Preoperative and postoperative blood testosterone levels in patients with acromegaly: a prospective study.

Purpose: To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients. Methods: A retrospective, single-center study focused on 252 male acromegaly patients aged 18 years-60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed. Results: Forty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences (p < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; p = 0.000] and serum prolactin level (OR = 1.023, p = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different (p < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; p = 0.001) and recovery from acromegaly (OR = 0.168; p = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up. Conclusion: The invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.

CXCR4, regulated by HIF1A, promotes endometrial breakdown via CD45+ leukocyte recruitment in a mouse model of menstruation.

Menstruation is a specific physiological phenomenon in female humans that is regulated by complex molecular mechanisms. However, the molecular network involved in menstruation remains incompletely understood. Previous studies have suggested that C-X-C chemokine receptor 4 (CXCR4) is involved; however, how CXCR4 participates in endometrial breakdown remains unclear, as do its regulatory mechanisms. This study aimed to clarify the role of CXCR4 in endometrial breakdown and its regulation by hypoxia-inducible factor-1 alpha (HIF1A). We first confirmed that CXCR4 and HIF1A protein levels were significantly increased during the menstrual phase compared with the late secretory phase using immunohistochemistry. In our mouse model of menstruation, real-time PCR, western blotting, and immunohistochemistry showed that CXCR4 mRNA and protein expression levels gradually increased from 0 to 24 h after progesterone withdrawal during endometrial breakdown. HIF1A mRNA and HIF1A nuclear protein levels significantly increased and peaked at 12 h after progesterone withdrawal. Endometrial breakdown was significantly suppressed by the CXCR4 inhibitor AMD3100 and the HIF1A inhibitor 2-methoxyestradiol in our mouse model, and HIF1A inhibition also suppressed CXCR4 mRNA and protein expression. In vitro studies using human decidual stromal cells showed that CXCR4 and HIF1A mRNA expression levels were increased by progesterone withdrawal and that HIF1A knockdown significantly suppressed the elevation in CXCR4 mRNA expression. CD45+ leukocyte recruitment during endometrial breakdown was suppressed by both AMD3100 and 2-methoxyestradiol in our mouse model. Taken together, our preliminary findings suggest that endometrial CXCR4 expression is regulated by HIF1A during menstruation and may promote endometrial breakdown, potentially via leukocyte recruitment.

Injectable self-assembled dual-crosslinked alginate/recombinant collagen-based hydrogel for endometrium regeneration.

The disadvantages of mainstream therapies for endometrial injury are difficult to resolve, herein, we suggest an omnibearing improvement strategy by introducing an injectable multifunctional self-assembled dual-crosslinked sodium alginate/recombinant collagen hydrogel. The hydrogel possessed a reversible and dynamic double network based on dynamic covalent bonds and ionic interactions, which also contributed to excellent capability in viscosity and injectability. Moreover, it was also biodegradable with a suitable speed, giving off active ingredients during the degradation process and eventually disappearing completely. In vitro tests exhibited that the hydrogel was biocompatible and able to enhance endometrial stromal cells viability. These features synergistically promoted cell multiplication and maintenance of endometrial hormone homeostasis, which accelerated endometrial matrix regeneration and structural reconstruction after severe injury in vivo. Furthermore, we explored the interrelation between the hydrogel characteristics, endometrial structure, and postoperative uterine recovery, which would benefit deep research on regulation of uterine repair mechanism and optimization of hydrogel materials. The injectable hydrogel could achieve favourable therapeutic efficacy without the need of exogenous hormones or cells, which would be of clinical value in endometrium regeneration.

Potential therapeutic drug targets and pathways prediction for premature ovarian insufficiency -Based on network pharmacologic method.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of premature ovarian insufficiency (POI) is gradually increasing, the proportion is rising especially in female infertility patients. The risk of death of POI patients with cardiovascular disease also increases significantly. The cause of POI is complex and unclear, and clinical treatment is still in the exploratory stage, are two major constraints of treating POI. Traditional Chinese medicine (TCM) is widely used in the treatment of POI, and it is a good way to combine the development of modern new drugs with the help of TCM to predict the therapeutic targets. AIM OF THE STUDY: In this study, four herbs commonly used in clinical treatment of POI, namely Radix Paeoniae, Polygonatum sibiricum, Rehmannia glutinosa and Eucommia ulmoides were selected to predict their mechanism in the treatment of POI, using network pharmacology methods. Then verify the predicted targets by animal test. Aim to find more effective POI potential core treatment targets and main pathways. MATERIALS AND METHODS: We screened the active ingredients of drugs from the TCM System Pharmacology Analysis Platform (TCMSP), Performed target prediction of active ingredients from databases such as SwissTargetPrediction and compare and analyze the POI-related targets retrieved from them to obtain potential targets for drug treatment of POI. Used STRING database to construct a protein interaction network, Cytoscape 3.7.2 software to construct an active ingredient-target-pathway network, and DAVID database to conduct the Kyoto Encyclopedia of Genes and Genomes (KEGG) on the intersection targets and gene ontology (GO) enrichment analysis. RESULTS: The result is: there were 25 key targets for the treatment of POI with Radix Paeoniae Alba, 31 for the treatment of POI by Eucommia ulmoides, 28 for the treatment of POI by Polygonatum sibiricum, and 8 key targets for the treatment of Rehmannia glutinosa. The intersection targets of four herbs were defined as the core targets, which are CYP19A1, EGF, ESR1, ESR2, MDM2, AR, PCYP17A1, PPARG. Four Chinese herbs treat POI mainly through HIF-1 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Estrogen signaling pathway etc. A mouse model of POI was constructed based on the results of network pharmacology to verify the predicted targets. The results showed that the protein expression of the core target changed, and the estrogen level was increased by reducing the expression of peroxisome proliferator-activated receptor gamma (PPARG). CONCLUSIONS: This study predicts the mechanism of multiple herbs in the treatment of POI, screens out more potential therapeutic drug targets and main pathways of POI treatment and provides new ideas for the subsequent development of POI therapeutic drugs.

Clinical outcomes of levonorgestrel-releasing intrauterine device present during controlled ovarian stimulation in patients with early stage endometrioid adenocarcinoma and atypical endometrial hyperplasia after fertility-sparing treatments: 10-year experience in one tertiary hospital in China.

BACKGROUND: To evaluate the oncologic and pregnancy outcomes of patients with early stage endometrioid adenocarcinoma (EMC) and atypical endometrial hyperplasia (AEH) treated with controlled ovarian stimulation (COS) with or without levonorgestrel-releasing intrauterine device (LNG-IUD) after fertility-sparing treatment (FSTs). METHODS: A total of 67 patients with EMC or AEH who achieved complete response after FSTs and underwent COS between January 2010 and December 2019 were retrospectively reviewed. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence after COS. RESULTS: The average age was 32.9 ± 3.46 years. 23.9 % of these patients relapsed after COS during the follow-up period. The 2-year cumulative recurrence rate was 14.9 % (9.1 % and 20.6 % in the LNG-IUD and control groups, respectively). Compared with the control group, the recurrence rate was lower in patients with LNG-IUDs present during COS (12.1 % vs 35.5 %, p = 0.027). The clinical pregnancy (42.4 % vs 52.9 %, p = 0.392) and live birth (21.2 % vs 29.4 %, p = 0.444) rates were similar between the LNG-IUD and control groups. Age, body mass index (BMI), histology, FST type and time to complete response were not related to prognosis after COS. After adjusting for age and BMI in a multivariate Cox regression model, the use of LNG-IUD during COS was a favorable factor for better oncologic outcomes after COS (HR 0.263, 95 %CI 0.084-0.822, p = 0.022). CONCLUSIONS: Patients with early stage EMC and AEH treated with assisted reproductive technology after FSTs might benefit from LNG-IUDs present during COS.

Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Repairs Endometrial Epithelial Cells Injury Induced by Hypoxia via Regulating miR-663a/CDKN2A Axis.

Aim: Thin endometrium remains a severe clinical challenge with no effective therapy to date. We aimed at exploring the role and molecular mechanism of human umbilical cord mesenchymal stem cell- (hucMSC-) derived exosomes (hucMSC-Ex) in repairing hypoxic injury of endometrial epithelial cells (EECs). Methods: Exosomes were harvested from the conditioned medium of hucMSC and characterized using western blot, transmission electron microscopy (TEM), flow cytometry, and nanoparticle tracking analysis (NTA). EECs were subjected to hypoxic conditions before cocultured with hucMSC-Ex. Cell viability, apoptosis, and migration were determined with CCK-8, flow cytometry, and wound healing assay, respectively. Apoptosis/EMT-related proteins were detected by western blot. The miRNA profiling was determined by RNA sequencing. The expression of miR-663a and CDKN2A was measured by qRT-PCR. MiR-663a in EECs was overexpressed by transfecting with miR-663a mimics. Results: Mesenchymal stem cells (MSCs) markers CD73, CD90, and CD106 were positively expressed in hucMSCs. Exosome isolated from hucMSC expressed CD63 and TSG101, and were 100-150 nm in diameter. HucMSC-Ex promoted cell proliferation inhibited by hypoxia. And hucMSC-Ex also inhibited hypoxia-induced apoptosis, migration, and EMT of EECs by upregulating the expression of Bcl-2 and E-cadherin and downregulating Bax and N-cadherin levels. Further, bioinformatics research found that hucMSC-Ex coculture can significantly upregulate the expression of miR-663a and decrease the expression of CDKN2A in hypoxia-induced EECs. Furthermore, miR-663a overexpression inhibited CDKN2A expression and increased the expression of Bcl-2 and E-cadherin in hypoxia-induced EECs. Conclusions: HucMSC-Ex promoted cell proliferation, inhibited cell apoptosis, migration, and EMT in hypoxia-induced EECs, thereby alleviating hypoxia-induced EECs injury, which may be related to its regulation of miR-663a/CDKN2A expression. Our study indicated that hucMSC-Ex might benefit for repairing thin endometrium.

Clinical Re-evaluation on Bioequivalence and Relative Bioavailability of Micronized Progesterone Hard Capsule (Yimaxin) and Micronized Progesterone Soft Capsule (Utrogestan) under Vaginal and Oral Administration Routes.

BACKGROUND AND OBJECTIVE: To clinically re-evaluate relative bioavailability and bioequivalence of micronized progesterone (hard capsule) Yimaxin and micronized progesterone (soft capsule) Utrogestan under vaginal and oral administration routes. METHODS: From December 2017 to June 2018, a total of 16 postmenopausal healthy women were recruited and received a total of four rounds of drug treatment with cross-over design, respectively Yimaxin and Utrogestan under vaginal and oral administration routes. Changes in the subjects' hormone levels after medication were monitored and an endometrial biopsy after a course of treatment was performed in our hospital. RESULT: The Geomeans of AUC0-t of Yimaxin and Utrogestan under vaginal administration route were 252.15 and 115.46, respectively, with a ratio of 2.19, and under oral administration route were 244.64 and 413.68, respectively, with a ratio of 0.59. The Geomeans of Cmax of Yimaxin and Utrogestan under vaginal administration route were 28.11 and 12.21, respectively, with a ratio of 2.30, and under oral administration route were 53.12 and 129.85, respectively, with a ratio of 0.41. CONCLUSION: Yimaxin was not bioequivalent to Utrogestan. Yimaxin had higher exposure to the drug in vivo at the same dose when administered vaginally, and Utrogestan had higher exposure to the drug in vivo at the same dose when administered orally.

Single-dose administration of a short-acting gonadotropin-releasing hormone agonist does not affect cycle outcome in frozen-thawed embryo transfer cycles.

OBJECTIVE: This prospective study aimed to assess the effect of short-acting gonadotropin-releasing hormone agonist (GnRHa) administration on pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles. METHODS: Patients who planned to have FET in Peking Union Medical College Hospital (China) were recruited for this study and randomly assigned into two groups. Patients in the experimental group (n = 460) received triptorelin acetate on the day of embryo transfer along with routine luteal support. Patients in the control group (n = 433) only received luteal support. One dose (0.1 mg) of a short-acting GnRHa was administered on the day of blastocyte transfer. The rates for clinical pregnancy, biochemical pregnancy, implantation, miscarriage, and ectopic pregnancy were compared between the groups. RESULTS: There were no significant differences in the number and quality of blastocytes transferred between the two groups. In the experimental and control groups, the clinical pregnancy rate was 56.3% and 50.58%, the biochemical pregnancy rate was 15.78% and 18.94%, and the median implantation rate was 39.98% and 38.01%, respectively, with no significant difference between the groups. Biochemical pregnancy and abortion and the ectopic pregnancy rate were not significantly different between the two groups. CONCLUSION: In FET cycles, a GnRHa does not affect the pregnancy outcome.

Pharmacokinetics of hard micronized progesterone capsules via vaginal or oral route compared with soft micronized capsules in healthy postmenopausal women: a randomized open-label clinical study.

PURPOSE: This study aimed to evaluate the pharmacokinetics of hard micronized progesterone capsules (Yimaxin) via the vaginal or oral route compared with soft micronized progesterone capsules (Utrogestan) in a Chinese population. METHODS: A prospective single-center randomized open-label trial was conducted in 16 healthy postmenopausal women. They were randomized into two groups to receive four phases of treatment: vaginal Yimaxin, vaginal Utrogestan, oral Yimaxin, or oral Utrogestan, with different sequences. RESULTS: By the vaginal route, steady-state maximum concentration (Cmax) of Yimaxin and Utrogestan was 29.13±8.09 and 12.30±1.60 mg/L, time to Cmax 9.72±10.50 and 11.03±9.62 hours, central compartment volume of distribution 4.26±1.86 and 10.40±2.32 L, clearance rate 0.18±0.05 and 0.38±0.10 L/h, and AUC 261.42±74.36 and 116.83±19.72 h·ng/mL, respectively. By the oral route, Cmax of Yimaxin and Utrogestan was 62.97±40.59 and 169.53±130.24 mg/L, time to Cmax was 2.88±1.35 and 2.06±1.55 hours, central compartment volume of distribution 132.16±52.13 and 85.08±55.07 L, clearance rate 3.43±1.07 and 2.50±1.04 L/h, and AUC 274.86±160.28 and 472.00±250.54 h·ng/mL, respectively. By the vaginal route, Cmax, minimum concentration, AUC0-72, and AUC of Yimaxin were higher than Utrogestan, while by the oral route the Cmax, AUC0-72, and AUC of Utrogestan were higher than Yimaxin. CONCLUSION: Pharmacokinetic parameters were different between Yimaxin and Utrogestan on vaginal and oral administration. By the oral route, the metabolism and absorption of Utrogestan was superior to Yimaxin, while by the vaginal route Yimaxin was superior.

Factors Associated with Effectiveness of Treatment and Reproductive Outcomes in Patients with Thin Endometrium Undergoing Estrogen Treatment.

BACKGROUND: Thin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endometrial thickness (EMT). The aim of this retrospective cohort study was to investigate the factors influencing the effectiveness of estrogen treatment and reproductive outcomes after the treatment in patients with thin endometrium. METHODS: Relevant clinical data of 101 patients with thin endometrium who had undergone estrogen treatment were collected. Possible factors influencing the effectiveness of treatment were analyzed retrospectively by logistic regression analysis. Eighty-seven infertile women without thin endometrium who had undergone assisted reproduction served as controls. The cases and controls were matched for age, assisted reproduction method, and number of embryos transferred. Reproductive outcomes of study and control groups were compared using Student's t-test and the Chi-square test. RESULTS: At the end of estrogen treatment, EMT was ≥8 mm in 93/101 patients (92.1%). Effectiveness of treatment was significantly associated with maximal pretreatment EMT (P = 0.017) and treatment duration (P = 0.004). The outcomes of assisted reproduction were similar in patients whose treatment was successful in increasing EMT to ≥8 mm and the control group. The rate of clinical pregnancy in patients was associated with the number of good-quality embryos transferred in both fresh (P = 0.005) and frozen-thawed (P = 0.000) embryo transfer cycles. CONCLUSIONS: Thinner EMT before estrogen treatment requires longer treatment duration and predicts poorer treatment outcomes. The effectiveness of treatment depends on the duration of estrogen administration. Assisted reproductive outcomes of patients whose treatment is successful (i.e., achieves an EMT ≥8 mm) are similar to those of controls. The quality of embryos transferred is an important predictor of assisted reproductive outcomes in patients treated successfully with exogenous estrogen.

[Clinical study on 48 cases with complete 17α-hydroxylase deficiency].

OBJECTIVE: To investigate efficient diagnosis and treatment of 17α-hydroxylase (17OHD) deficiency by summarizing clinical characteristics of those patients. METHODS: From January 1983 to January 2010, 48 cases with 17OHD in Peking Union Medical College Hospital were studied retrospectively. RESULTS: Among 48 patients with 17OHD, karyotype analysis showed, 12 cases with 46, XX and 36 cases with 46, XY. The 46, XX karyotype and 46, XY karyotype with complete 17OHD had typical clinical presentation of amenorrhea[12/12, 100% (36/36)], no typical spontaneous puberty [12/12, 13.9% (5/36)], Hypertension [11/12, 100% (36/36)], hypokalemia [K(+): (2.6 ± 0.7), (2.8 ± 0.7) mmol/L], hypergonadotropin [follicle-stimulatinghormone (FSH): (51 ± 35), (79 ± 46) U/L, luteinizing hormone (LH): (27 ± 14), (49 ± 37) U/L], impaired production of sex hormones [testosterone (T): 0.003, 0.005 nmol/L; estradiol (E(2)): 26.86, 10.64 pmol/L], hyper-progesterone[ (P): (32 ± 15), (29 ± 23) nmol/L], impaired production of 17α-hydroxyprogesterone (17α-OHP)[(2.5 ± 1.1), (2.4 ± 1.7) nmol/L], ACTH hypersecreation (91.8, 114.0 pmol/L). ACTH stimulating test did not elevated in 17α-OHP and cortisol. CONCLUSION: When patients with elevated basal serum levels of progesterone higher than that of ovulation period in addition to clinical symptoms, examination about 17OHD should be warranted.

[Treatment of malignant ovarian germ cell tumors with relapse or failed in primary therapy].

OBJECTIVE: To study the clinical characteristic, the optimal treatments and the prognosis for the recurrence and failure of primary treatment in malignant ovarian germ cell tumors (MOGCT). METHODS: The clinical data of 17 recurrent and failure of primary treatment in MOGCT cases treated in Pecking Union Medical College Hospital from January 1983 to May 2008 were analyzed retrospectively to evaluate failure of primary treatment and second treatment. RESULTS: Only the 4 cases of recurrent and failure of primary treatment of MOGCT were underwent comprehensive surgical staging. After primary surgery in 1 - 8 months, 16 cases received the non-standard chemotherapy were found the lesion again. The secondary debulking surgery was done for the 15 cases and also received the standard chemotherapy. Among of them, 8 cases were survival during follow up, 5 cases gave up the treatment and 4 patients were lost following up during the treatment. CONCLUSIONS: The standard primary treatment is the most important for the MOGCT. Even for the recurrence and failure of primary treatment of MOGCT, the satisfied cytoreductive surgery plus the standard chemotherapy also show the significant impact on the prognosis.

[Clinical analysis of thirteen cases of hypersensitivity reactions to carboplatin.].

OBJECTIVE: To characterize hypersensitivity reactions to chemotherapy with carboplatin in patients with gynecologic malignancies and serve use of carboplatin. METHODS: We retrospectively analyzed the clinical features, management, or outcome of carboplatin-related hypersensitivity reactions in 13 patients with gynecologic malignancies from 1983 to 2008. RESULTS: Twenty times hypersensitivity reactions happened in thirteen women with carboplatin hypersensitivity reactions. The earliest one was at the 5th cycle, the last one was at the 28th cycle; the average cycle was 11.6. The accumulative dosage of carboplatin was 1 900 - 11 400 mg. The average dose was 4840 mg, 2500 - 7200 mg were the main dose range. More than 5 cycles and (or) more than 2500 - 7200 mg of carboplatin administration significantly increased the incidence of hypersensitivity reactions in the twelve patients. Reactions were generally occurred at the first 5 - 10 minutes during intravenous infusion. The average time was 7.6 minutes. Symptoms included mild-to-moderate reactions and severe reactions. Thirteen patients experienced carboplatin hypersensitivity. Two out of 13 cases exhibited severe hypersensitivity reaction at the first time. The first hypersensitivity reactions was mild-to-moderate in 11 cases. When retreated with carboplatin, 4 exhibited no more reactions, 5 exhibited mild-to-moderate hypersensitiviry reactions, 2 exhibited severe reactions. Mild-to-moderate reactions were resolved by temporary interruption of carboplatin infusion, and (or) using steroid, while severe hypersensitivity reactions were resolved by more medicines. CONCLUSIONS: The hypersensitivity reactions in the patients receiving carboplatin are increased after multiple doses of the agent. The possible of retreat with the carboplatin for the mild-to-moderate reactions may be considered. Hypersensitivity reactions should be treated actively. The following chemotherapy should be planed individually. The primary chemotherapy protocol for the patients with severe hypersensitivity reactions should not be reconsidered.

[Expression of vascular endothelial growth factor receptors in the ectopic and eutopic endometrium of women with endometriosis].

OBJECTIVE: To study the localization and expression of the vascular endothelial growth factor receptors (VEGFR) Fms-like tyrosine kinase (Flt-1) and kinase insert domain-containing receptor (KDR) in human ectopic and eutopic endometrium of patients with endometriosis. METHODS: Specimens of endometriosis patients, aged (38 +/- 8) years, including 37 specimens of entopic endometrium, 34 specimens of ovarian chocolate cyst, 34 specimens of ovarian chocolate cyst, 15 specimens of red peritoneal endometriosis lesions, and 4 abdominal wall endometriosis lesions were collected. Specimens of endometrium of 33 patients with other gynecological diseases, aged (36 +/- 8) years, were collected during operation and used as controls. Immunohistochemistry was used to detect the location and expression of Flt-1 and KDR protein in different tissues. Western blotting was used to detect the protein expression of Flt-1 and KDR protein in different tissues. The mRNA expressions of Flt-1 and KDR were detected by RT-PCR. RESULTS: Flt-1 and KDR were expressed in the endometrial glandular epithelium and stromal cells besides the endometrial blood vessels. The positive expression rate of Flt-1 and KDR in the ectopic endometrium of endometriosis patients were 94.3% and 91.4% respectively, both significantly higher than those in the ovarian endometrial cyst (74.3% and 77.1% respectively, both P < 0.05), and similar to those in the eutopic endometrium of the endometriosis patients (93.8% and 90.6% respectively, both P > 0.05). In the eutopic endometrium of the endometriosis patients, the Flt-1 mRNA expression level was 2.4 +/- 1.2 and the Flt-1 protein expression level was 31 +/- 17, and the KDR mRNA expression level was 3.0 +/- 1.4 and the KDR protein expression level was 36 +/- 24, all significantly higher than those in the ovarian endometrial cyst (1.5 +/- 0.9 and 1.8 +/- 1.0 for the Flt-1 and KDR mRNA expressions, and 17 +/- 6 and 20 +/- 11 for the Flt-1 and KDR protein expressions, all P < 0.05), and similar to those in the eutopic endometrium of the non-endometriosis patients (1.9 +/- 0.8 and 2.3 +/- 1.3 for the Flt-1 and KDR mRNA expressions, and 24 +/- 18 and 25 +/- 16 for the Flt-1 and KDR protein expressions, all P > 0.05) CONCLUSION: VEGF may play certain biological role in the development of endometriosis through VEGFR (Flt-1 and KDR). The expression of Flt-1 and KDR in the endometriotic lesion appears to be associated with neovascualization.