Deciding on future fertility: considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation.

RESEARCH QUESTION: What are the considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation (OTC)? DESIGN: Semi-structured in-depth interviews were conducted with girls with Turner syndrome and their parents until data saturation was reached. Participants were recruited through purposive sampling. Data were analysed using a thematic analysis approach. RESULTS: Thirteen parents and five girls who opted for OTC, and seven parents and three girls who declined OTC, were interviewed. Parents and girls mentioned that OTC offered hope, an opportunity to have genetic offspring and clarity about their current fertility status. Most participants were not afraid of the risks of surgery and trusted healthcare providers with this procedure. In contrast, families had to deal with uncertainties, owing to the lack of information on the success rate and long-term consequences of OTC in this group. Families indicated that they had to go through an important decision-making process in a short period of time, because of the limited number of participants in the OTC study. CONCLUSION: A new opportunity and hope for future fertility were considerations for opting for OTC. However, OTC also came with uncertainties owing to the experimental nature of this procedure in girls with Turner syndrome. Healthcare providers could share these experiences with girls with Turner syndrome and their parents to improve fertility-preservation counselling in this group.

External quality control and training of semen analysis in the Netherlands: starting point for further reduction of outcome variability.

Semen analysis is characterized by high levels of intra- and inter-laboratory variability, due to a low level of standardization, high subjectivity of the assessments, and problems with automated procedures. To improve consistency of laboratory results, quality control and training of technicians are important requisites. The goals of this study are to evaluate the results of an external quality control (EQC) program and standardized training by ESHRE Basic Semen Analysis Courses (BSAC) on the variability in manual assessments of semen parameters. We performed retrospective analyses of (1) the interlaboratory variability in the Dutch EQC program and (2) the interobserver variability in BSACs for concentration, motility, and morphology assessments. EQC data showed that the interlaboratory coefficient of variation (CV) for concentration assessment decreased (range from 24.0%-97.5% to 12.7%-20.9%) but not for morphology and motility assessments. Concentration variability was lower if improved Neubauer hemocytometers were used. Morphology assessment showed highest CVs (up to 375.0%), with many outliers in the period of 2007-2014. During BSAC, a significant reduction of interobserver variability could be established for all parameters (P < 0.05). The absence of an effect in the EQC program for motility and morphology might be explained by respectively the facts that motility assessment was introduced relatively late in the EQC program (since 2013) and that criteria for morphology assessment changed in time. BSAC results might have been influenced by the pretraining level of participants and the influence of external factors. Both EQC and training show positive effects on reducing variability. Increased willingness by laboratories to change their methods toward standards may lead to further improvements.

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).

An objective and automated method for evaluating abdominal hyperalgesia in a rat model for endometriosis.

Chronic pain and subfertility are the main symptoms of concern in women with endometriosis. In order to find new therapeutic options to suppress the pain, translational animal models are indispensable. We have developed a new automated, experimental setup, with full consideration for animal wellbeing, to determine whether operant behaviour can reveal abdominal hyperalgesia in rats with surgically-induced endometriosis, in order to assess whether abdominal hyperalgesia affect behavioural parameters. Endometriosis was induced by transplantation of uterine fragments in the abdominal cavity. Control groups consisted of sham-operated rats and non-operated rats. We have developed an operant chamber (Skinnerbox) which includes a barrier. The rat can climb the barrier in order to reach the food pellet, increasing in this way the pressure to the abdomen. We show that endometriosis rats collect significantly less sugar pellets when compared with the control rats after the introduction of the barrier. In the Skinnerbox experiment, we showed that in a positive operant setting, the introduction of a barrier results in a contrast of operant behaviour of endometriosis rats and control groups, perchance as a result of abdominal discomfort/hyperalgesia due to surgically-induced endometriosis. This is a promising start for the further development of a refined animal model to monitor abdominal discomfort/hyperalgesia in rats with surgically-induced endometriosis.