Severe Early-Onset Intrahepatic Cholestasis of Pregnancy Following Ovarian Hyperstimulation Syndrome with Pulmonary Presentation after In Vitro Fertilization: Case Report and Systematic Review of Case Reports.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease, usually presented in the third trimester with pruritus, elevated transaminase, and serum total bile acids. Evidence shows that it can be developed in the first trimester, more commonly after in vitro fertilization (IVF) procedures, with the presence of ovarian hyperstimulation syndrome (OHSS). METHODS: A literature search was conducted in the PubMed/MEDLINE database of case reports/studies reporting early-onset ICP in spontaneous and IVF pregnancies published until July 2023. RESULTS: Thirty articles on early-onset ICP were included in the review analysis, with 19 patients who developed ICP in spontaneous pregnancy and 15 patients who developed ICP in IVF pregnancies with or without OHSS. Cases of 1st and 2nd trimester ICP in terms of "early-onset" ICP were pooled to gather additional findings. CONCLUSIONS: Proper monitoring should be applied even before expected pregnancy and during IVF procedures in patients with known risk factors for OHSS and ICP development (patient and family history), with proper progesterone supplementation dosage and genetic testing in case of ICP recurrence.

Extraperitoneal Cesarean Section after two Medial Laparotomies, Anus Prater, and Surgical Treatment of the Rectovaginal Fistula in a Patient with Crohn's Disease: A Case Report.

The aim of this case report is to show the advantages of the extraperitoneal cesarean section (ECS) approach in a pregnant patient with multiple previous abdominal transperitoneal colon surgeries and Crohn's disease. A pregnant nulliparous woman with Crohn's disease was admitted for delivery. After delivery, a large rupture and lesion of the rectum was observed. Suturing of the vagina, rectum and sphincter was performed by an abdominal surgeon. Because of a very large and irregularly shaped rectum rupture, the patient underwent infraumbilical medial laparotomy and sigmoidostomy. After 18 months, the patient started to experience vaginal discharge and Y-shaped rectovaginal fistula was confirmed. Surgical reconstruction was performed. The patient's second pregnancy began one year later. At 38 weeks of pregnancy, elective extraperitoneal cesarean section was performed. A healthy newborn was delivered. Follow-up showed full and fast recovery after the ECS. In cases of pregnant women who have had multiple colon surgeries, gynecology surgeons can choose to perform an ECS to avoid transperitoneal entrance into the abdomen. ECS avoids lysis of postoperative adhesions after repetitive gastrointestinal surgeries, the formation of new adhesions by lysis of the old adhesions, and most importantly, the possibility of colon or small intestine lesions during lysis of dense or firm adhesions.

CTLA4-Linked Autoimmunity in the Pathogenesis of Endometriosis and Related Infertility: A Systematic Review.

Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid in patients with endometriosis-related infertility. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a search of the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, and Clinical Trials research register. We included observational or prospective human and animal studies with any features related to endometriosis and/or infertility studies involving CTLA4-related pathogenesis published in English. The results of studies in which the size and characteristics of the observed groups were not stated were excluded. From the initial pool of 73 publications identified and screened, we finally included 5 articles to summarize the most recent knowledge about CTLA4-linked autoimmunity in the pathogenesis of endometriosis and related infertility. Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment, with pre-clinical evidence of anti-CTLA antibodies as a potential novel target therapy for endometriosis. However, CTLA4 gene analyses do not support findings of CTLA4-linked autoimmunity as a primary determinant of the pathogenesis of endometriosis. These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. Further studies are needed to investigate the clinical relevance of anti-CTLA target therapy, taking into account the potential adverse events and repercussions of novel immunologic therapy modalities. However, with the general scarcity of studies investigating this topic, the clinical importance of CTLA4 autoimmunity still remains unclear.

Acute Arterial Thrombosis of Lower Extremities in COVID-19 Patients.

Clinical signs and symptoms of COVID-19 varied from asymptomatic forms to severe, life-threatening conditions that required treatment in intensive care units. These severe forms of illness are connected with a hypercoagulable state due to excessive inflammation, hypoxia, immobilisation, and altered angiotensin-converting enzyme 2 (ACE-2). In total, 17 COVID-19 positive patients were diagnosed with peripheral arterial thrombosis (AT), 13 of them had COVID-19 pneumonia. Laboratory findings in patients with X-ray confirmed pneumonia showed a four times higher neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) and three times higher lactate dehydrogenase level (LDH) than patients without confirmed pneumonia. Patients with pneumonia had significantly more bilateral occlusions of the lower extremities and a significantly higher percentage with complete occlusion of the arteries than patients without pneumonia. The rate of limb loss was 35.3%. They were all from the group with COVID-19 pneumonia. Ten out of thirteen patients with pneumonia died due to acute respiratory distress syndrome (ARDS). All patients without pneumonia were discharged from the hospital. The aim of this retrospective study was to report the incidence of arterial thrombosis of lower extremities and their complications in the acute phase of the infection among COVID-19 patients admitted to the hospital for treatment.

Validation of the Croatian Version of the 8-Item Overactive Bladder Questionnaire (OAB-V8).

OBJECTIVES: The present study was conducted with the aim to translate, adapt, and validate the 8-item Overactive Bladder Questionnaire (OAB-V8) in Croatia. METHODS: This study included a total of 58 female patients with OAB and 66 healthy women. The translation to Croatian followed standardized procedure. All eligible participants completed OAB-V8 at inclusion and 2 weeks after to assess test-retest reliability. Cronbach α coefficient was calculated to assess internal consistency. RESULTS: Our study demonstrated high internal consistency for all items at both visits (Cronbach α between 0.799 and 0.847), with stable internal consistency reliability across items during the 2-week period. However, the exception is the item "waking up at night to urinate," which significantly changed during the 2-week period. Intraclass correlation for OAB-V8 items ranged from 0.810 to 1.0, with Spearman correlations greater than 0.9 for all items (P < 0.01). There were strong significant correlations between frequency of urination during daytime and uncomfortable and sudden urge to urinate, and between nocturia and waking up at night. Discriminative validity showed statistically significant score differences between patients and the control group. CONCLUSIONS: The Croatian version of the OAB-V8 was successfully translated, adapted, and validated so the questionnaire is now ready for use as a reliable tool for initial screening and assessing patients with OAB in everyday Croatian clinical practice.

The pharmacoeconomic impact of follitropin alpha biosimilars in IVF therapy in Europe: a report of the literature.

Introduction: To study the impact of biosimilars in assisted reproductive treatments, we performed a review of the literature. Biosimilars are a bioequivalent chemical drug referred to the original. Their production is strongly requested in order to reduce drug cost and reduce health economic impact on national health system. In assisted reproductive treatments different gonadotropin biosimilars are being produced.Areas covered: For this reason, we performed a review of the literature on follitropin alfa Gonal-F biosimilar, Ovaleap and Bemfola, to assess their cost efficacy in national health system. Cost effective (CE) analysis and incremental cost-effectiveness ratio (ICER) were used as parameters for biosimilar impact evaluation in the national health system economy. In particular, they had only slight impact on cost reduction of recombinant follitropin alfa products in Europe.Expert opinion: considering cost-effective analysis, Gonal-F remains the first choice for national health systems. However, well-designed powered methods are strongly needed to assess biosimilars cost-effectiveness.

Retrospective analysis of the use of two recombinant follitropin alfa injections in patients undergoing in vitro fertilization treatment with the gonadotropin-releasing hormone antagonist protocol.

AIM: To evaluate the clinical efficacy of biosimilar (Ovaleap) compared with the referenced follitropin alfa (Gonal-f), within the context of antagonistic multiple doses protocol of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques. METHODS: A retrospective, monocentric study included 229 infertile women aged 22 to 43 years who underwent their first cycle of COH for the purpose of the IVF or ICSI during the period of 2017. Eligible patients underwent ovarian stimulation with either Ovaleap (n = 152) or Gonal-f (n = 77) starting at Cycle Day 2 and were receiving gonadotropin-releasing hormone (GnRH) antagonist in either fixed or flexible antagonist protocol manner. RESULTS: Ovaleap-treatment resulted in fewer number of oocytes retrieved in regard to Gonal-f-treatment, with the median of seven oocytes retrieved in the Ovaleap group versus nine in the Gonal-f group (U = 5369.5, P = 0.3079). Clinical pregnancy rate was 24.3% in the overall study sample and 31.9% in women with embryo transfer, in the Ovaleap group. Similarly, in the Gonal-f group these rates were 25.0% and 34.5%, respectively. Only four patients experienced ovarian hyperstimulation syndrome, with one case in Ovaleap-treatment group and three cases in Gonal-f-treatment group. CONCLUSION: While the clinical efficacy profile favored using Gonal-f formulation of follitropin alfa, this analysis showed that there is no significant difference in the number of oocytes retrieved between Ovaleap and Gonal-f follitropin alfa formulations, used within GnRH antagonist protocols of COH.