An Illustrated Review of the Recent 2019 World Health Organization Classification of Neuroendocrine Neoplasms: A Radiologic and Pathologic Correlation.

ABSTRACT: Recent advances in molecular pathology and an improved understanding of the etiology of neuroendocrine neoplasms (NENs) have given rise to an updated World Health Organization classification. Since gastroenteropancreatic NENs (GEP-NENs) are the most common forms of NENs and their incidence has been increasing constantly, they will be the focus of our attention. Here, we review the findings at the foundation of the new classification system, discuss how it impacts imaging research and radiological practice, and illustrate typical and atypical imaging and pathological findings. Gastroenteropancreatic NENs have a highly variable clinical course, which existing classification schemes based on proliferation rate were unable to fully capture. While well- and poorly differentiated NENs both express neuroendocrine markers, they are fundamentally different diseases, which may show similar proliferation rates. Genetic alterations specific to well-differentiated neuroendocrine tumors graded 1 to 3 and poorly differentiated neuroendocrine cancers of small cell and large-cell subtype have been identified. The new tumor classification places new demands and creates opportunities for radiologists to continue providing the clinically most relevant report and on researchers to design projects, which continue to be clinically applicable.

State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

ABSTRACT: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

Imaging of Neuroendocrine Neoplasms; Principles of Treatment Strategies. What Referring Clinicians Want to Know.

ABSTRACT: Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings. Treatment strategies vary depending on the specific subtype of NEN. In this review, we will focus on treatment strategies and therapies including the information relevant to clinicians in order to undertake optimal management and treatment decisions, the implications of different therapies on imaging, and how to ascertain their possible complications and treatment effects.

Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses.

ABSTRACT: Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.

Risk factors of osteoporosis and osteopenia in postmenopausal women based on the L2-L4 BMD T score of the lumbar spine: a study in Iran.

OBJECTIVE: To determine the risk factors of osteoporosis and osteopenia of the spine in postmenopausal women. METHOD: An analytical cross-sectional study was performed on postmenopausal women. The T-score of the lumbar spine (L2-L4) was measured by densitometry and compared between osteoporotic, osteopenia, and normal women. RESULTS: One thousand three hundred fify-nine postmenopausal women were evaluated. The prevalence of osteopenia and osteoporosis was 58.2% and 12.8% respectively. Age, BMI, parity, total breastfeeding years, dairy use, calcium-D supplements, and regular exercise were significantly different in women with osteoporosis, osteopenia, and normal women. Ethnicity, diabetes, and previous fracture history were only other among women with osteoporosis (not osteopenia) and normal women. For osteopenia of the spine, age [AOR 1.08 (1.05-1.11; p < .001)] was the risk factor, and BMI = >30 [AOR 0.36 (0.28-0.58; p < .001)] and BMI 25-<30 [AOR 0.55 (0.34-0.88; p = .012)] were protective factors. Hyperthyroidism (AOR 23.43, p = .010), Kurdish ethnicity (AOR 2.96, p = .009), not having regular exercise (AOR 2.22, p = .012), previous fracture history (AOR 2.15, p = .041)], and age (AOR 1.14, p < .001)], were risk factors for osteoporosis, while BMI ≥30 [AOR 0.09, p < .001], BMI 25-<30 [AOR 0.28, p = .001], and diabetes [AOR 0.41, p = .038] were protective factors for osteoporosis of the spine. CONCLUSION: Hyperthyroidism, low BMI <25, parity ≥ 6, Kurdish ethnicity, not having regular exercise, history of previous fracture, and age, were risk factors for osteoporosis of the spine respectively, while low BMI and age were risk factors for osteopenia.

Hyaluronic acid gel application versus ovarian suspension for prevention of ovarian adhesions during laparoscopic surgery on endometrioma: a double-blind randomized clinical trial.

BACKGROUND: This study aimed to compare the effect of ovarian suspension and hyaluronic acid gel to prevent re-adhesions after laparoscopic endometrioma surgery. METHODS: This randomized clinical trial was conducted at Rasoul-e-Akram and Pars Hospitals, Tehran, Iran, 2016-18. Fifty patients with bilateral endometrioma and pelvic adhesions, the candidates of laparoscopic surgery, were included. In each patient, at the end of ovarian cystectomy and adhesiolysis, one of the ovaries was randomly sutured to the abdominal wall, and the HYAcorp Endogel covered the other; the adhesion rate was compared between the groups by ultrasonography, three-month after surgery. RESULTS: Mean age of patients was 32.6 years. Presurgical variables were similar between right and left ovaries and the study groups (P > 0.05). Postsurgical ultrasonography showed that ovarian soft markers, including < 1/3 ovarian adhesions (minimal adhesions) in 80.5% of ovaries of the Endogel group and 35.5% of the ovarian suspension group (P < 0.001) with higher ovarian mobility in the Endogel group (65% vs. 22%) (P = 0.001). In addition, site-specific tenderness and ovarian fading margin were lower in the Endogel group (P < 0.001). Trial registration Clinical trial registry number: IRCT2015081723666N1, 12.19.2015, Date of registration: 01/02/2016; https://en.irct.ir/trial/20174?revision=20174 . Date and number of IRB: 2015, I.R.IUMS.REC.1394.24703. CONCLUSION: Hyaluronic acid gel can be more effective than ovarian suspension in preventing ovarian adhesions after laparoscopic treatment of endometriosis.

Isonicotinic acid hydrazide (INH) versus extra-amniotic saline infusion (EASI) for cervical ripening at term: a randomised controlled trial.

The purpose of this trial was to compare extra-amniotic saline infusion (EASI) and intravaginal isoniazid (INH) for cervical ripening. This randomised clinical trial included 150 pregnant women who were undergoing induction of labour and who required pre-induction cervical ripening. Patients were randomly assigned to receive EASI or intravaginal INH. Bishop's score at the beginning of the study and before oxytocin infusion was not significantly different between INH and EASI groups. However, the time from first intervention to the beginning of the induction and also to the beginning of the active phase were significantly shorter in EASI group (p value ≤.001). Moreover, INH did not influence the labour process after the beginning of the active phase of labour. In conclusion, INH could be used for cervical ripening especially in the outpatient setting; however, it is a slower ripening agent compared to EASI.Impact StatementWhat is already known on this subject? To date there has been only one study about the safety and effectiveness of isoniazid (INH) in cervical ripening at term pregnancy which has compared INH with misoprostol.What do the results of this study add? The results of this study showed that vaginal INH is an effective agent for cervical ripening at term but in comparison to extra-amniotic saline infusion (EASI) it takes a longer time.What are the implications of these findings for clinical practice and/or further research? INH can be used in outpatient settings for cervical ripening at term pregnancy which makes it convenient for patient and cost effective for both patient and health system. Further studies are needed to discover the clinical efficacy of INH in comparison to other ripening methods and also the best dosage of INH for cervical ripening.

A systematic review on the prevalence of endometriosis in women.

Background & objectives: Endometriosis is one of the causes of female infertility, but the prevalence of endometriosis is not exactly known. We conducted a systematic review and meta-analysis to provide an estimate of the prevalence of endometriosis in women considering the stage of disease, diagnostic method, geographical distribution, clinical symptoms and sample size. Methods: MEDLINE, Web of Science, Google Scholar, Scopus and Cumulative Index of Nursing and Allied Health were searched to identify peer-reviewed studies published from January 1990 to December 2018 reporting the prevalence of endometriosis. Relevant additional articles were identified from the lists of the retrieved articles. Studies with cross-sectional design were included in the meta-analysis. Results: The overall prevalence of endometriosis was 18 per cent [95% confidence interval (CI): 16-20] and the prevalence of endometriosis by stage ranged from two per cent (95% CI: 1-4) for stage 4 to 20 per cent (95% CI: 11-28) for stage 1. The prevalence levels of endometriosis in women with infertility, chronic pelvic pain and asymptomatic were 31 (95% CI: 15-48), 42 (95% CI: 25-58) and 23 per cent (95% CI: 19-26), respectively. Interpretation & conclusions: The results of this study showed that the prevalence of endometriosis in developing countries was high. Future studies are needed to explore other factors affecting the prevalence of endometriosis worldwide, which may help develop future prevention programmes.

Uterine Isthmus Tourniquet during Abdominal Myomectomy: Support or Hazard? A Randomized Double-Blind Trial.

BACKGROUND AND OBJECTIVES: A tourniquet has been suggested as a useful means of reducing massive hemorrhage during myomectomy. However, it is not clear whether the restricted perfusion affects the ovaries. In the present study, we examined the effect of a tourniquet on ovarian reserve and blood loss during myomectomy. MATERIALS AND METHODS: In a randomized double-blind clinical trial, fertile nonobese patients scheduled for abdominal myomectomy at Rasool-e-Akram Hospital from February 2018 to June 2019 were randomized to a tourniquet (n = 46) or a non-tourniquet group (n = 35). Serum levels of anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) were measured before and 3 months after surgery, blood loss was recorded during surgery, and serum levels of hemoglobin (Hb) were recorded before surgery, 6 h and 3 days after surgery. SPSS version 21 was used for statistical analysis. RESULTS: Demographic, obstetric, and myoma characteristics were similar in the 2 groups (p > 0.05). The mean baseline values of AMH and FSH did not differ between groups (p > 0.05). After surgery, only FSH was higher in the control group (p = 0.043). Despite the time taken to fasten and open the tourniquet, the mean operating time was shorter in the tourniquet group (p < 0.001). Blood loss was higher in the control group (p = 0.005). The drop in Hb levels at 6 h after surgery was higher in the non-tourniquet group (p = 0.002). Blood loss was significantly associated with the duration of surgery (r = 0.523, p < 0.001). CONCLUSION: The use of a tourniquet during abdominal myomectomy significantly reduced the mean volume of blood loss compared to the non-tourniquet group, while it did not prolong the duration of surgery, nor reduced the ovarian reserve. A tourniquet is a safe and efficient measure during abdominal myomectomy.

The effect of diabetes on the risk of endometrial Cancer: an updated a systematic review and meta-analysis.

BACKGROUND: Previous studies conducted on the association between diabetes and the risk of endometrial cancer have reported controversial results that have raised a variety of questions about the association between diabetes and the incidence of this cancer. Thus, the aim of this systematic review and meta-analysis was to more precisely estimate the effect of diabetes on the risk of endometrial cancer incidence. METHODS: All original articles were searched in international databases, including Medline (PubMed), Web of sciences, Scopus, EMBASE, and CINHAL. Search was done from January 1990 to January 2018 without language limitations. Also, logarithm and standard error logarithm relative risk (RR) were used for meta-analysis. RESULTS: A total of 22 cohort and case-control studies were included in this meta-analysis, of which 14 showed statistically significant associations between diabetes and risk of endometrial cancer. Diabetes was associated with increased risk of endometrial cancer (RR = 1.72, 95% CI 1.48-2.01). The summary of RR for all 9 cohort studies was 1.56 (95% CI 1.21-2.01), and it was 1.85 (95% CI 1.53-2.23) for 13 case control studies. The summary of RR in hospital-based studies was higher than other studies. Thirteen of the primary studies-controlled BMI as a confounding variable, and the combined risk of their results was 1.62 (95% CI 1.34-1.97). CONCLUSIONS: Diabetes seems to increases the risk of endometrial cancer in women, and this finding can be useful in developing endometrial cancer prevention plans for women having diabetes.

Bilateral Hyperplasia of Bartholin's Gland: A Case Report.

A 37-year-old woman underwent surgery to remove bilateral vulvar masses. The masses were firm, non-tender, and immobile. Pathologic finding was a well-delineated creamy grayish mass with a homogenous grayish solid surface and mild edema, chronic inflammatory infiltration, and focal dilation of the ducts with squamous metaplasia. The diagnosis was hyperplastic and hypertrophied Bartholin's gland. Hyperplasia is a rare etiology for an enlarged Bartholin's gland. Clinical presentation of Bartholin's gland nodular hyperplasia is rather specific, although inflammatory lesion is the most common cause of swelling of the Bartholin's gland in all age groups. Bartholin's hyperplasia should be considered in cases with a solid mass. Total surgical excision is required for diagnosis. Only a few cases of Bartholin's gland hyperplasia have been reported in the literature. Our patient has been receiving regular follow-up examination and there is no evidence of dyspareunia, perineal pain, and recurrent disease 12 months after surgery.

Normal labor curve is affected by fetus gender: A cohort study.

Background: Fetal male gender may affect the progression of labor and could be a risk factor for labor arrest. This study was conducted to evaluate the effect of fetus gender on labor curve. Methods: In this cohort study, 1550 singleton term pregnant women in labor phase (either spontaneous or by induction) were enrolled. Results of regular cervical examination, dilation, length of labor stages, mode of delivery, and sex of the fetus, and birth weight were recorded for all participants. Labor progression curve was compared between two sex groups with independent t test and chi2 test. Results: Finally, 1527 women completed the study (47.8% female and 52.1% male). Mean duration from beginning of the active phase up to full dilatation, from 4 to 6 cm, 6 to 8 cm, and 8 to 10 cm dilatations, were significantly longer in the male sex group compared to the female (p˂0.05). All durations were also significantly different when parity was considered (p˂0.05). We could not show fetal sex as an independent risk factor for active phase arrest (OR Adjusted: 1.18, CI 95% 1.01:1.42). Conclusion: Active phase stage was slower and longer in women who carried male fetuses compared to those carrying female fetuses; however, fetal sex did not increase the risk of active phase arrest.

Comparison of intramuscular progesterone with oral nifedipine for treating threatened preterm labor: A randomized controlled trial.

Background: Threatened preterm labor (TPL) is the leading cause of hospitalization during pregnancy. Tocolytic agents are the primary therapeutic options for TPL. The aim of this study is to compare intramuscular progesterone with oral nifedipine as a tocolytic agent. Methods: This randomized controlled trial was carried out in a teaching hospital (Shahid Akbarabadi) in Tehran, Iran, from December 2011 to November 2012. Three hundred and fifteen singleton pregnant women aged >18 yrs at 26-34 weeks' gestation with the diagnosis of threatened preterm labor (TPL) were randomly received either intramuscular progesterone or oral nifedipine for tocolysis. Maternal and neonatal outcomes were then compared between the two interventions. P value less than 0.05 was considered statistically significant. IRCT registration number of this study is IRCT201112198469N1 Results: The success rate of progesterone and nifedipine in treating TPL were 83% and 82.7%, respectively. There was no significant difference between the two interventions with regard to gestational age at delivery, type of delivery, the time interval until the delivery, birth weight, NICU admission rate and hospital stays. Progesterone administration was associated with lower duration of NICU stay as compared with nifedipine (0.33±0.77 days vs.1.5±3.2 days, p<0.05). None of the two drugs caused any major side effects. Conclusion: Single dose intramuscular progesterone is as effective as oral nifedipine in treating TPL. It also significantly reduces the NICU stay.

Can combination of hysterosalpingography and ultrasound replace hysteroscopy in diagnosis of uterine malformations in infertile women?

BACKGROUND: Müllerian anomalies are associated with infertility. Hysteroscopy as the gold standard for evaluating Müllerian anomalies is an invasive, expensive and risky procedure which requires enough experience. Transvaginal sonography (TVS) and hysterosalpingography (HSG) are less invasive procedures, but there is little known about the accuracy of these tests. The aim of this study was to evaluate the accuracy of the combination of TVS and HSG with hysteroscopy as the gold standard. METHODS: Medical records of infertile women who were undertaken all three diagnostic modalities were reviewed to analyze their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Ninety-nine infertile women were assessed with a mean±SD age of 29.1±6.47 years, mean±SD duration of themarriage of 8.9±10.28 years, and mean±SD duration of infertility of 5.6± 4.16 years. The sensitivity, specificity, PPV, and NPV of TVS were 98.55%, 30%, 76.4%, and 90%, respectively. HSG had a sensitivity of 95.6%, specificity of 60%, PPV of 84.62%, and NPV of 85.71%.When both modalities were combined, the sensitivity, specificity, PPV, and NPV were 94.2, 66.67, 86.67, and 83.33%, respectively. The diagnostic accuracy of single TVS, HSG or combined techniques was statistically similar that was equal to 77.7, 84.8 and 85.8 % respectively. CONCLUSION: The accuracy of combination of two diagnostic modalities, 2D TVS and HSG is not higher than HSG alone for assessing uterine malformation in infertile women.

Advantages of Recombinant Follicle-Stimulating Hormone over Human Menopausal Gonadotropin in Intrauterine Insemination: A Randomized Clinical Trial in Polycystic Ovary Syndrome-Associated Infertility.

BACKGROUND: Various gonadotropin preparations have been used for ovarian stimulation in intrauterine insemination (IUI). The purpose of the current study was to compare human menopausal gonadotropin (hMG) and recombinant follicle-stimulating hormone (rFSH) combined with clomiphene citrate (CC) in IUI cycles for polycystic ovary syndrome-associated infertility. METHODS: In this prospective trial, couples prepared for IUI cycles were randomly allocated either to receive CC and rFSH (group A, n = 132) or CC and hMG (group B, n = 144) for ovarian stimulation. Outcomes including rates of clinical pregnancy, miscarriage, ovarian hyperstimulation syndrome, multiple pregnancy, cancellation and live birth were compared. RESULTS: The duration of gonadotropin therapy was shorter and total doses of gonadotropins was lower in the rFSH group. The number of stimulated follicles reaching >17 mm diameter was comparable between groups, but the mean follicular diameter was significantly higher in the rFSH group. The endometrium was also significantly thicker at the time of human chorionic gonadotropin administration in the rFSH group. However, pregnancy outcomes, including the rates of clinical pregnancy, ongoing pregnancy, live birth, miscarriage, ovarian hyperstimulation syndrome and cancellation, were similar between groups. CONCLUSION: IUI cycles in which rFSH is administered may result in shorter duration of treatment, a lower total gonadotropin dose and better follicular and endometrial characteristics on the day of human chorionic gonadotropin injection. © 2015 S. Karger AG, Basel.

In vitro fertilization outcome following embryo transfer with or without preinstillation of human chorionic gonadotropin into the uterine cavity: a randomized controlled trial.

BACKGROUND: Intrauterine injection of human chorionic gonadotropin (hCG) at embryo transfer (ET) has been shown to improve the outcome of assisted reproductive techniques. The aim of this study was to confirm previous findings. METHODS: In this randomized controlled trial, 483 infertile women who were candidates for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for the first time were randomly assigned to receive an intrauterine injection of 500 IU hCG or placebo (tissue culture media) before ET. The main outcome measures were implantation and clinical pregnancy rates. RESULTS: Both the hCG-treated group (n = 240) and control group (n = 243) were similar at baseline in terms of demographic and obstetrical characteristics. There were significant differences between the two groups regarding the implantation rate (23.6 vs. 12.2%, p < 0.001), pregnancy rate (54.6 vs. 35.8%, p < 0.001), clinical pregnancy rate (50 vs. 32.1%, p < 0.001), ongoing pregnancy rate (15.3 vs. 9.2%, p < 0.001) and live delivery rate (14.3 vs. 8.4%, p < 0.001). The rate of fertilization and abortion rates were not statistically different. CONCLUSION: Intrauterine injection of hCG before ET improves implantation and pregnancy rates and may be considered an adjuvant in IVF/ICSI.

Distal femoral epiphyses ossification center diameter and third trimester gestational age in Iranian population.

OBJECTIVE: The epiphyses ossification centers appear late in gestation, when traditional biometric measurements are the least accurate, and they can be useful in determining third trimesters gestational age. To evaluate fetal distal femoral epiphysis (DFE) size in various ages of gestation and establish a reference chart for Iranian population. MATERIALS & METHODS: DFE diameter was measured in 1300 normal singleton pregnancies, between 28 and 40 weeks. Mean diameter in each week of gestation was evaluated. RESULTS: The DFE is not visualized in 28 weeks' gestation. It appeared in a small proportion of the fetuses (5%) as early as the 29th week. DFE was detectable by ultrasonography increased dramatically to 56% at 33 weeks' reaching 94% at 36 weeks and 100% at 37 weeks gestation. CONCLUSION: Ultrasonographic visualization of the distal femoral epiphyses ossification center is a useful marker of fetal third trimesters gestational age.

Use of the Free Endometriosis Risk Advisor App as a Non-Invasive Screening Test for Endometriosis in Patients with Chronic Pelvic Pain and/or Unexplained Infertility.

Endometriosis is a prevalent condition that affects millions of individuals globally, leading to various symptoms and significant disruptions to their quality of life. However, the diagnosis of endometriosis often encounters delays, emphasizing the pressing need for non-invasive screening. This retrospective cross-sectional study aimed to evaluate the utility of the Endometriosis Risk Advisor (EndoRA) mobile application in screening for endometriosis in patients with chronic pelvic pain and/or unexplained infertility. The study consisted of 293 patients who met specific criteria: they were English-speaking individuals with chronic pelvic pain and/or unexplained infertility, owned smartphones, and had no prior diagnosis of endometriosis. The results demonstrated that the EndoRA score exhibited a high sensitivity of 93.1% but a low specificity of 5.9% in detecting endometriosis. The positive predictive value was 94.1%, while the negative predictive value was 5.0%. Although the study had limitations and potential selection bias, its findings suggest that EndoRA can serve as a valuable screening tool for high-risk individuals, enabling them to identify themselves as being at an increased risk for endometriosis. EndoRA's non-invasive nature, free access, and easy accessibility have the potential to streamline evaluation and treatment processes, thereby empowering individuals to seek timely care and ultimately improving patient outcomes and overall well-being.

Efficacy of Ibuprofen Lysine on First-Trimester AbortionRelated Pain and Hemorrhage: A Randomized TripleBlinded Clinical Trial.

BACKGROUND: Some recent trials have reported high efficacy for nonsteroidal anti-inflammatory drugs (NSAIDs) in relieving medical abortion-related pain. The aim of this study was to determine the beneficial effect of oral NSAIDs (ibuprofen lysine) in reduction of pain and hemorrhage in first-trimester medical abortion. METHODS: This randomized triple-blinded clinical trial was performed on 98 pregnant women who were candidate for medical abortion within the first-trimester period (gestational age<12 weeks). The participants were randomly assigned to receive ibuprofen lysine (684 mg orally every 4 hours) or placebo. All patients were initially treated with misoprostol (800 µg every 3 hours). Pain intensity and rate of hemorrhage were assessed every hour up to 15 hours after receiving the first dose of misoprostol by visual analogue scaling (VAS) and pictorial blood loss assessment chart (PBAC), respectively. RESULTS: Assessing the mean pain score within 15 hours of receiving misoprostol showed significantly lower pain intensity within the first 10 hours of assessment in the group receiving NSAID in comparison with the control group (P<0.001). The bleeding rate was also significantly lower in the NSAID group at the fifth (P=0.013) and ninth (P=0.040) hour of receiving misoprostol compared to the control group. We found no difference in abortion-related complication rate between the NSAID and placebo groups (8.3% versus 8.0%, P=0.952). CONCLUSION: The use of NSAIDs (ibuprofen lysine) is a good pharmacological analgesic option for relieving medical abortionrelated pain and hemorrhage.