Trophoblastic microcirculation occlusion as an adjunct to electric vacuum aspiration for the treatment of endogenous cesarean scar pregnancy.

OBJECTIVE: To describe a simple adjunct treatment option, trophoblastic microcirculation occlusion (TMO), which could change subsequent high-risk electric vacuum aspiration in patients with an endogenous cesarean scar pregnancy (CSP) into a routine conventional surgical procedure. Electric vacuum aspiration for the treatment of CSP may be associated with several significant complications, including hemorrhage and tissue remnants. Consequently, a second intervention, such as uterine artery embolization, resectoscopy, or methotrexate, may be required, thus complicating the surgical treatment of CSP. DESIGN: We demonstrate the principle and detailed technique of TMO treatment using animations, video clips, and slides. The study was approved by the institutional review board of Hangzhou Women's Hospital. SETTING: Tertiary maternity hospital. PATIENT(S): The video shows a 30-year-old woman with a 5-week endogenous CSP. The procedural steps were repeated in another 6 patients suffering from endogenous CSP (Table 1). Written informed consent was obtained from each patient. INTERVENTION(S): In patients with a CSP, the syncytiotrophoblastic cells erode the helicine arteries in the inner uterine myometrium. The cytotrophoblastic cells extend as villi tissue into the syncytiotrophoblast. Maternal blood enters the intervillous space between the cytotrophoblast and syncytiotrophoblast. The syncytiotrophoblast, cytotrophoblast, and intervillous space constitute the trophoblastic microcirculation, which subsequently becomes the main blood supply to the gestational sac (Fig. 1). During TMO treatment, the trophoblastic microcirculation is identified by contrast-enhanced ultrasound with the cubital vein injected with sulfur hexafluoride microbubbles (Bracco, Switzerland). A 21-gauge needle (200 mm long) was punctured vaginally into the uterine myometrium surrounding the syncytiotrophoblast at 3 different points, and a total of 8 mL sclerosant was injected directly to seal the trophoblastic microcirculation. Complete compression of the helicine arteries for trophoblastic blood supply is the key to TMO treatment (Fig. 2, see video interpretation for detailed information). A repeat contrast-enhanced ultrasound was performed after injection to confirm a significant reduction of blood flow in the trophoblast. An electric vacuum aspiration was performed 24 hours after TMO treatment to remove the products of conception completely. Surgical safety was enhanced by deep sedation and concurrent transabdominal ultrasound guidance. The levels of ß-human chorionic gonadotropin (ß-hCG) were measured weekly until a nonpregnant level was achieved. A follow-up ultrasound then was performed to confirm that the treatment was complete. MAIN OUTCOME MEASURE(S): The clinical value and feasibility of TMO treatment as an adjunct before high-risk electric vacuum aspiration for the management of endogenous CSP. RESULT(S): The TMO treatment was performed successfully in all 7 patients; the clinical outcomes are presented in Table 2. The TMO treatment significantly reduced the risk of hemorrhage during electric vacuum aspiration. No complications were detected perioperatively. Patients were discharged on day 1 postoperatively. Follow-up ultrasound, performed when the levels of ß-hCG had fallen to normal, failed to identify any remnants of the uterine corpus. One patient achieved an intrauterine pregnancy 7 months postoperatively and gave birth to a live baby at 39 weeks of gestation via repeat cesarean section. No cesarean scar dehiscence was observed. CONCLUSION(S): Surgical abortion of an endogenous CSP, with a high risk of intraoperative hemorrhage, can be performed with minimal blood loss in a single electric vacuum aspiration when assisted by TMO treatment. This technique provides good results in terms of bleeding reduction that are comparable to those in conventional patients. The TMO treatment can be accomplished via ultrasound-guided needle puncture, a technique that is available widely in the practice of reproductive medicine with a reduced need for consumable resources. The use of a simple adjunct treatment option, TMO, expands the indications of electric vacuum aspiration. This sequential treatment allows for completion of clinical management without the need for uterine artery embolization, resectoscopy, or methotrexate, thus simplifying the originally complicated form of surgical treatment for CSP.

Clomiphene citrate mild stimulation improved follicular development outcomes in PCOS women with high luteinizing hormone and poor ovarian response: A case report.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a main cause of anovulatory infertility in women of reproductive age. About 30% to 50% of patients with PCOS has high serum basal luteinizing hormone (LH) levels, and almost 5% of PCOS women with high LH have poor ovarian response (POR). We reported a case of a PCOS woman with high basal LH levels who canceled due to POR during two consecutive controlled ovarian stimulation treatments, which was considered to be related to the suppression of LH levels during downregulation. Clomiphene citrate (CC) combined with human menopausal urinary gonadotropin (HMG) mild regimen did not affect LH levels and obtained good follicular development, providing a new treatment insight for patients with PCOS combined with POR. PATIENT CONCERNS: A 28-year-old PCOS woman with high basal LH levels, underwent IVF assisted pregnancy treatment in our hospital, whom canceled due to POR during two traditional controlled ovulation induction program. Follicular development was finally achieved with CC milder protocol. DIAGNOSIS: This patient with the diagnosis of PCOS was undergone IVF assisted pregnancy treatment in our hospital. INTERVENTIONS: CC protocol supports the development of follicular. OUTCOMES: CC protocol resulted in better follicular development and high-quality embryos due to the continuous maintenance of an elevated LH levels. CONCLUSION: PCOS women with poor ovarian response required relatively higher LH to maintain the normal development of follicles.

Association Between Ambient Air Pollutants Exposure and Preterm Birth in Women Who Underwent in vitro Fertilization: A Retrospective Cohort Study From Hangzhou, China.

Objectives: Exposure to air pollutants has been linked to preterm birth (PTB) after natural conception. However, few studies have explored the effects of air pollution on PTB in patients who underwent in vitro fertilization (IVF). We aimed to investigate the association between ambient air pollutants exposure and PTB risk in IVF patients. Methods: This retrospective cohort study included 2,195 infertile women who underwent IVF treatment from January 2017 and September 2020 in Hangzhou Women's Hospital. Totally 1,005 subjects who underwent a first fresh embryo(s) transfer cycle were analyzed in this study. Residential exposure to ambient six air pollutants (PM2.5, PM10, SO2, NO2, CO, O3) during various periods of the IVF timeline were estimated by satellite remote-sensing and ground measurement. Cox proportional hazards models for discrete time were used to explore the association between pollutants exposure and incident PTB, with adjustment for confounders. Stratified analyses were employed to explore the effect modifiers. Results: The clinical pregnancy and PTB rates were 61.2 and 9.3%, respectively. We found that PM2.5 exposure was significantly associated with an increased risk of PTB during 85 days before oocyte retrieval [period A, adjusted hazard ratio, HR=1.09, 95%CI: 1.02-1.21], gonadotropin start to oocyte retrieval [period B, 1.07 (1.01-1.19)], first trimester of pregnancy [period F, 1.06 (1.01-1.14)], and the entire IVF pregnancy [period I, 1.07 (1.01-1.14)], respectively. An interquartile range increment in PM10 during periods A and B was significantly associated with PTB at 1.15 (1.04-1.36), 1.12 (1.03-1.28), and 1.14 (1.01-1.32) for NO2 during period A. The stratified analysis showed that the associations were stronger for women aged <35 years and those who underwent two embryos transferred. Conclusions: Our study suggests ambient PM2.5, PM10, and NO2 exposure were significantly associated with elevated PTB risk in IVF patients, especially at early stages of IVF cycle and during pregnancy.

Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells.

Extracellular vesicles derived from trophoblasts (T-EVs) play an important role in pregnancy, but the mechanism is not entirely clear. In this study, we found that HLA-E, which is mostly confined to the cytoplasm of trophoblast cells, was secreted by T-EVs. The level of HLA-E in T-EVs from unexplained recurrent spontaneous abortion (URSA) patients was lower than that in normal pregnancy (NP) and RSA patients who had an abnormal embryo karyotype (AK-RSA). T-EVs promoted secretion of IFN-γ and VEGFα by decidual NK (dNK) cells from URSA patients via HLA-E, VEGFα was necessary for angiogenesis and trophoblast growth, and IFN-γ inhibited Th17 induction. Glycolysis and oxidative phosphorylation (OxPhos) were involved in this process. Glycolysis but not OxPhos of dNK cells facilitated by T-EVs was dependent on mTORC1 activation. Inhibition of T-EV production in vivo increased the susceptibility of mice to embryo absorption, which was reversed by transferring exogenous T-EVs. T-EVs promoted secretion of IFN-γ and VEGFα by dNK cells to maintain pregnancy via Qa-1 in abortion-prone mouse models. This study reveals a new mechanism of pregnancy maintenance mediated by HLA-E via T-EVs.

Pregnancy confirmed after controlled ovarian stimulation for infertility: A case report.

RATIONAL: Induction of ovarian stimulation by use of the gonadotropin-releasing hormone agonist (GnRHa) long protocol in the luteal phase is a common practice and results in stable pregnancy and live births; it is often used in patients with normal ovarian function. Some patients with normal ovulation may be pregnant before ovulation induction, which can be easily confirmed by asking the patient about cessation of menstruation. However, some pregnancy complications may cause vaginal bleeding along with normal menstrual blood loss; in such a situation, hormone levels can often mirror that seen in pituitary down-regulation and the value of ß-HCG may be less than 5 mIU/mL. Under these conditions, the physician might start the cycle of ovarian stimulation. During ovarian stimulation, the increase in ß-HCG can cause premature luteinization and follicle maturation disorder, and poor embryo quality, which can easily be overlooked. In this study, we report a case of pregnancy at the end of controlled ovarian stimulation induced by GnRHa long protocol in the luteal phase, followed by follicle maturation disorder and poor embryo quality. This case provided a reference and served as a cautionary note that could perhaps obviate occurrence of similar cases. PATIENT CONCERNS: A 30-year-old woman with a diagnosis of unexplained infertility was scheduled for in vitro fertilization embryo culture (IVF) at our clinic. Pregnancy was confirmed at the end of controlled ovarian stimulation, which was followed by follicular maturation disorder and poor embryo quality. DIAGNOSIS: The patient with a diagnosis of unexplained infertility was scheduled for IVF at our clinic. INTERVENTIONS: Oocyte retrieval was still arranged for her after confirmation of pregnancy. As per the ß-HCG level and the trans-vaginal ultrasound examination findings, we considered 2 possibilities: an adverse intrauterine pregnancy or extra-uterine pregnancy. Therefore, we decided to terminate the pregnancy; hence, 50 mg/d of mifepristone was given for 2 days, combined with 200 µg misoprostol. OUTCOMES: Elevated ß-HCG level had an adverse effect on maturation and fertilization of oocytes, and even embryo quality. CONCLUSION: Once pregnancy is confirmed, ovulation induction should be terminated as soon as possible.

Anti-Müllerian Hormone Accelerates Pathological Process of Insulin Resistance in Polycystic Ovary Syndrome Patients.

Insulin resistance (IR) is one of the most common features of polycystic ovary syndrome (PCOS), which is related to obesity. Whether increased anti-Müllerian hormone (AMH) levels in PCOS are involved in the pathogenesis of insulin resistance remains unclear. We investigated serum levels of leptin and AMH along with basic clinical and metabolic parameters in 114 PCOS patients and 181 non-PCOS women. PCOS patients presented higher fasting blood glucose, insulin concentrations and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in addition to body mass index (BMI), lipids profiles and hormone levels. HOMA-IR showed a positive correlation with BMI, AMH, leptin, and low-density lipoprotein-cholesterol (LDL-c) levels. Interestingly, AMH is strongly positively correlated with HOMA-IR and insulin concentrations for 1st and 2nd hours of glucose treatment after fasting. Among PCOS women with BMI≥25 kg/m2, high AMH level group showed an increased HOMA-IR when compared to normal AMH level. However, among PCOS women with normal BMI, women with high AMH presented an elevated fasting insulin levels but not HOMA-IR when compared to normal AMH group. In vitro treatment of isolated islet cells with high concentration of leptin (200 ng/ml) or high leptin plus high concentration of AMH (1 ng/ml) significantly enhanced insulin secretion. Importantly, co-treatment of AMH plus leptin upregulates the expression of pro-apoptotic proteins, such as Bax, caspase-3, and caspase-8 after incubating with a high level of glucose. These results suggest that AMH may involve in the pathological process of pancreatic ß-cells in obese PCOS women.

Screening and identification of endometrial proteins as novel potential biomarkers for repeated implantation failure.

Inadequate endometrial receptivity may be responsible for the low implantation rate of transferred embryos in in vitro fertilization (IVF) treatments. Patients with repeated implantation failure (RIF) impact the clinical pregnancy rate for IVF. We collected endometrial tissue during the implantation window of hysteroscopy biopsies from September 2016 to December 2019 and clinical data were collected simultaneously. Patients were divided into RIF and pregnant controls group according to pregnancy outcomes. A total of 82 differentially expressed endometrial proteins were identified, including 55 up-regulated proteins (>1.50-fold, P < 0.05) and 27 down-regulated proteins (<0.67-fold, P < 0.05) by iTRAQ labeling coupled with the 2D LC MS/MS technique in the RIF group. String analysis found interactions between these proteins which assembled in two bunches: ribosomal proteins and blood homeostasis proteins. The most significant enriched Gene Ontology terms were negative regulation of hydrolase activity, blood microparticle, and enzyme inhibitor activity. Our results emphasized the corticosteroid-binding globulin and fetuin-A as the specific proteins of endometrial receptivity by Western-blot. Our study provided experimental data to establish the objective indicator of endometrial receptivity, and also provided new insight into the pathogenesis of RIF.

Proteomic Analysis of the Alterations in Follicular Fluid Proteins During Oocyte Maturation in Humans.

Many components in ovarian follicles (follicular fluid, cumulus cells, granular cells, etc.) dynamically change during folliculogenesis and play a positive or negative role in oocyte maturation. Infertile women who underwent intracytoplasmic sperm injection (ICSI) treatment in the reproductive medicine centre of Hangzhou Women's Hospital between October 2018 and October 2021 were included. The ovarian follicular fluid and cumulus cells of diminished ovarian response (DOR) patients and control subjects with medical records of clinical data were collected. In total, 31 differentially expressed proteins, including 10 upregulated proteins (>1.50-fold, P<0.05) and 21 downregulated proteins (<0.67-fold, P<0.05), were identified in mature vs. immature oocytes by iTRAQ labelling coupled with 2D LC-MS/MS. GO analysis revealed that 'cell population proliferation' was the most diverse enrichment trend between up/downregulated proteins, while phagosome process and the PI3K-Akt signaling pathway were the two most significant pathways revealed by KEGG enrichment classification. Human prostatic acid phosphatase (PAP, ACPP) and CD5 antigen-like (CD5L) were two proteins verified by ELISA to be differentially expressed between MII and Gv oocytes (P<0.0001 and P<0.0001, respectively). Further measurement found significantly lower level of ACPP in follicular fluids and cumulus cells of DOR patients (P=0.028 and P=0.004, respectively), as an indicator of oocyte quality. Otherwise, CD5L level is upregulated in follicular fluid of DOR patients (P<0.0001). Our study provided experimental data to establish the objective indicator of oocyte maturation in the microenvironment of ovarian follicles, and also provided new insight into the measurement of oocyte quality.

Association of exosomal microRNAs in human ovarian follicular fluid with oocyte quality.

The postponement of childbearing by women has led to an increase in infertility. The reproductive aging process leads to a decrease in both the quantity and quality of oocytes. The aim of this study was to investigate exosomal microRNAs in human ovarian follicular fluid and explore their potential association with oocyte quality. We collected ovarian follicle fluid from 68 patients and assigned the patients to A (superior oocyte quality) or B (poor oocyte quality) group according to their oocyte quality. Exosomal miRNAs were extracted, library constructed and sequenced using the Illumina HiSeq platform. Subsequently, we analyzed exosomal miRNA expression, predicted the miRNA target genes, and enriched Gene Ontology terms using GOSeq. Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed using miRanda. A total of 47 miRNAs were found to be significantly differentially expressed between group A and group B (p < 0.05). Among nine differentially expressed miRNAs that were previously known, seven were upregulated in group B. In silico analysis indicated that several of these exosomal miRNAs were involved in pathways implicated in oocyte quality. Analysis of the expression of exosomal miRNAs in human ovarian follicular fluid showed that they were critical for maintaining oocyte quality. Our findings provide the basis for further investigations of the functions of exosomal miRNAs in the ovarian microenvironment and suggest that these exosomal miRNAs may be potential biomarkers for evaluating oocyte quality. The findings are potentially important to maintain oocyte quality in clinical settings.

Cesarean scar pregnancy combined with arteriovenous malformation successfully treated with transvaginal fertility-sparing surgery: A case report and literature review.

INTRODUCTION: A cesarean scar pregnancy (CSP), when combined with an arteriovenous malformation (AVM), is a rare, but potentially life-threatening condition that may be associated with uncontrolled hemorrhage. Hysterectomy is indicated when conservative treatment fails. Preservation of fertility is challenging. PATIENT CONCERNS: We reported a 33-year-old woman with a CSP combined with an AVM who failed methotrexate administration as conservative treatment. DIAGNOSES: A CSP combined with an AVM was diagnosed via three-dimensional color Doppler angiogram and magnetic resonance imaging. INTERVENTIONS: Transvaginal removal of the ectopic gestation and repair of the uterine defect was performed without incident. OUTCOMES: The fertility of the patient was preserved and hysterectomy was avoided. CONCLUSION: Transvaginal fertility-sparing surgery may be successfully performed to prevent hysterectomy when conservative treatment fails in patients with a CSP combined with an AVM.

A Benign Uterine Leiomyoma with Disturbing Appearance.

Herein, we described a 53-year-old woman who underwent laparoscopic uterine myomectomy. The cut surface of the leiomyoma showed a grain appearance, instead of a whorled feature. The disturbing appearance was an unexpected surprise to the surgeon. The diagnosis of benign uterine leiomyoma was established through intraoperative frozen section and was identical to the subsequent permanent pathology.

Macrophage colony-stimulating factor (M-CSF) is an intermediate in the process of luteinizing hormone-induced decrease in natriuretic peptide receptor 2 (NPR2) and resumption of oocyte meiosis.

BACKGROUND: Luteinizing hormone (LH) regulation of the ligand, natriuretic peptide precursor type C, and its receptor, natriuretic peptide receptor 2 (NPR2), is critical for oocyte maturation; however, the mechanism is not fully understood. Macrophage colony-stimulating factor (M-CSF) has recently been shown to be involved in oocyte maturation and ovulation. In the present study we determined whether or not M-CSF plays a role in the intermediate signal that mediates LH regulation of NPR2 in resumption of oocyte meiosis. METHODS: Immature female C57BL/6 mice were injected i.p. with 5 IU of equine chorionic gonadotropin (eCG) to stimulate follicle development. After 44-48 h, the eCG-stimulated mice were injected i.p. with an ovulatory dose of 5 IU of human chorionic gonadotropin (hCG). The ovaries were excised at selected times. Pre-ovulatory follicles (POFs) and cumulus-oocyte complexes were cultured in different media. Immunohistochemical and quantitative real-time PCR analyses were used to assess the expression of M-CSF, M-CSF receptor (M-CSF-R), and NPR2. The presence of germinal vesicle breakdown (GVBD) was examined under a stereomicroscope to morphologically evaluate resumption of oocyte meiosis. RESULTS: NPR2 was mainly expressed in cumulus cells of pre-ovulatory follicles, while M-CSF and M-CSF-R were expressed in both mural granulosa and cumulus cells. The levels of M-CSF/M-CSF-R and NPR2 decreased within 4 h after treatment of hCG. M-CSF not only reduced the expression of NPR2 mRNA via its receptor (M-CSF-R), but also increased the proportion of GVBD in oocytes. CONCLUSION: M-CSF serves as an intermediate signal, thus inducing a vital decrease in the NPR2 levels in cumulus cells, and regulates the process of LH-induced resumption of meiosis.