• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.4
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• pp.170-180
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• 2019

Objectives: The purpose of this study is to report the case of Korean medicine treatment on primary ovarian insufficiency. Methods: The patient in this case was 29-year-old female who was diagnosed with primary ovarian insufficiency. She had irregular menstruation and hypomenorrhea more than 6 months. She also suffered from hot flash and vaginal dryness. She was treated over 1 year with Korean medicine treatment, such as herbal medicine, acupuncture, and pharmacopuncture. We assessed the clinical symptoms, menstrual status and serum hormone level during the treatment. Results: After treatment, symptoms of primary ovarian insufficiency were relieved, level of serum FSH decreased and level of serum E2 increased. We maintained the treatment over 1 year and kept follow-up measurements of serum hormone level. Conclusions: This study shows that Korean medicine treatment can be effective in treating primary ovarian insufficiency. The report suggests the long treatment procedure for primary ovarian insufficiency.

• Clinical and Experimental Reproductive Medicine
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• v.46 no.2
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• pp.43-49
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• 2019

Primordial follicle activation is a process in which individual primordial follicles leave their dormant state and enter a growth phase. While existing hormone stimulation strategies targeted the growing follicles, the remaining dormant primordial follicles were ruled out from clinical use. Recently, in vitro activation (IVA), which is a method for controlling primordial follicle activation, has provided an innovative technology for primary ovarian insufficiency (POI) patients. IVA was developed based on Hippo signaling and phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/forkhead box O3 (FOXO3) signaling modulation. With this method, dormant primordial follicles are activated to enter growth phase and developed into competent oocytes. IVA has been successfully applied in POI patients who only have a few remaining remnant primordial follicles in the ovary, and healthy pregnancies and deliveries have been reported. IVA may also provide a promising option for fertility preservation in cancer patients and prepubertal girls whose fertility preservation choices are limited to tissue cryopreservation. Here, we review the basic mechanisms, translational studies, and current clinical results for IVA. Limitations and further study requirements that could potentially optimize IVA for future use will also be discussed.

• Clinical and Experimental Reproductive Medicine
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• v.42 no.2
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• pp.58-61
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• 2015

Objective: The XIST gene is considered to be an attractive candidate gene for skewed X-chromosome inactivation and a possible cause of primary ovarian insufficiency (POI). The purpose of this study was to investigate whether the XIST gene promoter mutation is associated with idiopathic POI in a sample of the Korean population. Methods: Subjects consisted of 102 idiopathic POI patients and 113 healthy controls with normal menstrual cycles. Patients with the following known causes of POI were excluded in advance: cytogenetic abnormalities, prior chemo- or radiotherapy, or prior bilateral oophorectomy. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The mean age of onset of ovarian insufficiency was $28.7{\pm}8.5years$ and the mean values of serum luteinizing and follicle-stimulating hormones and estradiol in the POI group were $31.4{\pm}18.2mIU/mL$, $74.5{\pm}41.1mIU/mL$, and $30.5{\pm}36.7pg/mL$, respectively. We found no cytosine to guanine (C43G) variation in the XIST gene in both POI patients and controls. Conclusion: The C43G mutation in the promoter region of the XIST gene was not present in the Korean patients with idiopathic POI in our study, in contrast to our expectation, suggesting that the role of XIST in the pathogenesis of POI is not yet clear.

• Clinical and Experimental Reproductive Medicine
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• v.46 no.1
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• pp.1-7
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• 2019

With the progress of regenerative medicine, mesenchymal stem cells (MSCs) have received attention as a way to restore ovarian function. It has been reported that MSCs derived from bone marrow, adipose, umbilical cord blood, menstrual blood, and amniotic fluid improved ovarian function. In light of previous studies and advances in this field, there are increased expectations regarding the utilization of MSCs to restore ovarian function. This review summarizes recent research into potential applications of MSCs in women with infertility or primary ovarian insufficiency, including cases where these conditions are induced by anticancer therapy.

• Journal of Menopausal Medicine
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• v.24 no.3
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• pp.196-203
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• 2018

Objectives: This study was aimed to establish the most effective premature ovarian failure (POF) mouse model using Cyclophosphamide (CTX), busulfan (Bu), and cisplatin considering treatment duration of anticancer drugs and natural recovery time. Methods: POF was induced by intraperitoneally injecting CTX (120 mg/kg)/Bu (12 mg/kg) for 1 to 4 weeks or cisplatin (2 mg/kg) for 3 to 14 days to C57BL/6 female mice aged 6 to 8 weeks. Controls were injected with equal volume of saline for the same periods. Body weight was measured every week, and ovarian and uterine weights were measured after the last injection of anticancer drug. To assess ovarian function, POF-induced mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin, and then mated with male. After 18 hours, zygotes were retrieved and cultured for 4 days. Finally, the mice were left untreated for a period of times after the final injection of anticancer drug, and the time for natural recovery of ovarian function was evaluated. Results: After 2 weeks of CTX/Bu injection, ovarian and uterine weights, and ovarian function were decreased sharply. Cisplatin treatment for 10 days resulted in a significant decrease in ovarian and uterine weight, and ovarian function. When POF was induced for at least 2 weeks for CTX/Bu and for at least 10 days for cisplatin, ovarian function did not recover naturally for 2 weeks and 1 week, respectively. Conclusions: These results suggest that CTX/Bu should be treated for at least 2 weeks and cisplatin for at least 10 days to establish the most effective primary ovarian insufficiency mouse model.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.4
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• pp.127-131
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• 2012

Primordial follicles are formed prenatally in mammalian ovaries, and at birth they are fated to be activated to primary follicles, to be dormant, or to die. During the early stage of folliclulogenesis, the oocyte undergoes dynamic alterations in expression of numerous genes, which are regulated by transcription factors. Several germ-cell specific transcriptional regulators are critical for formation and maintenance of follicles. These transcriptional regulators include: Figla, Lhx8, Nobox, Sohlh1, and Sohlh2. A subset of these transcriptional regulators is mutated in women with ovarian insufficiency and infertility. Establishment of this oocyte pool is essential for fertility. This review focuses on these transcriptional regulators of female primordial follicles.

• Clinical and Experimental Reproductive Medicine
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• v.41 no.1
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• pp.29-32
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• 2014

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-K$\ddot{u}$ster-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.

• Journal of Genetic Medicine
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• v.9 no.2
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• pp.73-77
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• 2012

Purpose: Fragile X carrier detection before or at early pregnancy through a wide screening program may not only confer a risk of having offspring with Fragile X syndrome (FXS), but may also confer a risk for Fragile X-associated primary ovarian insufficiency and Fragile X-associated tremor/ataxia syndrome. However, prior to the implementation of such a program, the carrier prevalence in a population and the availability of effective screening test should be evaluated. The aim of our study was to determine the prevalence of premutation carriers and to evaluate the feasibility of screening test. Materials and Methods: The blood samples were obtained from 8,641 pregnant women with no family history of mental retardation. We performed a three-primer CGG repeat primed (RP) PCR using the AmplideX$^{TM}$ FMR1 PCR kit (Asuragen, Inc. Austin, TX, USA). Samples showing full mutation alleles were reflexed to Southern blot analysis for methylation status and sizing. Results: Among the 8,641 women, we found 8 premutation carriers (1:1,090, 0.09%) and 46 women with an intermediate allele (1:190, 0.53%). No woman was found to carry the fully mutated allele. All the detected alleles were within the CGG repeat range of 8-117. Among the 8,641 samples, 29 and 30 CGG repeats represent 66.6% of all cases. The CGG RP PCR method provides robust detection of expanded alleles and resolves allele zygosity, thus minimizing the number of samples that require Southern blot analysis. Conclusion: This is the first study that has focused on the prevalence of FXS premutation carriers and FMR1 allele distribution in normal pregnant women. These data have important implications for population-based fragile X carrier screening in Korea.