Association between oocyte retrieval technique and number of oocytes retrieved.

PURPOSE: To assess if there is an optimal oocyte retrieval (OR) technique to retrieve a maximum number of oocytes and mature oocytes (MII). METHODS: Retrospective cohort study in which nine physicians completed a survey on OR techniques. Number of oocytes/follicle cohort, MIIs/follicle cohort, and MIIs/oocytes retrieved (%MII) were assessed for each technique for patients undergoing OR from 3/2013 to 7/2019. Data were stratified by number of follicles on ultrasound on day of trigger (< 6, 6-10, > 10). RESULTS: Patient demographics were equivalent between techniques. For < 6 follicles, three techniques resulted in significantly fewer oocyte/follicle (0.97 ± 0.48, 0.95 ± 0.66, and 0.90 ± 0.41) compared to the top-performing technique (TPT) (1.11 ± 0.55). For 6-10 follicles, two techniques resulted in significantly fewer oocyte/follicle (0.95 ± 0.39 and 0.93 ± 0.35) compared to the TPT (1.06 ± 0.42). A different technique had higher %MII (0.77 ± 0.19) compared to two techniques (0.74 ± 0.21 and 0.72 ± 0.22). For > 10 follicles, two techniques resulted in significantly fewer oocyte/follicle (1.01 ± 0.42 and 1.07 ± 0.40) compared to the TPT (1.15 ± 0.41). These two techniques also resulted in fewer MII/follicle (0.75 ± 0.33 and 0.81 ± 0.34 vs. 0.87 ± 0.34). There was no consistent TPT across follicle number groups or for all outcome variables. CONCLUSIONS: There does not appear to be a clear TPT, even for patients with few follicles. Providers who perform OR in a similar fashion to physicians at our institution should feel confident that those techniques obtain equivalent oocyte yields.

Embryo attrition in planned PGT-A: predicting the number of available blastocysts for transfer.

PURPOSE: During a typical IVF cycle, there is unavoidable attrition from oocytes retrieved to blastocysts formed. Some patients will not have blastocysts available to biopsy or embryos for transfer. The purpose of this study was to predict the number of transferable blastocysts available for patients based on their age and number of 2pn zygotes. METHODS: This was a retrospective cohort study of all fresh autologous IVF and ICSI cycles in which PGT-A was planned from 1/2012 to 3/2020. In total, 746 cycles from 571 patients were analyzed. Patient cycles were stratified into two groups: less than four 2pn zygotes (n = 85) and at least four 2pn zygotes (n = 661). Cycles were then stratified by patient age. Cycle outcomes, including number of cleavage-stage embryos, blastocysts, euploid blastocysts, and low level mosaic blastocysts, were determined. RESULTS: Cleavage-rate was independent of age and number of 2pn zygotes and ranged between 96 and 100%. Blastocyst conversion and euploid blastocyst conversion rates were directly correlated to age, ranging from 52 to 83% for blastocyst conversion and 0-28% for euploid blastocyst conversion. For patients above the age of 40 years with less than four 2pn zygotes, the risk of having no transferable embryos was 99.7%. CONCLUSION: While the literature demonstrates higher live birth rates with the use of PGT-A in women of advancing age, this is inconsequential if there is no embryo available to transfer. Women over 40 years with less than four 2pn zygotes should consider transfer of one or more untested embryos either on day 3 or on day 5.

Blastocyst conversion rate and ploidy in patients with structural rearrangements.

OBJECTIVE: The primary objective of this study was to test the hypotheses that compared to IVF cycles undergoing preimplantation genetic testing for aneuploidy (PGT-A) with or without testing for monogenic disorders (PGT-M), IVF cycles undergoing PGT for structural rearrangements (PGT-SR) will have (1) a poorer blastocyst conversion rate and (2) fewer usable blastocysts available for transfer. Secondarily, the study aimed to compare pregnancy outcomes among PGT groups. PATIENTS: Retrospective cohort study including cycles started from January 1, 2012, to March 30, 2020, with the intent of pursuing PGT-A, PGT-A with PGT-M, and PGT-SR, with trophectoderm biopsy on days 5 or 6. RESULTS: A total of 658 women underwent 902 cycles, including 607 PGT-A, 216 PGT-A&M, and 79 PGT-SR cycles. When compared with the blastocyst conversion rate for the PGT-A group (59.4%), and after adjustment for patient age, total number of mature oocytes, BMI, and ICSI, there were no significant differences for either the PGT-A&M (69.7%, aRR 1.03, 95% CI 0.96-1.10) or PGT-SR (63.2%, aRR1.04, 95% CI 0.96-1.13) groups. Compared to the PGT-A group, the proportion of usable blastocysts was statistically significantly lower in the PGT-SR group: 35.1% versus 24.4% (aRR 0.57, 95% CI 0.46-0.71) and the PGT-A&M group: 35.1% versus 31.5% (aRR 0.68, 95% CI 0.58-0.81). Implantation, pregnancy, and miscarriage rates were equivalent for all groups. CONCLUSION: Patients with structural rearrangements have similar blastocyst development but significantly fewer usable blastocysts available for transfer compared to PGT-A testers. Nevertheless, with the transfer of a usable embryo, PGT-SR testers perform as well as those testing for PGT-A.

CARTR Plus: the creation of an ART registry in Canada.

STUDY QUESTION: What is the status of fertility treatment and birth outcomes documented over the first 6 years of the Canadian Assisted Reproductive Technologies Register (CARTR) Plus registry? SUMMARY ANSWER: The CARTR Plus registry is a robust database containing comprehensive Canadian fertility treatment data to assist with providing evidence-based rationale for clinical practice change. WHAT IS KNOWN ALREADY: The rate of infertility is increasing globally and having data on fertility treatment cycles and outcomes at a population level is important for accurately documenting and effecting changes in clinical practice. STUDY DESIGN SIZE DURATION: This is a descriptive manuscript of 183 739 fertility treatment cycles from 36 Canadian clinics over 6 years from the CARTR Plus registry. PARTICIPANTS/MATERIALS SETTING METHODS: Canadian ART treatment cycles from 2013 through 2018 were included. This manuscript described trends in type of fertility treatment cycles, pregnancy rates, multiple pregnancy rates, primary transfer rates and birth outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Over the 6 years of the CARTR Plus registry, the number of treatment cycles performed ranged from less than 200 to greater than 1000 per clinic. Patient age and the underlying cause of infertility were two of the most variable characteristics across clinics. Similar clinical pregnancy rates were found among IVF and frozen embryo transfer (FET) cycles with own oocytes (38.9 and 39.7% per embryo transfer cycle, respectively). Fertility treatment cycles that used donor oocytes had a higher clinical pregnancy rate among IVF cycles compared with FET cycles (54.9 and 39.8% per embryo transfer cycle, respectively). The multiple pregnancy rate was 7.4% per ongoing clinical pregnancy in 2018, which reflected a decreasing trend across the study period. Between 2013 and 2017, there were 31 811 pregnancies that had live births from all ART treatment cycles, which corresponded to a live birth rate of 21.4% per cycle start and 89.1% of these pregnancies were singleton live births. The low multiple pregnancy rate and high singleton birth rate are associated with the increase in single embryo transfers. LIMITATIONS REASONS FOR CAUTION: There is potential for misclassification of data, which is present in all administrative health databases. WIDER IMPLICATIONS OF THE FINDINGS: The CARTR Plus registry is a robust resource for ART data in Canada. It provides easily accessible aggregated data for Canadian fertility clinics, and it contains data that are internationally comparable. STUDY FUNDING/COMPETING INTERESTS: There was no funding provided for this study. The authors have no competing interests to declare.

The Canadian Assisted Reproductive Technologies Register (CARTR) Plus database: a validation study.

STUDY QUESTION: Are data accurately documented in the Canadian Assisted Reproductive Technologies Register (CARTR) Plus database? SUMMARY ANSWER: Measures of validity were strong for the majority of variables evaluated while those with moderate agreement were FSH levels, oocyte origin and elective single embryo transfer. WHAT IS KNOWN ALREADY: Health databases and registries are excellent sources of data. However, as these databases are typically not established for the primary purpose of performing research, they should be evaluated prior to utilization for research both to inform the study design and to determine the extent to which key study variables, such as patient characteristics or therapies provided, are accurately documented in the database. CARTR Plus is Canada's national register for collecting extensive information on IVF and corresponding pregnancy outcomes, and it has yet to be validated. STUDY DESIGN SIZE DURATION: This study evaluating the data translation CARTR Plus database examined IVF cycles performed in 2015 using data directly from patient charts. Six clinics across Canada were recruited to participate, using a purposive sampling strategy. Fixed random sampling was employed to select 146 patient cycles at each clinic, representing unique patients. Only a single treatment cycle record from a unique patient at each clinic was considered during chart selection. PARTICIPANTS/MATERIALS SETTING METHODS: Twenty-five data elements (patient characteristics, treatments and outcomes) were reabstracted from patient charts, which were declared the reference standard. Data were reabstracted by two independent auditors with relevant clinical knowledge after confirming inter-rater reliability. These data elements from the chart were then compared to those in CARTR Plus. To determine the validity of these variables, we calculated kappa coefficients, sensitivity, specificity, positive predictive value and negative predictive value with 95% CI for categorical variables and calculated median differences and intraclass correlation coefficients (ICC) for continuous variables. MAIN RESULTS AND THE ROLE OF CHANCE: Six clinics agreed to participate in this study representing five Canadian provinces. The mean age of patients was 35.5 years, which was similar between the two data sources, resulting in a near perfect level of agreement (ICC = 0.99; 95% CI: 0.99, 0.99). The agreement for FSH was moderate, ICC = 0.68 (95% CI: 0.64, 0.72). There was nearly perfect agreement for cycle type, kappa = 0.99 (95% CI: 0.98, 1.00). Over 90% of the cycles in the reabstracted charts used autologous oocytes; however, data on oocyte source were missing for 13% of cycles in CARTR Plus, resulting in a moderate degree of agreement, kappa = 0.45 (95% CI, 0.37, 0.52). Embryo transfer and number of embryos transferred had nearly perfect agreement, with kappa coefficients greater than 0.90, whereas that for elective single or double embryo transfer was much lower (kappa = 0.55; 95% CI: 0.49, 0.61). Agreement was nearly perfect for pregnancy type, and number of fetal sacs and fetal hearts on ultrasound, all with kappa coefficients greater than 0.90. LARGE-SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: CARTR Plus contains over 200 variables, of which only 25 were assessed in this study. This foundational validation work should be extended to other CARTR Plus database variables in future studies. WIDER IMPLICATIONS OF THE FINDINGS: This study provides the first assessment of the quality of the data translation process of the CARTR Plus database, and we found very high quality for the majority of the variables that were analyzed. We identified key data points that are either too often lacking or inconsistent with chart data, indicating that changes in the data entry process may be required. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Canadian Institutes of Health Research (CIHR) (Grant Number FDN-148438) and by the Canadian Fertility and Andrology Society Research Seed Grant (Grant Number: N/A). The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Association between prophylactic low-molecular-weight heparin use in pregnancy and macrosomia: analysis of the Ottawa and Kingston birth cohort.

Essentials Low-molecular-weight heparin (LMWH) is used to prevent venous thromboembolism (VTE) in pregnancy. We evaluated the association between LMWH and large for gestational age (LGA) infants. We found no significant associations between LMWH use and LGA. LMWH does not appear to increase the risk for the delivery of an LGA infant. SUMMARY: Background Low-molecular-weight heparin (LMWH), an anticoagulant, is the recommended drug for thromboprophylaxis and treatment of venous thromboembolism (VTE) in pregnancy. During pregnancy, LMWH is routinely prescribed to mothers with an increased risk of VTE or with a history of thrombosis. Although clinical reports of larger offspring born to women administered LMWH have been noted, no studies to date have evaluated or associated the use of LMWH and large for gestational age (LGA) infants. Objectives To determine whether there is an association between LMWH usage in mothers and the prevalence of LGA. Patients/Methods We performed an analysis of the Ottawa and Kingston (OaK) Birth Cohort and report characteristics of LMWH and association LGA (> 10%ile). We used coarsened exact matching (CEM) methods to account for bias and confounding. Results A total of 7519 women from the OaK Birth Cohort were included; 59 were administered LMWH during pregnancy (0.78%). Mothers prescribed LMWH had significantly greater BMI (P = 0.0001), age (P = 0.0001) and parity (P = 0.02). Gestational length was shorter among women administered LMWH compared to those without treatment (37.7 ± 2.0 vs. 39.2 ± 2.0, P < 0.0001), an iatrogenic finding. The odds ratio of an LGA delivery among women administered LMWH was 1.02 (95% confidence interval [CI], 0.48-2.16; P = 0.96) in unadjusted analyses and was 1.15 (95% CI, 0.49-2.71) in the matched sample adjusted for maternal age, BMI and gestational age. Conclusions These results, although exploratory, provide indirect evidence of no increased risk of LGA infants among women prescribed LMWH.

ΔF508 mutation screening of healthy individuals from two populations in Espírito Santo State, Brazil.

The ΔF508 mutation is the most common cause of cystic fibrosis and its prevalence varies worldwide. For instance, up to 20-fold variations in its frequency have been recorded across different areas of Brazil. This study aimed to compare the distribution of ΔF508 among healthy individuals of admixed Portuguese descent from Espírito Santo (ES), a state in Southeastern Brazil, to that in a subpopulation of Pomeranian descent, considered to be an isolated group in which the European gene pool has been preserved, living in Santa Maria do Jetibá (also in ES). We found this mutation to be present at a frequency of 0.81% among the Pomeranian group, and 0% in the general ES population. No genetic differentiation was noted between the two populations examined (FST = 0.004), and these frequencies were found to be similar to those estimated in other states of Southeastern Brazil. Although the population of Santa Maria de Jetibá has retained Pomeranian traits, such as language, fair skin, and eye color, to date, there is no evidence of inbreeding in this group (FIS = -0.004). Screening healthy individuals for the ΔF508 mutation can facilitate genetic counseling for cystic fibrosis, as well as inform evolutionary and population studies.

Fetal death and preterm birth associated with maternal influenza vaccination: systematic review.

BACKGROUND: Before 2012, few studies had addressed pregnancy outcomes following maternal influenza vaccination; however, the number of publications on this topic has increased recently. OBJECTIVES: To review comparative studies evaluating fetal death or preterm birth associated with influenza vaccination during pregnancy. SEARCH STRATEGY: We searched bibliographic databases from inception to April 2014. SELECTION CRITERIA: Experimental or observational studies assessing the relationship between influenza vaccination during pregnancy and fetal death or preterm birth. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data from studies meeting the inclusion criteria. MAIN RESULTS: We included one randomised clinical trial and 26 observational studies. Meta-analyses were not considered appropriate because of high clinical and statistical heterogeneity. Three studies of fetal death at any gestational age reported adjusted effect estimates in the range 0.56-0.79, and four of five studies of fetal death at <20 weeks reported adjusted estimates between 0.89 and 1.23, all with confidence intervals including 1.0. Adjusted effect estimates for four of five studies of fetal death at ≥20 weeks ranged from 0.44 to 0.77 (two with confidence intervals not crossing 1.0), whereas a fifth reported a non-significant effect in the opposite direction. Among 19 studies of preterm birth, there was no strong evidence suggesting any increased risk, and meta-regression did not explain the moderate between-study heterogeneity (I(2) = 57%). AUTHORS' CONCLUSIONS: Most studies reported no association between fetal death or preterm birth and influenza vaccination during pregnancy. Although several reported risk reductions, results may be biased by methodological shortcomings of observational studies of influenza vaccine effectiveness.