• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.355-362
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• 1999

Objective: This study was performed to compare the clinical response to controlled ovarian hyperstimulation (COH) of in vitro fertilization and embryo transfer (IVF-ET) according to the size of baseline ovarian cyst. Method: From February 1992 to March 1999, a retrospective analysis was done of 272 cases who underwent COH using mid-luteal phase long protocol of gonadotropin-releasing hormone agonist (GnRH-a) for IVF-ET. These cases were divided into four group; group 1 (n=63) had cysts with mean diameters between 20.0 and 29.0 mm on their baseline ultrasound on cycle day 3, group 2 (n=57, $30.0{\sim}49.0mm$), group 3 (n=68, >50.0 mm) and control group (n=84). Cases were excluded according to the following criteria; pure male factor infertility, the presence of only one ovary, high CA-125 level and previous endometriosis. Results: There were no statistically significant differences between cases with baseline ovarian cyst <50.0 mm in diameter and control group in any of the parameters. However, cases with baseline ovarian cyst>50.0 mm in mean diameter needed more amount of human menopausal gonadotropin (hMG), showed significantly lower estradiol ($E_2$) level, the number of follicle >15.0 mm on the day of human chorionic gonadotropin (hCG) administration, the number of oocytes retrieved, the number of mature oocytes, and pregnancy rate compared with control group. Conclusion: This study suggests that cases with baseline ovarian cyst <50.0 mm in diameter do not adversely impact on IVF-ET outcome. However, cases with baseline ovarian cyst >50.0 mm in diameter had adverse effects on various parameters. Therefore, to improve the outcome of IVF-ET in these cases, ovarian cyst aspiration prior to initiating COH may be required.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3997-4000
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• 2012

MicroRNAs (miRNAs) play roles in the clinic, both as diagnostic and therapeutic tools. The identification of relevant microRNAs is critically required for ovarian cancer because of the prevalence of late diagnosis and poor treatment options currently. To identify miRNAs involved in the development or progression of ovarian cancer, we analyzed gene expression profiles downloaded from Gene Expression Omnibus. Comparison of expression patterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 508 genes that were commonly up-regulated and 1331 genes that were down-regulated in the cancer specimens. Function annotation of these genes showed that most of the up-regulated genes were related to cell cycling, and most of the down-regulated genes were associated with the immune response. When these differentially expressed genes were mapped to MiRTarBase, we obtained a total of 18 key miRNAs which may play important regulatory roles in ovarian cancer. Investigation of these genes and microRNAs should help to disclose the molecular mechanisms of ovarian carcinogenesis and facilitate development of new approaches to therapeutic intervention.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1145-1148
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• 2014

Background: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 $mg/m^2$ every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

• Reproductive and Developmental Biology
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• v.35 no.3
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6973-6979
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• 2015

Background: Ovarian cancer is the third most common cause of cancer in Indian women. Despite an initial 70-80% response rate, most patients relapse within 1-2 years and develop chemoresistance. Hence, identification or repositioning of drugs to resensitise ovarian cancer cells to existing chemotherapy is needed. Traditionally immortalized cell lines have been used in research, but these may contain genetic aberrations and chromosomal abnormalities serving as poor indicators of normal cell phenotype and progression of early-stage disease. The use of primary cells, maintained for only short periods of time in vitro, may serve as the best representative for studying in vivo conditions of the tissues from which they are derived. In this study we have attempted to evaluate the effect of metformin (an antidiabetic drug) in primary ovarian cancer cells because of its promising effect in other solid tumours. Materials and Methods: Primary cultures of epithelial ovarian cancer cells established from ascitic fluid of untreated ovarian cancer patients were used. The cells were treated with metformin at doses standardized by MTT assay and its ability to induce apoptosis was studied. The cells were analysed for apoptosis and apoptosis related proteins by flow cytometry and western blotting respectively. Results: Metformin induced apoptosis in ovarian cancer cells, provoking cell cycle arrest in the G0/G1 and S phase. It induced apoptosis in ovarian cancer cells by, down-regulating Bcl-2 and up-regulating Bax expression. Conclusions: Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins. These data are relevant to ongoing translational research efforts exploring the chemotherapeutic potential of metformin.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7193-7196
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• 2013

Ovarian cancer patients need a surveillance program for the detection of tumor progression after completion of treatment. The methods generally consist of history taking, physical examination, tumor marker monitoring and imaging. However, the details of recurrence detection with each method are not well defined. To clarify this issue, ovarian cancer patients who achieved complete or partial responses and developed tumor progression at the follow up time between January 2004 and December 2010 in University Hospital Chiang Mai, Thailand, were reviewed. Clinical data, CA 125 level and imaging results at the tumor progression time were recorded and analyzed. There were 144 ovarian cancer patients meeting the inclusion criteria with the mean age of 51 years and 62.5% of them were in an advanced stage. Complete response was achieved in 89 patients (61.8%) after primary treatment. The median progression free survival and overall survival were 15.5 months and 37.5 months, respectively. Abnormal symptoms presented in 49.3% of the studied patients and 59.7% developed physical examination abnormalities. In addition, CA 125 was elevated in 89.6% while in 74.3% of tumor progression was identified by CT-scan. Short treatment time period and a high level of CA 125 were significant independent prognostic factors in these patients. In conclusion, careful history taking, physical examination and monitoring of CA 125 levels are important methods for tumor progression detection in a surveillance program for epithelial ovarian cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8121-8125
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• 2014

Background: Ovarian mucinous carcinoma has a poor prognosis in advanced stages and a poor response to conventional chemotherapy. An efficient treatment is not yet available. We heere investigated HER2 expression and the potential for trastuzumab therapy in ovarian mucinous tumors. Materials and Methods: Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tissue from 27 ovarian mucinous tumors including 14 carcinomas and 13 borderline tumors diagnosed in the Pathology Department, Farhet Hached Hospital, Sousse, between 1993 and 2013. The HercepTest (DAKO) was used for immunohistochemistry. Results: HER2 expression was observed in only one borderline tumor (7.7%) and in 14.3% of mucinous carcinomas of the ovary. Conclusions: Our results suggest that trastuzumab therapy would be an option for patients with mucinous carcinoma when the tumor has HER2 overexpression.

• Clinical and Experimental Reproductive Medicine
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• v.47 no.3
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• pp.207-212
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• 2020

Objective: Glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) is a subunit of a ligand-gated ion channel that regulates the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by controlling the release of gonadotropin-releasing hormone. Few studies have investigated the association between the GRIA1 gene and human infertility. This study evaluated the association of the GRIA1 rs548294 C > T and rs2195450 G > A polymorphisms with the ovarian response to human menopausal gonadotropin (HMG) in Iranian women. Methods: One hundred women with histories of at least 1 year of infertility were included. On the second day of menstruation, patients were injected with HMG; on the third day, blood samples were collected. After hormonal analysis, the GRIA1 rs548294 C > T and rs2195450 G > A genotypes of samples were identified via the restriction fragment length polymorphism method, and on day 9, the number of follicles was assessed via ultrasound. Results: For the GRIA1 rs548294 C > T and rs2195450 G > A single nucleotide polymorphisms, the subjects with CT and GG genotypes, respectively, displayed the highest mean FSH level, LH level, and number of follicles on day 9 of the menstrual cycle (p< 0.05). Significant positive correlations were observed between LH and FSH (p< 0.01), LH and follicle count (p< 0.01), FSH and age (p< 0.05), follicle count and age (p= 0.048), and FSH and follicle count (p< 0.01). Conclusion: This study showed a significant relationship between GRIA1 polymorphisms and ovarian response to the induction of ovulation. Therefore, determining patients' GRIA1 genotype may be useful for improving treatment and prescribing suitable doses of ovulation-stimulating drugs.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.1
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• pp.69-79
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• 2021

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART. Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing. Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively). Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

• Clinical and Experimental Reproductive Medicine
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• v.51 no.2
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• pp.158-162
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• 2024

Objective: The aim of this study was to compare the outcomes of in vitro fertilization (IVF) in patients with a poor ovarian response who used methyltestosterone, versus those using a placebo, in an infertility clinic setting. Methods: This clinical trial included 120 women who had undergone IVF with intracytoplasmic sperm injection due to poor ovarian reserve and infertility. The study took place at the Yas Infertility Center in Tehran, Iran, between January 1, 2018 and January 1, 2019. In the intervention group, 25 mg of methyltestosterone was administered daily for 2 months prior to the initiation of assisted reproductive treatment. The control group was given placebo tablets for the same duration before starting their cycle. Each group was randomly assigned 60 patients. All analyses were performed using SPSS ver. 23 (IBM Corp.). Results: The endometrial thickness in the intervention group was 7.57±1.22 mm, whereas in the control group, it was 7.11±1.02 (p=0.028). The gonadotropin number was significantly higher in the control group (64.7±13.48 vs. 57.9±9.25, p=0.001). However, there was no significant difference between the two groups in the antral follicular count. The chemical and clinical pregnancy rates in the intervention group were 18.33% and 15% respectively, compared to 8.33% and 6.67% in the control group. The rate of definitive pregnancy was marginally higher in the intervention group (13.3% vs. 3.3%, p=0.05). Conclusion: The findings of this study suggest that pretreatment with methyltestosterone significantly increases endometrium thickness and is associated with an increase in the definitive pregnancy rate.