Comparing the cumulative live birth rate of cleavage-stage versus blastocyst-stage embryo transfers between IVF cycles:a study protocol for a multicentre randomised controlled superiority trial (the ToF trial)

Introduction In vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen-thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited. Methods and analysis We have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients' treatment burden. Ethics and dissemination The study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals. Trial registration number Netherlands Trial Register (NL 6857)

A Controlled Study on Vaginal Blood Flow During Sexual Arousal Among Early-Stage Cervical Cancer Survivors Treated With Conventional Radical or Nerve-Sparing Surgery With or Without Radiotherapy

Objective: Sexual problems among cervical cancer survivors may in part be caused by reduced vaginal blood flow due to damaged hypogastric nerves during radical hysterectomy with pelvic lymphadenectomy and/or by radiation-induced vaginal changes after pelvic radiotherapy. A nerve-sparing modification of radical hysterectomy (NSRH) may preserve vaginal blood flow. Vaginal blood flow during sexual arousal was compared between different treatment modalities. Methods: We investigated premenopausal women treated for early-stage cervical cancer with radical hysterectomy (n = 29), NSRH (n = 28), NSRH with radiotherapy (n = 14), and controls (n = 31). Genital arousal and subjective sexual arousal in response to sexual stimuli were measured using vaginal photoplethysmography and a questionnaire. Results were compared by using a between-study (treatment groups) by within-study (stimulus) design. Results: Participants were aged 29 to 51 years (mean, 42 years) and at 1 to 14 years (mean, 5 years) after treatment. Measured vaginal blood flow in women treated with NSRH was similar to controls. Women treated with radical hysterectomy had a significantly lower vaginal blood flow compared with controls overall and lower compared with the NSRH group during sexual stimulation. Women treated with radiotherapy had a vaginal blood flow intermediate between the other groups without significant differences. The erotic films were equally effective in enhancing subjective sexual arousal among treatment groups. Conclusions: Cervical cancer treatment with radical hysterectomy disrupts the vaginal blood flow response, and this may be prevented by conducting an NSRH. Treatment with radiotherapy did not significantly impact vaginal blood flow, but further investigation is needed with a larger sampl