Time-Lapse Incubation for Embryo Culture-Morphokinetics and Environmental Stability May Not Be Enough: Results from a Pilot Randomized Controlled Trial.

Background: Does the Time-lapse Incubator (TLI) add value to reproductive outcomes when its two components, undisturbed culturing and morphokinetic embryo grading, are separated. Methods: A prospective pilot, randomized, controlled, double-blinded, single-center study was conducted during the years 2016-2020. In total, 102 patients were randomized into three groups: (1) conventional incubation with morphological evaluation only (n = 34), (2) TLI with both morphological and morphokinetic evaluations (n = 32), and (3) TLI with morphological evaluation only (n = 36). All arms were cultured in ESCO-MIRI® incubators. A total of 1061 injected mature oocytes were evaluated (420 in arm 1, 285 in arm 2, and 356 in arm 3). The primary outcome was live birth rates. Secondary outcomes included clinical and cumulative pregnancy rates as well as embryo quality. Embryos in arm 3 were retrospectively evaluated for their morphokinetic score. Results: No significant difference was found in the live birth rate for single embryo transfer cycles (SET) (35% vs. 31.6% vs. 24%, p = 0.708) or double embryo transfer (DET) cycles (41.7% vs. 38.5% vs. 36.4%, p = 0.966). Comparable pregnancy rates, clinical pregnancy rates, and cumulative pregnancy were found for similar top-quality embryos for days 2, 3, and blastocyst stages across groups. A similar number of embryos were suitable for either transfer or cryopreservation within the different groups. For 62.8% of the embryos in arm 3, the morphokinetic and morphologic evaluations were similar. In only 2/36 (5.6%) treatment cycles, the use of morphokinetic scoring may have helped the patient avoid undergoing an additional treatment cycle. In the other cases, morphokinetic scoring would not have changed the end point of pregnancy. Conclusions: The two components of the TLI system-undisturbed culturing and morphokinetic embryo grading-do not appear to have a significant additional value in reproductive outcome, although these results should be validated by an RCT.

Preimplantation genetic testing for aneuploidy in patients with low embryo numbers: benefit or harm?

PURPOSE: We sought to explore the utility of preimplantation genetic testing for aneuploidy (PGT-A) in a poor prognosis group of women with few embryos available for transfer. METHODS: This was a retrospective matched cohort study examining records for first or second-cycle IVF patients with 1 to 3 blastocysts. The study group comprised 130 patients who underwent PGT-A on all embryos. The control group included 130 patients matched by age, BMI, and blastocyst number and quality who did not undergo PGT-A during the same time period. RESULTS: The live birth rate (LBR) per embryo transfer (ET) were similar in the PGT-A and control groups, and the spontaneous abortion (SAB) rate was the same (23%). However, we found a significantly higher LBR per oocyte retrieval in the control group vs the PGT-A group (43% vs 20%, respectively) likely due to the many no-euploid cycles in the PGT-A group. In a subgroup analysis for age, the similar LBR per ET persisted in women < 38. However, in older women, there was a trend to a higher LBR per ET in the PGT-A group (43%) vs the control group (22%) but a higher LBR per oocyte retrieval in the control group (31%) vs the PGT-A group (13%). CONCLUSIONS: Overall, we observed a significant increase in LBR per oocyte retrieval in women in the control group compared to women undergoing PGT-A, and no difference in SAB rate. Our data suggests that PGT-A has no benefit in a subpopulation of women with few embryos and may cause harm.

Anti-mullerian hormone (AMH) reference values in the CALIPER cohort of healthy community children and adolescents.

The assessment of anti-mullerian hormone (AMH) pre- and post-gonadotoxic treatment helps define reproductive potential in young female adults facing cancer treatment. Normative childhood AMH levels are not well defined. Our objective was to help establish accurate pediatric reference intervals (RIs) for which AMH can be used to assess AMH in pediatric/adolescent survivors. Healthy female volunteers aged 6-<19 years were recruited from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. 300 serum samples were analyzed for AMH using an automated assay. Basic demographics and menstrual cycle data on the subjects were recorded at time of sample collection. Serum AMH distribution and RIs (2.5th and 97.5th percentiles) were established in four age groups. One recommended RI (0.98-7.84 ng/mL) was established for females aged 6-<19 years after outlier removal. Females 6-<9 years demonstrated significantly lower mean AMH concentration than did females 9-<12 years (Mean ± SD: 3.18 ± 1.62 and 4.16 ± 2.55 ng/mL, respectively), who in turn demonstrated significantly higher AMH concentrations than those aged 12-<15 years (Mean ± SD: 3.75 ± 1.61 ng/mL). Statistical differences are unlikely to be clinically meaningful. Menstrual status and ethnicity did not significantly impact AMH concentrations (p = 0.787 and p = 0.0965, respectively). This is the largest series of its kind using a contemporary, automated, single-batched AMH assay in a healthy pediatric female cohort. In conjunction with future data points and longitudinal data, the RI established may be a useful adjunct to reproductive health counselling delivered to pediatric cancer patients requiring fertility damaging therapies.

National Canadian Survey on the Management of Noneuploid Embryos.

OBJECTIVE: To comprehensively describe current preimplantation genetic testing for aneuploidy (PGT-A) practices and management of non-euploid embryos in Canada. METHODS: This was a cross-sectional study utilizing an online survey distributed by email to all medical directors of fertility clinics with independent in vitro fertilization (IVF) embryology laboratories. The survey was designed to determine practice patterns regarding PGT-A usage; PGT-A reference laboratory, platform, and thresholds for classifying embryos; and management of embryos classified as mosaic, inconclusive, or aneuploid. RESULTS: Twenty-five medical directors (69%) participated in the survey. The majority of clinics (91%) offered PGT-A screening, with 45% of clinics offering PGT-A as routine screening. The majority of clinics (90%) that offered PGT-A received mosaicism data; 61% of these clinics had transferred mosaic embryos, and 94% would transfer mosaic embryos. Clinics that performed ≥1000 IVF cycles annually were more likely to have transferred mosaic embryos (100% vs. 45.5%; P = 0.043). The mean percentage of IVF cycles using PGT-A was lower in clinics that had transferred mosaic embryos (12.3% vs. 30.4%; P = 0.033). Only 1 clinic had transferred an aneuploid embryo, but 2 other clinics would consider this option. The majority of clinics (61%) that receive mosaicism data would recommend noninvasive prenatal testing (NIPT) following mosaic embryo transfer, with 22% of clinics indicating that this would be the only genetic test offered. CONCLUSION: We report significant practice variation in PGT-A and management of non-euploid embryos across Canada and highlight areas where consensus should be encouraged.

Breast cancer and fertility: an update.

PURPOSE OF REVIEW: This review will summarize key fertility issues in young women with breast cancer. The detrimental effects of treatment modalities on ovarian and hormonal function will be reviewed. Options for fertility protection and preservation will also be outlined, as well as the unique issues facing women in pregnancy with a previous breast cancer diagnosis. RECENT FINDINGS: Gonadotropin-releasing hormone analogues continue to be in debate for their protective impact on the ovaries during the time of gonadotoxic treatment. Success rates in the cryopreservation of embryos, oocytes and gonadal tissue continue to improve. Concurrently, advancing reproductive technologies are developing promising techniques for obtaining mature oocytes from ovarian tissue and from early ovarian follicles. The pursuit of a pregnancy after breast cancer treatment is an additional challenge. Increasing bodies of evidence support the safety of pregnancy after breast cancer and the possibly improved survival. Still, there is an uncertainty regarding recommended intervals from diagnosis to conception. Preimplantation genetic diagnosis for hereditary breast cancer mutations is also becoming of increasing interest. SUMMARY: The fertility impact of breast cancer treatment in young women is of ongoing concern. The effects should be universally addressed and options should be outlined with young women prior to commencement of treatment.

Can online learning adequately prepare medical students to undertake a first female pelvic examination?

OBJECTIVE: To determine whether a novel web-based learning module could adequately prepare first-year undergraduate medical students to skilfully perform their first female pelvic examination. METHODS: First-year Queen's University medical students without prior training or experience in female pelvic examination were recruited for this study. After viewing key segments of the learning module, students were evaluated while performing a pelvic examination on a female volunteer using a standardized assessment checklist (total score = 30 points). Descriptive and comparative statistics were generated. RESULTS: Forty-five students participated with a mean age of 24 years (range 20 to 40). The mean score (±SD) on the assessment checklist was 23.9 ± 3.6 points, (range 17 to 30). All study participants received a passing grade of ≥ 50% (15/30 points), and 53.3% (24/45) received an honours grade of ≥ 80% (24/30 points). Of the participants, 88.9% (40/45) agreed that they were well prepared for their first female pelvic examination after viewing the training video. Mean scores were similar for male students (23.9, n = 22) and female students (23.8, n = 23) (P = 0.90, t test). Mean scores were not higher in those who watched key segments of the learning module more than once. CONCLUSION: This learning module viewed immediately prior to a simulated clinic session afforded first-year medical students the necessary knowledge and skills to perform a first female pelvic examination. This was accomplished with as little as one viewing, and could lead to savings in organizational costs and instruction time for medical school curricula.