Search

Objective: To investigate if the immunotherapy with corticosteroids would improve the pregnancy rate in infertile patients with endometriosis who undergo in vitro fertilization and embryo transfer (IVF-ET). Methods: Forty-two infertile patients with endometriosis plus tubal factor and 87 pure tubal infertility patients who underwent IVF-ET in our unit were allocated randomly to the corticosteroid treatment group and the control group. Results: The prevalence of autoantibodies (antinuclear antibody, lupus anticoagulant, anticardiolipin antibody, rheumatoid factor) was elevated significantly in patients with endometriosis plus tubal factor compared with pure tubal infertility patients (38.1% vs 2.3%). Twenty-one patients with endometriosis plus tubal factor underwent 54 cycles of IVF-ET, receiving corticosteroids. Forty-three patients with pure tubal factor underwent 81 cycles of IVF-ET, receiving corticosteroids. Twenty-one patients with endometriosis plus tubal factor who underwent 57 cycles of IVF-ET and 44 patients with pure tubal factor who underwent 84 cycles of IVF-ET served as controls, not receiving corticosteroids. In patients with endometriosis plus tubal factor, there was a significantly higher clinical pregnancy rate per cycle in the treatment group, with 42.6% (23/54) compared with 22.8% (13/57) in the control group but no differences between 2 groups in spontaneous abortion rate (21.7% vs 15.4%) and multiple pregnancy rate (17.4% vs 15.4%). In patients with pure tubal infertility, there were no significant differences between the treatment group and control group in clinical pregnancy rate (40.7% vs 34.5%), spontaneous abortion rate (12.1% vs 10.3%) or multiple pregnancy rate (18.2% vs 10.3%). In the endometriosis plus tubal infertility group with autoantibodies, the clinical pregnancy rate per cycle was significantly higher in the treatment group at 40.9% compared with 14.8% in the control group. In endometriosis plus tubal infertility group without autoantibodies, there was no significant difference between 2 groups with respect to the clinical pregnancy rate per cycle (43.8% vs 30.0%). Conclusions: This study suggests that immunotherapy with corticosteroids could improve the clinical pregnancy rate in endometriosis patients undergoing IVF-ET and may be more effective in patients with positive autoantibodies.

Problem We evaluated whether the expression of NF-кB p65 subunit is increased in the eutopic endometrium and/or in the ovarian endometrioma of women with advanced stage endometriosis, and ascertained in vitro effects of proinflammatory cytokines on the expression and DNA binding of NF-кB p65 subunit in endometrial cells. Method of Study Immunohistochemistry was performed to compare the nuclear NF-кB p65 subunit immunoreactivity between women with and without advanced stage endometriosis. The nuclear NF-кB p65 subunit expression and DNA binding were also analyzed in endometrial cells treated with tumor necrosis factor-alpha (TNF-α) or interleukin-1beta (IL-1β) utilizing Western blot analysis, enzyme-linked immunosorbent assay, and electrophoretic mobility shift assay. Results The immunoreactivity of the nuclear NF-кB p65 subunit was significantly increased in the eutopic endometrium as well as in the ovarian endometrioma of women with endometriosis compared with the controls. In vitro treatment of endometrial cells with TNF-α and IL-1β led to a significant increase in nuclear NF-кB p65 subunit expression and DNA binding. Conclusions The nuclear expression of NF-κB p65 is increased in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis, which strongly suggests that NF-кB signaling plays a crucial role in the pathogenesis and/or pathophysiology of endometriosis.

This clinical study was designed to identify and compare the pregnancy rates of simultaneous program of natural-cycle IVF and cryopreserved-thawed ET (NICE) with those of natural-cycle IVF and cryopreserved-thawed ET.All three groups comprised spontaneously ovulating infertile women under the age of 40 and without any male factor present. The NICE program was performed in 36 patients (47 cycles) who had previously undergone IVF-ET resulting in cryopreserved embryos. As control groups, the natural-cycle IVF was performed in 45 patients (80 cycles), and the cryopreserved-thawed ET alone in 29 patients (40 cycles).The cancellation rate of the initiated cycles prior to ET was 19.1% (9/47) in the NICE group, 23.8% (19/80) in the natural-cycle IVF group, and 2.5% (1/40) in the cryopreserved-thawed ET group. The mean number of embryos transferred was 4.0 +/- 1.1 (2-5) in the NICE group, 1.0 in the natural-cycle IVF group, and 4.2 +/- 1.8 (1-5) in the cryopreserved-thawed ET group. The clinical pregnancy rates per aspiration cycle (32.5%) and per ET cycle (34.2%) in the NICE group were significantly higher than those (14.9, 16.4%) in the natural-cycle IVF group. The clinical and delivered pregnancy rates per ET (34.2, 26.3%) in the NICE group were higher than those (20.5, 15.4%) in the cryopreserved-thawed ET group, without statistical significance.Since the NICE program results in saving the fresh oocyte for patients participating in cryopreserved-thawed ET, more favorable pregnancy rates may be obtained from NICE cycles in women ovulating normally who had previously undergone IVF-ET with embryo cryopreservation.

Endometriosis is a common gynecological condition characterized by enhanced proliferation, adhesiveness, invasiveness, and survival of endometrial cells after retrograde menstruation. Originally identified as a cytoskeletal regulatory kinase, p21-activated kinase 4 (Pak4) regulates diverse cellular activities that might be altered in the establishment and progression of endometriosis.The aim was to evaluate the effects of sex steroids and proinflammatory cytokines on the Pak4 expression in endometrial cells along with the functional change caused by inhibition of Pak4 expression as well as to see whether the Pak4 expression is altered in endometriosis.Pak4 expression was analyzed using immunohistochemistry and Western blot analysis. Viability and invasiveness were assayed after transfection of endometrial cells with Pak4 small interfering RNA.The Pak4 expression was significantly decreased in the stromal cells during the secretory phase as well as by in vitro treatment with progesterone. The immunoreactivity of Pak4 was significantly increased in the eutopic endometrium as well as in the ovarian endometriotic cyst of women with endometriosis compared with the control subjects. TNF-α induced a significant increase in the Pak4 expression in endometrial cells in vitro, whereas IL-1β had no effects. Transfection of endometrial cells with Pak4 small interfering RNA led to a significant decrease in viability and invasiveness in endometrial cells.These findings suggest that Pak4 is regulated by progesterone and TNF-α in endometrial cells and that the increased expression of Pak4 might lead to the establishment and progression of endometriosis by enhanced cellular viability and invasiveness in endometrial cells.

The desired objective of controlled ovarian stimulation (COS) is to allow the growth of a cohort of follicles and to facilitate the recovery of a large number of fertilizable oocytes. However, poor responders with low ovarian reserve often fail to respond adequately despite the maximal dose of gonadotropins administered, with the results that the number as well as quality of oocytes harvested may be very low. These results lead to a significant decrease of pregnancy rate in IVF cycles. Therefore, successful COS for poor responders continues to be a major challenge in IVF program. In this review, I will describe strategies for improvement of ovarian response to COS in poor responders. The strategies described may provide a means of augmenting follicular recruitment by endocrinological manipulation for poor responders undergoing IVF.

Purpose: In pursuit of high precision in target localization and steeper dose fall-off in stereotactic radiosurgery, we investigated the impact of optimizing dose-limiting auto-shell function on the quality of Cyberknife (CK) plans in treating brain metastases (BMs). Methods: Nineteen BMs previously treated using CK were selected for this study. The original CK plans (CK_original) had been produced using one to three dose-limiting auto-shells at prescription dose (PD) level and low dose levels of 10 to 30% of PD. In each case, a modified CK plan (CK_modified) was generated using five dose-limiting shells at PD level, intermediate dose level of 50% of PD, and low dose levels with an optimal shell-dilation size based on our experience. In addition, a Gamma Knife plan (GK) was also produced using the original contour set. Thus, a triplet data set of dosimetric parameters was generated and analyzed. Results: While no differences in conformity index (mean±SD 1.22 ± 0.1, 1.18 ± 0.1, and 1.24 ± 0.1 in CK_original, CK_modified, and GK, respectively; over all P > 0.05) and tumor coverage (mean±SD 99.5 ± 0.4%, 99.5 ± 0.3%, and 99.4 ± 0.2% in CK_original, CK_modified, and GK, respectively; over all P > 0.05) were observed among the plans, the normal tissue volume receiving 50% of PD was significantly decreased in CK_modified and GK compared with CKoriginal by 1.28 and 1.27-fold, respectively (P < 0.001, each). No significant differences in dose fall-off were observed between CK_modified and GK (P = 0.345). Conclusion: By optimizing auto-shell function, a significantly steeper dose fall-off can be achieved in CK system, while maintaining high precision in target localization.

�Objective: To evaluate the effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase (MDP-EL) in comparison with standard GnRH agonist luteal long protocol (LP) in each non-obese and obese polycystic ovary syndrome (PCOS) women undergoing IVF. Methods: Two hundred eleven infertile women with PCOS were recruited and randomized to undergo either GnRH antagonist MDP-EL (antagonist group) or standard GnRH agonist luteal LP (agonist group). IVF cycle outcomes were compared between the two groups. Results: Total dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the antago nist group than in the agonist group. Incidence of severe ovarian hyperstimulation syndrome was significantly lower in the antagonist group. However, IVF and pregnancy outcomes were similar in the two groups. When all subjects were divided into non-obese and obese subgroups, in non-obese PCOS subgroup, IVF and pregnancy outcomes were comparable in the antagonist and agonist groups but total dose and days of rhFSH were also significantly fewer in the antagonist group. Similar findings were also observed in obese PCOS subgroup. Conclusion: GnRH antagonist MDP-EL is at least as effective as GnRH agonist LP and may be a more patient-friendly alternative in controlled ovarian stimulation for PCOS patients undergoing IVF, independent of body mass index.

This study was performed to assess the expression levels of vascular endothelial growth factor receptor (VEGFR)-1, -2 and -3 mRNA in eutopic endometrial tissue and their effects on in vitro fertilization-embryo transfer (IVF-ET) outcomes in women with endometriosis.Twenty women with endometriosis III or IV (study group) and 20 with tubal infertility only (control group) were evaluated. Controlled ovarian stimulation in all patients consisted of the long protocol using gonadotrophin-releasing hormone agonist. Prior to the administration of 0.1 mg triptorelin daily in the mid-luteal phase of the preceding menstrual cycle, a biopsy specimen was taken from the endometrial cavity, and the expression levels of VEGFR-1, -2 and -3 mRNA were analyzed with real-time reverse transcription-polymerase chain reaction.There were no significant differences in the numbers of retrieved oocytes and mature oocytes, fertilization rate and clinical pregnancy rate between the study and control groups. However, the implantation rate was significantly lower in the study group (P 0.05). The relative amounts of VEGFR-1, -2 and -3 mRNA were significantly higher in the study group than in the control group (P 0.001 each). The relative amounts of VEGFR-1 and -3 mRNA were significantly higher in the non-pregnant than in the pregnant subgroup of the study group (P 0.01, P 0.05, respectively).Increased expression of VEGFR in the endometrium, especially VEGFR-1 and -3, may be related to the development of endometriosis and may reduce the receptivity of the endometrium.

We evaluated whether the proinflammatory cytokines can regulate p21-activated kinase (Pak1) expression in endometrial cells as well as whether its expression is increased in endometriotic cysts. We found that interleukin-1β up-regulates Pak1 expression in endometrial stromal cells (ESC) and that the immunoreactivity of Pak1 is increased in the endometriotic cysts.

BACKGROUND: Myolysis is one of the procedures that is claimed to provide significant improvement in myoma status without hysterectomy. Myolysis procedures have been generally performed via laparoscopy, and there are limited data on transvaginal radiofrequency (RF) myolysis. This study investigated the feasibility, efficacy and safety of transvaginal ultrasound-guided RF myolysis. METHODS: Transvaginal ultrasound-guided RF myolysis was performed on 69 premenopausal women with symptomatic uterine myomas as an outpatient procedure. Outcomes were assessed I, 3, 6 and I2 months after RF myolysis. Myoma volumes were measured by ulrasonography. Menorrhagia was evaluated by the number of soaked normal-sized sanitary products used per menstrual period and overall symptoms were evaluated using the symptom severity subscale of the uterine fibroids symptom questionnaire. RESULTS: Mean (± SD) age of patients was 39.8 ± 6.5 years. Mean baseline volume of the dominant myomas was 304.6 ± 229.I cm3 and its volume at 3 months following RF myolysis decreased compared with the previous examination (P = 0.002). An improvement of menorrhagia occurred I 3, 6 and I2 months after operation (all P < 0.00I versus baseline). Overall symptoms at I, 3, 6 and I2 months after RF myolysis also improved (all P < 0.00I versus baseline). No major complications were observed or reported. After I2 months, three patients had successfully conceived and delivered and there were no complications during labor or delivery. CONCLUSIONS: Transvaginal ultrasound-guided RF myolysis might be a safe, effective and minimally invasive outpatient procedure for uterine myoma in terms of size reduction, symptom improvement and safety.

Based on the findings of several reports that have shown an increased plasma level of di-(2-ethylhexyl) phthalate (DEHP) in women with endometriosis, the present study was designed to evaluate whether in vitro treatment with DEHP can increase viability of endometrial cells. Utilizing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay, fluorescent activated cell sorter analysis, and microscopic evaluation after Hoechst staining, we revealed that in vitro treatment with DEHP leads to increased viability of Ishikawa cells as well as endometrial stromal cells in serum-free condition and following exposure to hydrogen peroxide, which suggests that exposure to phthalate might play a role in the establishment of endometriosis.

To investigate recurrent miscarriages in Koreans in terms of causative factors and the prognosis for subsequent successful pregnancies in primary and secondary recurrent miscarriages cases.The study retrospectively examined the clinical records of 222 recurrent miscarriage cases that were presented at the Department of Obstetrics and Gynecology, Asan Medical Center, Seoul, Korea, from July 1989 to June 2008. The cases were classified according to the cause and pregnancy rates after the primary and secondary abortions were compared using the chi2 test.The etiologic analysis indicated that anatomic abnormality (29.4%) was the most common cause of recurrent miscarriage in Koreans, followed by immunologic (26.7%), inexplicable (24.1%), endocrinologic (15.0%) and genetic (11.2%) causes. The subsequent successful pregnancy rate was higher in the secondary recurrent miscarriage group than the primary recurrent miscarriage group (47.9% vs. 31.7%, p0.05).The causative factors of recurrent miscarriages in Koreans differed from those reported in Western studies on the frequency of causes. The prognosis for subsequent successful pregnancies was better in the secondary recurrent miscarriage group, as we expected.

The intracellular antioxidant system, based on glutathione (GSH), plays a key role in endometrial detoxification reactions and has been proposed to be involved in the pathogenesis endometriosis. This study was designed to evaluate whether estradiol (E(2)) and proinflammatory cytokines have any effects on expression of glutathione in endometrial stromal cells (ESCs).Glutathione levels were measured utilizing high-performance liquid chromatography following in vitro culture and treatment of ESCs with estradiol, tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1beta).The GSH level in E(2) (10(-8) m) treatment group was significantly higher than in the control group at 48 h (P0.05). In vitro treatment of ESCs with TNF-alpha 10 ng/mL as well as E(2) (10(-8) m) plus TNF-alpha 10 ng/mL for 48 hr also led to a significant increase in GSH level (P0.05; P0.05, respectively). Both IL-1beta 10 ng/mL and E(2) (10(-8) m) plus IL-1beta 10 ng/mL for 48 hr increased GSH level significantly (P0.05; P0.05, respectively) as well.These findings might suggest that increased production of estradiol and proinflammatory cytokines in the peritoneal cavity possibly leads to the establishment of endometriosis through increased level of GSH.

Id genes are involved in proliferation and differentiation in various cell types. However, it remains to be fully investigated how Id genes are regulated in highly dynamic uterine tissue. Using cDNA microarray, we previously observed that Id-1 was upregulated in uteri from ovariectomized (OVX) mice exposed to 17beta-estradiol (E2). Here, we further examined the expression pattern of Id-1 and its regulation of by E2 and progesterone (P4) in the mouse uterus. Increased Id-1 transcripts in OVX mice uterus exposed to E2 were efficiently reduced by pretreatment with ICI 182,780 (an antagonist for nuclear estrogen receptor), suggesting that E2 induced expression of Id-1 is mediated via classical estrogen receptor (ER). In contrast, P4 treatment did not enhance or antagonize the action of E2 on Id-1 expression. Laser capture microdissection revealed that Id-1 is exclusively expressed in luminal epithelial cells. Notably, Id-1 was significantly upregulated at implantation sites on day 4.5 of pregnancy due to strong expression of Id-1 in blastocyst stage embryos. The present results show that the expression of Id-1 in the mouse uterus is tightly regulated by E2 via classical ER genomic pathway, not P4 suggesting an important role in uterine physiological events such as the estrous cycle and implantation process.

To evaluate the association between serum estradiol (E2) level and intraocular pressure (IOP) in Korean postmenopausal womenFrom January 2000 to December 2006, serum concentration of E2 and IOP were measured in 8,674 postmenopausal women. Serum concentration of E2 was measured by radioimmunoassay. The IOP was measured using Goldmann's applanation tonometer. All data were analyzed with correlation analysis, Student's t test and analysis of variance.The mean age of the study subjects was 59.57 +/- 8.54 years. The mean E2 concentration was 22.17 +/- 6.08 pg/mL and the mean IOP was 12.23 +/- 2.20 mm Hg for the average of both eyes. In correlation analysis, no significant association was found between IOP and age or IOP and serum E2 concentration. When we divided a total of 8,674 women into 4 groups according to the E2 concentration (or = 10, 10-20, 20-30 and30 pg/mL, respectively), the IOPs of the 4 groups did not differ significantly.This study suggests that the IOP in Korean postmenopausal women might not be directly associated with serum E2 concentration.

The present study was designed to evaluate whether the expression of p21-activated kinase 1 (Pak1), which recently has been shown to be increased in the eutopic endometrium of women with endometriosis, is also increased in adenomyotic nodules as well as in the eutopic endometrium in women with adenomyosis. Comparative immunohistochemical study using a monoclonal antihuman Pak1 antibody revealed that the expression of Pak1 is increased in the eutopic endometrium of women with adenomyosis during the secretory phase, along with its increased expression in adenomyotic nodules, suggesting a possible role of Pak1 in the establishment of adenomyosis.

This prospective randomized study was performed to investigate the effectiveness of minimal stimulation using recombinant human FSH (rhFSH) and GnRH antagonist compared with GnRH antagonist multiple-dose protocol (MDP) in low responders undergoing IVF/intracytoplasmic sperm injection. Our study demonstrated that minimal stimulation in natural cycles provides similar pregnancy rates to the GnRH antagonist MDP with fewer dose and days of rhFSH used and thus can be a cost-effective alternative as a last chance before oocyte donation in low responders.

Aims: This study compared the clinical outcome of patients undergoing outside-in transobturator tape (TOT) or inside-out transobturator tape (TVT-O) procedures for female stress urinary incontinence (SUI). Methods: The study examined the medical records of 615 patients who underwent TOT (376 patients) or TVT-O (239 patients) for SUI, and compared patient characteristics, operation time, duration of hospital stay, cure rates, and complication rates, by conducting a 1-year follow-up survey. Results: The TOT and TVT-O groups were found to be similar in terms of operation time, duration of hospital stay, surgical outcome (both before and after adjustment for age, parity, menopause, and previous pelvic surgery, cure rate (87.8% for TOT and 85.3% for TVT-O) and complication rate (14.4% for TOT, 15.5% for TVT-O). The complication rates after operations did not differ significantly between the two groups. Complications over the 1-year follow-up included urinary retention, de novo urgency, leg pain, vaginal mesh erosion, and hematoma, and all resolved following appropriate treatment. Conclusions: The TOT and TVT-O procedures appeared to be equally clinically effective and safe when used to treat female SUI.

This prospective randomized study was performed to compare the efficacy of GnRH antagonist multiple-dose protocol (MDP) with or without oral contraceptive pill (OCP) pretreatment and GnRH agonist low-dose long protocol (LP) in 82 patients undergoing IVF/intracytoplasmic sperm injection (ICSI). GnRH antagonist MDP with OCP pretreatment was at least as effective as GnRH agonist low-dose LP in low responders, and can benefit the low responders by reducing the amount of FSH and the number of days of stimulation required for follicular maturation.

Objective To investigate the effects of pioglitazone on ovarian stimulation, in vitro fertilization (IVF) outcome, and intraovarian stromal blood flow in patients with polycystic ovary syndrome (PCOS). Design Prospective, randomized, controlled trial. Setting University-affiliated infertility clinic. Patient(s) Sixty infertile patients with PCOS resistant to clomiphene citrate. Intervention(s) An IVF protocol involving use of a gonadotropin-releasing hormone (GnRH) antagonist and oral contraceptive pretreatment. Patients were randomized into two groups: pioglitazone (30 mg daily) in the study group or placebo in the control group, commenced on the day on which oral contraceptive intake began. Main Outcome Measure(s) Ovarian stimulation, IVF outcome, and resistance index of the intraovarian stromal artery. Result(s) The resistance index value on the day of human chorionic gonadotropin (hCG) injection in the study group was statistically significantly higher in the study group than in controls. The serum estradiol level and number of retrieved oocytes were statistically significantly lower in women treated with pioglitazone. However, the number of mature oocytes and fertilized oocytes, and the clinical pregnancy rate were similar in both groups. Conclusion(s) Pioglitazone therapy reduced intraovarian stromal blood flow and might be beneficial in improving both the response to ovarian stimulation and IVF outcome in PCOS patients.

Objective Nuclear factor kappa-B (NF-κB) is a critical proinflammatory regulator that has been suggested to play a pivotal role in the pathogenesis and pathophysiology of endometriosis. In the present study, we aimed to evaluate whether the expression of NF-κB p65 subunit is increased in the eutopic endometrium and/or in the adenomyosis nodule of women with adenomyosis. Methods Thirty-three women with histologically confirmed adenomyosis after laparoscopic or transabdominal hysterectomy were recruited. Women with carcinoma in situ of uterine cervix without evidence of adenomyosis or endometriosis (n=32) served as controls. Formalin-fixed, paraffin-embedded archival tissues were sectioned and immunostained utilizing a monoclonal anti-human NF-κB p65 subunit antibody, and the immunoreactivity of NF-κB p65 subunit was compared between women with and without adenomyosis. Results The immunoreactivities of both the nuclear and the cytoplasmic NF-κB p65 subunit were significantly increased in the stromal cells in the eutopic endometrium as well as in the adenomyosis nodule of women with adenomyosis compared with controls, respectively. The nuclear expression of NF-κB p65 subunit was significantly higher in the glandular cells in the eutopic endometrium as well as the adenomyosis nodule of women with adenomyosis compared with controls, respectively. Conclusion The expression of NF-κB p65 is increased in the eutopic endometrium and adenomyosis nodule of women with adenomyosis, which strongly suggest that NF-κB plays a critical role in the pathogenesis and/or pathophysiology of adenomyosis.

Human embryonic stem cells (hESCs) are pluripotent, whereby they can proliferate endlessly and differentiate into many different cell types. At the molecular level, little is known of the mechanisms underlying their capability for self-renewal and differentiation. In the present study, we established two new hESC lines (AMC-hES1 and AMC-hES2) and demonstrated the existence of a regulator that may be a key molecule in hESC dynamics. Spa-1 is a principal Ras-proximate 1 (Rap1) GTPase-activating protein in hematopoietic progenitor cells that regulates Rap1-related signal transduction and is expressed restrictively in human adult tissues (bone marrow, thymus, and spleen). To investigate its functions in hESCs, we examined spa-1 expression profiles during hESC differentiation and used RNA interference (RNAi) to downregulate spa-1 in these cells. Our results show that Spa-1 is expressed in undifferentiated hESCs and is downregulated during hESC differentiation. In addition, the process of passing from the mode of self-renewal to that of differentiation in hESCs was regulated by spa-1 via Rap1/Raf/mitogen-activated protein kinase kinase/extracellular signal-related kinase signaling. An RNAi expression vector against spa-1 (pSUPER.retro.puro) was transfected into hESCs, which were seen to differentiate into three germ layers in spite of being in the undifferentiated condition. Based on our findings, therefore, it appears that spa-1 may be involved in hESC dynamics, and our results provide fundamental information regarding the self-renewal and differentiation of hESCs.

In a spontaneous menstrual cycle, during the follicular phase, only one follicle out of a cohort of 10-20 usually completes maturation and ovulates to release a mature oocyte. The aim of ovarian stimulation in assisted reproductive technology (ART) protocols is to overcome the selection of a dominant follicle and to allow the growth of a cohort of follicles. This strategy leads to an increase in the number of oocytes and hence embryos available for transfer, thereby increasing the chance of transferring up to three viable embryos. However, the chance of pregnancy and also live birth begins to dramatically decline after the age of 35, and successful treatment for these patients continues to be a major challenge in ART programs. Preimplantation genetic screening studies over the last decade have identified a dramatic increase in the rate of aneuploidy as a major contributor to the reduction in embryo viability in older patients. It has also been demonstrated that women of advanced maternal age may have oocytes that are compromised by a significant reduction in the amount of mitochondrial DNA in their cytoplasm. The strategies outlined in this review may provide a means of augmenting follicular recruitment and cytoplasmic integrity by utilizing pharmacogenomics and manipulating endocrinology to improve the prognosis for these women. Recent studies indicate that androgen supplementation may be one area to explore further. The availability of recombinant human leutinizing hormone (rhLH) has made it possible to investigate the role of LH in the endocrinology of follicular recruitment: it appears that a defect in the balance of LH/ follicle-stimulating hormone (FSH) might be involved in the subtle age-related decline in follicular recruitment, and patients of older reproductive age undergoing ART might benefit from the addition of LH and/or hGH. Further studies are required to investigate the physiological mechanisms behind this observation and to assess the possible effect of LH and/or hGH supplementation on the age-related decline in pregnancy rate.

Problem Antiphospholipid antibodies (APA) are thought to be involved in recurrent pregnancy loss. Therefore, we investigated the impact of APA on pregnancy outcome in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Method of study Blood samples taken from 54 Korean women referred for IVF were tested for the presence of APA, anticardiolipin antibody IgG and IgM and lupus anticoagulant. The standard gonadotropin-releasing hormone agonist long protocol was used for ovarian stimulation. Results Nine patients (16.7%) were positive and 45 (83.3%) were negative for APA. There were no significant differences between the two groups in clinical characteristics such as age, infertility duration, and response to controlled ovarian hyperstimulation. However, pregnancy outcome significantly differed between the two groups (p

Human embryonic stem cells (hESCs) have the potential to differentiate into various cell types, and the three germ layers in vivo and in vitro. They are therefore useful in transplantation and tissue engineering. Here, we describe the expression patterns of selected steroid receptor mRNAs - estrogen receptor-alpha (ER-alpha), ER-beta, glucocorticoid receptor (GR), and progesterone receptor (PR) - in undifferentiated hESCs and embryoid bodies (EBs) cultured for 2, 4, and 6 d, as assessed by real-time PCR, in order to define the possible influence of steroid hormones on the differentiation of hESCs. These receptor mRNAs were expressed in undifferentiated hESCs and EBs. The expression of PR mRNA only decreased during the differentiation of EBs but not of hESCs. Immunohistochemical analysis gave strong staining of ER-alpha, ER-beta, and GR proteins in the nuclei of hESCs and EBs, whereas PR was not detected. We also examined the potential of these steroid hormones to direct the differentiation of hESCs in vitro. The expression of 11 cell-specific markers representing 3 germ layers and 5 tissue types was used to assess the differentiation of hESCs. We found that certain endodermal marker genes were either only expressed in the estrogen-treated group or their expression was stimulated in that group, suggesting that steroid hormones can control the differentiation of hESCs into various cell types.

Small proline-rich (SPRR) proteins are structural components of the cornified cell envelope (CE), a specialized structure beneath the plasma membrane of stratified squamous epithelia. They are divided into four families, of which SPRR2 is the most complex consisting of 11 members (2a-2k) in the mouse. To assess the possible influence of estrogen on expression of the SPRR2 family in the uterus, we examined the effect of 17b-estradiol (E2) on SPRR2 mRNA levels on ovariectomized (OVX) adult mice. We employed a combination of laser capture microdissection (LCM) and semiquantitative RT-PCR to examine expression in particular uterine cell types - luminal epithelia, and stromal and muscle cells. We also used quantitative real-time PCR to measure levels of the mRNA of several SPRR2 proteins in the mouse uterus over the estrous cycle and during early pregnancy. Expression of SPRR2a, 2b, 2c, 2d, 2e, 2f and 2g mRNA was increased by estrogen treatment. SPRR2a, 2b, 2d and 2e were highly expressed on day 1 and 2 of pregnancy, but decreased markedly by days 3-6. Interestingly, several members of the SPRR2 family were preferentially up-regulated at implantation sites compared to inter-implantation sites around day 4 of pregnancy. They were abundant during proestrus and estrus but declined rapidly during metestrus. These results indicate that estrogen is a key regulator of the expression of the SPRR2 family in the mouse uterus during the estrous cycle and early pregnancy. In addition, they suggest that some members of the family play an important role in uterine processes such as the estrous cycle, early pregnancy and implantation.

We explored the possibility that a sustained elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) may be a cellular abnormality common to both insulin resistance and hypertension. In high-fat diet (HFD) fed rats, the steady-state glucose infusion rate (GIR) during the euglycemic hyperinsulinemic clamp was reduced by 40% (P.05) and mean arterial pressure (MAP) was elevated by 20 mm Hg (P.01) in comparison to the normal chow-fed rats. Intravenous injection of 5,5'-dimethyl derivative of bis(o-aminophenoxy)ethane-N,N,N',N' tetraacetic acetoxymethyl ester (dimethyl-BAPTA/AM), an effective intracellular Ca(2+) chelator, 90 minutes before the clamp not only restored about 50% of the reduced GIR, but also normalized MAP in the HFD rats. The chelator injection also significantly increased GIR by 25% (P.01) and reduced MAP about 30 mm Hg (P.01) in the spontaneously hypertensive rats (SHR). In addition, we have recently shown in the HFD rats that an injection of dimethyl-BAPTA/AM normalizes elevated [Ca(2+)](i) in adipocytes. These results together demonstrate that lowering [Ca(2+)](i) simultaneously ameliorates both insulin resistance and hypertension and provide presumptive evidence that sustained high levels of [Ca(2+)](i) may play a common pathophysiologic role in these 2 diseases.

Background Sunitinib has been recommended as the primary treatment in the patients with metastatic renal cell carcinoma (mRCC) among the vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). However, there are no published clinical data that compared directly the efficacy of targeted agents in the first line setting. This study investigated the efficacy and toxicity of sorafenib and sunitinib as primary treatment for patients with mRCC. Methods To compare the efficacy and toxicities between sorafenib and sunitinb, clinical database was used to identify all patients with mRCC treated with VEGF TKIs in Asan Medical Center from April 2005 to March 2011. Among 304 patients, we identified 49 and 220 patients who were treated first with sorafenib and sunitinib, respectively. Results The patients in the sorafenib group were older than those in the sunitinib group (62 vs 56.5 years, p = 0.019). Disease control rate (DCR) of 71% and 74% were achieved in sorafenib and sunitinib groups, respectively (p = 0.687). After a median follow-up duration of 27.6 months, progression free survival (PFS), time to treatment failure (TTF), and overall survival (OS) were not significantly different between the groups (sorafenib vs. sunitinib, PFS 8.6 months vs. 9.9 months, p = 0.948; TTF 6.6 months vs. 7.2 months, p = 0.665; OS; 25.7 months vs. 22.6 months, p = 0.774). Patients treated with sorafenib required dose reduction due to toxicities less frequently than those treated with sunitinib (37% vs. 54%, p = 0.034). Haematological toxicities of grade 3 or 4 were more common in the sunitinib group than in the sorafenib group (45% vs. 4%, p 60 years), duration from diagnosis to treatment ( Conclusion Sorafenib showed comparable efficacy to sunitinb and demonstrated fewer and less severe toxicities in the treatment of mRCC patients. Disclosure All authors have declared no conflicts of interest.

To evaluate the effect of calcium and vitamin D supplementation on follicular fluid (FF) tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations and IVF/ICSI outcomes in infertile patients with polycystic ovary syndrome (PCOS). A total of one hundred infertile patients with PCOS were randomized to receive calcium and vitamin D (treatment group, n=50) or placebo (control group, n=50) on the starting day of oral contraceptive (OC) pretreatment, followed by controlled ovarian stimulation (COS) using GnRH antagonist for IVF/ICSI. Calcium 400 mg/d with vitamin D 1000 IU/d or placebo was administered once daily from the starting day of OC to the day of human chorionic gonadotropin (hCG) injection. There were no significant differences in patient´s characteristics between the treatment and control groups. There were also no differences in total dose and days of recombinant human FSH (rhFSH) administered and the numbers of retrieved, mature and fertilized oocytes between the two groups. However, number of grade 1 or 2 embryos was significantly higher in the treatment group than in the control group (p< .001). FF TNF-α and IL-6 concentrations at oocyte retrieval were significantly lower in the treatment group (p=.001, p< .001, respectively). Embryo implantation rate was higher in the treatment group with borderline significance (p=0.075). Clinical pregnancy rate and miscarriage rate were similar in the two groups. Calcium and vitamin D treatment can reduce FF TNF-α and IL-6 levels in COS cycles, and therefore may be beneficial in improving pregnancy outcome in patients with PCOS undergoing IVF/ICSI.

through procedure at an OSH via a sagittal incision for treatment of the imperforate anus. A small vagina was identified high on the right which was found to be “short” and connected to a “short uterus” with an associated tube and ovary. It was surgically lengthened with flaps from the labia and connected to the introitus. A small fistula going from the vagina to a ureteral remnant from a dysplastic kidney was identified, divided, and ligated. She subsequently did well. Signs of pubertal development were evident at age 10 e 11, with normal breast development and accelerated growth; however, menarche was absent. At age 14, she presented for evaluation of primary amenorrhea and pain. Ultrasound identified two uterine horns, a right ovary, and a distended fluid filled vagina. MRI showed a hematocolpos which appeared contiguous with the right corpus and tube. Left rudimentary uterine corpus and tube were not fluid filler. A re-do vaginoplasty was planned. EUA demonstrated extensive scar tissue with a stricture at 1.5cm from the introitus. Given the history of prior urologic and rectal surgery, and the fact that her unicornuate system was not midline, intra-operative ultrasound was used to identify the inferior aspect of the hematocolpos. With ultrasound guidance a long spinal needle was advanced until it was noted to enter the inferior aspect of the obstructed vagina (Figure 2). Once the angle and direction of dissection was determined, electrocautery was used to carry the dissection upwards. The intervening tissue was excised and 900cc of old blood was evacuated. Vaginal mucosa was identified and a standard pull through vaginalplasty was performed. Vaginal pull through is the standard treatment for lower vaginal agenesis. With a single midline uterus, cervix and upper vagina, the distal aspect of the obstructed upper vagina can be identified by palpation, and

Objective: To investigate the impact of fibroids on the blood flow of the uterine and subendometrial arteries and in vitro fertilization (IVF) out comes. Methods: In this study, we analyzed 86 IVF/intracytoplasmic sperm injection (ICSI) cycles in which a gonadotropin-releasing hormone antagonist protocol was used for controlled ovarian stimulation between January 2008 and March 2009. The subjects comprised 86 infertile women with (fibroid group, n = 43) or without (control group, n = 43) uterine fibroids. Results: Patient characteristics were similar between the fibroid and control groups. The IVF/ICSI outcomes in patients with fibroids were simi lar to those of patients in the control group. The resistance index (RI) and pulsatile index (PI) of the uterine and subendometrial arteries on the day of embryo transfer were also comparable between the two groups. IVF outcomes and uterine hemodynamics in patients with multiple ( ≥ 2) fibroids were similar to those of patients with a single fibroid. However, clinical pregnancy and implantation rates were significantly lower in patients with fibroids who experienced uterine cavity distortion than in patients with fibroids who had a normal uterine cavity (both p < 0.05). The RI and PI of the subendometrial artery were significantly higher on the day of embryo transfer in patients with fibroids who expe rienced uterine cavity distortion than in patients with fibroids who had a normal uterine cavity (both p < 0.05). Conclusion: Fibroids which distorting the uterine cavity might impair the subendometrial artery blood flow clinical pregnancy rate and em bryo implantation rate in infertile patients undergoing IVF. Otherwise, IVF outcomes were not influenced by the presence of uterine fibroids.

Objective To evaluate the effect of second-line conservative surgery on in vitro fertilization (IVF) outcome in comparison with IVF without second-line surgery in infertile women with ovarian endometrioma recurrence after primary conservative surgery. Methods In this retrospective cohort study, 121 consecutive IVF/intracytoplasmic sperm injection cycles that were performed after second-line surgery (n=53) or without second-line surgery (control group, n=68) between January 2006 and December 2011 in 121 infertile women with ovarian endometrioma(s) recurrence after primary conservative surgery for moderate to severe endometriosis were included. The two groups were compared in terms of controlled ovarian stimulation and IVF outcomes. Results There were no differences in patients' characteristics between the two groups. Total dose and days of gonadotropins administered were significantly higher in the second-line surgery group than in the control group (P

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is a multifactorial polygenic disorder with a broad spectrum of clinical manifestations. Although pathogenesis is still unclear, androgen receptor (AR) gene polymorphism may be one of the etiologic factors of PCOS. AR gene polymorphism has been also associated with other forms of androgen pattern diseases. We report a PCOS woman with heterozygous AR gene mutation who gave birth to a baby with andorgen insensitivity syndrome.

One of the key factors of early development is the specification of competence between the oocyte and the sperm, which occurs during gametogenesis. However, the starting point, growth, and maturation for acquiring competence during spermatogenesis and oogenesis in mammals are very different. Spermatogenesis includes spermiogenesis, but such a metamorphosis is not observed during oogenesis. Glycosylation, a ubiquitous modification, is a preliminary requisite for distribution of the structural and functional components of spermatids for metamorphosis. In addition, glycosylation using epididymal or female genital secretory glycans is an important process for the sperm maturation, the acquisition of the potential for fertilization, and the acceleration of early embryo development. However, nonemzymatic unexpected covalent bonding of a carbohydrate and malglycosylation can result in falling fertility rates as shown in the diabetic male. So far, glycosylation during spermatogenesis and the dynamics of the plasma membrane in the process of capacitation and fertilization have been evaluated, and a powerful role of glycosylation in spermatogenesis and early development is also suggested by structural bioinformatics, functional genomics, and functional proteomics. Further understanding of glycosylation is needed to provide a better understanding of fertilization and embryo development and for the development of new diagnostic and therapeutic tools for infertility.

This study was carried out to investigate the influence of transforming growth factor-alpha (TGF-alpha) on the expression of mRNA for matrix metalloproteinase-2 (MMP-2), MMP-9, and epidermal growth factor receptor (EGFR) in mouse blastocysts and the effect on the production and activation of MMP-2 and MMP- 9 during blastocyst outgrowth.Two-cell mouse embryos were cultured for 96 h in the presence or absence of various concentrations of TGF-alpha. Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of mRNA for MMP-2, MMP-9, and EGFR in in vitro cultured blastocysts. To investigate the effect on the production and activation of MMP-2 and MMP-9 during blastocyst outgrowth, the conditioned medium collected after 3 and 5 days of embryo culture were assayed for MMP activity by gelatin zymography.The relative mRNA levels of MMP-2 and MMP-9 in blastocysts treated with TGF-alpha were higher than that of the control in a concentration-dependent manner. The relative mRNA level of EGFR in blastocysts treated with TGF-alpha was higher than that of the control. In conditioned medium collected after 3 days of embryo culture, TGF-alpha induced the gelatinase activities of proMMP-9 in all groups and activated MMP-2 in the 10 and 100 ng/mL TGF-alpha treated groups. In conditioned medium collected after 5 days, TGF-alpha induced the gelatinase activities of proMMP-9 in all groups and activated MMP-9 in the TGF-alpha treated group. TGF-alpha also induced the gelatinase activities of activated MMP-2 in the 1 and 10 ng/mL TGF-alpha treated groups and the control.These results suggest that the addition of TGF-alpha to in vitro culture medium is proper to create a favorable environment for preimplantation embryo development and implantation.

Twin pregnancy consisting of complete hydatidiform mole (H-mole) and a coexisting fetus occurs with an estimated incidence of 1 per 22,000–100,000 pregnancies. The incidence of this unusual twin pregnancy with complete H-mole and a coexisting fetus after in vitro fertilization and embryo transfer (IVF–ET) is not thought to be greater than that of general population. We present an unusual twin pregnancy with complete H-mole and a coexisting fetus that occurred following IVF–ET, which was terminated at 21 weeks of gestation and developed into nonmetastatic gestational trophoblastic tumor.

To estimate whether hearing sensitivity in postmenopausal women is associated with serum estradiol level or bone mineral density.Serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and hearing sensitivity were measured in 1830 postmenopausal women. Serum estradiol level was measured by radioimmunoassay, and dual energy x-ray absorptiometry was used to measure bone mineral densities of the lumbar vertebrae and femoral neck. Hearing sensitivity was evaluated by pure tone audiometry. Age, serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and the proportion of women on hormone replacement therapy were analyzed in women with and without hearing loss.On univariate analysis, significant differences were found in mean age, serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and the proportion of women on hormone replacement therapy between the two groups (mean +/- standard deviation, 59.4 +/- 5.6 versus 56.9 +/- 4.7 years, P.001; 8.4 +/- 3.8 versus. 9.9 +/- 8.7 pg/mL, P.001; 0.85 +/- 0.14 versus 0.88 +/- 0.15 g/cm(2), P.01; 0.65 +/- 0.10 versus 0.68 +/- 0.10 g/cm(2), P.005; 0.006% versus 0.03%, P.05, respectively). On multiple logistic regression analysis, significant association was found between age and hearing loss and between serum estradiol level and hearing loss (P.001, P =.02, respectively).This study suggests that a lower level of serum estradiol possibly impedes hearing sensitivity in postmenopausal women.

This study was performed to investigate the effect of of transdermal testosterone gel (TTG) on controlled ovarian stimulation (COS) and IVF outcomes and ovarian morphology according to pretreatment duration in poor responders. A total of 120 women were recruited for this pilot study. They were randomized into control, 2 weeks, 3 weeks or 4 weeks TTG treatment groups. For three TTG treatment groups, 12.5 mg TTG was applied daily for 2 weeks, 3 weeks or 4 weeks in preceding period of study stimulation cycle. After 3 weeks of TTG pretreatment, significant increase of antral follicle count (AFC) and significant decreases of mean follicular diameter (MFD) and resistance index (RI) value of ovarian stromal artery were observed (p=0.026, p

Objective: To determine if basal serum follicle stimulating hormone (FSH) level could be a prognostic factor of the clinical outcome in intracytoplasmic sperm injection (ICSI) cycles in the couples with male factor infertility Materials and Methods: From December 1995 to March 1998, total 118 patients underwent in vitro fertilization and embryo transfer (IVF-ET) with ICSI due to male factor infertility were included in this study. Patients were allocated to the low basal FSH group (< 8.5 mIU/ml) and the high basal FSH group (< 8.5 mIU/ml). The basal levels of FSH were measured in the 3rd day of menstrual cycle preceding ovarian stimulation cycle in total IVF cycles by immunoradiometric assay (IRMA). Statistical analysis was performed using Student's t-test, Fisher's exact test, and X2 test as appropriate. Statistical significance was defined as p < 0.05. Results: The total dose of exogeneous gonadotropin required in the high basal FSH group was significantly higher than that in the low basal FSH group. The numbers of retrieved oocytes and oocytes with grade I, II were significantly higher in the low basal FSH group. The clinical pregnancy rate per cycle in the low basal FSH group (16.2%) was significantly higher than that in the high basal FSH group (4.0%). Conclusion: These results suggested that the basal serum FSH levels could be predictive of pregnancy outcome and the results of controlled ovarian hyperstimulation (COH) in ICSI cycles.

Hatching has been suggested to occur as a result of protease-mediated lysis and the blastocoele tension. However, even if rupturing is initiated at multiple sites, interestingly only a single site is used for escape. This implies that there are several mechanisms involved in hatching. In this study, the involvement of actin filaments in mouse embryo hatching was examined. We treated mouse embryos with cytochalasin B for 12 h or 24 h at the morula, middle blastocyst, expanded blastocyst, lobe-formed blastocyst and hatching blastocyst stages, and measured the amount and distribution of actin filaments using a confocal microscope. At morula, middle blastocyst, lobe-formed blastocyst and hatching blastocyst stages embryonic development was completely arrested by cytochalasin B. However, when transferred to cytochalasin-B-free medium, the embryos resumed development and escaped the zona pellucida. In the expanded blastocysts development was almost completely inhibited by cytochalasin B, but rupturing occurred in some embryos. However, development stopped completely at the ruptured stage. Distribution of actin filaments was prominent at rupturing and hatching sites regardless of cytochalasin B treatment. The amount of actin filaments was prominent at hatching embryos compared with other developmental stages of embryos. These actin filaments were distributed intensively between the trophectodermal cells, and formed locomotion patterns. Taken together, these results suggest that not only tension and lytic enzymes are required to rupture, but the activity of actin filaments may have a crucial role in the process of hatching.

PROBLEM: To investigate whether antithyroid antibodies (ATAs) affect the pregnancy outcome in euthyroid women undergoing in vitro fertilization-embryo transfer (IVF-ET). METHOD OF STUDY: Thyroid peroxidase antibody (TPOA) and thyroglobulin antibody (TGA) were measured by radioligand assay kits that were used as ATAs in 79 patients with tubal or unexplained infertility who were enrolled in an IVF-ET program. Women who were positive for antinuclear antibody, lupus anticoagulant, anticardiolipin antibody, and rheumatoid factor were excluded from our study. The study group comprised 28 (29.1%) euthyroid women who were positive for TPOAs, TGAs, or both. Fifty-one euthyroid women without ATAs served as control subjects. The results were analyzed with linear regression analysis, Student's t-test, Mann-Whitney U test, Kruskal-Wallis analysis of variance, 2 test, and Fisher's exact test. RESULTS: There were no significant differences between the study group and the control group in patient characteristics such as age, infertility duration, and hormonal profile. There were also no significant differences between the two groups with respect to the number of retrieved oocytes, the fertilization rate, the number of embryos frozen, and the number of embryos transferred. There were no correlations between ATA (TPOA and TGA) titers and the fertilization rate. The clinical pregnancy rate per cycle was significantly lower in the study group, with 26.3% (10/38), compared with 39.3% (35/89) in the control group. The biochemical pregnancy rate per cycle and the miscarriage rate were significantly higher in the study group, 18.4% (7/38) and 40.0% (4/10), respectively, compared with 5.6% (5/89) and 11.4% (4/35), respectively, in the control group. In the study group, both TPOA and TGA titers were significantly higher in the biochemical pregnancy group than in the clinical pregnancy group or the nonpregnancy group. In 10 women with ATAs who achieved pregnancy after IVF-ET, both TPOA and TGA titers were significantly higher in the miscarriage group than in the ongoing pregnancy/delivery group. CONCLUSION: ATAs in euthyroid women with tubal or unexplained infertility have an association with a poor pregnancy outcome after IVF-ET treatment.

We report an unusual case in which a rapidly growing adenomyosis was identified during the first trimester in a 35-year-old infertile woman achieving pregnancy after controlled ovarian hyperstimulation. Relevant images are shown by magnetic resonance imaging.

Perivascular epithelioid cell neoplasm (PEComa) is a rare tumor with unknown malignant potential. We report a case of a 6-year-old child with history of brain tumor (pineoblastoma), who presented with intermittent vaginal spotting for 6 months. A vaginoscopy revealed a 1.5×1.0-cm mass on the vaginal wall. Pathological examination demonstrated that the tumor was composed of clear cells with organoid patterns, which were immunohistochemically positive for HMB-45 and TFE3, and negative for CK, HNF1-B, SOX10, Melan A, and S-100 protein. These findings were consistent with PEComa arising from the vagina. Regular follow-up with magnetic resonance imaging has shown no signs of recurrence. This case shows that early detection of PEComa and subsequent regular follow-ups are important because of the neoplasm's unknown malignant potential.

Radical trachelectomy is a promising fertility-sparing treatment for patients with early stage cervical cancer who want to preserve their fertility. However, isthmic stenosis occurs frequently in patients who received radical trachelectomy and it is one of the causes of infertility following radical trachelectomy. Moreover, despite the treatment for recanalization of isthmic stenosis, recanalization can fail or isthmic stenosis can recur. Herein we report a successful pregnancy and birth by direct intraperitoneal insemination in an infertile woman with failure of recanalization of isthmic stenosis after laparoscopic radical trachelectomy.

Objective To investigate the causes of amenorrhea in Korean women. Methods Medical records from 1,212 women with amenorrhea who visited the Department of Obstetrics and Gynecology, Asan Medical Center, between January 1989 and December 2011 were retrospectively reviewed. Amenorrhea was categorized as either primary or secondary. Results Primary amenorrhea was identified in 132 of the patients (10.9%) and secondary amenorrhea in 1,080 (89.1%). The most frequent causes of primary amenorrhea were gonadal dysgenesis (28.0%, 37/132); Mayer-Rokitansky-Küster-Hauser syndrome (20.0%, 27/132); and constitutional delay and androgen insensitivity syndrome (8.3%, 11/132; 8.3%, 11/132, respectively). Secondary amenorrhea was due to polycystic ovary syndrome (48.4%, 523/1,080); premature ovarian insufficiency (14.0%, 151/1,080); and nutrition-related hypogonadotropic hypogonadism (8.3%, 90/1,080). Conclusion In this retrospective study, gonadal dysgenesis was the most common cause of primary amenorrhea and polycystic ovary syndrome was the most common cause of secondary amenorrhea in Korean women.