A model for predicting low progesterone levels on the day of embryo transfer in hormonally prepared vitrified-warmed embryo transfer cycles: A secondary analysis of a prospective cohort study.

AIM: To develop a model that predicts low progesterone (P) levels on the day of embryo transfer (ET) based on patient and cycle characteristics, including serum estradiol (E2 ) concentration after vaginal administration of micronized E2 for endometrial preparation. METHODS: A prospective cohort of 193 patients scheduled for cryopreserved blastocyst transfer during an artificial endometrial preparation cycle, using micronized E2 vaginally for first 4 days (4 mg/day), followed by oral administration (6 mg/day). Blood sampling for E2 was performed prospectively on day-5 of vaginal administration and analysis was performed retrospectively. On sixth day of P treatment (daily 300 mg of vaginal micronized P tablets), P levels were measured on ET day. Primary outcome measure was serum P levels after vaginal E2 administration. RESULTS: Patients with low P levels on the day of ET (<7.8 ng/mL, 25th percentile) were heavier (p < 0.001) and exhibited lower day 5 serum E2 levels (p < 0.001) compared with patients with adequate P levels. Multivariate linear regression analysis revealed that weight (p = 0.003) and day 5 E2 levels (p < 0.001) were independently associated with the P levels. The sensitivity, specificity, and positive and negative predictive values (%) were 71.4, 55.6, 35.4, and 85.1 for weight ≥ 65 kg; 71.4, 61.8, 38.9, and 86.4 for day 5 E2 ≤ 1615 pg/mL; 59.2, 83.3, 54.7, and 85.7 for the combination of these two variables; and 82.9, 62.5, 54.7, and 87.0 for the sequential inclusion of these variables, respectively. CONCLUSIONS: Low day 5 E2 levels following vaginal administration and high weight are independently associated with low P levels on the day of ET. Predictive performance is enhanced when these variables are considered sequentially or in combination.

Investigation of the effects of trophectoderm morphology on obstetric outcomes in fifth day blastocyst transfer in patients undergoing in-vitro-fertilization

Objective: Trophectoderm (TE) cells are the first differentiating cells in embryo development and have epithelial features. TE cells, which associate with implantation of the blastocyst into the uterine endometrium, contribute to the formation of the placenta. Inner cells mass (ICM) together with TE cells are used for determining embryo quality. The aim of this study was to investigate the role of TE and ICM cells on pregnancy outcome in 5th day blastocyst transferred in-vitro-fertilization (IVF) pregnancy. Material and Methods: This was a retrospective study using data from all patients who applied for blastocyst transfer IVF between January 2015 and March 2019 at the Reproductive Endocrinology and Infertility Center of Akdeniz University Faculty of Medicine, Department of Obstetrics and Gynecology. ALPHA Istanbul consensus evaluation system was used for grading of the blastocyst. The embryo quality, expansion, ICM and TE morphology of the 5th day transferred blastocyst was assessed, together with abortion rate, live birth rate, pregnancy complications, and pregnancy outcomes. Results: There was a significantly increased risk of preeclampsia (PE) (7.8% vs 1.1%; p=0.041), preterm delivery (PD) (36% vs 17.7%; p=0.037), and antenatal bleeding rates (13.6% vs 5%; p=0.021) in TE-C compared to the TE-A + TE-B blastocysts. Furthermore, a higher rate of obstetric complications was observed in ICM-C compared to ICM-A and B (p=0.003). There was a significant correlation between TE morphology and implantation success, ongoing pregnancy rate, and abortion incidence. Conclusion: These results suggest that TE cell morphology is related to implantation success and pregnancy outcomes, especially in terms of the risk of abortion, PE, PD, and antenatal bleeding. It may be advisable to counsel women concerning possible poor obstetric outcome due to poor ICM quality. Future prospective and controlled studies are needed to clarify this association.

Endometrial compaction does not predict the reproductive outcome after vitrified-warmed embryo transfer: a prospective cohort study.

RESEARCH QUESTION: Does endometrial compaction, determined by both transvaginal (TVUS) and abdominal ultrasonography (AUS), improve reproductive outcomes in vitrified-warmed embryo transfer (FET) cycles, and is there a correlation between compaction and serum progesterone concentrations on day of embryo transfer? DESIGN: Prospective observational cohort study at a single tertiary care IVF centre including 204 patients undergoing high-quality vitrified-warmed blastocyst transfer in a hormone replacement therapy (HRT) cycle. The change in endometrial thickness (EMT) between end of oestrogen-only phase and day of embryo transfer, as measured by sequential TVUS, was used to categorize endometrium as undergoing compaction (≥5% decrease), no change, or expansion (≥5% increase). EMT was also examined using AUS at the time of embryo transfer. Primary outcome measure was ongoing pregnancy rates. RESULTS: Thirty-one cycles (15.2%) demonstrated compaction, whereas 123 (60.3%) expanded and 50 (24.5%) remained unchanged as measured by sequential TVUS. Ongoing pregnancy rates did not differ among cycles with compaction (58.1%), those with expansion (56.9%), and those with no change (60.0%; P=0.932). Furthermore, oestrogen, progesterone and oestrogen/progesterone concentrations on day of embryo transfer were comparable among all groups. Using AUS, endometrial compaction was seen in 46 cycles (22.5%), and there was a positive correlation between body mass index and AUS-measured EMT change (ρ = 0.161, P = 0.021). In the group with AUS-determined endometrial compaction, AUS measurements showed a significantly thinner EMT on day of embryo transfer (8.3 mm; interquartile range [IQR] [7.5; 9.2] versus 9.3 mm; IQR [8.4; 11.4], P < 0.001) and higher for EMT change (1.3 mm; IQR [0.8; 1.7] versus 0.1 mm; IQR [-1.1; 1.0], P < 0.001) compared with TVUS measurements. CONCLUSIONS: Endometrial compaction during HRT-FET does not predict ongoing pregnancy.

Blastocyst versus cleavage transfers: who benefits?

PURPOSE: This retrospective cohort study determined the relative efficacy of blastocyst and cleavage-stage transfers in patients with differing numbers of zygotes. METHODS: A total of 1116 women whose embryo transfers were planned independently of patient characteristics were included. Cleavage-stage (D3) and blastocyst-stage (D5) transfer outcomes were analyzed per number of zygotes. The D5 group included transfer cancellations as the intention-to-treat population. The effect of the embryo transfer date on the clinical outcomes (clinical pregnancy and implantation rates) was analyzed using multivariate logistic regression. RESULTS: Among the patients, 584 and 532 underwent D3 and D5 embryo transfers, respectively. The clinical pregnancy rates were significantly higher in D5 patients with ≥ 6 zygotes (25.7% vs 48.3%). The multivariate logistic regression analysis for clinical pregnancy did not show significant differences between the blastocyst and cleavage-stage transfers in patients with ≤ 5 zygotes (0.874 [0.635-1.204]). Compared to the cleavage-stage, blastocyst-stage transfers for patients with ≥ 6 zygotes resulted in a three-fold increase in clinical pregnancy rates (3.122 [1.797-5.425]). CONCLUSION: Blastocyst transfers were not inferior to cleavage-stage embryo transfers among patients with few zygotes and were preferable for patients with several zygotes.

On the origin of zygosity and chorionicity in twinning: evidence from human in vitro fertilization.

Assisted reproduction is presumed to increase monozygotic twin rates, with the possible contribution of laboratory and medical interventions. Monozygotic dichorionic gestations are supposed to originate from the splitting of an embryo during the first four days of development, before blastocyst formation. Single embryo transfers could result in dichorionic pregnancies, currently explained by embryo splitting as described in the worldwide used medical textbooks, or concomitant conception. However, such splitting has never been observed in human in vitro fertilization, and downregulated frozen cycles could also produce multiple gestations. Several models of the possible origins of dichorionicity have been suggested. However, some possible underlying mechanisms observed from assisted reproduction seem to have been overlooked. In this review, we aimed to document the current knowledge, criticize the accepted dogma, and propose new insights into the origin of zygosity and chorionicity.

Uterine involvement by endometriosis: Sonographic features from elusive findings to apparent adenomyosis.

OBJECTIVE: The primary aim of this study is to investigate whether there are any minor sonographic uterine findings, not typical for adenomyosis, in endometriosis patients. The secondary objective is to determine the prevalence of sonographic features of adenomyosis in an infertile population with endometriosis. STUDY DESIGN: The investigation was of 291 infertile women with endometriosis, either manifesting endometrioma (OMA) or diagnosed through laparoscopy, who were investigated for two-dimensional transvaginal sonographic (2D-TVS) features of adenomyosis. These patients were grouped as either having endometriosis with adenomyosis (EwA,n = 121) or without adenomyosis (EwoA, n = 170). Additionally, patients without both endometriosis and 2D-TVS features of adenomyosis constituted the control group (n = 170). RESULTS: At least one 2D-TVS feature of adenomyosis was detected in 41.6 % (n = 121) of women with endometriosis. Asymmetrical myometrial thickening of uterine walls (57.9 %), hyperechogenic islands (47.1 %), and fan-shaped shadowing (46.9 %) were relatively more prevalent 2D-TVS findings among EwA patients. Multiple OMA (p = 0.038), OMA ≥ 4 cm (p = 0.034), and total OMA volumes were found to be higher (p = 0.004) in the EwA group. Additionally, uterine volumes were found to be 96.7 cm3, 73.0 cm3, and 64.2 cm3 in the EwA, EwoA, and control groups, respectively (EwA vs EwoA, p < 0.001; EwoA vs control, p <0.001). Multivariate linear regression analysis revealed that the presence of endometriosis was independently associated with an increase in uterine volume (ß = 0.243, p < 0.001). CONCLUSION: A stepwise and statistically significant volume increase from the control group to the EwoA and then to the EwA group may reflect a spectrum of uterine involvement in endometriosis. This might indicate that many uterine endometriosis cases are still hidden from view, possibly demonstrating an "iceberg phenomenon".

The Effect of Instant Urinary Catheterization on Pregnancy Outcomes after Intracytoplasmic Sperm Injection and Embryo Transfer.

AIM: To evaluate the effect of instant urinary catheterization on pregnancy rates in women who are on bed rest after embryo transfer (ET). METHODS: This retrospective study included patients who underwent intracytoplasmic sperm injection (ICSI) treatment at the Akdeniz University Fertility Clinic between January 2015 and March 2016. All patients were advised bed rest for an hour after ET. The clinic's electronic database was screened to identify the uterine anatomy of the patients, transferred embryo quality, and urinary catheterization status. Only women with an anteverted and anteflexed uterus and cycles that resulted in high-quality blastocyst transfers were included in this analysis. Finally, 71 cycles with urinary catheterization and 81 cycles with no catheterization were analyzed. RESULTS: The clinical (53.5 vs. 40.7%, p = 0.115) and ongoing pregnancy (43.7 vs. 35.8%, p = 0.323) rates were comparable between urinary catheterization and non-catheterization groups. Multivariate analysis by logistic regression including confounding factors revealed that urinary catheterization was independently associated with clinical pregnancy (OR 2.06, 95% CI 1.03-4.13, p = 0.041). However, no significant association was detected between catheterization and the clinically more relevant, ongoing pregnancy (OR 1.65, 95% CI 0.82-3.30, p = 0.160). CONCLUSION: Our preliminary findings on the use of instant urinary catheterization after ET are promising and justify further investigation in larger prospective studies.

Artificial oocyte activation after intracytoplasmic morphologically selected sperm injection: A prospective randomized sibling oocyte study.

This study aimed to evaluate the effect of artificial oocyte activation (AOA) by calcium ionophore after intracytoplasmic morphologically selected sperm injection (IMSI) on fertilization, cleavage rate and embryo quality. A total of 194 oocytes from 21 cycles from women with a history of low fertilization rate accompanying teratozoospermia were enrolled over a 3-month period. Mature oocytes from each patient were randomly allocated into two groups after IMSI. In the study group, half of the patients' oocytes (n = 97) were exposed to AOA, and in the control group (n = 97), AOA was not applied. The mean number of mature oocytes, fertilization and cleavage rates were similar between the study and control groups (p > 0.05 for each). However, fertilized oocytes of the AOA group were less likely to produce top quality embryos when calculated per fertilized oocyte (28/80; 35.0% versus 38/71; 53.5%, respectively; p = 0.024) and also per cycle (13/21; 61.9% versus 20/21; 95.24%, respectively; p = 0.006). Our study indicates that AOA may not improve fertilization rates after IMSI and may even reduce the ability of a successfully fertilized oocyte to develop into a top quality embryo. AOA should, therefore, be applied to cases with a defined oocyte activating deficiency.

Dichlorvos-induced testicular toxicity in male rats and the protective role of vitamins C and E.

Dichlorvos is an organophosphorus insecticide that is used worldwide for pest control in agriculture and household use. Vitamins C and E are potential antioxidants protecting cells from oxidative stress. Vitamin C+vitamin E, dichlorvos, a combination of vitamin C+vitamin E+dichlorvos, or corn oil (control) were given to rats via oral gavage for 7 weeks. Body and testis weights, sperm parameters, hormone levels, histo- and cytopathological changes in testes were investigated at the end of 24 h and the 4th and 7th weeks comparatively with the control group. Body and testis weights, sperm morphology, FSH, LH, and testosterone levels were decreased significantly at the end of 4th and 7th weeks in the dichlorvos- and vitamins+dichlorvos-treated groups. A statistically significant decline in sperm motility and testosterone levels occurred by the end of 7th week in the dichlorvos- and vitamins+dichlorvos-treated groups. Light and electron microscopy revealed necrosis, edema and cellular damage in testicular tissues of the dichlorvos- and vitamins+dichlorvos-treated rats at the end of 4th and 7th weeks. In conclusion, dichlorvos caused subacute and subchronic reproductive toxicity, but vitamins did not confer protection.

Clinical outcome of magnetic activated cell sorting of non-apoptotic spermatozoa before density gradient centrifugation for assisted reproduction.

PURPOSE: Magnetic activated cell sorting (MACS) eliminates apoptotic spermatozoa based on the presence of externalized phosphatidylserine residues. We evaluated the outcome of male fertility treatment when intracytoplasmic sperm injection (ICSI) into human oocytes was performed with non-apoptotic MACS-selected spermatozoa. METHODS: 196 couples were treated by ICSI following spermatozoa preparation by MACS (study group; 122 couples) or density gradient centrifugation (DGC) (control group; 74 couples). Fertilization, cleavage, pregnancy, and implantation rates were analyzed. RESULTS: The percentage of sperm with normal morphology after MACS selection was improved. Cleavage and pregnancy rates were higher, respectively, in the study group than in control. A slightly higher implantation rate was also observed in the study group. CONCLUSIONS: MACS selection of human spermatozoa increased cleavage and pregnancy rates in oligoasthenozoospermic ART cases. This novel method for selecting non-apoptotic spermatozoa for ICSI is safe and reliable, and may improve the assisted reproduction outcome.