OBJECTIVES: The purpose of this study is to investigate the expression of CDK (Cyclin dependent kinase) inhibitor, p57(kip2) in human ovarian corpus luteum, benign and malignant ovarian tumors. METHODS: 46 women undergoing laparoscopic surgery or laparotomy for ovarian tumors were enrolled. Total 46 formalin-fixed, paraffin-embedded sections of corpus luteum, benign and malignant ovarian tumors were stained by immunohistochemistry for expression of p57(kip2). RESULTS: p57(kip2) was stained in theca cell of growing follicle but not induced in human corpus luteum. There was the expression of p57(kip2) in mature teratoma, immature teratoma and endometrioma but not in epithelial ovarian tumors. CONCLUSIONS: These results showed that p57(kip2) expression may be not important in luteinization of the ovary and seemed not to play a role in development of epithelial ovarian tumors. However, it may involve pathogenesis of mature teratoma, immature teratoma and endometrioma.
Corpus Luteum ; Endometriosis ; Female ; Humans ; Immunohistochemistry ; Laparoscopy ; Laparotomy ; Lutein ; Luteinization ; Ovary ; Teratoma ; Theca Cells

OBJECTIVE: To evaluate the efficacy of GnRH antagonist multiple dose protocol (MDP) in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) comparing with the standard GnRH agonist long protocol (GnRH-a LP). METHODS: From January 2000 to September 2002, 57 infertile women with tubal factor alone who had undergone IVF-ET were enrolled in the present study. Study group consisted of 28 patients in 28 cycles in which GnRH antagonist Cetrorelix 0.25 mg was given daily when the leading follicle reached 14 mm in mean diameter until the human chorionic gonadotropin (hCG) injection. Control group consisted of 29 patients in 29 cycles in which COH was performed using standard GnRH-a luteal LP. RESULTS: Patient's characteristics were comparable in both groups. Premature luteinization was not developed in all patients in each group. The number of ampules and duration of exogenous gonadotropins required were significantly lower in the study group than those in the control group (p<0.05; p<0.001, respectively). There were no significant differences in the number of follicles >or=14 mm diameter on the day of hCG injection, the number of oocytes retrieved, fertilization rate, and the number of grade I, II embryos between the two groups, but the numbers of mature oocytes retrieved and fertilized oocytes were significantly lower in the study group than in the control group (p<0.01, p<0.01). The clinical pregnancy rate seemed to be lower in the study group, but the difference did not achieve significance (28.6% vs 34.5%). There were also no differences in the miscarriage rate and multiple pregnancy rate between the two groups. CONCLUSION: This study demonstrates that GnRH antagonist Cetrorelix MDP can result in the comparable pregnancy outcome as the GnRH-a LP and furthermore reduce the total dose of gonadotropins and duration of stimulation.
Abortion, Spontaneous ; Chorionic Gonadotropin ; Embryo Transfer* ; Embryonic Structures* ; Female ; Fertilization ; Fertilization in Vitro* ; Gonadotropin-Releasing Hormone* ; Gonadotropins ; Humans ; Lutein ; Luteinization ; Oocytes ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Pregnancy, Multiple

Sex cord-stromal tumors of the ovary are the third most common types of neoplasms that develop in the ovary and account for about 5-8% of all ovarian malignancies. Juvenile granulosa cell tumor (JGCT) is one of the sex cord-stromal tumors of the ovary has distinct differences from adult granulosa cell tumor (AJCT) with regard to clinical and pathological features as well as biological behavior most frequently occuring in the first two decades of life. Usually Call-exner bodies are rare, and luteinization is frequent in JGCT. The tumor may be solid, cystic, or both. In premenarcheal girls, juvenile granulosa cell tumor usually (82%) elicits the signs of sexual precocity. The tumor should removed as soon as the diagnosis is established. Surgery is the best treatment choice for low stage juvenile granulosa cell tumor in children, but for those with high stage juvenile granulosa cell tumor or recurrent tumor, the best treatment and sensitivity of tumor to radiation therapy and chemotherapy have not yet been determined clearly. About 90% are diagnosed in early stage so, prognosis of juvenile granulosa cell tumor in children is good in most cases, but tumor with more advanced stage has worse clinical outcome correlated with its stage, presence of ruptures, grade of nuclear atypia, degree of mitotic activity. And the clinical stage at the time of diagnosis is considered most important prognostic factor. We experienced a case of ruptured juvenile granulosa cell tumor so, we present a case with brief review of literature.
Adult ; Child ; Diagnosis ; Drug Therapy ; Female ; Granulosa Cell Tumor* ; Granulosa Cells* ; Humans ; Lutein ; Luteinization ; Ovary ; Prognosis ; Rupture ; Sex Cord-Gonadal Stromal Tumors

Juvenile granulosa cell tumor (JGCT) is one of the sex cord stromal tumors of the ovary ocurring in the first two decades of life. These tumors are different from adult granulosa cell tumor (AJCT) with regard to clinical and pathological fetures. Follicles are often irregular, Call-exner bodies are rare, and luteinization is frequent. The tumor may be solid, cystic, or both. The most common presenting symptoms are abnormal uterine bleeding and pain. Breast swelling, pain and tenderness may also be associated with unopposed estrogen secretion by granulosa cell tumors. The tumor should be removed as soon as the diagnosis is estabilished. The juvenile granulosa cell tumor has a good overall prognosis because fewer than 5% of these tumors in children are malignant.
Adult ; Breast ; Child ; Diagnosis ; Estrogens ; Female ; Granulosa Cell Tumor* ; Granulosa Cells* ; Humans ; Lutein ; Luteinization ; Ovary* ; Prognosis ; Sex Cord-Gonadal Stromal Tumors ; Uterine Hemorrhage

OBJECTIVE: The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol. METHODS: This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. RESULTS: The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group (17.3+/-7.2 vs. 11.0+/-7.2; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. CONCLUSION: Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer.
Cardiopulmonary Resuscitation ; Chorionic Gonadotropin ; Embryo Transfer ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone* ; Humans ; Lutein* ; Luteinization* ; Oocytes ; Ovulation Induction* ; Pregnancy ; Pregnancy Outcome* ; Pregnancy Rate ; Pregnancy* ; Progesterone ; Prospective Studies ; Spermatozoa

Dynamic changes in steroidogenesis occur in ovarian granulosa cells during ovulation after the LH surge. The ovulatory LH surge induces rapid up-regulation of steroidogenic acute regulatory (StAR) protein and rapid down-regulation of aromatase (Cyp19a1) in granulosa cells undergoing luteinization during ovulation. These rapid changes in StAR and Cyp19a1 gene expression after the LH surge efficiently facilitate progesterone production, which plays a crucial role in ovulation and the following luteinization. Recently, it has become clear that epigenetic regulation such as histone modifications and DNA methylation play a key role in gene expression through the chromatin remodeling of the promoter region. This study reports the in vivo evidence that epigenetic mechanisms including histone modifications, DNA methylation and chromatin remodeling are involved in the rapid changes of StAR and Cyp19a1 gene expression in granulosa cells undergoing luteinization during ovulation.
Aromatase ; Chromatin Assembly and Disassembly ; DNA Methylation ; Down-Regulation ; Epigenomics ; Female ; Gene Expression ; Granulosa Cells ; Histones ; Lutein* ; Luteinization* ; Ovulation ; Progesterone ; Promoter Regions, Genetic ; Up-Regulation

OBJECTIVE: Nitric oxide (NO) produced in ovary may contribute to follicle maturation, ovulation, oocyte maturation and luteinization. In this study, the effect of nitric oxide on the spontaneous maturation of mouse oocyte was observed. Method: The index of oocyte maturation was checked by the germinal vesicle breakdown (GVBD) and appearance of polar body (PB) under microscope in the denuded oocytes and oocyte-cumulus complexes (OCCs) from mouse ovarian follicles after 24 hours pregnant-mare serum gonadotropin treatment. RESULTS: The GVBD appeared 50 %, 1 hour and 80 %, 2 hrs after changes of oocytes from dibutyryl cAMP (dbcAMP, 0.5 mM) contained media into dbcAMP-free media. dbcAMP (0.5 mM) completely blocked the GVBD until 24 hrs but dbcGMP (5 mM) delayed the GVBD by 1 hr. Sodium nitroprusside, the NO generator, inhibited the GVBD dose-dependently at 2 hr incubation in denuded and OCCs. The appearance of GVBD was not different between control and dbcGMP or SNP in denuded oocytes and OCCs at 24 hrs incubation. The guanylate cyclase activity in denuded oocyte cytosol was not detected whereas the guanylate cyclase activity in OCCs cytosol was 1.3 nmole/min/mg protein which was increased about 3 times by SNP (100 micrometer). CONCLUSION: These results suggest that the NO in ovary may delay the spontaneous oocyte maturation in early stage by acting on the maturation signaling protein as well as guanylate cyclase.
Animals ; Bucladesine ; Cytosol ; Female ; Gonadotropins ; Guanylate Cyclase ; Lutein ; Luteinization ; Mice* ; Nitric Oxide* ; Nitroprusside ; Oocytes* ; Ovarian Follicle ; Ovary ; Ovulation ; Polar Bodies ; Staphylococcal Protein A

OBJECTIVE: To investigate outcomes of stimulated IVF cycles in which GnRH antagonist was omitted on the ovulation triggering day. METHODS: A total of 86 women who underwent controlled ovarian hyperstimulation with recombinant FSH and GnRH antagonist flexible multiple-dose protocols were recruited and prospectively randomized into the conventional group (group A) or cessation group (group B). The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading follicle reached 14 mm in diameter and was continuously administered until the hCG triggering day (group A, 43 cycles) or until the day before hCG administration (group B, 43 cycles). The maturity of oocytes, fertilization rate, embryo quality, and implantation and clinical pregnancy rates were evaluated. RESULTS: The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in group B than group A (2.5+/-0.9 vs. 3.2+/-0.8 ampoules, p<0.05). There was no premature luteinization in any of the subjects. The proportion of mature oocytes and fertilization rate were not significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs. 66.4%, respectively). There were no significant differences in the implantation or clinical pregnancy rates. CONCLUSION: Our prospective randomized study suggested that cessation of GnRH antagonist on the hCG administration day during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising its effects on pregnancy rates.
Embryonic Structures ; Estradiol ; Female ; Fertilization ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Humans ; Lutein ; Luteinization ; Oocytes ; Ovulation ; Ovulation Induction ; Pregnancy ; Pregnancy Rate ; Prospective Studies

OBJECTIVES: We investigated whether luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist (E/G-ant) priming protocol improves clinical outcomes in poor responders to controlled ovarian stimulation for in vitro fertilization (IVF)-embryo transfer, and identified underlying mechanisms. METHODS: This restrospective study consisted of 65 poor responders who underwent the E/G-ant priming protocol. Sixty-four other poor responders undergoing conventional protocols without pretreatment were included as the control group. Clinical outcomes were compared between 2 groups. RESULTS: The E/G-ant priming protocol group exhibited improvements over the control group in terms of the number of retrieved oocytes (3.58±2.24 vs. 1.70±1.45; P=0.000), mature oocytes (2.68±2.11 vs. 1.65±1.23; P=0.000), fertilized oocytes (2.25±1.74 vs. 1.32±1.26; P=0.001), good embryos (1.62±0.91 vs. 1.14±0.90, P=0.021). Day 3 follicle-stimulating hormone (FSH; 8.40±4.84 vs. 16.39±13.56; P=0.000) and pre-ovulation progesterone levels (0.67 vs. 1.28 ng/mL; P=0.016) were significantly higher in the control group than in the E/G-ant priming group. The overall rate of positive human chorionic gonadotropin tests was higher in the E/G-ant priming group than in the control group (32.3% vs.16.1%; P=0.039). Also, clinical pregnancy rate (26.2% vs. 12.5%; P=0.048) and the rate of live births (23.1% vs. 7.1%; P=0.023) were significantly higher in the E/G-ant priming group than in the control group. CONCLUSION: The E/G-ant priming protocol would lead to promising results in poor responders to IVF by suppressing endogenous FSH and by preventing premature luteinization.
Chorionic Gonadotropin ; Embryonic Structures ; Estrogens ; Fertilization in Vitro ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; In Vitro Techniques ; Live Birth ; Lutein ; Luteinization ; Oocytes ; Ovulation Induction ; Pregnancy Rate ; Progesterone

Pregnancy maintenance is dependent on the presence of a functional corpusluteum (CL) for a few weeks after implantation. However, the factors responsible for the rescue of the CL during earlypregnancy have not been fully clarified. This study was designed to evaluate whether the change in size of the CL ofearly pregnancy, serum concentration of progesterone, 17alpha-hydroxyprogesterone,or beta-hCG correlated with the gestational age or were predictive of pregnancyoutcome. We retrospectively analysed thirty-six women between 4~9 weeks' gestation. All women underwent transvaginal ultrasound measurement of the CL size andgestational sac(or crown-rump length). Blood was drawn from each patient on the day of the ultrasound examinationto measure hormone concentration. Fifteen women experienced vaginal bleeding and abdominal pain.Among them, four women were aborted. There was no significant positive correlation between CL size and serumprogesterone, 17alpha-hydroxyprogesterone or beta-hCG both in normal and abnormal pregnancy. A positive correlation was observed between the gestational age and progesterone orbeta-hCG in normal pregnancy, but not in abnormal pregnancy(threatened or spontanousabortion). In conclusion, close correlation between the gestational age and serum concentrationof progesterone or beta-hCG may reflect the normal function of CL. Therefore, abnormal response of CL or abnormal production of beta-hCG cause a disturbancein progesterone secretion leading to the abnormal pregnancy.
Corpus Luteum* ; Female ; Gestational Age ; Humans ; Pregnancy Maintenance ; Pregnancy* ; Progesterone* ; Retrospective Studies ; Ultrasonography ; Uterine Hemorrhage