Systematic review and meta-analysis of single-dose and non-single-dose methotrexate protocols in the treatment of ectopic pregnancy.

BACKGROUND: It remains unclear which methotrexate protocol for the treatment of ectopic pregnancy has a higher success rate or a higher adverse effect rate. OBJECTIVE: To compare the treatment success rates and adverse effect rates of single-dose and non-single-dose (two-dose and multi-dose) methotrexate protocols in the treatment of ectopic pregnancy. SEARCH STRATEGY: Various databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched on July 1, 2017, using search terms including "methotrexate" and "pregnancy." SELECTION CRITERIA: Randomized controlled trials comparing different methotrexate protocols for the treatment of ectopic pregnancy were included. DATA COLLECTION AND ANALYSIS: Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare treatment success rates and adverse effect rates. MAIN RESULTS: The single-dose and non-single-dose protocols had similar success rates (RR 1.00, 95% CI 0.96-1.04; 11 trials, 1121 patients, I2 =18%). The non-single-dose protocols had a higher adverse effect rate than did the single-dose protocol (RR 0.73, 95% CI 0.59-0.91; nine trials, 934 patients, I2 =0%). CONCLUSIONS: The single-dose methotrexate protocol was the optimal protocol for the medical treatment of ectopic pregnancy.

Levonorgestrel-Releasing Intrauterine Systems Versus Oral Cyclic Medroxyprogesterone Acetate in Endometrial Hyperplasia Therapy: A Meta-Analysis.

BACKGROUND: This study aimed to compare the levonorgestrel-releasing intrauterine system (LNG-IUS) with oral cyclic medroxyprogesterone acetate (MPA) in endometrial hyperplasia therapy using randomized controlled trials (RCTs). METHODS: The study searched MEDLINE, EMBASE, CENTRAL, and other databases. All regression outcomes were calculated for dichotomous outcomes in terms of relative risk (RR) and 95% confidence intervals (CIs) using a Mantel-Haenszel random effects model. RESULTS: The search found 543 articles but selected 342 articles after the removal of duplicates. A meta-analysis found five RCTs (377 patients). The study did not analyze RR for total outcome because of high heterogeneity (I 2 = 87%). In a subgroup analysis of studies with non-obese women, the LNG-IUS treatment appeared to have a higher regression rate than oral MPA (RR 1.41; 95% CI 1.23-1.62; 4 trials, 265 patients; I 2 = 0%). In a subgroup analysis of studies with obese women, LNG-IUS appeared to have a regression rate similar to that of oral MPA (RR 1.03; 95% CI 0.94-1.13; 1 trial, 60 patients). In a subgroup analysis according to histology in the non-obese group, the LNG-IUS treatment appeared to have a higher regression rate than oral cyclic MPA in a meta-analysis of women with non-atypical endometrial hyperplasia (RR 1.36; 95% CI 1.07-1.73; 2 trials, 92 patients; I 2 = 6%) and mixed endometrial hyperplasia (atypical and non-atypical) (RR 1.44; 95% CI 1.21-1.71; 2 trials, 173 patients; I 2 = 0%). CONCLUSIONS: The LNG-IUS treatment has a higher regression rate than cyclic MPA in non-atypical endometrial hyperplasia and mixed endometrial hyperplasia therapy for non-obese women but has a similar regression rate, albeit limited, for obese women.

Comparison of Laparoscopic Cornual Resection and Cornuotomy for Interstitial Pregnancy.

STUDY OBJECTIVE: To compare the clinical efficacy and safety of laparoscopic cornuotomy and cornual resection in the treatment of interstitial pregnancy. DESIGN: Retrospective chart review between 2006 and 2014 (Canadian Task Force classification II-2). SETTING: Two academic tertiary care hospitals. PATIENTS: Seventy-five patients with interstitial pregnancy treated by laparoscopy. MEASUREMENT AND MAIN RESULTS: In the 75 patients, 53 who underwent cornual resection and 22 who underwent cornuotomy, we evaluated operating time, changes in hemoglobin levels after surgery, the rate of major complications, and the incidence of persistent interstitial pregnancy. The mean operating time was significantly shorter for cornuotomy than for cornual resection (59.36 ± 19.32 minutes vs. 77.11 ± 23.97 minutes, respectively). Changes in hemoglobin level after the operation, rates of major complications, and the incidence of persistent interstitial pregnancy were not significantly different in the 2 surgery groups. CONCLUSION: Laparoscopic cornuotomy yielded clinical results comparable to those of cornual resection. Laparoscopic cornuotomy may reduce the time of operation, and had the same incidence of persistent interstitial pregnancy as cornual resection.

Association between pregnancy and adnexal torsion: A population-based, matched case-control study.

The purpose of this study was to determine the effect of pregnancy on adnexal torsion (AT). We conducted a matched case-control study using the Korean Health Insurance Review and Assessment Service-National Inpatients Sample (HIRA-NIS) from 2009 to 2011. AT patients were defined as women with both a diagnostic code (N835) and a surgical code for AT. The AT patients were randomly matched 1:4 with women without AT by age and year of claim. In total, 545 AT cases and 2180 controls were enrolled from a total of 1,843,451 women. After adjustment for such covariates as age, pregnancy was found to be associated with a lower rate of AT (adjusted odds ratio 0.314, 95% confidence interval [CI] 0.237-0.416, P value <0.01) and ovarian hyperstimulation syndrome was associated with a higher rate of AT (adjusted odds ratio 20.091, 95% CI 3.607-111.908, P value <0.01). We found that pregnancy is a negative risk factor for AT. However, a further study is needed to elucidate the mechanisms underlying these results.

Graves Disease Is Associated With Endometriosis: A 3-Year Population-Based Cross-Sectional Study.

The aim of this cross-sectional study was to compare the prevalence of thyroid diseases between women with and without endometriosis.We established the endometriosis group according to diagnosis codes, surgery codes, and gonadotropin-releasing hormone agonist codes using the Korean Health Insurance Review and Assessment Service-National Inpatients Sample (HIRA-NIS) from 2009 to 2011. Four controls were randomly matched to each endometriosis case. Thyroid disease cases were selected using the thyroid disease diagnosis code (E0X).Among the 1,843,451 women sampled, 5615 had endometriosis; 22,460 controls were matched to the endometriosis cases. After adjustment for age and sampling year, Graves disease was associated with endometriosis (odds ratio [OR]: 2.52; 95% CI: 1.30-4.88; P < 0.01), while hypothyroidism was not (OR: 1.17; 95% CI: 0.90-1.52; P = 0.25). Autoimmune hypothyroidism was also not associated with endometriosis (OR: 1.61; 95% CI: 0.88-2.94; P = 0.12).This study revealed an association between Graves disease and endometriosis.

Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study.

BACKGROUND: A cross-sectional study has reported that nickel allergy is associated with endometriosis. However, causal studies of this association are limited. OBJECTIVE: The objective of this study was to compare the prevalence of nickel allergy in women with and without endometriosis. METHODS: We used a National Health Insurance Service (NHIS) sample cohort dataset that included approximately 1 million individuals from South Korea; the data were obtained between January 01, 2002, and December 31, 2013. We selected the endometriosis group according to diagnosis code (N80.X), surgery codes, and drug codes during the years 2009~2013. The controls were randomly matched to the endometriosis patients at a ratio of 4:1 by age and socioeconomic status. Patients with nickel allergy were defined in the cohort dataset as those with a simultaneous diagnosis code (L23.0) and patch test code during 2002~2008. RESULTS: In total, 4,985 women were selected from the NHIS cohort database and divided into an endometriosis group (997 women) and a control group (3,988 women). The number of patients with nickel allergy in the endometriosis group was eight (0.8%), and that in the control group was thirteen (0.3%). After adjustment for age and socioeconomic status, the rate of nickel allergy in was higher in the endometriosis group than in the control group [odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044]. CONCLUSIONS: We found that nickel allergy is a risk factor for endometriosis.

Menopause and blood mercury levels: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011.

This study aimed to evaluate the association between menopause and blood mercury concentrations in South Korean women. Women aged ≥20 years who participated in the Korean National Health and Nutrition Examination Survey 2008-2011 were included in this study. Primary and secondary analyses included women aged ≥20 years (n = 1,642) and 45-55 years (i.e., perimenopausal; n = 325), respectively. For all analyses, the mercury levels were log-transformed. The linear regression model for mercury levels was adjusted for age, body mass index, household income, menopausal status, hormone replacement therapy, use of oral contraceptives, smoking history, alcohol intake, physical activity, number of pregnancies, serum ferritin levels, and fish consumption. After adjusting for covariates, log-transformed blood mercury levels were significantly lower in women who were menopausal [ß-coefficient -0.1488; 95 % confidence interval -0.2586, -0.0389; P = 0.01) than in those who were premenopausal. A similar relationship was identified in perimenopausal women (ß-coefficient -0.1753; 95 % confidence interval -0.3357, -0.015; P = 0.03). The blood mercury concentration was lower in postmenopausal women than in premenopausal women. There was a significant positive correlation between blood mercury concentrations and both the frequency of alcohol intake and serum ferritin levels.

Crown-rump length measured in the early first trimester as a predictor of low birth weight.

The aim of this study is to assess the association between crown-rump length (CRL) measured before the 10th gestational week and birth weight. Results from 316 transvaginal ultrasonography scans at the 46th, 53rd, 60th, 67th, and 74th days of pregnancy were compared in low birth weight (LBW) versus normal birth weight groups. A positive correlation between CRL and birth weight was observed when CRL was measured at days 60, 67, and 74. CRL measured on the 67th day of pregnancy was significantly smaller in the LBW group than in the normal birth weight group. A cut-off value of CRL=26.5 mm measured at day 67 has the highest power to predict LBW.

A case of ovarian pregnancy after ipsilateral partial salpingectomy.

We present a case report of an ovarian pregnancy after ipsilateral partial salpingectomy. A 19-year-old woman was admitted with vaginal bleeding and right lower abdominal pain. She had a history of right partial salpingectomy caused by a tubal pregnancy. The pregnancy test result was positive, and a right adnexal mass was identified by ultrasonography. Laparoscopy revealed a right ovarian pregnancy. Thus the possibility of ipsilateral ectopic pregnancy should be considered even when the patient has a history of salpingectomy total or partial.

Subserosal pregnancy in a previous myomectomy site: a variant of intramural pregnancy.

A 35-year-old woman with a history of myomectomy underwent in vitro fertilization and became pregnant. Transvaginal ultrasound revealed a gestational sac within the subserosal area of the posterior uterine wall. The patient was treated successfully with conservative surgery, and the pathologic evaluation of the excised mass demonstrated chorionic villi involving myometrium. Early in a subsequent pregnancy, placental invasion through the sinus tract was detected. However, the pregnancy outcome was uneventful. This constitutes the first report of subserosal implantation in the uterine body. Our findings suggest that the probable pathogenesis of this rare variant of intramural pregnancy is implantation through a sinus tract made during a previous uterine surgery.

Early and late hormonal responses to the microdose gonadotropin-releasing hormone agonist in normal menstruating women.

OBJECTIVE: To assess the effect of a microdose gonadotropin-releasing hormone (GnRH) agonist on the LH, FSH, and E2 secretion in normal menstruating women. DESIGN: Prospective study. SETTING: Tertiary teaching hospital. PATIENT(S): Five normal menstruating women. INTERVENTION(S): Five microg of triptorelin was injected daily in 5 women for 7 days beginning from the cycle day 3. In the next cycle, the same amount of triptorelin was injected into the same women daily for 3 days. MAIN OUTCOME MEASURE(S): Serial serum FSH, LH, and E2 levels. RESULT(S): The FSH levels peaked (27.53 +/- 6.34 IU/L) after 5 hours, and the LH levels peaked (34.35 +/- 7.81 IU/L) by 4 hours. The increased gonadotropin levels persisted even after the second and third day of the GnRH-agonist injections, although the peak levels were not as high as observed with the first injection (19.56 IU/L in the second day, 9.15 IU/L in the third day for FSH; 32.18 IU/L in the second day, 13.59 IU/L in the third day for LH). The down-regulation of gonadotropins was established in 4 days. When the GnRH-agonist was administered for 7 days, the E2 level began to increase 6 days after the last injection. When the GnRH-agonist was administered for 3 days, the E2 level began to increase 3 days after the last injection. CONCLUSION(S): Pituitary down-regulation could be achieved even with a microdose of GnRH agonist. The increased level of gonadotropins persisted for 3 days at this dose. The duration of the down-regulation was influenced by the duration of GnRH-agonist administration.

Immunohistochemical and quantitative competitive PCR analyses of midkine and pleiotrophin expression in cervical cancer.

OBJECTIVE: The aim of this study was to determine midkine (MK) and pleiotrophin (PTN) expression in cervical cancer. METHODS: Prospective study in tertiary teaching hospital. Normal and cancerous cervical tissues were obtained from healthy women (n = 19) and from patients with cervical cancer (n = 42). The expressions of MK and PTN mRNA and protein were examined by quantitative competitive PCR and by immunohistochemistry. MK and PTN mRNA and protein expressions were examined with respect to tumor stage and size. RESULTS: The expressions of midkine and pleiotrophin mRNA in cervical cancer were higher than those in the normal cervix (MK, 175.59 +/- 63.3 vs 1.00 +/- 0.18 fmol, respectively; PTN, 3.18 +/- 1.25 vs. 0.86 +/- 0.12 fmol, respectively, P < 0.05), and their expressions were not correlated with cervical cancer stage or size of the tumor. The expressions of MK and PTN protein in cancerous tissue were higher than those in the normal cervix (P < 0.05). Moreover, the protein expression of MK, but not of PTN, correlated with tumor stage and size. The expressions of MK and PTN were not correlated with vascular density. CONCLUSIONS: Our results suggest that increased midkine mRNA and protein expressions are associated with the carcinogenesis of cervical cancer.