Alteration of apoptosis-related genes in postmenopausal women with uterine prolapse.

INTRODUCTION AND HYPOTHESIS: We aimed to compare expression levels of antiapoptotic and proapoptotic genes in parametrial and vaginal tissues from postmenopausal women with and without pelvic organ prolapse (POP). We hypothesized that the expression of genes that induce apoptosis may be altered in vaginal and parametrial tissues in postmenopausal women with POP. METHODS: Samples of vaginal and parametrial tissues were obtained from postmenopausal women with (n = 10) and without (n = 10) POP who underwent vaginal or abdominal hysterectomy. Expression levels of antiapoptotic (BCL-2, BCL-XL) and proapoptotic (BAX, BAD) genes were studied by real-time reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Gene expression levels of BCL-2 (P < 0.001), BCL-XL (P < 0.001), BAX (p = 0.001), and BAD (p = 0.004) were all higher in vaginal tissues from the POP group compared with the non-POP group. Similarly, gene expression levels of BCL-2 (p < 0.001), BCL-XL (p < 0.001), BAX (p < 0.001), and BAD (p < 0.001) in parametrial tissues were also significantly higher in the POP group compared with the non-POP group. Additionally, expression levels of BCL-2 (p = 0.05), BCL-XL (p < 0.05), BAX (p = 0.05), and BAD (p = 0.07) in the POP group were higher in parametrial tissue than in vaginal tissue samples. CONCLUSIONS: Antiapoptotic and proapoptotic gene expression levels differed significantly between postmenopausal women with and without POP. Bcl-2 family genes were overexpressed in the parametrium of patients with POP compared with vaginal tissue, suggesting that the processes responsible for POP have a greater effect on parametrial tissue than vaginal tissue during the development of POP.

Serum homocysteine and asymmetric dimethylarginine levels in patients with premature ovarian failure: a prospective controlled study.

OBJECTIVE: To investigate serum homocysteine and asymmetric dimethylarginine (ADMA) levels in patients with premature ovarian failure (POF). STUDY DESIGN: A total of 69 women, 32 with POF and 37 apparently healthy women were included in the study. Fasting blood samples were drawn to measure serum homocysteine and ADMA levels using ELISA method. RESULTS: The study and control group had a mean age of 37.3 + 2.6, 37.5 + 2.5 years; a mean homocysteine level of 13.54 + 5.19, 12.71 + 3.99 mmol/l and a mean ADMA level of 1.32 + 0.27, 1.26 + 0.36 mmol/l, respectively. There were no statistically significant differences between the two groups in terms of homocysteine and ADMA levels (with p values of 0.465 and 0.423, respectively). A negative significant correlation was found between estradiol and ADMA (p <0.05). CONCLUSION: Homocysteine and ADMA levels did not change in comparison with the control group, which suggests that estrogen deficiency in patients with POF does not have any effect on homocysteine and asymmetric dimethylarginine levels.

Asymptomatic microperforated transverse vaginal septum presenting with primary infertility: a rare form of mullerian anomaly.

Transverse vaginal septum is a rare type of mullerian anomaly resulting from failure of the canalization of the vaginal plate at the point where the urogenital sinus meets the mullerian duct and usually presents at menarche with symptoms of outflow tract obstruction. Instead, patients with a perforated septum often have normal menses and usually present with difficulties with intercourse or infertility. A 24-year-old patient with 5 years of infertility is reported. Following assessment, isolated microperforated transverse vaginal septum (U0C0V3 according to the new classification system of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy for congenital uterine anomalies) was detected with no additional urogenital anomaly and simple excision of the septum and end-to-end vaginal anastomosis was performed. The patient became pregnant spontaneously 2 months after the operation when sexual intercourse was permitted. Transverse vaginal septum, which presented itself with no clinical findings and only primary infertility, is discussed with a review of the existing literature.

Juvenile cystic adenomyosis mimicking uterine malformation: a case report.

Cystic adenomyosis is a rare form of adenomyosis mostly seen in middle aged women. We report a case of cystic adenomyosis in a juvenile patient presenting with severe dysmenorrhea refractory to any given medication. The patient initially was diagnosed as uterus bicornis with an obstructed rudimentary horn. Surgical exploration and excision of the cystic mass relieved the symptoms of the patient.

Effects of estrogen, raloxifene, and hormone replacement therapy on serum C-reactive protein and homocysteine levels.

OBJECTIVES: To investigate the effects of conjugated equine estrogen (CEE), CEE plus medroxyprogesterone acetate (MPA), CEE plus Nomegestrol acetate (NA), and raloxifene on serum high sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) levels in healthy postmenopausal women. MATERIALS: One hundred seven healthy postmenopausal women were recruited in a prospective, randomized, and placebo-controlled 6 months study. Of these, 18 were hysterectomized and received daily oral 0.625 mg CEE. Eighty nine non-hysterectomized women were randomly allocated to one of four groups: a group (22 patients) treated with CEE, 0.625 mg/daily plus MPA 2.5 mg/daily; a group (22 patients) treated with CEE, 0.625 mg/daily plus NA 5 mg/daily; a group (23 patients) treated with raloxifene hydrochloride, 60 mg once daily; and a placebo group (22 patients). Hcy and hs-CRP were measured at baseline and at 3 and 6 months. RESULTS: CEE (20%, P=0.03) and CEE+MPA (59%, P=0.006) increased serum hs-CRP levels significantly, whereas CEE+NA decreased serum hs-CRP by 25% (P=0.01). Raloxifene had no significant effect on serum hs-CRP levels during and after the treatment. In all active treatment groups serum Hcy levels decreased significantly compared to baseline and placebo. CONCLUSIONS: Conjugated equine estrogen, hormone replacement therapies, and raloxifene lower serum Hcy levels to a comparable extent in postmenopausal women. Hs-CRP, as a cardiovascular risk factor, is not influenced by raloxifene, whereas CEE and CEE plus MPA significantly increase hs-CRP levels. Treatment with CEE plus NA reduces serum hs-CRP levels.

Anesthetic effect of intrauterine lidocaine plus naproxen sodium in endometrial biopsy.

OBJECTIVE: To compare the efficacy of intrauterine lidocaine with oral naproxen sodium on pain perception of the patients during endometrial biopsy using the Pipelle instrument and to investigate their effects when used in combination. METHODS: One-hundred twenty women were randomly assigned to receive either 5 mL of intrauterine 2% lidocaine or saline and either 550 mg of naproxen sodium or a similar-appearing placebo tablet. Subsequently, each woman completed a 10-cm visual analog scale for subjective pain experience and a physician scored visible signs of the women's distress during the procedure using a 3-point observer scale. RESULTS: There was no statistically significant difference between the 4 groups in age, vaginal parity, history of chronic pelvic pain, menopausal status, tenaculum use, previous endometrial biopsy, or difficulty in passing the cervical os. The mean pain scores of the women in the naproxen only (5.8 +/- 2.2) and lidocaine only (5.9 +/- 2.2) groups were not significantly different compared with placebo group (7.1 +/- 2.0). However, the mean pain score in the lidocaine plus naproxen group (4.6 +/- 1.8) compared with the placebo group showed significant reduction in pain (P <.05). Pain rated by the physician was significantly lower in the lidocaine plus naproxen group compared with other groups, and a significant correlation was noted between the visual analog pain score and the patients' distress recorded by the physician (r =.791, P <.001). One patient in the naproxen-only group had vasovagal syncope after the procedure. CONCLUSION: Intrauterine lidocaine instillation significantly decreases pain associated with Pipelle endometrial biopsy when used in combination with oral naproxen sodium. LEVEL OF EVIDENCE: I

Regression of endometrial explants in rats treated with the cyclooxygenase-2 inhibitor rofecoxib.

OBJECTIVE: To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor rofecoxib on endometrial explants and on peritoneal vascular endothelial growth factor (VEGF) levels in the rat endometriosis model. DESIGN: Prospective, placebo-controlled study. SETTING: Laboratory at Dokuz Eylül University. ANIMAL(S): Twenty-six rats with experimentally induced endometriosis. INTERVENTION(S): Rats were treated for 3 weeks with oral rofecoxib (3 mg/kg per day; n = 9); single subcutaneous injection of depot leuprolide acetate (1 mg/kg; n = 9); or vehicle (control; n = 8). MAIN OUTCOME MEASURE(S): Change in explant area and histologic examination by semiquantitative analysis of endometriotic explants and measurement of peritoneal VEGF levels. RESULT(S): Three weeks of treatment with rofecoxib statistically significantly decreased the implant size (62.4%) compared with control (16.6%), and this effect was comparable with the decrease in leuprolide (64.3%). Histologic examination of the explants indicated mostly atrophy and regression in treatment groups, and semiquantitative analysis showed statistically significantly lower scores in rats treated with rofecoxib and leuprolide compared with controls. Both rofecoxib and leuprolide statistically significantly decreased VEGF levels compared with controls. CONCLUSION(S): Rofecoxib causes regression and atrophy of the endometriotic lesions and is as effective as a GnRH agonist with an accompanying decrease in the VEGF levels.

Effects of betamethasone and thyroid releasing hormone on fetal lung maturation: an experimental and morphometric study.

OBJECTIVE: To determine the effects of betamethasone and thyroid releasing hormone (TRH) on morphologic fetal rabbit lung maturation when administered separately and in combination. MATERIAL AND METHODS: Twenty-five pregnant rabbits were divided into five groups. Study groups were as follows: TRH or betamethasone alone (between 24 and 27th days of gestation), TRH + betamethasone or betamethasone + TRH (second dose of drugs were added in the last 2 days), and the control. The pregnancies were terminated on the 27th day of gestation. Weights and volumes of the fetal lungs were determined and the results were compared. RESULTS: Mean lung weights in all treatment groups were significantly heavier than controls (P < 0.05). The differences between mean lung weights of TRH alone, TRH + betamethasone, and betamethasone alone groups were not statistically significant (P > 0.05), but the mean lung weight of betamethasone + TRH group was significantly lower than the other treatment groups (P < 0.05). Mean lung volume of TRH alone group was significantly higher than control group; however, there were no significant differences between other treatment groups and the control. No correlation was found between the lung weights and volumes in all groups (r = 0.1, P > 0.05). CONCLUSION: Only TRH alone treatment produced a significant increase in both fetal lung volume and weight compared to the control group. Administering TRH alone can lead to increased lung maturation. Combining TRH to corticosteroid treatment significantly decreased mean fetal lung weight, instead of an increase. According to these results combined used of these two substances probably counteract each others effect, instead of having a synergism.

Tubo-ovarian abscess mimicking ovarian tumor in a sexually inactive girl.

Tubo-ovarian abscess is a serious complication of pelvic inflammatory disease rarely seen in sexually inactive girls. Early diagnosis and treatment are essential to prevent further sequela including infertility, ectopic pregnancy, and chronic pelvic pain. We present a case of 19-year-old sexually inactive girl who presented with abdominal pain and pelvic mass resembling ovarian tumor. Unilateral tubo-ovarian abscess with extensive bowel adhesions was determined at laparotomy. Drainage of the abscess and postoperative antibiotic therapy cured the patient.

Laparoscopic treatment of recurrent ectopic pregnancy in the ipsilateral salpinx after ovulation induction and intrauterine insemination.

OBJECTIVE: To report a case of recurrent ectopic pregnancy in the ipsilateral salpinx after and intrauterine insemination treated by laparoscopy. CASE REPORT: A 33-year-old woman with unexplained infertility sought evaluation at our hospital due to pelvic pain after ovulation induction and intrauterine insemination. She had a history of a right salpingectomy. Transvaginal ultrasonography did not reveal an intrauterine pregnancy, but showed a suspected extrauterine gestational sac on the operated adnexal area with free fluid in the pouch of Douglas. The patient was diagnosed with a recurrent ruptured ectopic pregnancy and an emergency laparoscopy was performed. CONCLUSION: Recurrent ectopic pregnancy in the ipsilateral fallopian tube is rare, but it is important to be suspicious of the diagnosis to prevent serious morbidity. This case also demonstrates transtubal or transperitoneal migration of the gametes because ovulation and ectopic pregnancy occurred on opposite sides.

Prolonged breast-feeding is an independent risk factor for postmenopausal osteoporosis.

OBJECTIVES: This study investigated the effects of parity and age at first pregnancy and breast-feeding, as well as duration of BF for total and per child on postmenopausal osteoporosis. STUDY DESIGN: The study was conducted among 542 cases who were divided based on the presence or absence of osteoporosis. Patients were separated according to their first pregnancy and breast-feeding age as before or after 27 years. Osteoporosis was defined as a T score of -2.5 or lower. MAIN OUTCOME MEASURES: Parity, age at first pregnancy and breast-feeding, breast-feeding period for total and average duration per child according to a questionnaire were assessed. RESULTS: Osteoporosis group had significantly lower parity compared to non-osteoporosis group. The age at first pregnancy and breast-feeding<27 age were significantly more frequent in osteoporosis group. They also had prolonged breast-feeding period. Women who had a breast-feeding period per child>1 year under age 27 was higher in osteoporosis group. In multivariate analysis, women who breast-fed>1 year per child had the highest risk for osteoporosis (odds ratio: 12.92; 95% confidence interval, 3.1-52.6) and osteoporosis risk for women who breast-fed>1 year per child under age 27 was 7.1. Increased parity was associated with a significant protective effect for osteoporosis. CONCLUSIONS: Extended breast-feeding period per child>1 year is the highest risk factor for osteoporosis independent of first breast-feeding age. However, high parity has a protective effect.

The levels of hepatocyte growth factor in serum and follicular fluid and the expression of c-Met in granulosa cells in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the levels of hepatocyte growth factor (HGF) in follicular fluid (FF) and the expression of c-Met in granulosa cells (GCs) with respect to the quality of the oocyte and embryo both in patients with polycystic ovary syndrome (PCOS) and in the normal ovary during controlled ovarian hyperstimulation cycles. DESIGN: Prospective controlled study. SETTING: University hospital. PATIENT(S): Fifty-nine women undergoing IVF treatment (of whom 21 had PCOS and 38 were in the control group). INTERVENTION(S): A total of 168 FF samples were collected at the time of oocyte retrieval. The HGF levels were measured by ELISA, and the mRNA expression of c-Met in GCs was detected by real-time polymerase chain reaction. MAIN OUTCOME MEASURE(S): The predictive values of HGF levels in serum and FF and the mRNA expression of c-Met in GCs for successful fertilization and oocyte-embryo quality. RESULT(S): The levels of HGF in serum and FF and the c-Met expression in GCs were similar between the PCOS and control groups. Granulosa cells of fertilized oocytes (2PN) had a significantly higher level of c-Met expression than that in oocytes that failed to fertilize. The mean HGF level in FF was significantly higher in the grade 1 embryos than in the grades 2-4 embryos. CONCLUSION(S): This study suggests that HGF/c-Met signaling may be a crucial determinant of fertilization success.

Tuba ovarian abscesses formation from decidualized ovarian endometrioma after appendiceal endometriosis presenting as acute appendicitis in pregnancy.

BACKGROUND: Acute appendicitis with appendicial endometriosis is a very infrequently encountered condition during pregnancy. Decidualization is the hypertrophy of endometrial stromal cells by the effect of progesterone. Similarly, in pregnancy, ectopic stromal endometrial cells in endometriosis can also be transformed by the same mechanism and ectopic decidua (deciduosis) may occur. CASE: Here we report a 30 year old pregnant woman presenting twice with acute abdominal symptoms requiring surgery for appendicial and ovarian endometriosis and deciduosis. We emphasize that deciudualized endometriosis may first present during pregnancy with acute abdomen necessitating emergency laparotomy and complicating the course of gestation. CONCLUSION: To our knowledge only 9 cases in which decidualized endometriotic tissue causing acute abdomen necessitating surgery during pregnancy were reported in the literature. What makes our case special is that the patient needed two laparotomies during the pregnancy period which was a very stressful situation for both the patient and the physicians.

Serum lipid levels in women with premature ovarian failure.

OBJECTIVE: The aim of this study was to investigate serum lipid and hormone levels in women with premature ovarian failure (POF) and compare them with those of healthy women of similar age. METHODS: We measured fasting total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), high-density lipoprotein, estradiol (E2), follicle-stimulating hormone (FSH), progesterone, and testosterone levels in 47 women with POF not using any hormone therapy and 60 healthy women of the same age range not using oral contraceptives or any other hormonal medication. RESULTS: There were no statistically significant differences between the groups in terms of age, body mass index (BMI) and smoking status (P = 0.054, 0.250, and 0.656, respectively). The mean E2 levels of the POF and control groups were 27.9 ± 2.3 and 87.8 ± 75.2 pg/mL, respectively (P < 0.001). Women with POF presented with significantly higher TC and LDL levels (P = 0.006 and 0.040, respectively). However, no difference was found between the groups with regard to triglyceride and high-density lipoprotein levels (P = 0.128 and 0.062, respectively). We determined that there was a significant negative correlation between E2 and TC levels (r = -0.291, P = 0.047) in the POF group. However, no correlation could be identified between E2 and lipids in the control group. Likewise, no correlation was present between FSH and lipids in both groups. We divided the control group according to basal FSH level. Group A consisted of the women with a serum FSH level lower than 7 IU/L, and group B consisted of the women with a serum FSH level of 7 IU/L or higher. There was no difference between the groups in age, body mass index, E2 concentration, and smoking status. The FSH level of group A was significantly lower than that of group B (P < 0.001). We found no difference between groups A and B with regard to lipid levels. CONCLUSIONS: Higher TC and LDL levels in women with POF compared with the control group suggest that estrogen deprivation in women with POF leads to unfavorable lipid changes.

Effect of laparoscopic excision of endometriomas on ovarian reserve: serial changes in the serum antimüllerian hormone levels.

OBJECTIVE: To investigate the effect of laparoscopic endometrioma stripping on serum antimüllerian hormone (AMH) and the correlation between the clinicopathologic factors. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Sixty-five women with endometriomas. INTERVENTION(S): All patients underwent laparoscopic cystectomy. Serum AMH, FSH, LH, E(2), and antral follicle count (AFC) were measured preoperatively, at 6 weeks, and at 6 months postoperatively. Specimens were analyzed histopathologically. MAIN OUTCOME MEASURE(S): The primary end point was to assess the ovarian reserve damage based on alterations of AMH and the secondary end point was to detect the changes in FSH, LH, E(2), and AFC. RESULT(S): Serum AMH decreased significantly at the sixth month (61%) postoperatively. The FSH level increased significantly at the sixth week, but returned to normal at the sixth month. The AFC increased significantly at the sixth week and at the sixth month. The AMH level decrease was more evident in patients with the cyst <5 cm (65.7% vs. 41.3%). The AMH decrease was more in bilateral compared with unilateral endometriomas (67% versus 57%, respectively). No correlation was detected between the histopathologic analyses and tAMH level. Initially the AMH level was the only independent factor affecting the AMH decrease (odds ratio, 3.68; 95% confidence interval 1.66-8.14). CONCLUSION(S): Laparoscopic cystectomy of ovarian endometriomas causes a significant and progressive decline in serum AMH levels.

Retrospective analysis of follicle loss after laparoscopic excision of endometrioma compared with benign nonendometriotic ovarian cysts.

OBJECTIVE: To evaluate follicle loss in ovarian tissue after laparoscopic excision by the stripping technique in endometriomas versus benign nonendometriotic ovarian cysts. METHODS: Cystectomy samples obtained from 127 ovaries from 104 patients (mean age, 29.05 ± 05 years; range, 19-40 years) by laparoscopic excision (61 endometriomas and 66 benign nonendometriotic cysts) were evaluated for follicle loss. The samples including normal ovarian tissue were graded on a semiquantitative scale from 0 to 4, where 0 was complete absence of follicles and 4 was the pattern of primary and secondary follicles seen in a normal ovary. The results from endometriomas were compared with those from nonendometriotic cysts. RESULTS: There were no differences in mean tissue thickness, or number of primordial, primary, or secondary follicles between the endometriomas and the nonendometriotic cysts (P > 0.05). Ovarian cortex was detected in 92% and 82% of the endometriomas and nonendometriotic samples, respectively, (P = 0.081). Semiquantitative scoring of ovarian tissue was significantly higher in endometriomas (1.64 ± 1.35 versus 1.11 ± 1.22, P = 0.022). CONCLUSION: In up to 92% of the cystectomy samples, normal ovarian tissue was found adjacent to the benign cyst; however, functional follicle loss was slightly, but significantly, higher in the endometriomas.

Influence of follicular fluid GDF9 and BMP15 on embryo quality.

OBJECTIVE: To evaluate the association between follicular fluid levels of propeptide and mature forms of growth differentiation factor (GDF) 9 and bone morphogenetic protein (BMP) 15 with subsequent oocyte and embryo quality. DESIGN: Prospective clinical study. SETTING: University hospital. PATIENT(S): Eighty-one infertile patients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). INTERVENTION(S): The expression levels of the propeptide and mature forms of follicular fluid GDF9 and BMP15 were determined by western blot analysis. The levels of follicular fluid hormones (FSH, E2, and P) were measured with automated chemiluminescent enzyme immunoassays. MAIN OUTCOME MEASURE(S): The relationships between the levels of GDF9 and BMP15, hormones, oocyte maturation, and embryo quality. RESULT(S): Mature GDF9 levels were significantly correlated with the nuclear maturation of oocytes. The mean mature GDF9 level was 4.87±0.60 in the high-embryo-quality group and 1.45±0.81 in the low-embryo-quality group. There were no statistically significant differences in embryo quality among the patients regarding propeptide GDF9 and BMP15 expression status. There was a negative correlation between follicular fluid levels of P and the mature form of GDF9. CONCLUSION(S): Higher mature GDF9 levels in the follicular fluid were significantly correlated with oocyte nuclear maturation and embryo quality.

Long-term effects of GnRH agonist, GnRH antagonist, and estrogen plus progesterone treatment on apoptosis related genes in rat ovary.

OBJECTIVE: To define the long-term effects of GnRH antagonist, GnRH agonist, and estrogen plus progesterone treatments on apoptosis and apoptosis-related gene expressions, including bcl2, bax, and cyt c in rat ovary. DESIGN: Prospective placebo-controlled experimental study. SETTING: Obstetrics and Gynecology and Medical Biology and Genetics university departments. ANIMAL(S): Forty female wistar rats that were 3 to 4 months of age. INTERVENTION(S): Forty rats were randomly divided into 4 groups of 10 each. In group 1 (control) each rat received normal saline as placebo by gastric lavage. In group 2 (GnRH agonist) 1 mg/kg leuprolide acetate in depot form was given for 30 days. In group 3 (GnRH antagonist) each animal received 0.1 mg/kg cetrorelix every 2 days. In group 4 (estrogen plus progesterone) 0.5 mg/kg estradiol valerate and norethisterone enantate in depot form was given every 30 days. After 60 days, the animals were killed. MAIN OUTCOME MEASURE(S): Assessment of morphology, histology of ovaries, determination of the number of apoptotic cells, and analysis of apoptosis-related gene expression of bcl2, bax, and cyt c in the rat ovaries. RESULT(S): Long-term GnRH antagonist treatment significantly increased bax gene expression, but the ratio of bcl2:bax gene expression was constant compared with control group. The GnRH agonist treatment significantly increased cyt c gene expression, and estrogen plus progesterone treatment significantly decreased bcl 2 and significantly increased cyt c expressions. In the estrogen plus progesterone group, ovaries were cystic and larger than in the other groups. There was no significant morphologic change between the other groups. CONCLUSION(S): Long-term administration of GnRH agonist, GnRH antagonist, and estrogen plus progesterone can modulate the apoptosis-related genes in rat ovary. Although GnRH antagonist treatment does not influence apoptosis, GnRH antagonist and estrogen plus progesterone treatments seem to influence apoptosis in rat the ovary. Further clinical studies focusing on the effect of these agents on apoptosis-related genes could be performed.