High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer.

STUDY QUESTION: Does high gonadotropin dosage affect euploidy and pregnancy rates in PGS cycles with single embryo transfer? SUMMARY ANSWER: High gonadotropin dosage does NOT affect euploidy and pregnancy rates in PGS cycles with single embryo transfer. WHAT IS KNOWN ALREADY: PGS has been proven to be the most effective and reliable method for embryo selection in IVF cycles. Euploidy and blastulation rates decrease significantly with advancing maternal age. In order to recruit an adequate number of follicles, the average dosage of gonadotropins administered during controlled ovarian stimulation in IVF cycles often increases significantly with advancing maternal age. STUDY DESIGN, SIZE, AND DURATION: A retrospective study of SNP (Single Nucleotide Polymorphism) PGS outcome data from blastocysts biopsied on day 5 or day 6 was conducted to identify differences in euploidy and clinical pregnancy rates. Seven hundred and ninety four cycles of IVF treatment with PGS between January 2013 and January 2017 followed by 651 frozen embryo transfers were included in the study (506 patients, maternal age (y.o.) - 37.2 ± 4.31). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 4034 embryos were analyzed (5.1 ± 3.76 per case) for euploidy status. All embryos were vitrified after biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. All cycles were analyzed by total gonadotropin dosage (<3000 IU, 3000-5000 IU and >5000 IU), by number of eggs retrieved (1-5, 5-10, 10-15 and >15 eggs) and patient's age (<35, 35-37, 38-40 and ≥41 y.o.). Clinical pregnancy rate was defined by the presence of a fetal heartbeat at 6-7 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: Euploidy rates within the same age group were not statistically different regardless of the total dosage of gonadotropins used or the number of eggs retrieved. In the youngest group of patients (<35 y.o. - 187 IVF cycles) euploidy rates ranged from 62.3% (<3000 IU were used in the IVF cycle) to 67.5% (>5000 IU were used in the IVF cycle) (OR = 0.862, 95% CI 0.687-1.082, P = 0.2) and from 69.5% (1-5 eggs retrieved) to 60.0% (>15 eggs retrieved) (OR = 0.658, 95% CI 0.405-1.071, P = 0.09). Similar data were obtained in the oldest group of patients (≥41 y.o. - 189 IVF cycles): euploidy rates ranged from 30.7 to 26.4% (OR = 0.811, 95% CI 0.452-1.454, P = 0.481) when analyzed by total dosage of gonadotropins used in the IVF cycle and from 40.0 to 30.7% (OR = 0.531, 95% CI 0.204-1.384, P = 0.19), when assessed by the total number of eggs retrieved. Ongoing pregnancy rates were similar, not only within particular age groups, but also between different age groups regardless of the total dosage of gonadotropins used: ranging from to 63.6% (<3000 IU, < 35 y.o.) to 54.8% (>5000 IU, ≥41 y.o) (OR = 0.696, 95% CI 0.310-1.565, P = 0.38). LIMITATIONS, REASONS FOR CAUTION: Retrospective study and heterogeneity of patients included. WIDER IMPLICATIONS OF THE FINDINGS: These data are reassuring for the common practice of increasing gonadotropin dosages in PGS cycles, particularly in older woman. STUDY FUNDING/COMPETING INTEREST(S): No formal funding has been received for this study. TRIAL REGISTRATION NUMBER: N/A.

Association between growth dynamics, morphological parameters, the chromosomal status of the blastocysts, and clinical outcomes in IVF PGS cycles with single embryo transfer.

PURPOSE: The purpose of the present study is to examine interconnection between speed of embryo development, the genetic status of the blastocysts, and clinical outcomes in IVF preimplantation genetic screening (PGS) cycles with single embryo transfer (SET). METHODS: The retrospective comparative study has been performed between January 2013 and January 2016. Seven hundred thirty-seven cycles of IVF treatment with PGS, followed by 503 SETs, were included in the study. Normally fertilized oocytes were hatched on day 3, were cultured to the blastocyst stage, and were biopsied only when at least three to seven cells were herniating from zona pellucida on the morning of day 5 (≤118 h) or day 6 (≥139 h). A total of 3705 embryos were analyzed for euploidy rates and blastocyst morphology. All embryos were vitrified after the biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. RESULTS: The euploidy rate was significantly higher among embryos biopsied on day 5 versus day 6: 59.44 ± 4.1 and 48.19 ± 3.8, respectively, p < 0.05. The difference in euploidy rates between embryos biopsied on day 5 versus day 6 in matched age groups increased from 5.83 to 25.46% with advancing maternal age. Our data demonstrated no statistically significant difference in euploidy rates between good-quality embryos biopsied on day 5 in the group of patients <38 years old and embryos in PGS cycles using donor oocytes: 71.12% (336/472) and 75.68% (221/292), respectively, p = 0.174, χ 2 = 1.848. In 270 out of 503 SETs, transferred embryos were biopsied on day 5 (ongoing pregnancy rate was 64.6% in a group of patients <38 years old, and in a group of patients ≥38 years old, ongoing PR was 64.2%). In 233 out of 503 cycles, transferred embryos were biopsied on day 6 (ongoing PR was 46.6% in a group of patients <38 years old, and in a group of patients ≥38 years old, ongoing PR was 50.8%). In all study groups, the ongoing pregnancy rate was higher when the transferred embryo was available for biopsy on day 5. CONCLUSIONS: Good- and fair-quality embryos available for biopsy on day 5 have higher euploidy rates and have a higher chance to result in an ongoing pregnancy. Euploidy rate has significant variations within the same age group depending on the morphology of the blastocysts.

Evolving role of assisted reproductive technologies.

During the past 3 decades, staggering advances have been made in the field of assisted reproductive technology (ART). This review provides an overview of the history of ART, current ART practices, and future directions within the field.

Development and testing of a vaginal pressure sensor to measure intra-abdominal pressure in women.

AIMS: Elevated intra-abdominal pressure (IAP) may be a potentially modifiable risk factor for pelvic floor disorders. However, limited evidence exists due to the lack of instruments suitable to measure abdominal pressures in real world settings. The aim of this study was to develop and test a vaginal sensor prototype to measure intra-abdominal pressure in women. METHODS: We developed a non-directional vaginal sensor by housing pressure-sensing circuit boards in 1.2 x 3 cm radially symmetric silicon capsules. We characterized the response in a standardized pressure chamber. Eight women wore a sensor intra-vaginally while undergoing filling cystometry. We compared peak pressures during coughing, valsalva, squatting, and jumping to those obtained using a #10 French rectal balloon urodynamics catheter. We calculated Pearson's correlation coefficients between rectal and vaginal sensors for each event. RESULTS: The vaginal sensors exhibited linear responses during initial bench testing. Each transducer correlated well with the rectal balloon catheter during coughing, valsalva, and squatting (r = 0.97, 0.94, and 0.97, respectively). However, the rectal balloon catheter recorded higher peak and lower, often negative, trough pressures during jumping. The vaginal sensor showed no such artifact. CONCLUSIONS: This vaginal pressure sensor can be used as a surrogate for measuring intra-abdominal pressure in women without advanced prolapse. By measuring pressure at the physiological source, the vaginal sensor is less prone to extraneous noise and error than current transducers. Using this prototype, we will next develop a remote wireless version to capture a range of abdominal pressures experienced outside of the laboratory setting.

Development of a novel intra-vaginal transducer with improved dynamic response.

Limitations of standard clinical pressure transducers have hampered our ability to provide reliable measurements of intra-abdominal pressure (IAP) during physical activities. To overcome these limitations, a novel intravaginal transducer (IVT) capable of accurate, reliable, and continuous IAP measurements during normal activity was developed. The design was validated through comparison with standard clinical pressure transducers in both bench top and clinical tests. The IVT demonstrated an improved dynamic response when compared to a standard rectal balloon catheter. Additionally, the radially symmetric design allows for accurate measurement within non-fluid-filled tissue cavities and simple placement within the vaginal canal. This is an advantage over sensor-tipped transducers which are only reliable in fluid-filled compartments. The IVT design presented here is preliminary to a wireless version that will allow for IAP measurement during activities outside the clinic.

Human embryos secrete microRNAs into culture media--a potential biomarker for implantation.

OBJECTIVE: To determine whether human blastocysts secrete microRNA (miRNAs) into culture media and whether these reflect embryonic ploidy status and can predict in vitro fertilization (IVF) outcomes. DESIGN: Experimental study of human embryos and IVF culture media. SETTING: Academic IVF program. PATIENT(S): 91 donated, cryopreserved embryos that developed into 28 tested blastocysts, from 13 couples who had previously completed IVF cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relative miRNA expression in IVF culture media. RESULT(S): Blastocysts were assessed by chromosomal comparative genomic hybridization analysis, and the culture media from 55 single-embryo transfer cycles was tested for miRNA expression using an array-based quantitative real-time polymerase chain reaction analysis. The expression of the identified miRNA was correlated with pregnancy outcomes. Ten miRNA were identified in the culture media; two were specific to spent media (miR-191 and miR-372), and one was only present in media before the embryos had been cultured (miR-645). MicroRNA-191 was more highly concentrated in media from aneuploid embryos, and miR-191, miR-372, and miR-645 were more highly concentrated in media from failed IVF/non-intracytoplasmic sperm injection cycles. Additionally, miRNA were found to be more highly concentrated in ICSI and day-5 media samples when compared with regularly inseminated and day-4 samples, respectively. CONCLUSION(S): MicroRNA can be detected in IVF culture media. Some of these miRNA are differentially expressed according to the fertilization method, chromosomal status, and pregnancy outcome, which makes them potential biomarkers for predicting IVF success.

MicroRNA expression in the human blastocyst.

OBJECTIVE: To determine the most highly expressed microRNAs (miRNAs) in human blastocysts and to compare miRNAs in euploid versus aneuploid embryos and in male versus female embryos. DESIGN: Experimental study of human embryos: 14 blastocysts (four male, five female, and five aneuploid) were evaluated for miRNA expression with the use of an array-based quantitative real-time polymerase chain reaction (qPCR). Highly expressed and differentially expressed miRNAs were confirmed with the use of qPCR in an expanded set of 27 blastocysts (seven male, eleven female, and nine aneuploid). SETTING: Academic IVF program. PATIENT(S): Thirteen couples donated 91 cryopreserved embryos for this study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relative miRNA expression in individual blastocysts. RESULT(S): The most highly expressed miRNA in euploid embryos was miR-372. Many of the highly expressed miRNAs have been shown to be critical to mammalian embryo development and to maintenance of stem cell pluripotency. Several differentially expressed miRNAs were discovered based on chromosomal makeup, including sex of the embryo. CONCLUSION(S): Human blastocysts express miRNAs, which may be important to their survival. Differential miRNA expression based on sex implies some degree of differentiation at the blastocyst stage of development. Differential miRNA expression between euploid and aneuploid embryos may be an early indicator of their prognosis or a mechanism behind their eventual fate.