Value-based healthcare in fertility care using relevant outcome measures for the full cycle of care leading towards shared decision-making: a retrospective cohort study.

OBJECTIVE: To determine if the introduction of value-based healthcare (VBHC) in fertility care can help to create realistic expectations in patients resulting in increased patient value, by demonstrating the relevance of defining outcome measures that truly matter to subfertile patients. DESIGN: Retrospective cohort study. SETTING: Tertiary fertility centre. RESULTS: Time to pregnancy (TTP) and ongoing pregnancy rate (OPR), as a proxy for the live birth rate, for the full cycle of fertility care, regardless of which and how many treatment cycles performed, were identified as the most relevant medical outcome measures. Outcome measures were incorporated into a digital dashboard by using anonymised and validated patient data from the electronic patient file. We were able to present the TTP and OPR for the population as a whole as well as stratified for age, diagnosis, gravidity and type of gamete source used thereby resulting in a virtual 'patient like me' resembling the individual patient in the consultation room. CONCLUSION: We have shown that, by applying VBHC principles, relevant outcome measures can be generated and stratified for different patient characteristics, in order to develop a virtual 'patient like me'. This virtual 'patient like me' can be used in the consulting room in the form of a digital dashboard, attributing to create realistic patient expectations. This facilitates healthcare providers and patients in shared decision-making.

A multicentre double-blinded randomized controlled trial on the efficacy of laser-assisted hatching in patients with repeated implantation failure undergoing IVF or ICSI.

STUDY QUESTION: Does assisted hatching increase the cumulative live birth rate in subfertile couples with repeated implantation failure? SUMMARY ANSWER: This study showed no evidence of effect for assisted hatching as an add-on in subfertile couples with repeated implantation failure. WHAT IS KNOWN ALREADY: The efficacy of assisted hatching, with regard to the live birth rate has not been convincingly demonstrated in randomized trials nor meta-analyses. It is suggested though that especially poor prognosis women, e.g. women with repeated implantation failure, might benefit most from assisted hatching. STUDY DESIGN, SIZE, DURATION: The study was designed as a double-blinded, multicentre randomized controlled superiority trial. In order to demonstrate a statistically significant absolute increase in live birth rate of 10% after assisted hatching, 294 participants needed to be included per treatment arm, being a total of 588 subfertile couples. Participants were included and randomized from November 2012 until November 2017, 297 were allocated to the assisted hatching arm of the study and 295 to the control arm. Block randomization in blocks of 20 participants was applied and randomization was concealed from participants, treating physicians, and laboratory staff involved in the embryo transfer procedure. Ovarian hyperstimulation, oocyte retrieval, laboratory procedures, embryo selection for transfer and cryopreservation, the transfer itself, and luteal support were performed according to local protocols and were identical in both the intervention and control arm of the study with the exception of the assisted hatching procedure which was only performed in the intervention group. The laboratory staff performing the assisted hatching procedure was not involved in the embryo transfer itself. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were eligible for inclusion in the study after having had either at least two consecutive fresh IVF or ICSI embryo transfers, including the transfer of frozen and thawed embryos originating from those fresh cycles, and which did not result in a pregnancy or as having had at least one fresh IVF or ICSI transfer and at least two frozen embryo transfers with embryos originating from that fresh cycle which did not result in a pregnancy. The study was performed at the laboratory sites of three tertiary referral hospitals and two university medical centres in the Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative live birth rate per started cycle, including the transfer of fresh and subsequent frozen/thawed embryos if applicable, resulted in 77 live births in the assisted hatching group (n = 297, 25.9%) and 68 live births in the control group (n = 295, 23.1%). This proved to be statistically not significantly different (relative risk: 1.125, 95% CI: 0.847 to 1.494, P = 0.416). LIMITATIONS, REASONS FOR CAUTION: There was a small cohort of subfertile couples that after not achieving an ongoing pregnancy, still had cryopreserved embryos in storage at the endpoint of the trial, i.e. 1 year after the last randomization. It cannot be excluded that the future transfer of these frozen/thawed embryos increases the cumulative live birth rate in either or both study arms. Next, at the start of this study, there was no international consensus on the definition of repeated implantation failure. Therefore, it cannot be excluded that assisted hatching might be effective in higher order repeated implantation failures. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated no evidence of a statistically significant effect for assisted hatching by increasing live birth rates in subfertile couples with repeated implantation failure, i.e. the couples which, based on meta-analyses, are suggested to benefit most from assisted hatching. It is therefore suggested that assisted hatching should only be offered if information on the absence of evidence of effect is provided, at no extra costs and preferably only in the setting of a clinical trial taking cost-effectiveness into account. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR 3387, NL 3235, https://www.clinicaltrialregister.nl/nl/trial/26138). TRIAL REGISTRATION DATE: 6 April 2012. DATE OF FIRST PATIENT'S ENROLMENT: 28 November 2012.

In Vitro Maturation of Oocytes in Women at Risk of Ovarian Hyperstimulation Syndrome-A Prospective Multicenter Cohort Study.

BACKGROUND: In vitro maturation (IVM) is an artificial reproductive technology in which immature oocytes are harvested from the ovaries and subsequently will be matured in vitro. IVM does not require ovarian hyperstimulation (OH) and thus the risk of ovarian hyperstimulation syndrome (OHSS) is avoided. In this study, we assessed the live birth rate per initiated IVM cycle in women eligible for in vitro fertilization/intracytoplasmic sperm injection (IVF/ ICSI) and at risk for OHSS. Furthermore, we followed women who were not pregnant after IVM and committed to a conventional IVF/ICSI procedure. MATERIALS AND METHODS: In this multicenter prospective cohort study, we started 76 IVM cycles using recombinant follicle stimulating hormone (rFSH) priming in 68 patients. There were 66 oocyte retrievals, in which a total of 628 oocytes were collected. We incubated the immature oocytes for 24-48 hours and fertilized those that reached metaphase II by ICSI. RESULTS: Three hundred eighty six (61% oocytes) achieved metaphase II. The fertilization rate was 55%. We performed 59 embryo transfers (1.9 embryos per transfer) in 56 women, including 3 frozen embryo transfers. There were four ongoing pregnancies (5.3% per initiated cycle) leading to the birth of a healthy child at term. None of the patients developed OHSS. The ongoing pregnancy rate of the first conventional IVF/ICSI cycle after an unsuccessful IVM cycle was 44%, which was unexpectedly high. CONCLUSION: We concluded that IVM led to live births but with low effectiveness in our study. Earlier reported IVM success rates are higher which can be caused by a more extended experience in these centers with the intricate laboratory process. However, a possible selection bias in these studies cannot be ruled out. Furthermore, IVM might have a beneficial effect on further IVF/ICSI treatments due to its "ovarian drilling" effect.