
Background:N-acetylcysteine (NAC) is a supplement commonly used in patients with polycystic ovary syndrome (PCOS). The expansion of oocyte-associated cumulus cells (CCs) and the quality of the oocyte are critical factors influencing fertilization rates and clinical pregnancy outcomes in assisted reproductive techniques (ARTs). Genes such as phosphofructokinase (PFKP) and pyruvate kinase isoform M2 (PKM2) are involved in glucose metabolism and are crucial in the regulation of oocyte competence and developmental potential. The purpose of the current study was to evaluate the effects of letrozole and NAC on the expression of PFKP and PKM2 in CCs of PCOS patients undergoing ART. Methods:The study evaluated 20 PCOS women undergoing ART to assess the effect of letrozole and NAC on the expression levels of PKM2 and PFKP genes in cumulus cells. Women were randomly assigned using a simple randomization method into four groups: control, NAC, letrozole, and NAC plus letrozole, with five women in each group. Gene expression levels of PKM2 and PFKP were measured using real-time PCR. Results:The expression level of PKM2 was significantly higher in the letrozole plus NAC group compared to the control group (p<0.05). In NAC group, PFKP was significantly expressed compared to the control group (p<0.05). There were no significant differences among the other groups compared to the control group. Conclusion:NAC can improve the quality of oocytes by increasing the expression level of genes involved in the glucose metabolism (PKM2, PFKP) of CCs, thereby potentially improving ART success rate in PCOS patients. Therefore, administering NAC along with letrozole can have a synergistic effect on increasing the expression level of genes associated with blastocyst quality in PCOS patients.
Background:Polycystic ovary syndrome (PCOS) is a heterogeneous condition that encompasses several cardiometabolic and endocrinological disorders. Studies have shown that its pathogenesis aligns with several underlying mechanisms associated with recurrent pregnancy loss (RPL). Cellular communication network (CCN)-3 protein is a well-studied adipokine involved in tumorigenesis, organogenesis, inflammation, fibrosis, and glucose metabolism. The purpose of the current study was to determine the association of CCN3 levels with a number of parameters involved in PCOS pathogenesis. Methods:This is a case-control study including 120 PCOS patients (60 cases with RPL; PCOS-RPL and 60 cases with infertility; PCOS-Inf and 60 healthy controls). Circulating levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP), homocysteine, and CCN3 were measured using ELISA kits. Results:Circulating levels of CCN3 were significantly elevated in PCOS-RPL and PCOS-Inf subgroups when compared to the control group (7.61±3.03 and 6.85±2.54 vs. 3.12±0.82, p<0.001). Serum CCN3 positively correlated with fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) in the control group (p<0.05) and PCOS group (p<0.001). Moreover, CCN3 was significantly associated with PCOS (OR 4.808, 95%CI [2.744-8.423], p<0.001). Conclusion:According the results of this study CCN3 may be involved in the pathogenesis of PCOS. However, future studies are needed to evaluate the possibility of utilizing CCN3 in the diagnosis and treatment of the disease.
Background:The association between varicocele and male infertility has always been a subject of ongoing debate. Lactoferrin (LF) belongs to the transferrin family with iron-binding properties and exhibits many beneficial biological properties. The purpose of the current study was to assess seminal levels of LF in infertile oligoasthenoteratozoospermic (OAT) men with varicocele. Methods:Sixty-nine men were allocated into three groups; healthy fertile men (as controls) (n=20), infertile OAT men without varicocele (n=19), and infertile OAT men with varicocele (n=30). All men underwent history taking, genital examination, semen analysis, and determination levels of seminal LF by ELISA method. Statistical analysis was carried out using Kruskal-Wallis test followed by post-hoc analysis (Conover) for comparisons involving more than two groups, and the Mann-Whitney U test for comparisons between two groups. Spearman correlation test was used to assess the relationship between variables. The p>0.05 was set as statistically significant. Results:The median seminal LF level of the healthy fertile controls demonstrated significantly increased levels compared to both groups of infertile OAT men with or without varicocele (p<0.000001). The median seminal LF level of the infertile OAT men with varicocele grade III demonstrated a significant decrease compared to infertile OAT men with grade II (p=0.0057). Collectively, seminal LF levels exhibited significant positive correlations with sperm concentration, total sperm motility, and normal sperm morphology. Conclusion:LF can be an imperative seminal biomarker that decreases in infertile OAT men especially if associated with varicocele.
Background:Azoospermia, the complete absence of sperm in the ejaculate, is a major cause of male infertility. Sertoli cells are essential for spermatogenesis, and disruptions in innate immune immune pathways, particularly Toll-like receptors (TLRs), may impair their function. This study investigated the expression of TLR1-10 and downstream signaling molecules (MYD88, NFKB, TRIF, IRF3, and TRAM) in Sertoli cells of azoospermic patients. Methods:Testicular tissue were collected from 20 azoospermic men undergoing testicular sperm extraction (TESE). Patients were categorized into two TESE positive (sperm present, n=10) and TESE negative (sperm absent, n=10). Sertoli cells were isolated using enzyme digestion and purified via fluorescence-activated cell sorting (FACS). Gene expression of TLR1-10 and signaling molecules was quantified by RTPCR. Data were analyzed using independent-samples T-test, with significance set at p< 0.05. Results:Significant downregulation was detected in TLR10 (20.6-fold, p<0.0001), TLR9 (4.6-fold, p<0.05), TLR7 (4.8-fold, p<0.01), TLR6 (12.4-fold, p<0.05), TLR5 (13.5-fold, p<0.001), TLR4 (3.2-fold, p<0.05), and TLR3 (3.1-fold, p<0.01). Among signaling molecules, MYD88 (4.1-fold, p<0.01) and IRF3 (4.2-fold, p<0.05) showed significant reductions, indicating impaired immune signaling in Sertoli cells of TESE-negative men. Conclusion:Altered expression of TLRs and associated signaling molecules in Sertoli cells of azoospermic men suggests innate immune dysregulation as a potential mechanism underlying defective spermatogenesis. These findings highlight immune privilege-associated pathways as possible targets for developing diagnostic biomarkers and novel therapeutic approaches for male infertility.
Background:Cortical folding during fetal brain development reflects neural maturation. Fetal growth restriction (FGR) may disrupt this process, potentially affecting neurodevelopmental outcomes. Although ultrasound enables noninvasive sulcal assessment, so normative data and objective tools are lacking. The purpose of the current study was to assess the impact of FGR on fetal cortical development using neurosonography and establish a third-trimester nomogram for cortical maturation. Methods:This prospective study included 425 singleton pregnancies (330 appropriate-for-gestational-age [AGA], 54 symmetrical FGR, and 41 asymmetrical FGR) at 28-36 weeks. Conducted at a Tehran tertiary center (2023-2024), the study included cases with normal anatomy and negative aneuploidy screening. Neurosonographic parameters including Sylvian fissure (SF), insula, parieto-occipital fissure (POF), cavum septum pellucidum (CSP) width, and ventricular diameter were measured and the ratios calculated relative to biparietal diameter (BPD). ANOVA and post-hoc tests were applied and statistical significance was set at p<0.05. Results:No significant differences in neurosonographic ratios (e.g., SF/Insula, POF/BPD, CSPW/BPD) were found between AGA and FGR groups. However, unadjusted SF and insular depths were reduced in symmetrical FGR fetuses with head circumference (HC) <10th percentile. Asymmetrical FGR showed no differences. A gestational-age-based nomogram was developed for AGA fetuses. Conclusion:While absolute sulcal measurements vary with head size in FGR, biometric adjustments (e.g., BPD ratios) improve cortical maturation assessment. The study supports ratio-based neurosonography and provides normative data for objective fetal brain evaluation.
Background:Cesarean scar pregnancy (CSP) is a rare yet serious condition involving implantation of the gestational sac at the site of a prior cesarean delivery. The management becomes increasingly complex with the addition of placenta percreta. In this paper, a case of CSP complicated by placenta percreta was reported which was successfully managed through a multidisciplinary approach. Case Presentation:A 35-year-old G4P3 woman was diagnosed with CSP at 6 weeks of gestation. Despite counseling on the risks, she opted to continue the pregnancy. Placenta percreta was diagnosed at 18 weeks. A multidisciplinary team monitored the pregnancy closely, leading to the delivery of a healthy infant at 32 weeks via cesarean delivery and subsequent hysterectomy. Conclusion:Multidisciplinary management and close follow-up are crucial in managing high-risk CSP cases, especially those complicated by abnormal placentation.
Background:Accessory cavitated uterine mass (ACUM) is a rare, unclassified Müllerian anomaly characterized by distinct imaging features. It is typically located within the uterus, close to the round ligament, and has a uterus-like structural arrangement. The patient may present with pelvic pain or dysmenorrhea. Most of these cases are misdiagnosed because of a lack of awareness about this unusual entity. Case Presentation:Three cases of ACUM in young patients who experienced prolonged symptoms and had incomplete family structures were reported in this paper. Initially, two of these cases were misdiagnosed during ultrasound examinations (USG). The subsequent magnetic resonance imaging (MRI) revealed characteristic imaging features consistent with ACUM, which provided significant psychological relief to both the patients and their families. Two patients received hormonal therapy, both of whom were unmarried. The third patient, however, indicated a wish to conceive and was therefore initiated on analgesics. All three patients chose to forgo surgical intervention, opting instead for medical management despite its limited success in alleviating their symptoms. This decision was made to minimize obstetric risks associated with surgical interventions in potential future pregnancies. Conclusion:Laparoscopy or open surgery is the mainstay treatment for a permanent relief from the symptoms. However, surgical treatment should be offered with caution as no data are available in medical literature regarding the effect of surgically induced myometrial scarring on patients' reproductive outcomes. Since most of these patients were young and nulligravida, the therapy had to be personalized in accordance with the patient's preference and family status.
Background:Endometriosis is a prevalent condition among women, often leading to infertility. Laparoscopic surgery is widely employed as a therapeutic intervention for endometriosis. This study investigated the prognostic factors influencing the outcome of laparoscopic surgery for endometriosis. Methods:This cross-sectional study included 60 women with endometriosis referred for laparoscopic surgery at Amiralmomenin Hospital, Zabol, Iran, between 2022 and 2024. Pain intensity was measured using a visual analog scale (VAS). Statistical analyses were performed using SPSS version 26. Descriptive statistics summarized the data, while univariate analyses (t-tests and chi-square tests) assessed relationships between variables. Multivariate logistic regression identified independent predictors of pain reduction and pregnancy outcomes. Results:Patients with moderate endometriosis showed statistically significant pain reduction from 8.8 preoperatively to 1.8 at 9 months (p<0.001) and 2.2 at 12 months post-surgery (p=0.003). Those with severe endometriosis had non-significant pain reduction (8 to 6 at 12 months, p=0.12). Both intrauterine (9 to 1.1 at 12 months, p<0.001) and extrauterine involvement groups (8.6 to 3.3, p=0.004) demonstrated significant pain improvement, with no significant difference between the groups (p=0.779). Regarding fertility outcomes, treatment before the age of 30 significantly increased pregnancy likelihood (AOR=20.57, 95%CI 1.4-295.3), while other factors including BMI, CA125 levels, and parity showed no significant associations (all p>0.05). Conclusion:These preliminary findings suggest that laparoscopic surgery may reduce pain in moderate endometriosis, while the age under 30 may be associated with improved pregnancy outcomes. However, given the study's limited sample size and wide confidence intervals, these results require validation in larger, multicenter cohorts.
Background:Ectopic pregnancy remains one of the most common causes of pregnancy-related deaths in the first trimester. About 2.4% of ectopic pregnancies occur in the interstitial part of the fallopian tubes. Given the nonspecific symptoms and the increased risk of hemorrhage associated with interstitial pregnancy localization, early diagnosis is crucial and should be based not only on clinical presentation but also on adjunctive diagnostic modalities. Early diagnosis leads to better treatment-related outcomes. Tubal ectopic pregnancies rarely progress into the second trimester and are typically diagnosed during the first trimester. Case Presentation:A 25-year-old primigravida at 20 weeks of gestation was initially diagnosed with a single live intrauterine pregnancy but presented with hypovolemic shock and was intraoperatively found to have an unruptured ectopic pregnancy. Postoperatively, the patient remained hemodynamically stable and was discharged on the fifth day. To date, the highest gestational age reported for a tubal ectopic pregnancy is 14 weeks. Conclusion:Ectopic pregnancies should be diagnosed in the first trimester via expert ultrasound. In this case, delayed second-trimester ultrasound in a low-income patient led to missed diagnosis. Clinical judgment must guide antenatal care, and surgery should not be delayed despite an unidentified source of hemoperitoneum.
Background: The fundamental mechanisms behind the causes and development of endometriosis are still poorly understood. Therefore, identifying biomarkers that can help with early detection and targeted treatment is crucial for effective management of this disease. This study aimed to compare total antioxidant capacity (TAC), the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the concentrations of interleukin-6 (IL-6) and phenylalanine (Phe) across different stages of endometriosis. Methods: The plasma samples were collected from women with endometriosis who had undergone laparoscopic surgery. The stages were confirmed by a gynecologist, with 30 plasma samples from stages I-II (mild) and 30 from stages III-IV (severe). The obtained measurement data were first normalized and tested for normality, followed by analysis using the t-test and Mann-Whitney U test. The p-value below 0.05 was considered statistically significant. The sample size was determined based on Cohen's guideline of 30. Biomarker levels were assessed using ELISA and colorimetric techniques. Results: TAC levels, GPx, and SOD activities, as well as Phe concentration significantly differed between endometriosis stages I-II and III-IV (p<0.05). These measured biomarkers were higher in stage I-II. On the other hand, although IL-6 levels were higher in stages III–IV, the differences between stages were not statistically significant. Conclusion: The potential of TAC, SOD, GPx, and Phe as biomarkers for the early diagnosis and treatment of endometriosis underscore the roles of inflammation and oxidative stress in the pathogenesis of the disease, providing insights that may aid in developing more targeted diagnostic and therapeutic strategies.
Background: Reactive oxygen species (ROS) are critical factors for oocyte maturation and early embryogenesis; however, excessive ROS can induce oxidative stress, impairing mitochondrial function, DNA integrity, and embryo competence. The role of oxidative status in buffalo follicular fluid (FF) remains underexplored. This study assessed the relationship between total oxidant status (TOS) in buffalo FF and the developmental competence of oocytes retrieved by ovum pick-up (OPU) for subsequent in vitro fertilization (OPU-IVF). Methods: Follicular fluid and cumulus–oocyte complexes (COCs) were collected from 62 healthy buffaloes. Oocytes were matured and fertilized in vitro, and the animals were classified based on blastocyst yield: G1 (no blastocysts), G2 (≥2 blastocysts), and G3 (>3 blastocysts). TOS was measured spectrophotometrically. The relationship between TOS and oocyte competence was analyzed by ROC (G1 vs. G3) and Spearman correlation (G1 vs. G2), with p<0.05 considered statistically significant. Results: G2 group with >2 blastocyst exhibited lower TOS levels (1.10±0.51 µmol H₂O₂ Eq/L) than G1 (2.15±0.92; p=0.004), with higher follicle counts, oocyte yield, cleavage rate, and blastocyst production (p<0.05). ROC analysis identified a TOS threshold of 1.12 µmol H₂O₂ Eq/L (area under the curve [AUC]=0.851), and TOS in-versely correlated with the proportion of high-quality blastocysts (r=-0.553, p= 0.021). Conclusion: Elevated oxidative stress in FF compromises oocyte developmental competence and embryo quality. TOS may serve as a predictive biomarker, supporting antioxidant-based optimization of assisted reproductive technology (ART) in buffalo.
Background: The supplementation of human chorionic gonadotropin (hCG) into culture medium in rescue in vitro maturation (r-IVM) has been reported to improve the maturation rates of immature oocytes derived from stimulated cycles. However, the impact of this enrichment on embryo quality is yet to be understood. The purpose of the current study was to investigate the effect of hCG on the embryo quality following r-IVM. Methods: A total of 152 immature oocytes consisting of germinal vesicles (GV) and metaphase I (MI) were collected and classified into 1) control group (n=73; GV=22, MI=51) cultured in culture medium only, and 2) experimental group (n=79; GV= 23, MI=56) cultured in culture medium supplemented with 0.5 IU hCG. Study parameters were analyzed using Student’s T-test or Kruskal Wallis and chi-square at a 95% confidence level. Results: After 24 hr, the maturation rate of the control and experimental groups was comparable (57% vs. 70%, p=0.58). Following intracytoplasmic sperm injection (ICSI), the fertilization rate was significantly higher in the experimental group than in the control group (49% vs. 36%; p=0.03). However, the number of good-quality embryos was similar in the groups (16% vs. 6%). Conclusion: Our study suggests that hCG supplementation into the culture medium during r-IVM does not affect embryo quality but improves the fertilization rate. Further research is needed to scrutinize the role of hCG in fertilization.
Background: Few studies evaluated cavum septum pellucidum (CSP) and cor-pus callosum (CC) indices in late gestation. This study assessed CSP and CC in-dices, along with frontal lobe measurements, and examined correlations among parameters. Methods: A cross-sectional study was conducted at Imam Khomeini Hospital Complex on 150 fetuses at ≥36 weeks’ gestation. Transabdominal ultrasound was used to measure CSP length, width, trace length, and area in the axial view; frontal lobe thickness from anterior and posterior CSP margins in horizontal and vertical directions; and CC lengths and thicknesses. CSP trace length and area were also obtained in the midsagittal view. Data were analyzed using SPSS 23. Results: Mean gestational age, biparietal diameter (BPD), head circumference (HC), and estimated fetal weight (EFW) were 37.56±1.08 weeks, 90.73±3.20 mm, 326.58± 10.59 mm, and 2987.82±333.68 gr. In the trans-thalamic view, median CSP length, width, trace length, and area were 8.92 mm, 6.05 mm, 2.81 mm, and 0.49 mm². Median CSP height in the coronal view was 5.85 mm. In the midsagittal view, mean CC outer-to-outer length, inner-to-inner length, CSP trace length, and CSP area were 41.31±4.81 mm, 29.73±4.17 mm, 2.56±0.63 mm, and 0.36±0.19 mm². All CC and CSP indices correlated significantly with HC (p<0.05). Frontal bone–to–CSP anterior and posterior distances in axial and near-field views also correlated with HC (p=0.0001). Conclusion: This study provides normative measurements for CC, CSP, and frontal lobe indices at ≥36 weeks’ gestation. These values support late-gestation brain assessment and early identification of newborns potentially at risk for neurodevelopmental concerns.
Background: The aim of this study was to analyze the trends of multiple births at both national and provincial levels in Iran from 2014 to 2023. Methods: Data on the number of live births and multiple births from 2014 to 2023 at national and provincial levels were obtained from the Iran’s Bureau of Vital Statistics. The multiple birth rate (MBR), defined as the number of live births from multiple births per 1,000 live births, was calculated annually. To examine temporal trends and detect significant changes in MBR over the study period, joinpoint regression analysis was performed. Annual percent change (APC) and average annual percent change (AAPC) were calculated for the entire period. Result: The national AAPC in the MBR was estimated at 2.38% (95%CI: 1.95 to 2.76) over the entire study period. A significant shift in trend was identified in 2020. Specifically, the APC from 2014 to 2020 was 0.24%. However, from 2020 to 2023, the APC markedly increased to 6.8%, reflecting a substantial rise in MBR during this latter period. Furthermore, the study findings demonstrated that nearly all provinces across the country have exhibited an upward trend in MBR in recent years. Conclusion: The increasing trend of multiple births in Iran aligns with global patterns. Several factors may have contributed to this rise, including increased maternal age at childbirth, higher prevalence of infertility, expanded use of assisted reproductive technologies (ARTs), and shifts in population policies.
Background: In women with polycystic ovary syndrome (PCOS), the optimal endometrial preparation strategy for frozen embryo transfer (FET) remains unclear. This clinical trial aimed to compare a long-term protocol with a stimulated cycle protocol in FET cycles of PCOS women, with clinical pregnancy rate per embryo transfer as the primary outcome. Methods: This non-randomized, open-label, two-arm clinical trial was conducted at Fatemieh Hamedan Hospital, Iran, involving 340 women with PCOS. Participants were allocated to the long-term or stimulated cycle protocols based on clinical scheduling and physician decision. The long-term protocol included low-dose combined oral contraceptives for 14 days, GnRH agonist downregulation, estradiol valerate (4–6 mg/day for ≥10 days), and progesterone before embryo transfer. The stimulated cycle protocol involved recombinant FSH with ultrasound monitoring, hCG trigger for oocyte maturation, and intramuscular progesterone (50 mg/day) for luteal phase support. For each participant one FET cycle was analyzed. Results: Baseline characteristics were similar between groups (n=170 each). The long-term protocol showed higher clinical pregnancy rates (35.9%) compared to the stimulated cycle (22.9%) (OR=1.92; 95%CI: 1.15–3.19; p=0.011). Chemical pregnancy rates also favored the long-term protocol (34.7% vs. 21.8%) (OR=1.91; 95%CI: 1.17–3.09; p=0.008). Endometrial thickness was significantly greater in the long-term protocol (8.7±0.9 mm vs. 8.4±0.8 mm; p=0.004). Conclusion: Although the long-term protocol showed higher clinical pregnancy rates in unadjusted analyses, after adjusting for confounders, protocol type was not independently associated with clinical pregnancy. Larger randomized trials are needed to confirm these findings, and adverse outcomes should be assessed in future studies.
Background: Low-dose aspirin (ASA) is used in obstetrics for different indications, mainly to prevent preeclampsia. This study investigated the underlying mechanism of ASA’s effect on the fetus’s cardiovascular functions. Methods: 42 pregnant women at 18-24 weeks of gestation, identified as high-risk for preeclampsia, received 160 mg of ASA daily. Fetal Doppler ultrasound was performed before and three weeks after ASA treatment, assessing ductus venosus, middle cerebral, umbilical, and uterine arteries pulsatility indices as well as pulmonary, aorta, and superior vena cava (SVC) diameters in the three-vessel view, including pulmonary/aorta and SVC/aorta ratios. All analyses were performed using SPSS software version 27, with a significance threshold set at p<0.05. A paired t-test was used to assess differences in means. The Chi-square and Fisher’s exact test analyzed nominal variables. Results: Post-intervention analysis revealed significant improvements in abnormal uterine artery resistance (p<0.001) and abnormal pulsatility index of the umbilical artery, middle cerebral artery, and ductus venosus (p<0.001 for all). Moreover, 160 mg/day aspirin administration significantly increased mitral E/A (early filling velocity/atrial contraction velocity: 0.397±0.029; p<0.001), diameters of aorta (4.390±0.852; p<0.001), pulmonary artery (4.895± 1.087; p<0.001), and SVC (2.511±0.535; p<0.001), while significantly decreasing left ventricular myocardial performance index (p<0.05). Conclusion: Daily administration of 160 mg of aspirin enhances fetal vascular and cardiac function. Evaluating fetal cardiovascular parameters beyond routine uterine artery Doppler, especially in high-risk pregnancies, and initiating ASA therapy in cases of insidious abnormalities, may help delay or prevent fetal complications such as intrauterine growth restriction (IUGR) by improving cardiovascular function.
Background: Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent hepatic disorder exclusive to pregnancy, associated with significant maternal morbidity and increased risk of adverse perinatal outcomes. Recurrence in subsequent pregnancies and comorbidities such as gestational diabetes and hypertensive disorders further complicate clinical management. This case presentation, an attempted to describe the diagnostic and therapeutic challenges in managing recurrent ICP, especially in the context of overlapping maternal comorbidities and limited diagnostic resources. Case Presentation: A case of a 32-year-old Iranian woman, gravida 3 para 2, with a history of one intrauterine fetal death and one neonatal death, was ultimately diagnosed with recurrent ICP. In her third pregnancy, elevated bile acid levels were confirmed by routine monitoring from 20 weeks’ gestation, peaking at 333 µmol/L by 32 weeks. Despite intensive medical therapy including ursodeoxycholic acid, hydroxychloroquine, corticosteroids, and low-molecular-weight heparin, her pruritus worsened and bile acid levels escalated, prompting preterm cesarean delivery. The neonate experienced complications, including respiratory distress, suspected Hirschsprung’s disease, sepsis, and hyperbilirubinemia. Management included continuous positive airway pressure (CPAP), broad-spectrum antibiotics, surgery, phototherapy, and parenteral nutrition. Multidisciplinary intervention enabled neonatal recovery, and maternal symptoms resolved postpartum. Conclusion: This case underscores the complexities of managing recurrent ICP, particularly in resource-limited settings. It highlights the critical need for early diagnosis, vigilant monitoring, and a multidisciplinary approach to mitigate the risk of stillbirth and improve perinatal outcomes. Additionally, it suggests that recurrent ICP may present earlier or with greater intensity in subsequent pregnancies, necessitating more comprehensive surveillance and tailored management strategies for affected mothers.