1.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
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.
2.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
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.
3.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
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.
4.miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone
Su-Yeon LEE ; Youn-Jung KANG ; Jinie KWON ; Yoshihiro NISHI ; Toshihiko YANASE ; Kyung-Ah LEE ; Mi Kyoung KOONG
Clinical and Experimental Reproductive Medicine 2020;47(3):194-206
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.
5.Can high serum anti-Mullerian hormone levels predict the phenotypes of polycystic ovary syndrome (PCOS) and metabolic disturbances in PCOS patients?.
Yu Im HWANG ; Na Young SUNG ; Hwa Seon KOO ; Sun Hwa CHA ; Chan Woo PARK ; Jin Yeong KIM ; Kwang Moon YANG ; In Ok SONG ; Mi Kyoung KOONG ; Inn Soo KANG ; Hye Ok KIM
Clinical and Experimental Reproductive Medicine 2013;40(3):135-140
OBJECTIVE: To evaluate correlations between serum anti-Mullerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS. METHODS: A total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) > or =25 kg/m2 (n=34). RESULTS: The mean age was 25.9+/-5.7 year and mean AMH level was 10.1+/-5.4 ng/mL. The BMI (kg/m2) was higher in group 1 (24.2+/-6.3) than in group 2 (21.9+/-4.3, p=0.046) or group 3 (21.6+/-3.3, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH (7.7+/-3.9 ng/mL vs. 10.7+/-5.6 ng/mL), p=0.004) and low-density lipoprotein levels (93.1+/-21.2 mg/dL vs. 107.5+/-39.3 mg/dL, p=0.031), and showed higher total T (0.74+/-0.59 ng/mL vs. 0.47+/-0.36 ng/mL, p=0.001), free T (2.01+/-1.9 vs. 1.04+/-0.8 pg/mL, p=0.0001), and free androgen index (6.2+/-7.9 vs. 3.5+/-3.0, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters. CONCLUSION: For PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly.
Age Factors
;
Androgens
;
Anti-Mullerian Hormone
;
Body Mass Index
;
Carbamates
;
Consensus
;
Female
;
Humans
;
Hyperandrogenism
;
Lipoproteins
;
Obesity
;
Organometallic Compounds
;
Ovary
;
Phenotype
;
Polycystic Ovary Syndrome
6.The effectiveness of earlier oocyte retrieval in the case of a premature luteinizing hormone surge on hCG day in in vitro fertilization-embryo transfer cycles.
Min Hye CHOI ; Sun Hwa CHA ; Chan Woo PARK ; Jin Young KIM ; Kwang Moon YANG ; In Ok SONG ; Mi Kyoung KOONG ; Inn Soo KANG ; Hye Ok KIM
Clinical and Experimental Reproductive Medicine 2013;40(2):90-94
OBJECTIVE: To evaluate the efficacy of earlier oocyte retrieval in IVF patients with a premature LH surge on hCG day. METHODS: One hundred forty IVF patients (164 cycles) with premature LH surge on hCG day were included, retrospectively. We divided them into 2 study groups: LH surge with timed ovum pick-up (OPU) 36 hours after hCG injection (group B, 129 premature cycles), and LH surge with earlier OPU within 36 hours after hCG injection (group C, 35 cycles). Control groups were tubal factor infertility without premature LH surge (group A, 143 cycles). RESULTS: The mean age (year) was statistically higher in group C than in groups A or B (38.2+/-5.4 vs. 36.2+/-4.2 vs. 36.8+/-4.9, respectively; p=0.012). The serum LH levels (mIU/mL) on hCG day were significantly higher in group B and C than in group A (22.7+/-14.9 vs. 30.3+/-15.9 vs. 3.2+/-2.9, respectively; p>0.001). Among groups A, B, and C, 4.9%, 31.7%, and 51.4% of the cycles, respectively, had no oocytes, and the overall rates of cycle cancellation (OPU cancellation, no oocyte, or no embryos transferrable) were 15.4%, 65.9%, and 74.3%, respectively. The fertilization rate (%) was significantly higher in group B than in group C (73.2+/-38.9 vs. 47.8+/-42.9, p=0.024). The clinical pregnancy rate was significantly higher in group C than in groups A and B (44.4% vs. 27.3% vs. 9.1%, respectively, p=0.021). However, the miscarriage rate was also higher in group C than in group B (22% vs. 0%, respectively, p=0.026). CONCLUSION: Earlier OPU may not be effective in reducing the risk of cycle cancellation in patients with premature LH surge on hCG day. A larger scale study will be required to reveal the effectiveness of earlier ovum retrieval with premature LH surge.
Abortion, Spontaneous
;
Embryonic Structures
;
Female
;
Fertilization
;
Fertilization in Vitro
;
Humans
;
Infertility
;
Lutein
;
Luteinizing Hormone
;
Oocyte Retrieval
;
Oocytes
;
Ovum
;
Pregnancy
;
Pregnancy Rate
;
Retrospective Studies
7.Blastocyst transfer in frozen-thawed cycles.
Ae Ra HAN ; Chan Woo PARK ; Hyoung Song LEE ; Kwang Moon YANG ; In Ok SONG ; Mi Kyoung KOONG
Clinical and Experimental Reproductive Medicine 2012;39(3):114-117
OBJECTIVE: It is well known that fresh blastocyst transfer results in better pregnancy outcomes with a smaller number of transferred embryos compared with cleavage stage embryo transfer. However, in terms of frozen-thawed blastocyst transfer, only a few studies are available. We aimed to evaluate clinical outcomes of frozen-thawed embryo transfer (FET) with blastocysts. METHODS: Retrospective analysis of FET cycles with blastocysts (B-FET) between Jan 2007 and June 2009 was performed. Age-matched FET cycles with cleavage stage embryos (C-FET) during the same period were collected as controls. A total of 58 B-FET cycles were compared with 172 C-FET cycles and also compared with those of post-thaw extended culture blastocysts from frozen pronuclear stage embryos (22 cycles). RESULTS: There was no difference in the patient characteristics of each group. The embryos' survival rates after thawing were comparable (>90%) and there was no difference in the implantation rate or clinical and ongoing pregnancy rate among the three groups. CONCLUSION: In FET, blastocyst transfers may not present better pregnancy outcomes than cleavage stage embryo transfers. A further large-scale prospective study is needed.
Blastocyst
;
Embryo Transfer
;
Embryonic Structures
;
Female
;
Humans
;
Pregnancy
;
Pregnancy Outcome
;
Pregnancy Rate
;
Retrospective Studies
;
Survival Rate
8.Comparison of assisted reproductive technology outcomes in infertile women with polycystic ovary syndrome: In vitro maturation, GnRH agonist, and GnRH antagonist cycles.
Min Hye CHOI ; Sun Hee LEE ; Hye Ok KIM ; Sun Hwa CHA ; Jin Young KIM ; Kwang Moon YANG ; In Ok SONG ; Mi Kyoung KOONG ; Inn Soo KANG ; Chan Woo PARK
Clinical and Experimental Reproductive Medicine 2012;39(4):166-171
OBJECTIVE: We compared the assisted reproductive technology (ART) outcomes among infertile women with polycystic ovary syndrome (PCOS) treated with IVM, conventional IVF, GnRH agonist, and GnRH antagonist cycles. METHODS: The prospective study included a total of 67 cycles in 61 infertile women with PCOS. The women with PCOS were randomized into three IVF protocols: IVM/IVF with FSH and hCG priming with immature oocyte retrieval 38 hours later (group A, 14 cycles), GnRH agonist long protocol (group B, 14 cycles), and GnRH antagonist multi-dose flexible protocol (group C, 39 cycles). IVF outcomes, such as clinical pregnancy rate (CPR), implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR), were compared among the three groups. RESULTS: Age, BMI, and basal FSH and LH levels did not differ among the three groups. The number of retrieved oocytes and 2 pronucleus embryos was significantly lower in group A compared with groups B and C. The CPR, IR, MR, and LBR per embryo transfer showed no differences among the three groups. There was no incidence of ovarian hyperstimulation syndrome in group A. CONCLUSION: The IR, MR, and LBR in the IVM cycles were comparable to those of the GnRH agonist and GnRH antagonist cycles. The IVM protocol, FSH and hCG priming with oocyte retrieval 38 hours later, is an effective ART option that is comparable with conventional IVF for infertile women with PCOS.
Abortion, Spontaneous
;
Cardiopulmonary Resuscitation
;
Embryo Transfer
;
Embryonic Structures
;
Female
;
Gonadotropin-Releasing Hormone
;
Humans
;
Incidence
;
Live Birth
;
Oocyte Retrieval
;
Oocytes
;
Ovarian Hyperstimulation Syndrome
;
Ovary
;
Polycystic Ovary Syndrome
;
Pregnancy
;
Pregnancy Rate
;
Prospective Studies
;
Reproductive Techniques, Assisted
9.Laparoscopic management of early primary peritoneal pregnancy: a case report.
Hwa Seon KOO ; Ju Youn BAE ; Inn Soo KANG ; Mi Kyoung KOONG ; Hye Ok KIM ; Sun Hwa CHA ; Min Hye CHOI ; Ji Young KIM ; Kwang Moon YANG
Clinical and Experimental Reproductive Medicine 2011;38(2):109-114
Peritoneal pregnancy is an implantation in the peritoneal cavity exclusive of tubal, ovarian, or intra-ligamentary implantations. This is a rare obstetric complication with high maternal mortality and even higher perinatal mortality, and secondary type was most common. Risk factors for peritoneal pregnancy are previous history of extrauterine pregnancy or tubal surgery pelvic post-inflammatory status or presence of an intra-uterine device. As it is a life-threatening condition, expectant management carries a risk of sudden life-threatening intra-abdominal bleeding and a generally poor fetal prognosis. So, when it is recognized, immediate termination of pregnancy is usually recommended. Early diagnosis of peritoneal pregnancy is difficult, but is important by their life threatening progress course to patients. Recently, we experienced primary peritoneal pregnancy which meets both the original and modified criteria. In this paper, we reported the case of early diagnosed and successfully treated peritoneal pregnancy despite of their diagnosis was incidentally.
Early Diagnosis
;
Female
;
Hemorrhage
;
Humans
;
Maternal Mortality
;
Perinatal Mortality
;
Peritoneal Cavity
;
Pregnancy
;
Pregnancy, Ectopic
;
Prognosis
;
Risk Factors
10.Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study.
Ae Ra HAN ; Hye Ok KIM ; Sun Wha CHA ; Chan Woo PARK ; Jin Yeong KIM ; Kwang Moon YANG ; In Ok SONG ; Mi Kyoung KOONG ; Inn Soo KANG
Clinical and Experimental Reproductive Medicine 2011;38(2):103-108
OBJECTIVE: To investigate adverse pregnancy outcomes in non-obese women with polycystic ovary syndrome (PCOS) compared with obese-PCOS and control groups. METHODS: Women with PCOS who underwent assisted reproductive technology (ART) from August, 2003 to December, 2007, were considered. A total of 336 women with PCOS were included in the study group and 1,003 infertile women who had tubal factor as an indication for ART were collected as controls. They were divided into four groups: a non-obese PCOS group, obese-PCOS group, non-obese tubal factor group, and obese tubal factor group, with obesity defined by a body mass index over 25 kg/m2, and reviewed focusing on the basal characteristics, ART outcomes, and adverse pregnancy outcomes. RESULTS: There was no difference among the groups' the clinical pregnancy rate or live birth rate. Regarding adverse pregnancy outcomes, the miscarriage rate, multiple pregnancy rate, and prevalence of preterm delivery and pregnancy induced hypertension were not different among the four groups. The incidence of small for gestational age infant was higher in the PCOS groups than the tubal factor groups (p<0.02). On the other hand, the morbidity of gestational diabetes mellitus (GDM) was not high in the non-obese PCOS group but was in the obese groups. And in the obese PCOS group, the newborns were heavier than in the other groups (p<0.02). CONCLUSION: Non-obese PCOS presents many differences compared with obese PCOS, not only in the IVF-parameters but also in the morbidity of adverse pregnancy outcomes, especially in GDM and fetal macrosomia.
Abortion, Spontaneous
;
Body Mass Index
;
Case-Control Studies
;
Diabetes, Gestational
;
Female
;
Fetal Macrosomia
;
Gestational Age
;
Hand
;
Humans
;
Hypertension, Pregnancy-Induced
;
Incidence
;
Infant
;
Infant, Newborn
;
Live Birth
;
Obesity
;
Ovary
;
Polycystic Ovary Syndrome
;
Pregnancy
;
Pregnancy Outcome
;
Pregnancy Rate
;
Pregnancy, Multiple
;
Prevalence
;
Reproductive Techniques, Assisted

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