Effectiveness of a mobile preconception lifestyle programme in couples undergoing in vitro fertilisation (IVF): the protocol for the PreLiFe randomised controlled trial (PreLiFe-RCT).

INTRODUCTION: Infertility and in vitro fertilisation (IVF; with or without intracytoplasmic sperm injection) result in considerable emotional and financial burden. Increasing evidence suggests that lifestyle factors, including diet, physical activity and personal well-being, are associated with IVF-success rates. Currently, IVF is not routinely combined with a lifestyle programme. The preconception lifestyle (PreLiFe) randomised controlled trial (RCT) assesses the effects of a new mobile PreLiFe programme in couples undergoing IVF. METHODS AND ANALYSIS: A multicentre RCT including 460 heterosexual couples starting IVF in Belgian fertility clinics. IVF couples are randomised between an attention control group or the PreLiFe programme for a period of 12 months or until an ongoing pregnancy is confirmed by ultrasound. The attention control programme includes a mobile application with treatment information (ie, appointments and medication instructions) in addition to standard care. The PreLiFe programme includes a mobile application with the same treatment information in combination with a lifestyle programme. This new lifestyle programme includes tailored advice and skills training on diet, physical activity and mindfulness in combination with text messages and telephone interaction with a healthcare professional trained in motivational interviewing. The primary outcome of this RCT is the cumulative ongoing pregnancy rate within 12 months after randomisation. Secondary outcomes include changes in diet, physical activity, emotional distress, body mass index, waist circumference, quality of life and other reproductive outcomes including IVF discontinuation, clinical pregnancy rate and time to pregnancy. Additionally, partner support and the feasibility (use and acceptability) of the PreLiFe programme will be evaluated in the intervention group. Analysis will be according to intention to treat. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethical Committee of the Leuven University Hospital (Belgium) and the other recruiting clinics. The findings of this RCT will be disseminated through presentations at international scientific meetings and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03790449; Pre-results.

Impact of luteal phase support with vaginal progesterone on the clinical pregnancy rate in intrauterine insemination cycles stimulated with gonadotropins: a randomized multicenter study.

OBJECTIVE: To evaluate the effect of luteal phase support (LPS) in intrauterine insemination (IUI) cycles stimulated with gonadotropins. DESIGN: Randomized multicenter trial. SETTING: Academic tertiary care centers and affiliated secondary care centers. PATIENT(S): Three hundred and ninety-three normo-ovulatory patients, <43 years, with body mass index ≤30 kg/m2, in their first IUI cycle, with at least one patent tube, a normal uterine cavity, and a male partner with total motile sperm count ≥5 million after capacitation. INTERVENTION(S): Gonadotropin stimulation, IUI, randomization to LPS using vaginal progesterone gel (n = 202) or no LPS (n = 191). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live-birth rate, miscarriage rate, and duration of the luteal phase. RESULT(S): The primary outcome, the clinical pregnancy rate, was not statistically different between the treatment group (16.8%) and the control group (11%) (relative risk [RR] 1.54; 95% confidence interval [CI], 0.89-2.67). Similarly, the secondary outcome, the live-birth rate, was 14.9% in the treatment group and 9.4% in the control group (RR 1.60; 95% CI, 0.89-2.87). The mean duration of the luteal phase was about 2 days longer in the treatment group (16.6 ± 2.2 days) compared with the control group (14.6 ± 2.5 days) (mean difference 2.07; 95% CI, 1.58-2.56). CONCLUSION(S): Although a trend toward a higher clinical pregnancy rate as well as live-birth rate was observed in the treatment group, the difference with the control group was not statistically significant. CLINICAL TRIAL REGISTRATION NUMBER: NCT01826747.

Frozen-thawed embryo transfer in a natural or mildly hormonally stimulated cycle in women with regular ovulatory cycles: a RCT.

STUDY QUESTION: Can ovarian stimulation with low dose hMG improve the implantation rate (IR) per frozen-thawed embryo transferred (FET) when compared with natural cycle in an FET programme in women with a regular ovulatory cycle? SUMMARY ANSWER: Both IR and live birth rate (LBR) per FET were similar in the group with mild ovarian stimulation and the natural cycle group. WHAT IS KNOWN ALREADY: Different cycle regimens for endometrial preparation are used prior to FET: spontaneous ovulatory cycles, cycles with artificial endometrial preparation using estrogen and progesterone hormones, and cycles stimulated with gonadotrophins or clomiphene citrate. At present, it is not clear which regimen results in the highest IR or LBR. More specifically, there are no RCTs in ovulatory women comparing reproductive outcome after FET during a natural cycle and during a hormonally stimulated cycle. STUDY DESIGN, SIZE, DURATION: A total of 410 women scheduled for FET during 579 cycles (December 2003-September 2013) were enrolled in an open-label RCT to natural cycle (NC FET group, n = 291) or to a cycle hormonally stimulated with s.c. gonadotrophins (hMG FET group, 37.5-75 IU per day, n = 288). A total of 672 embryos were transferred during 434 cycles (332 embryos and 213 cycles in the NC FET group; 340 embryos and 221 cycles in the hMG FET group). Assuming a = 0.05 and 80% power, it was calculated that 219 frozen-thawed embryos were required for transfer in each group to demonstrate a difference of 10% in IR. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were eligible according to the following inclusion criteria: regular ovulatory cycle, female age ≥21 years and ≤45 years, informed consent. FET cycles with preimplantation genetic screening were excluded. The primary outcome was IR per embryo transferred. Secondary outcomes included IR with fetal heart beat (FHB), LBR per embryo transferred and endometrial thickness on the day of hCG administration. Statistical analysis was by intention to treat and controlled for the presence of multiple measures, as eligible women could be randomized in more than one cycle. Chi-square and independent t-test were used to compare categorical and continuous variables. The relative risk (RR) was estimated using a Poisson model with log link. Hierarchical models with random intercepts for patient and cycle were considered to account for clustering of cycles within patients and of embryos within cycles. MAIN RESULTS AND THE ROLE OF CHANCE: The primary outcome, IR per embryo transferred, was not statistically different between the NC FET group (41/332 (12.35%)) and in the hMG FET group (55/340 (16.18%)) (RR 1.3 (95% confidence interval (CI) 0.9-2.0), P = 0.19). Similarly, the secondary outcome, IR with FHB per embryo transferred, was 34/332 (10.24%) in the NC FET group and 48/340 (14.12%) in the hMG FET group (RR 1.4 (95% CI 0.9-2.1), P = 0.15). The LBR per embryo transferred was 32/332 (9.64%) in the NC FET group and 45/340 (13.24%) in the hMG FET group (RR 1.4 (95% CI 0.9-2.2), P = 0.17). Endometrial thickness was also similar in both groups [8.9 (95% CI 8.7-9.1) in the NC FET group and 8.9 (95% CI 8.7-9.1) in the hMG FET group]. The duration of the follicular phase was significantly shorter (P < 0.001) in the hMG FET group [13.7 days (95% CI 13.2-14.2)] than in the NC FET group [15.4 days (95% CI 14.8-15.9)]. LIMITATIONS, REASONS FOR CAUTION: Randomization of cycles instead of patients; open-label design; relatively long period of recruitment. WIDER IMPLICATIONS OF THE FINDINGS: Our observation that the IR per embryo transferred is not significantly increased after FET during natural or gonadotrophin stimulated cycle, suggests that the effect of mild hormonal stimulation with gonadotrophins is smaller than what was considered clinically relevant with respect to reproductive outcome after FET. These data suggest that endometrial receptivity is not relevantly improved, but also not impaired after hormonal stimulation with gonadotrophins. Since FET during a natural cycle is cheaper and more patient-friendly, we recommend this regimen as the treatment of choice for women with regular cycles undergoing FET. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT00492934. TRIAL REGISTRATION DATE: 26 June 2007. DATE OF FIRST PATIENT'S ENROLMENT: 1 December 2003.