Clinical outcomes of three- or five-day treatment with clomiphene citrate combined with gonadotropins and a timed intercourse cycle in polycystic ovary syndrome patients / 대한생식의학회지

OBJECTIVE: This study aimed to investigate the effect of a new clomiphene citrate (CC) regimen on preventing thin endometrial lining in polycystic ovary syndrome (PCOS) patients receiving CC plus gonadotropin treatment with a timed intercourse cycle. METHODS: A total of 114 women with PCOS were included in this trial. Patients were divided into two groups and treated in accordance with the controlled ovarian stimulation (COS) protocol. In group A, 104 COS cycles in 67 patients were included, and in each cycle 150 mg CC was given for three days, starting from day 3. In group B, 69 COS cycles in 47 patients were included, in which 100 mg CC was given for five days, starting from day 3. The thickness of the endometrium was measured on the day of human chorionic gonadotropin (hCG) injection. Timed intercourse was recommended at 24 and 48 hours after the hCG injection. RESULTS: Additional doses of human menopausal gonadotropin and the number of days of hCG administration were not significantly different between the two groups. Endometrial thickness on the day of hCG administration was significantly larger in group A than group B (9.4+/-2.1 mm vs. 8.5+/-1.7 mm, p=0.004). The pregnancy rate was significantly higher in group A than in group B (38.4% vs. 21.7%, p=0.030). CONCLUSION: Three-day CC treatment resulted in a significantly higher pregnancy rate than the standard five-day CC treatment in a timed intercourse cycle in PCOS patients. Facilitating adequate endometrial growth via the early discontinuation of CC might be a crucial factor in achieving a higher pregnancy rate.

Preliminary clinical outcome of novel strategy for the maximization of cumulative pregnancy rates per retrieval in normal responders / 대한생식의학회지

OBJECTIVE: We devised a novel strategy, a GnRH antagonist protocol with a GnRH agonist trigger followed by frozen-thawed blastocyst transfers with long zona dissection (LZD). The purpose of this study was to investigate the clinical outcomes of this new strategy according to age. METHODS: Ninety women aged less than 35 (group A) and 32 women aged 35 to 39 (group B) underwent the GnRH antagonist protocol with a GnRH agonist trigger in order to obtain many oocytes and prevent early-onset ovarian hyperstimulation syndrome (OHSS). All oocytes were cultured to the blastocyst stage and all blastocysts grade 3BB or better were cryopreserved. Embryo transfers were only performed in freeze-thaw cycles to prevent late-onset OHSS and to overcome embryo-endometrium dyssynchrony. LZD was performed just after thawing to improve hatching and implantation rates. RESULTS: The average numbers of retrieved oocytes and blastocysts grade 3BB or better were 12.8+/-5.5 and 4.4+/-2.6 in group A and 10.9+/-7.4 and 2.5+/-2.2 in group B, respectively, and OHSS did not occur in any of the women. Implantation rates were 46.7% in group A and 39.3% in group B. Cumulative clinical pregnancy rates per retrieval were 77.8% in group A and 62.5% in group B. Cumulative ongoing pregnancy rates per retrieval were 71.1% in group A and 53.1% in group B. CONCLUSION: GnRH antagonist protocol with GnRH agonist trigger followed by frozen-thawed blastocyst transfers with LZD can generate many blastocysts without OHSS and maximize cumulative pregnancy rates per retrieval. This strategy is more effective in young women aged less than 35 than in women aged 35 to 39.

The hyperexpressions of putative stem cells in the eutopic endometrium of patients with advanced endometriosis / 대한산부인과학회지

OBJECTIVE: Recently it has been proposed that stem cells may be associated with the pathogenesis of endometriosis. The purposes of this study are to investigate whether the eutopic endometrial cells of women with or without endometriosis show the characteristics of stem cells in vitro and have a difference of the expressions of the undifferentiated stem cell markers as OCT-4 and CXCR4. METHODS: A total of 6 women with advanced endometriosis and a total of 10 women without endometriosis, adenomyosis or leiomyoma were included in this study. The eutopic endometrial cells, which were obtained from the menstrual blood at menstrual cycle day 2 to 4, were cultured in vitro for approximately 2 weeks, subsequently the putative very small stem cells were separated by Percoll density gradient method and were cultured. The expressions of OCT-4 and CXCR4 were analyzed by real time RT-PCR. RESULTS: The eutopic endometrial cells of the group of endometriosis compared with the control group showed the different morphological characteristics in vitro; more commonly heterogeneous supportive cells, very small round cells less than 3 micrometer and 5~15 micrometer sized hyperchromatic round cells. After the separation of very small round cells by Percoll density gradient method, these cells showed the several characteristics of stem cells; self-renewal, asymmetric cell division, colony formation and embryoid body-like formation. Also These cells showed the similar characteristics of very small embryonic-like stem cells; the mobile cells smaller than erythrocyte, the cell migration or adhesion to supportive cells, the sphere formation by cell aggregation and the formation of new differentiated cell by cell fusion. The expressions of OCT-4 and CXCR4 in the group of endometriosis are respectively 5.66 times and 17.69 times as high as the control group (P<0.05). CONCLUSION: The very small round cells less than 3 micrometer and 5~15 micrometer sized hyperchromatic round cells, which showed the several characteristics of stem cells in vitro, were more common in eutopic endometrial cells of patients with endometriosis and the expressions of OCT-4 and CXCR4 were significantly higher. This study suggests that stem cells might play a key role in the pathogenesis of endometriosis and OCT-4 and CXCR4 might be used as a tool for diagnosis or follow-up.

Acute Kidney Injury due to Menstruation-related Disseminated Intravascular Coagulation in an Adenomyosis Patient: A Case Report

The authors report a case of acute kidney injury (AKI) resulting from menstruation-related disseminated intravascular coagulation (DIC) in an adenomyosis patient. A 40-yr-old woman who had received gonadotropin for ovulation induction therapy presented with anuria and an elevated serum creatinine level. Her medical history showed primary infertility with diffuse adenomyosis. On admission, her pregnancy test was negative and her menstrual cycle had started 1 day previously. Laboratory data were consistent with DIC, and it was believed to be related to myometrial injury resulting from heavy intramyometrial menstrual flow. Gonadotropin is considered to play an important role in the development of fulminant DIC. This rare case suggests that physicians should be aware that gonadotropin may provoke fulminant DIC in women with adenomyosis.

Comparison of pregnancy and implantation rates in fresh embryo transfer (ET) and frozen-thawed ET cycles in infertile women with polycystic ovarian syndrome / 대한산부인과학회지

OBJECTIVE: Aim of this study is to evaluate the pregnancy and implantation rates in fresh-embryo transfer (ET) and frozen-thawed ET cycles in women with polycystic ovarian syndrome (PCOS). METHODS: PCOS was diagnosed by the Rotterdam criteria. In 4 cases of 72 stimulation cycles, ET was not conducted due to severe ovarian hyperstimulation syndrome (OHSS). Sixty eight cycles of fresh-ET and 40 cycles of frozen-thawed ET were included in this retrospective study. Age, gravidity, body mass index, infertility duration were compared between two groups. Number of embryos transferred, implantation rate, clinical pregnancy rate and multiple pregnancy rate were compared between two groups by using chi-square test and student's t-test. RESULTS: Number of embryos transferred showed significant difference between two groups. Fresh-ET group was 4.7 and frozen-thawed ET group was 2.8 (P<0.001). However, overall clinical outcomes with fresh-ET and frozen-thawed ET cycles were similar. Implantation rates were 8.3% vs 11.5%, clinical pregnancy rates were 27.9% vs 25.0% and multiple pregnancy rates were 36.8% vs 20.0%. CONCLUSION: Although more number of embryos were transferred in fresh-ET cycles, the clinical outcomes were similar between fresh-ET and frozen-thawed ET cycles. It may be due to decreased uterine receptivity in fresh-ET cycles. Frozen-thawed ET may be used as alternative plan for cases of severe OHSS and decreased uterine receptivity expected.

Effect of the decidualization of human endometrial cells on the hatching rates of the vitrified and the fresh mouse blastocysts / 대한산부인과학회지

OBJECTIVE: To compare the hatching rates of the vitrified and the fresh mouse blastocysts co-cultured with decidualized or non decdualized human endometrial cells and to confirm the necessity of assisted hatching in the vitrified mouse blastocyst. METHODS: Stromal and epitherial cells isolated from human endometrial tissue were co-cultured and decidualized with TGF-beta 1 and progesterone. The vitrified and the fresh mouse blastocysts were co-cultured with human decidualized or non-decidualized endometrial cells, respectively and the hatching rates were investigated. RESULTS: Epithelial and stromal cells isolated from endometrial tissue were cultured seperately for 24 hours and stained by immunohistochemical staining for cytokeratin (epithelial cells) or vimentin (stromal cells). The immunohistochemical study was positive for cytokeratin or vimentin and confirmed that epithelial and stromal cells were isolated from endometrial tissue successfully. The co-cultured human stromal and epitherial cells were decidualized by administration of TGF-beta 1 and progesterone. The hatching rates of the fresh and the vitrified mouse blastocysts co-cultured with decidualized human endometrial cells were 89% and 31%, respectively. The hatching rates of the fresh and the vitrified mouse blastocysts co-cultured with non-decidualized human endometrial cells were 82% and 27%, respectively. The hatching rates were significantly higher in fresh mouse blastocysts than in vitrified mouse blastocysts regardless of decidualization of human endometrial cells (P<0.05). CONCLUSION: The hatching rate was significantly higher in fresh mouse blastocysts than in vitrified mouse blastocysts. This results showed that the cryopreservation procedure caused the zona hardening of mouse blastocyst and the decidualization of endometrial cells did not affect to hatching rate of the vitrified mouse blastocysts. We confirmed that assisted hatching was necessary for improving the hatching rate of cryopreserved mouse blastocysts.

Disseminated intravascular coagulation developed after controlled ovarian hyperstimulation in woman with adenomyosis / 대한산부인과학회지

Disseminated intravascular coagulation (DIC) is usually developed after infection, metastatic cancer or complicated pregnancy. We experienced a case of infertile woman with adenomyosis, who had not been predisposed any common risk factors but had acute DIC during menstruation after controlled ovarian stimulation. The patient received anticoagulation therapy with supplementation of coagulation factors, followed by surgical removal of uterus 3 months later. We assumed that DIC resulted from rapidly aggravated lesion during controlled ovarian stimulation and massive intramuscular hemorrhage during menstruation. So, we report the case with brief review of literatures.

Expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 as prognostic factors in endometrial cancer / 부인종양

OBJECTIVE: Homeostasis of the extracellular matrix (ECM) is maintained by the action of a specific system of proteolytic enzymes known as matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP). The MMP/TIMP system regulates the composition and turnover of ECM to control the site and extent of connective tissue remodeling. In pathologic conditions, MMP play a key role in degradation of basement membrane and extracellular matrix, and is responsible for cancer invasion, progression and metastasis. The aim of this study is to evaluate the correlation between expressions of MMP/TIMP and clinicopathologic factors in endometrial cancer. METHODS: Expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 were assessed by immunohistochemistry in a total of 55 endometrial cancers and were analyzed by the correlation between expressions of MMP/TIMP and clinicopathologic factors in endometrial cancer. RESULTS: Expression rates of MMP-2,-9, TIMP-1, and TIMP-2 were 71.7%, 54.9%, 41.2%, and 76.5% respectively. Expression of MMP-2 was correlated with the group of positive lymph node metastasis in endometrial cancer (p=0.04). Specially, coexpression of MMP-2 and TIMP-2 was significantly more frequent in the group of positive lymph node metastasis (p<0.01) and the group of positive peritoneal CONCLUSION: The expressions of MMP and TIMP were not a significant difference in survival analysis, but this study was recognized that the coexpression MMP-2 and TIMP-2 is correlated with lymph node metastasis and positive peritoneal cytology.