Enhancing endometrial receptivity in FET cycles: exploring the influence of endometrial and subendometrial blood flow along with endometrial volume.

Introduction: Fetal health and a receptive and healthy endometrium are two essential factors in achieving successful implantation. If the endometrium is unreceptive, postponing the transfer cycle to a suitable time can enhance the chances of pregnancy. This study aims to assess the impact of endometrial and sub-endometrial blood flows measured by Doppler ultrasound, as well as endometrial volume, on endometrial receptivity in frozen embryo transfer (FET) cycles. Methods: 112 patients with a mean age of 33.93 ± 4.93 years underwent in vitro fertilization (IVF). Serum ß-hCG level was used to confirm pregnancy, and among the participants, 50 (44.6%) achieved pregnancy after IVF. Results: The study results revealed a significant difference in endometrial blood flow between the pregnant and non-pregnant groups, with a higher pregnancy rate observed in participants exhibiting multi-focal and spare endometrial blood flows (p < 0.05). Furthermore, there was a notable association between endometrial blood flow and pregnancy outcome, as indicated by higher ongoing pregnancy rates in those with multi-focal and spare endometrial blood flows (p < 0.05). However, no significant differences were observed in endometrial variables such as volume, length, width, thickness, and pattern between the pregnant and non-pregnant groups. Additionally, contextual parameters showed no significant relationship with pregnancy outcome (p > 0.05). The study also found that endometrial measurement indices did not have a significant impact on pregnancy outcomes, with no significant differences observed between the groups (p > 0.05). Conclusion: In conclusion, endometrial blood flow is crucial for a successful pregnancy after IVF, while the predictive value of the endometrial volume is limited for pregnancy outcomes.

Reproductive outcomes with delayed blastocyst development: the clinical value of day 7 euploid blastocysts in frozen embryo transfer cycles.

Embryos of optimal development reach blastocyst stage 116 ± 2 h after insemination. Usable D7 blastocysts represent nearly 5% of embryos in IVF with acceptable pregnancy and live birth rates, however data are still limited. Therefore, this study aimed to analyze the ongoing pregnancy rate (OPR) of D7 blastocysts in single euploid frozen embryo transfer (FET) cycles. An observational study was performed including 1527 FET cycles with blastocysts biopsied on D5 (N = 855), D6 (N = 636) and D7 (N = 36). Blastocysts were classified as good (AA/AB/BA), fair (BB) or poor (AC/BC/CC/CA/CB) (Gardner scoring). FETs were performed in natural cycles (NC) or hormone replacement therapy (HRT) cycles. Patient's age differed significantly between D5, D6 and D7 blastocysts FET cycles (33.2 ± 5.6, 34.4 ± 5.3 and 35.9 ± 5.2, P < 0.001). OPRs were higher when D5 euploid blastocysts were transferred compared with D6 and D7 (56.0% vs. 45.3% and 11.1%, P < 0.001). Poor quality blastocysts were predominant in D7 blastocyst FET cycles (good quality: 35.4%, 27.2%, 5.6%; fair quality: 52.1%, 38.5%, 11.1%; poor quality: 12.5%, 34.3%, 83.3%, P < 0.001 for D5, D6 and D7 blastocysts; respectively). OPR was significantly reduced by D7 blastocyst FETs (OR = 0.23 [0.08;0.62], P = 0.004), patient's BMI (OR = 0.96 [0.94;0.98], P < 0.001), HRT cycles (OR = 0.70 [0.56;0.88], P = 0.002) and poor quality blastocysts (OR = 0.33 [0.24;0.45], P < 0.001). OPR is significantly reduced with D7 compared with D5/D6 euploid blastocysts in FET cycles. The older the patient, the more likely they are to have an FET cycle with blastocysts biopsied on D7, therefore culturing embryos until D7 can be a strategy to increase OPR outcomes in patients ≥38 years.

Multicentre study on rates and reasons for treatment discontinuation in patients with remaining cryopreserved embryos.

RESEARCH QUESTION: What is the discontinuation rate among patients with remaining cryopreserved embryos in Belgium and what are the reasons for discontinuation? DESIGN: Multicentre, cross-sectional study across 11 Belgian fertility clinics. Patients were eligible (n = 1917) if they had previously undergone an unsuccessful fresh embryo transfer (fresh group) or frozen embryo transfer (FET) (in-between group) and did not start a subsequent FET cycle within 1 year despite having remaining cryopreserved embryos. The denominator was all patients with embryos cryopreserved during the same period (2012-2017) (n = 21,329). Data were collected through an online anonymous questionnaire. RESULTS: The discontinuation rate for patients with remaining cryopreserved embryos was 9% (1917/21329). For the final analysis, 304 completed questionnaires were included. The most important reasons for discontinuing FET cycles were psychological (50%) and physical (43%) burden, effect on work (29%), woman's age (25%) and effect on the relationship (25%). In 69% of cases, the patient themselves made the decision to delay FET treatment. In 16% of respondents, the decision to delay FET was determined by external factors: treating physician (9%), social environment (4%), close family (3%) and society (3%). Suggested improvements were psychological support before (41%), during (51%) and after (51%) treatment, as well as lifestyle counselling (44%) and receiving digital information (43%). CONCLUSIONS: The discontinuation rate is remarkably high in patients with remaining cryopreserved embryos who have a good prognosis. Respondents stressed the need to improve the integration of psychological and patient-tailored care into daily assisted reproductive technology practice.

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.

Comparison of the prevalence and severity of nausea and vomiting in the first trimester between singleton pregnancies conceived from stimulated in vitro fertilization and frozen embryo transfer cycles.

OBJECTIVE: The objective of this prospective study is to compare the prevalence and severity of nausea and vomiting in the first trimester between singleton pregnancies conceived from stimulated in vitro fertilization (IVF) and frozen embryo transfer cycles (FET). METHODS: All women were recruited at 6 weeks gestation and filled in the modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) to document whether they had any experience of nausea and vomiting weekly till 12 weeks gestation. The primary outcome was the prevalence of nausea and vomiting and the secondary outcomes included severity of nausea and vomiting and pregnancy outcomes. RESULTS: A total of 360 pregnant women were recruited and 171 were in the stimulated IVF group and 189 in the FET group. The overall return rate was 82.2% (81.8% in the stimulated IVF group and 82.5% in the FET group). Nausea and vomiting were worse in the FET group compared with the IVF group. There were significantly more women who felt nauseated or sick in the FET group (p value = 0.032 for week 11 and p value = 0.046 for week 12); significantly more women with a longer duration of nausea in the FET group (p value = 0.044 for week 7 and p value = 0.030 for week 8); significantly more women with more vomiting in a day in the FET group (p value = 0.042) and significantly more women with retching or dry heaves in the FET group (p value = 0.030 for week 8 and p value = 0.028 for week 11). CONCLUSION: Nausea and vomiting were significantly more prevalent and severe in the FET group when compared with the stimulated IVF group.

Does Adenomyosis Influence ICSI Clinical Outcome? A Systematic Analysis and Impact of GnRH Agonist Pretreatment for Women with Adenomyosis in ICSI-FET Cycle: A Retrospective Cohort Study.

Objective: To evaluate the impact of adenomyosis on pregnancy outcome in ICSI/FET cycles and the beneficial effect of GnRH agonist pretreatment, conservative surgery or combination therapy on pregnancy outcome. Materials and Methods: This is a retrospective cohort study where 613 ICSI cycles done in the period from Jan 2018 to Dec 2020 in Sudha infertility centre, Erode were analyzed. Study populations include 235 women with adenomyosis undergoing ICSI/FET cycle. Result: Overall, the outcome in terms of clinical pregnancy rate, miscarriage rate, live birth date and ongoing pregnancy rate was lower in women with adenomyosis following ICSI/FET cycles. We found significant improvement in clinical pregnancy rate who had pretreatment with GnRH agonist, conservative surgery or combination therapy. Conclusion: Adenomyosis as such has detrimental effect on ICSI clinical outcome. Pretreatment with GnRH agonist and conservative surgery and GnRH agonist long protocol could be beneficial. Further large scale prospective comparative studies are needed to confirm this result.

Endometrial preparation for vitrified-warmed embryo transfer with or without GnRH-agonist pre-treatment in patients with polycystic ovary syndrome: a randomized controlled trial.

RESEARCH QUESTION: What are the effects on pregnancy outcome in patients with polycystic ovary syndrome (PCOS) in endometrial preparation cycles for vitrified-warmed embryo transfer with or without gonadotrophin releasing hormone (GnRH) agonist pre-treatment? DESIGN: A total of 212 patients with PCOS referred to Royan Institute, Tehran, Iran, between 20 August 2017 to 20 June 2018 were included. The patients were randomly assigned to receive oestradiol after downregulation with GnRH agonist (group A) or without GnRH agonist down-regulation (group B). RESULTS: A total of 188 patients with PCOS completed the trial, 93 patients in group A and 95 patients in group B. Basal oestradiol and LH levels were significantly higher in group B (26.66 versus 41.61, P = 0.01 and 0.93 versus 5.33, P < 0.0001, respectively). Clinical pregnancy rates were not significantly different in both groups (31.2% versus 33.7%). Similarly, no significant differences were found between groups A and B in miscarriage (9.7% versus 11.6%), implantation (0.58 versus 0.51) and live birth (21.7% versus 22.1%) rates and for medical complications during pregnancy and neonatal anomalies. CONCLUSIONS: Our findings indicate that endometrial preparation for frozen-thawed embryo transfer with and without ovarian suppression by GnRH agonist provides similar results.

Endometrial and Subendometrial Vascularity by Three-Dimensional (3D) Power Doppler and Its Correlation with Pregnancy Outcome in Frozen Embryo Transfer (FET) Cycles.

PURPOSE OF THE STUDY: To study the role of endometrial and subendometrial blood flow measured by 3D power Doppler as predictors of pregnancy in frozen embryo transfer (FET) cycles. METHODS: A hospital-based prospective study of two hundred and twenty-one (221) women undergoing FET cycles with a triple-line endometrium ≥7 mm on day 14 endometrial and subendometrial blood flow was assessed using 3D power Doppler, and various indices endometrial volume, subendometrial volume and their vascularisation index (VI), flow index (FI) and vascularisation flow index (VFI) were obtained and compared between the pregnant and the non-pregnant group. Primary outcome was clinical pregnancy. RESULTS: Out of 221 women, 97(43.89 %) became pregnant, while 124 (56.10 %) failed to become pregnant. The endometrial volume was comparable between the two groups. Endometrial VI, FI and VFI were significantly higher in the pregnant as compared to the non-pregnant group. There was a significant difference in subendometrial VI and VFI between the two groups, but FI was similar. CONCLUSIONS: Endometrial and subendometrial vascularity by 3D power Doppler can be a useful parameter in predicting pregnancy in FET cycles.

Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles?

OBJECTIVE: To compare the effect of progesterone (P) on the day of trigger in fresh assisted reproduction technology (ART) transfer cycles versus its effect on subsequent frozen embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: Large private ART practice. PATIENT(S): Fresh autologous and FET cycles from 2011-2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): A paired analysis of patients who underwent both a fresh transfer and subsequent FET cycle and an unpaired analysis of data from all fresh transfer cycles and all FET cycles were performed. We analyzed 1,216 paired and 4,124 unpaired cycles, and P was negatively associated with birth in fresh but not FET cycles in all analyses. Interaction testing of P and cycle type indicated P had a different association with birth in fresh versus FET cycles. When P was ≥ 2 ng/mL at the time of trigger, live birth was more likely in FET versus fresh cycles in the paired analysis (47% vs. 10%), in the unpaired analysis (51% vs. 14%), and in unpaired, good blastocyst only transfer subgroup (51% vs. 29%). Live birth was similar in FET cycles, with P ≥ 2 ng/mL versus P < 2 ng/mL (51% vs. 49%). Conversely, live birth was lower in fresh cycles, with P ≥ 2 ng/mL versus P <2 ng/mL (15% vs. 45%). CONCLUSION(S): Elevated P levels on the day of trigger during the initial fresh cycle were negatively associated with live birth in the fresh transfer cycles but not in subsequent FET cycles. Freezing embryos and performing a subsequent FET cycle ameliorates the effect of elevated P on live-birth rates.

Delivery rates after elective single cryopreserved embryo transfer related to embryo survival.

OBJECTIVE: The objective of this study was to assess if eSCET (elective Single Cryopreserved Embryo Transfer) outcome is related to blastomere survival rate. The final objective was to avoid multiple pregnancies and offer the best chances to women to achieve pregnancy even during their frozen-thawed embryo transfer (FET) cycles. STUDY DESIGN: Patients were included in this prospective observational study if they met the following criteria: (i) women age <37 years old; (ii) IVF of ICSI cycle rank ≤2, (iii) eSET proposed during fresh embryo transfer cycle and (iv) ≥1 good quality cryopreserved embryos available (<20% fragmentation and 4-5 blastomeres at day-2 or 7-9 blastomeres at day-3). Live birth rates (LBR) were compared into eSCET groups according to embryo survival (partially damaged or intact transferred embryo). RESULTS: We observed among selected patients, that partial loss of blastomeres (1 blastomere for day-2 embryos, 1 or 2 blastomeres for day-3 embryos) following FET cycles did not affect LBR compared with intact embryo. CONCLUSION: These results underline the relevance of eSCET as a strategy to reduce multiple pregnancies frequency without reducing LBR.