Recryopreservation (recryo) is occasionally applied in clinical, while the underlying mechanism of impaired clinical outcomes after recryo remains unclear. In this study, frozen embryo transfer (FET) cycles of single blastocyst transfer in an academic reproductive medicine center were enrolled. According to the number of times blastocysts experienced cryopreservation, they were divided into the cryopreservation (Cryo) group and the Recryo group. Donated human blastocysts were collected and detected for mechanism exploration. It was found that recryo procedure resulted in impaired blastocyst developmental potential, including decreased implantation rate, reduced biochemical pregnancy rate, declined clinical pregnancy rate, higher early miscarriage rate, and lower live birth rate. Moreover, recryo led to impaired trophectoderm (TE) function, exhibiting lower human chorionic gonadotropin levels 12 days after FET. In addition, single-cell RNA sequencing showed that the expression of genes involved in cell adhesion and embryo development were altered. More specifically, activated endoplasmic reticulum (ER) pathway and induced apoptosis were further verified by immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay involving in the recryo procedure. In conclusion, recryo could interfere with the process of blastocyst implantation by impairing TE function, affecting blastocyst adhesion, activating ER stress pathway and inducing apoptosis. It provides caution to embryologists about the potential risk of recryopreservation.

OBJECTIVE: Do different timings of progesterone administration for day 5 and day 6 blastocysts affect the live birth rate (LBR) of artificial frozen embryo transfer (FET) cycles?
METHODS: This retrospective cohort study included 1362 patients who underwent artificial FET cycles. The effects of 6 and 7 days of progesterone administration prior to blastocyst transfer on clinical outcomes were compared in day 5 and day 6 blastocysts. Univariable and multivariable regression analyses were undertaken.
RESULTS: In all patients, LBR was comparable between the two groups (51.8% versus 47.9%, P = 0.165). For day 6 blastocysts, after adjusting for confounders, the 7-day progesterone regimen resulted in a significantly higher LBR (44.8% versus 36.4%, P = 0.039, adjusted OR = 1.494, 95% CI 1.060-2.106) and lower pregnancy loss rate (15.4% versus 25.2%, P = 0.031, adjusted OR = 0.472, 95% CI 0.260-0.856) compared with the 6-day progesterone regimen. For day 5 blastocysts, there were no significant differences in pregnancy outcomes between the two regimens, but the rate of low birthweight was higher with the 7-day progesterone regimen than with the 6-day progesterone regimen (13.9% versus 6.7%, P = 0.032).
CONCLUSIONS: In all blastocyst analyses, no difference in LBR was found between the 6- and 7-day progesterone regimens in artificial FET cycles. For day 6 blastocysts, LBR was significantly higher with the 7-day progesterone regimen than with the 6-day progesterone regimen, whereas for day 5 blastocysts, pregnancy outcomes were comparable between the two regimens.

OBJECTIVE: To evaluate whether the type of frozen embryo transfer (FET) regimen - ovulation-induced regimens vs. hormone replacement therapy regimens (HRT) - is associated with live birth rates and the risk of hypertensive diseases of pregnancy (HDP) in women with polycystic ovary syndrome (PCOS).
METHODS: All studies in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched using a combination of MeSH terms and keywords. Inclusion criteria included studies on women with a diagnosis of PCOS, utilization of FET, and reporting of pregnancy and/or obstetric outcomes. Studies were excluded if they were case series or conference abstracts or used other FET regimens. A random effects meta-analysis was performed. Primary outcomes include relative risk (RR) of live birth and HDP.
RESULTS: Eleven studies were included in the meta-analysis for the final review. Ovulation-induced regimens were associated with a higher live birth rate (8 studies, RR 1.14 [95% CI 1.08, 1.21]) compared to HRT regimens. The risk of HDP (3 studies RR 0.78 [95% CI 0.53, 1.15]) was not significantly different. Ovulation-induced regimens were associated with a lower miscarriage rate (9 studies, RR 0.67 [95% CI 0.59-0.76]). Rates of clinical pregnancy (10 studies, RR 1.05 [95% CI 0.99, 1.11]) and ectopic pregnancy (7 studies, RR 1.40 [95% CI 0.84, 2.33]), were not significantly different.
CONCLUSIONS: This SR/MA demonstrates that for women with PCOS, ovulation-induced FET regimens are associated with higher rates of live birth and lower rates of miscarriage compared to HRT regimens.

UNASSIGNED: This study investigated whether RNA-Seq-based endometrial receptivity test (rsERT)-which provides precision for the optimal hour of the window of implantation (WOI)-can improve clinical outcomes of frozen embryo transfer (FET) cycles in patients with a history of repeated implantation failure (RIF).
UNASSIGNED: Patients with a history of RIF who received at least one autologous high-quality blastocyst during the subsequent FET cycle were retrospectively enrolled and divided into two groups: rsERT and FET, comprising patients who underwent rsERT-guided pET (n=115) and standard FET without rsERT (n=272), respectively.
UNASSIGNED: In the rsERT group, 39.1% (45/115) of patients were receptive. rsERT patients showed a higher probability of achieving both positive human chorionic gonadotropin (63.5% vs. 51.5%, P=0.03) and clinical pregnancy (54.8% vs. 38.6%, P=0.003) rates. In subgroup analysis, rsERT patients with non-receptive results had higher clinical pregnancy rates than patients undergoing FET (58.6% vs. 38.6%, P=0.003). rsERT patients with receptive results guided by rsERT with a precise WOI time had higher, although non-significant, clinical pregnancy rates (48.9% vs. 38.6%, P=0.192) than patients who underwent standard-time FET.
UNASSIGNED: Hourly precise rsERT can significantly improve the probability of achieving clinical pregnancy in patients with RIF, especially in those with non-receptive rsERT results.

OBJECTIVE: To investigate whether operative hysteroscopy in addition to vacuum aspiration for the management of early pregnancy loss effectively increases the success rate of subsequent frozen embryo transfer.
METHODS: Propensity score-matched cohort study.
METHODS: Women with a miscarriage at 5 to 16 gestational weeks during an IVF cycle in Peking University Third Hospital from 2015 to 2022.
METHODS: Hysteroscopy plus vacuum aspiration versus conventional vacuum aspiration.
METHODS: Live birth rate in the subsequent frozen embryo transfer.
RESULTS: 347 women who underwent vacuum aspiration plus hysteroscopy and 2,562 women who underwent conventional vacuum aspiration were included in the analysis. After propensity score matching (1:1 ratio), 325 women were included in each group. Compared to women who underwent vacuum aspiration, those who underwent vacuum aspiration plus hysteroscopy were associated with a lower rate of live birth in the propensity-based matched cohort (22% vs 30%, aOR = 0.68 (0.47, 0.97)). Biochemical, clinical and multiple pregnancy rates were not significantly different, as was miscarriage rate. In the overall cohort, 11 women experienced surgery reintervention in the vacuum aspiration group (0.4%), while no one required surgery reintervention in the vacuum aspiration plus hysteroscopy group.
CONCLUSIONS: Women who underwent vacuum aspiration plus hysteroscopy might be associated with lower rates of live birth compared to those who underwent vacuum aspiration. Further studies are necessary to establish this relationship definitively.

UNASSIGNED: Non-previa placenta accreta spectrum (PAS) is associated with assisted reproductive technology (ART), particularly frozen embryo transfer during hormone replacement therapy (HRC-FET). We especially aimed to evaluate the prevalence and risk factors for non-previa PAS in HRC-FET pregnancies.
UNASSIGNED: Overall, 279 women who conceived through ART at three ART facilities and delivered at a single center were included in this retrospective study. Data regarding endometrial thickness at embryo transfer, previous histories, and type of embryo transfer-HRC-FET, frozen embryo transfer during a natural ovulatory cycle (NC-FET), and fresh embryo transfer (Fresh-ET)-were collected. Univariable logistic regression analyses were conducted.
UNASSIGNED: The prevalence of non-previa PAS was 27/192 (14.1%) in the HRC-FET group and 0 (0.0%) in both the NC-FET and Fresh-ET groups. Significantly high odds ratio [95% confidence interval] of non-previa PAS was associated with a history of artificial abortion (6.45 [1.98-21.02]), endometrial thickness <8.0 mm (6.11 [1.06-35.12]), resolved low-lying placenta (5.73 [2.13-15.41]), multiparity (2.90 [1.26-6.69]), polycystic ovarian syndrome (2.62 [1.02-6.71]), and subchorionic hematoma (2.49 [1.03-6.04]).
UNASSIGNED: A history of artificial abortion, endometrial thickness <8.0 mm, and resolved low-lying placenta may help in antenatal detection of a high-risk population of non-previa PAS in HRC-FET pregnancies.

OBJECTIVE: To determine whether polycystic ovary syndrome (PCOS) increases adverse pregnancy and birth outcomes in women undergoing frozen embryo transfer (FET).
METHODS: Retrospective cohort study. The PCOS group was matched 1:2 with the control group population using propensity score matching (PSM).
METHODS: During an 8-year period, 2,955 patients aged 20 to 40 years who underwent FET and delivered between January 2015 and December 2022 at the Reproductive Medical Center of Ruijin Hospital were evaluated for adverse pregnancy outcomes.
METHODS: None.
METHODS: All patients were assessed for specific pregnancy complications and birth outcomes, with a sub-group analysis conducted to compare PCOS patients with and without hyperandrogenism.
RESULTS: Women with PCOS demonstrated higher rates of gestational diabetes mellitus (24.9% vs. 16.4%; relative risk (RR) 1.51 [95% confidence interval (CI): 1.26-1.82]; P <0.001), gestational hypertension (12.2% vs. 8.9%; RR 1.37 [95% CI: 1.05-1.80]; P = 0.022), preterm prelabour rupture of membranes (7.0% vs. 3.6%; RR 1.92 [95% CI: 1.29-2.86]; P = 0.001), cervical length shortening (1.8% vs. 0.4%; RR 8.39 [95% CI: 1.56-12.49]; P = 0.002), large-for-gestational age (17.4% vs. 13.7%; RR 1.27 [95% CI: 1.02-1.57]; P = 0.032), and low birth weight (19.9% vs. 16.0%; RR 1.25 [95% CI: 1.02-1.52]; P = 0.030) in overall PSM analysis. Newborns of patients with PCOS had a higher risk of preterm birth < 37 weeks (10.5% vs. 6.6%; RR 1.59 [95% CI: 1.12-2.26]; P = 0.009) in singleton pregnancies. PCOS patients with hyperandrogenism showed a higher incidence of cervical length shortening (5.5% vs. 0.5%; adjusted odds ratio (AOR) 15.62 [95% CI: 2.25-108.48]; P = 0.005) compared to those without, after adjusting for relevant confounders.
CONCLUSIONS: PCOS increases the incidence of adverse pregnancy outcomes after FET cycles. Our study suggests women with PCOS may warrant further monitoring and additional counseling before and during pregnancy.

UNASSIGNED: The serum P concentrations are suggested to have an impact on pregnancy outcome. However there is no consensus about the optimal progesterone cut-off during the luteal phase. Few studies evaluated the effectiveness of a \"rescue protocol\" for low serum P concentrations and most of these studies used vaginal progesterone administration. There is paucity of data on the effectiveness of rescue protocol using intramuscular progesterone (IM-P) in frozen-thawed embryo transfer (FET).
UNASSIGNED: This study is a retrospective cohort study included 637 single or double blastocyst FETs with artificially prepared endometrium receiving 100 mg IM progesterone (P) after incremental estrogen treatment. Serum P concentrations were evaluated using blood samples obtained 117-119 hours after the first IM-P administration and 21 ± 2 hours after the last IM-P administration. Patients with serum P concentrations <20.6 ng/ml on the ET day were administrated 400 mg vaginal progesterone for rescue.
UNASSIGNED: Demographic and cycle characteristics were similar between patients receiving rescue vaginal P (embryo transfer (ET)-day P concentration < 20.6 ng/ml) and patients who did not need rescue vaginal P (ET-day P concentration ≥ 20.6 ng/ml). Clinical pregnancy, miscarriage, and live birth rates were similar between two groups: 52.9%(45/85) vs 59.6%(326/552), p=0.287; 11.1%(5/45) vs 14.1%(46/326), p=0.583; and 47.1%(40/85) vs 50.7%(280/552), p=0.526, respectively. Logistic regression analysis revealed that the female age (p = 0.008, OR=0.942, 95% CI = 0.902-0.984) and embryo quality (ref: good quality for moderate: p=0.02, OR=0.469, 95% CI =0.269-0.760; for poor: p=0.013, OR= 0.269, 95% CI = 0.092-0.757) were independent variables for live birth. Following rescue protocol implementation, ET-day P concentration was not a significant predictor of live birth.
UNASSIGNED: Rescue vaginal P administration for low ET day serum P concentrations following IM-P yields comparable live birth rates.

BACKGROUND: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis.
METHODS: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses.
RESULTS: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis.
CONCLUSIONS: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms.
METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET).
RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups.
CONCLUSIONS: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.