Are there associations between clinical and embryological factors with pregnancy loss following transfer of a single euploid embryo?

First trimester pregnancy losses are commonly attributed to chromosomal abnormalities. The causes of pregnancy loss following transfer of a euploid embryo are not fully elucidated. The aim of this study was to evaluate clinical and embryological parameters for pregnancy failure following the transfer of a single euploid embryo. Pregnancy outcomes of single euploid embryo transfers from a single centre between January 2017 and March 2020 were retrospectively evaluated. Several clinical and embryological parameters were evaluated in consideration to pregnancy outcomes; total pregnancy loss and live birth. Endometrial preparation type, number of previous frozen embryo transfer cycles, history of recurrent pregnancy loss, higher body mass index, presence of endometriosis and/or adenomyosis and embryo quality were found to be significantly different between two groups. Morphokinetic parameter analysis of 523 euploid embryos using time-lapse imaging did not show any statistical differences between the two groups, however a significantly higher rate of uneven blastomeres in the cleavage stage was observed in the total preganncy loss group. Evaluation of clinical and embryological data can reveal possible factors associated with pregnancy loss that can facilitate improved patient consultation. Feasible interventions can potentially increase the chance of achieving a live birth.

Factors influencing the number of mature oocytes and cryopreservable blastocysts in hyperresponder patients triggered with a GnRH analog.

PURPOSE: This study aimed to investigate which patient and cycle characteristics may affect the number of mature oocytes and cryopreservable blastocysts in the GnRH analog trigger cases. METHODS: This was a retrospective cohort study of 2749 GnRHa trigger cycles in patients at risk of OHSS, including a group of PGT patients, between 2011 and 2020 at Istanbul Memorial Hospital, ART and Reproductive Genetics Center. Patient and cycle characteristics were evaluated using the Generalized Linear Mixed Model (GLMM). The number of mature oocytes and the number of cryopreservable blastocysts were evaluated. RESULTS: A one-unit increase in female age, daily gonadotropin dose, E2 level on day 2, and LH level on trigger day significantly decreased the number of mature oocytes retrieved (p < 0.001) and the number of cryopreservable blastocysts as p < 0.001, p < 0.001, p < 0.001, and p = 0.003, respectively. The duration of GnRH antagonist use also decreased the number of mature oocytes retrieved (p < 0.001) but not the number of cryopreservable blastocysts. CONCLUSION: The GLMM used in our study showed that a one-unit increase in female age, daily gonadotropin dose, E2 level on day 2, and LH level on trigger day significantly decreased the number of mature oocytes retrieved and the number of cryopreservable blastocysts.

Prediction of risk factors for first trimester pregnancy loss in frozen-thawed good-quality embryo transfer cycles using machine learning algorithms.

PURPOSE: Can the risk factors that cause first trimester pregnancy loss in good-quality frozen-thawed embryo transfer (FET) cycles be predicted using machine learning algorithms? METHODS: This is a retrospective cohort study conducted at Sisli Memorial Hospital, ART and Reproductive Genetics Center, between January 2011 and May 2021. A total of 3805 good-quality FET cycles were included in the study. First trimester pregnancy loss rates were evaluated according to female age, paternal age, body mass index (BMI), diagnosis of infertility, endometrial preparation protocols (natural/artificial), embryo quality (top/good), presence of polycystic ovarian syndrome (PCOS), history of recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), severe male infertility, adenomyosis and endometriosis. RESULTS: The first trimester pregnancy loss rate was 18.2% (693/ 3805). The presence of RPL increased first trimester pregnancy loss (OR = 7.729, 95%CI = 5.908-10.142, P = 0.000). BMI, which is > 30, increased first trimester pregnancy loss compared to < 25 (OR = 1.418, 95%CI = 1.025-1.950, P = 0.033). Endometrial preparation with artificial cycle increased first trimester pregnancy loss compared to natural cycle (OR = 2.101, 95%CI = 1.630-2.723, P = 0.000). Female age, which is 35-37, increased first trimester pregnancy loss compared to < 30 (OR = 1.617, 95%CI = 1.120-2.316, P = 0.018), and female age, which is > 37, increased first trimester pregnancy loss compared to < 30 (OR = 2.286, 95%CI = 1.146-4,38, P = 0.016). The presence of PCOS increased first trimester pregnancy loss (OR = 1.693, 95%CI = 1.198-2.390, P = 0.002). The number of previous IVF cycles, which is > 3, increased first trimester pregnancy loss compared to < 3 (OR = 2.182, 95%CI = 1.708-2.790, P = 0.000). CONCLUSIONS: History of RPL, RIF, advanced female age, presence of PCOS, and high BMI (> 30 kg/m2) were the factors that increased first trimester pregnancy loss.

What to advise to patients with only one good quality blastocyst, PGT-A or not? Outcomes of 2064 cycles.

PURPOSE: To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) is beneficial for patients who have only one blastocyst available for biopsy or transfer. METHODS: This retrospective study was based on 1126 single blastocyst PGT-A and 938 non-PGT-A cycles, a total of 2064 ART cycles which resulted in a single good quality blastocyst in women between 20 and 45 years old. The PGT-A group had 225 single euploid embryo transfer cycles and the non-PGT-A group had 938 single blastocyst embryo transfer cycles. RESULTS: In the generalized linear mixed model (GLMM), female age and PGT-A variables were found to be significant variables on pregnancy outcomes. In the PGT-A cases, regardless of the effect of other variables, the probabilities of clinical pregnancy and live birth were found to be 3.907 and 3.448 fold higher respectively than in the non-PGT-A cases (p < 0.001). In non PGT-A cases, the probability of a total pregnancy loss was found to be 1.943 fold higher (p = 0.013). CONCLUSION: PGT-A in the presence of a single blastocyst significantly increases clinical pregnancy and live birth rates and decreases total pregnancy losses regardless of age. In addition, aneuploid embryo transfer cancelations prevent ineffective and potentially risky transfers.

Incidence of multiple births in relation to current regulations in Turkey regarding embryo transfer.

BACKGROUND: Before 2010, there were no regulations in Turkey regarding the number of embryos to be transferred in one cycle. In March 2010, regulations restricting this number were implemented by the Turkish Ministry of Health. These specify the transfer of a maximum of one embryo in the first and second cycles and a maximum of two embryos in subsequent cycles in women aged < 35, and a maximum of two embryos in women aged ≥35 in any one cycle. Our study evaluates the effect of these regulations. METHODS: This large retrospective single center study first evaluates the incidence of multiple pregnancies before and after the implementation of the 2010 regulations. Secondly, it compares the clinical outcomes of double blastocyst transfer (DBT) and single blastocyst transfer (SBT) performed in compliance with these regulations from 2014 onwards. RESULTS: After the introduction of the 2010 regulations, the multiple pregnancy rate decreased significantly from 37.9 to 15.7%. The singleton live birth rate increased significantly, whereas multiiple live birth rates significantly decreased (p = < 0.001). When the clinical outcomes of SBT and DBT performed in compliance with regulations from 2014 onwards were evaluated, in patients < 35 years, the multiple pregnancy rate decreased from 47.2% in the DBT group to 1.7% in the SBT group (p = < 0.001). In patients ≥35 years, in the DBT group, the twin birth rate was again high at 28.4%, whereas in the SBT group, it was only 1.8% (p = < 0.001). Importantly, there was no statistically significant difference in clinical pregnancy rates between these two groups. CONCLUSION: Turkish regulations have led to an encouragement of double embryo transfer (DET) as a routine practice, with many patients understanding it as an absolute right to have two embryos transferred. The results of our study suggest that, especially in the light of the success of blastocyst transfer, the Turkish regulations should be amended to limit the use of DET and encourage the use of single embryo transfer except in exceptional cases and particularly in women under 35 years old.

Mucinous endometrial cancer: Clinical study of the eleven cases.

OBJECTIVE: In this study, we analyzed surgico-pathologic factors of mucinous type endometrial carcinoma and examined its frequency of recurrence. METHODS: In this study, eleven cases, definitely diagnosed as pure mucinous type endometrium carcinoma between January 1993 and May 2013, were reviewed. RESULTS: Of 1640 women with endometrium carcinoma, 11 (0.67%) of them had a mucinous cell type. Mean age of the study group was 55 years. According to the FIGO 2009, 10 (90.9%) cases were evaluated as stage I and 1 (9.1%) as stage IIIC1. The presence of lymph node metastasis was noticed in only one (12.5%) of eight patients who underwent lymphadenectomy. In this case, metastasis was detected in the pelvic lymph node. Four patients underwent adjuvant therapy as pelvic radiotherapy. Median follow-up time was 50 months (range, 5-84). Recurrence was observed in one (9.1%) patient with stage IIIC1 endometrial cancer in 30 months after primary surgery. The site of recurrence was only in the upper abdominal region. CONCLUSION: Based on our study, mucinous endometrial carcinoma has good prognostic factors, and long term survival can be achieved surgically alone in patients with stage I.

Analysis of patients with stage IIIC endometrial cancer.

OBJECTIVE: We aimed to define the factors that are related to recurrence and survival in patients with stage IIIC endometrial carcinoma in this study. MATERIALS AND METHODS: A total of 147 patients who underwent staging surgery and had a diagnosis of stage IIIC1 to IIIC2 endometrial cancer according to the International Federation of Gynecology and Obstetrics 2009 were included. Patients whose data could not be obtained and patients with a diagnosis of uterine sarcoma and with synchronous tumors were excluded. RESULTS: Mean age of the patients was 58.6 years. Among these patients, 63 had stage IIIC1 and 84 had stage IIIC2 disease. Extrauterine spread was detected in 22% of the patients. Median number of paraaortic (PA) and pelvic lymph nodes removed were 16.5 and 38, respectively. Paraaortic and pelvic nodal involvements were detected in 84 patients and 125 patients, respectively. Radiotherapy was applied more commonly as an adjuvant therapy. Three-year progression-free survival (PFS) and 3-year disease-specific survival (DSS) were 65% and 84%, respectively. Seventy percent of the recurrences were outside the pelvis. Site of metastatic lymph nodes and the number of metastatic PA lymph nodes were associated with 3-year PFS and lymphovascular space invasion; site of metastatic lymph nodes and the presence of recurrence were associated with 3-year DSS in the univariate analysis. Although any surgicopathological factor was not related to 3-year PFS, only the presence of recurrence was an independent prognostic factor for a 3-year DSS in the multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002-0.183). CONCLUSIONS: The number of debulked metastatic lymph nodes and PA involvement were associated with recurrence in the univariate analysis. The presence of recurrence was the only independent prognostic factor detecting survival. Therefore, systematic lymphadenectomy involving PA lymph nodes instead of sampling should be performed in patients with high risk for nodal involvement in endometrial cancer.