Kyung Joo Hwang

Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells

Abstract.  Objectives: To characterize mesenchymal stem cell‐like cells isolated from human amniotic fluid for a new source of therapeutic cells. Materials: Fibroblastoid‐type cells obtained from amniotic fluid at the time of birth. Methods: The ability of ex vivo expansion was investigated until senescence, and stem cell‐like characteristics were analyzed by examining differentiation potential, messenger RNA expression and immunophenotypes. Results and Conclusions: A morphologically homogenous population of fibroblastoid‐type (HAFFTs) cells, similar to mesenchymal stem cells from bone marrow (BM‐MSCs), was obtained at the third passage. The cells became senescent after 27 passages over a period of 8 months while undergoing 66 population doublings. Under appropriate culture conditions, by the 8th passage they differentiated into adipocytes, osteocytes, chondrocytes and neuronal cells, as revealed by oil red O, von Kossa, Alcian blue and anti‐NeuN antibody staining, respectively. Immunophenotype analyses at the 17th passage demonstrated the presence of TRA‐1–60; SSEA‐3 and‐4; collagen types I, II, III, IV and XII; fibronectin; α‐SMA; vimentin; desmin; CK18; CD44; CD54; CD106; FSP; vWF; CD31; and HLA ABC. Reverse transcriptase–polymerase chain reaction analysis of the HAFFTs from passages 6–20 showed consistent expression of Rex‐1, SCF, GATA‐4, vimentin, CK18, FGF‐5 and HLA ABC genes. Oct‐4 gene expression was observed up to the 19th passage but not at the 20th passage. HAFFTs showed telomerase activity at the 5th passage with a decreased level by the 21st passage. Interestingly, BMP‐4, AFP, nestin and HNF‐4α genes showed differential gene expression during ex vivo expansion. Taken together, these observations suggest that HAFFTs are pluripotent stem cells that are less differentiated than BM‐MSCs, and that their gene expression profiles vary with passage number during ex vivo expansion.

High frequency of endometrial polyps in endometriosis

STUDY OBJECTIVE To evaluate the effectiveness of hysteroscopy and the frequency of endometrial polyps in women with endometriosis. DESIGN Retrospective clinical study (Canadian Task Force classification II-2). SETTING Infertility unit at a university-affiliated hospital. PATIENTS One hundred eighty-three infertile women, 92 with endometriosis and 91 controls without the disease. INTERVENTION Laparoscopy and scoring of endometriosis according to the American Fertility Society classification, and confirmation of endometrial polyps by pathologic examination. MEASUREMENTS AND MAIN RESULTS There was no significant difference between groups with regard to age, mean duration of infertility, and frequency of primary or secondary infertility. Endometrial polyps were found in 43 women (46.7%) with endometriosis and in 15 controls (16.5%, p = 0.0000). Their frequency did not differ significantly according to stage of endometriosis. CONCLUSIONS We strongly recommend hysteroscopy if endometriosis is detected in a woman undergoing evaluation for infertility, even if hysterosalpingography and transvaginal ultrasonography do not suggest endometrial polyps.

Endometrium from women with endometriosis shows increased proliferation activity

Examination of 631 infertile women, including 434 women with endometriosis and 197 without endometriosis, revealed an increasing incidence of endometrial polyps, especially in the test subjects with endometriosis, and advanced stages of endometriosis. Expression of Ki-67 and Bcl-2 proteins and MTT assay results were significantly higher in endometrium of patients with endometriosis than in patients without endometriosis. These showed increased proliferation activity and cell proliferation markers not only clinically but also pathologically.

Gonadotropin-Releasing Hormone Agonist Reduces Aromatase Cytochrome P450 and Cyclooxygenase-2 in Ovarian Endometrioma and Eutopic Endometrium of Patients with Endometriosis

Aims: To investigate whether the GnRH agonist may reduce aromatase P450 and COX-2 in the eutopic endometrium of patients with endometriosis and ovarian endometrioma. Materials and Methods: Endometrial specimens and ovarian endometrioma were obtained from 15 women with endometriosis undergoing laparoscopic surgery. The stromal cells of the eutopic endometrium and ovarian endometroma were cultured in the presence of the GnRH agonist (leuprolide acetate 0, 1, 5 and 10 μM) for 24 h. To investigate the effects of the GnRH agonist on the eutopic endometrium in vivo, biopsy samples of the endometrium (n = 5) among the patients who underwent laparoscopy were obtained after GnRH agonist therapy. The protein production of aromatase cytochrome P450 and COX-2 was examined by Western blot. Results: Proteins of aromatase P450 and COX-2 were reduced in the eutopic endometrium of patients with endometriosis treated with the GnRH agonist for 3 months. The stromal cells in the culture of endometrial explants and ovarian endometrioma which were treated with the GnRH agonist reduced the aromatase P450 and COX-2. Conclusion: The GnRH agonist reduced aromatase P450 and COX-2 by direct action on the eutopic endometrium of patients with endometriosis and ovarian endometrioma.

A randomized, multi-center, clinical trial to assess the efficacy and safety of alginate carboxymethylcellulose hyaluronic acid compared to carboxymethylcellulose hyaluronic acid to prevent postoperative intrauterine adhesion.

STUDY OBJECTIVE To estimate the efficacy of alginate carboxymethylcellulose hyaluronic acid (ACH) gel to prevent intrauterine adhesions after hysteroscopic surgery in comparison with carboxymethylcellulose hyaluronic acid (CH) gel, which is known as an effective adhesion inhibitor. DESIGN Randomized, multicenter, single-blind, clinical trial (Canadian Task Force classification I). SETTING Tertiary university hospital. PATIENTS One hundred eighty-seven patients with a surgically treatable intrauterine lesion (myomas, polyps, septa, intrauterine adhesion, dysfunctional uterine bleeding). INTERVENTIONS Patients were randomized to 2 groups: hysteroscopic surgery plus intrauterine application of ACH or CH. MEASUREMENTS AND RESULTS The rate of adhesion formation and the adhesion severity score with type and extent were calculated 4 weeks after surgery. The ACH group had results that were comparable to the CH group in terms of the development of intrauterine adhesions at 4 weeks follow-up. The adhesion severities were not different between the 2 groups. In a subgroup without baseline intrauterine adhesion, the ACH group showed a lower intrauterine adhesion rate than the CH group (p = .016). CONCLUSIONS ACH had a comparable efficacy to CH in terms of the adhesion rate and severity. In the case of no baseline intrauterine adhesion, intrauterine application of ACH after hysteroscopic surgery had a lower rate of intrauterine adhesion than application of CH.

Comparison of in vitro maturation media of immature oocytes: the effectiveness of blastocyst culture media

OBJECTIVE To compare three different in vitro maturation (IVM) media for immature oocytes. DESIGN Experimental study. SETTING In vitro fertilization laboratory. ANIMAL(S) BDF1 female and male mice. INTERVENTION(S) Retrieval and maturation of cumulus-enclosed germinal vesicle-stage oocytes according to one of three protocols: group A, conventional IVM medium; group B, blastocyst culture medium; and group C, tissue culture medium (TCM) 199. MAIN OUTCOME MEASURE(S) Maturation, fertilization, and developmental rates of immature oocytes. RESULT(S) A total of 653 immature oocytes were cultured in vitro and then analyzed. No difference was found in maturation rates and fertilization rates in comparing groups A and B. However, the IVM rates were statistically significantly increased in groups A and B compared with group C. No difference was found in fertilization rates between media, but the developmental competency to blastocyst stage was statistically significantly higher in group B compared with group C. CONCLUSION(S) The developmental competency of immature oocytes did not differ between conventional IVM medium and blastocyst culture medium, but TCM-199 was found to be unsuitable. Evidence from mice as test subjects suggests that both conventional IVM medium and blastocyst culture medium are suitable for IVM, and that blastocyst culture medium may be a good choice for conventional IVM of immature oocytes.

Peroxisome proliferator-activated receptor γ agonist suppresses human telomerase reverse transcriptase expression and aromatase activity in eutopic endometrial stromal cells from endometriosis

Objective To investigate the effect of peroxisome proliferator activated receptor γ (PPARγ) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPARγ agonist). Results We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPARγ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin E2 production in the ESCs of endometriosis. Conclusion This study suggests that PPARγ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

Effectiveness of emergency contraception in women after sexual assault.

Objective To assess the effectiveness of emergency single-dose levonorgestrel contraception in preventing unintended pregnancies among woman who visited the emergency department (ED) due to sexual assault (SA). Methods We conducted a retrospective chart review in a university hospital in South Korea. Cases from November 10, 2006 to November 9, 2009 were enrolled. Information from the initial visit to the ED and subsequent follow-up visits to the gynecology outpatient clinic was collected. Results In total, 1,179 women visited the ED due to SA. Among them, 416 patients had a gynecological examination and 302 patients who received emergency contraception (EC) (1.5 mg single-dose levonorgestrel) at the ED due to SA were enrolled. Ten patients did not return for follow-up examinations. In follow-up visits at the outpatient clinic, two pregnancies were confirmed, which showed the failure rate of the EC to be 0.68%. Conclusion Single-dose levonorgestrel EC is extremely effective at preventing pregnancy among victims of SA.

Fertility preservation for patients with gynecologic malignancies: The Korean Society for Fertility Preservation clinical guidelines

Fertility preservation plays a central role in cancer care since an increasingly large number of cancer patients are surviving as a result of improvements in diagnostic and therapeutic strategies. Physicians who take part in the initial diagnosis and management of gynecologic cancer should understand the importance of fertility preservation. Since indications for fertility preservation are limited to early-stage gynecologic cancer, a surgeon must carefully consider each indication. Before performing fertility-sparing surgery, health professionals should compare its oncologic and pregnancy outcomes with those of other standard treatments. Individualized treatment strategies should be delivered depending on the patients situation, and physicians should provide timely information and appropriate counseling.

Perceptions of Postmenopausal Symptoms and Treatment Options among Middle-Aged Korean Women

Purpose To investigate the perceptions of postmenopausal symptoms and treatment options among middle-aged Korean women. Materials and Methods This cross-sectional study included 2330 Korean women. The women were administered a structured questionnaire to collect sociodemographic data and information regarding menopause and its treatment. Results More than half (65%) of the participants perceived menopause as a disease, and 66.8% knew hormone therapy (HT) is available for menopausal symptom treatment. However, only 19.7% of participants visited clinics for HT. The most common reasons for having negative views about HT were its adverse reactions (47.3%) and concerns about developing cancer (41.1%). For symptom management, 36.5% of the participants tried lifestyle modification instead of HT. Conclusion The majority of Korean women regarded menopause as a disease. They were aware of HT for menopausal symptom treatment, but the use of HT was relatively low. Education about the safety and positive effects of HT and the importance of professional healthcare should be provided.