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Our objective was to evaluate the effect of treatment with human chorionic gonadotropin (hCG) at the time of transfer of in vitro–produced (IVP) beef embryos on pregnancy outcomes in lactating multiparous Jersey cows. Grade 1, stage 7 (expanded blastocyst), IVP beef embryos were produced from black Angus-based dams using 3 proven high-fertility Angus sires and were frozen for direct transfer. In a preliminary experiment, lactating multiparous Jersey cows were randomized to a 2 × 2 factorial arrangement of treatments to test the main effect of recipient synchronization protocol (Double-Ovsynch; DO; n = 169 vs. a synchronized estrus; ED; n = 180) and were randomly assigned within recipient protocol to serve as untreated controls (DO-CON, n = 78; ED-CON, n = 44) or to receive i.m. treatment with 2,500 IU of hCG (DO-hCG, n = 79; ED-hCG, n = 46) at the time of embryo transfer (ET). The recipient utilization rate was greater for DO (93%) than for ED (50%) cows, and an interaction was present between recipient synchronization protocol and hCG treatment in which DO-hCG cows had more pregnancies per ET (P/ET) at 26, 33, and 61 d than DO-CON, ED-hCG, and ED-CON cows. Based on a partial budget analysis, the cost per pregnancy for DO cows was $135.35 less than for ED cows. In experiment 2, lactating multiparous Jersey cows were submitted to a Double-Ovsynch protocol (DO, n = 386) and were randomly assigned to serve as untreated controls (CON, n = 192) or were treated with 2,500 IU hCG (hCG, n = 194) at ET. Progesterone concentrations and total luteal volume 7 d after ET were greater for hCG than for CON cows. In contrast to the preliminary experiment, treatment with hCG did not affect P/ET at 26, 33, or 61 d, and treatment with hCG did not affect pregnancy loss from 26 to 61 d. In conclusion, treatment with 2,500 IU of hCG at ET increased P4 concentrations and total luteal volume 7 d after ET but did not increase pregnancy outcomes or decrease pregnancy loss in lactating multiparous Jersey cows receiving frozen/thawed IVP beef embryos. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of fresh embryo transfer and frozen-thawed embryo transfer on perinatal outcomes among patients with PCOS. Method: Patients who underwent in vitro fertilization and embryo transfer at the reproductive medicine center of the Affiliated Hospital of Guangdong Medical University from February 2013 to March 2021 were retrospectively analyzed. Patients were divided into the fresh embryo transfer group and frozen-thawed embryo transfer group according to whether fresh embryo transfer was performed. According to their conditions, patients were further classified into the ET-PCOS group (group A, n = 104), ET-non-PCOS group (group B, n = 212), FET-PCOS group (group C, n = 102), or FET-non-PCOS group (group D, n = 148); the general data, laboratory indicators and pregnancy outcomes of the patients were statistically analyzed, and the perinatal outcomes and related factors between the groups were compared and analyzed. Results: The level of E2 on the HCG test day in the ET group was lower than that in the FET group. The natural birth rate of group D was lower than that of group A and group B, and the cesarean section rate was higher than that of group A and group B; the clinical pregnancy rate of group A was higher than that of group B and group D, and the difference was statistically significant (P < 0.05). There was no significant difference in the total abortion rate, early abortion rate or late abortion rate between the groups (P > 0.05). There was no significant difference in gestational age, neonatal sex or neonatal weight between the groups (P > 0.05). The incidence of placenta previa in Group B was significantly lower than that in Group D, and the difference was significant (P < 0.05). The incidence of fetal distress in Group B was significantly lower than that in Groups C and D, and the incidence of neonatal jaundice in Group D was significantly higher than that in Groups A and B (P < 0.05). In the multivariate analysis, the number of high-quality embryos was independent factors affecting clinical pregnancy, and the embryo transfer method was an independent factor affecting fetal distress and neonatal jaundice. Conclusion: Young PCOS patients without risk of OHSS have a high clinical pregnancy rate with fresh transplant cycles. PCOS disease itself has no significant effect on the perinatal outcomes of the mother or singleton infant. Frozen-thawed embryo transfer may increase the incidence of low placenta, fetal distress and neonatal jaundice. [ABSTRACT FROM AUTHOR]

The study investigates whether a 3-day pretreatment course with a GnRH antagonist in the early follicular phase has an impact on the number of retrieved COCs in a GnRH antagonist stimulation protocol. This is a retrospective single center crossover study involving women who did not conceive after one GnRH antagonist stimulation cycle ("standard cycle") and proceeded with another GnRH antagonist stimulation cycle preceded by early administration of GnRH antagonist for 3 days ("pretreatment cycle") with fresh embryo transfer or frozen embryo transfer. 430 patients undergoing 860 cycles were included. The mean female age was 34.4 ± 4.8 years. Indications for fertility treatment included unexplained infertility (34.3%), male-factor infertility (33.3%), age (16.9%), PCOS (8.2%), tubal (4.7) and endometriosis (2.6%). All cycles were divided into two groups: group 1 (standard, 430 cycles) and group 2 (pretreatment, 430 cycles). The mean duration of stimulation was similar in both groups (10.3 vs 10.3 days, p = 0.28). The starting dose of gonadotropin (234.9 vs 196.8 IU, p<0.001), total amount of gonadotropin used (2419 vs 2020 IU, p<0.001), the total number of retrieved COCs (10 vs 7.8 p<0.001) and the number of mature oocytes (8 vs 5.8 p<0.001) were significantly higher in group 2 than in group 1. The Generalized estimating equation (GEE) regression analysis showed that the pretreatment strategy had a significant positive effect on the number of COCs (coefficient 2.4, p <0.001 after adjusting for known confounders (age, indication, stimulation dose, type, and duration of stimulation). In conclusion, A 3-day course of GnRH antagonist pretreatment increases the number of COCs obtained after ovarian stimulation. [ABSTRACT FROM AUTHOR]

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of astaxanthin compound nutrient (ACN) complementary therapy on pregnancy outcomes in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). This study enrolled 92 patients with PCOS who were continuously supplemented with ACN for three months prior to IVF/ICSI treatment from 2021 to 2023, and selected 92 patients who did not receive the treatment during the same period as controls. Baseline characteristics, ovulation induction outcomes, and pregnancy outcomes were compared between the two groups. In addition, the body mass index (BMI), anti-Müllerian hormone (AMH), antral follicle counting (AFC), fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistant (HOME-IR), and basal sex hormones of the supplementary group patients before and after treatment were compared. The results showed that there were no significant differences in the patient's duration of stimulation, total gonadotropin dose, peak E2 levels, and number of retrieved oocytes between the two groups. However, the number of 2 pronucleus (PN) fertilization, transferable embryos, and high-quality embryos was significantly higher in the ACN group compared with the control group. For both fresh and frozen embryo transplantation, positive pregnancy outcomes increased in PCOS patients who received supplementation of ACN for 3 months. In addition, after 3 months of supplementing with ACN, the patient's BMI, AMH, fasting insulin, HOME-IR, basal luteinising hormone (bLH), and basal testosterone (bT) decreased compared to before treatment. This study suggested that ACN improved insulin resistance, hormone levels, embryo quality and pregnancy outcomes in PCOS patients. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the influence of embryo storage on reproductive and neonatal results in patients undergoing in vitro fertilization (IVF) treatment. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, and BioMed Central databases were searched from inception up to June 2024 for studies comparing reproductive and neonatal outcomes in patients undergoing frozen embryo transfer within 12 months from embryo storage versus more than 12 months after embryo storage. Data were pooled by meta-analysis using a random effects model. Results: A total of 16 studies, involving 233,315 embryos were included. Patients undergoing frozen embryo within 12 months from embryo storage were associated with higher rates of live birth (OR 1.17, 95% CI 1.09–1.26, I2 = 78%) biochemical pregnancy (OR 1.26, 95% CI 1.08–1.47, I2 = 77.8%) clinical pregnancy (OR 1.24, 95% CI 1.12–1.38, I2 = 86.3%) and multiple pregnancy rate (OR 1.26, 95% CI 1.03–1.55, I2 = 69%). No significant differences between groups were shown in terms of survival rate (OR 1.52, 95% CI 0.65–3.58, I2 = 98.5%), miscarriage (OR 1.08, 95% CI 0.91–1.27, I2 = 77%), implantation rate (OR 1.17, 95% CI 0.90–1.52, I2 = 91.7%) and ectopic pregnancy (OR 0.98, 95% CI 0.80–1.20, I2 = 0%). In addition, prolonged embryo storage was not associated with higher rates of preterm delivery (OR 0.86, 95% CI 0.67–1.09, I2 = 8.3%), low weight at birth (OR 1.10, 95% CI 0.88–1.38, I2 = 24.3%) or congenital malformations (OR 0.90, 95% CI 0.65–1.25, I2 = 0.8%). Conclusion: Prolonged embryo storage over 12 months is associated with lower rates of live birth, biochemical pregnancy, clinical pregnancy, and multiple pregnancy. However, important covariates such as reasons for delay of transfer, embryo quality, and improper handling of embryos could not be ruled out as causes of this reduction. Given these limitations, these conclusions should be viewed with caution. [ABSTRACT FROM AUTHOR]

Purpose: Taking into consideration earlier attempts at assisted reproduction and previous pregnancies allows a more differentiated approach when counseling couples regarding their chances in assisted reproductive treatments. The aim of this study was to investigate whether the outcome of fresh embryo transfers affects subsequent same-cohort vitrified–warmed cycles. Methods: This retrospective cohort study analyzes the outcome of all fresh and frozen embryo transfers (n = 8118) between January 1, 2011, and December 31, 2022. All women who received fresh or frozen embryo transfers at Kepler University Hospital Linz were included. The use of donor eggs, previously cryopreserved oocytes, and freeze-all cycles were excluded from the analysis. Results: Positive serum βhCG after a fresh cycle has a significant impact on the chances of positive βhCG in a subsequent vitrified–warmed cycle (36.3% [33.2%, 39.5%]; P = 0.002). Negative βhCG after a fresh cycle does not predict the outcome of the following same-cohort embryo transfer (33.1% [30.7%, 35.7%], P = 0.726). Pregnancy rates of the first, second, third, and fourth same-cohort vitrified–warmed embryo transfer remain continuously high, with 32.8%, 30.8%, 28.9%, and 27.1%, respectively. Conclusions: Positive serum βhCG after a fresh embryo transfer has a positive predictive value for the outcome of a subsequent vitrified–warmed embryo transfer. Couples with a negative fresh cycle should not be discouraged from continuing fertility treatment using same-cohort frozen embryos. Trial registration: This study was prospectively registered at the German Clinical Trials Register on September 5, 2023 (DRKS00032552). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to determine whether intrauterine infusion of autologous platelet-rich plasma (PRP) gel increases endometrial thickness (EMT) and improves the outcomes of frozen-thawed embryo transfer (FET) in women with thin endometrium. Methods: This study included 111 women (aged 25–44 years) who had thin endometrium. All patients had at least one previous cycle canceled because of thin endometrium or previous embryo transfer cycles and an EMT < 7 mm. Forty-seven women underwent intrauterine infusion of autologous PRP gel on three occasions during endometrial preparation and the remaining women served as controls. The final EMT was measured by ultrasound before the start of the luteal phase, and FET-related outcome parameters were monitored. Results: Mean EMT was greater in women who received PRP gel than in those who did not (6.7 mm vs. 6.3 mm, respectively, p < 0.05). FET was attempted in all women. The 47 women who underwent infusion of PRP had a significantly higher pregnancy rate (18 pregnancies (38.3%), with 17 (36.2%) ongoing) compared with 64 control women (ten pregnancies (18.5%), nine (16.7%) ongoing). However, there was no significant reduction in the miscarriage rate. Conclusion: Intrauterine infusion of autologous PRP gel during endometrial preparation for FET cycles can improve the EMT, clinical pregnancy rate, and ongoing pregnancy rate in women with thin endometrium. [ABSTRACT FROM AUTHOR]

Purpose: Multiple factors have been shown to influence the rate of clinical pregnancy after FET in IVF treatment, including embryo quality, synchronization of embryo and endometrium, and endometrial receptivity (ER). The subendometrial blood flow conditions could also contribute potentially major effects toward the establishment and maintenance of pregnancy. We conducted a retrospective cohort study to examine the correlation between subendometrial blood flow, as determined by Doppler ultrasound, and pregnancy outcomes in IVF patients with a thin endometrium (endometrium thickness [EMT] ≤ 0.7 cm). Methods: This was a retrospective cohort study conducted at a university-affiliated reproductive hospital from January 2017 to April 2023. The EMT and subendometrial blood flows were assessed using transvaginal color Doppler ultrasound and evaluated by experienced clinical ultrasound physicians on the endometrial transformation day. The pregnancy outcomes were followed up and documented in clinical medical records through the IVF cohort study at our center. Results: In the patients with 0.5 cm ≤ EMT ≤ 0.7 cm, the embryo implantation rate was statistically significant increased in the patients with the presence of subendometrial blood flow (OR 1.484; 95% CI, 1.001–2.200; P = 0.049; aOR 1.425; 95% CI, 1.030–2.123; P = 0.003). Patients with discernible subendometrial blood flow have superior live birth (P = 0.028), clinical pregnancy (P = 0.049), and embryo implantation (P = 0.027) compared to the patients without subendometrial blood flow when the EMT is ≤ 0.7 cm. Conclusions: The presence of subendometrial blood flow detected by ultrasound was positively associated with successful embryo implantation and favorable pregnancy outcomes in patients with thin endometrium undergoing FET. [ABSTRACT FROM AUTHOR]

Purpose: To compare obstetrical and neonatal outcomes of embryo transfer cycles using fresh vs. frozen-thawed testicular sperm derived from microTESE in non-obstructive azoospermia (NOA) patients. Design: The retrospective cohort study included a total of 48 couples diagnosed with NOA who underwent 93 ET cycles, both fresh and frozen-thawed embryos, and resulted in pregnancy. ET cycles were divided into two groups according to sperm type, fresh (46 cycles, 49.5%) or frozen (47 cycles, 50.5%) testicular sperm. The primary outcome was the birth weight of newborns correlated with gestational week (birth weight percentile). Results: A comparison of patients' basic characteristics and ET cycle parameters showed no significant clinical differences between the groups. A total of 172 embryos were transferred, 86 (50%) in each group. A higher rate of good-quality blastocysts was found in the fresh testicular group (83.3% vs. 50%, p = 0.046). A comparison of pregnancy outcomes showed no significant differences in clinical pregnancy, implantation, or live birth rates. A total of 53 cycles resulted in live birth, 26 (49%) and 27 (51%) in the fresh and frozen groups, respectively. No difference was found in pregnancy length, delivery mode, or obstetrical complications. A total of 61 newborns were included, 31 (51%) and 30 (49%) in fresh and frozen testicular groups, respectively. No significant differences were found in mean birth weight or birth weight percentile between the groups. Conclusion: No significant differences were found in obstetrical outcomes when comparing ET cycles using fresh or frozen-thawed testicular sperm retrieved from microTESE. Moreover, there is no association between the sperm source and the birth weight of newborns. [ABSTRACT FROM AUTHOR]

Purpose: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective multicenter cohort study aimed to investigate the impact of diazepam administration during embryo transfer on reproductive outcomes, focusing primarily on the live birth rate. Secondary outcomes included the positive beta-hCG rate, clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate, and preterm birth rate. Methods: Data from 5607 embryo transfers, encompassing 465 cases with diazepam administration, were retrospectively analyzed. The study included single blastocyst transfers from 12 clinics in Portugal and Spain between January 2015 and December 2022. Results: Comparison of reproductive outcomes between patients receiving diazepam and those who did not showed no statistically significant differences. Positive beta-hCG rates (60.8% non-diazepam vs. 60.4% diazepam, p = 0.92, adjusted p = 0.32) and clinical pregnancy rates (45.6% non-diazepam vs. 46.2% diazepam, p = 0.81, adjusted p = 0.11) were comparable. Miscarriage rates (11.0% diazepam vs. 9.3% non-diazepam, p = 0.25, adjusted p = 0.26) and ectopic pregnancy rates (0.9% diazepam vs. 0.1% non-diazepam, p = 0.1, adjusted p = 0.20) were similar. Live birth rates (36.3% non-diazepam vs. 35.3% diazepam, p = 0.69, adjusted p = 0.82) and prematurity rates (0.3% non-diazepam vs. 0% diazepam, p > 0.99, adjusted p = 0.99) also exhibited no statistically significant differences. Conclusions: Based on the results, diazepam administration during embryo transfer did not show a discernible impact on reproductive outcomes, including live birth rates, suggesting its limited effectiveness in enhancing success. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association, if any, between the grade of the trophectoderm (TE) and the rate at which β-human-chorionic gonadotropin (β-HCG) rises in early pregnancy. Methods: This is a retrospective cohort study including 1116 singleton clinical pregnancies resulting from in vitro fertilization with single day 5 blastocyst transfer at an academic fertility center. TE quality was assessed by trained embryologists employing standard criteria. Three groups were formed based on the TE grade: grade A (n = 358), grade B (n = 628), and grade C (n = 130). Main outcome measure was the rise (%) in serum levels of β-HCG (days 12 to 14 post embryo transfer), using the following formula [(β-HCG D14 − β-HCG D12) * 100/β-HCG D12]. Results: Fresh embryo transfers accounted for 64.1% of the population. Overall, in adjusted models there were no significant differences in the β-HCG% rise when comparing the TE grade C group to TE grade A [adjβ (95%CI): 10.09 (− 0.05, 20.22)] or when comparing TE grade Β group to TE grade A [4.46 (− 2.97, 11.88)]. When the analysis was restricted to fresh embryo transfers, significant differences were observed in the % rise of β-HCG when comparing the TE grade C group to TE grade A [adjβ (95%CI): 21.71 (5.67, 37.74)], but not when comparing the TE grade B group to TE grade A [2.68 (− 5.59, 10.95)]. In frozen transfers, there were no significant differences. Conclusion: TE grade appears to impact early pregnancy serum β-HCG levels in the setting of a fresh day 5 embryo transfer, even after adjusting for potential confounders. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to evaluate if maternal age at transfer following autologous oocyte cryopreservation is associated with live birth rate (LBR). Methods: We performed a retrospective cohort study of all patients who thawed autologous oocytes and then underwent a single frozen euploid embryo transfer between 2011 and 2021 at a large urban university-affiliated fertility center. Each oocyte thaw patient was matched 2:1 to in vitro fertilization (IVF) patients who underwent single embryo transfer < 1 year after retrieval. Primary outcome was LBR. Secondary outcomes included implantation rates (IR) and spontaneous abortion rates (SABR). Results: A total of 169 oocyte thaw patients were matched to 338 IVF patients. As expected, oocyte thaw patients were older (median age 42.5 vs. 37.6 years, p < 0.001) and waited longer between retrieval and transfer than in vitro fertilization patients (median time 59 vs. 1 month, p < 0.001). In univariate analysis, implantation and LBR differed among oocyte thaw and IVF patients (p < 0.05), but SABR did not (p = 0.57). Transfer outcomes in oocyte thaw patients did not differ based on transfer age group (IR: p = 0.18; SABR: p = 0.12; LBR: p = 0.24). In a multiple logistic regression model, age at transfer was not predictive of live birth when controlling for age at retrieval, embryo morphology, and day of blastulation. Conclusions: Maternal age at transfer after oocyte cryopreservation is not predictive of LBR; this suggests that "an aging womb" does not impair LBR after oocyte thaw and empowers patients to return for transfer when ready for childbearing. [ABSTRACT FROM AUTHOR]

Objective: Gonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET. Methods: A total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups. Results: EMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group. Conclusion: Acupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of medroxyprogesterone acetate (MPA) treatment in comparison to those of gonadotropin releasing hormone (GnRH) antagonists for the prevention of premature luteinizing hormone surges during controlled ovarian hyperstimulation (OS) and the impact of these effects on developing embryos and pregnancy outcomes. Data from 757 cycles of GnRH antagonist treatment and 756 cycles of MPA treatment were evaluated at the Akdeniz University Faculty of Medicine Assisted Reproductive Treatment Center between October 2018 and April 2022. Patient records were obtained from the electronic database of the centre and analysed. In our centre, GnRH antagonist protocols were used between 2018 and 2020, and MPA protocols were used between 2020 and 2022. We chose our study population by year. Our study is a comparative retrospective study. All methods in this study were performed in accordance with the relevant guidelines and regulations. Patients using MPA were significantly older (33.9 ± 5.6 vs. 32.6 ± 5.6, p < 0.001) and had a lower number of antral follicles (AFC) (10.7 ± 8.6 vs. 11.9 ± 10.8, p = 0.007) than those using GnRH antagonists. Both MPA (2.9%) and GnRH antagonists (2.2%) had similar effectiveness in preventing premature ovulation (p = 0.415). There was no significant difference between the two groups in terms of the number of total developed embryos (1.3 ± 1.3 vs. 1.2 ± 1.2, p = 0.765). There was no significant difference in the clinical pregnancy rates with the first ET (%35.4 vs. %30.1, p = 0.074), per total number of transfers (35.3% vs. 30.1%, p = 0.077). MPA was found to be effective at preventing premature ovulation during OS treatment, and the incidence of developing embryo and pregnancy outcomes in patients using MPA were similar to those in patients using GnRH antagonists. Therefore, the use of MPA instead of GnRH antagonists during OS may be a viable alternative for patients not scheduled for fresh ET. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, hormone replacement therapy is the main treatment in Western medicine for patients with decreased ovarian function, but these patients are not sensitive to exogenous hormones, leading to unsatisfactory therapeutic effect. Zishen-Yutai pills can nourish the blood and calm the fetus, tonify the kidney and spleen, invigorate qi and strengthen the body. Studies have confirmed that Zishen-Yutai pill is effective in reducing follicle-stimulating hormone index and improving traditional Chinese medicine symptoms in patients with diminished ovarian reserve. However, few studies have been conducted to improve the implantation rate of patients by improving endometrial receptivity. OBJECTIVE: To evaluate the effect of Zishen-Yutai pills on the clinical outcome of patients with diminished ovarian reserve undergoing frozen-thawed embryo transfer again. METHODS: A total of 300 patients with diminished ovarian reserve who underwent frozen-thawed embryo transfer to assist pregnancy after the first failure in the Center of Reproductive Medicine, Changzhou Maternal and Child Health Care Hospital from January 2019 to December 2021 were selected as the study subjects. Subjects were randomly treated with a placebo or Zishen-Yutai pills in a ratio of 1:2, with 100 cases in the treatment group and 200 cases in the control group. However, 13 patients fell off due to lack of contact, refusal to take medicine or other reasons. Finally, 90 cases in the treatment group and 197 cases in the control group were included in the study. Oral medication was administered 7 days before frozen-thawed embryo transfer transplantation at a dose of 5 g/time, 3 times/day. To investigate whether taking Zishen-Yutai pills could improve the clinical outcome of patients with diminished ovarian reserve after frozen-thawed embryo transfer again, the primary outcome measures included clinical pregnancy rate, implantation rate, abortion rate, live birth rate, offspring birth weight and birth defects. RESULTS AND CONCLUSION: Compared with the control group, the clinical pregnancy rate (P < 0.05) and implantation rate (P=0.009) were significantly increased after the oral administration of Zishen-Yutai pills. Correlation analysis showed that taking the Zishen-Yutai pill was positively correlated with the number of implanted embryos (r=0.200, P=0.001) and clinical pregnancy (r=0.235, P=0.000). There was no correlation between taking Zishen-Yutai pills and indexes of endometrial thickness and blood flow. It is indicated that Zishen-Yutai pills can improve the clinical pregnancy rate and implantation rate of frozen-thawed embryo transfer recurrence in patients with diminished ovarian reserve. [ABSTRACT FROM AUTHOR]

Background: The utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs. Methods: The stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients' previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs. Results: Patients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs (2.23 ± 2.05 vs. 0.89 ± 0.99, P < 0.001), and a simultaneously higher proportion of the number of cleavage stage embryos (53.87% ± 31.38% vs. 39.80% ± 29.60%, P = 0.043), 2PN cleavage stage embryos (43.89% ± 33.01% vs. 27.22% ± 27.13%, P = 0.014), and TQEs (27.05% ± 26.26% vs. 14.19% ± 19.76%, P = 0.019) to the number of oocytes retrieved compared with the hCG trigger control cycles, respectively. The double trigger cycles achieved higher rates of cumulative clinical pregnancy (20.00% vs. 2.86%, P = 0.031), cumulative persistent pregnancy (14.29% vs. 0%, P < 0.001), and cumulative live birth (14.29% vs. 0%, P < 0.001) per stimulation cycle compared with the hCG trigger control cycles. Conclusion: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) may be suggested as a valuable new regimen for treating patients with low TQE yield in previous hCG trigger IVF/intracytoplasmic sperm injection (ICSI) cycles. [ABSTRACT FROM AUTHOR]

Purpose: To explore if a day 7 blastocyst is predictive of the reproductive potential of sibling day 5 or day 6 blastocysts? Methods: Retrospective cohort of autologous frozen embryo transfers (FET), February 2019 to April 2022. Cycles divided into groups 1 to 5, according to the day of embryo cryopreservation and the presence of a day 7 blastocyst sibling within the cohort: group 1/group 2—day 5 blastocyst without/with a day 7 sibling, group 3/group 4—day 6 blastocyst without/with a day 7 sibling, group 5—day 7 blastocyst. Clinical, ongoing pregnancy and miscarriage rates, cycle, and patient characteristics are reported. Multivariable generalized estimating equations (GEE) logistic regression analysis accounts for confounders and assesses the effect of a sibling day 7 blastocyst on ongoing pregnancy rates of day 5 or day 6 blastocyst FETs. Results: Ongoing pregnancy rates are 38.4%, 59.5%, 30.8%, 32.7%, and 4.4% in groups 1–5, respectively. When correcting for maternal age, number of oocytes retrieved and discarded per cohort, and ploidy, embryos cryopreserved on either day 6 or day 7 have reduced odds of ongoing pregnancy after FET compared to day 5 blastocysts (OR = 0.76, IQR [0.61–0.95], p-value = 0.01). However, the presence of a day 7 sibling does not significantly affect odds of ongoing pregnancy of day 5 or day 6 blastocysts compared to the same-day blastocyst without a day 7 sibling (p-value = 0.20 and 0.46, respectively). This finding is consistent within both the Preimplantation Genetic Testing for Aneuploidy (PGT-A) unscreened and screened (euploid) embryo subgroups. Conclusions: Day of embryo cryopreservation significantly affects ongoing pregnancy rates. However, day 7 embryos within a cohort do not affect the reproductive potential of sibling day 5 and day 6 blastocysts, suggesting that slow embryo development is an embryo-specific trait. [ABSTRACT FROM AUTHOR]

To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. Retrospective cohort. Large fertility clinic. A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible. [ABSTRACT FROM AUTHOR]

The article discusses the ruling in Le Page v. Center for Reproductive Medicine wherein the Alabama Supreme Court held that the parents of cryogenically preserved embryos, conceived through in-vitro fertilization (IVF), could sue under the state's Wrongful Death of a Minor Act for negligent destruction of the embryos. Topics include the impact of the ruling on the practice of IVF and how the bill SB 159 diminishes the negligible state of U.S. regulation that will protect IVF-generated embryos.

STUDY QUESTION Does double stimulation, followed by a fresh embryo transfer (DUOSTIM fresh) give a higher number of good-quality blastocysts as compared with a single stimulation in young low prognosis patients? SUMMARY ANSWER Compared to single stimulation, DUOSTIM fresh leads to a significantly higher number of good quality blastocysts, without hindering fresh embryo transfer outcomes. WHAT IS KNOWN ALREADY DUOSTIM (ovarian stimulation both in the follicular and luteal phase of the same cycle) is an innovative strategy to retrieve a higher number of oocytes in a shorter time frame, thus it is particularly appealing for poor ovarian responders. Three current limitations of dual stimulation are: (i) it is unclear whether outcomes of the second (luteal) wave result from the second stimulation, or a carry-over effect from previous follicular stimulation; (ii) the desynchronization between endometrium and ovaries and, (iii) lack of robust evidence. No previous studies explored DUOSTIM starting from the luteal phase, and with a fresh embryo transfer (DUOSTIM fresh). STUDY DESIGN, SIZE, DURATION This study is a randomized, controlled, single-center, superiority clinical trial comparing two different ovarian stimulation protocols: a double stimulation cycle versus a single stimulation cycle followed by fresh embryo transfer. The primary outcome was the number of good quality blastocysts obtained, while secondary outcomes included results from fresh embryo transfer (clinical pregnancy, miscarriage). A total of 120 women were enrolled in this study between October 2020 and October 2022, with a 1:1 allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS Only young (<40 years old) low prognosis (anti-Müllerian hormone <1.2 ng/ml) patients were recruited in the Reproductive Medicine Department of Dexeus University Hospital. In the investigational group, DUOSTIM fresh, the first stimulation was initiated in the luteal phase (Day 18–21 cycle) followed by a second stimulation 5 days post first oocyte retrieval, initiated in the follicular phase and a fresh embryo transfer of the best blastocyst generated (first or second cycle). The control group performed a follicular phase single stimulation cycle with a fresh embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 107 patients were analyzed, 53 in the investigational (DUOSTIM fresh) and 54 in the control arm (single stimulation). DUOSTIM fresh resulted in a significantly higher number of good quality blastocysts as compared to single stimulation (difference of mean 0.81, 95% CI 0.12–1.49). The mean percentage of cycles with embryo transfer was comparable (62.3% and 51.9%, respectively for double versus single stimulation). No significant differences were found for clinical outcomes following fresh embryo transfer with an ongoing pregnancy rate of 24.5% for DUOSTIM fresh versus 22.2%, for conventional IVF. Of interest comparisons between different stimulation cycles (A: luteal-phase DUOSTIM fresh, B: follicular - phase DUOSTIM fresh, and C: single stimulation) did not demonstrate any significant difference in terms of ovarian response with the mean (SD) number of mature oocytes being (A: 3.3 (2.9), B: 3.4 (3.4), and C: 3.5 (2.9), respectively). LIMITATIONS, REASONS FOR CAUTION Study sample size was calculated to detect differences on the mean number of good quality blastocysts. Therefore, results for secondary outcomes (embryo transfer rates and clinical pregnancy rates) should be interpreted with caution as exploratory findings that deserve future investigations. WIDER IMPLICATIONS OF THE FINDINGS Although DUOSTIM fresh results in a higher number of blastocysts as compared with a single stimulation in young low prognosis patients, the decision of performing dual stim should be evaluated with caution, considering that whether this may improve embryo transfers rate and pregnancy outcomes is still unclear. Results on cumulative-live-birth-rate are warranted. STUDY FUNDING/COMPETING INTEREST(S) The study was an investigator-initiated study supported by an unrestricted grant by Organon. N.P.P. has received grants from Merck Serono, Organon, Ferring Pharmaceutical, Theramex, and Besins Healthcare. N.P.P. has received consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. N.P.P. has received honoraria for lectures from Merck Serono, Organon, Theramex, Roche Diagnostics, IBSA, Besins Healthcare, and Ferring. A.R. has received Research grants, honoraria for lectures from Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins International, IBSA, Guerbet. The other authors declare that there is no conflict of interest to disclose with respect to the content of this article. TRIAL REGISTRATIO NUMBER NCT04446845. TRIAL REGISTRATION DATE 25 June 2020. DATE OF FIRST PATIENT'S ENROLMENT 30 October 2020. [ABSTRACT FROM AUTHOR]

STUDY QUESTION How does a gonadotrophin-releasing hormone (GnRH) agonist versus a GnRH antagonist protocol affect ovarian response when using an individualized fixed daily dose of follitropin delta for ovarian stimulation? SUMMARY ANSWER The BEYOND trial data demonstrate thatindividualized fixed-dose follitropin delta is effective when used in a GnRH agonist protocol, compared with a GnRH antagonist protocol, in women with anti-Müllerian hormone (AMH) ≤35 pmol/l and no increased risk of ovarian hyperstimulation syndrome (OHSS). WHAT IS KNOWN ALREADY The efficacy and safety of an individualized fixed daily dose of follitropin delta (based on body weight and AMH) have been established in randomized controlled trials (RCTs) using a GnRH antagonist protocol. Preliminary study data indicate that individualized follitropin delta is also efficacious in a GnRH agonist protocol (RAINBOW trial, NCT03564509). There are no prospective comparative data using individualized follitropin delta for ovarian stimulation in a GnRH agonist versus a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION This is the first randomized, controlled, open-label, multi-centre trial exploring efficacy and safety of individualized follitropin delta dosing in a GnRH agonist versus a GnRH antagonist protocol in participants undergoing their first ovarian stimulation cycle for IVF/ICSI. A total of 437 participants were randomized centrally and stratified by centre and age. The primary endpoint was the number of oocytes retrieved. Secondary endpoints included ongoing pregnancy rates, adverse drug reactions (including OHSS), live births, and neonatal outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants (18–40 years; AMH ≤35 pmol/l) were enrolled at specialist reproductive health clinics in Austria, Denmark, Israel, Italy, the Netherlands, Norway, and Switzerland. The mean number of oocytes retrieved was compared between the GnRH agonist and antagonist protocols using a negative binomial regression model with age and AMH at screening as factors. Analyses were based on all randomized subjects, using a multiple imputation method for randomized subjects withdrawing before the start of stimulation. MAIN RESULTS AND THE ROLE OF CHANCE Of the 437 randomized subjects, 221 were randomized to the GnRH agonist, and 216 were randomized to the GnRH antagonist protocol. The participants had a mean age of 32.3 ± 4.3 years and a mean serum AMH of 16.6 ± 7.8 pmol/l. A total of 202 and 204 participants started ovarian stimulation with follitropin delta in the GnRH agonist and antagonist groups, respectively. The mean number of oocytes retrieved was statistically significantly higher in the agonist group (11.1 ± 5.9) versus the antagonist group (9.6 ± 5.5), with an estimated mean difference of 1.31 oocytes (95% CI: 0.22; 2.40, P  =   0.0185). The difference in number of oocytes retrieved was influenced by the patients' age and ovarian reserve, with a greater difference observed in patients aged <35 years and in patients with high ovarian reserve (AMH >15 pmol/l). Both the GnRH agonist and antagonist groups had a similar proportion of cycle cancellations (2.0% [4/202] versus 3.4% [7/204]) and fresh blastocyst transfer cancellations (13.4% [27/202] versus 14.7% [30/204]). The estimated ongoing pregnancy rate per started cycle was numerically higher in the GnRH agonist group (36.9% versus 29.1%; difference: 7.74% [95% CI: −1.49; 16.97, P  =   0.1002]). The most commonly reported adverse events (≥1% in either group; headache, OHSS, nausea, pelvic pain, or discomfort and abdominal pain) were similar in both groups. The incidence of early moderate/severe OHSS was low (1.5% for the agonist group versus 2.5% for antagonist groups). Estimated live birth rates per started cycle were 35.8% and 28.7% in the GnRH agonist and antagonist groups, respectively (treatment difference 7.15%; 95% CI: −2.02; 16.31; P  =   0.1265). The two treatment groups were comparable with respect to neonatal health data for singletons and twins and for incidence of congenital malformations (2.7% and 3.3% for the GnRH agonist versus antagonist groups, respectively). LIMITATIONS, REASONS FOR CAUTION All participants had AMH ≤35 pmol/l and were ≤40 years old. Clinicians should remain cautious when using a GnRH agonist protocol in patients with AMH >35 pmol/l (i.e. those with an increased OHSS risk). The incidence of OHSS in the GnRH antagonist group may have been lower if a GnRH agonist trigger had been allowed. Outcomes of transfers with cryopreserved blastocysts were not followed up, therefore the cumulative live birth rates and neonatal outcomes after cryotransfer are unknown. WIDER IMPLICATIONS OF THE FINDINGS In women with AMH ≤35 pmol/l, an individualized fixed daily dose of follitropin delta resulted in a significantly higher number of oocytes retrieved when used in a GnRH agonist protocol compared with a GnRH antagonist protocol, with no additional safety signals observed and no additional risk of OHSS. Live birth rates following ovarian stimulation with individualized follitropin delta were not statistically different between the GnRH protocols; however, the trial was not powered to assess this endpoint. There were no safety concerns with respect to neonatal health after ovarian stimulation with follitropin delta in either protocol. STUDY FUNDING/COMPETING INTEREST(S) The trial was funded by Ferring Pharmaceuticals. EE, EP, and MS have no competing interests. AP has received research support from Ferring, and Gedeon Richter, and honoraria or consultation fees from Preglem, Novo Nordisk, Ferring, Gedeon Richter, Cryos, Merck A/S. BC has received consulting fees from Ferring and Merck, and his department received fees from Ferring to cover the costs of patient enrolment. MBS has received support to attend meetings and/or travel from Ferring, and was a board member for FertiPROTEKT e.V. until 2023. JS has received honoraria or consultation fees from Ferring and Merck, and support for attending meetings and/or travel from Ferring, Merck, and GoodLife. TS has received support/travel expenses from Ferring for attending a congress meeting, and participated in an advisory board for Merck. YS has received grants/research support from Ferring and support to attend a professional society congress meeting from Merck. RL and PP are employees of Ferring Pharmaceuticals. PP is a BOD member of PharmaBiome and owns stocks of Takeda Pharmaceuticals. TRIAL REGISTRATION NUMBER ClinicalTrials.gov identifier NCT03809429; EudraCT Number 2017-002783-40. TRIAL REGISTRATION DATE 7 April 2019. DATE OF FIRST PATIENT'S ENROLMENT 2 May 2019. [ABSTRACT FROM AUTHOR]

This study evaluated the relationship between CL features assessed by ultrasound (luteal tissue area and blood flow, BF) or rectal palpation (size), uterine tone (UT), plasma progesterone (P4) concentration on Day 7 (D7) and subsequent pregnancy outcomes in bovine embryo recipients. A total of 163 cows and heifers were included in this study. The expected day of ovulation after the synchronization protocol was designated as D0. On D7, ovaries and uterus were examined by ultrasonography and rectal palpation, and subjective scores (1–3 scale) were assigned for CL size, area and BF, and for UT. Blood samples were collected for further P4 analysis. Each embryo recipient then received a grade I frozen–thawed in vivo‐produced blastocyst, which was transferred to the uterine horn ipsilateral to the CL. Pregnancy diagnosis was performed on D35, and the results were retrospectively compared with the assigned scores for CL and UT. We observed a significant (p <.02) interaction between CL size and UT, with a progressive increase in the likelihood of pregnancy for recipients bearing a large CL among those with turgid UT. Ultrasound scoring of the CL using B‐mode and Doppler‐mode did not significantly predict pregnancy rates on D35 (p <.6 and p <.5, respectively). However, logistic regression analysis revealed a trend towards a quadratic effect (p <.08 and p <.06) indicating that the probability of pregnancy varied according to the area of luteal tissue and P4 concentrations, respectively. No significant (p >.05) association was found between the probability of pregnancy and the BF area of the CL. In summary, UT before embryo transfer may reflect successful recipient synchronization. Elevated P4 levels, assessed by CL size, may offset uterine contractility, mitigating adverse effects. Additionally, the CL area may be more important than its vascularization area when evaluating recipients D7 after ovulation. [ABSTRACT FROM AUTHOR]

Background: The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E2) and β-hCG concentrations post-embryo transfer (ET) for pregnancy outcomes, there is debate on the predictive value of E2. The objective of this study was to investigate the predictive efficacy of combining serum E2 and β-hCG levels on early reproductive outcomes 12 days after embryo transfer. Methods: A total of 1521 patients with β-hCG positive values on day 12 following frozen-thawed embryo transfer (FET) with natural endometrial preparation cycles (NCs) were gathered in affiliated Women's Hospital of Jiangnan University. Using logistic regression, the relationship between pregnancy outcome and early serum E2 and β-hCG concentrations was examined. The receiver-operating characteristic (ROC) analysis was used to assess the predictive accuracy of the serum E2 and β-hCG concentrations. Results: Notable distinctions were observed in the serum E2 and β-hCG levels on the twelfth day following FET with NCs between the groups classified as clinical pregnancy group (CP Group) and biochemical pregnancy group (BP Group). In addition, the cutoff values for E2 and β-hCG on day 12 following FET with NCs in cleavage embryo group (CE Group) were 129.25 pg/mL and 156.60 mIU/mL, respectively. The threshold values for E2 and β-hCG for the blastocyst group (B Group) were 174.45 pg/mL and 217.70 mIU/mL. Serum E2 day12 and β-hCG day12 were found to be substantially linked with clinical pregnancy by logistic regression analysis. Conclusions: Serum E2 and β-hCG concentrations were found to be significantly different between the CP Group and BP Group in infertility women underwent FET with NCs. Our retrospective cohort study's findings suggest that the combination of early E2 and β-hCG levels on day 12 post-FET could be used as a predictive tool to evaluate the likelihood of both positive and negative pregnancy outcomes in FET with NCs. [ABSTRACT FROM AUTHOR]

Purpose: This study was aimed to systematically evaluate the efficacy of artificial cycle-prepared frozen–thawed embryo transfer (FET) with or without gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment for women with polycystic ovary syndrome (PCOS). Methods: The analysis was carried out by searching the PubMed, EMBASE, and CNKI databases with a combination of keywords before October 2021. The available studies of the effects of GnRH-a pretreatment or no pretreatment on FET in PCOS patients were considered. The risk ratios (RRs) or standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated with using subgroups and sensitivity analysis. The quality evaluation for this analysis was followed. Results: Seventeen studies including 3646 women were analyzed. GnRH-a pretreatment was significantly associated with a higher implantation rate (RR = 1.12, 95%CI: 1.00–1.24) and clinical pregnancy rate (RR = 1.19, 95%CI: 1.08–1.32) than the placebo. Moreover, in the GnRH-a pretreatment group, significant differences were detected for increasing the endometrium thickness among PCOS patients (SMD = 0.56, 95%CI: 0.20–0.92). However, for RCTs subgroup, no differences were observed, even after sensitivity analyses. In addition, the miscarriage rates, ectopic pregnancy rates, multiple pregnancy rates, and live birth rates were similar in both two groups. Conclusions: Endometrial preparation using GnRH agonist pretreatment prior to FET seems to be the better choice for PCOS patients. However, well-designed RCTs are required for confirmation. [ABSTRACT FROM AUTHOR]

Preimplantation embryo culture, pivotal in assisted reproductive technology (ART), has lagged in innovation compared to embryo selection advancements. This review examines the persisting gap between in vivo and in vitro embryo development, emphasizing the need for improved culture conditions. While in humans this gap is hardly estimated, animal models, particularly bovines, reveal clear disparities in developmental competence, cryotolerance, pregnancy and live birth rates between in vitro-produced (IVP) and in vivo-derived (IVD) embryos. Molecular analyses unveil distinct differences in morphology, metabolism, and genomic stability, underscoring the need for refining culture conditions for better ART outcomes. To this end, a deeper comprehension of oviduct physiology and embryo transport is crucial for grasping embryo–maternal interactions' mechanisms. Research on autocrine and paracrine factors, and extracellular vesicles in embryo–maternal tract interactions, elucidates vital communication networks for successful implantation and pregnancy. In vitro, confinement, and embryo density are key factors to boost embryo development. Advanced dynamic culture systems mimicking fluid mechanical stimulation in the oviduct, through vibration, tilting, and microfluidic methods, and the use of innovative softer substrates, hold promise for optimizing in vitro embryo development. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis aimed to compare the therapeutic effects of rFSH versus uFSH/uHMG on ovarian stimulation in women undergoing assisted reproductive technology. Methods: The databases of PubMed, Embase, and the Cochrane Library were systematically searched to retrieve data on eligible trials from inception until July 2022. The relative risks (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were applied to assess categorical and continuous outcomes, and the pooled results were calculated using the random-effects model. Sensitivity, subgroup, and publication bias analyses were also performed. Results: Forty-eight trials that enrolled 10,127 women were included in this quantitative meta-analysis. There were no significant differences between rFSH and uFSH/uHMG in the clinical pregnancy rate (RR: 1.01; 95% CI 0.95–1.07; P = 0.760), live birth rate (RR: 0.98; 95% CI 0.91–1.06; P = 0.665), multiple pregnancy rate (RR: 0.92; 95% CI 0.77–1.09; P = 0.320), miscarriage rate (RR: 1.17; 95% CI 0.94–1.46; P = 0.151), and the incidence of ovarian hyperstimulation syndrome (RR: 1.25; 95% CI 0.91–1.70; P = 0.164). In addition, the administration of rFSH was associated with a higher number of oocyte retrieval compared with that of uFSH/uHMG (WMD: 0.61; 95% CI 0.03–1.20; P = 0.038), while no significant differences were found between rFSH and uFSH/uHMG in the dosage of gonadotrophin (WMD: 14.80; 95% CI − 136.97 to 166.57; P = 0.848) and the duration of ovarian stimulation (WMD: − 0.26; 95% CI − 0.62 to 0.10; P = 0.152). Thus, the exploratory analyses revealed several potential differences in the effects of rFSH versus uFSH/uHMG on ovarian stimulation. Conclusion: The administration of rFSH significantly increased the number of oocytes retrieved, whereas there were no significant differences between the efficacies of rFSH and uFSH/uHMG for pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between miR-135a-5p and endometrial receptivity. Methods: Peripheral blood was collected on the day of ovulation and the 5th day after ovulation for high-throughput sequencing from women who achieved clinical pregnancy through natural cycle frozen embryo transfer. RT-qPCR assessed miR-135a-5p expression in the endometrium tissue or cells during the mouse implantation window or decidualization. Scanning electron microscopy was utilized to observe pinopode morphology and quantity in mice overexpressing miR-135a-5p during the WOI. Human endometrial stromal cells (HESC) and artificial induction of mouse uterine decidualization were used to explore whether miR-135a-5p overexpression inhibits decidualization by regulating HOXA10 and BMPR2. Furthermore, the impact of miR-135a-5p on HESC proliferation and HTR8/SVneo invasion was explored. Results: A total of 54 women were enrolled in the study. bioinformatics analysis and animal models demonstrated that miR-135a-5p was significantly downregulated during the WOI, and its high expression can lead to abnormal pregnancy outcomes. Overexpression of miR-135a-5p resulted in the absence of pinopode in mouse endometrial tissue during the WOI. High miR-135a-5p levels were found to potentially inhibit endometrial tissue decidualization by downregulating HOXA10 and BMPR2 expression. Finally, CEBPD was identified as a potential regulator of miR-135a-5p, which would explain the decreased miR-135a-5p expression during the WOI. Conclusion: MiR-135a-5p expression is significantly downregulated during the WOI. High miR-135a-5p levels suppress pinopode development and endometrial tissue decidualization through HOXA10 and BMPR2, contributing to inadequate endometrial receptivity. [ABSTRACT FROM AUTHOR]

Purpose: To examine the interaction between serum progesterone concentration on the trigger day and choice of freeze-all and fresh transfer strategies on live birth in an unselected population as well as in patients over 35 years old. Methods: We performed a retrospective cohort study of 26,661 patients commencing their first IVF cycle in a large fertility centre between 2015 and 2019, including 4687 patients over 35 years old. We performed a multivariable fractional polynomial interaction analysis within a logistic regression model to investigate the interaction between serum progesterone concentration and the choice of freeze-all or fresh transfer strategy following the first transfer. Results: 15,539 patients underwent a fresh embryo transfer and 11,122 underwent a freeze-all strategy in their first IVF cycle. The freeze-all group had a higher live birth rate compared to the fresh group (43.9% vs 40.3%). After adjusting for confounding factors, there was a positive interaction between serum progesterone concentrations and the choice of a freeze-all versus fresh embryo transfer on live birth (p for interaction 0.0001), with a larger magnitude of effect when progesterone concentration was higher. Such an interaction was also observed in patients over 35 years old (p for interaction 0.01), but the treatment effect curve over progesterone concentrations was almost flat. Conclusions: In an unselected population, frozen transfer is associated with greater chances of live birth, especially in patients with higher serum progesterone concentration. In patients over 35 years old, the benefit of a freeze-all policy appears small across all serum progesterone concentrations. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of magnetic-activated cell sorting (MACS) or testicular sperm aspiration (TESA) to improve reproductive outcomes in cases with elevated sperm DNA fragmentation undergoing assisted reproduction. Methods: This randomized controlled trial included couples with failed IVF cycles and sperm DNA fragmentation > 30%. Sperm DNA fragmentation was assessed using the sperm chromatin structure assay (SCSA) method. Participants were randomly assigned to either the MACS or TESA group. Testicular sperm retrieval was performed for the TESA group, while MACS involved sperm selection using magnetic beads. Extended blastocyst culture, freeze all policy of blastocysts by vitrification, and frozen embryo transfer were undertaken as per clinic's standard operating protocols. Blastocyst formation rate, implantation rate, miscarriage rate, multiple pregnancy rate, and live birth rate were analyzed and compared between MACS and TESA groups. Results: There were no significant differences in female age, male age, or sperm DNA fragmentation index (DFI) between the MACS and TESA groups. The blastocyst conversion rate was slightly higher in the TESA group (39%) compared to the MACS group (32%). However, the MACS group had a higher implantation rate (50%) than the TESA group (35%). Miscarriage rates, multiple pregnancy rates, and live birth rates did not show statistically significant differences between the groups. A chi-squared test was conducted to compare categorical variables, and t-tests were done to compare continuous variables. Conclusion: In cases with raised sperm DNA fragmentation, sperm selection by MACS or TESA seems to offer comparable reproductive outcomes. There seems no superiority of one intervention over the other in cases with raised sperm DNA fragmentation undergoing assisted reproduction. Both interventions seem to be beneficial for couples seeking assisted reproduction with raised sperm DNA fragmentation. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate whether the clinical outcomes of cycles with frozen embryo transfer (FET) in hormonal replacement treatment supplemented with dydrogesterone (DYD) following detection of low circulating levels of progesterone (P4) were comparable to the results of cycles with otherwise normal serum P4 values. Methods: Extended analyses of a retrospective cohort that included FET cycles performed between July 2019 and March 2022 after a cycle of artificial endometrial preparation using valerate-estradiol and micronized vaginal P4 (400 mg twice daily). Whenever the serum P4 value was considered low on the morning of the planned transfer, 10 mg of DYD three times a day was added as a supplement. Only single-embryo transfers of a blastocyst were considered. The primary endpoint was live birth rate. Results: Five-hundred thirty-five FET cycles were analyzed, of which 136 (25.4%) underwent treatment with DYD. There were 337 pregnancies (63%), 207 live births (38.6%), and 130 miscarriages (38.5%). The P4 values could be modeled by a gamma distribution, with a mean of 14.5 ng/ml and a standard deviation of 1.95 ng/ml. The variables female age on the day of FET, ethnicity, and weight were associated with a variation in the serum P4 values. There were no differences in the results between cycles with or without the indication for DYD supplementation. Conclusions: Live birth rate did not vary significantly in females with low and normal serum P4 levels on the day of FET when DYD was used as rescue therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the embryological and pregnancy outcomes of women who failed in their first IVF treatment if they attempted a second cycle. Methods: For evaluating the embryological outcomes, the study cohort included 1,227 women who failed to obtain a live birth after the initial IVF cycle from September 2018 to August 2021 and returned for a second attempt. To evaluate reproductive outcomes including live birth rates (LBRs), 1227 women who returned for a second attempt were compared with 13,195 women undergoing their first oocyte retrieval with blastocyst culture attempted during the same study period. Results: In women who had a second cycle, the median number of oocyte retrieved (11 vs 9), fertilized oocytes (7 vs 5), usable embryos (6 vs 4) and blastocysts (3 vs 1) was higher in the second cycle compared to the first cycle (All p < 0.001). Blastocyst formation rates were significantly increased from 33% in the first cycle to 50% in the second cycle across the age group (p < 0.001). However, the primary transfer LBRs were significantly lower in the second cycle than that in the initial cycle (40.82% versus 51.79%, aOR: 0.74 [0.65, 0.84]). LBRs in the second cycle were 42.26%, 42.68%, 25.49% and 16.22% in women aged < 35, 35–37, 38–40, and > 40 years. Conclusion: There was a notable enhancement in laboratory outcomes following the second attempt in women whose initial IVF cycles were unsuccessful. However, the uncertainty inherent in the successful implantation and the consequent progression to live birth remains a significant challenge. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Embryo reinsertion into the same donor mare after embryo flushing would be useful for some reproductive techniques. However, this procedure has been unsuccessful in the past. This study envisages to gain insights into the mechanisms by which embryos fail after embryo flushing and reinsertion in the same mare. The results of this study showed that embryo mortality after embryo reinsertion is not due to luteal deficiency. In contrast, it seems that changes in the endometrial environment due to bacterial contamination and/or inflammation during the uterine lavage are more likely to be responsible for the destruction of most reinserted embryos. The effect of embryo reinsertion immediately after embryo flushing was studied. In Experiment 1, eight mares were used during 32 cycles (8 cycles in each group). For the first two groups, inseminated mares were flushed 8 days after ovulation and prostaglandin F2α was not administered: in group EF-ET (embryo flushing and embryo transfer) the embryo was reinserted in the same donor mare, while in the EF group, no further procedure was performed. In the third group (ET), non-inseminated mares (recipients) received a Day 8 embryo. Progesterone concentration was measured before EF/ET and 72 h after in the three groups. In Experiment 2, twelve mares were used during 17 cycles in two groups, EF-ET (n = 11) and ET (n = 6), as in Experiment 1, except that every mare was flushed 24 h after embryo transfer to retrieve the embryo. Fewer pregnancies resulted after transfer in EF-ET cycles (0/8, 0%) than in the ET group (6/8, 75%). Progesterone concentration decreased significantly (p = 0.05) 72 h after EF-ET but not in EF or ET cycles (p > 0.1). Three mares from the EF-ET showed full luteolysis and signs of endometritis. In Experiment 2, more (5/6; p = 0.08) grade 1 embryos were recovered in the ET compared to the EF-ET group (3/7); 4 embryos were graded 3–4 (were broken or had signs of degeneration) in the EF-ET group but none in the ET group. In both groups, capsule fragments were obtained as indicative of the presence of a recently destroyed embryo in the EF-ET (n = 3) and ET (n = 1) groups. Positive bacterial cultures were obtained in 2/11 and 1/6 embryo flushes from the EF-ET and ET groups, respectively. [ABSTRACT FROM AUTHOR]

The response letter published in the Journal of Assisted Reproduction & Genetics addresses comments on a study comparing sperm selection techniques for improved reproductive outcomes. The study considered a sperm DNA fragmentation threshold of 30%, not 25%, due to literature recommendations. Demographic characteristics of study participants were comparable, and statistical analysis was performed using a chi-square test. The study's primary outcome was blastocyst conversion rates, with both techniques showing comparable outcomes. The authors acknowledge the need for further research on sperm selection techniques in assisted reproduction. [Extracted from the article]

Background: The 2016 Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria redefined the poor responders as low prognosis patients. The embryo transfer strategy for POSEIDON patients remained to be addressed. This study aimed to investigate the optimized number of embryos to transfer for unexpected low-prognosis patients (POSEIDON Group 1 and Group 2) with blastocyst transfer in their first frozen cycle. Methods: A retrospective cohort study of 2970 patients who underwent frozen-thawed embryo transfer (FET) between January 2018 and December 2021. Patients from POSEIDON Group 1 (N = 219) and Group 2 (N = 135) who underwent blastocyst transfer in their first FET cycles were included and divided into the elective single embryo transfer (eSET) group and the double embryo transfer (DET) group. Results: For POSEIDON Group 1, the live birth rate per embryo transfer of the DET group was slightly higher than the eSET group (52.17% vs 46.15%, OR 0.786, 95% CI 0.462–1.337, P = 0.374; adjusted OR (aOR) 0.622, 95% CI 0.340–1.140, P = 0.124), while a significant increase of 20.00% in the multiple birth rate was shown. For Group 2, higher live birth rates were observed in the DET group compared to the eSET group (38.46% vs 20.48%, OR 0.412, 95% CI 0.190–0.892, P = 0.024; aOR 0.358, 95% CI 0.155–0.828, P = 0.016). The difference in the multiple birth rate was 20.00% without statistical significance. Univariate and multivariate analyses revealed that age (OR 0.759, 95% CI.624–0.922, P = 0.006 and OR 0.751, 95% CI 0.605–0.932, P = 0.009) and the number of transferred embryos (OR 0.412, 95% CI 0.190–0.892, P = 0.024 and OR 0.367, 95% CI 0.161–0.840, P = 0.018) were significant variables for the live birth rate in POSEIDON Group 2. Conclusions: The findings in the present study showed that eSET was preferred in the first frozen cycle for POSEIDON Group 1 to avoid unnecessary risks. Double embryo transfer strategy could be considered to improve the success rate for POSEIDON Group 2 with caution. Further stratification by age is needed for a more scientific discussion about the embryo transfer strategy for POSEIDON patients. [ABSTRACT FROM AUTHOR]

Whether single-cell RNA-sequencing (scRNA-seq) captures the same biological information as single-nucleus RNA-sequencing (snRNA-seq) remains uncertain and likely to be context-dependent. Herein, a head-to-head comparison was performed in matched normal-adenocarcinoma human lung samples to assess biological insights derived from scRNA-seq versus snRNA-seq and better understand the cellular transition that occurs from normal to tumoral tissue. Here, the transcriptome of 160,621 cells/nuclei was obtained. In non-tumor lung, cell type proportions varied widely between scRNA-seq and snRNA-seq with a predominance of immune cells in the former (81.5%) and epithelial cells (69.9%) in the later. Similar results were observed in adenocarcinomas, in addition to an overall increase in cell type heterogeneity and a greater prevalence of copy number variants in cells of epithelial origin, which suggests malignant assignment. The cell type transition that occurs from normal lung tissue to adenocarcinoma was not always concordant whether cells or nuclei were examined. As expected, large differential expression of the whole-cell and nuclear transcriptome was observed, but cell-type specific changes of paired normal and tumor lung samples revealed a set of common genes in the cells and nuclei involved in cancer-related pathways. In addition, we showed that the ligand-receptor interactome landscape of lung adenocarcinoma was largely different whether cells or nuclei were evaluated. Immune cell depletion in fresh specimens partly mitigated the difference in cell type composition observed between cells and nuclei. However, the extra manipulations affected cell viability and amplified the transcriptional signatures associated with stress responses. In conclusion, research applications focussing on mapping the immune landscape of lung adenocarcinoma benefit from scRNA-seq in fresh samples, whereas snRNA-seq of frozen samples provide a low-cost alternative to profile more epithelial and cancer cells, and yield cell type proportions that more closely match tissue content. Author summary: Single-cell transcriptomic datasets provide unprecedented opportunities to disentangle the complex tissue microenvironment and cellular origin of cancer. Data are scarce regarding the pros and cons of single-cell RNA sequencing (scRNA-seq) of freshly explanted human tissues over single-nuclei sequencing (snRNA-seq) from the same archived frozen tissues. Lung adenocarcinoma represents a medically valuable case study to compare the biological signal recovered through cells and nuclei sequencing. Here, we sequenced the transcriptome of 160,621 cells/nuclei in paired normal-adenocarcinoma lung samples. Cell type proportions varied widely between scRNA-seq and snRNA-seq with a predominance of immune cells in the former and epithelial cells in the later. Adenocarcinomas were characterized by an increase in cell type heterogeneity and a greater prevalence of malignant epithelial cells in both scRNA-seq and snRNA-seq. The cellular and gene expression transition that occur from normal lung to adenocarcinoma showed common and discordant biological insights whether cells or nuclei were examined. Research applications focussing on mapping the immune landscape of lung cancer benefit from scRNA-seq in fresh samples, whereas snRNA-seq of the same frozen samples provide a low-cost and more flexible alternative to profile more epithelial and cancer cells, and yield cell type proportions that more closely match tissue content. [ABSTRACT FROM AUTHOR]

Spermatozoa cryopreservation has been practiced for decades and is a very useful technique for long-term preservation of sperm fertility. The capability for semen cryopreservation varies across species, seasons, latitudes, and even for different ejaculates from the same animal. This article summarizes research results on sperm cryotolerance biomarkers in several species, focusing on three areas: spermatozoa cryotolerance biomarkers, seminal plasma proteins cryotolerance biomarkers, and other cryotolerance biomarkers. We discovered that sperm cryoresistance biomarkers are primarily related to sperm plasma membrane stability, the presence of antioxidant substances in sperm or seminal plasma, sperm cell energy metabolism, water and small molecule transport channels in the sperm plasma membrane, and antistress substances in sperm or seminal plasma. The research conducted using diverse livestock models can be employed to enhance the basic and applied reproduction of other mammals through the study of sperm cryotolerance biomarkers, as well as the substantial similarities between livestock and other organisms, including endangered species. [ABSTRACT FROM AUTHOR]

Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17–39 who underwent fresh embryo transfer and delivered a singleton neonate at a single center (pre-implantation genetic testing excluded) (2007–2022). Patients were classified as one of the following categories: poor responders—daily follicle-stimulating hormone (FSH) ≥ 150 IU yielding ≤ 3 retrieved oocytes; normal responders—4–15 oocytes; and high responders with ≥16 oocytes. The primary outcome was a composite of pre-eclampsia (mild or severe), small-for-gestational-age, gestational diabetes mellitus, and preterm birth (<37 weeks). We compared maternal and neonatal outcomes between the three groups. Multivariable logistic regression was used to control for confounders. Results: Overall, 507 women met the inclusion criteria. Of them, there were 44 (8.68%) poor responders, 342 (67.46%) normal responders, and 121 (23.87%) high responders. Poor responders, compared to normal and high responders, were characterized by a higher maternal age (34.64 ± 4.01 vs. 31.4 ± 5.04 vs. 30.01 ± 4.93, p < 0.001, respectively) and total FSH dosage (3028.41 ± 1792.05 IU vs. 2375.11 ± 1394.05 IU vs. 1869.31 ± 1089.63 IU, p < 0.001). The perinatal outcomes examined, including cesarean delivery (CD) rate and the composite outcome, were comparable between groups. Using multivariable logistic regression and adjusting for ovarian response group, maternal age, nulliparity, and estradiol level and endometrial thickness before ovulation triggering, poor response was not associated with CD rate or the composite outcome, with maternal age associated with CD (p = 0.005), and nulliparity with the composite outcome (p = 0.007). Similar results were obtained when comparing poor responders to each other group separately or to all other responders. Conclusions: Poor ovarian response is not associated with increased adverse maternal or neonatal outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Unexplained infertility is associated with a higher abortion rate and lower fertilization rate, implantation rate, clinical pregnancy rate and cumulative live birth rate. It is urgent to establish a clinical prediction model related to infertility of unknown cause to solve the problems of clinical prognosis and individualized medical services, and finally achieve the purpose of increasing the cumulative live birth rate of patients with infertility of unknown cause. OBJECTIVE: To construct and verify the prediction model of high-quality blastocyst formation in patients with unexplained infertility during in vitro fertilization. METHODS: A total of 419 patients with unknown infertility who underwent in vitro fertilization in the Assisted Reproduction Department of Changzhou Maternal and Child Health Care Hospital from March 2017 to June 2022 were retrospectively analyzed, including 317 patients with high-quality blastocysts and 102 patients without high-quality blastocysts. A prediction model was established and used as the model group. The model group was sampled 1 000 times by the Bootstrap method as the validation group. Firstly, the univariate analysis was used to screen the influencing factors of high-quality blastocyst formation of unknown infertility, and the best matching factors were selected by the least absolute shrinkage and selection operator (LASSO) algorithm. Multiple factors were included in the progressive Logistic regression to find out the independent influencing factors and draw a column graph. Finally, the subject working curve, calibration curve, clinical decision curve and clinical impact curve were used to verify the differentiation and accuracy of the prediction model as well as the clinical application efficiency. RESULTS AND CONCLUSION: (1) Univariate analysis of the factors influencing the formation of high-quality blastocyst of unknown infertility were age, insemination method, antimullerian hormone level, basal follicle-stimulating hormone level, basal luteinizing hormone level, human chorionic gonadotropin injection day follicle-stimulating hormone level, human chorionic gonadotropin day estradiol level, progesterone level on human chorionic gonadotropin day, the number of high-quality cleavage embryo (day 3) and the number of blastocyst formation (P < 0.05). (2) The best matching factors further screened by LASSO regression were age, insemination method, antimullerian hormone level, basal luteinizing hormone level, human chorionic gonadotropin injection day follicle-stimulating hormone level, human chorionic gonadotropin day estradiol level, the number of high-quality cleavage embryo (day 3) and the number of blastocyst formation (P < 0.05). Multifactor stepwise Logistic regression results showed that independent influencing factors on the formation of high-quality blastocysts for unexplained infertility were age, insemination method, antimullerian hormone level, the number of high-quality cleavage embryo (day 3), and the number of blastocyst formation. (3) Receiver operating characteristic curve exhibited that the area under the curve was 0.880(0.834, 0.926) in the model group and 0.889(0.859, 0.918) in the validation group. It showed that the prediction model had good differentiation. The average absolute error of the calibration curve was 0.036, indicating that the model had good accuracy. The Hosmer-Lemeshow test showed that there was no statistical difference between the prediction probability of blastocyst formation and the actual probability of blastocyst formation (P > 0.05). The clinical decision curve and clinical impact curve showed that the model group and the validation group had the maximum clinical net benefit when the threshold probability value was (0.16-0.96) and (0.08-0.93), respectively, and had better clinical application efficacy within the threshold probability range. These findings concluded that age, insemination method, antimullerian hormone, the number of highquality cleavage embryos (day 3), and the number of blastocyst formation were independent factors influencing the formation of the fine blastocyst in patients with unexplained infertility. The clinical prediction model constructed by these factors has good clinical prediction value and clinical application efficiency and can provide a basis for clinical prognosis and intervention as well as the formulation of individual medical programs. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to provide a detailed analysis of clinical and laboratory factors associated with skewed secondary sex ratio (SSR) after ART. Method: Retrospective cohort study of embryos resulting in live births, from frozen and fresh single blastocyst transfers. Embryos were cultured in either G-TL (n = 686) or Sage media (n = 685). Data was analyzed using a multivariate logistic regression model and a mixed model analysis. Results: Significantly more male singletons were born after culture in Sage media compared to G-TL media (odds ratio (OR) 1.34, 95% CI (1.05, 1.70), P = 0.02). Inner cell mass grade B vs A (OR 1.36 95% CI (1.05, 1.76), P = 0.02) and one previous embryo transfer (OR 1.49, 95% CI (1.03, 2.16), P = 0.03) were associated with a significantly higher probability of male child at birth. Factors associated with a reduced probability of male child were expansion grade 3 vs 5 (OR 0.66, 95% CI (10.45, 0.96), P = 0.03) and trophectoderm grade B vs A (OR 0.57, 95% CI (0.44, 0.74), P = 0.00). Male embryos developed significantly faster in Sage media compared to G-TL media for the stages of blastocyst (− 1.12 h, 95% CI (− 2.12, − 0.12)), expanded blastocyst (− 1.35 h, 95% CI (− 2.34, − 0.35)), and hatched blastocyst (− 1.75 h, 95% CI (− 2.99, − 0.52)). Conclusion: More male children were born after culture in Sage media compared to G-TL media. Male embryo development was affected by culture media. Our observations suggest that culture media impact male embryo quality selectively, thus potentially favoring the selection of male embryos. [ABSTRACT FROM AUTHOR]

Objective: To propose a new classification system (Urman‐Vitale Classification System) for intrauterine adhesions (IUAs) and to evaluate anatomical and fertility outcomes after hysteroscopic adhesiolysis accordingly. Methods: A retrospective analysis of consecutive patients treated over 11 years by a single operator in a tertiary care hospital. Women with sonographic suspicion of IUAs were scheduled for hysterosalpingography (HSG) and hysteroscopy for confirmation and treatment. IUAs were divided into five classes according to symptoms, ultrasound, HSG findings, and postsurgical hysteroscopic appearance. Hysteroscopic adhesiolysis was performed using a bipolar cutting electrode in an office setting. Evaluated outcomes were restoration of the uterine cavity, clinical pregnancy, pregnancy loss, and live birth rates. Results: A total of 227 patients (479 procedures) were included. Mean number of hysteroscopies increased in frequency with class of adhesions from Class 1 to Class 5 (1.0 ± 0.2 vs 2.3 ± 0.5; P = 0.001). Full restoration of the cavity was achieved in 100% of patients with Class 1 compared with 18.5% for Class 5 (43/43 vs 5/27; P = 0.001). Clinical pregnancy (Class 1 vs Class 4: P = 0.034; 1 vs 5: P = 0.006; 2 vs 5: P = 0.024) and live birth (Class 1 vs Class 4: P = 0.001; 1 vs 5: P = 0.006; 2 vs 4: P = 0.007; 2 vs 5: P = 0.0208) rates decreased with increasing severity of IUAs. Pregnancy loss rate was related to IUA severity (Class 1 vs Class 4: P = 0.012; 1 vs 5: P = 0.003: 2 vs 4: P = 0.014; 2 vs 5: P = 0.021). Conclusion: A classification based on symptoms, imaging findings, and postsurgical macroscopic appearance of the uterine cavity could be useful in predicting prognosis and fertility in women with IUAs. Synopsis: A new classification for intrauterine adhesions based on symptoms, imaging, and hysteroscopic appearance of the uterine cavity could simplify postsurgical prognosis and fertility. [ABSTRACT FROM AUTHOR]

STUDY QUESTION How does ovarian stimulation (OS), which is used to mature multiple oocytes for ART procedures, impact the principal cellular compartments and transcriptome of the human endometrium in the periovulatory and mid-secretory phases? SUMMARY ANSWER During the mid-secretory window of implantation, OS alters the abundance of endometrial immune cells, whereas during the periovulatory period, OS substantially changes the endometrial transcriptome and impacts both endometrial glandular and immune cells. WHAT IS KNOWN ALREADY Pregnancies conceived in an OS cycle are at risk of complications reflective of abnormal placentation and placental function. OS can alter endometrial gene expression and immune cell populations. How OS impacts the glandular, stromal, immune, and vascular compartments of the endometrium, in the periovulatory period as compared to the window of implantation, is unknown. STUDY DESIGN, SIZE, DURATION This prospective cohort study carried out between 2020 and 2022 included 25 subjects undergoing OS and 25 subjects in natural menstrual cycles. Endometrial biopsies were performed in the proliferative, periovulatory, and mid-secretory phases. PARTICIPANTS/MATERIALS, SETTING, METHODS Blood samples were processed to determine serum estradiol and progesterone levels. Both the endometrial transcriptome and the principal cellular compartments of the endometrium, including glands, stroma, immune, and vasculature, were evaluated by examining endometrial dating, differential gene expression, protein expression, cell populations, and the three-dimensional structure in endometrial tissue. Mann–Whitney U tests, unpaired t -tests or one-way ANOVA and pairwise multiple comparison tests were used to statistically evaluate differences. MAIN RESULTS AND THE ROLE OF CHANCE In the periovulatory period, OS induced high levels of differential gene expression, glandular-stromal dyssynchrony, and an increase in both glandular epithelial volume and the frequency of endometrial monocytes/macrophages. In the window of implantation during the mid-secretory phase, OS induced changes in endometrial immune cells, with a greater frequency of B cells and a lower frequency of CD4 effector T cells. LARGE SCALE DATA The data underlying this article have been uploaded to the Genome Expression Omnibus/National Center for Biotechnology Information with accession number GSE220044. LIMITATIONS, REASONS FOR CAUTION A limited number of subjects were included in this study, although the subjects within each group, natural cycle or OS, were homogenous in their clinical characteristics. The number of subjects utilized was sufficient to identify significant differences; however, with a larger number of subjects and additional power, we may detect additional differences. Another limitation of the study is that proliferative phase biopsies were collected in natural cycles, but not in OS cycles. Given that the OS cycle subjects did not have known endometrial factor infertility, and the comparisons involved subjects who had a similar and robust response to stimulation, the findings are generalizable to women with a normal response to OS. WIDER IMPLICATIONS OF THE FINDINGS OS substantially altered the periovulatory phase endometrium, with fewer transcriptomic and cell type-specific changes in the mid-secretory phase. Our findings show that after OS, the endometrial microenvironment in the window of implantation possesses many more similarities to that of a natural cycle than does the periovulatory endometrium. Further investigation of the immune compartment and the functional significance of this cellular compartment under OS conditions is warranted. STUDY FUNDING/COMPETING INTERESTS Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases (R01AI148695 to A.M.B. and N.C.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD109152 to R.A.), and the March of Dimes (5-FY20-209 to R.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or March of Dimes. All authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

The possibility of embryo cryopreservation is important for applying the genome resource banking (GRB) concept to those mammalian species that exhibit embryonal diapause in their early development. Odc1 encodes ODC1, which is a key enzyme in polyamine synthesis. RhoA is an essential part of Rho/ROCK system. Both Odc1 and RhoA play an important role in preimplantation embryo development. Studying these systems in mammalian species with obligate or experimentally designed embryonic diapause may provide insight into the molecular machinery underlying embryo dormancy and re‐activation. The effect of cryopreservation procedures on the expression of the Odc1 and RhoA in diapausing embryos has not been properly studied yet. The purpose of this work is to address the possibility of cryopreservation diapausing embryos and to estimate the expression of the Odc1 and RhoA genes in diapausing and non‐diapausing embryos before and after freeze–thaw procedures using ovariectomized progesterone treated mice as a model. Both diapausing and non‐diapausing in vivo‐derived embryos continued their development in vitro after freezing–thawing as evidenced by blastocoel re‐expansion. Although cryopreservation dramatically decreased the expression of the Odc1 and RhoA genes in non‐diapausing embryos, no such effects have been observed in diapausing embryos where these genes were already at the low level before freeze–thaw procedures. Future studies may attempt to facilitate the re‐activation of diapausing embryos, for example frozen–thawed ones, specifically targeting Odc1 or Rho/ROCK system. [ABSTRACT FROM AUTHOR]

Background: Current approaches to profile the single-cell transcriptomics of human pancreatic endocrine cells almost exclusively rely on freshly isolated islets. However, human islets are limited in availability. Furthermore, the extensive processing steps during islet isolation and subsequent single cell dissolution might alter gene expressions. In this work, we report the development of a single-nucleus RNA sequencing (snRNA-seq) approach with targeted islet cell enrichment for endocrine-population focused transcriptomic profiling using frozen archival pancreatic tissues without islet isolation. Results: We cross-compared five nuclei isolation protocols and selected the citric acid method as the best strategy to isolate nuclei with high RNA integrity and low cytoplasmic contamination from frozen archival human pancreata. We innovated fluorescence-activated nuclei sorting based on the positive signal of NKX2-2 antibody to enrich nuclei of the endocrine population from the entire nuclei pool of the pancreas. Our sample preparation procedure generated high-quality single-nucleus gene-expression libraries while preserving the endocrine population diversity. In comparison with single-cell RNA sequencing (scRNA-seq) library generated with live cells from freshly isolated human islets, the snRNA-seq library displayed comparable endocrine cellular composition and cell type signature gene expression. However, between these two types of libraries, differential enrichments of transcripts belonging to different functional classes could be observed. Conclusions: Our work fills a technological gap and helps to unleash frozen archival pancreatic tissues for molecular profiling targeting the endocrine population. This study opens doors to retrospective mappings of endocrine cell dynamics in pancreatic tissues of complex histopathology. We expect that our protocol is applicable to enrich nuclei for transcriptomics studies from various populations in different types of frozen archival tissues. [ABSTRACT FROM AUTHOR]

Mutually beneficial partnerships between genomics researchers and North American Indigenous Nations are rare yet becoming more common. Here, we present one such partnership that provides insight into the peopling of the Americas and furnishes another line of evidence that can be used to further treaty and Indigenous rights. We show that the genomics of sampled individuals from the Blackfoot Confederacy belong to a previously undescribed ancient lineage that diverged from other genomic lineages in the Americas in Late Pleistocene times. Using multiple complementary forms of knowledge, we provide a scenario for Blackfoot population history that fits with oral tradition and provides a plausible model for the evolutionary process of the peopling of the Americas. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether letrozole improved outcomes in subsequent controlled ovarian hyperstimulation (COH) cycles. Methods: This was a retrospective repeated measures cohort study examining COH cycles. Patients were included if they underwent two cycles for unexplained infertility, male factor infertility, or planned oocyte/embryo cryopreservation. The first cycles for all patients implemented a non-letrozole, conventional gonadotropin protocol. Second cycles for the study group included letrozole (2.5–7.5 mg for 5 days) with no medication change to second cycles amongst controls. Our primary objective was to compare oocyte yield. Cohorts were then subdivided by pursuit of oocyte (OC) or embryo (IVF) cryopreservation. Secondary outcome amongst the OC subgroup was oocyte maturation index (metaphase II (MII)/total oocytes). Secondary outcomes amongst the IVF subgroup were normal fertilization rate (2-pronuclear zygotes (2PN)/oocytes exposed to sperm), blastocyst formation rate (blastocysts/2PNs), and embryo ploidy (%euploid and aneuploid). Results: Fifty-four cycles (n = 27) were included in letrozole and 108 cycles (n = 54) were included in control. Oocyte yield was higher in second cycles (p < 0.008) in the letrozole group but similar in second cycles (p = 0.26) amongst controls. Addition of letrozole did not impact MII index (p = 0.90); however, MII index improved in second cycles amongst controls (p < 0.001). Both groups had similar rates of normal fertilization (letrozole: p = 0.52; control: p = 0.61), blast formation (letrozole: p = 0.61; control: p = 0.84), euploid (letrozole: p = 0.29; control: p = 0.47), and aneuploid embryos (letrozole: p = 0.17; control: p = 0.78) between cycles. Conclusions: Despite improved oocyte yield, letrozole did not yield any difference in oocyte maturation or embryo outcomes. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study investigates the correlation between vaginal microecology and pregnancy outcomes and explores their impact on endometrial microbiota composition during frozen embryo transfer (FET) cycles. Additionally, the impact of transvaginal Lactobacillus supplementation on reproductive outcomes in patients with previous failed cycles was assessed. Methods: A total of 379 patients undergoing FET at a reproductive medicine center were categorized into clinical pregnancy (CP), miscarriage (MISC), and non-pregnant (NP) groups. Vaginal specimens were collected for microecological evaluation prior to embryo transfer. Endometrial microbiota samples were obtained during embryo transfer for 16S rRNA gene sequencing analysis to assess endometrial microbiota composition. Vaginal microecological indicators, including pH, Lactobacillus dominance, and leukocyte esterase activity, were measured. Transvaginal Lactobacillus supplementation was investigated in 60 patients with previous failed cycles. Results: Vaginal microecology significantly correlated with pregnancy outcomes, with normal microecology associated with a higher clinical pregnancy rate. Vaginal pH and leukocyte esterase activity were significantly associated with clinical pregnancy. Furthermore, vaginal microecological differences significantly impacted endometrial microbiota composition. However, no significant differences were observed in endometrial microbiota composition among the CP, MISC, and NP groups. Notably, transvaginal Lactobacillus supplementation increased the clinical pregnancy rate without affecting the miscarriage rate. Conclusion: This study highlights that normal vaginal microecology, characterized by lower pH and leukocyte esterase negativity, is associated with a higher likelihood of clinical pregnancy following FET. Importantly, vaginal microecological differences influence endometrial microbiota composition. Moreover, transvaginal Lactobacillus supplementation appears promising in improving clinical pregnancy rates in patients with previous failed cycles. These findings contribute to a better understanding of the interplay between vaginal and endometrial microbiota and offer potential interventions to enhance reproductive success in assisted reproductive technologies. [ABSTRACT FROM AUTHOR]

Purpose: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). Methods: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. Results: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13–1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000–1999 pg/mL and 1000–1999 pg/mL versus 2000–2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73–0.95; aRR 0.91, 95% CI 0.85–0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000–2999 pg/mL versus 3000–3999 pg/mL, aRR 1.04, 95% CI 0.97–1.11; 3000–3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9–1.04). Conclusion: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000–2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of serum progesterone (P4) on the day of embryo transfer (ET) when dydrogesterone (DYD) and micronized vaginal progesterone (MVP) are combined as luteal phase support (LPS) in a hormone replacement therapy (HRT) frozen ET (FET) cycles. Methods: Retrospective study, including single euploid HRT FET cycles with DYD and MVP as LPS and P4 measurement on ET day. Initially, patients with P4 levels < 10 ng/ml increased MVP to 400 mg/day; this "rescue" was abandoned later. Results: 560 cycles of 507 couples were included. In 275 women, serum P4 level was < 10 ng/ml on the ET day. Among those with low P4 levels, MVP dose remained unchanged in 65 women (11.6%) and was increased in 210 women (37.5%). Women with P4 levels ≥ 10 ng/ml continued LPS without modification. Overall pregnancy rates in these groups were 61.5% (40/65), 54.8% (115/210), and 48.4% (138/285), respectively (p = n.s.). Association of serum P4 levels with ongoing pregnancy rates was analyzed in women without any additional MVP regardless of serum P4 levels (n = 350); multivariable analysis (adjusted for age, BMI, embryo quality (EQ)) did not show a significant association of serum P4 levels with OPR (OR 0.96, 95% CI 0.90–1.02; p = 0.185). Using inverse probability treatment weights, regression analysis in the weighted sample showed no significant association between P4 treatment groups and OP. Compared to fair EQ, the transfer of good EQ increased (OR 1.61, 95% CI 1.22–2.15; p = 0.001) and the transfer of a poor EQ decreased the odds of OP (OR 0.73, 95% CI 0.55–0.97; p = 0.029). Conclusion: In HRT FET cycle, using LPS with 300 mg/day MVP and 30 mg/day DYD, it appears that serum P4 measurement and increase of MVP in patients with P4 < 10 ng/ml are not necessary. [ABSTRACT FROM AUTHOR]