• Clinical and Experimental Reproductive Medicine
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• 제40권3호
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• pp.115-121
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• 2013

Objective: Letrozole and estradiol valerate are used to treat some hormonally-responsive symptoms and also in modeling of the polycystic ovary syndrome. However, the stereological analysis of the ovary has received less attention. Estimation of the whole ovary volume using the Cavalieri method can be applied in any orientation desired, but estimation of the mean volume of the oocytes requires isotropic uniform random sectioning. Here, a combined method was developed for estimating the parameters. To our knowledge, no comparison has been made of the effects of letrozole and estradiol on the ovary. Methods: Sixty rats were divided into 4 groups receiving estradiol (4 mg/kg), olive oil, letrozole (1 mg/kg), or normal saline. After 21 days, their ovaries were studied. Results: Relative to the control group, the total volume of the ovary and the cortex increased in the letrozole-treated and estradiol-treated rats. In addition, the number of the preantral, antral, and granulosa cells decreased by 43% to 56% in the letrozole- and estradiol-treated rats. On average, a 19% increase was observed in the atretic oocytes of the letrozole-treated and estradiol-treated rats, but the mean oocyte volume decreased by 29% to 44% in letrozole- and estradiol-treated rats. Furthermore, the letrozole-treated rats showed a 5-fold and 7-fold increase in the volume of the cysts and corpus luteum, respectively. A 3-fold increase was found in the volume of both the cysts and corpus luteum in the estradiol group. Conclusion: The structural changes of the ovary were most pronounced in the letrozole-treated animals.

• Clinical and Experimental Reproductive Medicine
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• 제36권4호
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• pp.255-263
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• 2009

목 적: 한국 가임기 여성의 다낭난소증후군 진단시에 복식 초음파를 이용하는 방법의 유용성과 정확도를 분석하여 국내 다낭난소증후군의 진단 기준 마련에 도움이 되고자 하였다. 연구방법: 이화여자대학교 목동병원에서 선별설문조사를 받은 15~44세 여성 8,793명에서 복식 초음파를 시행한 총 701명 중, 정상 월경을 하면서 안드로겐 과다 및 초음파의 다낭난소 소견이 없는 정상 대조군에서 복식 초음파를 시행한 185명과 초음파 검사 소견을 제외하고 NIH 진단 기준으로 다낭난소증후군을 진단 받은 248명의 환자에서 복식 초음파를 시행한 소견을 ROC (receiver operating characteristic) 곡선 분석하였다. 결 과: 정상 대조군의 평균 연령은 $23.64{\pm}4.26$세로 복식 초음파로 측정된 평균 난소 부피는 $6.03{\pm}1.89\;cm^3$, 평균 난포 개수는 $6.49{\pm}1.93$개였다. 복식 초음파를 진단에 사용할 경우 난소 부피를 이용하면 AURC (area under the ROC curve)가 0.761로 난소 부피>$9\;cm^3$ 기준일 때, 민감도 51.0%, 특이도 91.4%였다. 난포 개수에 대한 AURC는 0.733으로 ${\geq}9$개 기준일 때, 민감도 54.9%, 특이도 87.0%였으며, 난포 개수 ${\geq}10$개 기준일 때, 민감도 53.2%, 특이도 90.4%였다. 복식 초음파로 난소 부피와 난포 개수를 검사하여 다낭난소증후군의 선별 진단에 이용하기에는 부적합하였다. 결 론: 복식 초음파를 이용하여 다낭난소증후군을 진단하는 방법은 유용성과 정확도에서 신뢰할만하지 못하다.

• Reproductive and Developmental Biology
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• 제35권3호
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• pp.273-280
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• 2011

It was conducted the experiment, divided into three groups as normal, poor and polycystic ovary syndrome, to detect the change of protein patterns in follicular fluid on ovarian response following controlled ovarian hyperstimulation for human IVF outcome. In the normal group, it was confirmed reproducible 57 spots in the detected total 81 spots. Then 1 spot was not found in the other groups. In the poor responder group, it was found reproducible 53 spots in the detected total 98 spots. 6 spots were down-regulation and 7 spots were up-regulation comparable with normal group. There were not 5 spots in poor responder group comparable with other groups. In the polycystic ovary syndrome group, it was expressed reproducible 53 spots in the detected total 80 spots and 3 spots were just expressed in this group. However, 4 spots were not found in polycystic ovary syndrome. 9 spots were up-regulation comparable with normal group. Significant up and down-regulation spots among the each groups were identified. The results were a cytosolic carboxypeptidase, a signal-induced proliferation-associated protein 1, a ceruloplasmin, a keratin(type II cytoskeletal 1), a polypeptide N-acetylgalactosantinyltransferase 2, a serine/threonine-protein phosphatase 4 regulatory subunit 4. It was identified that 8 spots, 6 kinds of protein are corresponded with NCBInr database research, but 10 spots were failed in the identification. In conclusion, it has been confirmed change and expression of protein on the ovarian response following COH of human.

• Clinical and Experimental Reproductive Medicine
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• 제39권1호
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• pp.22-27
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• 2012

Objective: To evaluate the effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase (MDP-EL) in comparison with standard GnRH agonist luteal long protocol (LP) in each non-obese and obese polycystic ovary syndrome (PCOS) women undergoing IVF. Methods: Two hundred eleven infertile women with PCOS were recruited and randomized to undergo either GnRH antagonist MDP-EL (antagonist group) or standard GnRH agonist luteal LP (agonist group). IVF cycle outcomes were compared between the two groups. Results: Total dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the antagonist group than in the agonist group. Incidence of severe ovarian hyperstimulation syndrome was significantly lower in the antagonist group. However, IVF and pregnancy outcomes were similar in the two groups. When all subjects were divided into non-obese and obese subgroups, in non-obese PCOS subgroup, IVF and pregnancy outcomes were comparable in the antagonist and agonist groups but total dose and days of rhFSH were also significantly fewer in the antagonist group. Similar findings were also observed in obese PCOS subgroup. Conclusion: GnRH antagonist MDP-EL is at least as effective as GnRH agonist LP and may be a more patient-friendly alternative in controlled ovarian stimulation for PCOS patients undergoing IVF, independent of body mass index.

• Clinical and Experimental Reproductive Medicine
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• 제39권4호
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• pp.166-171
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• 2012

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.

• Clinical and Experimental Reproductive Medicine
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• 제41권2호
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• pp.80-85
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• 2014

Objective: To investigate: the prevalence of vitamin D deficiency in Korean women with polycystic ovary syndrome (PCOS), and the relationship between vitamin D status and clinical or metabolic features in this group. Methods: We recruited 38 women with PCOS using the Rotterdam criteria. A total of 109 premenopausal control women were matched with patients based on age and body mass index. Serum 25-hydroxy vitamin D concentrations less than 20 ng/mL were classified as frank vitamin D deficiency. Since vitamin D may play a significant role in metabolic disturbances in women with PCOS, correlations between clinical or metabolic parameters and vitamin D status were analyzed separately in patients and controls. Results: Women with PCOS showed no differences in the level of 25-hydroxy vitamin D ($19.6{\pm}6.6ng/mL$ in patients vs. $20.1{\pm}7.4ng/mL$ in controls, respectively, p=0.696) or prevalence of vitamin D deficiency (57.9% in patients vs. 56.5% in controls, respectively, p=0.880). In addition, we did not find any correlations between serum vitamin D level and clinical or metabolic profiles in either PCOS patients or controls. Conclusion: Our study found no differences in the absolute level of serum vitamin D between PCOS patients and matched controls. Prevalence of vitamin D deficiency was equally common among both patients and controls. Additionally, we did not find any correlations between serum vitamin D level and clinical or metabolic profiles, suggesting that the role of vitamin D in the pathogenesis of PCOS is not yet clear.

• Clinical and Experimental Reproductive Medicine
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• 제44권1호
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• pp.33-39
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• 2017

Objective: The aim of this study was to assess the changes of follicular fluid (FF) and serum levels of cerebellin precursor protein 1 (cbln1) and betatrophin in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with a gonadotropin-releasing hormone (GnRH) antagonist protocol. Methods: Twenty infertile women with PCOS and 20 control women diagnosed as poor responders undergoing ovarian stimulation with a GnRH antagonist were included. Blood samples were obtained during ovum pick-up. Follicular fluid from a dominant follicle was collected from the subjects. Using enzyme-linked immunosorbent assays, FF and serum levels of cbln1 and betatrophin were measured in both groups of participants. Metabolic and hormonal parameters were also determined and correlated with each other. Results: Both groups of women had similar serum and FF betatrophin levels ($55.0{\pm}8.9ng/mL$ vs. $53.1{\pm}10.3ng/mL$, p=0.11). The serum and FF betatrophin levels of poor responders were found to be similar ($49.9{\pm}5.9ng/mL$ vs. $48.9{\pm}10.7ng/mL$, p=0.22). Conversely, the FF cbln1 levels of PCOS women were found to be significantly higher than the serum cbln1 levels ($589.1{\pm}147.6ng/L$ vs. $531.7{\pm}74.3ng/L$, p<0.02). The FF cbln1 levels of control participants without PCOS were significantly higher than their serum cbln1 levels ($599.3{\pm}211.5ng/L$ vs. $525.3{\pm}87.0ng/L$, p=0.01). Positive correlations were detected among body mass index, insulin resistance, serum insulin, total testosterone, and betatrophin levels in the PCOS group. Conclusion: Follicular fluid betatrophin and cbln1 concentrations may play a pivotal role on follicular growth in PCOS subjects undergoing IVF/ICSI with an antagonist protocol.

• Clinical and Experimental Reproductive Medicine
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• 제43권2호
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• pp.82-89
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• 2016

Objective: The long interspersed elements (LINE-1, L1s) are a group of genetic elements found in large numbers in the human genome that can translate into phenotype by controlling genes. Growing evidence supports the role of epigenetic in polycystic ovary syndrome (PCOS). The purpose of this study is to evaluate the DNA methylation levels in LINE-1 in a tissue-specific manner using cumulus cells from patients with PCOS compared with normal controls. Methods: The study included 19 patients with PCOS and 22 control patients who were undergoing controlled ovarian hyperstimulation. After oocyte retrieval, cumulus cells were extracted. LINE-1 DNA methylation levels were analysed by bisulfite treatment, polymerase chain reaction, and restriction enzyme digestion. The Connection Up- and Down-Regulation Expression Analysis of Microarrays software package was used to compare the gene regulatory functions of intragenic LINE-1. Results: The results showed higher LINE-1 DNA methylation levels in the cumulus cells of mature oocytes in PCOS patients, 79.14 (${\pm}2.66$) vs. 75.40 (${\pm}4.92$); p=0.004, but no difference in the methylation of cumulus cells in immature oocytes between PCOS and control patients, 70.33 (${\pm}4.79$) vs. 67.79 (${\pm}5.17$); p=0.155. However, LINE-1 DNA methylation levels were found to be higher in the cumulus cells of mature oocytes than in those of immature oocytes in both PCOS and control patients. Conclusion: These findings suggest that the epigenetic modification of LINE-1 DNA may play a role in regulating multiple gene expression that affects the pathophysiology and development of mature oocytes in PCOS.

• Clinical and Experimental Reproductive Medicine
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• 제43권2호
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• pp.126-132
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• 2016

Objective: The purpose of this study was to identify useful clinical factors for the identification of patients with polycystic ovary syndrome (PCOS) who would benefit from in vitro maturation (IVM) treatment without exhibiting compromised pregnancy outcomes. Methods: A retrospective cohort study was performed of 186 consecutive patients with PCOS who underwent human chorionic gonadotropin-primed IVM treatment between March 2010 and March 2014. Only the first IVM cycle of each patient was included in this study. A retrospective case-control study was subsequently conducted to compare pregnancy outcomes between IVM and conventional in vitro fertilization (IVF) cycles. Results: Through logistic regression analyses, we arrived at the novel finding that serum $anti-M{\ddot{u}}llerian$ hormone (AMH) levels and the number of fertilized oocytes in IVM were independent predictive factors for live birth with unstandardized coefficients of 0.078 (95% confidence interval [CI], 1.005-1.164; p=0.037) and 0.113 (95% CI, 1.038-1.208; p=0.003), respectively. Furthermore, these two parameters were able to discriminate patients who experienced live births from non-pregnant IVM patients using cut-off levels of 8.5 ng/mL and five fertilized oocytes, respectively. A subsequent retrospective case-control study of patients with PCOS who had serum AMH levels ${\geq}8.5ng/mL$ showed that IVM had pregnancy outcomes comparable to conventional IVF, and that no cases of ovarian hyperstimulation syndrome were observed. Conclusion: Serum AMH levels are a useful factor for predicting pregnancy outcomes in PCOS patients before the beginning of an IVM cycle. IVM may be an alternative to conventional IVF for PCOS patients if the patients are properly selected according to predictive factors such as serum AMH levels.

• Clinical and Experimental Reproductive Medicine
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• 제40권2호
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• pp.100-105
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• 2013

Objective: The aim of this study was to investigate the effect of insulin sensitizing agents on hormonal and metabolic parameters as well as menstrual patterns in women with polycystic ovary syndrome (PCOS). Methods: One hundred and twenty-three patients with PCOS were included. Metformin was administered to patients at 1,500 mg or 1,700 mg daily for 3 months. If the patients had no improvement of the menstrual cycle or metformin-related adverse effects developed, the patients changed medication to a daily dose of either 15 mg pioglitazone or up to 45 mg. Then resumption of a regular menstrual cycle or recovery of ovulation was evaluated. Hormonal and metabolic profiles were compared between the response and non-response group to insulin sensitizing agents. Results: One hundred and five patients with PCOS were treated with metformin for 3 months. Forty-eight patients (45.7%) showed improvement of menstrual cycle regularity after 3 months of metformin use, whereas 57 patients (54.3%) had no change. The mean free testosterone measured after 3 months of treatment was significantly lower in metformin responders than in non-responders. The other parameters did not differ between the groups. Of the 23 patients who used pioglitazone for 3 to 6 months, 19 patients (82.6%) showed improvement in their menstrual cycles. Conclusion: Metformin treatment seems to be effective for the improvement of menstrual cyclicity irrespective of insulin resistance in women with PCOS. When metformin related adverse effect occurred, pioglitazone would be effective for aiding the resumption of the menstrual cycle.