Comparing the effectiveness of letrozole versus methotrexate for treatment of ectopic pregnancy: A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of two different regimens of Letrozole, an aromatase inhibitor, in the management of ectopic pregnancy compared to methotrexate. STUDY DESIGN: This randomized controlled trial was conducted on 88 women diagnosed with ectopic pregnancy with a baseline level of serum beta-human chorionic gonadotropin under 3000 mIU/mL between June 30, 2023, and December 30, 2023, at the Department of Obstetrics and Gynecology of the Vali-e-Asr Hospital affiliated with Tehran University of Medical Sciences. Participants were allocated into either methotrexate (n = 43), 5-day course Letrozole (n = 24), or 10-day course Letrozole (n = 21) treatments. The methotrexate group received a single dose of 50 mg/m2 dosage intramuscular methotrexate. The 5-day Letrozole group received a 2.5 mg Letrozole tablet three times daily for 5 days, whereas the 10-day Letrozole group received a 2.5 mg Letrozole tablet twice daily for 10 days. The primary outcome was the treatment response, defined as the achievement of a negative serum beta-human chorionic level without the need for additional methotrexate treatment or surgery. The secondary outcomes were the need for additional methotrexate dose or laparoscopic surgery intervention. The trial protocol was prospectively registered in ClinicalTrials.gov with code NCT05918718. RESULTS: The treatment response rates in methotrexate, 5-day Letrozole, and 10-day Letrozole groups were 76.7 %, 75.0 %, and 90.5 %, respectively, with no significant differences between the groups (P-value = 0.358). A total of 10 (23.3 %) patients from the methotrexate group, 3 (12.5 %) from the 5-day Letrozole group, and 2 (9.5 %) from the 10-day Letrozole group required an additional methotrexate dose, with no significant differences between the groups (P-value = 0.307). Furthermore, only 3 (12.5 %) patients, all from the 5-day Letrozole group, were suspected of tubal rupture and underwent surgery (P-value = 0.016). CONCLUSION: Our findings suggest Letrozole as a safe alternative to methotrexate in treating stable ectopic pregnancies, with a favorable treatment response rate. However, there is still a need for future larger studies to determine the applicability of Letrozole in the EP management. Also, the non-significant higher effectiveness of the 10-day Letrozole regimen than the 5-day Letrozole group underscores the need for future research to determine the optimal Letrozole regimen for the management of ectopic pregnancy.

Methotrexate as the first-line treatment of unruptured tubular ectopic pregnancies with high initial human chorionic gonadotropin levels: A retrospective cohort.

Objectives: To evaluate the effectiveness of the first-line medical management with Methotrexate (MTX) in the treatment of patients with stable tubal Ectopic Pregnancies (EPs) and varying ranges of Beta-Human Chorionic Gonadotropin (ß-HCG) levels. Materials and methods: In this retrospective cohort study, we reviewed the medical records of a total of 184 patients with the diagnosis of tubal EP, who received MTX as their first-line treatment. Patients with a baseline ß-HCG< 4800 mIU/mL received single-dose MTX (n = 136) and those with an initial ß-HCG≥ 4800 mIU/mL underwent the double-dose MTX regimen (n = 48). The treatment success was determined by evaluating the reported weekly ß-HCG levels of the patients. Results: Baseline ß-HCG and mass size in the single-dose group were 1895.1 ± 1463.4 mIU/mL and 2.2 ± 1.1 cm, respectively, compared to 17,867.6 ± 31,870.5 mIU/mL and 2.3 ± 1.1 cm in the double-dose group. Treatment duration was 30.6 ± 16.9 days for single dose and 41.0 ± 27.0 days for double dose, with additional MTX in 27.2% and 12.5% in respective groups. Single dose achieved a 92.6% success rate, and double dose, 81.3%, without serious adverse effects. No significant effects were seen for either baseline ß-HCG and mass size on the treatment success rates of both groups (p-value>0.05). However, the presence of Fetal Heart Rate (FHR) was associated with poorer responses only in the single-dose group (p-value=0.034). Conclusions: Medical management with MTX shows promise as a first-line treatment for tubal EPs with ß-HCG> 2000, suggesting a potential reassessment of existing guidelines in light of this emerging evidence. However, further research seems crucial in this field.

One Side Ovarian Rejuvenation: A Quasi-Experimental Study of the Effect of the Autologous Platelet Rich Plasma in Poor Ovarian Responders in IVF.

Background: The poor ovarian response is the most important limiting factor in the success of in vitro fertilization (IVF). The aim of this study was to evaluate the outcome of intraovarian injection of autologous platelet-rich plasma (aPRP) on the oocyte number and IVF outcomes in poor ovarian responders (POR). Methods: This quasi-experimental study was performed from August 2021 to December 2021, in Vali-e-Asr Infertility Clinic affiliated with Tehran University of Medical Sciences, Tehran, Iran. There were 12 POR patients selected based on the criteria of Bologna group 4 who underwent two IVF cycles with similar antagonist regimens in a 70-day-interval. Immediately after the Oocytes Pick-Up (OPU), there was a 4cc of autologous PRP multifocal intramedullary injection done into their right ovaries in the first IVF cycle (case group). On the other hand, their left ovaries were considered as the control group. The patients underwent the second IVF cycle after 70 days. Results: Those who had undergone aPRP experienced a significant increase of the mean of antral follicular count (AFC) (from 1.91±0.79 to 2.50±0.90, p=0.043). There was a significant increase in the number of embryos from the right ovary (intervention group) compared to the left ovary (control group) after PRP, but there was no significant difference in the number of embryos in the right ovary before and after the intervention (from 0.25 ±0.45 to 1.08±0.79, p=0.705). There was no significant change in the number of oocytes, AMH, and FSH in the case and control groups before and after the intervention (p>0.05). Conclusion: According to the results of this study, it seems that in females with POR, intraovarian aPRP had no effect on the outcomes (embryos number, number of oocytes, FSH and AMH level), except for an increase in AFC.

Ovarian small cell carcinoma by ovarian torsion feature: A cytopathology challenging case.

INTRODUCTION AND IMPORTANCE: Ovarian small cell carcinomas are a rare type of ovarian cancer that is highly aggressive and consists of two distinct types the hypercalcemic type (SCCOHT) and pulmonary type (SCCOPT). CASE PRESENTATION: A 23 years old girl was admitted to the emergency room with the presentation of acute abdomen. The ultrasound and Magnetic resonance imaging revealed a right adnexal huge mass with adnexal torsion. In laparotomy, she underwent unilateral salpingo-oophorectomy due to ovarian torsion and possible malignancy. The histopathological evaluation was challenging and was finalized by a team of pathologists as hypercalcemic small cell carcinoma. She refused reoperation and unfortunately relapsed during chemotherapy and died 6 months after the initial diagnosis. CLINICAL DISCUSSION: Conclusion: We do not yet have comprehensive information on small cell ovarian cancer. Cytopathology diagnosis is still challenging and the treatments are not usually effective. Further clinical trials and studies are recommended to find appropriate treatments for these patients.

Micro-scale probing of the Rat's oviduct detects its viscoelastic property needed for creating a biologically relevant substrate for In-Vitro- Fertilization.

Techniques used in assisted reproductive technology such as In-Vitro- Fertilization (IVF) process, often only replicate the biomechanical environment for embryo. Despite its importance, the biomechanics of the Oviduct tissue that is usually called Fallopian Tube in Human, the natural site of fertilization, has not been replicated nor sufficiently studied. This work studies the time-independent and time-dependent biomechanics of the oviduct tissue by realizing a viscoelastic model that accurately fit on the experimental indentation data collected on the mucosal epithelial lining of the oviduct tissue of rats. Nano-scale experiments with varying indentation rates ranging from 0.3 to 8 µms were conducted using atomic force microscopy (AFM) resulting in instantaneous elastic modulus ranging from 0.86 MPa to 6.46 MPa correspondingly. This result showed strong time dependency of the mechanical properties of the oviduct. An improved viscoelastic equation based on the fractional viscoelastic model was proposed. This modified relation successfully captured all the experimental data found at different rates (R2 > 0.8). Using the proposed model, the pure elasticity of the oviduct (i.e., about 317.2 kPa) and the viscoelastic parameters were found.

The association of the betatrophin level with metabolic and inflammatory parameters in infertile women with polycystic ovary syndrome: A case-control study.

Background: Betatrophin may be associated with metabolic diseases. Objective: To investigate the betatrophin level and its association with metabolic and inflammatory parameters in infertile women with polycystic ovary syndrome (PCOS) and other infertile women during the intrauterine insemination cycle. Materials and Methods: This case-control study was conducted with 90 infertile women (45 with PCOS and 45 without) chosen by convenience sampling, in the infertility clinic of Imam Khomeini Hospital in Tehran, Iran. Participants were interviewed to obtain their age, body mass index, and reproductive history. Fasting brachial venous blood samples were obtained on the 3 rd day of the menstrual cycle to measure the levels of betatrophin, fasting blood sugar, insulin, luteinizing hormone, follicle-stimulating hormone, low-density lipoprotein cholesterol, estradiol, and high-sensitivity C-reactive protein. Results: The results showed that the level of betatrophin in women with PCOS was significantly higher than in the control group (p = 0.05). Based on multiple linear regression analyses, the effects of metabolic and inflammatory parameters on betatrophin were not significant (p = 0.19). The results showed no significant difference between groups in folliculogenesis (p = 0.57). Conclusion: According to the results, betatrophin levels were higher in infertile women with PCOS than in those without. The findings suggest that there may be an association between increased betatrophin and increased incidence of PCOS. Further studies with a larger sample size are needed to investigate the role of betatrophin in insulin resistance and lipid metabolism, and its effects on infertility treatment outcomes.

Comparison of Dydrogesterone and GnRH Antagonists for Prevention of Premature LH Surge in IVF/ICSI Cycles: A Randomized Controlled Trial.

Objective: To compare the effect of dydrogesterone and Gonadotropin releasing hormone (GnRH) antagonists on prevention of premature luteinizing hormone (LH) surge and pregnancy outcomes in infertile women undergoing Invitro fertilization/ Intra cytoplasmic sperm injection (IVF/ICSI). Materials and methods: In a Randomized controlled trial (RCT), two-hundred eligible women undergoing in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) treatment were randomly assigned into two groups. Human menopausal gonadotropin (HMG) was administered for controlled ovarian stimulation (COS) in both groups. Intervention group (group 1) received 20 mg dydrogesterone from day 2 of menstrual cycle till trigger day and control group (group2) received GnRH antagonist from the day that leading follicle reached 13 mm in diameter till trigger day. Serum levels of LH, estradiol and progesterone were measured on the trigger day. The primary outcome measure was the incidence of a premature LH surge, and the secondary outcomes investigated were the chemical and clinical pregnancy rates in the first FET cycles. Results: There were no significant differences in patients' age, BMI, AMH levels, previous IVF cycle, and cause of infertility between the two groups. None of the patients in two groups experienced a premature luteinizing hormone surge. The numbers of retrieved oocytes, the MII oocytes and good quality embryos, were significantly higher in the intervention group than antagonist group (p < 0.05). The overall chemical pregnancy rate in intervention group (43/91: 46.2%) and control group (45/91: 49.5%) (p = 0.820) was similar. Meanwhile, the clinical pregnancy rate was similar between groups too. Conclusion: Regarding the cost, efficacy and easy usage of dydrogestrone, it may be reasonable to use it as an alternative to GnRH antagonist for the prevention of premature LH surge.

Maternal death due to COVID-19.

BACKGROUND: Despite 2.5 million infections and 169,000 deaths worldwide (as of April 20, 2020), no maternal deaths and only a few pregnant women afflicted with severe respiratory morbidity have been reported to be related to COVID-19 disease. Given the disproportionate burden of severe and fatal respiratory disease previously documented among pregnant women following other coronavirus-related outbreaks (SARS-CoV in 2003 and MERS-CoV in 2012) and influenza pandemics over the last century, the absence of reported maternal morbidity and mortality with COVID-19 disease is unexpected. OBJECTIVE: To describe maternal and perinatal outcomes and death in a case series of pregnant women with COVID-19 disease. STUDY DESIGN: We describe here a multiinstitution adjudicated case series from Iran that includes 9 pregnant women diagnosed with severe COVID-19 disease in their second or third trimester. All 9 pregnant women received a diagnosis of SARS-CoV-2 infection by reverse transcription polymerase chain reaction nucleic acid testing. Outcomes of these women were compared with their familial/household members with contact to the affected patient on or after their symptom onset. All data were reported at death or after a minimum of 14 days from date of admission with COVID-19 disease. RESULTS: Among 9 pregnant women with severe COVID-19 disease, at the time of reporting, 7 of 9 died, 1 of 9 remains critically ill and ventilator dependent, and 1 of 9 recovered after prolonged hospitalization. We obtained self-verified familial/household cohort data in all 9 cases, and in each and every instance, maternal outcomes were more severe compared with outcomes of other high- and low-risk familial/household members (n=33 members for comparison). CONCLUSION: We report herein maternal deaths owing to COVID-19 disease. Until rigorously collected surveillance data emerge, it is prudent to be aware of the potential for maternal death among pregnant women diagnosed as having COVID-19 disease in their second or third trimester.

The Effects of Maternal Opium Abuse on Fetal Heart Rate using Non-Stress Test.

BACKGROUND: Opium is one of the most commonly abused opiates in developing countries including Iran. Considering the importance of maternal health on the newborn, we aimed to assess the effect of opium abuse on fetal heart rate (FHR) characteristics in a sample of pregnant women in Zahedan, Southeast Iran. METHODS: This cross-sectional study was done on 100 pregnant women referring to Ali-Ibn-Abi Talib Hospital in Zahedan, during 2011-2013. The participants were divided into two groups comprising of opium abusers and healthy individuals. The participants received 500cc intravenous fluid containing dextrose and then non-stress test results were recorded for 20 minutes. RESULTS: We found no significant difference between the two groups with respect to their demographic characteristics. Fetal movements, variability, acceleration, and reactivity were significantly higher among addicted women (P<0.0001 for all). Periodic change was 9.8 times higher among opium abusers compared with the healthy women. Abnormal variability or oscillations of <15 beats/min, which indicates lack of beat-to-beat variability, was significantly higher in the fetuses of addicted mothers (P<0.0001). CONCLUSION: Considering significant abnormal patterns in FHR characteristics among the opium abuser group, mothers addicted to opium need specific prenatal care.

A rare case of primary amenorrhea with two etiologies, hypothalamic amenorrhea, transverse vaginal septum, and no hematocolpos.

We reported a rare case of hypothalamic amenorrhea and transverse vaginal septum. A 28-year-old woman presented with primary amenorrhea and no complaint of abdominal pain. Laparoscopy revealed a small rudimentary uterus with streak ovaries and a vaginal pouch. The patient with diagnosis of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome was subjected to a vaginoplasty in another fertility center. In our institute, after two courses of estrogen and progesterone, sonography revealed hematocolpos, while, under anesthesia, transverse vaginal septum was resected. Hysteroscopy revealed normal uterine cavity. She became pregnant 5 months postoperatively with controlled ovarian stimulation (COS) in conjunction with intrauterine insemination, and she has two healthy babies now. This case highlights the importance of careful evaluation of all primary amenorrheas. Clinicians should be aware of presence of more than one etiology which causes atypical presentations and accomplishes a systematic strategy for the evaluation of amenorrhea potential to avoid long-term side effects of a misdiagnosis.