessat U, Stehle M, Sommer L, Franz M, Conrad B, Hopf G, Balwanz A,Stitz E, Hellriegel KP, Shim S, Dewitz T, Vietoris S, Beha M, Marschner N,Otremba B, Reschke D.

BACKGROUND: Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties.

METHODS: We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer. We randomly assigned 1803 patients to receive goserelin (3.6 mg given subcutaneously every 28 days) plus tamoxifen (20 mg per day given orally) or anastrozole (1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every 6 months) for 3 years. The primary end point was disease-free survival; recurrence-free survival and overall survival were secondary end points.

RESULTS: After a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P=0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P=0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P=0.11). Adverse events were consistent with known drug-safety profiles.

CONCLUSIONS: The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. (ClinicalTrials.gov number, NCT00295646.)

J Assist Reprod Genet. 2009 Jan;26(1):13-7. doi: 10.1007/s10815-008-9278-2. Epub 2008 Nov 20.

Weigert M(1), Gruber D, Pernicka E, Bauer P, Feichtinger W.

PURPOSE: To investigate the incidence of Tubal Ectopic Pregnancies (TEP) in IVF-ET patients with respect to the status of the fallopian tubes after a previous TEP.

MATERIAL AND METHODS: This retrospective study compares patients undergoing 481 IVF-ET cycles after conservatively or surgically treated TEP(s) with a Control Group (idiopathic or male factor for IVF-ET indication). Medical reports of surgery and/or hysterosalpingograms prior to the IVF cycles classified the status of the fallopian tubes.

RESULTS: 12 TEPs (8.95%/Pregnancies (PR)) occurred in the Study Group. In the Control Group one TEP (0.75%/PR; p < 0.001) was found. Smoking increased the probability of TEPs (p = 0.0028) and of pathological pregnancies (abortion, biochemical and ectopic PR; (p = 0.0411)). For statistic evolution logistic regression (PROC GENMOD) and a repeated measure model were applied.

CONCLUSION: Women with a previous TEP should be informed about the significantly increased risk for a further TEP in IVF-ET treatment, especially if they are smoking.

Anticancer Res. 2008 Nov-Dec;28(6B):3977-84

Volgger B(1), Petru E, Angleitner-Boubenizek L, Weigert M, Reinthaller A, Lass H, Stempfl A, Gamper C, Deibl M, Marth C.

BACKGROUND: The influence of two regimens of erythropoetin beta on haemoglobin level, quality of life (QoL) and side-effects in patients with gynecological malignancies was assessed.

PATIENTS AND METHODS: A total of 119 patients during chemotherapy were randomized to either standard therapy with 10,000 IU erythropoetin beta three times a week (group A) or 20,000 IU twice a week (group B). Haemoglobin level and QoL were measured. Characteristics of the study population were analysed with descriptive statistical methods. Analysis of variance for repeated measurements was performed with haemoglobin level as dependent variable, and time and study arms as factors.

RESULTS: The rise in haemoglobin levels and QoL improvement were significant, without any difference between study arms. Adverse events were similar, except significantly more thromboembolic events in group B (0 vs. 8 events; p = 0.003).

CONCLUSION: Our results show similar improvements in haemoglobin level and QoL, but raise the question whether less frequent dosing regimes may result in increased rates of thromboembolic events.

Lancet Oncol. 2008 Sep;9(9):840-9.. Epub 2008 Aug 19

Gnant M(1), Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kässmann H, Piswanger-Sölkner JC, Seifert M, Ploner F, Menzel C, Dubsky P, Fitzal F, Bjelic-Radisic V, Steger G, Greil R, Marth C, Kubista E, Samonigg H, Wohlmuth P, Mittlböck M, Jakesz R; Austrian Breast and Colorectal Cancer Study Group (ABCSG).

Collaborators: Taucher T, Bachleitner-Hofmann T, Schoppmann S, Rudas M, PluschnigU, Hussian D, Sevelda U, Bartsch R, Locker G, Wenzel C, Dadak Ch, Obwegeser R, Asseryanis E, Möslinger-Gehmayr R, Hanzal E, Sam C, Mayer P, Rass C, Reitsamer R,Russ G, Bauernhofer T, Kasparek AK, Wagner P, Langsenlehner U, Krippl P, Balic M, Andritsch E, Schaberl-Moser R, Schippinger W, Lileg B, Weitzer W, Hofmann G,Mischinger HJ, Smola M, Stöger H, Depisch D, Lenauer A, Payrits T, Greul R, Hochreiner G, Wahl G, Fridrik MA, Tschmelitsch J, Reichenauer A, Wette V, StiererM, Selim U, Artner S, Schmidbauer U, Wunderlich M, Hofbauer F, Lang M, Kier P, Renner K, Pichler M, Weigert M, Sevelda F, Sevelda P, Denison U, Peters-Engl Ch, Kocher R, Stangl F, Winter R, Sandbichler P, Schennach W, Mühlthaler M, Pöstlberger S, Helfgott R, Schmidhammer C, Heck D, Kugler F, Aufschnaiter M,Michlmayr G, Schildberger R, Haid A, Köberle-Wührer R, Döller W, Melbinger E, Berger J, Lenzhofer R, Ludwig H, Sagaster P, Reiner G, Semmler D, Trapl H,Tichatschek R, Bosse C, Lechner P, Zeh B, Omann J, Urbania A, Holzmüller K, Neunteufel W, Widschwendtner M, Bergant A, Zeimet A, Hubalek M, Müller H, VolggerB, Ramoni A, Hartner E, Seewann HL.

BACKGROUND: The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting.

METHODS: ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646.

FINDINGS: 404 patients were prospectively included in the bone sub study and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (-11.3%, mean difference -0.119 g/cm(2) [95% CI -0.146 to -0.091], p<0.0001) and trochanter (-7.3%, mean difference -0.053 g/cm(2) [-0.076 to -0.030], p<0.0001). In patients who did not receive zoledronic acid, anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine (-13.6%, mean difference -0.141 g/cm(2) [-0.179 to -0.102] vs -9.0%, mean difference -0.095 g/cm(2) [-0.134 to -0.057], p

INTERPRETATION: Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years.

Acta Cytol. 2006 Mar-Apr;50(2):185-90

Weigl G(1), Pokieser W, Schuller B, Weigert M, Ulrich W, Sevelda P, Breitenecker G.

OBJECTIVE: To analyze factors in preoperative management and cytologic screening leading to a conization specimen free of neoplasia.

STUDY DESIGN: From January 2001 through December 2003, cervical conization was performed on 208 consecutive cases at the Gynecologic Department, Krankenhaus Lainz, Vienna. Indications for cone biopsy were based on suspicious internal and/or external conventional cytologic screening results followed by punch biopsies in selected cases.

RESULTS: Benign cervical lesions were diagnosed in 22 women (10.6%). Histologic results in negative cone biopsies were cervicitis (n = 12), infection with HPV without cervical intraepithelial neoplasia (n = 1), tubal metaplasia (n = 4) and combined diagnoses indicating no neoplasia (n = 5). Regarding cytologic screening results prior to conization, long-lasting infections with HPV can cause repeated findings of cells of unknown origin or reversible mild to moderate dysplasia eventually leading to conization specimens free of neoplasia. Furthermore, tubal metaplasia is a frequent pitfall in misinterpretation of cytologic smears.

CONCLUSION: Reevaluation of cytologic screening results after the final histologic diagnosis becomes available following cone biopsy is a key issue in continuous quality assurance for the diagnostic procedure. In this article we also present a method of stratifying screening results according to the correctness of the results. Along with other established measures of diagnostic performance, this may support benchmarking and interpretation of the overall cytologic screening quality.

J Assist Reprod Genet. 2002 Nov;19(11):539-40.

Weigert M, Kaali SG, Kulin S, Feichtinger W.

PURPOSE: Our objective was to investigate the lunar influence on IVF-ET outcomes.

METHODS: Between 1992 and 1999 we have completed 7572 preprogrammed IVF-ET treatment cycles with the same stimulation protocol in two outpatient units. (Vienna, Austria and Budapest, Hungary) Multiple regression (SAS; proc Logistic) and two separate analyses were performed on pregnancy rates using a harmonic sinoidal trend based on the synodic and anomalistic lunar cycles respectively.

RESULTS: The overall pregnancy rate was 30.9%. The amplitude of harmonic sinoidal, trend for the synodic lunar cycles was chi2 = 1.63,2d.f., p = 0.44 and chi2 = 6.27,2d.f., p = 0.044 for the anomalistic moon periods. For the anomalistic lunar months the amplitude of harmonic sinoidal trend was borderline in terms of higher pregnancy rates with the moon in Perigee.

CONCLUSION: The cause of seasonal changes in IVF-ET outcomes is probably very complex. Our results indicate that lunar influence may only be one of the contributing factors. Further studies are needed to clarify unexplained fluctuations of pregnancy outcomes.