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.

Conservatively treated borderline ovarian tumours, followed by IVF treatment: a case series.

Borderline ovarian tumours (BOT) often affect young females, in whom conservative treatment may be desired in order to preserve fertility. It is unknown whether in vitro fertilisation (IVF) increases the risk of recurrent disease. This case-series will focus on four patients diagnosed with BOT, who were initially treated conservatively and subsequently received IVF. Five recurrences occurred prior to IVF and three recurrences occurred after IVF in three individuals. After a mean follow-up of 104 months after initial conservative treatment and 43 months after IVF treatment, all four patients were alive and disease-free.

[Fertility preservation in female oncology patients]. / Fertiliteitspreservatie bij vrouwen met kanker.

Four women were referred to the department ofGynaecology for fertility preservation. A 33-year-old nulliparous woman with breast cancer stage pT1cN0M0 underwent an IVF-ICSI cycle; five embryos were frozen. Pre-implantation genetic diagnosis (PGD) because of BRCA2 gene mutation carriage was not carried out and more recently follow-up oocyte donation options are being considered. A second, 32-year-old nulliparous woman with breast cancer stage pT2N1M0 underwent an IVF cycle; seven embryos were frozen. The third patient was a 14-year-old girl with osteosarcoma of the distal femur, who underwent a laparoscopic unilateral ovariectomy, one day after referral, and cortical tissue was frozen. The fourth patient was a 33-year-old nulliparous woman without partner, with non-Hodgkin lymphoma stage IIA. She underwent laparoscopic ovariectomy and cortical tissue was frozen. Infertility due to cancer treatment and fertility preservation options should be discussed early in treatment planning. Patients' expectations and fertility preservation limitations are important to consider. Fertility preservation options can be conducted in specialised hospitals under institutional review board approval. It still has an experimental status.