PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study.

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.

Long-term Efficacy of Fibroid Devascularization with Ultrasound-Guided High-Intensity Focused Ultrasound.

RATIONALE AND OBJECTIVES: High-intensity focused ultrasound (HIFU) has been increasingly used for treatment of uterine leiomyoma. The superiority of HIFU therapy targeting uterine leiomyoma blood vessels, however, still needs to be further explored. This study aims to evaluate the long-term efficacy of fibroid devascularization with ultrasound-guided HIFU (USgHIFU) and the effects of treatment on the ovarian reserve and endometrial injury. MATERIALS AND METHODS: Fibroid devascularization was assessed with the Adler grade obtained by color Doppler flow imaging and power Doppler imaging (PDI). The targeted vessels were covered and then sonicated by HIFU focal spots. The patients were followed up at 1 month, 3 months, 6 months, 1 year, 2 years and 3 years after treatment. Adverse effects and complications were recorded. The non-perfusion volume rate (NPVR), fibroid volume shrinkage rate (FVSR), Adler Grade, symptom severity score (SSS) and uterine fibroid symptom and quality of life (UFS-QOL) were evaluated. Adverse events (AEs) were recorded. In Center 1, the enrolled patients completed the anti-Müllerian hormone (AMH) test before and at 6 months after treatment. RESULTS: A total of 117 eligible patients were consecutively enrolled to receive interventions and follow-up evaluations of the three centers from January 2019 to May 2023. The 1-month and 6-month NPVRs were 66.60% ± 33.14% and 51.12% ± 39.84%, respectively. The mean FVSRs at 1 month and 6 months after treatment were 38.20% and 43.89%, respectively. No significant difference was observed in AMH levels before and after treatment (p > 0.05). No irreversible endometrial injury was observed in MR images after HIFU treatment. No significant difference was observed in both 1-month and 6-month FVSRs among Center 1, 2 and 3 (p > 0.05). No severe AEs occurred. For long-term outcomes, significant differences were observed in Adler grade, FV, FVSR, SSS, reduction in SSS and UFS-QOL before and after treatment (p < 0.001) whereas no significant difference was observed in Adler grade among 3 months, 1 year, 2 years and 3 years after treatment (p > 0.05). The SSSs were reduced by 33.42% at 1 year, 42.32% at 2 years and 52.46% at 3 years after treatment. CONCLUSION: For patients with uterine fibroids, USgHIFU-induced devascularization is a safe and effective treatment option. It has little effect on ovarian function and the endometrial injury is reversible, which could be attractive for patients who plan to become pregnant.

TRPS1 regulates the opposite effect of progesterone via RANKL in endometrial carcinoma and breast carcinoma.

Medroxyprogesterone (MPA) has therapeutic effect on endometrial carcinoma (EC), while it could promote the carcinogenesis of breast cancer (BC) by activating receptor activator of NF-kB ligand (RANKL). However, the selective mechanism of MPA in endometrium and breast tissue remains obscure. Multiomics analysis of chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) were performed in cell lines derived from endometrial cancer and mammary tumor to screen the differential co-regulatory factors of progesterone receptor (PR). Dual-luciferase assays and ChIP-PCR assays were used to validate the transcriptional regulation. Co-immunoprecipitation (Co-IP) and immunofluorescence assays were carried out to explore molecular interactions between PR, the cofactor transcriptional repressor GATA binding 1 (TRPS1), and histone deacetylase 2 (HDAC2). Subsequently, human endometrial cancer/breast cancer xenograft models were established to investigate the regulation effect of cofactor TRPS1 in vivo. In the current study, we found that MPA downregulated RANKL expression in a time- and dose-dependent manner in EC, while had the opposite effect on BC. Then PR could recruit cofactor TRPS1 to the promoter of RANKL, leading to histone deacetylation of RANKL to repress its transcription in EC, whereas MPA disassociated the PR/TRPS1/HDAC2 complex to enhance RANKL histone acetylation in BC. Therefore, TRPS1, the coregulator recruited by PR played a critical role in the selective mechanism of progesterone in EC and BC and could become a potential candidate for targeted therapy to improve the anticancer effect of MPA on EC and avoid its carcinogenic effect on BC.

Design, Control, and Experiments of a Novel Robotic Uterine Manipulator With the Motorized 3-DoF Manipulation Rod.

To address the issue of declining performance over time with manual uterine manipulation during minimally invasive gynecologic surgery, we propose a novel uterine manipulation robot that consists of a 3-DoF remote center of motion (RCM) mechanism and a 3-DoF manipulation rod. This allows for tireless, stable, and safer manipulation in place of a human assistant. For the RCM mechanism, we propose a single-motor bilinear-guided mechanism that can achieve a wide range of pitch motion (-50  âˆ¼  34 degrees) while maintaining a compact structure. This novel uterine manipulation robot is equipped with a manipulation rod that has a tip diameter of only 6 mm, allowing it to accommodate almost any patient's cervix. The 30-degree distal pitch motion and ±45-degree distal roll motion of the instrument further improve uterine visualization. Additionally, the tip of the rod can be opened into a T-shape to minimize damage to the uterus. Laboratory experiments have shown the mechanical RCM accuracy of 0.373 mm and the maximum load of the distal pitch joint of 500 g. Feasibility has been demonstrated through ex-vivo and cadaver tests, as well as clinical trials.

Ovarian Mature Cystic Teratoma is an Independent Risk Factor for the Premature Rupture of Membranes in Pregnancy: A Single-Center Retrospective Study.

Background: Ovarian mature cystic teratomas (MCTs) are the most common tumors in pregnant women. The premature rupture of membranes (PROM) is a typical complication of pregnancy; however, the relationship between MCT and PROM is unknown. Therefore, we aimed to determine whether MCT is associated with the occurrence of PROM during pregnancy. Methods: The data of patients with adnexal masses during pregnancy between January 2017 and August 2021 were retrospectively analyzed. Ovarian cystectomy was performed during cesarean delivery or after vaginal delivery. Univariate and multivariate logistic regression models were used for statistical analysis. Results: A total of 234 patients with histopathological results were included. Among these patients, 21 occurred PROM during pregnancy, of which 11 were diagnosed with MCT. Compared with other subtypes, MCT (p=0.025) showed a stronger correlation with PROM and was an independent risk factor for PROM (odds ratio [OR], 2.811; 95% confidence interval [CI], 1.096-7.215; p=0.032). Furthermore, we found that MCT with a diameter >5 cm (p=0.0037) was more likely to promote the development of PROM than those that with a diameter <5 cm. Conclusion: MCT was an independent risk factor for PROM during pregnancy. Positive actions and preventative clinical treatments should be fully taken into consideration by clinicians for pregnant women with MCTs, especially those ≥5 cm in diameter, to reduce the clinical complications related to MCT-associated PROM.

Functional mechanisms of TRPS1 in disease progression and its potential role in personalized medicine.

The gene of transcriptional repressor GATA binding 1 (TRPS1), as an atypical GATA transcription factor, has received considerable attention in a plethora of physiological and pathological processes, and may become a promising biomarker for targeted therapies in diseases and tumors. However, there still lacks a comprehensive exploration of its functions and promising clinical applications. Herein, relevant researches published in English from 2000 to 2022 were retrieved from PubMed, Google Scholar and MEDLINE, concerning the roles of TRPS1 in organ differentiation and tumorigenesis. This systematic review predominantly focused on summarizing the structural characteristics and biological mechanisms of TRPS1, its involvement in tricho-rhino-phalangeal syndrome (TRPS), its participation in the development of multiple tissues, the recent advances of its vital features in metabolic disorders as well as malignant tumors, in order to prospect its potential applications in disease detection and cancer targeted therapy. From the clinical perspective, the deeply and thoroughly understanding of the complicated context-dependent and cell-lineage-specific mechanisms of TRPS1 would not only gain novel insights into the complex etiology of diseases, but also provide the fundamental basis for the development of therapeutic drugs targeting both TRPS1 and its critical cofactors, which would facilitate individualized treatment.

Myelin and Lymphocyte Protein (MAL): A Novel Biomarker for Uterine Corpus Endometrial Carcinoma.

PURPOSE: Myelin and lymphocyte protein (MAL) plays an essential role in esophageal cancer, classic Hodgkin's lymphoma and breast cancer. However, its role in uterine corpus endometrial carcinoma (UCEC) has not been explored. Therefore, the current study sought to explore the role of MAL in UCEC. PATIENTS AND METHODS: Differentially expressed genes (DEGs) were identified by using Limma package in R based on TCGA-UCEC data. Kaplan-Meier plotter analysis was performed to explore the prognostic value of MAL. Function enrichment analyses were performed using GSVA. Further, roles of MAL in UCEC were validated using clinical cohort, which included 120 tumor and adjacent tissues. qRT-PCR and immunohistochemistry analyze the samples. Chi-square tests were performed to explore the associations between MAL expressions and clinicopathological features. RESULTS: The findings showed that overexpression level of MAL in tumor was correlated with worse survival (p = 0.000424). MAL exhibited predictive power for survival time of UCEC patients (3 years: AUC = 0.635; 5 years: AUC = 0.635). Notably, high expression level of MAL was correlated with advanced stage of UCEC. MAL overexpression was significant in UCEC with microsatellite instability (MSI). Enrichment analysis showed that MAL was enriched mainly in MYC targets, epithelial mesenchymal transition and KRAS signaling. Furthermore, MAL was associated with infiltration of immune cells in the tumor micro-environment and immune checkpoint. Analysis showed a positive association between MAL and T cell (CD4+ memory resting). Correlation analysis showed that MAL was significantly positively correlated with several immune checkpoint, including CD274 (R = 0.3389, p = 0.0081), LAG3 (R = 0.2913, p = 0.0229), PDCD1LG2 (R = 0.5345, p < 0.0001). The prognosis value of MAL was confirmed through the experiment. CONCLUSION: The findings of the current study indicated that MAL is an effective prognostic biomarker and potential therapeutic target for UCEC patients. These results indicated that MAL functions as a diagnosis and therapeutic marker in UCEC treatment.

Ultrasound-Guided High-Intensity Focused Ultrasound for Devascularization of Uterine Fibroid: A Feasibility Study.

This study aimed to establish the feasibility of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for devascularization of uterine fibroids. Ultrasound color Doppler flow imaging (CDFI) and B-mode imaging were used to target fibroid vascularity. The vessels were covered and ablated by high-intensity focused ultrasound spots. In this study, 42 fibroids with a volume of 66.98 ± 4.00 cm3 were treated. No blood flow was detected by post-treatment CDFI in 40 fibroids. The 6-mo non-perfusion volume rate was 75.23% ± 34.77% (n = 40). The mean shrinkage in fibroid volume was 38.20% and 43.89%, respectively, at 1 and 6 mo after treatment (p < 0.001). The uterine fibroid symptom and quality of life scores were reduced by 9.43% at 1 mo and 26.66% at 6-mo after treatment (p < 0.001). No serious adverse event was observed. This study demonstrates the feasibility of USgHIFU-induced fibroid devascularization, and more studies are required for the evaluation of safety and efficacy.

Hypermethylated PCDHGB7 as a Biomarker for Early Detection of Endometrial Cancer in Endometrial Brush Samples and Cervical Scrapings.

Endometrial cancer (EC) is one of the most common gynecologic cancers in developed countries. Presently, it is imperative to develop a reliable, noninvasive, or minimally invasive detection method for EC. We explored the possibility of using DNA methylation marker from endometrial brush samples (with a "Tao brush") and cervical scrapes (with a "Pap brush") for early detection of EC. We analyzed the methylation data of EC and normal endometrial tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. An optimized methylation-sensitive restriction enzyme combined with real-time fluorescent quantitative PCR (MSRE-qPCR) was used for methylation detection. Included in the training set were 143 endometrial tissues, 103 Tao, and 109 Pap brush samples. The validation set included 110 Tao and 112 Pap brush samples. PCDHGB7 was significantly hypermethylated in EC compared with normal endometrial tissues in the TCGA and GEO data sets (AUC >0.95), which was verified in clinical samples. In the Pap brush samples, the AUC was 0.86 with 80.65% sensitivity and 82.81% specificity, whereas the Tao brush samples exhibited higher specificity (95.31%). The combination of Tao and Pap brush samples significantly increased the sensitivity to 90.32%. In the validation set, the final model yielded a sensitivity of 98.61%, specificity of 60.53%, positive predictive value of 82.56%, and negative predictive value of 95.83%. These results demonstrate the potential application of the novel methylation marker, hypermethylated PCDHGB7, in cervical scrapings and endometrial brush, which provides a viable, noninvasive, or minimally invasive method for early endometrial cancer detection across different clinical features and histologies to supplement current hysteroscopy diagnosis.

Feasibility and safety of cryoablation on the porcine ureter using a new balloon cryoprobe.

Cryoablation, as a well-characterized technology, has multifarious clinical applications. But few are reported on ureteral endometriosis. Thus, we examined the feasibility and safety of cryotherapy with a novel balloon cryoprobe on ureter in a live porcine model. During the freezing and thawing cycle, temperature was recorded in different parts of the ureter in real-time. Two-minute cryoablation could induce necrosis within range in 1 cm diameter on serosa layer. The temperature respectively dropped to -136.5 °C, -96.1 °C and -17.5 °C at the cryotherapy center, 1 cm and 1.5 cm from center on serosal side. The ureters were harvested immediately, 2 weeks or 3 months after cryotherapy. No perforation, stricture, adhesions, or hydronephrosis was observed. Histopathologic representations of ureters after cryoablation indicated that full thickness necroses of ureters were seen in all samples. The results demonstrated ureteral cryoablation using a novel balloon probe was feasible, safe, and effective. These findings provided us reference before cryoablation could be applied in clinical practice in treating ureteral endometriosis.

A practical method of using the anatomical space of the vesicouterine ligament for laparoscopic radical hysterectomy: a retrospective cohort study.

OBJECTIVE: To investigate the practicality of a new method using anatomical spaces for performing standard laparoscopic radical hysterectomy (LRH) without ureteral injury in patients with cervical cancer. METHODS: Clinicopathological characteristics and perioperative complications were retrospectively analysed in 440 patients with stages IB1 to IIB cervical cancer. The patients were assigned to two of the following groups: LRH by our method of using anatomical landmarks (anatomical space group, n = 217) and the traditional method (traditional group, n = 223). RESULTS: The mean operative duration and time of vesicouterine ligament (VUL) dissection were significantly shorter (173.87 ± 30.39 vs. 210.83 ± 44.55 minutes; 32.75 ± 7.23 vs. 43.48 ± 11.22 minutes), and blood loss was less in the anatomical space group compared with the traditional group. The rate of the intraoperative complication of ureteral injury was also significantly lower in the anatomical space group compared with the traditional group (0 vs. 5). CONCLUSIONS: LRH by the anatomical method, using the axillary space and other potential spaces as anatomical landmarks, results in less blood loss and reduced ureteral injury compared with the traditional method. This method is safe and practical for separating the ureter from the VUL in patients with cervical cancer.

Cryoablation used in fertility-sparing treatment for early endometrial cancer: A pig model experiment using a new designed balloon cryoprobe.

Young patients with early endometrial cancer have a strong desire to retain reproductive function, which require us to develop a therapeutic method that can not only assure the complete resection of tumor but also retain the uterine integrity. In the present study, we proposed a fertility-sparing surgery option that combined hysteroscopic resection with cryoablation to achieve this goal. To verify the safety and effectiveness of cryoablation for local uterine wall, we designed the experiment in pig model using a novel cryoablation balloon probe. In the process of freezing and thawing, the temperature of different parts of the uterus was measured in real time. The uterus was harvested immediately, three weeks after cryotherapy for histological evaluation. The results demonstrated cryoablation using the new cryoprobe is safe and effective. The effective freezing range can cover a range of 2 cm in diameter at least. This study provided us evidence before cryoablation could be applied in clinical practice of fertility-sparing treatment for young women with early endometrial cancer.

The involvement of eukaryotic initiation factor 5A in trophoblast cell function.

Abnormal growth and migration of trophoblast cells is one of the main causes of spontaneous abortion. Eukaryotic translation initiation factor 5A (eIF5A) plays an important role in trophoblast cell growth and migration; however, its underlying mechanism remains largely unknown. Here, we first confirmed that eIF5A knockdown reduced human chorionic trophoblast HTR8 cells viability, proliferation, and migration. Next, we sought to systematically identify the genes regulated by eIF5A and observed changes in the transcriptome profile of eIF5A-knockdown HTR8 cells by RNA-seq analysis. Especially, we found that inhibition of eIF5A reduced both the mRNA and protein levels of methyltransferase-like protein 14 (METTL14). Furthermore, inhibition of METTL14 expression resulted in the reduction of viability, proliferation, and migration of HTR8 cells. In addition, we showed that overexpression of METTL14 rescued the effects of eIF5A knockdown in HTR8 cells. Finally, we revealed that eIF5A and METTL14 expression was decreased in spontaneous abortion samples compared to that in elective-induced abortion samples. Collectively, our study demonstrated that eIF5A plays a crucial role in HTR8 cells via modulation of METTL14 expression and may serve as a novel potential target for spontaneous abortion diagnosis and treatment.

Predictive values of the ratio of beta-human chorionic gonadotropin for failure of salpingostomy in ectopic pregnancy.

BACKGROUND: We evaluated the predictors of unsuccessful salpingostomy that required surgical treatment or additional medical treatment after initial removal of ectopic pregnancy (EP) by laparoscopy. MATERIAL/METHODS: The study was an observational retrospective cohort study done at International Peace Maternity and Child Health Hospital in Shanghai, which included patients with ectopic pregnancy (EP). The predictors of persistent ectopic pregnancy (PEP) were measured either on serum ß-hCG ratios before and after salpingostomy or demographics (age, parity, in-vitro fertilization (IVF), abortion history, EP history, mass location, appendectomy history and diameter of EP lesion). We used nomogram analyses to evaluate the significant factors consisting of serum ß-hCG ratio, parity and performed IVF that predicted the failure or success of salpingostomy. RESULTS: We retrospectively analyzed 429 patients in this study who received salpingostomy for EP from January 2013 and December 2017. Of these patients, 29 (6.76%) were diagnosed with PEP after salpingostomy and 400 (93.24%) had satisfactory treatment. The median of serum ß-hCG ratio (after salpingostomy 24 h/after salpingostomy 48 h) 2.43 in PEP patients was lower than that in successful treatment patients (P<0.001). Logistic regression analyses identified several predictors for PEP, including parity, IVF and serum ß-hCG (after salpingostomy 24 h/after salpingostomy 48 h), with a higher clear predictive value (area under the curve [AUC]=0.865, 95% CI: 0.812-0.919, P<0.001). CONCLUSIONS: The serum ß-hCG ratio (after salpingostomy 24 h/after salpingostomy 48 h) in combination with parity and IVF are important predictors for PEP patients after surgery. These findings provide higher risk PEP patients for early interventions to improve outcome.

Effects of Levonorgestrel and progesterone on Oviductal physiology in mammals.

BACKGROUND: Our previous study indicated that emergency contraception, including levonorgestrel and progesterone, could lead to ectopic pregnancy following contraception failure. However, our understanding of the effects of levonorgestrel and progesterone on oviductal physiology is limited. METHODS: The receptivity of the fallopian tubal epithelium after levonorgestrel and progesterone treatment was examined through western blots for receptivity markers and JAr-spheroid-fallopian tubal epithelial cell attachment assays. The ciliary beat frequency was analyzed using an inverted bright-field microscope. Furthermore, an in vivo animal model of embryo-tubal transplantation was also studied to determine the effects of levonorgestrel- and progesterone-induced ciliary beat reduction. RESULTS: Our results showed that levonorgestrel and progesterone did not change the levels of fallopian tubal epithelial cell receptive markers, including LIF, STAT3, IGFBP1, ITGB3, MUC1, and ACVR1B, or affect JAr-spheroid implantation. However, levonorgestrel and progesterone reduced the ciliary beat frequency in fallopian tubes in a dose-dependent manner. An in vivo model also showed that levonorgestrel and progesterone could lead to embryo retention in the oviducts. CONCLUSIONS: These findings show that levonorgestrel and progesterone can reduce the ciliary beat frequency without altering receptivity, indicating a possible mechanism for progesterone- or levonorgestrel-induced tubal pregnancy.

Ulipristal Acetate Antagonizes the Inhibitory Effect of Progesterone on Ciliary Beat Frequency and Upregulates Steroid Receptor Expression Levels in Human Fallopian Tubes.

Ulipristal acetate (UPA) is a new selective progesterone receptor (PR) modulator used for emergency contraception. However, our understanding of its mechanisms of action on oviductal cilia is limited. The present study focused on the in vitro effects of UPA (0.1, 1, and 10 µmol/L) on the cilia and steroid receptors of human fallopian tubes. The ciliary beat frequency (CBF), the ultrastructure of cilia, and the levels of steroid receptors were measured. The effects of UPA on the progesterone-induced CBF reduction were also studied. Our results show that UPA dose dependently antagonizes the progesterone-induced CBF decrease, but it does not affect the CBF or the ultrastructure of the cilia. The UPA also upregulates the expression levels of the estrogen receptor α and the PR in the fallopian tubes. The results enable us to better understand the mechanisms by which UPA works as an emergency contraceptive and provides a scientific basis for its clinical application.

Levonorgestrel decreases cilia beat frequency of human fallopian tubes and rat oviducts without changing morphological structure.

Levonorgestrel, a derivative of progesterone, effectively protects women against unwanted pregnancy as an emergency contraceptive. Previous studies have not been successful in determining the mechanism by which levonorgestrel acts. In the present study we analysed cilia beat action and cilia morphology following levonorgestrel exposure in vitro and in vivo using both light and electron microscopy. There was a significant decrease in the ciliary beat frequency (CBF) of human fallopian tubes between mucosal explants bathed in 5 µmol/L levonorgestrel and those bathed in medium alone (P < 0.05). There was a tendency for CBF to decrease more in the ampulla than in isthmus, but there were no differences between the proliferative and secretory phases. In rat oviducts, levonorgestrel produced a similar reduction in CBF (~ 10%) compared with the saline control group (P < 0.05). Histological and ultrastructural analysis demonstrated no changes in the percentage of ciliated cells or in the classic '9 + 2' structure of cilia following levonorgestrel treatment in either system. Thus, levonorgestrel reduces CBF without damaging cilia morphology. Decreases in CBF may indicate a pathological role for levonorgestrel in the transportation of the ovum and zygote in the fallopian tube.

Risk factors and clinical features of ovarian pregnancy: a case-control study.

OBJECTIVE: To identify risk factors for ovarian pregnancy (OP) and compare clinical features between OP and tubal pregnancy (TP) patients. DESIGN: Case-control study. SETTING: University hospital. PARTICIPANTS: A case-control study was conducted from January 2005 to May 2014. Women diagnosed with OP were recruited as the case group (n=71), 145 women with TP and 146 with intrauterine pregnancy (IUP) were matched as controls at a ratio of 1:2:2. Women who refused interviews or provided incomplete information were excluded. RESULTS: OP risk was lower than TP risk in women with serological evidence of Chlamydia trachomatis infection (adjusted OR1 0.17, 95% CI 0.06 to 0.52), previous adnexal surgery (adjusted OR1 0.25, 95% CI 0.07 to 0.95), and current levonorgestrel emergency contraceptive use (adjusted OR1 0.24, 95% CI 0.07 to 0.78). In vitro fertilisation-embryo transfer (IVF-ET) carried a higher risk of OP (adjusted OR1 12.18, 95% CI 2.23 to 66.58) than natural conception. When Controlled by IUP women, current users of intrauterine devices (IUDs) carried a higher risk of OP than non-users of any contraceptives (adjusted OR2 9.60, 95% CI 1.76 to 42.20). ß-Human chorionic gonadotropin (hCG) levels on the day of surgery were higher in OP patients than in TP patients (p<0.01). Women with OP were less likely to initially present with vaginal bleeding than those with TP (p=0.02). Moreover, shock (p=0.02), rupture (p<0.01), haemoperitoneum (p<0.01) and emergency laparotomy (p<0.01) were more common in the OP group than in the TP group. CONCLUSIONS: IVF-ET and IUD use may be risk factors for OP, and OP patients tend to have high ß-hCG levels and a poor clinical outcome (shock, rupture, haemoperitoneum and need for emergency laparotomy). Our findings may contribute to the prevention and early diagnosis of OP.