Anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma in Korea: three case reports.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune paraneoplastic syndrome associated with ovarian teratomas. Most patients develop neurologic symptoms, including psychosis, memory deficits, seizures, or abnormal movements, and experience abdominal pain related to ovarian neoplasm. We present a case report of three patients diagnosed with anti-NMDAR encephalitis accompanied by ovarian teratomas at Ajou University Hospital in Korea. The patients demonstrated a different clinical course of the disease. However, upon diagnosis, all patients underwent surgical removal of the ovarian teratoma followed by intensive immunotherapy. The symptoms progressively improved following treatment. This is a case report of a rare autoimmune anti-NMDAR encephalitis associated with ovarian neoplasms, including immature teratoma.

Effect of in vitro testicular spermatozoa culture on pregnancy outcomes: an experience at a single university hospital.

BACKGROUND: There are no guidelines for the optimal incubation time or temperature to improve pregnancy outcomes in testicular sperm extraction-intracytoplasmic sperm injection (TESE-ICSI) cycles. We aimed to evaluate whether a 24-hour in vitro culture of testicular spermatozoa affects pregnancy outcomes in TESE-ICSI cycles. METHODS: This was a retrospective study of 83 TESE-ICSI cycles using testicular spermatozoa in 46 couples with male partners suffering from nonobstructive or obstructive azoospermia. Sperm retrieval was performed either on the oocyte retrieval (OR) day (65 cycles in 33 couples; group A) or on the day before OR (18 cycles in 13 couples; group B) followed by in vitro culture for 24 hours. The clinical characteristics and pregnancy outcomes, including the number of retrieved oocytes, fertilization rates, embryo transfer rates, implantation and clinical pregnancy rates, were compared between the two groups. RESULTS: There were no differences in terms of clinical characteristics except for the levels of luteinizing hormone (LH) in males. Group B had higher LH levels than group A (4.56±1.24 IU/L vs. 3.67±1.07 IU/L, p=0.017). Group B showed higher fertilization rate (72.4±32.1% vs. 59.2±21.7%, p=0.045), implantation rate (35.0±34.1% vs. 14.0±21.5%, p=010), pregnancy rate per cycle (80% vs. 39%, p=0.033), and clinical pregnancy rate per cycle (80% vs. 37.5%, p=0.024) than those of group A. CONCLUSION: Testicular sperm retrieval performed on the day before OR followed by in vitro culture can potentially improve pregnancy outcomes.

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.

Fertility preservation during cancer treatment: The Korean Society for Fertility Preservation clinical guidelines.

While many fertility preservation (FP) options now exist for reproductive-aged cancer patients, access to these services continues to be limited. A comprehensive FP program should be organized to serve oncofertility patients effectively. Also, much effort is needed from various individuals-patients, specialists from various fields, and consultants-to facilitate FP in a timely manner. Various challenges still exist in improving access to FP programs. To improve access to FP treatment, it is important to educate oncologists and patients via electronic tools and to actively navigate patients through the system. Reproductive endocrinology practices that receive oncofertility referrals must be equipped to provide a full range of options on short notice. A multidisciplinary team approach is required, involving physicians, nurses, mental health professionals, office staff, and laboratory personnel. The bottom line of FP patient care is to understand the true nature of each patient's specific situation and to develop a patient flow system that will help build a successful FP program. Expanding the patient flow system to all comprehensive cancer centers will ensure that all patients are provided with adequate information regarding their fertility, regardless of geography.

Fertility preservation for patients with breast cancer: The Korean Society for Fertility Preservation clinical guidelines.

With advances in the methods of cancer treatment used in modern medicine, the number of breast cancer survivors has been consistently rising. As the number of women who wish to become pregnant after being diagnosed with breast cancer increases, it is necessary to consider fertility preservation in these patients. However, medical doctors may be unaware of the importance of fertility preservation among cancer patients because most patients do not share their concerns about fertility with their doctors. Considering the time spent choosing and undergoing treatment, an early referral to a reproductive specialist is the best way to prevent a delay in cancer treatment. Since it is not easy to make decisions on matters related to cancer diagnosis and fertility, patients should be provided with enough time for decision-making, and to allow for this, an early referral will provide patients with sufficient time to choose an appropriate method of fertility preservation. The currently available options of fertility preservation for patients with breast cancer include cryopreservation of embryos, oocytes, and ovarian tissue and gonadotropin-releasing hormone agonist treatment before and during chemotherapy. An appropriate method of fertility preservation must be selected through consultations between individual patients and health professionals and analyses of the pros and cons of different options.

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 patient's situation, and physicians should provide timely information and appropriate counseling.

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

Although the survival rate of hematologic malignancies in young patients is very high, cytotoxic therapies such as chemotherapy and total body irradiation therapy can significantly reduce a patient's reproductive capacity and cause irreversible infertility. Early ovarian failure also commonly occurs following additional cancer treatment, bone marrow transplantation, or autologous transplantation. Because the risk of early ovarian failure depends on the patient's circumstances, patients with a hematologic malignancy must consult health professionals regarding fertility preservation before undergoing treatments that can potentially damage their ovaries. While it is widely known that early menopause commonly occurs following breast cancer treatment, there is a lack of reliable study results regarding fertility preservation during hematologic malignancy treatment. Therefore, an in-depth discussion between patients and health professionals about the pros and cons of the various options for fertility preservation is necessary. In this study, we review germ cell toxicity, which occurs during the treatment of hematologic malignancies, and propose guidelines for fertility preservation in younger patients with hematologic malignancies.

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.

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.

Current status of assisted reproductive technology in Korea, 2009.

Great advances have been made in the field of assisted reproductive technology (ART) since the first in vitro fertilization (IVF) baby was born in Korea in the year of 1985. However, it deserve to say that the invaluable data from fertility centers may serve as a useful source to find out which factors affect successful IVF outcome and to offer applicable information to infertile patients and fertility clinics. This article intended to report the status of ART in 2009 Korean Society of Obstetrics and Gynecology surveyed. The current survey was performed to assess the status and success rate of ART performed in Korea, between January 1 and December 31, 2009. Reporting forms had been sent out to IVF centers via e-mail, and collected by e-mail as well in 2012. With International Committee Monitoring Assisted Reproductive Technologies recommendation, intracytoplasmic sperm injection (ICSI) and non-ICSI cases have been categorized and also IVF-ET cases involving frozen embryo replacement have been surveyed separately. Seventy-four centers have reported the treatment cycles initiated in the year of 2009, and had performed a total of 27,947 cycles of ART treatments. Among a total of 27,947 treatment cycles, IVF and ICSI cases added up to 22,049 (78.9%), with 45.3% IVF without ICSI and 54.7% IVF with ICSI, respectively. Among the IVF and ICSI patients, patients confirmed to have achieved clinical pregnancy was 28.8% per cycle with oocyte retrieval, and 30.9% per cycle with embryo transfer. The most common number of embryos transferred in 2009 is three embryos (40.4%), followed by 2 embryos (28.4%) and a single embryo transferred (13.6%). Among IVF and ICSI cycles that resulted in multiple live births, twin pregnancy rate was 45.3% and triple pregnancy rate was 1.1%. A total of 191 cases of oocyte donation had been performed to result in 25.0% of live birth rate. Meanwhile, a total of 5,619 cases of frozen embryo replacement had been performed with 33.7% of clinical pregnancy rate per cycle with embryo transfer. When comparing with international registry data, clinical pregnancy rate per transfer from fresh IVF cycles including ICSI (34.1%,) was comparable to clinical pregnancy rate per transfer in European Society for Human Reproduction and Embryology report was 32.5% though lower than 45.0% for USA data. There was no remarkable difference in status of assisted reproductive technology in Korea between the current report and the data reported in 2008. The age of women trying to get pregnant was reconfirmed to be the most important factor that may have impact on success of ART treatment.

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.

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 microM) 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.

Tumor necrosis factor-alpha-induced cyclooxygenase-2 overexpression in eutopic endometrium of women with endometriosis by stromal cell culture through nuclear factor-kappaB activation.

OBJECTIVE: To investigate the role of NF-kappaB during the induction of COX-2 by TNF-alpha in the eutopic endometrium of women with and without endometriosis using stromal cell culture. STUDY DESIGN: Experimental study in cultured stromal cells of the eutopic endometrium of women with and without endometriosis in the presence of TNF-alpha. RESULTS: Within 5-20 minutes of stimulation with TNF-alpha, p-IkappaB was clearly observed in the eutopic endometrium of women with endometriosis and in that of women without endometriosis. COX-2 protein was significantly induced by treatment with TNF-alpha in both eutopic endometrial stromal cells of women with and without endometriosis (p < 0.05), but the degree of induction was significantly increased in eutopic endometrial stromal cells of women with endometriosis than those of women without endometriosis (p < 0.05). CONCLUSION: Overexpression of COX-2 by TNF-alpha in the eutopic endometrium of women with endometriosis may play a critical role in such pathophysiologic processes as endometriosis formation.

Transforming growth factor (TGF)-beta1-induced human endometrial stromal cell decidualization through extracellular signal-regulated kinase and Smad activation in vitro: peroxisome proliferator-activated receptor gamma acts as a negative regulator of TGF-beta1.

OBJECTIVE: To investigate the effect of transforming growth factor (TGF)-beta1 on the extracellular signal-regulated kinase (ERK) and Smad pathway and the role of peroxisome proliferator-activated receptor (PPAR)-gamma in cultured human endometrial stromal cells. DESIGN: Experimental study. SETTING: Infertility center of a tertiary university hospital. MATERIAL(S): Human endometrial tissues obtained by hysterectomy from patients with conditions other than endometrial diseases. INTERVENTION(S): Endometrial stromal cells were cultured under normal laboratory conditions. TGF-beta1, rosiglitazone (PPARgamma agonist), and PD98059 (ERK inhibitor) were added to endometrial stromal cell culture according to experimental purposes. MAIN OUTCOME MEASURE(S): Cell count, PRL expression, Smad and ERK phosphorylation, cyclooxygenase (COX)-2 expression, and prostaglandin E(2) (PGE(2)) release. RESULT(S): TGF-beta1 inhibited cellular proliferation and induced the expressions of COX-2, PGE(2), and PRL of cultured human endometrial stromal cells. These effects may be mediated by Smad and ERK phosphorylation. Treatment with rosiglitazone, a PPARgamma agonist, reversed the TGF-beta1 effect by antagonizing the activation of ERK and Smad that was induced by TGF-beta1. CONCLUSION(S): PPARgamma plays a negative role by directly acting on Smad and ERK phosphorylation in human endometrial cell decidualization that is induced by TGF-beta1 in vitro.

ATP-induced apoptosis of human granulosa luteal cells cultured in vitro.

OBJECTIVE: To investigate the role of extracellular adenosine triphosphatase (ATP) as an inducer of apoptotic cell death in human granulosa cells and to elucidate its underlying mechanism. DESIGN: Prospective study. SETTING: Gynecologic clinic and human reproduction research laboratory. PATIENT(S): Twenty-five patients undergoing IVF or IVF-ET. INTERVENTION(S): ATP treatment of granulosa luteal cells subjected to primary culture. MAIN OUTCOME MEASURE(S): Apoptosis was assessed by the annexin V binding assay and the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling assay. The receptor type that binds ATP, thus mediating ATP-induced apoptosis, was determined by using the calcium imaging and patch-clamp techniques. Mitochondrial depolarization was assessed by staining with the membrane potential-sensitive dye 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolyl carbocyanide iodide (JC-1). RESULT(S): ATP elevated [Ca(2+)](i) by mobilizing intracellularly stored Ca(2+). An ionic membrane current evoked by ATP was mediated by the Ca(2+)-activated K(+) channel. ATP induced a mitochondrial depolarization with a concomitant increase in cellular apoptosis. Treatment with hCG eliminated both ATP-induced mitochondrial depolarization and apoptosis. CONCLUSION(S): Extracellular ATP recognized by P(2Y) type purinoceptor triggers apoptosis in human granulosa luteal cells, and the downstream apoptotic cascade may act at least in part through mitochondria. The antiapoptotic effect of hCG has possible clinical implications in the treatment of disorders involving granulosa cell degeneration (such as follicular atresia).

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.

Expression of integrins, cyclooxygenases and matrix metalloproteinases in three-dimensional human endometrial cell culture system.

The objective of this investigation was to establish a three-dimensionally cultured human endometrium which could be used as a tissue model for the mechanism study of implantation in vitro. By using human endometrial stromal (ES) and epithelial cells (EE) from hysterectomy specimens, reconstruction of endometrium in culture was established by first layering a collagen gel containing ES cells, then overlaying with the Matrigel containing endometrial epithelial (EE) cells. Ultrastructural examination of the 48 h-endometrial cell culture revealed monolayered columnar EE cells with microvilli on the collagen layer containing ES cells and appearance of the tight junctions and desmosomes between EE cells, a cell layer closely resembling the native endometrium. Immunohistochemical characterization of the reconstructed endometrium showed a strong immunoreactivity for cytokeratin, integrin alpha1, alpha4 and beta3 subunits, cyclooxygenases-1 and -2, matrix metalloproteinases-1, -2, -3 and -9, and tissue inhibitor of metalloproteinases-1 and -2 in the EE cells comparable to the native endometrial epithelium. ES cells also showed stronger immunoreactivity for cyclooxygenases, integrins and MMPs, but less for cytokeratin. Gelatin zymographic analyses of the media obtained from the reconstructed endometrium model showed gelatinase activity bands at 57, 60, 72, 92 and 97 kDa molecular weight, respectively. The present study provides a possibility that our three-dimensionally cultured endometrium model could mimic the morphological and functional characteristics of the native endometrium. The model could be used to clarify the roles of various molecules involved in the human implantation.