Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials.

PROPOSE: The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles. METHOD: A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: "dual trigger," "GnRHa," "hCG," "IVF." Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR). RESULTS: We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]). CONCLUSION: The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity. RELEVANCE: After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.

Robotic Hysterectomy with Ureter Identification and Uterine Artery Ligation for Benign Gynecological Conditions: An Early-Year Single-Center Experience.

The use and application of robotic systems with a high-definition, three-dimensional vision system and advanced EndoWrist technology have become widespread. We sought to share our clinical experience with ureter identification and preventive uterine artery ligation in robotic hysterectomy. The records of patients undergoing robotic hysterectomy between May 2014 and December 2015, including patient preoperative characteristics, operative time, and postoperative outcomes, were analyzed. We evaluated the feasibility and safety of using early ureteral identification and preventive uterine artery ligation in robotic hysterectomy in patients with benign gynecological conditions. Overall, 49 patients diagnosed with benign gynecological conditions were evaluated. The mean age of the patients and mean uterine weight were 46.2 ± 5.3 years and 348.7 ± 311.8 g, respectively. Robotic hysterectomy achieved satisfactory results, including a short postoperative hospital stay (2.7 ± 0.8 days), low conversion rate (n = 0), and low complication rate (n = 1; 2%). The average estimated blood loss was 109 ± 107.2 mL. Our results suggest that robotic hysterectomy using early ureteral identification and preventive uterine artery ligation is feasible and safe in patients with benign gynecological conditions.

Association between Leukemia Inhibitory Factor Gene Polymorphism and Clinical Outcomes among Young Women with Poor Ovarian Response to Assisted Reproductive Technology.

BACKGROUND: Does the presence of single-nucleotide polymorphisms (SNPs) in the leukemia inhibitory factor (LIF) gene affect ovarian response in infertile young women? METHODS: This was a case-control study recruiting 1744 infertile women between January 2014 to December 2015. The 1084 eligible patients were stratified into four groups using the POSEIDON criteria. The gonadotropin-releasing hormone receptor (GnRHR), follicle-stimulating hormone receptor (FSHR), anti-Müllerian hormone (AMH), and LIF SNP genotypes were compared among the groups. The distributions of LIF and FSHR among younger and older patients were compared. Clinical outcomes were also compared. RESULTS: The four groups of poor responders had different distributions of SNP in LIF. The prevalence of LIF genotypes among young poor ovarian responders differed from those of normal responders. Genetic model analyses in infertile young women revealed that the TG or GG genotype in the LIF resulted in fewer oocytes retrieved and fewer mature oocytes relative to the TT genotypes. In older women, the FSHR SNP genotype contributed to fewer numbers of mature oocytes. CONCLUSIONS: LIF and FSHR SNP genotypes were associated with a statistically significant reduction in ovarian response to controlled ovarian hyperstimulation in younger and older women with an adequate ovarian reserve, respectively.

Engineered Immature Testicular Tissue by Electrospun Mats for Prepubertal Fertility Preservation in a Bioluminescence Imaging Transgenic Mouse Model.

Prepubertal boys with cancer may suffer from reduced fertility and maturity following gonadotoxic chemoradiotherapy. Thus, a viable method of immature testicular tissue (ITT) preservation is required in this cohort. In this study, we used poly-L-lactic acid electrospun scaffolds with two levels of fineness to support the development of ITT transplanted from transgenic donors to wild-type recipient mice. The purpose of this study was to evaluate the potential of ITT transplantation and spermatogenesis after using the two scaffolds, employing bioluminescence imaging for evaluation. The results suggest that ITT from 4-week-old mice possessed the most potential in spermatogenesis on the 70th day, together with the fine electrospun scaffolds. Moreover, bioluminescent imaging intensity was observed in recipient mice for up to 107 days, approximately six times more than the coarse electrospun scaffold and the control group. This occurs since the fine scaffold is more akin to the microenvironment of native testicular tissue as it reduces stiffness resulting from micronization and body fluid infiltration. The thermal analysis also exhibited recrystallization during the biodegradation process, which can lead to a more stable microenvironment. Overall, these findings present the prospect of fertility preservation in prepubertal males and could serve as a framework for future applications.

Tracking Immature Testicular Tissue after Vitrification In Vitro and In Vivo for Pre-Pubertal Fertility Preservation: A Translational Transgenic Mouse Model.

Pediatric cancer survivors experiencing gonadotoxic chemoradiation therapy may encounter subfertility or permanent infertility. However, previous studies of cryopreservation of immature testicular tissue (ITT) have mainly been limited to in vitro studies. In this study, we aim to evaluate in vitro and in vivo bioluminescence imaging (BLI) for solid surface-vitrified (SSV) ITT grafts until adulthood. The donors and recipients were transgenic and wild-type mice, respectively, with fresh ITT grafts used as the control group. In our study, the frozen ITT grafts remained intact as shown in the BLI, scanning electron microscopy (SEM) and immunohistochemistry (IHC) analyses. Graft survival was analyzed by BLI on days 1, 2, 5, 7, and 31 after transplantation. The signals decreased by quantum yield between days 2 and 5 in both groups, but gradually increased afterwards until day 31, which were significantly stronger than day 1 after transplantation (p = 0.008). The differences between the two groups were constantly insignificant, suggesting that both fresh and SSV ITT can survive, accompanied by spermatogenesis, until adulthood. The ITT in both groups presented similar BLI intensity and intact cells and ultrastructures for spermatogenesis. This translational model demonstrates the great potential of SSV for ITT in pre-pubertal male fertility preservation.

Immature Testicular Tissue Engineered from Weaned Mice to Adults for Prepubertal Fertility Preservation-An In Vivo Translational Study.

Male pediatric survivors of cancers and bone marrow transplantation often require adjuvant chemoradiation therapy that may be gonadotoxic. The optimal methods to preserve fertility in these prepubertal males are still under investigation. This manuscript presents an in vivo experiment which involved transplantation of immature testicular tissues (ITT) from transgenic donor, to wild-type recipient mice. Donors and recipients were age-mismatched (from 20-week-old donors to 3-week-old recipients, and vice versa) and the transplantation sites involved the abdomen, skin of the head, back muscle, and scrotum. The application of poly-l-lactic acid (PLLA) scaffold was also evaluated in age-matched donors and recipients (both 3-weeks-old). To quantitively evaluate the process of spermatogenesis after ITT transplantation and scaffold application, bioluminescence imaging (BLI) was employed. Our result showed that ITT from 3-week-old mice had the best potential for spermatogenesis, and the optimal transplantation site was in the scrotum. Spermatogenesis was observed in recipient mice up to 51 days after transplantation, and up to the 85th day if scaffold was used. The peak of spermatogenesis occurred between the 42nd and 55th days in the scaffold group. This animal model may serve as a framework for further studies in prepubertal male fertility preservation.

Length of estradiol exposure >100 pg/ml in the follicular phase affects pregnancy outcomes in natural frozen embryo transfer cycles.

STUDY QUESTION: Do the length of follicular phase estradiol exposure and the total length of the follicular phase affect pregnancy and live birth outcomes in natural frozen embryo transfer (FET) cycles? SUMMARY ANSWER: An estradiol level >100 pg/ml for ≤4 days including the LH surge day is associated with worse pregnancy and live birth outcomes; however, the total length of the follicular phase is not associated with pregnancy and live birth outcomes. WHAT IS KNOWN ALREADY: An estradiol level that increases above 100 pg/ml and continues to increase is indicative of the selection and development of a dominant follicle. In programmed FET cycles, a limited duration of follicular phase estradiol of <9 days results in worse pregnancy rates, but a prolonged exposure to follicular phase estradiol for up to 4 weeks does not affect pregnancy outcomes. It is unknown how follicular phase characteristics affect pregnancy outcomes in natural FET cycles. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included infertile patients in an academic hospital setting who underwent their first natural frozen autologous Day-5 embryo transfer cycle in our IVF clinic between 01 January 2013 and 31 December 2018. Donor oocyte and gestational carrier cycles were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcomes of this study were pregnancy and live birth rates. Patients were stratified into two groups based on the cohorts' median number of days from the estradiol level of >100 pg/ml before the LH surge: Group 1 (≤4 days; n = 1052 patients) and Group 2 (>4 days; n = 839 patients). Additionally, patients were stratified into two groups based on the cohorts' median cycle day of LH surge: Group 1 (follicular length ≤15 days; n = 1287 patients) and Group 2 (follicular length >15 days; n = 1071 patients). A subgroup analysis of preimplantation genetic testing for aneuploidies (PGT-A) embryo transfer cycles was performed. Logistic regression analysis, adjusted a priori for patient age, number of embryos transferred, and use of PGT-A, was used to estimate the odds ratio (OR) with a 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: In the length of elevated estradiol analysis, the pregnancy rate per embryo transfer was statistically significantly lower in patients with an elevated estradiol to surge of ≤4 days (65.6%) compared to patients with an elevated estradiol to surge of >4 days (70.9%; OR 1.30 (95% CI 1.06-1.58)). The live birth rate per embryo transfer was also statistically significantly lower in patients with an elevated estradiol to surge of ≤4 days (46.6%) compared to patients with an elevated estradiol to surge of >4 days (52.0%; OR 1.23 (95% CI 1.02-1.48)). In the follicular phase length analysis, the pregnancy rate per embryo transfer was similar between patients with a follicular length of ≤15 days (65.4%) and patients with a follicular length of >15 days (69.0%; OR 1.12 (95% CI 0.94-1.33)): the live birth rate was also similar between groups (45.5% vs 51.5%, respectively; OR 1.14 (95% CI 0.97-1.35)). In all analyses, once a pregnancy was achieved, the length of the follicular phase or the length of elevated oestradiol >100 pg/ml no longer affected the pregnancy outcomes. LIMITATIONS, REASONS FOR CAUTION: The retrospective design of this study is subject to possible selection bias in regard to which patients at our clinic were recommended to undergo a natural FET compared to a fresh embryo transfer or programmed FET. To decrease the heterogeneity of our study population, we only included patients who had blastocyst embryo transfers; therefore, it is unknown whether similar results would be observed in patients with cleavage-stage embryo transfers. The retrospective nature of the study design did not allow randomized to a specific ovarian stimulation or ovulation trigger protocol. However, all patients were managed with the standardized protocols at a single center, which strengthens the external validity of our results when compared to a study that only evaluates one specific stimulation protocol. WIDER IMPLICATIONS OF THE FINDINGS: Our observations provide cycle-level characteristics that can be applied during a natural FET cycle to help optimize embryo transfer success rates. Physicians should consider the parameter of number of days that oestradiol is >100 pg/ml prior to the LH surge when determining whether to proceed with embryo transfer in a natural cycle. This cycle-specific characteristic may also help to provide an explanation for some failed transfer cycles. Importantly, our findings should not be used to determine whether to recommend a natural or a programmed FET cycle for a patient, but rather, to identify natural FET cycles that are not optimal to proceed with embryo transfer. STUDY FUNDING/COMPETING INTEREST(S): No financial support, funding, or services were obtained for this study. The authors do not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Could PGT-A pick up true abnormalities that have clinical relevance? Retrospective analysis of 1043 embryos.

OBJECTIVE: To determine whether preimplantation genetic testing for aneuploidy (PGT-A) could pick up true abnormalities that have clinical relevance. MATERIALS AND METHODS: This was a retrospective cohort study of patients who underwent in vitro fertilization with PGT-A from 2015 to 2017. We evaluated the associations of aneuploidy and mosaicism with maternal age, the chromosome abnormalities present in individual chromosomes, and the effect of embryo sex on the proportion of each type of error in the four chromosomes most frequently affected. RESULT(S): A total of 1043 embryos from 255 patients (mean maternal age = 39 ± 4 years) were included in the initial analysis. Of these, 36% (377/1043) were euploid, 47% (487/1043) were aneuploid, 13% (140/1043) contained mosaicism, and 4% (39/1043) gave no result. We excluded the 39 embryos with no result; thus, 1004 embryos were included in the analysis. Increased aneuploidy was associated with increased maternal age, but the rate of embryo mosaicism was not. A combined analysis of aneuploidy with noncomplex abnormalities and mosaicism showed that chromosomes 22, 21, 16, and 15 were the most frequently involved. Chromosome 22 showed the highest proportion of mosaicism and chromosome 15 showed the highest proportion of aneuploidy. When we included embryo sex in the analysis, embryo sex was associated with these chromosome errors in the most susceptible chromosome, 22. CONCLUSION(S): PGT-A showed that chromosomes 22, 21, 16, and 15 were the most frequently involved among common chromosome abnormalities, comparable with those of published data analyzed from spontaneous abortion. This result suggested that PGT-A could pick up abnormalities that have clinical relevance to spontaneous abortion. Moreover, we identified a role of embryo sex in these chromosomal errors on chromosome 22.

Healthy live births after mosaic blastocyst transfers with the use of next-generation sequencing.

OBJECTIVE: To determine whether transfer of high-mosaicism (≥50%) embryos can result in healthy newborns. CASE REPORT: Two embryos resulting from controlled ovarian stimulation (COS) in Patient one, 41 years of age (y/o), underwent preimplantation genetic testing for aneuploidy (PGT-A), which demonstrated that one was mosaic (68%) and the other aneuploid; the mosaic embryo was transferred. Amniocentesis at 18 weeks of gestational age (GA) revealed a normal 46, XY karyotype. A phenotypically normal boy was delivered at 39 and 5/7 weeks of GA. For Patient two, 39 (y/o), nine embryos obtained after COS underwent PGT-A, indicating one euploid, four mosaic, and four aneuploid embryos. One euploid and one mosaic (50%) embryo were transferred, resulting in a twin pregnancy. Amniocentesis at 18 weeks of GA showed both fetuses had normal 46, XY karyotypes. Two phenotypically normal boys were delivered at 37 2/7 weeks of GA. CONCLUSION: Transfer of high-mosaicism embryos selected using current techniques can result in healthy euploid newborns. Amniocentesis suggested that mosaic embryos can be self-corrected before 18 weeks of GA.

Targeting myotonic dystrophy by preimplantation genetic diagnosis-karyomapping.

OBJECTIVE: To report a case with Myotonic dystrophy type I with successful preimplantation genetic diagnosis-karyomapping. CASE REPORT: A 34-year-old female carrier of myotonic dystrophy type I was treated at our clinic with a successful pregnancy after preimplantation genetic testing for monogenic disorders using karyomapping of her blastocysts. CONCLUSION: Myotonic dystrophy type I is an inherited autosomal dominant disease producing various neuromuscular disturbances. Offspring of carriers have a 50% chance of carrying CTG repeat sequences in the DMPK gene, and various time-consuming methodologies have been developed for genetic diagnosis. With a novel, efficient, and precise method by karyomapping using single nucleotide polymorphism arrays to diagnose single gene disorders, one could terminate the transmission of single gene disorder. Herein, we reported a 34-year-old female carrier of myotonic dystrophy type I achieve a successful pregnancy after preimplantation genetic testing for monogenic disorders using karyomapping method of her blastocysts.

A novel strategy of using corifollitropin alfa in the ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol in unselected patients: A patient-friendly alternative.

OBJECTIVE: To compare the outcomes of in vitro fertilization (IVF) and fresh embryo transfer (ET) using corifollitropin alfa in ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol and GnRH antagonist protocol. MATERIALS AND METHODS: A total of 245 unselected patients undergoing IVF/fresh ET were enrolled between January 1 and December 31, 2017, including 135 treated with ultrashort GnRHa protocol and 110 treated with antagonist protocol. The primary outcomes were number of total injections and outpatient department (OPD) visits before ovulation triggering. The secondary outcomes were the duration of stimulation, dosage of additional gonadotropin for ovarian hyperstimulation, rates of pregnancy, clinical pregnancy, live birth, ovarian response, and ovarian hyperstimulation syndrome (OHSS) rate. RESULTS: Patients treated with ultrashort GnRHa required less additional gonadotropin, fewer total injections, but had better ovarian responses, including more oocytes retrieved, more metaphase II oocytes, and more blastocysts than those treated with antagonist did. A premature LH surge occurred only in six patients treated with antagonist protocol. The rates of pregnancy (37.0% vs. 43.6%), clinical pregnancy (25.2% vs. 34.6%), and live birth (19.3% vs. 30.0%) did not differ significantly between the two groups. The OHSS rate was similar in the two groups. CONCLUSION: In unselected patients using corifollitropin alfa, the ultrashort GnRHa protocol needed lower dose of additional gonadotropin and fewer injections but produced similar pregnancy outcomes than antagonist protocol did, suggesting that the ultrashort GnRHa protocol could be an alternative.

Non-Apnea Sleep Disorder Increases the Risk of Subsequent Female Infertility-A Nationwide Population-Based Cohort Study.

Study Objectives: Non-apnea sleep disorder (NASD) increases the risk of hypertension, type 2 diabetes mellitus, chronic kidney disease, cardiovascular disease, and stroke. However, the risk and the time interval of NASD to female infertility has not been thoroughly understood. Our study aimed to determine whether NASD increases the subsequent risk of female infertility. Methods: This study utilized outpatient and inpatient data from the Longitudinal Health Insurance Database between 2000 and 2010 in Taiwan. We enrolled 50,154 females aged 20 to 45 years old and diagnosed with NASD as outpatients ≥2 times or hospitalized, 16,718 of them who matched our criteria were assigned to the study group. For each NASD patient, two comparison patients were frequency matched by age (each 5-year span), index date, and comorbidities as the control cohort with a total of 33,436 patients. We conducted Cox proportional hazard regression analysis to estimate the effects of NASD on female infertility. Results: The NASD cohort had an adjusted hazard ratio (HR) of subsequent female infertility of 3.718-fold higher than that of the cohort without sleep disorders. In the stratified age group, NASD had the highest impact on 26-30 years old, with an adjusted HR of 5.146 followed by 31-35 years old (adjusted HR = 3.356). The Kaplan-Meier analysis also showed that in the sixth year of follow-up, the incidence of female infertility was higher in the NASD cohort than in the general population cohort till the end of the follow-up. Conclusions: Our study demonstrates that NASD patients are at a higher risk of developing female infertility.

The impact of prenatal group B streptococcus screening as a national health policy in Taiwan.

OBJECTIVE: There was no national data on group B streptococcus (GBS) infections in Taiwan. Until 2012, when prenatal GBS screening was introduced to obstetric practices as a national health policy aimed at reducing neonatal GBS infections. The purpose of this study was to examine the impact of this national health policy on the incidence of maternal GBS colonization and neonatal GBS infection rate. Relatedly, the clinical characteristics of neonatal GBS infection were investigated to determine the correlations between the incidence of maternal GBS colonization and the neonatal GBS infection rate. MATERIALS AND METHODS: This population-based nationwide study used data for 2012-2013 from the National Health Insurance Research Database of Taiwan. A total of 789 newly diagnosed pregnant women with genital GBS infection were recruited. RESULTS: The maternal GBS screening rate was 93.2%. The maternal colonization rate of GBS was around 8.2%, and the incidence of neonatal GBS infection was 22.6%. The data indicate that no sepsis was developed in any of the cases, while fever was found in 3 cases (3/179, 1.7%) and UTI was found in 1 case (1/179, 0.6%). CONCLUSIONS: We conclude that a policy calling for universal maternal rectovaginal cultures for GBS with intrapartum antibiotic prophylaxis is a good national policy for reducing morbidity due to GBS infections in neonates in Taiwan.

OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis.

We investigated the role of oxidative stress-responsive kinase-1 (OSR1) and STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase (SPAK), upstream regulators of the Na+-K+-2Cl- cotransporter (NKCC1)-essential for spermatogenesis-in mouse models of male fertility. Global OSR1+/- gene mutations, but not global SPAK-/- or Sertoli cell (SC)-specific OSR1 gene knockout (SC-OSR1-/-), cause subfertility with impaired sperm function and are associated with reduced abundance of phosphorylated (p)-NKCC1 but increased p-SPAK expression in testicular tissue and spermatozoa. To dissect further in a SC-specific manner the compensatory effect of OSR1 and SPAK in male fertility, we generated SC-OSR1-/- and SPAK-/- double knockout (DKO) male mice. These are infertile with defective spermatogenesis, presenting a SC-only-like syndrome. Disrupted meiotic progression and increased germ cell apoptosis occurred in the first wave of spermatogenesis. The abundance of total and p-NKCC1 was significantly decreased in the testicular tissues of DKO mice. These results indicate that OSR1 and SPAK cooperatively regulate NKCC1-dependent spermatogenesis in a SC-restricted manner.

Estrogen Enhances the Cell Viability and Motility of Breast Cancer Cells through the ERα-ΔNp63-Integrin ß4 Signaling Pathway.

Estrogen induces ERα-positive breast cancer aggressiveness via the promotion of cell proliferation and survival, the epithelial-mesenchymal transition, and stem-like properties. Integrin ß4 signaling has been implicated in estrogen/ERα-induced tumorigenicity and anti-apoptosis; however, this signaling cascade poorly understood. ΔNp63, an N-terminally truncated isoform of the p63 transcription factor, functions as a transcription factor of integrinß4 and therefore regulates cellular adhesion and survival. Therefore, the aim of the present study was to investigate the estrogen-induced interaction between ERα, ΔNp63 and integrin ß4 in breast cancer cells. In ERα-positive MCF-7 cells, estrogen activated ERα transcription, which induced ΔNp63 expression. And ΔNp63 subsequently induced integrin ß4 expression, which resulted in AKT phosphorylation and enhanced cell viability and motility. Conversely, there was no inductive effect of estrogen on ΔNp63-integrinß4-AKT signaling or on cell viability and motility in ERα-negative MDA-MB-231 cells. ΔNp63 knockdown abolishes these estrogen-induced effects and reduces cell viability and motility in MCF-7 cells. Nevertheless, ΔNp63 knockdown also inhibited cell migration in MDA-MB-231 cells through reducing integrin ß4 expression and AKT phosphorylation. In conclusion, estrogen enhances ERα-positive breast cancer cell viability and motility through activating the ERα-ΔNp63-integrin ß4 signaling pathway to induce AKT phosphorylated activation. Those findings should be useful to elucidate the crosstalk between estrogen/ER signaling and ΔNp63 signaling and provide novel insights into the effects of estrogen on breast cancer progression.

Robotic surgery in complicated gynecologic diseases: experience of Tri-Service General Hospital in Taiwan.

OBJECTIVE: Minimally invasive surgery has been the trend in various specialties and continues to evolve as new technology develops. The development of robotic surgery in gynecology remains in its infancy. The present study reports the first descriptive series of robotic surgery in complicated gynecologic diseases in Taiwan. MATERIALS AND METHODS: From March 2009 to February 2011, the records of patients undergoing robotic surgery using the da Vinci Surgical System were reviewed for patient demographics, indications, operative time, hospital stay, conversion to laparotomy, and complications. RESULTS: Sixty cases were reviewed in the present study. Forty-nine patients had benign gynecologic diseases, and 11 patients had malignancies. These robot-assisted laparoscopic procedures include nine hysterectomy, 15 subtotal hysterectomy, 13 myomectomy, eight staging operation, two radical hysterectomy, five ovarian cystectomy, one bilateral salpingo-oophorectomy and myomectomy, two resections of deep pelvic endometriosis, one pelvic adhesiolysis, three sacrocolpopexy and one tuboplasty. Thirty-three patients had prior pelvic surgery, and one had a history of pelvic radiotherapy. Adhesiolysis was necessary in 38 patients to complete the whole operation. Robotic myomectomy was easily accomplished in patients with huge uterus or multiple myomas. The suturing of myometrium or cervical stump after ligation of the uterine arteries minimized the blood loss. In addition, it was much easier to dissect severe pelvic adhesions. The dissection of para-aortic lymph nodes can be easily accomplished. All these surgeries were performed smoothly without ureteral, bladder or bowel injury. CONCLUSION: The present analyses include various complicated gynecologic conditions, which make the estimation of the effectiveness of robotic surgery in each situation individually not appropriate. However, our experiences do show that robotic surgery is feasible and safe for patients with complicated gynecologic diseases.

Immunologic regulation in pregnancy: from mechanism to therapeutic strategy for immunomodulation.

The immunologic interaction between the fetus and the mother is a paradoxical communication that is regulated by fetal antigen presentation and/or by recognition of and reaction to these antigens by the maternal immune system. There have been significant advances in understanding of abnormalities in the maternal-fetal immunologic relationship in the placental bed that can lead to pregnancy disorders. Moreover, immunologic recognition of pregnancy is vital for the maintenance of gestation, and inadequate recognition of fetal antigens may cause abortion. In this paper, we illustrate the complex immunologic aspects of human reproduction in terms of the role of human leukocyte antigen (HLA), immune cells, cytokines and chemokines, and the balance of immunity in pregnancy. In addition, we review the immunologic processes of human reproduction and the current immunologic therapeutic strategies for pathological disorders of pregnancy.

Quantitative DNA methylation analysis detects cervical intraepithelial neoplasms type 3 and worse.

BACKGROUND: DNA methylation may be used a potential biomarker for detecting cervical cancer. The authors of this report used quantitative methylation analysis of 4 genes in a full spectrum of cervical lesions to test its potential clinical application. METHODS: This hospital-based, retrospective, case-control study was conducted in 185 patients and included patients who had a normal uterine cervix (n = 53), cervical intraepithelial neoplasm type 1 (CIN1) (n = 37), CIN2 (n = 22), CIN3 (n = 24), carcinoma in situ (CIS) (n = 22), squamous cell carcinoma (SCC, n = 20), and adenocarcinoma (AC) (n = 7). Methylation levels of the genes sex-determining region Y, box 1 (SOX1); paired box gene 1 (PAX1); LIM homeobox transcription factor 1α (LMX1A), and NK6 transcription factor-related locus 1 (NKX6-1) were determined by using real-time methylation-specific polymerase chain reaction (PCR) amplification. Cutoff values of the percentage of methylation reference (PMR) for different diagnoses were determined to test the sensitivity and specificity and to generate receiver operating characteristic (ROC) curves. Two-sided Mann-Whitney U tests were used to test differences in PMR between groups. RESULTS: The PMRs of the 4 genes were significantly higher in CIN3 and worse (CIN3+) lesions than the PMRs in specimens of normal cervix and CIN1 or CIN2 (P < .001). ROC curve analysis demonstrated that the sensitivity, specificity, and accuracy for detecting CIN3+ lesions were 0.88, 0.82, and 0.95, respectively, for SOX1; 0.78, 0.91, and 0.89, respectively, for PAX1; 0.77, 0.88, and 0.90, respectively, for LMX1A; and 0.93, 0.97, and 0.97, respectively, for NKX6-1. CONCLUSIONS: The current results indicated that quantitative PCR-based testing for DNA methylation of 4 genes holds great promise for cervical cancer screening and warrants further population-based studies using standardized DNA methylation testing.

Ifosfamide-induced encephalopathy in patients with uterine sarcoma.

OBJECTIVE: To report two cases of recurrent uterine sarcoma that developed ifosfamide-induced encephalopathy (IIE) with successful management. CASE REPORTS: The patient in the first case developed grade 4 toxicity and had a partial response after the fourth dose of intravenous methylene blue was administered. Full recovery occurred 4 days after the development of IIE. The patient in the second case, who had grade 3 toxicity, had completely recovered 32 hours after the first dose of thiamine. CONCLUSION: Careful evaluation of patients with recurrent gynecologic cancers and vigilance during infusion of chemotherapeutic regimens are important in reducing the risk and timely management of IIE. Both methylene blue and thiamine appear to be effective treatments for IIE.