Ex ovo omnia-why don't we know more about egg quality via imaging?

Determining egg quality is the foremost challenge in assisted reproductive technology (ART). Although extensive advances have been made in multiple areas of ART over the last 40 years, oocyte quality assessment tools have not much evolved beyond standard morphological observation. The oocyte not only delivers half of the nuclear genetic material and all of the mitochondrial DNA to an embryo but also provides complete developmental support during embryonic growth. Oocyte mitochondrial numbers far exceed those of any somatic cell, yet little work has been done to evaluate the mitochondrial bioenergetics of an oocyte. Current standard oocyte assessment in in vitro fertilization (IVF) centers include the observation of oocytes and their surrounding cell complex (cumulus cells) via stereomicroscope or inverted microscope, which is largely primitive. Additional oocyte assessments include polar body grading and polarized light meiotic spindle imaging. However, the evidence regarding the aforementioned methods of oocyte quality assessment and IVF outcomes is contradictory and non-reproducible. High-resolution microscopy techniques have also been implemented in animal and human models with promising outcomes. The current era of oocyte imaging continues to evolve with discoveries in artificial intelligence models of oocyte morphology selection albeit at a slow rate. In this review, the past, current, and future oocyte imaging techniques will be examined with the goal of drawing attention to the gap which limits our ability to assess oocytes in real time. The implications of improved oocyte imaging techniques on patients undergoing IVF will be discussed as well as the need to develop point of care oocyte assessment testing in IVF labs.

Embryo re-expansion does not affect clinical pregnancy rates in frozen embryo transfer cycles: a retrospective study.

PURPOSE: A retrospective study examining the effects of embryo re-expansion before transfer on pregnancy outcomes for frozen embryo transfers (FET). METHODS: A total of 486 FET cycles from November 2017 through December 2019 were studied. These cycles included patients using autologous, donor oocytes, and donor embryo with patients ranging from ages 23 to 48 years with infertility diagnoses. Programmed FET priming was performed with exogenous estrogen and progesterone. All blastocysts were cultured in trigas incubators for 20 min to 4 h and 42 min. Pictures of each blastocyst after thaw and before transfer were taken utilizing the Hamilton Thorne Zilos laser software (Beverly, MA). The longest portion of the embryo was measured in µm. Pregnancy was defined by a positive hCG, and ongoing clinical pregnancy was defined by the presence of fetal cardiac activity. Wilcoxon rank sum tests were used to access differences in change parameters. RESULTS: There is no significant difference in the amount of embryo expansion or contraction to achieve an ongoing pregnancy. The difference remained non-significant when stratified by embryo expansion or contraction. The amount of change over time and percent change from the first measurement were also not associated with achieving an ongoing pregnancy. This remained true after adjustment for patient age and whether or not a biopsy was performed. CONCLUSIONS: Embryos that do not re-expand after warming appear to have a similar chance of achieving a successful pregnancy as those that do re-expand.

Sperm morphology from the actual inseminated sample does not predict clinical pregnancy following intrauterine insemination.

OBJECTIVE: To determine the effect of sperm morphology from the specific sample used for intrauterine insemination (IUI) on clinical pregnancy rates (CPR). DESIGN: Prospective cohort study. SETTING: Academic fertility clinic. PATIENTS: Couples undergoing IUI July 2016-January 2017. INTERVENTIONS: Morphology slides were prepared from the semen sample produced for IUI. MAIN OUTCOME MEASURES: CPR was measured by detection of cardiac activity. Multiple logistic regression modeling was performed to determine the association of sperm morphology with CPR, controlling for age, antimüllerian hormone level, and post-wash total motile sperm count. RESULTS: Semen analyses, including Kruger strict criteria for morphology from the actual sample inseminated, were reviewed for 155 couples, comprising 234 total treatment cycles. The percent normal morphology significantly differed between the preliminary semen analysis and the IUI sample (-2.0% +3.7% (95% CI -2.55, -1.53). Of the total 234 treatment cycles, 8.6% resulted in clinical pregnancy. When categorized by strict morphology >4%, <4%, and <1%, the CPR was 6.6%, 9.8%, and 10.9%, respectively. In couples with otherwise normal semen parameters (isolated teratospermia), CPR by >4%, <4%, and <1% normal forms was 7.2%, 9.8%, and 11.1%, respectively. There was no significant association between the percent normal morphology and CPR in multivariate analysis. CONCLUSIONS: This study evaluating the morphology of the actual inseminated sample did not find differences in CPR following IUI among couples with normal and abnormal sperm morphology, including severe teratospermia. Abnormal sperm morphology should not exclude couples from attempting IUI.

Surgically Extracted Epididymal Sperm from Men with Obstructive Azoospermia Results in Similar In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes Compared with Normal Ejaculated Sperm.

PURPOSE: Controversy exists around the use of epididymal sperm for in vitro fertilization and intracytoplasmic sperm injection for couples with obstructive azoospermia, and the ability to reliably predict fertility outcomes with surgically extracted epididymal sperm remains limited. To provide additional clinical context, we sought to compare in vitro fertilization/intracytoplasmic sperm injection outcomes of epididymal sperm from couples with obstructive azoospermia to outcomes of couples using normal, ejaculated sperm. MATERIALS AND METHODS: We performed a case-control analysis of 40 couples who underwent office based epididymal sperm retrieval for obstructive azoospermia followed by in vitro fertilization/intracytoplasmic sperm injection compared with a control group of 38 female, age matched couples with no evidence of female factor infertility who underwent in vitro fertilization/intracytoplasmic sperm injection with normal, ejaculated sperm. Primary outcome was live birth on the initial embryo transfer. RESULTS: Epididymal samples yielded a median total motile sperm count of 9.1 million, compared to 81 million for ejaculated sperm. On the primary embryo transfer fertilization rate (71% vs 77%, p=0.2), blastulation rate (48% vs 59%, p=0.09), clinical pregnancy rate (70% vs 58%, p=0.4), and live birth rate (58% vs 47%, p=0.4) did not differ between epididymal and ejaculated sperm groups. CONCLUSIONS: For couples with a male partner with obstructive azoospermia epididymal sperm in vitro fertilization/intracytoplasmic sperm injection outcomes compare similarly with age matched controls undergoing in vitro fertilization/intracytoplasmic sperm injection using normal, ejaculated sperm. These results may help reproductive surgeons provide reassurance about the use of obstructed epididymal sperm as well as help guide discussions about anticipated outcomes of in vitro fertilization/intracytoplasmic sperm injection.

Time to blastulation is superior to individual components of embryo grading for live-birth prediction.

OBJECTIVE: To compare components of the embryo grading system with time for blastocyst formation (i.e., day of embryo transfer) for predicting live-birth rate in frozen embryo transfer cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility clinic. PATIENTS: From January 2015 to October 2018, 870 frozen embryos transferred in a total of 509 women and 728 cycles at our institution. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Probability of live birth per cycle. RESULTS: In unadjusted analysis of embryo grading components, both inner cell mass (ICM) and trophectoderm grades demonstrated a correlation with live-birth rates. However, this effect was lost in the ICM subgroup analysis by day of embryo transfer and preserved only in declining trophectoderm grades of day-6 transfers. In the adjusted analysis for prediction of live birth, only day of transfer was statistically significant. When assessing the composite score by Society for Assisted Reproductive Technology (SART) embryo grading, good embryos that blastulated on day 6 were statistically significantly less likely than day-5 embryos to result in live birth (risk ratio 0.70; 95% confidence interval, 0.58-0.85). Finally, in a predictive model adjusted for all individual components of embryo grade, the day of blastulation was the only statistically significant contributor. CONCLUSIONS: Time to blastulation is superior to other individual components of embryonic grading for prediction of live birth.

Should embryos developing to blastocysts on day 7 be cryopreserved and transferred: an analysis of pregnancy and implantation rates.

OBJECTIVE: To compare pregnancy rates (PRs) using blastocysts cryopreserved on day 7 with those cryopreserved on days 5 and 6. DESIGN: Retrospective observational cohort study. SETTING: Infertility center performing IVF. PATIENT(S): Eight hundred women with infertility undergoing frozen ET. INTERVENTION(S): Blastocysts cryopreserved on days 5, 6, and 7 after retrieval were thawed and transferred. MAIN OUTCOME MEASURE(S): Ongoing PRs (pregnancy developing appropriately into the second trimester). Thaw survival, implantation rates, and clinical PRs were also calculated. RESULT(S): A total of 1,406 embryos were thawed with a survival of 90.7% for day 5, 83.7% for day 6, and 78.7% for day 7. Implantation rates were 43.3%, 28.9%, and 28.9%, respectively. Ongoing PRs were 43.9%, 32.9%, and 26.7%, respectively. CONCLUSION(S): Blastocysts cryopreserved on day 7 have a lower, but clinically important potential. Embryos that do not achieve blastocyst stage on day 6 should not be universally discarded, but should be observed in culture 1 more day as 27% may result in an ongoing pregnancy.