Supplementation with vitamin D improves the embryo quality in in vitro fertilization (IVF) programs, independently of the patients' basal vitamin D status.

PURPOSE: The study aims to demonstrate the effects of Vitamin D (VD) supplementation, prior to oocyte pick-up within IVF protocols, in women with diverse VD status at the enrollment. METHODS: A total of 204 women eligible for intra-cytoplasmatic sperm injection (ICSI) cycles were included in the study and two homogeneous groups were selected from the database. Both group of patients with normal VD baseline level (> 40 ng/ml) and patients with low VD baseline level (< 20 ng/ml) were divided into control group and treatment group. The control group followed the standard procedure. The treatment group was supplemented with vitamin D3 as cholecalciferol in combination with Myo-Inositol, folic acid, and melatonin 3 months before standard procedure, once a day in the evening. RESULTS: VD levels significantly increased in the study group of low baseline VD, both in serum and in the follicular fluid compared to controls. The treatment induced a significant improvement of the embryo quality in both group of patients considered. CONCLUSION: Supplementation of VD in patients undergoing ICSI procedures significantly improved the number of top-quality embryos compared with the control group, either starting from VD normal baseline values or starting from low values. TRIAL REGISTRATION NUMBER: 07/2018.

Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women's mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles' activation, which could cause an aberrant mechano-sensitive pacemaker activation-deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

Electro-Metabolic Coupling of Cumulus-Oocyte Complex.

Oocyte-cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus-oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca2+ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells.

Reproductive Outcomes in Young Women with Early-Stage Cervical Cancer Greater than 2 cm Undergoing Fertility-Sparing Treatment: A Systematic Review.

Background and Objectives: Despite advancements in detection and treatment, cervical cancer remains a significant health concern, particularly among young women of reproductive age. Limited data exists in the literature regarding fertility-sparing treatment (FST) of cervical cancers with tumor sizes greater than 2 cm. The objective of this systematic review was to evaluate the reproductive outcomes of women diagnosed with cervical cancer greater than 2 cm who underwent FST. Materials and Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies (retrospective or prospective) that reported reproductive outcomes of patients with cervical cancer >2 cm were considered eligible for inclusion in this systematic review (CRD42024521964). Studies describing only the oncologic outcomes, involving FST for cervical cancers less than 2 cm in size, and case reports were excluded. Results: Seventeen papers that met the abovementioned inclusion criteria were included in the present systematic review. In total, 443 patients with a cervical cancer larger than 2 cm were included in this systematic review. Eighty pregnancies occurred, with 24 miscarriages and 54 live births. Conclusions: FST appears to be a viable option for women of childbearing age diagnosed with cervical cancer larger than 2 cm. However, careful consideration is advised in interpreting these encouraging results, as they are subject to limitations, such as variability in study designs and potential biases. In addition, reproductive outcomes should be further cross-referenced with oncologic outcomes to clarify the potential risk-benefit ratio. It is critical to conduct further research using standardized approaches and larger participant groups to strengthen the validity of the conclusions drawn.

Laparoscopic management of a cornual pregnancy following failed methotrexate treatment: case report and review of literature.

To describe a rare case of a singleton 8-week cornual pregnancy (CP), treated by laparoscopic incision of the uterine wall, the ectopic pregnancy was removed and the uterine site was sutured with interrupted sutures. A 21-year-old woman was admitted for suspected singleton CP at week 8. Clinical examination, b-hCG increase, and transvaginal ultrasonography (TU) were used to monitor the suspected diagnosis of an ectopic pregnancy. Following failure of methotrexate administration, surgeons performed a laparoscopy. The CP removal was performed by laparoscopic incision, enucleating the corneal mass and suturing the uterine site of the ectopic pregnancy with interrupted sutures. Intraoperative and postoperative complications and uterine integrity preservation were studied. Postoperative recovery period was normal, without intraprocedural or postprocedural complications.Uterine integrity was preserved. No further therapeutic interventions were needed in follow-up. This study confirmed the feasibility, safety and efficacy of performing a safe, minimally invasive, laparoscopic treatment of an early unruptured CP, without intraoperative and postoperative complications, with a normal postoperative recovery period and preservation of uterine integrity.

Laparoscopic treatment of ovarian granulosa cells tumor developed in the pelvic anterior preperitoneal space 20 years after laparotomic salpingo-oophorectomy: case report and review of literature.

Granulosa cells (GC) tumors are rare tumors which account for approximately 2-3% of all ovarian malignancies with a favorable prognosis. We report a case of a 54-year-old postmenopausal woman who developed an ovarian GC tumor in the pelvic anterior preperitoneal space 20 years after laparotomic salpingo-oophorectomy due to small part of the cyst could drop or remain entrapped into the abdominal wound during the closure of laparotomy 20 years before. Then, the patient underwent a second laparoscopic procedure with peritoneal washing, a type A radical hysterectomy, omentectomy, appendectomy, and pelvic and para-aortic lymphadenectomy. This rare case of ovarian GC tumor developing in the site of previous laparotomy demonstrates the importance of a correct and clean surgical procedure to avoid the risk of leaving even small portions of the cyst exposing the patients to either the risk of malignancy or additional surgical procedures.Precis: This rare case of ovarian granulosa cells tumor developed from residual ovarian tissue intrapped into the abdominal wound 20 years after laparotomic ovariectomy.

Chronic Endometritis, a Common Disease Hidden Behind Endometrial Polyps in Premenopausal Women: First Evidence From a Case-Control Study.

STUDY OBJECTIVE: To investigate the correlation between endometrial polyps (EPs) and chronic endometritis (CE). DESIGN: Single-center retrospective case-control study. SETTING: Academic center. PATIENTS: A total of 480 premenopausal women with abnormal uterine bleeding (AUB) were enrolled. Group A included 240 women suffering from EPs (diagnosed by hysteroscopy and histology), and group B included 240 patients without EPs at hysteroscopy. INTERVENTIONS: In group A, 2 separate samples were obtained from the EPs (group A polyps) and endometrium (group A endometrium). In group B, a single sample of endometrial tissue was evaluated (group B endometrium). All tissue samples were subjected to immunohistochemistry for CD-138 for plasma cell identification. MEASUREMENTS AND MAIN RESULTS: The primary study endpoint was to compare the rates of CE in group A endometrium versus group B endometrium. The secondary endpoint was to evaluate the consistency in CD-138 immunoreactivity between group A polyps and compared with group A endometrium. A higher prevalence of CE was observed in group A endometrium compared with group B endometrium (p < .0001). The total percentage of EPs showing CD-138 positivity was 76.7% (184 of 240). CE was more frequent in women with CD-138+ EPs compared to those with CD-138- EPs (p < .0001). CONCLUSIONS: EPs were commonly associated with CE in the premenopausal women suffering from AUB. Moreover, the majority of EPs were positive for CD-138 staining, suggesting a possible hidden association between chronic inflammation and EPs.

Independent association between uterine malformations and cervical insufficiency: a retrospective population-based cohort study.

OBJECTIVE: The purpose of our study was to explore maternal and fetal outcomes in the second and third trimester in women with uterine malformations. STUDY DESIGN: This was a retrospective population-based cohort study including women with a diagnosis of uterine malformation arised from workup for infertility or recurrent pregnancy loss, was accidental during pregnancy, or was noticed at the time of cesarean delivery. RESULTS: A total of 280,721 pregnancies met the inclusion criteria and were divided into two study groups: (1) pregnancies in women with uterine malformations (n = 1099); and (2) controls (n = 279,662). The rate of women presenting uterine malformations was 0.39%. The prevalence of cervical os insufficiency was significantly higher in women with a uterine malformation than in the control group (3.6 vs. 0.4%, p < 0.001). A multivariate analysis, performed to evaluate risk factors for cervical insufficiency in women with uterine malformations. Mullerian anomalies (OR 6.19, 95% CI 4.41-8.70, p < 0.001), maternal age (OR 1.05, 95% CI 1.04-1.06, p < 0.001), recurrent abortions (OR 12.93, 95% CI 11.43-14.62, p < 0.001), and ethnicity (OR 2.86, 95% CI 2.454-3.34, p < 0.001) were found to be independently associated with the development of cervical insufficiency. CONCLUSION: Uterine anomalies have a strong association with cervical insufficiency. Women with uterine anomalies have an increased risk to develop pregnancy complications that arise from a loss in cervical function during the midtrimester or early third trimester.

Evaluation of the cervix tissue homogeneity by ultrasound elastography in infertile women for the prediction of embryo transfer ease: a diagnostic accuracy study.

BACKGROUND: Ultrasound elastography is a non-invasive medical imaging technique able to quantitatively characterize the stiffness of a given tissue. It has been shown to predict the risk for cervical insufficiency and preterm delivery, and to allow differentiation of malignancy from normal tissue. The present study sought to evaluate whether cervical tissue dishomogeneity, as assessed by cervical ultrasound elastography, may predict the embryo transfer (ET) ease in infertile women undergoing IVF/ICSI. METHODS: We evaluated 154 infertile patients with no history of previous ET or intrauterine insemination. Cervical stiffness was evaluated in six regions of interest (ROI), compared two by two to obtain strain ratio (SR) values. Since a SR value of 1 was suggestive of tissue homogeneity, we computed 1-SR/SR-1 values to obtain a measure of the degree of cervical tissue dishomogeneity that we named "dishomogeneity index" (DI). Ultrasound-guided ET was performed by an expert operator blinded to the results of cervical elastography. The prediction ability of elastography on ET ease was evaluated by binary logistic regression, and the predictive accuracy of the independent variables was quantified with area under the curve (AUC) estimates derived from receiver operating characteristic (ROC) curve. RESULTS: ET resulted to be easy in 99 out of 154 patients (64,2%), difficult in 54 patients (35%), and impossible in one. DI values in cervical medial lips region correctly classified 86.9% of patients, according to binary logistic regression, with a sensitivity of 81.4% and a specificity of 89,9%, positive likelihood ratio (LR) 8.07 and negative LR of 0.21. A DI cut-off value of 0.29 predicted a difficulty of ET with a sensitivity of 88,9% and a specificity of 85%. CONCLUSIONS: Cervical ultrasound elastography, by allowing the identification of cervical tissue dishomogeneity, may be of help in predicting the ET ease in infertile women candidates to IVF/ICSI.

Prescribing exercise for prevention and treatment of gestational diabetes: review of suggested recommendations.

Exercise has been proved to be safe during pregnancy and to offer benefits for both mother and fetus; moreover, physical activity may represent a useful tool for gestational diabetes prevention and treatment. Therefore, all women in uncomplicated pregnancy should be encouraged to engage in physical activity as part of a healthy lifestyle. However, exercise in pregnancy needs a careful medical evaluation to exclude medical or obstetric contraindications to exercise, and an appropriate prescription considering frequency, intensity, type and duration of exercise, to carefully balance between potential benefits and potential harmful effects. Moreover, some precautions related to anatomical and functional adaptations observed during pregnancy should be taken into consideration. This review summarized the suggested recommendations for physical activity among pregnant women with focus on gestational diabetes.

Hysteroscopy as a valid tool for endometrial pathology in patients with postmenopausal bleeding or asymptomatic patients with a thickened endometrium: hysteroscopic and histological results.

OBJECTIVE: This study compares hysteroscopic and histopathological results in postmenopausal women with abnormal uterine bleeding (AUB) and asymptomatic postmenopausal women with a thickened endometrium. MATERIALS AND METHODS: This is a retrospective study of 570 cases hysteroscopically examined between January 2008 and July 2012. The patients were followed up at the Istituto Tumori 'Giovanni Paolo II', Bari, Italy. RESULTS: A total of 320 of the 570 cases were selected. The inclusion criteria were transvaginal ultrasound, hysteroscopy and endometrial biopsy. In the AUB group, if the hysteroscopy results were normal, a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100, 95, 71 and 100%, respectively, were achieved, while in the asymptomatic group these values were 100, 97, 90 and 100%, respectively. For both the group with polyps and that with myomas, the sensitivity, specificity, PPV and NPV were 100%. For endometrial hyperplasia, hysteroscopy showed a sensitivity, specificity, PPV and NPV of 81, 96, 87 and 93%, respectively, in the AUB group, while in the asymptomatic group, the sensitivity was 60%, the specificity and PPV were 100%, and the NPV was 98%. The sensitivity of hysteroscopy for endometrial cancer was 63%, the specificity 97%, the PPV 77%, and the NPV 95%. CONCLUSIONS: In postmenopausal women with a thickened endometrium with or without AUB, hysteroscopy allows for an accurate diagnosis in benign endometrial pathology. Hysteroscopy also allows directed biopsies of suspicious lesions, which is useful in malignant endometrial pathology.

Artificial Intelligence, Intrapartum Ultrasound and Dystocic Delivery: AIDA (Artificial Intelligence Dystocia Algorithm), a Promising Helping Decision Support System.

The position of the fetal head during engagement and progression in the birth canal is the primary cause of dystocic labor and arrest of progression, often due to malposition and malrotation. The authors performed an investigation on pregnant women in labor, who all underwent vaginal digital examination by obstetricians and midwives as well as intrapartum ultrasonography to collect four "geometric parameters", measured in all the women. All parameters were measured using artificial intelligence and machine learning algorithms, called AIDA (artificial intelligence dystocia algorithm), which incorporates a human-in-the-loop approach, that is, to use AI (artificial intelligence) algorithms that prioritize the physician's decision and explainable artificial intelligence (XAI). The AIDA was structured into five classes. After a number of "geometric parameters" were collected, the data obtained from the AIDA analysis were entered into a red, yellow, or green zone, linked to the analysis of the progress of labor. Using the AIDA analysis, we were able to identify five reference classes for patients in labor, each of which had a certain sort of birth outcome. A 100% cesarean birth prediction was made in two of these five classes. The use of artificial intelligence, through the evaluation of certain obstetric parameters in specific decision-making algorithms, allows physicians to systematically understand how the results of the algorithms can be explained. This approach can be useful in evaluating the progress of labor and predicting the labor outcome, including spontaneous, whether operative VD (vaginal delivery) should be attempted, or if ICD (intrapartum cesarean delivery) is preferable or necessary.

Influence of ovarian torsion on reproductive outcomes and mode of delivery.

Purpose: To investigate differences in reproductive outcomes among patients before and following ovarian torsion. Study design: In this retrospective cohort study, we investigated the reproductive outcomes of patients who underwent surgery for ovarian torsion between 1988 and 2015 in a tertiary medical center. Data on deliveries before and after ovarian torsion were compared. Results: During the study period, 199 women underwent surgery due to ovarian torsion. The majority (91.4%; n = 182) underwent detorsion, and 8.6% (n = 17) underwent unilateral adnexectomy. At the time of the torsion, 27.6% (n = 55) of patients were pregnant. Among women who suffered from ovarian torsion, about half (52%) of the deliveries occurred before the torsion and 48% following the torsion. No significant difference in the live birth rate was noted (p = 0.19). The fertility treatment rate in our cohort was 7.5% before and 5% after the torsion (p = 0.01). In addition, live birth, cesarean delivery, and fertility treatment rates were similar in women who underwent detorsion vs. those who had adnexectomy. Conclusion: Surgically treated ovarian torsion does not appear to negatively influence fertility and live birth potential.

Isthmocele and Infertility.

Isthmocele is a gynecological condition characterized by a disruption in the uterine scar, often associated with prior cesarean sections. This anatomical anomaly can be attributed to inadequate or insufficient healing of the uterine wall following a cesarean incision. It appears that isthmocele may impact a woman's quality of life as well as her reproductive capacity. The incidence of isthmocele can range from 20% to 70% in women who have undergone a cesarean section. This review aims to sum up the current knowledge about the effect of isthmocele on fertility and the possible therapeutic strategies to achieve pregnancy. However, currently, there is not sufficiently robust evidence to indicate the need for surgical correction in all asymptomatic patients seeking fertility. In cases where surgical correction of isthmocele is deemed necessary, it is advisable to evaluate residual myometrial thickness (RMT). For patients with RMT >2.5-3 mm, hysteroscopy appears to be the technique of choice. In cases where the residual tissue is lower, recourse to laparotomic, laparoscopic, or vaginal approaches is warranted.

Vitamin and Carotenoid Intake and Outcomes of In Vitro Fertilization in Women Referring to an Italian Fertility Service: A Cross-Sectional Analysis of a Prospective Cohort Study.

BACKGROUND: Nutrition may impact reproductive health and fertility potential. The role of dietary antioxidants in affecting conception and birth outcomes is a topic of emerging interest. METHODS: This cross-sectional analysis from a prospective cohort study aims to explore the relationship between the intake of antioxidants, vitamins, and carotenoids and the outcomes of assisted reproduction techniques. Information on the socio-demographic characteristics, health histories, lifestyle habits, and diet information of subfertile couples referred to a fertility center was obtained. RESULTS: A total of 494 women were enrolled. According to the four IVF outcomes considered, 95% of women achieved good quality oocytes, 87% achieved embryo transfer, 32.0% achieved clinical pregnancies, and 24.5% achieved pregnancy at term. Associations were found between age and the number of good quality oocytes (p = 0.02). A moderate level of physical activity in the prior 5 years was associated with a better rate of achieving clinical pregnancy (p = 0.03). Smoking habits, alcohol intake, and caffeine consumption did not show associations with any outcome. No associations were found, even after accounting for potential confounders, with the intake of vitamins C, D, E, and α-carotene, ß-carotene, beta-cryptoxanthin, lutein, and folate. CONCLUSION: Further research is needed to understand how antioxidant intake may have a role in modulating fertility.

Inadvertent Administration of 72 µg of Follitropin-Δ for Three Consecutive Days Does Not Appear to Be Dangerous for Poor Responders: A Case Series.

Follitropin delta (Δ) is a recombinant human follicle-stimulating hormone (rFSH), like natural human FSH, that can stimulate the development and growth of multiple follicles. Treatment with Follitropin-Δ may cause mild to severe adverse reactions, such as the risk of developing ovarian hyperstimulation syndrome, resulting in nausea, vomiting and diarrhea, weight loss, respiratory difficulty, stomach swelling and discomfort of the pelvic area, headaches, and fatigue. To date, the effects of a Follitropin-Δ overdosage are unknown, and no data are reported in the scientific literature or in the drug data sheet. Therefore, this study aimed to describe the effects of Follitropin-Δ overdosages in poorly responding women who underwent IVF cycles. This is a descriptive case series of four nulligravid, poorly responding patients, two of whom made requests for fertility preservation. Four poorly responding patients who were prescribed 20.0 µg/day of Follitropin-Δ for three consecutive days wrongly injected the total cartridge of 72 µg Follitropin-Δ every day. After the incorrect injection of Follitropin-Δ, the patients continued their controlled ovarian stimulation and underwent vaginal ovarian pick up. The analyzed patients had no side effects or adverse reactions. The evaluations reported in this case series showed that the accidental use of 72 µg/day of Follitropin-Δ for three days did not cause side effects or adverse reactions in poor responders.

"Lights and Shades" of Fertility Preservation in Transgender Men Patients: A Clinical and Pathological Review.

Fertility preservation (FP) is becoming a critical issue in transgender men who desire biological offspring in the future. The prevalence of transgender individuals in the United States is increasing, and as a result, the demand for gender-affirming surgeries (GAS) and associated FP techniques is rising. Despite the growing demand, there is currently no personalized approach to FP for transgender men, and the available techniques have limitations that require further investigation. In the present review we carefully examine the existing literature on this topic to highlight the shortcomings of current methods and areas where additional research is needed to advance the field. Hormonal therapy (HT), which is an integral part of gender transition in transgender men, can have a significant impact on fertility and may increase the risk of various diseases. Moreover, GAS usually leads to permanent sterility in these patients. Therefore, it is essential to provide patients with accurate information about the benefits and potential risks of different FP techniques, taking into account the patient's reproductive goals. This review underscores the complex and multifaceted nature of FP in transgender men and emphasizes the need for further research to develop more effective and personalized approaches to FP for this population.

Role of mode of induction and delivery and women's satisfaction after induction of labour at term: An observational study.

This cross-sectional study aimed at evaluating the impact of different modalities of induction of labour (IOL) and delivery on levels of woman' satisfaction. All women aged 18 years or older, who underwent IOL for at-term pregnancy (≥41 weeks of gestation) in randomly selected days during the study period in 6 participating centres were eligible for the study. The questionnaire investigated women's opinion regarding information about induction, pain control, length of induction, their experience about induction, labour and delivery and their attitude towards induction in a subsequent pregnancy. Women were also asked to fill in the Italian version of the Birth Satisfaction Scale-Revised (BSS-R). A total of 300 women entered the study. The answer to the question about a "positive attitude towards induction in a subsequent pregnancy was "absolutely yes" or "yes" respectively in the 77.8%, 52.8% and 48.6% of women who were induced with oral drugs, vaginal drugs and Cook balloon (heterogeneity chi-square p = 0.05). The corresponding values for women who delivered vaginally or by caesarean section (CS) were 63.3% and 36.4% (chi-square p = 0.0009). The mean BSS-R total score was higher among women who underwent IOL with oral drugs than with vaginal drugs (p < 0.0001) or Cook Balloon (p < 0.0001), and among women who delivered vaginally than in those who delivered by CS (p < 0.0001). Women were asked "What do you think is important for a method of induction?": 47.3% (95% CI 41.7%-53.0%) of women answered that "should make the induction as painless as possible", 47.0% (95% CI 41.4%-52.7%) "should induce labour quickly", 44.3% (95% CI 38.8%-50.0%) "should be safe for baby". This study showed that vaginal delivery was associated with a higher rate of satisfaction among induced women. Considering mode of induction, oral drugs were associated with a higher level of satisfaction. Control of pain and quick induction were the most appreciated characteristics.