The impact of microfluidics sperm processing on blastocyst euploidy rates compared with density gradient centrifugation: a sibling oocyte double-blinded prospective randomized clinical trial.

OBJECTIVE: To compare the euploidy rates among blastocysts created from sibling oocytes injected with sperm and processed using microfluidics or density gradient centrifugation. DESIGN: Sibling oocyte randomized controlled trial. SETTING: Single university-affiliated infertility practice. PATIENTS: A total of 106 patients aged 18-42 years undergoing fresh in vitro fertilization treatment cycles with preimplantation genetic testing between January 2021 and April 2022 contributed 1,442 mature oocytes, which were injected with sperm and processed using microfluidics or density gradient centrifugation. INTERVENTION(S): The sperm sample is divided and processed using a microfluidics device and density gradient centrifugation for injection into sibling oocytes. MAIN OUTCOME MEASURE(S): The primary outcome was the embryo euploidy rate. Secondary outcomes included fertilization, high-quality blastulation, and ongoing pregnancy rates. RESULT(S): The blastocyst euploidy rate per mature oocyte was not significantly different in the study group compared with the control group (22.9% vs. 20.5%). The blastocyst euploidy rate per biopsied embryo was also similar between the 2 groups (53.0% vs. 45.7%). However, the fertilization rate per mature oocyte injected was found to be significantly higher in the study group compared with the control group (76.0% vs. 69.9%). The high-quality blastulation rate per mature oocyte injected was similar between the 2 groups, as was the total number of embryos frozen. There were no differences in the number of participants with no blastocysts for biopsy or the number of participants with no euploid embryos between the 2 groups. Among the male factor infertility and recurrent pregnancy loss subgroups, there were no differences in euploidy rates, fertilization rates, blastulation rates, or total numbers of blastocysts frozen, although the study was underpowered to detect these differences. Seventy-seven patients underwent frozen embryo transfer; there were no significant differences in pregnancy outcomes between the 2 groups. CONCLUSION(S): Microfluidics processing did not improve embryo euploidy rates compared with density gradient centrifugation in this sibling oocyte study, although fertilization rates were significantly higher. CLINICAL TRIAL REGISTRATION NUMBER: NCT04744025.

Puberty Suppression Followed by Testosterone Therapy Does Not Impair Reproductive Potential in Female Mice.

More adolescents are coming out as transgender each year and are put on puberty blockers to suppress natal puberty, which is then followed by cross-hormone treatment to achieve puberty of the desired gender. Studies to examine the effects of puberty suppression and virilizing therapy on future reproductive potential among transgender males are lacking. This study used a translational murine in vitro fertilization model to examine the effects of female puberty suppression with depot leuprolide acetate (LA), followed by virilizing therapy with testosterone cypionate (T), on embryologic and pregnancy outcomes. LA effectively inhibited puberty when mice were treated beginning at 3 weeks of age. LA treatment was associated with higher mouse weight but lower ovarian weight. LA-treated mice ovulated developmentally competent eggs in response to gonadotropin administration, albeit at a higher dose than controls. Ovaries from mice treated with LA and T produced oocytes that had morphologically normal meiotic spindles after in vitro maturation and responded to gonadotropin stimulation. Eggs from mice treated with LA and T were fertilizable and produced developmentally competent embryos that led to births of fertile pups. These results suggest that fertility may not be impaired after puberty suppression and cross-hormone therapy for transgender males.

The association of obesity with euploidy rates in women undergoing in vitro fertilization with preimplantation genetic testing.

PURPOSE: The purpose of this study was to determine the impact of body mass index (BMI) on euploidy rates for in vitro fertilization (IVF) cycles with preimplantation genetic testing (PGT) utilizing primarily next-generation sequencing (NGS). METHODS: This retrospective cohort study included women aged ≤ 45 years who underwent IVF/PGT between September 2013 and September 2020 at a single university-affiliated fertility center. The primary outcome was euploidy rate. Secondary outcomes included peak serum estradiol (E2), number of oocytes retrieved, oocyte maturation rate, high-quality blastulation rate, clinical loss rate (CLR), clinical pregnancy rate (CPR), and ongoing pregnancy/live birth rate (OPR/LBR). RESULTS: The study included 1335 IVF cycles that were stratified according to BMI (normal, n = 648; overweight, n = 377; obese, n = 310). The obese group was significantly older with significantly lower baseline FSH, peak E2, high-quality blastulation rate, and number of embryos biopsied than the normal group. Overall euploidy rates were not significantly different between BMI groups (normal 36.4% ± 1.3; overweight 37.3% ± 1.8; obese 32.3% ± 1.8; p = 0.11), which persisted after controlling for covariates (p = 0.82) and after stratification of euploidy rate by age group and by number of oocytes retrieved per age group. There were no significant differences in CLR, CPR, and OPR/LBR across BMI groups. CONCLUSIONS: Despite a lower high quality blastulation rate with obesity, there is not a significant difference in euploidy rates across BMI groups in women undergoing IVF/PGT.

Rationale and study design of a double-blinded prospective randomized clinical trial comparing euploidy rates among embryos created from sibling oocytes injected with sperm processed by microfluidics or by density gradient centrifugation.

BACKGROUND: During the in vitro fertilization (IVF) process, sperm must be processed prior to insemination. While the most common method, density gradient centrifugation, can potentially damage sperm during centrifugation, a recent advancement in sperm processing uses a microfluidics system which selects for the most highly motile sperm. In selecting for these sperm which may be of higher quality, the euploidy rates of embryos created as a result may also be improved. The primary aim of this study is to compare the euploidy rates per mature oocyte between embryos created from sibling oocytes injected with sperm processed by microfluidics sorting or by density gradient centrifugation. METHODS: This is a double-blinded prospective randomized sibling oocyte study including patients undergoing treatment with IVF with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing (PGT). After controlled ovarian hyperstimulation, oocytes from each patient will be separated into two groups. Each group will be randomized to sperm processed using either microfluidics or density gradient centrifugation and embryos biopsied for PGT to assess euploidy rates. A sample size of 686 oocytes in each group for a total of 1372 oocytes will provide 80% power to detect a significant difference in the euploidy rates per mature oocyte between the two groups. An ancillary study examining the relationship between sperm processing method and sperm DNA fragmentation will be assessed. CONCLUSION: This study will offer insight into the sperm's contribution to embryo euploidy, and has the potential to provide an alternative method of improving euploidy rates in clinical practice.

Pregnancy outcomes after frozen-thawed embryo transfer using letrozole ovulation induction, natural, or programmed cycles.

OBJECTIVE: To evaluate and compare pregnancy outcomes between letrozole ovulation induction, natural, and programmed frozen-thawed embryo transfer (FET) cycles in a population based in the United States. DESIGN: Retrospective cohort study. SETTING: Single university-affiliated infertility practice. PATIENT(S): A total of 3,148 FET cycles consisting of patients aged ≤45 years transferring blastocysts that were created from autologous oocytes between January 2015 and July 2021. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was the ongoing pregnancy rate (OPR) or live birth rate (LBR). The secondary outcomes included clinical pregnancy and clinical loss rates (CLRs). RESULT(S): The OPR/LBR was higher among letrozole FETs than among programmed FETs (adjusted risk ratio [aRR] 1.11, 95% confidence interval [CI] 1.02-1.21) but comparable to natural FETs (aRR 1.05, 95% CI 0.96-1.14). The OPR/LBR was comparable between natural and programmed FETs (aRR 1.06, 95% CI 0.99-1.13). The CLR was lower in the natural FET group than in the programmed FET group (aRR 0.62, 95% CI 0.46-0.84). There were no differences in CLRs between letrozole and programmed FETs and between letrozole and natural FETs. Among ovulatory women, the OPR/LBR among letrozole FETs was higher than that among programmed FETs (aRR 1.16, 95% CI 1.05-1.28). The CLR among ovulatory women was significantly lower in both letrozole FETs (aRR 0.44, 95% CI 0.22-0.87) and natural FETs (aRR 0.59, 95% CI 0.43-0.80) than in programmed FETs. Among anovulatory women, the OPR/LBR in the letrozole FET group was similar to that in the programmed FET group (aRR 0.95, 95% CI 0.79-1.13). CONCLUSION(S): Letrozole and natural FET clinical outcomes were improved compared with programmed FET outcomes.

Embryologic outcomes among patients using a microfluidics chip compared to density gradient centrifugation to process sperm: a paired analysis.

PURPOSE: To evaluate embryologic outcomes among paired IVF cycles in which a microfluidics chip was utilized compared to density gradient centrifugation for sperm processing. METHODS: This was a retrospective cohort study of 88 paired IVF cycles from patients aged 18-44 years at a university-affiliated IVF center. Fresh cycles from patients undergoing ICSI with sperm processed by a microfluidics chamber (microfluidics cycles) were compared to the same patients' previous ICSI cycles in which sperm was processed via density gradient centrifugation (control cycles). The primary outcome was the high-quality blastulation rate. RESULTS: High-quality blastulation rate per oocyte retrieved was significantly higher in the microfluidics group compared to the control group (21.1% versus 14.5%, p < 0.01) as was the blastulation rate per 2PN (42.7% versus 30.8%, p < 0.01). Fertilization rates were significantly higher in the microfluidics group. The euploidy rate per oocyte retrieved was significantly higher in the microfluidics group compared with the control group (8.5% versus 4.3%, p = 0.04), while the euploidy rate per embryo biopsied was comparable (32.6% versus 21.8%, p = 0.09). In patients with male factor infertility, the high-quality blastulation rate was similar between the control and microfluidics cycles. There was a significantly higher blastulation rate among microfluidics cycles in patients without a diagnosis of male factor infertility (p < 0.01). CONCLUSION: In this study, several embryologic outcomes, including fertilization rate, high-quality blastulation rate, and euploidy rate, were significantly higher in the microfluidics group compared to the control group. Microfluidics sperm processing may be a way to improve embryologic outcomes.

Black race associated with lower live birth rate in frozen-thawed blastocyst transfer cycles: an analysis of 7,002 Society for Assisted Reproductive Technology frozen-thawed blastocyst transfer cycles.

OBJECTIVE: To evaluate if racial/ethnic differences in pregnancy outcomes persisted in frozen-thawed embryo transfer (FET) cycles on a national level. DESIGN: Retrospective cohort study. SETTING: Clinic-based data. PATIENT(S): A total of 189,000 Society for Assisted Reproductive Technology FET cycles from 2014-2016 were screened, of which 12,000 cycles had available fresh cycle linkage information and ultimately, because of missing data, 7,002 FET cycles were included. Cycles were stratified by race (White, Black, Asian, and Hispanic). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live birth rate. Secondary outcomes were implantation rate, clinical pregnancy rate, multiple pregnancy rate, and clinical loss rate (CLR). RESULT(S): Live birth rate was significantly lower in the Black vs. White and Asian, but not Hispanic group. Implantation rate was also significantly lower and CLR higher in the Black group compared with all other groups (all P<.01). Black women had a lower risk of live birth (adjusted risk ratio, 0.82; 95% confidence interval [CI], 0.73-0.92) and a higher risk of clinical loss (adjusted risk ratio, 1.59; 95% CI, 1.28-1.99) compared with White women. There was no significant difference between groups in clinical pregnancy rate or multiple pregnancy rate. When the analysis was limited to preimplantation genetic testing FET cycles, there remained a significantly lower implantation rate in the Black group compared with all other groups (all P<.01). CONCLUSION(S): Black race remains an independent predictor of reduced live birth rate in FET cycles, likely because of higher CLR.

Reduction in multiple pregnancy rate in donor oocyte-recipient gestational carrier (GC) in vitro fertilization (IVF) cycles in the USA with single-embryo transfer and preimplantation genetic testing.

PURPOSE: To evaluate the utilization of single-embryo transfer (SET) and preimplantation genetic testing (PGT) in gestational carrier IVF cycles in the USA with donor oocyte and examine the impact on live birth and multiple gestation. METHODS: Retrospective cohort study using the Society of Assisted Reproductive Technology (SART) clinic database of 4776 donor oocyte-recipient IVF cycles in which a GC was used. The cycles were separated into 4 groups by use of PGT and number of embryos transferred as follows: (1) PGT and single-embryo transfer (PGT-SET); (2) PGT and multiple embryo transfer (PGT-MET); (3) no PGT and SET (NoPGT-SET); (4) no PGT and MET (NoPGT-MET). Primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). RESULTS: More than one blastocyst was transferred in 48.7% (2323/4774) of the cycles. When ≥1 blastocyst was transferred, with or without the use of PGT, the MPR was 45.5% and 42.0%, respectively. In comparison, in the PGT-SET and NoPGT-SET groups, the MPR was 1.4% (8/579) and 3.3% (29/883), respectively. Live birth rates increased with the use of PGT-A and with MET. CONCLUSION: This study shows that SET, with or without PGT, is associated with a significantly reduced MPR in donor oocyte-recipient GC IVF cycles while maintaining high LBR. It also demonstrates that many infertility centers in the USA are not adhering to ASRM embryo transfer guidelines. Our findings highlight an opportunity to increase GC safety, which ultimately may lead to widened access to this increasingly restricted service outside the USA.

Impact of trophectoderm biopsy on obstetric and perinatal outcomes following frozen-thawed embryo transfer cycles.

STUDY QUESTION: Does trophectoderm biopsy for preimplantation genetic testing (PGT) increase the risk of obstetric or perinatal complications in frozen-thawed embryo transfer (FET) cycles? SUMMARY ANSWER: Trophectoderm biopsy may increase the risk of hypertensive disorders of pregnancy (HDP) in pregnancies following FET cycles. WHAT IS KNOWN ALREADY: Trophectoderm biopsy has replaced blastomere biopsy as the standard of care to procure cells for PGT analysis. Recently, there has been concern that trophectoderm biopsy may adversely impact obstetric and perinatal outcomes. Previous studies examining this question are limited by use of inappropriate control groups, small sample size or reporting on data that no longer reflects current IVF practice. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study conducted at a single university-affiliated fertility center. A total of 756 patients who underwent FET with transfer of previously vitrified blastocysts that had either trophectoderm biopsy or were unbiopsied and resulted in a singleton live birth between 2013 and 2019 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Obstetric and perinatal outcomes for patients aged 20-44 years who underwent FET with transfer of previously vitrified blastocysts that were either biopsied (n = 241) or unbiopsied (n = 515) were analyzed. Primary outcome was odds of placentation disorders including HDP and rate of fetal growth restriction (FGR). Binary logistic regression was performed to control for potential covariates. MAIN RESULTS AND THE ROLE OF CHANCE: The biopsy group was significantly older, had fewer anovulatory patients, was more often nulliparous and had fewer embryos transferred compared to the unbiopsied group. After controlling for potential covariates, the probability of developing HDP was significantly higher in the biopsy group compared with unbiopsied group (adjusted odds ratio (aOR) 1.943, 95% CI 1.072-3.521; P = 0.029).There was no significant difference between groups in the probability of placenta previa or placenta accreta. There was also no significant difference in the rate of FGR (aOR 1.397; 95% CI, 0.815-2.395; P = 0.224) or the proportion of low (aOR 0.603; 95% CI, 0.336-1.084; P = 0.091) or very low (aOR 2.948; 95% CI, 0.613-14.177; P = 0.177) birthweight infants comparing biopsied to unbiopsied groups. LIMITATIONS, REASON FOR CAUTION: This was a retrospective study performed at a single fertility center, which may limit the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS: Trophectoderm biopsy may increase the risk of HDP in FET cycles, however, a prospective multicenter randomized trial should be performed to confirm these findings. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: NA.

Maternal and perinatal outcomes in programmed versus natural vitrified-warmed blastocyst transfer cycles.

RESEARCH QUESTION: Do maternal and perinatal outcomes differ between natural and programmed frozen embryo transfer (FET) cycles? DESIGN: Retrospective cohort study at a university-affiliated fertility centre including 775 patients who underwent programmed or natural FET cycles resulting in a singleton live birth using blastocysts vitrified between 2013 and 2018. RESULTS: A total of 384 natural and 391 programmed FET singleton pregnancies were analysed. Programmed FET resulted in higher overall maternal complications (32.2% [126/391] versus 18.8% [72/384]; P < 0.01), including higher probability of hypertensive disorders of pregnancy (HDP) (15.3% [60/391] versus 6.3% [24/384]; P < 0.01), preterm premature rupture of membranes (2.6% [10/391] versus 0.3% [1/384]; P = 0.02) and caesarean delivery (53.2% [206/387] versus 42.8% [163/381]; P = 0.03) compared with natural FET. After controlling for potential confounders, including age, body mass index, parity, smoking status, history of diabetes or chronic hypertension, infertility diagnosis, number of embryos transferred and use of preimplantation genetic testing, the adjusted odds ratio for HDP was 2.39 (95% CI 1.37 to 4.17) and for overall maternal complications was 2.21 (95% CI 1.51 to 3.22) comparing programmed with natural FET groups. The groups did not significantly differ for any perinatal outcomes analysed, including birth weight (3357.9 ± 671.6 g versus 3318.4 ± 616.2 g; P = 0.40) or rate of birth defects (1.5% [6/391] versus 2.1% [8/384]; P = 0.57), respectively. CONCLUSION: Vitrified-warmed blastocyst transfer in a programmed cycle resulted in a twofold higher probability of HDP compared with transfer in a natural cycle. Natural FET cycle should, therefore, be recommended as first line for all eligible patients undergoing FET to reduce the risk of HDP.

In vitro fertilization outcomes after preimplantation genetic testing for chromosomal structural rearrangements comparing fluorescence in-situ hybridization, microarray comparative genomic hybridization, and next-generation sequencing.

OBJECTIVE: To compare in vitro fertilization (IVF) outcomes for preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) using various testing platforms. DESIGN: Retrospective cohort. SETTING: Large academic IVF center. PATIENTS: Fifty-one balanced translocation carriers undergoing IVF with PGT-SR who completed a total of 91 cycles, including 31 fluorescence in-situ hybridization (FISH), 24 microarray comparative genomic hybridization (aCGH), and 36 next-generation sequencing (NGS) testing cycles. INTERVENTIONS: PGT-SR. MAIN OUTCOME MEASURES: Primary outcome of live-birth rate and secondary outcomes including implantation rate, clinical loss rate, and percentages of normal or balanced, unbalanced, and aneuploid embryos detected. RESULTS: There was no statistically significant difference in LBR, though there was a tendency toward a higher LBR for NGS testing (14 of 19, 73.7%) compared with FISH (8 of 18, 44.4%) and aCGH (10 of 20, 50.0%). The implantation rate was statistically significantly higher for NGS (16 of 20, 80.0%) compared with FISH (11 of 25, 44.0%) and aCGH (16 of 30, 53.3%). There was no statistically significant difference in clinical pregnancy losses. There was a lower percentage of normal or balanced embryos with FISH (12.5%) compared with aCGH (23.7%) and with NGS (20.7%). CONCLUSIONS: This is the first report of PGT-SR outcomes for translocation carriers directly comparing PGT-SR using FISH, aCGH, and NGS. Our findings suggest an improvement in pregnancy outcomes parallel to the advancement in technology and are reassuring for continued use of NGS for this population.

Evolution of Knowledge, Awareness, and Practices regarding Zika Virus from 2016 to 2017.

Objective: Our team created a knowledge, attitudes, and practice (KAP) survey in order to assess changes over time in healthcare provider and community member awareness of Zika virus symptoms, transmission, treatment, and current and future concerns. Study Design: The cross-sectional survey was issued at an academic medical center in Washington, DC, and via an online link to healthcare providers and community members between June and August 2016. Survey distribution was then repeated the following year, from March to April 2017. Outcomes were compared by survey year and healthcare provider versus community member status using SAS Program Version 9.4. Results: Significant differences in knowledge, attitudes, and practices existed between 2016 and 2017 survey time points. By 2017, more respondents had knowledge of various Zika virus infection characteristics; however healthcare provider knowledge also waned in certain areas. Attitudes towards Zika virus infection displayed an overall decreased concern by 2017. Practice trends by 2017 demonstrated fewer travel restrictions to Zika-endemic areas and increased mosquito protective measures within the US. Conclusions: Our results provide novel insight into the transformation of knowledge, attitudes, and practice of community members and healthcare providers regarding Zika virus since its declaration as a public health emergency of international concern in 2016.

Pregnancy intentionality in relation to non-planning impulsivity.

BACKGROUND: Half of US pregnancies are unintended. Understanding risk factors is important for reducing unintended pregnancy rates. AIM: We examined a novel risk factor for unintended pregnancies, impulsivity. We hypothesized that non-planning impulsivity, but not motor or attentional impulsivity, would be related to pregnancy intention. METHODS: Pregnant women (N = 116) completed self-report measures during their second or third trimester. Impulsivity was measured using the Barratt Impulsiveness Scale (BIS-15); subscales measured motor, attentional and non-planning impulsivity (subscale range: 5-20). On each subscale, high impulsivity was indicated by a score of ≥11. Pregnancy intention was assessed by asking women whether they were trying to become pregnant at the time of conception (yes or no). Crude and multivariable-adjusted logistic regression models estimated the cross-sectional association between impulsivity and unplanned pregnancy. RESULTS: Thirty-four percent of women reported that their current pregnancy was unplanned, and 32% had high non-planning impulsivity. Fifty-one percent of women with high non-planning impulsivity reported an unplanned pregnancy versus 25% of women with low impulsivity. Women with high non-planning impulsivity had 3.53 times the odds of unplanned pregnancy compared to women with low non-planning impulsivity (adjusted OR =3.53, 95% CI: 1.23-10.14). Neither motor (adjusted OR =0.55, 95% CI: 0.10-2.90) nor attentional (adjusted OR =0.84, 95% CI: 0.25-2.84) impulsivity were related to pregnancy intentionality. CONCLUSIONS: High non-planning impulsivity may be a risk factor for unplanned pregnancy. Further research should explore whether increasing the use of long-acting reversible contraceptives or integrating if-then planning into contraceptive counseling among women with higher non-planning impulsivity can lower unplanned pregnancy rates.