Cleavage Patterns of 9600 Embryos: The Importance of Irregular Cleavage.

This prospective, observational study investigated the incidence of irregular cleavage (IRC) among human embryos and its influence on IVF treatment outcomes. It included 1001 women who underwent 1976 assisted reproduction treatments during 2016-2021 in a single IVF clinic. Embryo morphokinetics were analyzed and evaluated for the association between IRC and women's characteristics, treatment characteristics, and pregnancy outcomes. The incidence of IRC was 17.5% (1689/9632 embryos). Of these, 85% of the embryos had one IRC, 15% had multiple IRC and 35% of IRC events occurred during the embryo's first cell cycle. IRC embryos were found to correlate with male factor (p = 0.01) and higher ICSI rate (p = 0.01). Age, BMI, parity, basal FSH level, stimulation protocol, and number of retrieved oocytes did not differ between groups. Embryos with early IRC or more than one IRC had lower blastulation rates (p = 0.01 for each). Fresh cycles with IRC embryos had a lower clinical pregnancy rate (p = 0.01) and embryos with early IRC had a lower live birth rate (p = 0.04) compared to embryos without IRC. Frozen transfer cycles of blastocyst embryos, with or without IRC, had comparable results. In conclusion, the number of abnormal cleavage events and their timing are important factors in the prognosis of the developing human embryo.

Embryonic Development in Relation to Maternal Age and Conception Probability.

Data regarding association between early embryo development and maternal age is limited and inconclusive. This study has two aims: to evaluate differences in the cleavage stage of embryos in young versus advanced maternal age (AMA) women. To compare the early embryonic development of embryos that result in pregnancy versus no pregnancy. A retrospective study of early embryonic development which was recorded and analyzed using time-lapse imaging was conducted. The kinetic markers of time to pronuclei fading (tPNf) and appearance of two to eight cells (t2-t8) were assessed. For embryos cultured to blastocyst, times to morula (tM), start of blastulation (tSB) cavitated, and expanded blastocyst (tB, tEB) were also recorded. A total of 2021 oocytes from 364 intracytoplasmic sperm injection (ICSI) cycles were evaluated, of which 1223 (60.5%) were derived from young patients and 798 (39.5%) from those of AMA. The mean time points to t3, t4, t5, t6, tSB, tB, and tEB were significantly shorter for embryos derived from younger women, as compared to older women (p < 0.05). Overall, women who conceived presented a faster embryonic development, for both age groups. The mean time points of t2 and t8 were significantly shorter in patients who conceived versus not conceived (p < 0.05). We concluded that older women's age is associated with delayed embryonic development. Embryos that yielded pregnancy cleaved faster compared to those which did not, in both age groups. Thus, when considering which embryo to transfer to women of AMA, selecting the faster-developing embryos may improve the chances of conception.

More is not always better-lower estradiol to mature oocyte ratio improved IVF outcomes.

AIM: To find a cut-off ratio of estradiol/metaphase II oocyte (E2/M2) ratio and to evaluate the correlation with patients' characteristics, embryo morphokinetics using EmbryoScope™ and IVF cycle outcomes. MATERIAL AND METHODS: For this retrospective cohort study, records of all fresh cycles that were cultured and scored by EmbryoScope™ were evaluated. The peak E2/M2 ratio was calculated on the day of human chorionic gonadotropin (hCG) administration and correlated to embryo morphokinetic quality and cycle outcomes. A receiver operating characteristics analysis was calculated for the E2/M2 ratio and clinical pregnancy rates. RESULTS: A total of 2461 oocytes were collected from 319 patients. Receiver operating characteristics analysis revealed a cutoff of 204 as a discriminative point to predict clinical pregnancy with a sensitivity of 69.5% and specificity of 62.1% (P < 0.001). E2/M2 > 204 group were older, had higher E2 concentration, fewer M2 oocytes despite elevated gonadotrophin doses. E2/M2 ratio ≤ 204 was correlated with higher fertilization rate, better embryo quality, higher pregnancy and live birth rates, and more frozen embryos. CONCLUSION: E2/M2 ratio < 204 yielded the best probability to achieve good quality embryos with good morphokinetic scores and better pregnancy outcomes and may be used to predict IVF cycle outcomes. Advanced maternal age and low ovarian response received higher concentrations of gonadotrophins, which resulted in higher E2/M2 ratio. Milder stimulation to those patients may improve their cycle outcomes.

Degenerative Oocytes in the Aspirated Cohort Are Not Due to the Aspirating Needle: a Prospective Randomized Pilot Study with Sibling Oocytes.

The aim of this study is to compare two different needles (17G vs. 20-17G variable diameter) used for OPU and to assess whether the different stress forces along the needle affect the presence of degenerative oocytes, oocyte quality, and embryo morphokinetics. Prospective, randomized study enrolled women undergoing in vitro fertilization (IVF) intracytoplasmic sperm injection (ICSI) from August 2016 through August 2018 in an IVF unit at a tertiary care medical center. Ovaries were randomly aspirated using either a 20-17G needle or a 17G needle. The embryologist was blinded to the aspirating needle and sibling oocytes were separated according to needle used for fertilization and further evaluation. Oocytes were scored negatively if one of the following parameters was abnormal immediately after OPU: polar body shape, zona pellucida, cytoplasm, perivitelline space, or vacuoles. The presence of degenerative oocytes was noted at OPU. A total of 580 oocytes from 43 women were evaluated, 293 in the 17G needle group and 287 in the 20-17G group. Oocyte scoring was comparable between the two different needles (- 1.99 ± 1.9 vs. - 1.88 ± 1.69; P = 0.13), as were embryo quality and pregnancy rate. Cohorts with degenerative oocytes had lower oocyte scores (- 2.11 ± 1.81 vs. - 1.60 ± 1.50; P = 0.001) and poorer performance and fertilization rates (62.5% vs. 78.5%; P < 0.001) than did cohorts with no degenerative oocytes. Cycles with degenerative oocytes in the cohort at OPU demonstrated poorer oocyte quality and decreased fertilization, regardless of the needle used. 1.5.2016 NIH number NCT02749773.

Degenerated oocyte in the cohort adversely affects IVF outcome.

The presence of Degenerated Oocyte (DEG) was mostly described after intracytoplasmic sperm injection (ICSI), with fewer reports on DEG at the time of ovum pick-up (OPU). This study aims to assess morphokinetics of embryos cultured in a time-lapse incubator and compare cohorts with and without DEG at OPU. In a retrospective cohort study from January 1, 2016 until September 31, 2017 a total of 399 IVF/ICSI cycles and 2980 embryos were evaluated. In 81 of 399 cycles at least one DEG oocyte was observed at the time of OPU. The remaining 318 cycles with no DEG oocyte were compared as a control group. In the DEG group, significantly more oocytes were collected per patient (12.9 ± 7.2 vs. 10.1 ± 6.1. P < 0.001). Fertilization rate, pregnancy and clinical pregnancy rates were comparable between the two groups, however, the morphokinetics and developmental scores of the embryos were significantly worse in the DEG group, (KID 3.4 ± 1.6 vs. 3.2 ± 1.6 P = 0.002 and ESHRE 1.5 ± 1.1 vs. 1.4 ± 1.0 P = 0.046). Significantly more patients achieved top-quality embryos in the NON DEG group (58.8% vs. 53.0%, P = 0.03), however, comparable delivery rate was achieved in both groups. In the DEG group, the frequency of DEG oocyte per cycle was negatively correlated with pregnancy rate. GnRH agonist protocol and the 17-20G needle used for OPU were significant predictors for the presence of DEG oocyte at OPU. In conclusions DEG oocyte may negatively affect IVF outcome, however, younger patients, and significantly more oocytes collected in the DEG group compensate for the IVF results.

Lipid droplets in granulosa cells are correlated with reduced pregnancy rates.

BACKGROUND: Lipids are an important source for energy production during oocyte maturation. The accumulation of intracellular lipids binds to proteins to form lipid droplets. This may lead to cellular lipotoxicity. The impact of lipotoxicity on cumulus and granulosa cells has been reported. This pilot study evaluated their correlation to oocyte and embryo quality. DESIGN: Prospective case-control study. SETTING: Referral IVF unit. PATIENTS: Women younger than age 40, undergoing IVF with intracytoplasmic sperm injection. INTERVENTIONS: 15 women with BMI > 30 (high BMI) and 26 women with BMI < 25 (low BMI) were enrolled. IVF outcomes were compared between groups based on BMI. Lipid content in cumulus and granulosa cells was evaluated using quantitative and descriptive methods. Lipid profile, hormonal profile and C-reactive protein were evaluated in blood and follicular fluid samples. Demographic and treatment data, as well as pregnancy rates were collected from electronic medical records. RESULTS: Higher levels of LDL and CRP, slower cell division rate and lower embryo quality were found in the group with high BMI. There was no difference in pregnancy rates between groups. In light of these findings, treatment outcomes were reanalyzed according to patients who became pregnant and those who did not. We found that patients who conceived had significantly lower fat content in the granulosa cells, reflected by mean fluorescence intensity recorded by flow cytometry analysis (23,404 vs. 9370, P = 0.03). CONCLUSIONS: BMI has no effect on lipid content in cumulus and granulosa cells, and does not affect likelihood of pregnancy. However, women who achieved pregnancy, regardless of their BMI, had lower lipid levels in their granulosa cells. This finding is important and further study is needed to evaluate lipid content in granulosa cells as a potential predictor of IVF treatment success.

The influence of obesity, smoking, and serum follicular stimulating hormone in azoospermic patients on testicular sperm extraction-intra cytoplasmic sperm injection outcomes: A retrospective cohort study.

To examine the effect of serum follicle-stimulating hormone (sFSH) level, body-mass index (BMI) and smoking on Testicular Sperm Extraction-Intracytoplasmic Sperm Injection (TESE-ICSI), and pregnancy outcomes.In this retrospective study, data were extracted from files of 52 azoospermic men who underwent TESE and in-vitro fertilization (IVF)-ICSI in our IVF unit. Demographic information, treatment cycle follow-up and pregnancy outcomes were collected.Fifty-two patients underwent 79 TESE due to azoospermia in 143 IVF cycles. Smoking was found to significantly affect sperm motility in TESE specimens before freezing (45.5% vs 14.8%; P <.001); however, this finding did not influence the pregnancy rate. Male FSH was inversely correlated with testicle volume (r = -0.595, P <.0001). Body weight did not affect semen parameters after TESE or ICSI outcomes.Among azoospermic patients with extremely poor sperm quality, male BMI, male FSH or smoking did not have an adverse effect sperm parameters or pregnancy and delivery rates.