The Role of Different Medical Therapies in the Management of Adenomyosis: A Systematic Review and Meta-Analysis.

Background/Objectives: Adenomyosis is a benign condition characterized by the presence of endometrial tissue within the myometrium. Despite surgery being a valuable approach, medical options are considered as the first-line approach and have been investigated in the treatment of adenomyosis, although strong evidence in favor of these is still lacking. This study aims to gather all available data and determine the effectiveness of the aforementioned medical options in patients with associated pain and not currently seeking pregnancy, both in comparison to placebo and to one another. Methods: For this study, PubMed and EMBASE were used as data sources, searched up to January 2024. A systematic review and meta-analysis were performed in accordance to guidelines from the Cochrane Collaboration. The primary outcomes investigated were changes in dysmenorrhea, quantified by means of VAS scores, HMB in terms of number of bleeding days, and changes in uterine volume determined at ultrasound. Twelve eligible studies were selected. Results: The results highlighted that dienogest yields a reduction in dysmenorrhea that is significantly superior to that of the rest of the medical treatments investigated (p-value of <0.0002). On the other hand, GnRH agonists seem to play a more prominent role in reducing uterine volume (p-value of 0.003). While it was not possible to determine which medical treatment better decreased the number of bleeding days, it was observed that COC performed significantly worse than the other treatments studied (p-value of 0.02). Conclusions: While this meta-analysis provides valuable insights in the comparative efficacy of different treatments, the paucity of relevant studies on the topic might impact the reliability of some of the conclusions drawn.

Rescue intrauterine insemination in women failing to retrieve oocytes at ovum pick-up: report of a case series.

PURPOSE: Failure to collect oocytes at the time of oocyte pick-up is an unfavorable outcome of in vitro fertilization (IVF) cycles. In these cases, prompt intrauterine insemination (IUI) could be an option (rescue IUI), but this possibility has been poorly studied. METHODS: Rescue IUI is routinely offered in our unit in women failing to retrieve oocytes, provided that they have at least one patent tube, normal male semen analysis, and the total number of developed follicles is ≤ 3. We therefore reviewed all oocyte retrievals performed from 2006 to 2022 in our unit to identify these cases. As a comparator, we referred to preplanned IUI performed during the same study period. The 95% confidence interval (95% CI) of proportions was calculated using a binomial distribution model. RESULTS: Rescue IUI was performed in 96 out of 3531 oocyte retrievals (2.7%; 95% CI 2.2-3.3%). Six live births were obtained, corresponding to 6.2% (95% CI 2.3-13.1). All pregnancies were singletons. CONCLUSIONS: Rescue IUI in women failing to retrieve oocytes is a possible option that may be considered in selected cases. The efficacy is low, but the procedure is simple, and without significant risks. Generalizability to a conventional IVF protocol setting is however limited.

The need to restore generative identity in women undergoing assisted reproductive technology: Development and psychometric validation of the fertility reparation inventory.

OBJECTIVE: This study described the development and psychometric evaluation of the fertility reparation inventory, providing measures of manic and expiatory reparation as symbolic dynamics of restoring one's procreative and generative identity through Assisted Reproductive Technology (ART). METHODS: Two cross-sectional studies were conducted on female patients undergoing ART (N = 150) and women from the general population (N = 250), respectively. Exploratory factor analysis and confirmatory factor analysis assessed construct validity and reliability. Pearson's bivariate correlations were used to provide convergent evidence of validity with omnipotence, perceived infertility-related stress, anxiety, depression, need for reparation, fear of punishment, and hope. RESULTS: The results confirmed a two-factor solution of the 12-item instrument, with adequate fit, a very good internal consistency, and well-supported forms of convergent validity. CONCLUSION: This study provides a meaningful psychodynamic contribution, in both theoretical and empirical terms, for the understanding of emotional dynamics and psychological issues underlying the demand for ART.

Immigration and Adverse Pregnancy Outcomes in an Italian Free Care Hospital.

INTRODUCTION: The ever-increasing wave of immigration in Italy has posed demanding challenges in the management of the new multiethnic obstetric population. The aim of this study was to compare pregnancy and perinatal outcomes between immigrants and the native population in an Italian public hospital. MATERIALS AND METHODS: Singleton pregnant women (≥ 24 weeks of gestation) who delivered during a 3-year period in an Italian free care hospital were included. Long-term (≥ 2 years of residence) immigrant patients were divided into 4 groups according to their ethnic origin: Europeans, Asians, Latin Americans, and Africans. Perinatal indicators of obstetric outcomes were collected and compared between immigrants and Italians. RESULTS: Of the 3556 patients included, 1092 were immigrants and 2464 Italians. The immigrant cohort experienced a higher rate of macrosomia (1.8% vs 0.6%; p = 0.001), very low birth weight (1.3% vs 0.6%; p = 0.048), very early preterm delivery (1.4% vs 0.4%; p = 0.048), and gestational diabetes mellitus (1.8% vs 0.5%; p = 003) compared with the native population. The overall rate of cesarean sections was greater among Italians (56% vs 45.8%; p < 0.001). Among ethnic groups, Europeans and Latin Americans reported a higher rate of preterm delivery (20.2% and 19%, respectively; p < 0.001). Latin Americans carried also a greater risk of fetal macrosomia (3.6%; p < 0.008), while the rate of very low birth weight was higher among Europeans and Africans (2% and 1.8%, respectively; p < 0.04). CONCLUSION: Obstetricians should pay special attention to the potential disparities in pregnancy outcomes between immigrants and the native population. Future efforts should focus on reducing preterm delivery and glucose dysmetabolism among pregnant immigrants.

Breast imaging screening in a BRCA1-mutated lactating patient: A potential pitfall mimicking malignancy.

Breast imaging screening during lactation poses a real clinical challenge, especially in high-risk patients. We presented the case of a 34-year-old BRCA1-mutated woman showing marked, asymmetric background parenchymal enhancement on the right breast suspicious for malignancy in the context of annual screening magnetic resonance imaging. The patient revealed that she was still occasionally breastfeeding her two-year-old child only from right side. Ultrasound evaluation reported typical benign lactational findings on the right enhancing breast. An in-depth understanding of expected/ physiologic breast changes during lactation and an accurate clinical-radiological correlation are required to appropriately guide patient management and avoid misdiagnosis.

The role of alpha lipoic acid in female and male infertility: a systematic review.

OBJECTIVE: Infertility is an increasingly frequent health condition, which may depend on female or male factors. Oxidative stress (OS), resulting from a disrupted balance between reactive oxygen species (ROS) and protective antioxidants, affects the reproductive lifespan of men and women. In this review, we examine if alpha lipoic acid (ALA), among the oral supplements currently in use, has an evidence-based beneficial role in the context of female and male infertility. METHODS: We performed a search from English literature using PubMed database with the following keywords: 'female infertility', 'male infertility', 'semen', 'sperm', 'sub-fertile man', 'alpha-lipoic acid', ' alpha lipoic acid', 'lipoid acid', 'endometriosis', 'chronic pelvic pain', 'follicular fluid' and 'oocytes'. We included clinical trials, multicentric studies and reviews. The total number of references found after automatically and manually excluding duplicates was 180. After primary and secondary screening, 28 articles were selected. RESULTS: The available literature demonstrates the positive effects of ALA in multiple processes from oocyte maturation (0.87 ± 0.9% of oocyte in MII vs 0.81 ± 3.9%; p < .05) to fertilization, embryo development (57.7% vs 75.7% grade 1 embryo; p < .05) and reproductive outcomes. Its regular administration both in sub-fertile women and men shows to reduce pelvic pain in endometriosis (p < .05), regularize menstrual flow and metabolic disorders (p < .01) and improve sperm quality (p < .001). CONCLUSIONS: ALA represents a promising new molecule in the field of couple infertility. More clinical studies are needed in order to enhance its use in clinical practice.

Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility.

Microbiota are microorganismal communities colonizing human tissues exposed to the external environment, including the urogenital tract. The bacterial composition of the vaginal microbiota has been established and is partially related to obstetric outcome, while the uterine microbiota, considered to be a sterile environment for years, is now the focus of more extensive studies and debates. The characterization of the microbiota contained in the reproductive tract (RT) of asymptomatic and infertile women, could define a specific RT microbiota associated with implantation failure. In this pilot study, 34 women undergoing personalized hormonal stimulation were recruited and the biological samples of each patient, vaginal fluid, and endometrial biopsy, were collected immediately prior to oocyte-pick up, and sequenced. Women were subsequently divided into groups according to fertilization outcome. Analysis of the 16s rRNA V4-V5 region revealed a significant difference between vaginal and endometrial microbiota. The vaginal microbiota of pregnant women corroborated previous data, exhibiting a lactobacilli-dominant habitat compared to non-pregnant cases, while the endometrial bacterial colonization was characterized by a polymicrobial ecosystem in which lactobacilli were exclusively detected in the group that displayed unsuccessful in vitro fertilization. Overall, these preliminary results revisit our knowledge of the genitourinary microbiota, and highlight a putative relationship between vaginal/endometrial microbiota and reproductive success.

Could art cycles have a detrimental effect on ovarian reserve? A retrospective case control study.

BACKGROUND: Even if it is supposed damage of repeated ART (assisted reproductive technology) cycles on oocyte pool, there is still no evidence in literature. Aim of the study is to investigate whether infertile women who undergo to several ART cycles can show a lower ovarian reserve measured by AMH (Anti-Mullerian hormone) levels. METHODS: The study includes 282 infertile women, between 18 and 42 years, and allocated into two groups: 159 women previously submitted to two or more ART cycles (group A) and 123 women never submitted naïve to-ART cycles (group B). We tested whether AMH, FSH, LH and E2 levels were significantly different between the two groups, stratifying according to age. RESULTS: Regardless to the age ranges bands, the AMH in group A was statistically significant lower than in group B with a statistical significance (P=0.047). In particular women aged over 35 previously submitted to one or more ART cycles showed lower AMH levels, than those paired with age, which had never been treated with ART. CONCLUSIONS: Despite the limitations of the study, our data demonstrate a reduced AMH levels in women aged over 35 previously submitted to two or more repeated ART-cycles compared to patients never treated before. The strength of this study is the actuality of the topic that has not been discussed before in detail.

Current management of ovarian endometriomas.

The choice of treatment in case of ovarian endometriomas is one of the most discussed topics in Reproductive Medicine. Management options include expectancy, medical treatment, surgery, in vitro fertilization (IVF), or a combination of the above. The main presenting symptom, i.e. pain or infertility, usually guide the choice of treatment. Medical treatment is usually preferred as the first line option when pain is the associated symptom, whereas surgery or IVF are preferred in case of associated infertility. In most cases, however, the symptoms may overlap, and often a patient with infertility complains also of chronic pelvic pain, and vice versa. In addition, in many cases the patient may be asymptomatic, usually presenting with the incidental diagnosis of an ovarian endometrioma. Therefore, a strict categorization in two separate pathways of either associated pain or associated infertility, as the one outlined in current guidelines, may not represent the real clinical scenario. In this context, a personalized approach, taking into account several additional variables that are not considered in guidelines, is mandatory. In the present review, a symptom-driven approach to the management of ovarian endometriomas, that goes beyond the pain/infertility categorization, is described, considering additional parameters that guide the choice of treatment, with a patient-centered, personalized approach.

Ultrasonography reappraisal of tubal patency in assisted reproduction technology patients: comparison between 2D and 3D-sonohysterosalpingography. A pilot study.

BACKGROUND: The aim of this study was to compare 2D and 3D-sonohysterosalpingography (2D-3D-HyFoSy) with previous diagnostic laparoscopy in the diagnosis of tubal patency, and compare each procedure in terms of procedure's time, perceived pain and complication rate. METHODS: We prospectively recruited infertile women, previously submitted to laparoscopy and randomly allocated into 2D-HyFoSy (group I) and 3D-HyFoSy (group II). We analyzed the results in term of sensitivity, specificity, positive predictive value and negative predictive value in tubal patency evaluation of both procedures in comparison with laparoscopy. RESULTS: We enrolled 50 women, 25 in group I and 25 in group II. 2D-HyFoSy findings obtained in group I, were concordant with laparoscopy in 81% of cases, with a sensitivity of 80% and a specificity of 92%. In group II, a correspondence was present in 88% of examinations, with a sensitivity and specificity of 98% and 91.4% respectively. 3D-HyFoSy was found to be faster and less painful than 2D (P<0.001). CONCLUSIONS: In the diagnosis of tubal occlusion, in the high-risk population, it seems advisable to us using the 3D-HyFoSy as the first-level examination, while, in low-risk patients, if the tubes appear obstructed in 2D-HyFoSy, the 3D-HyFoSy should be indicated before submitting patients to operative laparoscopy.

Overcoming platinum resistance in ovarian cancer treatment: from clinical practice to emerging chemical therapies.

INTRODUCTION: The objective of this review is to summarize results from clinical trials that tested cytotoxic drugs and target strategies for the treatment of platinum resistant (PR) recurrent ovarian cancer (ROC) with particular attention to Phase III and ongoing trials. Areas covered: Since platinum free interval (PFI) represents the most important predictive factor for response to platinum re-treatment in ROC, non-platinum regimens are conventionally considered the most appropriate approaches. Impressive progress has been made in recent decades, resulting in the identification of most effective cytotoxic agents and in the development of new target strategies. However, the efficacy of most of these drugs for the treatment of PR disease is still limited. Expert opinion: The most favorable benefit for the treatment of PR disease, has been described by the AURELIA trial that showed a 3.3 months increase in progression free survival (PFS) when bevacizumab was combined with non-platinum single agent chemotherapy in bevacizumab-naïve patients. Nevertheless, the use of novel agents is associated to important costs for just little gains in survival. Thus, in our opinion the economic evaluation, such as the incorporation of quality of life into the clinical studies is crucial for the development of future trials for PR-ROC.

Hypertension and early menopause after the use of assisted reproductive technologies in women aged 43 years or older: Long-term follow-up study.

AIM: The aim of this study was to investigate the long-term consequences to women's health and the onset of menopause in healthy women of advanced reproductive age who conceived by assisted reproductive technologies (ART). METHODS: Healthy women who conceived by ART (72) and controls (80) were selected among 320 women ≥ 43 years, who delivered between January 2010 and December 2011 in the Department of Gynecological and Obstetrical Sciences and Urological Sciences of "Sapienza" University of Rome. Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and presence of hypertension and diabetes were analyzed at three days, six months, and three years after delivery. The onset of menopause was analyzed after three years. RESULTS: In the ART group, SBP, DBP and hypertension were higher at three days, six months, and three years after delivery. Menopausal age was significantly lower. CONCLUSION: The impact of ART in healthy women of advanced reproductive age in the years after delivery is not limited to the possible development of cardiovascular risk factors, such as hypertension, but can also influence the age of onset of menopause.

A rare case of sudden death due to hypotension during cesarean section in a woman suffering from pheochromocytoma and neurofibromatosis.

Sudden death following acute hypotension due to an undiagnosed pheochromocytoma (PHEO) is a rare event. Moreover, histopathology of the myocardium in such cases is rarely reported. We present a case of a woman who died during delivery. A 37-year-old parturient, who was 38 weeks pregnant, suffering from neurofibromatosis underwent a cesarean section following peridural anesthesia. Acute hypotension, acute intra-operative pulmonary edema and supraventricular paroxysmal tachyarrhythmia occurred during delivery, followed by death. The autopsy revealed the presence of a PHEO, confirmed immunohistochemically with chromogranin-A (CgA), CD20 antibody (L26), anti-Keratocan antibody (KER-1) and neuron-specific enolase (NSE), and a PHEO-induced cardiomyopathy. The physiopathology of both stress-induced cardiomyopathy and PHEO-induced cardiomyopathy, as well as the role of anesthesia in provoking the death, are discussed. The association of an undiagnosed PHEO with neurofibromatosis as the cause of sudden death in pregnancy is an obstetric urgency that raises forensic pathology issues.

Dysregulation of diurnal salivary cortisol production is associated with spontaneous preterm delivery: a pilot study.

OBJECTIVES: The purpose of this study was to evaluate whether the diurnal fluctuation of salivary cortisol and its overall diurnal secretion are associated with the length of gestation in patients who were admitted to the hospital with an assigned diagnosis of possible preterm labor (PL) at a gestational age of 28-33 weeks. METHODS: In 22 patients, maternal saliva samples were collected for a cortisol assay 4 times per day (8 AM, 12 AM, 4 PM and 8 PM) on day 4 and day 6 after antenatal corticosteroid prophylaxis to prevent neonatal respiratory distress syndrome. RESULTS: Eight patients who ultimately delivered before term (32.6 ± 1.7 gestation weeks) showed an inverted fluctuation of salivary cortisol on both days 4 and 6, morning cortisol levels being significantly lower than evening levels. In contrast, in 14 patients who delivered at term (39.5 ± 0.6 gestation weeks), the physiological diurnal fluctuation of salivary cortisol was maintained. In addition, a distinctive feature of women delivering before term was a significantly hampered salivary cortisol diurnal production measured on day 6. CONCLUSIONS: Corticoadrenal activity is dysregulated and anticipates very preterm delivery in women with an assigned diagnosis of possible PL.

Menopausal symptoms after the discontinuation of long-term hormone replacement therapy in women under 60: a 3-year follow-up.

BACKGROUND: Prescriptions for hormone replacement therapy (HRT) declined following the publication of the Women's Health Initiative study. The number of women who experience recurrence of menopausal symptoms after discontinuation of long-term HRT (LT-HRT), the length of time these symptoms last and the preferred alternative treatments remain unknown. METHODS: This prospective 3-year follow-up study analyses the prevalence and intensity of menopausal symptoms that occur in young postmenopausal women who discontinued LT-HRT. Symptoms were evaluated using the Menopause Rating Scale. RESULTS: Women (254) who discontinued LT-HRT (mean use: 6.9 ± 2.3 years) were recruited. Mean age at menopause was 48.1 ± 3.4 years. Mean age at discontinuation was 56.8 ± 3.7 years. 23% of the women were lost to follow-up. Of the remaining 196 women, 93% experienced a recurrence of menopausal symptoms within the first year, 25% resumed low-dose HRT, 62% used vaginal estrogens, 54% used phytoestrogens, and 2% used alternative therapies. A decrease in symptom prevalence and intensity was observed during the 3-year follow-up. CONCLUSIONS: Symptoms re-appeared in a significant proportion of patients within the first year after discontinuation of LT-HRT. However, after 3 years, the majority of these women were asymptomatic. Patients who discontinue LT-HRT may require a more detailed follow-up immediately after the discontinuation of treatment.

Maternal C-reactive protein at hospital admission is a simple predictor of funisitis in preterm premature rupture of membranes.

AIM: To analyze the prognostic value of maternal serum C-reactive protein (CRP) in predicting funisitis in patients with preterm premature rupture of membranes (pPROM). METHODS: 66 patients (gestational age 24-33 weeks) hospitalized 1-12 h after pPROM were enrolled. White blood cell count (WBC), platelet count (PLT) and plasma concentration of CRP were assessed every 3 days. Histological evidence of chorioamnionitis and funisitis was obtained post-partum. Receiver operating characteristic (ROC) curves were employed to evaluate the role of maternal CRP in predicting funisitis. RESULTS: Funisitis was found in 24 patients (36.3%); 42 patients (63.7%) without funisitis were considered as controls. PLT and WBC at admission and before delivery did not show significant differences and were not statistically different between the two groups. Patients with funisitis had significantly higher CRP levels both at admission to hospital and 24- 48 h before delivery. ROC curve analysis showed that CRP at admission (area under the curve: 0.671, p = 0.021) and before delivery (area under the curve: 0.737, p = 0.001) are predictive of funisitis. CONCLUSIONS: High maternal serum CRP levels (>20,000 µg/l) in pPROM patients at admission to hospital may be an early marker which indicates, with a good diagnostic performance, the presence of funisitis.