Use of serum copper and zinc levels in the diagnostic evaluation of endometrioma and epithelial ovarian carcinoma.

OBJECTIVE: The aim of this study is to evaluate serum copper (Cu) and zinc (Zn) levels in patients with epithelial ovarian cancer and endometrioma. MATERIALS AND METHODS: We included 21 epithelial ovarian cancer patients, 47 endometrioma patients, 31 healthy women of reproductive age, and 10 healthy women in menopause. Cu and Zn levels and Cu/Zn ratios were compared. RESULTS: In the endometrioma group, Cu levels (P = 0.04) and Cu/Zn ratio (P < 0.01) were higher, while Zn levels (P < 0.01) were lower compared to the control group. The threshold value of 1.15 with 62% sensitivity and 61% specificity was calculated for the Cu/Zn ratio using the ROC curve (AUC = 0.688; P = 0.005). In the ovarian cancer group, Cu levels (P ≤ 0.01) and Cu/Zn ratio (P = 0.02) were higher, whereas Zn levels (P ≤ 0.02) were lower compared to the control group. The Cu/Zn ratio threshold value of 1.37 was calculated with 76% sensitivity and 90% specificity (AUC = 0.829; P = 0.004). The Zn level was lower (P = 0.02), and the Cu/Zn ratio was higher (P = 0.01) in the ovarian cancer group compared to the endometrioma group. CONCLUSION: The threshold value of the Cu/Zn ratio for ovarian cancer could be determined with a specificity of 90%, whereas the sensitivity and specificity of the Cu/Zn ratio for endometrioma were low.

The Asian Society of Endometriosis and Adenomyosis guidelines for managing adenomyosis.

This is the first guidelines for adenomyosis from the Asian Society of Endometriosis and Adenomyosis.

Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg intravaginal progesterone tablet.

Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation (COH)-intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore, considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH-IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300 mg or 600 mg of intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility, basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups. Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple pregnancy rates were comparable in both groups. We, therefore, claim that 300 mg of intravaginal micronized P should be the maximum dose of LPS in IUI cycles.

Outcome of intracytoplasmic sperm injection using fresh and cryopreserved-thawed testicular spermatozoa in 83 azoospermic men with Klinefelter syndrome.

AIM: To report the outcome of intracytoplasmic sperm injection (ICSI) cycles using fresh or cryopreserved-thawed testicular spermatozoa of men with Klinefelter syndrome (KS). METHODS: Medical records of 83 azoospermic men with KS who underwent testicular sperm extraction (TESE) were reviewed. The clinical parameters for predicting sperm retrieval and fertilization, implantation, pregnancy and live birth rates of ICSI cycles in these patients were evaluated. RESULTS: A total of 88 TESE procedures were performed with sperm retrieval rates of 39.8% per cycle (35/88) and 42.1% per patient (35/83). None of the studied clinical parameters were found to be informative in predicting successful sperm recovery. A total of 41 embryo transfer cycles were carried out using fresh testicular spermatozoa in 30, cryopreserved-thawed spermatozoa in 10 and cryopreserved-thawed embryo replacement in one. The fertilization and clinical pregnancy rates were comparable at 52.7% and 51.6% with fresh and 48.3% and 60% with cryopreserved-thawed testicular spermatozoa groups, respectively. Twenty-two clinical pregnancies were obtained, including 14 singletons, five twins, two triplets and one quadruplet and ended with the delivery of 13 singletons and six twins. In total, out of 25 delivered fetuses, four died (3 female, 1 male) following delivery and 21 newborns (14 female, 7 male) were healthy with a female to male ratio of 2:1. Conclusions We concluded that no clinical or laboratory parameter predicts the presence of spermatozoa in patients with KS, except the TESE procedure itself. The use of fresh or cryopreserved-thawed spermatozoa on ICSI cycle outcomes are equally successful in patients with KS.

Circulating and myometrial markers of oxidative stress in pregnant women with fetal growth restriction.

AIM: The objective of this study was to identify the relationship between fetal growth restriction (FGR) and oxidative stress. The mechanisms that protect against oxidative stress in the local microenvironment were investigated by comparing the activities of the markers, both in the circulation and myometrium. MATERIALS AND METHODS: Myometrial tissue and serum levels of malondialdehyde (MDA), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) markers were measured in 20 FGR and 20 healthy pregnancies. RESULTS: The mean duration of gestation at delivery was shorter (P = 0003) and the mean birthweight was lower P < 0001) in the FGR study group compared with the control group, as expected. While MDA and CAT concentrations were higher in the serum (P < 0.02 and P < 0.01, respectively), but lower in the myometrial samples (P < 0.01) in the FGR versus the control group, XO and myometrial SOD values were comparable in both groups. CONCLUSIONS: Although our data demonstrated that FGR is associated with oxidative stress, the exact role and mechanism of the oxidant and antioxidant imbalance is obscure. We speculate that despite limited local synthesis of CAT, effective and efficient removal of MDA in the uterine environment explains high MDA and CAT serum concentrations in women with FGR. Alternatively, a well-functioning myometrial system could rescue the fetus from reactive oxygen species, as demonstrated by lowered MDA and depleted CAT resulting from hyperconsumption. Elevated serum MDA and CAT levels in the serum may reflect the 'spillover' of these markers from the uterus to the circulation.

Disturbed release of cholecystokinin in pregnant women with hyperemesis gravidarum.

AIMS: We aimed to investigate cholecystokinin (CCK) release in pregnant women with and without hyperemesis gravidarum (HG). MATERIAL AND METHODS: In this case-control study including 40 pregnant women with HG and 40 women with healthy uncomplicated pregnancies, serum CCK levels in addition to hematological, biochemical and hormonal parameters were investigated. RESULTS: Serum CCK values were found to be significantly lower in pregnant women with HG (P < 0.001). Additionally, while serum blood urea nitrogen and free thyroxine levels were significantly higher, sodium, potassium, and thyroid stimulating hormone levels were significantly lower in women with HG than in control women. No correlation was detected between CCK and other parameters like ketonuria and thyroid function tests. CONCLUSIONS: CCK release has been found to be halved in pregnant women with HG, which supports the hypothesis that gastrointestinal motility is increased in pregnant women with HG. A causal effect remains to be confirmed.

Luteal phase support with estrogen in addition to progesterone increases pregnancy rates in in vitro fertilization cycles with poor response to gonadotropins.

In this study, our objective was to determine the effect of adding estradiol hemihydrate (E2) to progestin (P) for luteal phase support on pregnancy outcome in in vitro fertilization (IVF) cycles with poor response to gonadotropins. Ninety-five women with poor ovarian response who underwent controlled ovarian hyperstimulation (COH) with gonadotropin releasing hormone (GnRH) agonist or GnRH antagonist plus gonadotropin protocol for IVF were prospectively randomized into three groups of luteal phase support after oocyte retrieval. Group 1 (n = 33) received only intravaginal progesterone gel (Crinone 8% gel). Group 2 (n = 27) and Group 3 (n = 35) received intravaginal progesterone plus oral 2 and 6 mg estradiol hemihydrate, respectively. Main outcome measures were overall and clinical pregnancy rates (PRs) per patient. Serum LH, E2 and P levels at 7th and 14th days of luteal phase were also measured. Overall and clinical PRs were significantly higher in 2 mg E2 + P than P-only group (44% versus 18% and 37% versus 12.1%, respectively). There were no statistically significant differences between 6 mg E2 + P versus P-only and 2 mg E2 + P versus 6 mg E2 + P groups regarding PRs. Addition of 2 mg/day E2 in addition to P for luteal support significantly increase overall and clinical PRs in cycles with poor response to gonadotropins after IVF.

Use of dienogest in endometriosis: a narrative literature review and expert commentary.

Objective: Endometriosis affects up to 10% of women of reproductive age, and the main goal of treatment is to relieve symptoms. Progestins have been the mainstay of endometriosis suppression, of which dienogest has become an important option in many parts of the world. This is an expert literature review, with recommendations on the use of dienogest in the context of various clinical considerations when treating endometriosis.Methods: A search of PubMed was conducted for papers published between 2007 and 2019 on the use of dienogest in endometriosis. Experts reviewed these and included those they considered most relevant in clinical practice, according to their own clinical experience.Results: Evidence regarding the long-term use (>15 months) of dienogest for the management of endometriosis is presented, with experts concluding that the efficacy of dienogest should be assessed primarily on its impact on pain and quality of life. Fertility preservation, the option to avoid or delay surgery, and managing bleeding irregularities that can occur with this treatment are also considered. Counseling women on potential bleeding risks before starting treatment may be helpful, and evidence suggests that few women discontinue treatment for this reason, with the benefits of treatment outweighing any impact of bleeding irregularities.Conclusions: Overall, the evidence demonstrates that dienogest offers an effective and tolerable alternative or adjunct to surgery and provides many advantages over combined hormonal contraceptives for the treatment of endometriosis. It is important that treatment guidelines are followed and care is tailored to the woman's individual needs and desires.

Serum angiogenic profile in abnormal placentation.

OBJECTIVE: To evaluate the circulating soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) levels in women with abnormal placentation and to compare the data with the results of women with normal pregnancy. MATERIAL AND METHODS: Serum biomarkers of angiogenesis and maternal and perinatal characteristics of 68 pregnant women, all in the third trimester, who were diagnosed to have vaginal bleeding due to complete placenta previa with and without concomitant placenta accreta, increta and percreta as the study group and 30 pregnant women without any placentation abnormality who eventually delivered at ≥37 weeks of gestational age as the control group were evaluated. RESULTS: There was no statistical difference in the maternal serum values of sFlt1, PlGF, sFlt1/PlGF ratio and VEGF in groups with placental abnormality as compared to controls. Not even a single case of preeclampsia and intrauterine fetal growth restriction was encountered in the study group. CONCLUSION: We demonstrated that regardless of the localization and the degree of the myometrial invasion of the placenta in the uterus, the circulatory biomarkers of angiogenesis and vascularization were comparable.

Two successful pregnancies achieved by converting an in vitro fertilization cycle to an intrauterine insemination cycle in five cases with documented premature ovulation.

We here report two successful pregnancies obtained by converting an in vitro fertilization (IVF) cycle to an intrauterine insemination (IUI) cycle in five poor responder patients whose oocyte pick-up (OPU) procedures were canceled due to documented premature ovulation immediately before OPU. To our knowledge, this is the first article that demonstrates that switching an IVF cycle to an IUI cycle when premature ovulation occurs on the day of OPU can produce successful pregnancies, even in poor responder patients.

The cellular immunity and oxidative stress markers in early pregnancy loss.

OBJECTIVE: We investigated whether changes in cellular immunity and oxidative stress in pregnancy have any association with spontaneous miscarriage. MATERIAL AND METHODS: Circulating adenosine deaminase (ADA) activity as a marker of cellular immunity and malondialdehyde (MDA) and catalase (CAT), glutathione peroxidase (GPx) as markers of T lymphocyte activation and parameters of oxidative stress and antioxidant defense were compared between 40 women with early pregnancy loss and another 40 women with ungoing healthy pregnancy. RESULTS: Women with miscarriage had higher serum ADA and GPx levels when compared with women with normal pregnancy (p = 0.034 and p < 0.001, respectively). Although serum MDA level was slightly higher in women with miscarriage, the difference was not significant (p = 0.083). CAT levels were alike in both groups. CONCLUSION: We have demonstrated an increased cellular immunity and perhaps a compensated oxidative stress related to increased antioxidant activation in women with early spontaneous pregnancy loss.

The role of interleukin-17 in intrahepatic cholestasis of pregnancy.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease, is characterized by pruritus, abnormal liver function and elevated serum bile acid levels. The main cause of ICP has not yet been identified. We aimed to provide a new perspective to the pathogenesis of by investigating the possible association of circulating interleukin-17 (IL-17) that is a recently discovered proinflammatory cytokine levels with ICP. MATERIALS AND METHODS: In this controlled cross-sectional study, maternal venous blood samples were obtained from 33 consecutive pregnant women with ICP (15 with mild and 18 with severe forms of the disease) and 25 healthy women with uncomplicated pregnancies (as the control group) and IL-17 levels were compared among the groups. RESULTS: Although serum IL-17 levels were significantly higher in the severe ICP group than in the control group (p = 0.022), there were no significant differences between the mild and severe ICP groups or between the control and mild ICP groups. CONCLUSION: Explaining the mechanisms of hepatocyte injury might contribute to the existing therapeutic strategies for treating cholestatic diseases. Changes in IL-17 levels may shed light on the pathogenesis of ICP.

Evaluation of ventricular repolarization in pregnant women with intrahepatic cholestasis.

BACKGROUND: Bile acids can induce arrhythmia by altering cardiomyocyte contractility or electrical conduction. The aim of this study was to investigate, by means of QT dispersion parameter detected by simple standard electrocardiogram (ECG), ventricular repolarization changes in pregnant women with and without intrahepatic cholestasis of pregnancy (ICP). METHODS: In this case-control study including 75 pregnant women with cholestasis and 35 healthy, uncomplicated pregnancy cases, electrocardiographic QT interval durations and QT dispersion (QT-disp) parameters, corrected for the patients' heart rate using the Hodges formula, were investigated. RESULTS: Maximum corrected QT interval values were significantly higher in the severe ICP group than in the control group (p < 0.001) and significantly higher in the severe ICP group than in the mild ICP group (p = 0.01). The values of the mild ICP and control groups were similar. Corrected QT-disp values were also significantly higher in both ICP groups than in the control group and significantly higher in the severe ICP group than in the mild ICP group. CONCLUSION: Cholestatic diseases predispose patients to cardiovascular complications. Our data clearly demonstrated that QT-disp values were significantly altered in pregnant women with cholestasis when compared to the normal ones. This simple ECG parameter can be used to screen high-risk women, in order to better target counseling regarding lifestyle modifications and to conduct closer follow up and management of women with a history of ICP.

Age-related changes in ovarian volume, antral follicle counts and basal FSH in women with normal reproductive health.

OBJECTIVE: To investigate the relation between ultrasound-based ovarian volume and antral follicle counts and hormonal parameters of ovarian reserve in a group of women with normal reproductive health. STUDY DESIGN: Prospective study. One hundred eight women with at least one previous pregnancy reaching term were divided into three age groups (group 1 = 35-39 years, group 2 = 40-44 years, and group 3 = 45-50 years). Basal hormone measurements and transvaginal ultrasonography estimation of ovarian volume and follicle counts were performed in the early follicular phase (day 3) of the menstrual cycle. RESULTS: There were significant differences in FSH (P < .0001) and E2 (P < .002) levels when group I was compared to groups II and III. There was a significant decrease in mean follicle counts (MFC) between groups I and III (P < .05). The decrease in mean ovarian volume (MOV) with age was not statistically significant. Age strongly correlated with MFC (r = -.38, P < .001) and weakly with MOV (r = -.29, P < .05). However, basal FSH correlated positively with age (r = .50, P < .001) and negatively with MOV (r = -.590, P < .001) and MFC (r = -.658, P < .001). Basal E2 correlated with MOV (r = .50, P < .001) and MFC (r = .50, P < .001). There was also a strong positive correlation between MFC and MOV (r = .777, P < .001). CONCLUSION: There was a decrease in MOV and MFC with aging coincident with increasing basal FSH levels after age 35 in women with normal reproductive health.

Birth of a healthy boy using fresh testicular sperm in a patient with Klinefelter syndrome combined with Kartagener syndrome.

OBJECTIVE: To report a case of Klinefelter syndrome combined with Kartagener syndrome. DESIGN: Case report. SETTING: Private IVF center. PATIENT(S): A 35-year-old man with Klinefelter syndrome combined with Kartagener syndrome causing primary infertility. INTERVENTION(S): Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Sperm recovery, fertilization, and live birth. RESULT(S): Ovulation induction of the female partner, recovery of spermatozoa by TESE from the male partner and ICSI of 9 metaphase II oocytes resulted in two fertilized oocytes. The delivery of a healthy boy with normal anatomy and 46,XY karyotype was achieved after the transfer of only one 4-cell grade 1 embryo. CONCLUSION(S): To our knowledge, this case with nonmosaic Klinefelter syndrome combined with Kartagener's syndrome is unique and demonstrates the revolutionary aspects of assisted reproductive technologies (ART) concerning male factor infertility.

Smooth endoplasmic reticulum aggregations in all retrieved oocytes causing recurrent multiple anomalies: case report.

OBJECTIVE: To document the relationship between smooth endoplasmic reticulum (SER) aggregations and recurrent fetal anomalies. DESIGN: Case report. SETTING: Private IVF center. PATIENT(S): A 28-year-old woman with an 11-year history of primary infertility. INTERVENTION(S): Three consecutive cycles of intracytoplasmic sperm injection (ICSI) in the same patient. MAIN OUTCOME MEASURE(S): Clinical pregnancy, live birth, fetal anomaly. RESULT(S): In three consecutive ICSI cycles, a total of 59 MII oocytes were retreived in the same patient, all displaying SER aggregations. The fertilization rate per cycle was 80%, 50%, and 42%, respectively. A total of 12 embryos were transferred in three ICSI cycles, of which 11 were grade 1 embryos. Two of the three cycles ended up with clinical ongoing pregnancies but with multiple fetal anomalies. CONCLUSION(S): This is the first case reported with SER aggregations in all retrieved oocytes in three consecutive ICSI cycles. The repetetive multiple fetal anomalies possibly related to oocyte dysmorphism are of concern.

Postoperative pain control after cesarean section: can diclofenac sodium be used instead of meperidine?

OBJECTIVE: To determine the advantages and disadvantages of the use of diclofenac sodium instead of meperidine for postcesarean section pain control. METHODS: A total of 130 patients who had undergone cesarean section at the Department of Obstetrics and Gynecology of Gazi University Hospital were prospectively randomised to receive one of two postoperative pain control regimens. The first group of patients received intramuscular diclofenac sodium at a dose of 2 x 75 mg and additional breakthrough meperidine was given intramuscularly at 50 mg dosages each time, if necessary. Patients in the second group received only 6 x 50 mg meperidine. RESULTS: Twenty-seven of the 65 patients in the diclofenac group complained of unrelieved pain within the subsequent 24 h postoperatively. Patients receiving diclofenac alone or a combination of diclofenac + meperidine were less sedated and the time to the first passing of flatus was shorter than that in the patients treated with only meperidine. CONCLUSIONS: Diclofenac alone was safe and effective for the majority of the patients and it decreased the opioid requirements in the remaining patients.

Comparison of basal and clomiphene citrate induced FSH and inhibin B, ovarian volume and antral follicle counts as ovarian reserve tests and predictors of poor ovarian response in IVF.

PURPOSE: To compare basal and clomiphene citrate (CC) induced follicle-stimulating hormone (FSH), estradiol (E2), and inhibin B levels with ultrasound indices of ovarian reserve in infertile women and to test the prognostic value of these tests on response to ovarian stimulation in in vitro fertilization (IVF). METHODS: Fifty-six patients had basal and CC induced serum hormone levels and ultrasound measured mean ovarian volume (MOV) and mean antral follicle counts (MFC). Thirty-two patients were then appropriately selected to have a total of 41 cycles of IVF/ICSI treatment. RESULTS: Women with diminished ovarian reserve had lower MOV, MFC, day 3 and day 10 inhibin B levels (p < 0.001). Only basal and CC induced FSH and inhibin B correlated with MOV and MFC. Poor responders in IVF/ICSI had higher basal FSH (p < 0.05), lower basal and induced inhibin B levels (p < 0.05), and lower MOV and MFC (p < 0.01) than normal responders. Ovarian volume alone was better than age and basal hormones in predicting poor ovarian response, while abnormal CC test was the only independent significant factor in predicting ovarian response. However, age was the only independent predictor of pregnancy in IVF as compared to hormonal and ultrasound indices of ovarian reserve. CONCLUSION: CC test and ovarian volume are better than other hormonal and sonographic tests in predicting the response to ovarian stimulation in IVF cycles.

Single-dose methotrexate for the treatment of unruptured ectopic pregnancy.

OBJECTIVE: The objective of this study was to review our experience with single dose intramuscular methotrexate (MTX) for the treatment of ectopic pregnancy and to evaluate major confounding factors that relate to the success of therapy. PATIENTS AND METHODS: The selection criteria were patients who had a stable hemodynamic status and an ectopic gestational mass of <4 cm. on ultrasound. Patients were not excluded from MTX therapy either by a baseline serum beta-hCG titer or by the presence of fetal cardiac activity demonstrated on ultrasonography. Thirty- four of 86 patients diagnosed with ectopic pregnancy and treated with single-dose MTX between July 1999 and November 2001 were reviewed retrospectively. RESULTS: The mean pre-treatment beta-hCG level was 2,490+/-2,912 mIU/ml. Twenty-two patients (73.3%) were successfully treated with a single-dose of MTX. Eight patients (26.6%) required a second dose 1 week after the first injection and 2 patients received three doses. Thirty of the 34 patients (88%) were successfully treated with MTX. The mean pre-treatment beta-hCG level was significantly lower in patients who were successfully treated with MTX than in patients who failed MTX therapy (1,932+/-2,361 mIU/ml vs. 6,955+/-2,690 mIU/ml respectively, p<0.05). The mean pre-treatment serum beta-hCG level was higher in patients who had a second MTX injection as compared to patients who were successfully treated with a single injection of MTX (3,272+/-3,551 mIU/ml vs. 1,280+/-2,273 mIU/ml respectively, p>0.05). The mean time to resolution of beta-hCG was 26.5 days (10 to 37 days) with MTX. All 3 patients who failed medical therapy had beta-hCG level >4,000 mIU/ml and 2 of them had positive fetal cardiac activity. CONCLUSION: In conclusion, this study showed that medical treatment of ectopic pregnancy with systemic single-dose methotrexate seems to be an option for some patients with unruptured tubal pregnancy.