Assessing couples' preferences for fresh or frozen embryo transfer: a discrete choice experiment.

STUDY QUESTION: What are couples' preferences for fresh embryo transfer versus freezing of all embryos followed by frozen embryo transfer and the associated clinical outcomes that may differentiate them? SUMMARY ANSWER: Couples' preferences are driven by anticipated chances of live birth, miscarriage, neonatal complications, and costs but not by the differences in the treatment process (including delay of embryo transfer linked to frozen embryo transfer and risk of ovarian hyperstimulation syndrome (OHSS) associated with fresh embryo transfer). WHAT IS KNOWN ALREADY: A policy of freezing all embryos followed by transfer of frozen embryos results in livebirth rates which are similar to or higher than those following the transfer of fresh embryos while reducing the risk of OHSS and small for gestational age babies: it can, however, increase the risk of pre-eclampsia and large for gestational age offspring. Hence, the controversy continues over whether to do fresh embryo transfer or freeze all embryos followed by frozen embryo transfer. STUDY DESIGN, SIZE, DURATION: We used a discrete choice experiment (DCE) technique to survey infertile couples between August 2018 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: We asked IVF naïve couples attending a tertiary referral centre to independently complete a questionnaire with nine hypothetical choice tasks between fresh and frozen embryo transfer. The alternatives varied across the choice occurrences on several attributes including efficacy (live birth rate), safety (miscarriage rate, neonatal complication rate), and cost of treatment. We assumed that a freeze-all strategy prolonged treatment but reduced the risk of OHSS. An error components mixed logit model was used to estimate the relative value (utility) that couples placed on the alternative treatment approaches and the attributes used to describe them. Willingness to pay and marginal rates of substitution between the non-cost attributes were calculated. A total of 360 individual questionnaires were given to 180 couples who fulfilled the inclusion criteria, of which 212 were completed and returned Our study population included 3 same sex couples (2 females and 1 male) and 101 heterosexual couples. Four questionnaires were filled by one partner only. The response rate was 58.8%. MAIN RESULTS AND THE ROLE OF CHANCE: Couples preferred both fresh and frozen embryo transfer (odds ratio 27.93 and 28.06, respectively) compared with no IVF treatment, with no strong preference for fresh over frozen. Couples strongly preferred any IVF technique that offered an increase in live birth rates by 5% (P = 0.006) and 15% (P < 0.0001), reduced miscarriage by 18% (P < 0.0001) and diminished neonatal complications by 10% (P < 0.0001). Respondents were willing to pay an additional £2451 (95% CI 604 - 4299) and £761 (95% CI 5056-9265) for a 5 and 15% increase in the chance of live birth, respectively, regardless of whether this involved fresh or frozen embryos. They required compensation of £5230 (95% CI 3320 - 7141) and £13 245 (95% CI 10 110-16 380) to accept a 10 and 25% increase in the risk of neonatal complications, respectively (P < 0.001). Results indicated that couples would be willing to accept a 1.26% (95% CI 1.001 - 1.706) reduction in the live birth rate for a 1% reduction in the risk of neonatal complications per live birth. Older couples appeared to place less emphasis on the risk of neonatal complications than younger couples. LIMITATIONS, REASONS FOR CAUTION: DCEs can elicit intentions which may not reflect actual behaviour. The external validity of this study is limited by the fact that it was conducted in a single centre with generous public funding for IVF. We cannot rule out the potential for selection or responder bias. WIDER IMPLICATIONS OF THE FINDINGS: If a strategy of freeze all was to be implemented it would appear to be acceptable to patients, if either success rates can be improved or neonatal complications reduced. Live birth rates, neonatal complication rates, miscarriage rates, and cost are more likely to drive their preferences than a slight delay in the treatment process. The results of this study have important implications for future economic evaluations of IVF, as they suggest that the appropriate balance needs to be struck between success and safety. A holistic approach incorporating patient preferences for expected clinical outcomes and risks should be taken into consideration for individualized care. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study. A.M. is the chief investigator of the randomized controlled trial 'Freeze all'. S.B. is an Editor in Chief of Human Reproduction Open. The other co-authors have no conflicts of interest to declare. Graham Scotland reports non-financial support from Merck KGaA, Darmstadt, Germany, outside the submitted work. TRIAL REGISTRATION NUMBER: N/A.

Preventive and Therapeutic Role of Dietary Inositol Supplementation in Periconceptional Period and During Pregnancy: A Summary of Evidences and Future Applications.

Although inositol dietary deficiency in the general population has not been demonstrated at the serum level, several findings are emerging regarding the impact of inositol supplementation in periconceptional period and in early phases of pregnancy. We are aimed to summarize all experimental (murine in vivo and in vitro murine embryo studies) and clinical (human) evidences regarding the role of inositol in the prevention and treatment of folate-resistant embryo neural tube defects (FR-NTDs) and gestational diabetes mellitus (GDM). We also collected all information regarding the effect that inositol supplementation may have in the metabolic reassessment of early and late pregnancy in order to draw evidence-based conclusions and suggest further studies defining the potential therapeutic role of this molecule in human reproduction. The systematic review of literature clearly showed that inositol supplementation in preconceptional period and in early phase of pregnancy reduces the risk of developing GDM in patients at increased risk. Furthermore, continued intake during pregnancy improves the metabolic status of affected patients, but further studies are needed to confirm this end point. All women at risk of FR-NTDs assuming inositol from the periconceptional period until late pregnancy are reported to have healthy newborns without any significant complications linked to inositol supplementation.

Ultrasound techniques in the diagnosis of deep pelvic endometriosis: algorithm based on a systematic review and meta-analysis.

OBJECTIVE: To collate all available evidence with respect to ultrasound techniques in the management of deep pelvic endometriosis (DPE) and compare the sensitivity and specificity of each to determine the most suitable site-specific method. We aim to provide clinicians with information to improve the diagnosis and management of patients with DPE. DESIGN: Systematic review of the literature and meta-analysis. SETTING: Not applicable. PATIENT(S): None. INTERVENTIONS(S): Review of MEDLINE, EMBASE, ScienceDirect, Cochrane Library. MAIN OUTCOME MEASURE(S): For each study we calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and positive/negative likelihood ratio regarding DPE sites. We then compared the specificity and sensitivity of each technique. Forest plots with the corresponding 95% confidence interval using fixed/random effects for each approach (both separately and summarized according to the weight of any single study) were used. RESULT(S): A key word search strategy identified 441 manuscripts, 35 of which were eligible for the review (32 for meta-analysis). Standard transvaginal sonography (TVS) showed specificity greater than 85% for all DPE sites, despite sensitivity ranging between 50% (bladder, vaginal wall, and rectovaginal septum) and 84% (rectosigmoid). Modified techniques such as bladder site tenderness-guided TVS showed a value of 97.4% for both sensitivity and specificity. Rectal endoscopy-sonography and rectal water contrast TVS were both superior to TVS in detecting rectosigmoid endometriosis with sensitivities and specificities over 92%. Promising data were reported by using rectal water contrast TVS for rectovaginal septum disease (sensitivity, 97.1%; specificity, 99.3%). CONCLUSION(S): The summary of data regarding diagnostic specificity and sensitivity of TVS in women undergoing surgery for deep endometriosis may allow us to conclude that TVS should remain the first-line method in the evaluation of patients with suspicion of DPE. When TVS is insufficient, second-line "modified-techniques" should be considered. Choosing the most effective technique is a challenge and should be based on patient history and clinical signs/symptoms.