Progesterone in frozen embryo transfer cycles: assays, circulating concentrations, metabolites, and molecular action.

Programmed or medicated frozen embryo transfer cycles rely on exogenous progesterone (P) administration to prepare the endometrium for implantation and maintain pregnancy. Presently, the optimal route and dose of P replacement for frozen embryo transfer are not known. In addition, there is a paucity of data and insufficient understanding regarding the metabolism and actions of P in implantation and pregnancy maintenance. In the present review, we discuss how different P assay methodologies affect the determination of P thresholds for implantation and pregnancy maintenance. In addition, we discuss the importance of free P and its regulation in the endometrium and show the complexity of molecular signaling that is required for P-dependent endometrial receptivity. We concluded that future studies should focus on defining accurate circulating and endometrial P concentrations, both for total and free P, and how these concentrations correlate with endometrial receptivity and clinical outcomes.

GnRH agonist pretreatment for frozen embryo transfer among women with polycystic ovary syndrome: a narrow systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Frozen embryo transfer (FET) is usually recommended for women with polycystic ovary syndrome (PCOS) undergoing In vitro fertilization (IVF). While there is no consensus as to the optimal protocol of endometrial preparation for FET. The effect of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment for FET among women with PCOS remains controversial. PURPOSE: We intend to explore whether GnRH-a pretreatment could improve clinical outcomes for women with PCOS undergoing FET. METHODS: PubMed, Embase, ClinicalTrials.gov, Cochrane Library, and Web of Science were searched up to May 16, 2024. Eligible studies involved patients with PCOS undergoing FET and receiving GnRH-a pretreatment for endometrial preparation, with artificial cycle (AC) as the control therapy. Only randomized controlled trials (RCTs) published in Chinese and English were included. Data extraction was performed independently by two authors. Effect was quantified using odd ratios (ORs) with 95% confidence intervals (CIs) using random-effect models with the Mantel-Hansel (M-H) method in Revman software. Quality of outcomes was evaluated using the GRADEpro system. Primary outcomes contained the clinical pregnancy rate, miscarriage rate, and live birth rate. Secondary outcomes included the incidence of preterm labor and gestational diabetes mellitus (GDM). RESULTS: Ninety-seven records were initially retrieved, with 21 duplicates and 65 articles excluded after title and abstract screening. Seven studies were excluded due to retrospective design, leaving three RCTs with 709 participants. Among them, 353 received GnRH-a pretreatment as the intervention group and 356 received AC as the control group. No significant differences were observed in the clinical pregnancy rate (OR 1.09, 95% CI 0.75 to 1.56, P = 0.66), miscarriage rate (OR 0.73, 95% CI 0.28 to 1.90, P = 0.52), live birth rate (OR 0.87, 95% CI 0.61 to 1.25, P = 0.46), and the risk of preterm labor (OR 1.45, 95% CI 0.79 to 2.65, P = 0.23) and GDM (OR 0.73, 95% CI 0.37 to 1.48, P = 0.39) between the two groups. CONCLUSIONS: In this meta-analysis, GnRH-a pretreatment does not confer any advantages and appears unnecessary for women with PCOS undergoing FET. Additional RCTs should focus on maternal complications and the health of offspring.

Assisted reproductive technology and prolonged third stage of labour: a multicentre study in Japan.

RESEARCH QUESTION: What are the risk factors for a prolonged third stage of labour, closely related to postpartum haemorrhage, and what is the effect of assisted reproductive technology (ART) on the third stage of labour? DESIGN: Clinical data of women who delivered vaginally at term at 12 primary maternity hospitals in Japan (2010-2018) (n = 25,336) were obtained; 1148 (4.5%) conceived through ART and 2246 (8.9%) through non-ART treatments. The risk of a prolonged third stage of labour (defined as ≥20 min) was evaluated by univariable and multivariable regression analyses. Adjusted odds ratios (aOR) of a prolonged third stage of labour were evaluated, stratified by the type of ART, with natural conception as a reference. RESULTS: Multivariable analysis showed that pregnancy achieved through ART (aOR 4.38, 95% CI 3.12 to 6.15), history of spontaneous miscarriage (OR 1.40, 95% CI 1.06 to 1.84) and prolonged labour (OR 1.52, 95% CI 1.09 to 2.12) were identified as independent risk factors. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC-FET) and blastocyst-stage embryo transfer were significantly associated with a prolonged third stage of labour (aOR 4.07, 95% CI 2.75 to 6.04, aOR 4.11, 95% CI 2.58 to 6.57 and aOR 2.13, 95% CI 1.15 to 3.95, respectively). No significant difference was observed in the duration of third stage of labour between natural conception and non-ART treatment (P = 0.61). CONCLUSION: Pregnancy achieved through ART, particularly FET, HRC-FET and blastocyst-stage embryo transfer, was a significant risk factor for a prolonged third stage of labour.

Progesterone-modified natural cycle preparation for frozen embryo transfer.

RESEARCH QUESTION: Is there any difference in clinical outcomes between the progesterone-modified natural cycle (P4mNC) and hormone replacement therapy (HRT) endometrial preparation protocols after single euploid blastocyst frozen embryo transfer (FET) cycles? DESIGN: A retrospective cohort study was performed at a single, private, high-volume fertility centre. Patients who underwent single euploid blastocyst FET between January 2017 and December 2019 were included. A total of 1933 FET cycles were reviewed, and 723 FET cycles from 548 patients met the inclusion criteria. Two groups were compared according to endometrial preparation: 327 P4mNC-FET and 396 HRT-FET cycles. The primary outcome was the live birth rate. The secondary outcomes included the clinical pregnancy rate and the miscarriage rate. RESULTS: There were no differences in the clinical pregnancy rate (50.2% versus 47.0%, P = 0.688), miscarriage rate (9.8% versus 14.5%, P = 0.115) and live birth rate (45.0% versus 39.6%, P = 0.331) between the P4mNC-FET and HRT-FET groups after covariate adjustments. CONCLUSIONS: There were no differences in the clinical outcomes between the P4mNC-FET and HRT-FET cycles. These results indicate that P4mNC-FET cycles produce clinical outcomes comparable to those of more traditional HRT-FET while allowing greater flexibility in the timing of embryo transfer.

Let's not abandon programmed frozen embryo transfers yet: a countercurrent perspective.

The countercurrent opinion given in this paper is that the optimal management of frozen embryo transfers (FET) is not a one-size-fits-all matter, but rather one that should be decided after considering all the various parameters and options. This choice should notably encompass patients' individual characteristics - including variable risks of obstetric complications - and weigh out the respective advantages of each FET option in each case. While there may be real advantages for natural-cycle FET in many cases, these need to be balanced against both practical and clinical issues. Contrary to several prevailing, sometimes loudly expressed suggestions, there is not a one single effective approach when it comes to choosing a mode of scheduling FET.

A Case Report of Successful Live Pregnancy Following Embryo Transfer in a Thin Endometrium.

Managing a thin endometrium is a common challenge in assisted reproductive treatments. The thickness of the endometrium is crucial for embryo implantation, with younger patients generally having higher success rates even with a thinner lining. A frozen embryo transfer cycle often allows for a more thorough assessment of the endometrium compared to a fresh transfer. We present a case of a 36-year-old woman who presented to our fertility center with primary infertility for six years. Despite having regular menstrual cycles, her endometrial thickness consistently measured between 5 and 6.0 mm on ultrasonography. She underwent ovarian stimulation using an antagonist protocol, resulting in the retrieval of oocytes and the freezing of three embryos. However, three frozen embryo transfer cycles were cancelled due to inadequate endometrial thickness (ranging from 4.3 to 5.2 mm). In the fourth cycle, she was treated with gonadotropins with the goal of achieving two to three follicles and improved endometrial thickness. Triggering was performed on day 15, followed by the transfer of one frozen embryo at an endometrial thickness of 5.7 mm. Her beta-human chorionic gonadotropin (hCG) level was positive, with an initial value of 136.9 mIU/mL, and she subsequently delivered a healthy baby. This case highlights the challenges of managing a thin endometrium in assisted reproductive techniques. Through persistent efforts and tailored treatment protocols, a successful live birth was achieved despite recurrent thin endometrium. This case underscores the importance of individualized treatment strategies in overcoming endometrial challenges in infertility treatments.

Personalized embryo transfer guided by rsERT with hourly precision improves pregnancy outcomes in patients with a receptive window of implantation: a pilot study.

PURPOSE: To investigate whether personalized embryo transfer (pET) predicted by a modified RNA-sequencing-based endometrial receptivity test (rsERT) model can improve intrauterine pregnancy rate (IPR) in patients with a receptive window of implantation (WOI). DESIGN: A retrospective pilot study was conducted in the Center for Reproductive Medicine, Central South University, from January 2018 to December 2023. A total of 524 patients with receptive WOI results from rsERT were assigned into two groups based on whether they underwent conventional embryo transfer (conventional ET) or pET. Patients in the conventional ET were matched with those in the pET group at a 1:1 ratio using propensity score matching (PSM). RESULTS: Before PSM, the IPR (55.73% vs. 46.19%, P = 0.032) and implantation rate (IR) (47.51% vs. 34.03%, P = 0.000) in the pET group were significantly higher than that in the conventional ET group. However, the number and types of transferred embryos differed significantly between the two groups. After adjusting for confounding factors, IPR (57.38% vs. 44.81, P = 0.016) and IR (46.81% vs. 33.10%, P = 0.001) remained significantly higher in the pET group compared to the conventional ET group. The implantation failure rate was significantly lower in the pET group compared to controls (42.62% vs. 55.19%, P = 0.016). Additionally, the multiple-pregnancy rate was significantly higher in the pET group compared to the conventional ET group (10.29% vs. 1.68%, P = 0.001). CONCLUSIONS: Women with receptive WOI results could benefit from the receptivity-timed pET predicted by the newly refined rsERT. These findings provide a basis for future research in precision medicine for embryo transfer.

Congenital heart defects in children born after assisted reproductive technology: a CoNARTaS study.

BACKGROUND AND AIMS: Children born after assisted reproductive technology (ART) have worse perinatal outcomes compared with spontaneously conceived children. This study investigates whether children conceived after ART have a higher risk of congenital heart defects (CHDs) compared with children born after spontaneous conception (SC). METHODS: All 7 747 637 liveborn children in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1987-2015), where 171 735 children were conceived after ART, were included. National ART and medical birth registry data were cross-linked with data from other health and population registries. Outcomes were major CHDs, severe CHDs, 6 hierarchical CHD lesion groups, and 10 selected major CHDs, diagnosed prenatally or up to 1 year of age (Denmark, Finland, and Sweden) and prenatally or at birth (Norway). The association between ART and CHDs was assessed with multivariable logistic regression analysis, with adjustment for available confounders. RESULTS: Major CHDs were detected in 3159 children born after ART (1.84%) and in 86 824 children born after SC [1.15%; adjusted odds ratio (AOR) 1.36; 95% confidence interval (CI) 1.31-1.41]. Risk was highest in multiples, regardless of conception method. Severe CHDs were detected in 594 children born after ART (0.35%) and in 19 375 children born after SC (0.26%; AOR 1.30; 95% CI 1.20-1.42). Risk was similar between ICSI and IVF and between frozen and fresh embryo transfer. CONCLUSIONS: Assisted reproductive technology-conceived children have a higher prevalence of major CHDs, being rare, but severe conditions. The absolute risks are, however, modest and partly associated with multiple pregnancies, more prevalent in ART.

Effect of ART treatments on maternal and neonatal outcomes in singleton live births: A large-scale retrospective cohort study.

Background: The increased risk of pregnancy complications in the ART population has been reported, but the source of these risks remains controversial. The study aims to evaluate the association between ART treatments and patient characteristics with maternal and neonatal outcomes. Methods: This was a retrospective analysis of 45,159 singleton pregnant women at a hospital between 2018 and 2021. The maternal and neonatal outcomes included pregnancy-induced hypertension (PIH), preeclampsia (PE), gestational diabetes mellitus (GDM), placental abruption (PA), placenta accreta spectrum (PAS), postpartum hemorrhage (PPH), cesarean section, iatrogenic and spontaneous preterm birth, small for gestational age (SGA), low birth weight (LBW), macrosomia, and birth defects. We assessed the outcomes among the fresh embryo transfer (ET), frozen embryo transfer (FET), and spontaneous conception (SC) groups. Potential risk factors were further analyzed in the ART population. Results: FET was associated with higher risks for PIH (SC: AOR, 1.97(1.51-2.57); fresh ET: AOR, 1.68(1.03-2.72)), PE (SC: 2.28(1.86-2.80); fresh ET: AOR, 1.61(1.11-2.33)), PAS (SC: AOR, 3.89(3.39-4.46); fresh ET: AOR, 2.23(1.70-2.92)), PPH (SC: AOR, 3.46(2.76-4.34)); fresh ET: 2.09(1.39-3.14)), and macrosomia (SC: 1.53(1.25-1.86); fresh ET: AOR, 2.87(1.89-4.35). Fresh ET was associated with higher risks for PA (SC: AOR, 2.19(1.51-3.18); FET: AOR, 0.39(0.17-0.90)), SGA (SC: AOR, 1.56(1.06-2.31), FET: AOR, 0.42(0.19-0.91)), and LBW (SC: AOR, 2.24(1.82-2.77), FET: AOR, 0.63 (0.44-0.89)), and fresh ET is an independent risk factor for PA and SGA. Furthermore, the risk of GDM was associated with the biological characteristic of low-fertility patients. Conclusions: Embryo status (fresh or frozen) is a key factor affecting the maternal and neonatal outcomes in ART treatments, while biological characteristics of infertile patients also play a certain role.

Embryo retention and live birth in frozen embryo transfer cycles: a cohort study.

OBJECTIVE: To study the effect of embryo retention in the transfer catheter on pregnancy outcome in frozen embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SUBJECTS: This retrospective study involved a total of 39,118 women who underwent FET cycles at a tertiary-care academic medical from January 2016 to December 2022. EXPOSURE: Women were divided into control group (n=38,933) and embryo retention group (n=185). The women in the embryo retention group were propensity score matched with those in the control group at a 1:4 ratio. MAIN OUTCOME MEASURES: The primary outcome was live birth. The second outcomes were biochemical pregnancy, clinical pregnancy, miscarriage, and ectopic pregnancy. RESULTS: The overall incidence of embryo retention in the transfer catheter was 0.47% (185/39,118). The pregnancy outcome in the embryo retention group after propensity score matching was comparable to that before propensity score matching, with a reduced likelihood of biochemical pregnancy (odds ratio [OR] 0.83, 95% confidence interval [CI], 0.72-0.95; P=0.007), clinical pregnancy (OR 0.81, 95% CI, 0.69-0.96; P=0.017), and live birth (OR 0.80, 95% CI, 0.66-0.97; P=0.026). In addition, the birth weight in the embryo retention group was higher compared to the control group (P=0.021). However, no differences were observed in terms of miscarriage, ectopic pregnancy, cesarean delivery, as well as gestational age both before and after propensity score matching. CONCLUSION: Embryo retention in the transfer catheter decreases the chance of biochemical pregnancy, clinical pregnancy, and live birth in FET cycles.

Improvement of endometrial thickness and in vitro fertilization outcomes in patients with Asherman's refractory endometrium using autologous mesenchymal stem cells from the stromal vascular fraction.

OBJECTIVE: Patients with Asherman's Syndrome (AS) and an endometrial thickness (EMT) less than 7 mm are infertile women with suboptimal endometrium due to uterine scarring or endometrial atrophy. This study aimed to examine the effect of intrauterine injections of adipose-derived mesenchymal stem cells (ADMSC) from the Stromal Vascular Fraction (SVF) of adipose tissue on EMT and in vitro fertilization (IVF) outcomes: which are improvements in EMT and pregnancy rates. METHODS: This double-arm retrospective study included 41 AS patients with hysteroscopic adhesiolysis. Twenty-one patients with AS refractory endometrium (Group 2) were given ADMSC to improve EMT, and 20 non-treated, age-matched patients served as controls (Group 1). For Group 2, SVF was isolated from 15 ml of adipose tissue and transmyometrial injected into the patient's uterine cavity. For all patients, EMT was examined using ultrasound before embryo transfer. RESULTS: In Group 2, after ADMSC treatment, EMT significantly improved (3.2 ± 1.8 mm, P<0.001). Afterward, three patients spontaneously became pregnant, and eighteen underwent frozen embryo transfer. A significant increase in implantation (66.7% vs. 4.8%, P = 0.002) and live birth rates (0.0% vs. 47.6%, P = 0.001) were recorded. No significant difference was observed in EMT, cycle implantation, or clinical pregnancy between the two groups, but the live birth rate in Group 2 after ADMSC treatment was higher than in Group 1. CONCLUSION: The results demonstrate that autologous intrauterine ADMSC injection can improve EMT, implantation, and pregnancy rates in AS patients with refractory endometrium. This research underscores the life-changing potential of autologous ADMSC treatment for patients with refractory endometrium, providing a promising avenue for future treatments.

Impact of different progesterone timings on live birth rates for blastocyst frozen embryo transfer cycles.

RESEARCH QUESTION: 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? DESIGN: 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.

Recryopreservation impairs blastocyst implantation potential via activated endoplasmic reticulum stress pathway and induced apoptosis.

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.

Perinatal outcomes are similar in programmed and modified natural frozen embryo transfer cycles.

RESEARCH QUESTION: How do perinatal outcomes differ between programmed and modified natural frozen embryo transfer (FET) cycles? DESIGN: A retrospective cohort study of 839 patients was undertaken at a university-affiliated fertility practice undergoing single blastocyst FET cycles between 2014 and 2020. The primary outcome measures were the incidence of ischaemic placental disease, small for gestational age (SGA), intrauterine growth restriction (IUGR), preterm delivery, birth weight, and mode of delivery. RESULTS: When comparing programmed FET cycles with modified natural FET cycles, there was no increased risk of ischaemic placental disease [adjusted risk ratio (aRR) 0.83, 95% CI 0.61-1.14], IUGR (unadjusted RR 0.50, 95% CI 0.14-1.77), preterm delivery (aRR 1.11, 95% CI 0.72-1.70) or SGA (aRR 0.69, 95% CI 0.40-1.19). Patients in the programmed cohort had increased risk of caesarean delivery (aRR 1.32, 95% CI 1.10-1.59). These outcomes were unchanged when limited to patients undergoing their first FET cycle. CONCLUSIONS: There are no differences in patient and neonatal clinical outcomes between programmed and modified natural FET cycles. The choice of FET protocol should remain a shared decision between patient and provider.

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study.

RESEARCH QUESTION: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring? DESIGN: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors. RESULTS: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544). CONCLUSION: This study suggests that children born through FET have increased risk of developing food allergy in early childhood.

Transcriptomic Analysis of Vitrified-Warmed vs. Fresh Mouse Blastocysts: Cryo-Induced Physiological Mechanisms and Implantation Impact.

Blastocyst vitrification has significantly improved embryo transfer methods, leading to higher implantation success rates and better pregnancy outcomes in subsequent frozen embryo transfer cycles. This study aimed to simulate the transcriptional changes caused by vitrifying human blastocysts using mouse blastocysts as a model and to further investigate these changes' effects. Utilizing a human vitrification protocol, we implanted both vitrified and fresh embryos into mice. We observed the implantation success rates and performed transcriptomic analysis on the blastocysts. To validate the results from messenger RNA sequencing, we conducted reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to measure the expression levels of specific genes. Based on mRNA profiling, we predicted the microRNAs responsible for the regulation and used qPCR basic microRNA assays for validation. Our observations revealed a higher implantation success rate for vitrified embryos than fresh embryos. Transcriptomic analysis showed that vitrified-warmed blastocysts exhibited differentially expressed genes (DEGs) primarily associated with thermogenesis, chemical carcinogenesis-reactive oxygen species, oxidative phosphorylation, immune response, and MAPK-related signaling pathways. RT-qPCR confirmed increased expression of genes such as Cdk6 and Nfat2, and decreased expression of genes such as Dkk3 and Mapk10. Additionally, gene-microRNA interaction predictions and microRNA expression analysis identified twelve microRNAs with expression patterns consistent with the predicted results, suggesting potential roles in uterine epithelial cell adhesion, trophectoderm development, invasive capacity, and immune responses. Our findings suggest that vitrification induces transcriptomic changes in mouse blastocysts, and even small changes in gene expression can enhance implantation success. These results highlight the importance of understanding the molecular mechanisms underlying vitrification to optimize embryo transfer techniques and improve pregnancy outcomes.

Comparison of Clinical Outcomes in the Slow-Developing Blastocysts With or Without Preimplantation Genetic Testing-Aneuploidy on Day 6 in the Frozen-Thawed Cycle.

OBJECTIVES: This study investigated the potential of the slow-developing blastocysts using preimplantation genetic testing-aneuploidy (PGT-A) in patients undergoing frozen-thawed embryo transfer, stratified by age. METHODS: A retrospective analysis was performed including a total of 743 cycles, the first frozen embryo transfer (FET) cycle with single embryo transfer, who underwent treatment between January 2020 and July 2023 in a single fertility centre, Gangnam CHA Fertility Center. A total of 743 cycles, in which we performed intracellular sperm injection and freeze-all strategy, from 743 patients were included. The patient group was divided into 4 groups as follows: group 1 (G1), 208 FET on day 5; group 2 (G2), 177 FET with PGT-A on day 5; group 3 (G3), 220 FET on day 6; group 4 (G4), 138 FET with PGT-A on day 6. We also divided into 2 groups-under 35 years of age and over 35 years of age-and performed the analysis separately for each group. RESULTS: In the under 35 years of age group, there were no significant differences in clinical pregnancy and miscarriage rates in G1 and G2 (67.2% vs. 63.8%, not statistically significantly different). Also, G4 had a higher clinical pregnancy rate than G3, but it was not significant (51.8% vs. 54.7%, not statistically significantly different). In the 35 years or older group, G2 had higher pregnancy rates than G1 and lower miscarriage rates (clinical pregnancy rate: 43.3% vs. 67.7%, P = 0.001, miscarriage rate: 22.5% vs. 3.4%, P = 0.001). In addition, G4 had a higher pregnancy rate than G3 and a lower miscarriage rate (clinical pregnancy rate: 31.8% vs. 46.9%, P = 0.003, miscarriage rate: 22.9% vs. 2.2%, P = 0.023). CONCLUSIONS: In the under-35-year-old group, PGT-A on day 5 and day 6 showed a high pregnancy rate and a low miscarriage rate. Therefore, using PGT-A seems advantageous for patients of an advanced maternal age.

Pregnancy complications and birth outcomes in women with polycystic ovary syndrome undergoing frozen embryo transfer.

OBJECTIVE: To determine whether polycystic ovary syndrome (PCOS) increases adverse pregnancy and birth outcomes in women undergoing frozen embryo transfer (FET). DESIGN: Retrospective cohort study. The PCOS group was matched 1:2 with the control group population using propensity score matching. SETTING: Not applicable. PATIENT(S): During an 8-year period, 2,955 patients aged 20-40 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. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): All patients were assessed for specific pregnancy complications and birth outcomes, with a sub-group analysis conducted to compare patients with PCOS 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<.001), gestational hypertension (12.2% vs. 8.9%; RR, 1.37; 95% CI, 1.05-1.80; P=.022), preterm prelabor rupture of membranes (7.0% vs. 3.6%; RR, 1.92; 95% CI, 1.29-2.86; P=.001), cervical length shortening (1.8% vs. 0.4%; RR, 8.39; 95% CI, 1.56-12.49; P=.002), large-for-gestational age (17.4% vs. 13.7%; RR, 1.27; 95% CI, 1.02-1.57; P=.032), and low birth weight (19.9% vs. 16.0%; RR, 1.25; 95% CI, 1.02-1.52; P=.030) in overall propensity score matching 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=.009) in singleton pregnancies. Patients with PCOS with hyperandrogenism showed a higher incidence of cervical length shortening (5.5% vs. 0.5%; adjusted odds ratio, 15.62; 95% CI, 2.25-108.48; P=.005) compared with those without, after adjusting for relevant confounders. CONCLUSION(S): Polycystic ovary syndrome 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.

Vitrification preservation of good-quality blastocysts for more than 5 years reduces implantation and live birth rates.

STUDY QUESTION: Does vitrification cryopreservation of embryos for more than 5 years affect the pregnancy outcomes after frozen embryo transfer (FET)? SUMMARY ANSWER: Vitrification cryopreservation of good-quality blastocysts for more than 5 years is associated with a decrease in the implantation rate (IR) and live birth rate (LBR). WHAT IS KNOWN ALREADY: Previous studies have predominantly focused on embryos cryopreserved for relatively short durations (less than 5 years), yet the impact of extended cryopreservation duration on pregnancy outcomes remains a controversial issue. There is a relative scarcity of data regarding the efficacy and safety of storing embryos for 5 years or longer. STUDY DESIGN, SIZE, DURATION: This retrospective study involved 36 665 eligible vitrified-thawed embryo transfer cycles from 1 January 2016 to 31 December 2022, at a single fertility center in China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were divided into three groups according to embryo storage time: Group 1 consisted of 31 565 cycles, with storage time of 0-2 years; Group 2 consisted of 4458 cycles, with a storage time of 2-5 years; and Group 3 included 642 cycles, with storage time exceeding 5 years. The main outcome measures were IR and LBR. Secondary outcome variables included rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage, as well as neonatal outcomes. Reproductive outcomes were analyzed as binary variables. Multivariate logistic regression analysis was used to explore the effect of preservation time on pregnancy outcomes after correcting for confounding factors. In addition, we also assessed neonatal outcomes, such as large for gestational age (LGA) and small for gestational age (SGA). MAIN RESULTS AND THE ROLE OF CHANCE: IRs in the three groups (0-2, 2-5, and >5 years) were 37.37%, 39.03%, and 35.78%, respectively (P = 0.017), and LBRs in the three groups were 37.29%, 39.09%, and 34.91%, respectively (P = 0.028). After adjustment for potential confounding factors, compared with the 0-2 years storage group, prolonged embryo vitrification preservation time (2-5 years or >5 years) did not affect secondary outcomes such as rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage (P > 0.05). But cryopreservation of embryos for more than 5 years reduced the IR (adjusted odds ratio (aOR) 0.82, 95% CI 0.69-0.97, P = 0.020) and LBR (aOR 0.76, 95% CI 0.64-0.91, P = 0.002). Multivariate stratified analysis also showed that prolonging the cryopreservation time of blastocysts (>5 years) reduced the IR (aOR 0.78, 95% CI 0.62-0.98, P = 0.033) and LBR (aOR 0.68, 95% CI 0.53-0.87, P = 0.002). However, no effect on cleavage embryos was observed (P > 0.05). We further conducted stratified analyses based on the number and quality of frozen blastocysts transferred, and the results showed that the FET results after transfers of good-quality blastocysts in the >5 years storage group were negatively affected. However, the storage time of non-good-quality blastocysts was not significantly associated with pregnancy outcomes. Regarding the neonatal outcomes (of singletons), embryo vitrification preservation time had no effect on preterm birth rates, fetal birth weight, or neonatal sex ratios. However, as the storage time increased, rates of SGA (5.60%, 4.10%, and 1.18%) decreased, while rates of LGA (5.22%, 6.75%, and 9.47%) increased (P < 0.05). After adjusting for confounding factors, the increase in LGA and the decrease in SGA were significantly correlated with the duration of storage time. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study using data from a single fertility center, even though the data had been adjusted, our findings still need to be validated in further studies. WIDER IMPLICATIONS OF THE FINDINGS: With the full implementation of the two-child policy in China, there may be more patients whose embryos have been frozen for a longer time in the future. Patients should be aware that the IR and LBR of blastocysts are negatively affected when the cryopreservation time is longer than 5 years. Couples may therefore consider shortening the time until FET treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Nature Science Foundation of China (No. 82101672), Science and Technology Projects in Guangzhou (No. 2024A03J0180), General Guidance Program for Western Medicine of Guangzhou Municipal Health Commission (No. 20231A011096), and the Medical Key Discipline of Guangzhou (2021-2023). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.