Comparison of Expression of Endometrial Prolactin in infertile Women with Luteal Phase Defect According to Clomiphene Citrate Administration / 대한불임학회지

OBJECTIVE Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citrate-treated infertile women with luteal phase defect. METHODS: The endometrial samples from infertIle women wIth luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. RESULTS: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). CONCLUSION: in this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

Expression of Genes Related to Multidrug Resistance and Apoptosis in Human Ovarian Cancer Cell Lines, Sensitive and Resistant to Cisplatin / 대한산부인과학회잡지

OBJECTIVE: The resistance mechanisms of tumor cells to chemotherapeutic drugs are known as the followings; the alterations in the drug transport and activation, the enhanced expression of the DNA repair and replication and the decreased apoptosis. The aim of this study is to examine a relative difference on the level of the mRNA expression of the multidrug resistance (MDR)-related and the apoptosis-associated genes between cisplastin-sensitive and cisplatin-resistant human ovarian cancer cell line. METHODS: MDR-associated genes (lrp, mdr1/p-glycoprotein, mrp) and PKC isozymes (alpha, beta1, beta2, epsilon, eta, theta), DNA mismatch repair (MMR) genes (hMLH1, hMSH2, hMSH3, hMSH6), DNA topology-related genes (topoisomerase IIalpha and beta) and apoptosis-related genes (p53, p21, mdm2, fas (Apo-1), trail (Apo-2L) were analyzed in cisplatin-sensitive ovarian cancer cell line A2780 and -resistant cell line A2780cp by complementary DNA polymerase chain reaction. RESULTS: The mdr1 and PKC eta in mRNA level were expressed in A2780cp, but not in A2780. The mRNA expressions of lrp, p21 and mdm2 were more increased in A2780cp than drug sensitive variant A2780, but not significantly correlated. In contrast mRNA expression of hMLH1, a kind of DNA MMR gene, was remarkably decreased and mRNA expression of hMSH2 was slightly decrease in A2780cp. However, the levels of mrp, topo II alpha and beta, hMSH3, hMSH6, p53, fas and trail were not affected. CONCLUSION: These results showed that mdr1/p-gp expression may be an important determinant of MDR phenotype in resistant cell line to chemotherapeutic agents, and PKC isozymes and DNA MMR genes may be responsible for cisplatin resistant in ovarian cancer.

A Case of Primary Carcinoma of the Fallopian Tube / 대한산부인과학회잡지

Primary carcinoma of the fallopian tube is very rare and accounts for less than 1% of all gynecologic malignancies. Nonspecific symptoms are presented, so primary carcinoma of the fallopian tube was confirmed postoperatively on the basis of the pathologic examination. The evaluation and treatment are similar to that of the ovarian cancer. We have experienced a case of primary carcinoma of the fallopian tube, especially fimbrial portion and report with a brief review of the literature

A Case of Huge Ovarian Tumor Associated with Hypothyroidism / 대한산부인과학회잡지

In adult women, hypothyroidism has significant effect on reproduction. Hypothyroidism is associated with oligomenorrhea, amenorrhea, anovulation, hypermenorrhea, menorrhagia, infertility, spontaneous abortion, stillbirth or preterm delivery. It can cause ovarian tumor, which clinically resembles ovarian hyperstimulation syndrome or multicystic ovarian tumor. We have experienced a case of spontaneously regressed huge ovarian tumor which was found in patient. With hypothyroidism. So we report this case with a brief review of literature.

Expression of Leukemia Inhibitory Factor (LIF) in the Clomiphene Citrate Treated Infertile Women with Luteal Phase Defect / 대한산부인과학회잡지

OBJECTIVE: Although the regulation of implantation is not clearly understood, recent studies have revealed that many cytokines and growth factors play an essential role in preimplantation endometrial development. Among the cytokines, the expression of leukemia inhibitory factor (LIF) is absolutely essential for implantation, although its precise role is not fully understood. Clomiphene citrate is most commonly used drug in the treatment of infertility, but pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to the antiestrogenic effect of it on the cervical mucus and endometrium. The our purpose was to evaluate the endometrial expression of LIF in clomiphene citrate treated infertile women with luteal phase defect and association of clomiphene citrate and unsatisfactory endometrial development. METHODS: The endometrial samples from women with luteal phase defect (n=27) were examined. The endometrial tissue was obtained during secretory phase in 5 cases, and during proliferative phase in 6 cases without clomiphene citrate treatment. In 16 cases, the endometrial tissue was obtained by biopsy during secretory phase after clomiphene citrate treatment. Immunohistochemical staining was performed for LIF in the endometrial tissues. And then the expression of LIF was compared between clomiphene citrate treatment group and no treatment group during secretory phase, and secretory and proliferative phase were compared in the no treatment group. RESULTS: The endometrial expression of LIF was not significantly different between clomiphene citrate treated group and no treated group (p. value=0.123) and between proliferative phase and secretory phase without clomiphene citrate (p. value=0.306). The expressions of LIF were detected mostly in glandular epithelial cells and not in the stromal cells. CONCLUSION: We demonstrated that LIF was expressed in glandular epithelial cells rather than stromal cells and there was not menstrual cycle dependent difference of endometrial expression of LIF in infertile women with luteal phase defect. And our finding suggested that clomiphene citrate did not affect the secretory phase endometrial expression of LIF in infertile women with luteal phase defect.

Effects of Coculture of Vero Cells on the Development of Frozen-thawed Two-cell Stage ICR Mouse Embryos / 대한산부인과학회잡지

OBJECTIVE: The rate of developmental progression of frozen-thawed embryos is lower than that of nonfrozen embryos in mice, cows, humans and other mammalians. This study was designed and performed to evaluate the beneficial effects of coculture of Vero cells on the development of frozen-thawed two-cell stage embryos of ICR strain mice. MATERIASL AND METHODS: The late two-cell stage mouse embryos were obtained from oviducts of 5~6 week old mated ICR mice superovulated with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Two-cell stage mouse embryos were frozen slowly with 1,2-propanediol and sucrose as cryoprotectants and thawed rapidly, followed by stepwise dilution. The frozen-thawed embryos were cultured in Ham's F-10+10% Fetal Bovine Serum (FBS) basal culture medium with and without Vero cells. The rates of development in both groups were compared every 24 hours for 5 days. RESULTS: Vero cells did not significantly stimulate the rate of embryonal development compared to controls at 24 hours after culture, 124 (69.3%) and 68 (61.3%), respectively (p=0.161). On day 4, however, 55 (30.7%) cocultured embryos had developed to expanded-hatching blastocysts, which was the significantly higher number than that of the embryos in controls: 16 (14.4%) (p=0.002). In addition, more embryos in coculture developed to hatching-hatched blastocysts (43[24.0%]) compared to the controls (10[9.0%]) (p=0.001). CONCLUSION: Coculture of cryopreserved embryos after thawing with Vero cells seems to be an useful tool to remove the postthaw deleterious effects of freezing and to obtain better quality embryos appropriate for transfer. These beneficial effects of Vero cell coculture appear to become more prominent as the embryonic development progresses over time.

Accuracy of Cervical Pap Smear / 대한부인종양콜포스코피학회잡지

BACKGROUND: Carcinoma of the uterine cervix is a theoretically preventable disease because its precursor lesions can be detected by cervical Papanicolau smears and appropriately treated, Although cervical cytology screening programmes have resulted in the redution of cervical cancer incidence and mortality, Pap smear have been subjected to intense scrutiny and criticism in recent years. The focus of criticism has been the false-negative Pap smear, and the false-negative Pap smear is the major quality issue currently facing the physicians. To reduce the false-negative rate of Pap smear, it is essential to improve the accuracy of Pap smear. But false-negative rate of Pap smear has been reported variously. OBJECTIVE: This study was undertaken to evaluate accuracy of Pap smear by study false-negative and false-positive rate of Pap smear and to determine whether false-negative and false-positive rate had any correlations with clinical factors. STUDY DESIGN: The study population was comprised of 346 women, who were undertaken gynecologic operation at the Department of Obstetrics & Gynecology at Hanyang University hospital between March, 1997 and April, 1998. All patients were taken Pap smear before operation. In 93 women of these, preoperative diagnosis were cervical intraepithelial neoplasia and carcinoma in situ of uterine cervix, and in 253 women of these, preoperative diagnosis were benign disease as uterine myoma or adenomyosis, etc. All of their surgical specimen were examined. Pap smear, pathology, medical charts of all patients were reviewed retrospectively, and false-negative rate and false-positive rate were calculated. Clinical factors that associated with false-negative and false-positive rate were evaluated. Fishers exact test and Pearson chi-square test were used of statistical analysis, RESULTS: False-negative rate of Pap smear was 7.2%, false-positive rate was 4.6%, corresponding rate with histology was 88.2%. Sensitivity and specificity of PAP smear were 87.0% and 97.0% respctively. According to gross finding of uterine cervix, erosion was 46.6% in cervical intraepithelial neoplasia, 67.8% in carcinoma in situ, 66.6% in microinvasive carcinoma of uterine cervix and 55.3% of 103 erosion findings was cervical intraepithelial neoplasia, carcinoma in situ or microinvasive carcinoma. 23.1% of cervical lesion were normal gross finding. Menopause was associated with false-negative rate and previous vaginal infection history, previous cervical minor operation, delivery mode, contraception method, pelvic inflammatory disease history, vaginal bleeding at Pap smear and gross finding of cerbix were not associated. There were no clinical factors that were associated with false-positive rate. CONCLUSION: Compared with other reports, false-negative rate(7.2%) and false-positive rate(4.6%) of Pap smear was lower and corresponding rate(88.2%) was higher in Hanyand university hospital. Because of higher false-negative rate in menopausal women, it need more careful to take and interpretate Pap smear in these group.

A Case Successive Ovulation Induction with an Extended Therapy of Clomiphene in a Patient with Clomiphene-resistant Anovulatory Disorders / 대한산부인과학회잡지

Clomiphene citrate is the simplest and least expensive from of ovulation induction therapy. In most cases, women who fail to ovulate in response to maximal doses of clomiphene became candidates for treatment with gonadotropins or pulsatile GnRH. Recently, as an alternative to the use of gonadotropins and ovarian surgery, there are some studies of the effectiveness of extended duration clomiphene among the anovulatory women who were resistant to a standard 5-day course of treatment with clomiphene. We have experienced a case of successive ovulation induction and pregnancy with an extended 10-day course of clomiphene in women with clomiphene-resistant anovulatory disorders and reproted with brief reviews of related literatures.