Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial.

STUDY QUESTION: What is the impact of initiating GnRH antagonist co-treatment for in vitro fertilization (IVF) on cycle day (CD) 2 compared with CD 6 on live birth rate (LBR) per started cycle and on the cumulative live birth rate (CLBR)? SUMMARY ANSWER: Early initiation of GnRH antagonist does not appear to improve clinical outcomes of IVF compared with midfollicular initiation. WHAT IS KNOWN ALREADY: During ovarian stimulation for IVF, GnRH antagonist co-treatment is usually administered from the midfollicular phase onwards. Earlier initiation may improve the follicular phase hormonal milieu and therefore overall clinical outcomes. STUDY DESIGN, SIZE, DURATION: This open-label, multicentre randomized controlled trial was conducted between September 2009 and July 2011. A web-based program was used for randomization and 617 IVF-intracytoplasmic sperm injection (ICSI) patients were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Recombinant FSH (150-225 IU) was administered daily from CD 2 onwards in both groups. The study group (CD2; n = 308) started GnRH antagonist co-treatment on CD 2, whereas the control group (CD6; n = 309) started on CD 6. MAIN RESULTS AND THE ROLE OF CHANCE: There were no significant differences in clinical outcomes between the two groups. A non-significant trend towards a higher LBR per started cycle and CLBR was observed in the CD6 group compared with the CD2 group (LBR: 24.0 versus 21.5%, P = 0.5; CLBR: 29.9 versus 26.7%, P = 0.6). LIMITATIONS, REASONS FOR CAUTION: The study was terminated prematurely because no significant difference was observed in clinical outcomes after 617 inclusions. A much larger study population would be needed to detect a small significant difference in favour of either study arm, which raises the question of whether this would be relevant for clinical practice. WIDER IMPLICATIONS OF THE FINDINGS: The present study shows that the additional treatment burden and costs of starting GnRH antagonist on CD 2 instead of on CD 6 are not justified, as early initiation of GnRH antagonist does not improve LBRs. STUDY FUNDING/COMPETING INTEREST(S): This study was partially supported by a grant from Merck Serono. O.H., M.J.C.E, A.V., P.A.D., R.E.B., G.J.E.O., C.A.G.H., G.C.D.M., H.J.V., P.F.M.H. and A.B. have nothing to declare. F.J.B. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gedeon Richter, Merck Serono, MSD and Roche. B.J.C. has received fees and grant support from the following companies (in alphabetic order): Ferring, Merck Serono and MSD. C.B.L has received fees and grant support from the following companies (in alphabetic order): Auxogen, Ferring, Merck Serono and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gennovum, MSD, Merck Serono, Organon, Schering Plough and Serono. N.S.M. has received fees and grant support from the following companies (in alphabetic order): Anecova, Ferring, Merck Serono, MSD, Organon and Serono. TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov, no. NCT00866034.

Papillary carcinoma in struma ovarii: an unusual presentation.

Struma ovarii is the presence of thyroid tissue as the major cellular component in an ovarian tumour. Papillary carcinoma in struma ovarii is exceptionally rare. We report a case of papillary carcinoma in struma ovarii in a postmenopausal 51-year-old female who initially presented clinically with hyperthyroidism. Serology, however, did not confirm hyperthyroidism. During a re-admission to our hospital later that year she appeared to have had periods of postmenopausal vaginal haemorrhage. An abdominal mass was located by radiography and pathological investigation revealed a papillary carcinoma in struma ovarii. Some striking features of this unusual presentation of importance to the internal medicine physician are discussed.

Uterine endometrial thermal balloon therapy for the treatment of menorrhagia: long-term multicentre follow-up study.

BACKGROUND: Initial reports from observational and randomized trials of uterine endometrial thermal balloon therapy (UBT) suggested good results as judged by return to eumenorrhoea or less and patient satisfaction. Long-term follow-up data remained limited by the small numbers of patients and duration of follow-up. We present long-term (4-6 years) follow-up data from a cohort of women previously treated with UBT for menorrhagia. METHODS: Of the 260 questionnaires sent to women eligible for long-term follow-up from 10 centres, 188 (72%) replies were received. The primary outcome measure was avoidance of hysterectomy. RESULTS: In women who responded to the questionnaire, 25 had undergone hysterectomy and 21 had had repeat ablation. At 4-6 years after UBT, the probability of avoiding hysterectomy was 86% of all women, and of avoiding re-ablation was 88% of non-hysterectomized women. Overall, the probability of avoiding any surgery was 75%. Women with an axial or retroverted uterus were at greater risk of hysterectomy or re-ablation. Among the participants, 47% of the non-hysterectomized women were amenorrhoeic, 30% were hypomenorrhoeic, 13.6% were eumenorrhoeic and 8.5% had heavy periods. CONCLUSIONS: This is the first long-term follow-up report of a second-generation endometrial ablation procedure and confirms our initial experience. The high rate of hysterectomy avoidance over 5 years or more is very encouraging for this technology.