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

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.

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

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 gynecologic malignancies: The Korean Society for Fertility Preservation clinical guidelines / 대한생식의학회지

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 breast cancer: The Korean Society for Fertility Preservation clinical guidelines / 대한생식의학회지

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 hematologic malignancies: The Korean Society for Fertility Preservation clinical guidelines / 대한생식의학회지

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.

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.

Effectiveness of emergency contraception in women after sexual assault / 대한생식의학회지

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.

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.

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

OBJECTIVE: To investigate the effect of peroxisome proliferator activated receptor gamma (PPARgamma) 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 (PPARgamma 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, PPARgamma agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin E2 production in the ESCs of endometriosis. CONCLUSION: This study suggests that PPARgamma 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.

Diagnosis and treatment of uterine didelphys with obstructed hemivagina and ipsilateral renal agenesis / 대한산부인과학회지

Uterine malformations consist of a group of miscellaneous congenital anomalies of the female genital system, and these anomalies are the result of major disturbances in the development, such as formation or fusion of the Mullerian or paramesonephric ducts during fetal life. The Mullerian anomalies have been estimated to occur in up to 0.001~10%, and these anomalies may be associated with numerous congenital anomalies, and ipsilateral renal anomalies especially are the most common. The uterine didelphys with obstructed hemivagina and ipsilateral renal agenesis clinically may result in dysmenorrhea, low abdominal pain, endometriosis or pelvic mass after menarche. Furthemore the delayed diagnosis causes infertility and poor pregnancy outcome due to continued retrograde menstruation which leads to endometriosis and distorted pelvic anatomy. These anomalies could be diagnosed with ultrasonography and MRI that have the high sensitivity and specificity. Excision of vaginal septum and marsupialization are appropriate treatments to relieve symptoms and reserve fertility. We report 7 cases of uterine didelphys with obstructed hemivagina and ipsi-unilateral renal agenesis with a brief review of relevant literatures to help understand these anomalies.

Sonohysterography-Guided Biopsy of Focal Endometrial Abnormalities: Technical Feasibility and Diagnostic Accuracy

PURPOSE: To assess the feasibility and diagnostic accuracy of a sononohysterography-guided biopsy in an evaluation of focal endometrial lesions. MATERIALS AND METHODS: Sixty-five consecutive patients with focal endometrial lesions detected on baseline sonohysterography were enrolled prospectively. The biopsy was performed under real-time sonohysterography guidance, using a 3.1 mm Pipelle endometrial sampler as the primary biopsy device. The feasibility was evaluated from the technical success rates and the number of "diagnostic" specimen for the histological diagnosis. The diagnostic accuracy was assessed by comparing the biopsy results with the final pathological diagnosis obtained by the surgical procedure. RESULTS: Sonohysterography-guided biopsy was performed successfully in 59(90.8%) out of 65 patients. The reasons for failure in 6 patients were a failure to pass through the cervix (n=3); failure to target a focal lesion (n=2); and inadequate uterine distension (n=1). The biopsy specimen was "diagnostic" in 49 (83.1%) out of 50 patients, and "non-diagnostic" in 10 patients with insufficient tissue (n=6) and indeterminate cellular features for a histological diagnosis (n=4). The cytology results of the sonohysterographically-guided biopsy correlated well with the pathological diagnosis in 35 (92.1%) out of 38 patients who underwent subsequent surgical procedures. CONCLUSION: Sonohysterography-guided biopsy is technically feasible and can be an accurate method for diagnosing focal endometrial lesions. It could be considered to be a reliable office triage as an alternative to hysteroscopic biopsy in patients with focal endometrial abnormalities.

Gonadotropin-releasing hormone agonist treatments reduce aromatase and cyclooxygenase-2 in ovarian endometrioma and eutopic endometium in women with endometriosis / 대한산부인과학회지

OBJECTIVE: We investigated whether GnRH agonists reduce aromatase cytochrome P450 and cyclooxygenase-2 by direct action in the eutopic endometrium of endometriosis and ovarian endometrioma. METHODS: Endometrial specimens and endometriotic tissues were obtained from infertility women undergoing laparoscopic surgery. Biopsy samples of the endometrium were obtained before and after GnRH agonist therapy. The stromal cells of eutopic endometrium in women with endometroisis and ovarian endometrioma were cultured in the presence of GnRH agonist (leuprolide acetate 0, 1, 5, and 10 uM) for 24 hours. The expression of aromatase cytochrome P450 and COX-2 was examined by Western blot. RESULTS: Protein of aromatase cytochrome P450 and COX-2 were decreased in the eutopic endometrium of patients treated with GnRH agonist for 3 months. The stromal cells culture of endometrial explants and ovarian endometrioma with GnRH agonist reduced aromatase cytochrome P450 and COX-2. Phosphorylated ERK was decreased in endometriotic stromal cultures with GnRH agonist. CONCLUSION: These findings demonstrate that GnRH agonist not only promoted a hypoestrogenic state but also reduced aromatase cytochrome P450 and COX-2 by direct action on eutopic endometrium in patients with endometriosis and ovarian endometrioma.

Increased Incidence of Endometrial Polyps in Women with Endometriosis; the Association with Severity / 대한불임학회지

OBJECTIVE: The aim of this study was to evaluate the correlation between severity of endometriosis and the incidence of endometrial polyp. METHODS: The study population consisted of six hundred thirty-one women who had undergone laparoscopic operation due to infertility, severe dysmenorrhea or ovarian tumors. We divided two groups: 434 women with endometriosis (study group) and 197 women without the disease (control group). The presence of endometriosis was documented by diagnostic or therapeutic laparoscopic operation and the disease severity was scored according to revised The American Fertility Society classification. We confirmed the endometrial polyps by pathologic examination after hysteroscopic polypectomy, and compared endometrial polyp incidence according to severity of endometriosis. RESULTS: There was no significant difference between groups with regard to age, mean duration of infertility. Endometrial polyps were found in 274 women (63.0%) with endometriosis and in 58 controls (29.8%, p=0.0000). The incidence of endometrial polyps differed significantly according to stage of endometriosis. The incidence of endometrial polyps were 77/142 (54.2%), 58/90 (64.4%), 73/108 (67.6%, p<0.05), 66/94 (70.2%, p<0.05) in endometriosis stage I, II, III, and IV. There was a linear correlation between stage of endometriosis and endometrial polyps incidence (p=0.008). CONCLUSION: Endometriosis is accompanied by endometrial polyps. This results showed positive correlation between severity of the endometriosis and incidence of endometrial polyps. It is the possible mechanism for low pregnancy rate in the severe endometriosis

Effect of Transforming Growth Factor (TGF)-beta and Peroxisome Proliferator-Activated Receptor (PPAR)-gamma in Endometrial Decidualization / 대한산부인과학회지

OBJECTIVE: To ascertain the expression of transforming growth factor (TGF)-beta receptors in normal human endometrium during the menstrual cycle, and the action of TGF-beta and peroxisome proliferator-activated receptor (PPAR)-gamma during endometrial decidualization using cultured human endometrial stromal cells. METHODS: Human endometrial tissues were examined immunohistochemically for the expression of TGF-beta receptors and Smad. Western blotting, confocal microscopy and viable cell counting were performed on cultured human endometrial stromal cells which were treated with TGF-beta (10 ng/mL) and PPAR-gamma agonists (Rosiglitazone(R) 50 nM). Thereafter we compared the effect of TGF-beta and PPAR-gamma on the Smad phosphorylation, prolactin expression, and cellular proliferation in vitro human endometrial decidualization. RESULTS: The results revealed significantly increased expression of both TGF-beta receptor-I and -II proteins in the secretory stromal cells compared to the epithelial cells of human endometrium. The degree of expression and translocation into the nucleus of the phosphorylated Smad2/3 was also increased in the secretory endometrium compared to the proliferative endometrium. In the stromal cell culture, the decidualization process associated with TGF-beta and pSmad is inhibited by the PPAR-gamma agonist. In contrast to the PPAR-gamma agonist, TGF-beta inhibits cellular proliferation. CONCLUSION: TGF-beta/Smad signaling pathway is essential for endometrial decidualization and closely related to cellular differentiation. PPAR-gamma plays a conflicting role by directly acting on the Smad protein and blocking the TGF-beta/Smad signaling pathway.

Role of ERK (Extracellular Signal Regulated Kinas) and PPAR gamma(Peroxisome Proliferator-Activated Receptor Gamma) on TGF-beta1 Induced Human Endometrial Stromal Cell Decidualization / 대한불임학회지

OBJECTIVE: To investigate the role of ERK and PPAR gamma on the TGF-beta1 induced human endometrial stromal cell decidualization in vitro. METHOD: Endometrial stromal cells are cultured under the following condition: DMEM/F12 (10% FBS, 1 nM E2 and 100 nM P4). TGF-beta1 (5 ng/ml), Rosiglitazone (50 nM), and PD98059 (20 microgram) were added according to experimental purposes. Trypan-Blue and hematocytometer were utilized to count cell number. Enzyme-linked immunosorbent assay (ELISA) and western blotting were utilized to detect proteins. RESULT: TGF-beta1 inhibited proliferation of cultured human endometrial stromal cells and induced expression of PGE2 and prolactin. This effect was mediated by Smad and ERK activation. Administration of rosiglitazone, PPAR gamma agonist, prevented TGF-beta1 effect on cell proliferation. Furthermore, Rosiglitazone inhibited TGF-beta1 induced activation of ERK, consequently reduced PGE2 and prolactin production. CONCLUSION: TGF-beta1 induced decidualization of endometrial stromal cell through Smad and ERK phosphorylation. PPAR gamma acts as a negative regulator of human endometrial cell decidualization in vitro.

Diagnosis and treatment guidelines of congenital mullerian anomalies / 대한산부인과학회지

Anatomic gynecologic anomalies occur when there is failure of normal embryonic ductal development. These include conditions such as congenital absence of vagina, lateral fusion defect and vertical fusion defect of the Mullerian duct. The treatment of Mullerian anomalies should be based on accurate diagnosis and comprehension of the developmental process. Congenital uterine anomalies occur in approximately 1 in 2000 newborn female infants. It is also important to provide adequate consultation and explanation to all family members with regard to the aim of treatment, possible complications that may ensue, and changes in future fertility potential.

Increased Proliferating Activity and Bcl-2 Protein Expression in Eutopic Endometrium with Endometriosis / 대한산부인과학회지

OBJECTIVE: To evaluate the expression of proliferating activity and Bcl-2 protein property in eutopic endometrium with endometriosis. METHODS: Endometrial tissues were obtained for endometrial biopsy from 2 groups of women. The study groups were 10 samples, which consisted of eutopic endometrial tissue with endometriosis. The remaining 10 samples were control group, which consisted of eutopic endometrial tissue without endometriosis. Expressions of Ki-67 and Bcl-2 protein were immunohistochemically investigated by polyclonal antibody. The computer program (Image pro (+), USA) was used to analysis the staining intensity of tissue samples objectively. Endometrial cells were cultured for 72 hours and the MTT colorimetric assay was used to detect cell proliferation. RESULTS: In the group of eutopic endometrium with endometriosis, the activity of cell proliferation was significantly increased. The expression of Ki-67 protein and MTT assay were significantly higher than those in the control group. And expression of Bcl-2 protein was significantly higher than those in the control group (P<0.05). CONCLUSION: Eutopic endometrium with endometriois showed increasing Bcl-2 protein expression and increasing proliferation. It was believed to be associated with endometrial pathological abnormalities in endometriosis.

Clinical Experiences of 7 Cases of Heterotopic Pregnancy / 대한산부인과학회지

OBJECTIVE: Although heterotopic pregnancy is a rare disorder, it is on an increasing tendency due to frequent use of intrauterine device, pelvic inflammatory disease, ovulation induction, assisted reproductive technology. This study was performed the clinical experiences of seven patients with heterotopic pregnancy. METHODS: Seven patients diagnosed as heterotopic pregnancy were analyzed by various factors such as age, symptoms, beta-hCG levels, gestational age at the time of diagnosis, postoperative course, sites of ectopic pregnancy, use of assisted reproductive technology, multiple pregnancy, and mode of surgery. RESULTS: The mean age of patients was 29.1 years, and chief complaint was abdominal pain. Laparotomy was done in 5 patients, and laparoscopy was done in 2 patients. Four of seven patients delivered at term, two were twins, two singletones. CONCLUSION: In heterotopic pregnancy, identification of intrauterine pregnancy without confirmation of ectopic pregnancy is associated with poor prognosis for both mother and fetus, and hence early dignosis and careful examination are need. Ectopic pregnancy should be removed and intrauterine pregnancy should be maintained.

Value of laparoscopy in infertile women with normal hysterosalpingograms / 대한산부인과학회지

OBJECTIVE: To evaluate the value of laparoscopy in infertile women with normal hysterosalpingograms. METHODS: Retrospectively analyzed the laparoscopic findings of 79 infertility patients with normal hysterosalpingograms. RESULTS: Of the 79 patients, 28 (35.4%) showed normal laparoscopic findings, while in 51 (64.6%) patients, it was abnormal. Abnormal findings consisted of stage I-II endometriosis in 23 patients (45.1%), stage III-IV endometriosis in 5 (9.8%), peritubal adhesions in 7 (13.7%), and pelvic adhesions in 12 (23.5%). Among patients in whom patent fallopian tubes were demonstrated by hysterosalpingography, there were 2 (4.0%) patients each with tubal obstruction and hydrosalpinx. CONCLUSION: Even in patients who showed normal findings on a hysterosalpingogram, it is thought that laparoscopy in selected cases may provide enhanced efficacy in terms of cost and time effectiveness.

Analysis of X Chromosome Inactivation in Women with Premature Ovarian Failure / 대한산부인과학회잡지

OBJECTIVE: Premature ovarian failure (POF) is a highly heterogenous condition, and its etiology remains unknown in approximately two-thirds of cases. POF can be caused by Turner syndrome, genetic disease, iatrogenic agents such as chemotherapy and radiotherapy, infection and autoimmune disease. X chromosome inactivation is the random process in females during early embryogenesis to achieve dosage compensation with males. But skewed X chromosome inactivation occurs in the female carriers, secondary to cell-autonomous selection against cells in which the abnormal X chromosome is active. Highly skewed X chromosome inactivation is likely to occur in POF which caused by subcytogenetic X chromosome deletion or translocation and X-linked gene mutation. The present study was performed to investigate whether highly skewed inactivation of X chromosome is observed in POF. METHODS: Eighty-six women with premature ovarian failure were studied and eighty-three normal women were enrolled as a control group. X chromosome inactivation pattern were determined by studying methylation pattern of androgen receptor gene. RESULTS: Seventy-six of the 86 POF patients were informative for X chromosome inactivation assay, 8 (10.5%) of them showed highly skewed X chromosome inactivation. In the age matched control group, 3 (4.1%) out of the 74 subjects showed highly skewed X chromosome inactivation. However, this finding is not statistically significant (p=0.2274). Among highly skewed X inactivation, one case of premature ovarian failure revealed 46,XX,del(X)(p21) by high resolution band karyotyping. Therefore highly skewed X inactivation can provide clues to evaluate the causes in POF. CONCLUSION: This study suggests that screening of skewed X chromosome inactivation for the POF will be useful to detect subcytogenetic X chromosome deletion or translocation and X-linked gene mutation associated with POF.