Predicting the fetal weight by ultrasonography for isolated polyhydramnios: Comparison of 14 formulas.

OBJECTIVE: To recalculate the estimated fetal weight (EFW) based on ultrasound measurements in patients complicated with isolated polyhydramnios, using 14 current formulas to observe which formula better predicts the EFW. METHODS: This study examined pregnant women who gave birth in the hospital between January 2015 and January 2020. Maximum vertical pocket (MVP) was classified as, mild, moderate, and severe polyhydramnios, and the patients' measurements were reanalyzed using 14 formulas. The estimation of birth weight (EBW) alongside observed birth weight (OBW) facilitated the computation of statistical indices, namely the mean absolute percentage error (MAPE) expressed as [(EBW - OBW)/OBW × 100], the mean percentage error (MPE) denoted as (EBW - OBW)/(OBW × 100), and their corresponding 95% confidence intervals. RESULTS: A total of 564 polyhydramnios patients were included in the study. When looking at the MAPE, the lowest rate (7.65) was found in the Hadlock 2 formula. Hadlock 1, Hadlock 3, and Shinozuka formulas demonstrated MAPE values most closely aligned with Hadlock 2. Weiner I and Thurnau were the formulas with the highest MAPE values. When the cut-off values for MAPE were taken as 10%, 4/14 of the formulas (Weiner I-II, Vintzleos and Thurnau) gave results above 10%. Among 14 formulas, 3 (21.4%) had positive (sonographic overestimation) (Hadlock 3, Shinozuka, and Vintzleos) and the other 11 (78.6%) had negative MPE (sonographic underestimation). CONCLUSION: The Hadlock 2 formula had the lowest MAPE in predicting birth weight in patients with polyhydramnios, closely followed by the Hadlock 1, Hadlock 3, and Shinozuka formulas.

Granulocyte colony-stimulating factor in assisted reproductive technology treatment does not increase the risk of adverse perinatal outcomes in twin pregnancies.

The aim of the study is to compare the perinatal outcomes of twin pregnancies resulting from assisted reproductive technology (ART) treatment in which granulocyte colony-stimulating factor (G-CSF) was used with those in which it was not. In this retrospective study, the clinical data of 122 dichorionic diamniotic twin pregnancies were reviewed. Pregnancies were divided into two groups, G-CSF-treated and non-G-CSF treated. Maternal age, gestational week at birth, oligohydramnios, gestational hypertension, pre-eclampsia, preterm birth, first-trimester bleeding, gestational diabetes, rupture of membrane, foetal congenital anomalies, admission to the neonatal intensive care unit, birth weight (BW), small for gestational age, BW discordance, Apgar score and placental weight were compared between the groups.IMPACT STATEMENTWhat is already known on this subject? Granulocyte colony-stimulating factor (G-CSF) administrations increase pregnancy outcomes and do not have a negative effect on perinatal outcomes in singleton pregnancies.What the results of this study add? This study showed that the perinatal outcome of dichorionic diamniotic twin pregnancies conceived after assisted reproductive technology (ART) treatment was similar in the GSF administrated and non-GSF administrated groups.What the implications are of these findings for clinical practice and/or further research? Using G-CSF to increase the success of ART does not seem to have an adverse outcome in the dichorionic diamniotic twin pregnancies.

Associations between IL-1α, IL-1ß, TNFα, and IL-6 variations, and susceptibility to transposition of the great arteries.

BACKGROUND: To evaluate the relationship between IL-1α -889C/T (rs1800587), IL-1ß -511C > T (rs16944), TNFα -308G > A (rs1800629), TNFα -238G > A (rs361525), IL-6 -174G > C (rs1800795), and IL-6 -572G > C (rs1800796) polymorphisms and the susceptibility to transposition of the great arteries (TGA). METHODS: A prospective analysis was performed on mothers whose newborns were diagnosed as having TGA. For each case of TGA, a mother who gave birth to a healthy neonate in the same period was randomly selected for the control group. The sample size was calculated before planning the study with 80% power and 5% alpha. RESULTS: Twenty-seven mothers whose newborn had TGA anomalies (group 1) and 27 mothers whose newborn had no TGA (group 2) were included in the study. There were no significant differences between the groups in terms of maternal age, pregestational body mass index, gestational age at birth and infant sex (p > 0.05). The genotype and allele distributions of IL-1α -889C/T (rs1800587), IL-1ß -511C > T (rs16944), TNFα -308G > A (rs1800629), TNFα -238G > A (rs361525), IL-6 -174G > C (rs1800795) and IL-6 -572G > C (rs1800796) gene variants were not different between the two groups (p > 0.05). CONCLUSIONS: There was no relation between IL-1α, IL-1ß, IL-6, and TNFα promoter gene polymorphisms and TGA occurrence in our study group. TRIAL REGISTRATION: This present prospective case-control study was conducted in Baskent University Hospital, Ankara, Turkey, between May 2020 and November 2021. Ethical approval was obtained from the university's Clinical Research Ethics Commitee (No: KA20/211) in accordance with the Declaration of Helsinki.

A novel technique for prediction of preterm birth: fetal nasal flow Doppler.

OBJECTIVES: Absence of fetal breathing movements (FBM) has been found to be a good predictor of preterm delivery in symptomatic patients. However, analysis of FBM patterns and Doppler measurement of them for preterm birth prediction have not been performed before. In this study, we aimed to investigate and analyze FBM patterns in symptomatic preterm labor patients by fetal ultrasonography and nasal Doppler. METHODS: This was a multicenter, prospective cohort study. Singleton pregnant patients between 24 and 37 gestational weeks diagnosed with preterm labor were included in the study. Patients were evaluated in three groups: no FBM (Group 1), regular FBM (Group 2), irregular FBM (Group3). RESULTS: Seventy-three patients were available for the final analysis after exclusion. Preterm delivery rate in 24 h in groups were 91.7, 32.7 and 100%, respectively. The absence of FBM (Group 1) was statistically significant for preterm delivery in for both 24 (91.7 vs. 42.6%, p=0.002) and 48 h (91.7 vs. 49.2%, p=0.006) when compared with fetal breathing positive Group 2 and 3. In fetal nasal Doppler analyses in Group 2, the inspiration/expiration number rate was significantly lower in the patients who delivered in 24 h (0.98±0.2 vs. 1.25±0.57, p=0.015). By using fetal nasal Doppler, combination of absence of FBM or irregular FBM or regular FBM with inspiration number/expiration number (I/E) <1.25 detects 94.6% of patients who will eventually deliver in the first 24 h after admission. CONCLUSIONS: Examining FBM patterns and using nasal Doppler may help the clinician to differentiate those who will deliver preterm and may be an invaluable tool for managing preterm labor patients.

Comparison of placental α microglobulin-1 protein assay (Amnisure) with speculum examination for the diagnosis of premature preterm rupture of membranes (PPROM): a clinical evaluation.

In this study, we aimed to compare the clinical outcomes of Premature Preterm Rupture of Membranes (PPROM) cases diagnosed by classical speculum examination and by placental alpha microglobulin-1 protein (PAMG-1) assay. The medical records of all patients with singleton pregnancies that were diagnosed with PPROM were retrospectively reviewed. Singleton pregnancies with PPROM diagnosis that was confirmed either by direct visualisation of amniotic fluid leaking through the cervix or by placental alpha microglobulin-1 protein (PAMG-1) assay if no amniotic fluid leakage was documented were included in the study. Demographics, prenatal and postnatal characteristics were reviewed from the medical charts and were recorded. The study included 138 pregnancies with PPROM; 111 patients in clinical speculum examination group and 27 in PAMG-1 assay group. There were no significant differences in maternal and pregnancy characteristics between the clinical speculum examination and PAMG-1 assay groups. Foetal outcomes were comparable between clinical speculum examination and PAMG-1 assay groups. In the clinical speculum examination group, there were nine (8.1%) chorioamnionitis cases, however, there were no chorioamnionitis cases in the PAMG-1 assay group during the latency period (p = .21).Impact statementWhat is already known on this subject? Placental alpha microglobulin-1 protein assay uses immunochromatography method to detect trace amount of placental alpha microglobulin-1 protein in vaginal fluids and has high sensitivity and specificity for ROM diagnosis. However, to the best of our knowledge, the clinical outcome of ROM cases detected by classical speculum examination and by placental alpha microglobulin-1 protein assay has not been compared in the literature previously.What do the results of this study add? Although statistically insignificant, cases diagnosed by PAMG-1 assay had lower risk of chorioamnionitis during latency period.What are the implications of these findings for clinical practice and/or further research? Whether cases diagnosed by PAMG-1 assay represent a milder form of rupture of membranes than cases diagnosed by classical speculum examination group warrants further research.

Clinical management of coronavirus disease 2019 (COVID-19) in pregnancy: recommendations of WAPM-World Association of Perinatal Medicine.

These guidelines follow the mission of the World Association of Perinatal Medicine, which brings together groups and individuals throughout the world with the goal of improving outcomes of maternal, fetal and neonatal (perinatal) patients. Guidelines for auditing, evaluation, and clinical care in perinatal medicine enable physicians diagnose, treat and follow-up of COVID-19-exposed pregnant women. These guidelines are based on quality evidence in the peer review literature as well as the experience of perinatal expert throughout the world. Physicians are advised to apply these guidelines to the local realities which they face. We plan to update these guidelines as new evidence become available.

Multi-center results on the clinical use of KANET.

An extensive review of the literature on the diagnostic and clinical accuracy of Kurjak's antenatal neurodevelopmental test (KANET) and the summarized results of the multi-center study involving 10 centers revealed that four-dimensional ultrasonography (4D US) has become a powerful tool and KANET a valuable test that empowers the clinicians worldwide to evaluate the fetal behavior in a systematic way and contribute to the detection of fetuses that might be at high risk for neurological impairments and in particular cerebral palsy (CP). After 10 years of clinical use, many published papers and multi-center studies, hundreds of trained physicians and numerous tests performed all over the world, KANET has proven its value and has been showing encouraging results so far. The aim of this paper is to show the results from the studies done so far and to reveal the clinical value of the KANET. We expect that data from the larger ongoing collaborative study, the short- and long-term postnatal follow-up will continue to improve our knowledge. Ultimately, we all strive to prevent the CP disorders, autism spectrum disorder (ASD) and other neurological impairments and we are convinced that KANET might be helpful in the realization of this important aim.

Are There Any Predictors of Endometrial Premalignancy/Malignancy within Endometrial Polyps in Infertile Patients?

BACKGROUND: In the literature, there is no detailed analysis on the prediction factors for premalignancy/malignancy within endometrial polyps (EPs) in infertile patients. In this study, we aimed to determine the frequency of endometrial premalignancy/malignancy within EPs in infertile patients undergoing office hysteroscopic polypectomy and identify the factors that can potentially predict an endometrial premalignancy/malignancy within EPs. METHOD: A total of 957 infertile patients undergoing office hysteroscopy were diagnosed with EPs between February 2011 and August 2018. Patients were divided into 2 groups according to the pathological examination of EPs as benign (Group 1; n = 939) and premalignant/malignant (Group 2; n = 18). The medical records of all patients included in the study were reviewed retrospectively. RESULTS: In this cohort, prevalence of endometrial premalignancy/malignancy within EPs was 18/957 (1.88%). On univariate analysis, age, polyp size, diabetes, hypertension, and causes of infertility did not differ between the 2 groups. On multivariate analysis, diffuse polypoid appearance of the endometrial cavity on office hysteroscopy (hazard ratio [HR] 4.1; 95% CI 1.576-10.785), duration of infertility, (HR 4; 95% CI 1.279-12.562), and body mass index (HR 7.9; 95% CI 2.591-24.258) were found to be independent predictors of endometrial premalignancy/malignancy within polyps in infertile patients. CONCLUSION: When diffuse polypoid appearance of the endometrial cavity is detected in an infertile patient during office hysteroscopy, hysteroscopy-guided resection and endometrial curettage should be performed. The pathological specimen should be sent for histopathological evaluation to diagnose possible endometrial premalignancy/malignancy within polyps.

The importance of prenatal 3-dimensional sonography in a case of a segmental overgrowth syndrome with unclear chromosomal microarray results.

PIK3CA-related overgrowth spectrum, caused by mosaic mutations in the PIK3CA gene, is associated with regional or generalized asymmetric overgrowth of the body or a body part in addition to other clinical findings. Three-dimensional ultrasonography (3-D US) has the capability to display structural abnormalities in soft tissues or other organs, thereby facilitating identification of segmental overgrowth lesions. We present a case suspected of having a segmental overgrowth disorder based on 3-D US, whose chromosomal microarray result was abnormal, but apparently was not the cause of the majority of the fetus's clinical features.

Use of translabial three-dimensional power Doppler ultrasound for cervical assessment before labor induction.

OBJECTIVE: To compare translabial three-dimensional (3D) power Doppler ultrasound with Bishop score and transvaginal ultrasound measurements for cervical assessment before induction of labor with dinoprostone or cervical ripening balloon. MATERIALS AND METHODS: Translabial cervical volume and length, vascularization indices and transvaginal cervical length were measured. Results were compared among women who had vaginal delivery at 24 h or less and more than 24 h after the insertion of the dinoprostone vaginal insert or cervical ripening balloon and among women who had vaginal delivery and cesarean delivery for failure to go into labor or failure to progress. RESULTS: There was no correlation between the time to delivery after a ripening agent was applied and translabial cervical volume, translabial cervical length, vascularization index (VI), flow index (FI), vascularization flow index (VFI), transvaginal cervical length and Bishop scores. The ultrasonographic measurements were no different among women who had vaginal delivery at 24 h or less and more than 24 h and among women who had vaginal delivery and cesarean delivery for failure to go into labor or failure to progress. CONCLUSION: In this study, we failed to demonstrate the superiority of translabial 3D ultrasonography over Bishop score and transvaginal ultrasonography for predicting the success of induction of labor.

Estimation of fetal weight by ultrasonography after preterm premature rupture of membranes: comparison of different formulas.

OBJECTIVE: To compare different ultrasonographic fetal weight estimation formulas in predicting the fetal birth weight of preterm premature rupture of membrane (PPROM) fetuses. METHODS: Based on the ultrasonographic measurements, the estimated fetal weight (EFW) was calculated according to the published formulas. The comparisons used estimated birth weight (EBW) and observed birth weight (OBW) to calculate the mean absolute percentage error [(EBW-OBW)/OBW×100], mean percentage error [(EBW-OBW)/OBW×100)] and their 95% confidence intervals. RESULTS: There were 234 PPROM patients in the study period. The mean gestational age at which PPROM occured was 31.2±3.7 weeks and the mean gestational age of delivery was 32.4±3.2 weeks. The mean birth weight was 1892±610 g. The median absolute percentage error for 33 formulas was 11.7%. 87.9% and 21.2% of the formulas yielded inaccurate results when the cut-off values for median absolute percentage error were 10% and 15%, respectively. The Vintzileos' formula was the only method which had less than or equal to 10% absolute percentage error in all age and weight groups. CONCLUSIONS: For PPROM patients, most of the formulas designed for sonographic fetal weight estimation had acceptable performance. The Vintzileos' method was the only formula having less than 10% absolute percentage error in all gestational age and weight groups; therefore, it may be the preferred method in this cohort. Amniotic fluid index (AFI) before delivery had no impact on the performance of the formulas in terms of mean percentage errors.

Incorporating first trimester analytes to predict delivery of a large for gestational infant in women with impaired glucose tolerance.

AIM: To investigate first trimester maternal characteristics of women with impaired glucose tolerance that deliver large for gestational age (LGA) infants. METHODS: Nested analysis from a prospective study of singleton pregnancies enrolled at first trimester. We studied women with an abnormal 1 h glucose challenge test that had normal follow-up oral glucose tolerance testing. Maternal characteristics, ultrasound parameters and serum analytes were stratified by subsequent delivery of an LGA infant. Parameters identified as significant on univariate analysis were used for a derivation of prediction by logistic regression. Odds ratio and prediction performance was determined using receiver operator curve (ROC) statistics. RESULTS: A total of 33/114 (28.9%) women meeting the criteria delivered LGA infants. Maternal height (cm), and first trimester pregnancy-associated protein-A and free ß-hCG (MoM) predicted delivery of an LGA infant (ROC area under curve 0.73; 95% CI 0.63-0.83). At a cutoff value of 0.172 the prediction rule achieved 91% sensitivity, 44% specificity, 41% positive predictive and 92% negative predictive value. CONCLUSION: Maternal height and first trimester high free ß-hCG and PAPP-A levels may be used as predictors for delivery of LGA infants in women with impaired glucose tolerance.

Finding the best formula to predict the fetal weight: comparison of 18 formulas.

BACKGROUND: To compare the accuracy of 18 formulas in predicting fetal weight and also to make a comparison of these formulas in low-birth-weight fetuses (<2,500 g) and in fetuses weighing >4,000 g. METHODS: Four-hundred-and-ninety-five pregnant patients were enrolled. The estimated fetal weight was calculated using 18 different formulas. The mean percentage error, the mean absolute percentage error and reliability analysis were used to compare the performance of the formulas. RESULTS: The Cronbach's alpha was the highest in the formulas Hadlock I (0.977 (95% CI = 0.972-0.980)), Hadlock III (0.977 (95% CI = 0.972-0.980)) and Ott (0.975 (95% CI = 0.970-0.979)) in all fetuses. It was the highest in formulas Ott (0.383 (95% CI = 0.091-0.581)), Hadlock IV (0.371 (95% CI = 0.074-0.572)) and Combs (0.369 (95% CI = 0.071-0.571)) in fetuses >4,000 g. It was the highest in formulas Coombs (0.957 (95% CI = 0.940-0.569)), Ott (0.956 (95% CI = 0.939-0.968)) and Hadlock IV (95% CI = 0.956 (0.938-0.968)) in fetuses <2,500 g. CONCLUSION: We noted that formulas Hadlock I, Hadlock III and Ott may be used to predict the estimated fetal weight accurately in all fetuses in our study. Formulas Ott, Hadlock IV and Coombs may be preferred to predict EFW in fetuses <2,500 g and >4,000 g. Better formulas should be developed to predict the fetal weight in fetuses >4,000 g.

Factors that increase reactivity during fetal nonstress testing.

PURPOSE OF REVIEW: The most common method of antepartum fetal surveillance is the nonstress test (NST). Although it has satisfactory false-negative rates, dubious nonreactive results may challenge the physician. Any method or factor increasing the reactive NST results or shortening the time to attain a reactive test may be considerably useful. RECENT FINDINGS: Most of the studies have found no effect of maternal glucose administration on fetal heart rate and fetal activity, specificity of NST, time to reactivity and percentage of reactive NST results when compared with the control group. Maternal intake of 70% cocoa or caffeine had stimulating action on the fetal reactivity, and this effect on the fetal heart rate was more marked with high concentrations of cocoa (80%). Studies on maternal positioning during NST had equivocal results. Fetal manipulation has no impact on the NST reactivity. Vibroacoustic and halogen light stimulation may be associated with a reduction in time to reactivity. SUMMARY: These methods may increase the reactivity during a NST and may facilitate the antenatal fetal surveillance.

Fetal echogenic bowel in association with Zellweger syndrome.

Increased echogenicity of fetal bowel in the second trimester obstetrical ultrasound has been described in association with several pathologic conditions, such as growth restriction, aneuploidy, cystic fibrosis, congenital infections, and gastrointestinal malformations. Zellweger syndrome (ZS) is the prototype of peroxisomal disorders characterized by craniofacial dysmorphism and severe neurologic abnormalities. We report two cases with fetal echogenic bowel (FEB) but no associated anomalies and normal fetal growth. After birth, clinical and laboratory findings led to diagnosis of ZS. Association of FEB with neurometabolic disorders is limited to a few case reports in the medical literature. To the best of our knowledge, this is the first report of ZS associated with FEB.

Effect of body mass index on latency periods after history-indicated cervical cerclage.

BACKGROUND: The impact of maternal body mass index (BMI) on cervical cerclage outcomes is not clear in the literature. AIM: We sought to investigate the impact of BMI on history-indicated cervical cerclage outcomes in our unit. METHODS: We retrospectively reviewed 196 history-indicated cervical cerclage procedures. The results were analysed according to the BMI groups <25, 25-30 and ≥30 kg/m(2) . RESULTS: A total of 122 cases were available for the final analysis. Thirty-two (26.1%) of the women had normal BMI (BMI < 25), 69 (56.5%) were overweight (BMI = 25-30) and 21 (17.4%) were obese (BMI ≥ 30). The mean gestational age of delivery according to BMI groups <25, 25-30 and ≥30 were 37.2 ± 3.1, 36.0 ± 5.3 and 36.0 ± 4.9 weeks (P = 0.591), respectively. The mean latency periods according to BMI groups <25, 25-30 and ≥30 were 24.3 ± 3.2, 21.1 ± 5.1 and 21.4 ± 4.9 weeks (P = 0.171), respectively. We found no correlation between the BMI and latency periods (Spearman's rho = -0.252). The multivariable logistic regression model found no variable to affect preterm birth rates. CONCLUSIONS: The BMI has no impact on history-indicated cervical cerclage procedure outcomes. Normal weight, overweight and obese women had similar latency periods after history-indicated cervical cerclage. This high percentage of preterm birth risk necessitates close surveillance of these women for preterm birth.

Comparison of sublingual misoprostol with lidocaine spray for pain relief in office hysteroscopy: a randomized, double-blind, placebo-controlled trial.

STUDY OBJECTIVE: To compare the effectiveness of sublingual misoprostol with lidocaine pump spray for office hysteroscopy. DESIGN: Premenopausal women who had an indication for office hysteroscopy were included in this randomized, double-blind, placebo-controlled study. Eighty-two patients were evaluable for the final analysis. SETTING: A tertiary referral center. PATIENTS: Premenopausal women who had an indication for office hysteroscopy were included. Eighty-two patients were evaluable for the final analysis. INTERVENTIONS: Patients were randomized to receive either sublingual misoprostol and placebo of lidocaine or lidocaine pump spray applied to the cervix and placebo of misoprostol. MEASUREMENTS AND MAIN RESULTS: When compared with the lidocaine group, patients in the misoprostol group reported less pain by the immediate visual analog scale scores (2.2 ± 0.98 vs. 2.6 ± 0.99, p = .030), whereas visual analog scale scores at 10 minutes were similar between groups (2.1 ± 0.98 vs. 2.36 ± 1.06, p = .156). CONCLUSION: Sublingual misoprostol is more effective than lidocaine spray in pain reduction during office hysteroscopy. Misoprostol may cause vaginal spotting, which may impair the vision during hysteroscopy especially just after the menstrual period. Preventive measures should be taken to make the procedure pain free because the physician may underestimate pain perception during the procedure.

Effect of obesity on perioperative outcomes of laparoscopic hysterectomy.

OBJECTIVE: To compare the effect of obesity on perioperative outcomes in women undergoing laparoscopic hysterectomy. STUDY DESIGN: In this retrospective cohort study, perioperative outcomes of all women who underwent laparoscopic supracervical hysterectomy (LSH) or total laparoscopic hysterectomy (TLH) for benign conditions were compared between obese (body mass index > or = 30 kg/m2) and nonobese women. RESULTS: Baseline characteristics were similar between 320 (33.0%) obese and 550 (67%) nonobese women except for race and the rates of hypertension and diabetes. The adjusted rates of urinary tract injury, vaginal cuff dehiscence, postoperative fever, and ileus were similar between the groups. For obese women, however, bleeding requiring transfusion was almost 3-fold (3.1 vs. 1.1%, adjusted odds ratio [AOR] 2.93, 95% confidence interval [CI] 1.10-7.80) and laparotomy risk was approximately 2-fold (7.5 vs. 3.5%, AOR 2.35, 95% CI 1.30-4.24) increased. The rate of urinary tract injury was 3.2% when obese women had TLH, but it was 0.3% for LSH performed on nonobese women. Of all 7 cuff dehiscences, 5 (71%) occurred in nonobese women undergoing TLH. CONCLUSION: Obesity increased the risk of bleeding requiring transfusion and conversion to laparotomy but did not influence the other perioperative complications. On subgroup analysis, LSH in nonobese women seems to result in best outcomes.

Ovarian gonadoblastoma with dysgerminoma in a 15-year-old girl with 46, XX karyotype: case report and review of the literature.

OBJECTIVE: To present a challenging case of hCG positivity in a young patient and to review similar cases reported in the literature. METHODS: Literature search of gonadoblastoma cases with pure 46, XX karyotype using PubMed database. RESULTS: A 15-year-old girl with hCG positivity was investigated for the source and the initial diagnosis was an ectopic pregnancy. An ovarian tumor was identified after failed methotrexate therapy and the pathological diagnosis was gonadoblastoma with dysgerminoma. To the best of our knowledge, the case was unique in the literature for having the smallest diameter of a gonadoblastoma tumor with 46, XX karyotype. CONCLUSION: Differential diagnosis of perimenarcheal vaginal bleeding may be challenging for the clinician. Rare causes such as pregnancy both intrauterine and extrauterine and hormone producing tumors should be kept in mind.