Objective: Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR. Methods: We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction. Results: KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients. Conclusion miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.

Objective: Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR. Methods: We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction. Results: KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients. Conclusion miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.

Objective: Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR. Methods: We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction. Results: KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients. Conclusion miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.

Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

OBJECTIVE: The aim of this study was to evaluate the influences of uterine septum and their elimination on the reproductive outcomes in women who have history of recurrent spontaneous abortion (RSA) and/or infertility. METHODS: The medical records of reproductive outcomes in patients who have had history of RSA and infertility who were diagnosed with uterine septum only by hysterosalpingogram (HSG) between January 2008 and December 2009 were retrospectively analyzed. The subjects who have had severe male factor, tubal factors, other uterine factors, endocrine abnormalities, peritoneal factors, and abnormal karyotyping among both partners were excluded. In 27 patients, confirmation of diagnosis by laparoscopy and elimination of uterine septum by trans-vaginal hysteroscopy was done. Seventeen patients were strongly suspected to uterine septum on HSG but tried to get pregnancy without any other procedure for evaluation and management of uterine anomaly. Age matched 42 patients who have history of RSA and/or infertility and diagnosed to normal HSG finding at same period were randomly selected as control. The medical records of reproductive outcomes were analyzed and compared between groups. RESULTS: The mean time of observation after diagnosis was 21.8 months (10 to 32). 55.6% (15/27) of patients in patients who received trans-vaginal hysteroscopic uterine septotomy were success to get pregnancies and was significantly higher than that of 17 patients who did not receive proper management (23.5%, 4/17, p<0.05). In control population, 40.5% (17/42) were success to pregnancies and the differences were not statistically significant compared to both two study groups. The live birth rate which was excluded pregnancy loss by abnormal fetal karyotyping and congenital anomaly were 75% (9/12) in treated septated uterus group and 84.6% (11/13) in control group each which have no statistically significant different. In patients with septated uterus who did not receive proper management showed lower delivery rate (50%, 2/4) than that of other groups but was not statistically significant. CONCLUSION: According to present data, women with a uterine septum have an increased chance of successful pregnancy with improved obstetric outcome after proper management of the uterine cavity. And these results were showed in patients with no regard to their reproductive history. But, in case of failed to receive proper management, uterine septum can affect not only pregnancy ongoing but successful pregnancy too.
Abortion, Spontaneous ; Female ; Humans ; Hysteroscopy ; Infertility ; Karyotyping ; Laparoscopy ; Live Birth ; Male ; Medical Records ; Pregnancy ; Reproductive History ; Retrospective Studies ; Uterus

OBJECTIVE: To evaluate the significance and efficacy of trans-cervical fallopian tube catheterization (TFTC) in diagnosis and optimal treatment modality for tubal blockage. METHODS: The retrospective study was performed in those underwent TFTC from January 2005 to December 2009. A total of 342 fallopian tubes in 215 patients which showed tubal blockage in hysterosalpingography (HSG), were subjected to TFTC. Recanalization rate (RR) was compared according to portion of tubal blockage; proximal, isthmic and distal portion and blockage type; tapering, concave, and convex type. RESULTS: In total, RR was 72.5% (248/342 tube). According to the portion of tubal blockage, RR was 83.8% in proximal, 45.6% in isthmic and 100% in distal portion. RR was 92.3% in tapering, 80.2% in concave and 25.5% in convex type, respectively. There were 98 pregnancies in 156 patients after successful recanalization, which shows 62.7% pregnancy rate. CONCLUSION: TFTC were capable of recanalizing tubal blockage in 248 of 342 tubes in 156 of 215 patients (72.5%). The RR was increased with proximal portion and tapering type tubal blockage.
Catheterization ; Catheters ; Fallopian Tubes ; Female ; Humans ; Hysterosalpingography ; Infertility ; Pregnancy ; Retrospective Studies

OBJECTIVE: Low-dose aspirin have been proposed to improving endometrial receptivity and pregnancy rate in COH-IVF by increasing endometrial perfusion. However, the effect of low-dose aspirin in COH-IVF could be negligible because there have been large quantity of other important factors responsible for changing endometrial perfusion accompanied by COH procedure. In contrast, in frozen-thawed embryo transfer cycles which were not accompanied by COH procedure, the effects of low-dose aspirin in endometrial blood flow seems to be more certain than in COH-IVF cycles. In this study, we analyzed the effect of low-dose aspirin treatment on implantation and pregnancy rates in patients undergoing frozen-thawed embryo transfer METHODS: From January 2003 to December 2003, total 264 cycles from 264 patients who attended infertility clinic at Samsung Cheil Hospital were enrolled in this study. All cases included in this study, embryos were frozen and thawed at the pronuclear stage and three days after incubation, at least 2 or more good quality embryos were transferred into uterus. In study group, low dose aspirin (100 mg/day) was administrated from the first or second date of menstrual day to 9 days after embryo transfer. On the other hand, control group did not take any medicine except estradiol valerate for endometrial priming. Several variables including implantation and pregnancy rates were compared in both groups. After then, each groups were stratified by endometrial thickness checked at embryo transfer (ET) day such as (28 mm versus <8 mm) and same variables above described were compared between study and control groups. RESULTS: The mean age, infertility duration, endometrial thickness at embryo transfer day and mean number of transferred embryo were not significantly different in both groups. Also, implantation rates (study group: 15.8%, control group: 20.5%) and pregnancy rate (study group: 45.1%, control group: 43.5%) were not significantly different between two groups. (p>0.05) After we analyzed same variables stratified by endometrial thickness checked at embryo transfer day, we could not found any significant difference between study and control groups. CONCLUSIONS: Low-dose aspirin treatment seems to have no advantage of improving implantation and pregnancy rates in patients undergoing frozen-thawed embryo transfer.
Aspirin* ; Embryo Transfer* ; Embryonic Structures* ; Estradiol ; Hand ; Humans ; Infertility ; Perfusion ; Pregnancy Rate* ; Pregnancy* ; Uterus

OBJECTIVES: We aimed to investigate the clinical effect of low-dose intravenous immunoglobulin treatment in unexplained recurrent spontaneous aborters (RSA) with elevated peripheral CD56+ natural killer (NK) cell levels and to determine the pre-conceptional NK cell percentage predictive of subsequent successful pregnancy outcome. MATERIALS AND METHODS: Sixty four cases of unexplained recurrent miscarriage with elevated peripheral NK cells (>15%) were received low dose IVIg infusion at the dosage of 400 mg/Kg/month after confirmation of gestational sac and continued until 20 weeks. The patients were divided into two groups according to the pregnancy outcome: Group I was success of treatment defined as live birth at or after 25 gestational weeks and Group II was failure of treatment. The preconceptional levels of the peripheral blood NK cells were compared between two groups. RESULTS: Fifty-three pregnancies resulted in live births after 25 weeks and 11 resulted in abortion (Overall success rate of IVIG treatment was 82.8%). Preconceptional CD56+ NK cell percentage in group II (27.4+/-1.9%) was higher than those in group I (22.3+/-0.8%). By using ROC curve, optimal discrimination between success and failure of treatment was achieved with < or = 27% of preconceptional NK cell percentage. CONCLUSION: In RSA patients with elevated NK cells, we suggest that preconceptional peripheral blood CD56+ NK cell level could be a useful marker for predicting successful treatment outcome of low-dose IVIg infusion.
Abortion, Habitual ; Abortion, Spontaneous* ; Discrimination (Psychology) ; Female ; Gestational Sac ; Humans ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Killer Cells, Natural* ; Live Birth ; Pregnancy ; Pregnancy Outcome ; ROC Curve ; Treatment Outcome*

OBJECTIVE: To evaluate the effectiveness of aromatase inhibitor (AI) for ovulation induction in polycystic ovary syndrome (PCOS) patients with thin endometrium, hyper-responsiveness after clomiphene citrate (CC) treatment. MATERIAL AND METHODS: A prospective study was performed in 43 PCOS patients (50 cycles) with ovulatory dysfunction between March 2004 and September 2004. AI group (total 36 cycles) included the patients 1) with thin endometrium below 6 mm on hCG day after CC (n=17), 2) with more than 5 ovulatory follicles after 50mg of CC (n=4), 3) who do not want multiple pregnancy (n=14). Patients were treated with Letrozole 2.5mg for days 3 to 7 of the menstrual cycle. CC group (total 14 cycles) were treated with CC 50~100 mg. RESULTS: In PCOS patients, ovulation was occurred 97.2% after AI use. Between AI group and CC group, there was no significant difference in the mean age, duration of infertility, interval of menstruation, basal FSH, prior treatment cycles, and the day of hCG administration. But, the number of mature follicles (> or =15 mm) was lower in the AI group (1.08+/-0.45 vs. 1.64+/-0.75) (p=0.018), and the thickness of endometrium (mm) was significantly thicker in the AI group (10.35+/-1.74 vs. 9.23+/-1.61) (p=0.044), and E2 (pg/ml) concentration on hCG day was lower in the AI group (116.9+/-75.8 vs. 479.5+/-300.8) (p=0.001). Among the AI group, patients with prior thin endometrium (below 6 mm) during CC treatment showed 10.6+/-1.6 mm in the endometrial thickness and 106.6+/-66.8 pg/ml in E2 concentration. Patients with more than 5 ovulatory follicles after CC showed decreased follicle number (1.25+/-0.5) compared to prior CC cycle. CONCLUSIONS: In PCOS patients, AI group showed significantly thicker endometrium, lesser number of mature follicles, and lower E2 concentration on hCG day than CC group. AI might be useful alternative treatment for ovulation induction in PCOS patients with thin endometrium and hyper-responsiveness after CC treatment.
Aromatase* ; Clomiphene* ; Endometrium ; Female ; Humans ; Infertility ; Menstrual Cycle ; Menstruation ; Ovulation ; Ovulation Induction ; Polycystic Ovary Syndrome* ; Pregnancy ; Pregnancy, Multiple ; Prospective Studies

OBJECTIVE: The purposes of this study are to evaluate the obstetric outcome in pregnancies resulting from oocyte donation and to assess the factors related to the obstetric complications. METHODS: The obstetric outcome in pregnancies from the oocyte donation (n=37) was compared with that in pregnancies from conventional IVF program (n=137) in our IVF center between January 1995 and December 2000. Control group was selected by age, parity, and order of gestation matched to the study group. Pregnancy induced hypertension (PIH) was defined as blood pressure >140/90 mmHg on two or more occasions at least 6 hours apart with or without proteinuria after 20 weeks of gestation and not associated with chronic hypertension. Small for gestational age (SGA) was defined as birth weight below tenth percentile for gestational weeks. The data was analyzed using the Statistical Package for Social Sciences (SPSS). RESULTS: Early pregnancy loss rates were 37.8% (14/37) and 23.4% (32/137) in study and control group, respectively (P>0.05). PIH related factors such as mean age, parity and order of gestation were not significantly different among the two groups. However, the incidence of PIH in oocyte donation group (30.0%, 6/20) was significantly higher than control group (8.8%,9/102). There was no significant difference in the incidence of SGA between the two groups. When oocyte donation group was stratified by relationship of oocyte donor to infertile patient (sibling versus non-sibling), the incidence of early pregnancy loss and PIH was significantly higher (chi square test, P<0.05) in non-sibling group (42.3%, 11/26; 38.5%, 5/13) than in control group (23.4%, 32/137; 8.8%, 9/102). CONCLUSION: The incidence of PIH was significantly higher in pregnancies after oocyte donation. Notably, the pregnancies from non-sibling oocyte donors had much higher incidence of early pregnancy loss and PIH than pregnancies from sibling oocyte donors or control group. Therefore, the occurrence of early pregnancy loss and PIH may be related to other factors than age, parity or multiple pregnancy.
Birth Weight ; Blood Pressure ; Female ; Gestational Age ; Humans ; Hypertension ; Hypertension, Pregnancy-Induced ; Incidence ; Oocyte Donation* ; Oocytes* ; Parity ; Pregnancy ; Pregnancy, Multiple ; Primary Ovarian Insufficiency* ; Proteinuria ; Siblings ; Social Sciences ; Tissue Donors