The challenge of FIGO type 3 leiomyomas and infertility: Exploring therapeutic alternatives amidst limited scientific certainties.

Uterine leiomyomas (ULs) are non-cancerous tumors composed of smooth muscle cells that develop within the myometrium and represent the most prevalent pathological condition affecting the female genital tract. Despite the volume of available research, many aspects of ULs remain unresolved, making it a "paradoxical disease" where the increase in available scientific literature has not been matched by an increase in solid evidence for clinical management. Fertility stands at the top of the list of clinical issues where the role of ULs is still unclear. The leiomyoma subclassification system, released by the International Federaion of Gynecology and Obstetrics (FIGO) in 2008, introduced a new and more effective way of categorizing uterine fibroids. The aim was to go beyond the traditional classification "subserosal, intramural and submucosal", facilitating a detailed examination of individual ULs impact on the female reproductive system. The "type 3 UL" is a special type of myoma, characterized by its complete myometrial development while encroaching the endometrium. It is a unique "hybrid" between a submucous and an intramural UL, that may exert a detrimental "double hit" mechanism, which is of particular interest in patients wishing pregnancy. To date, no robust evidence is available regarding the management of type 3 ULs. The aim of this narrative review is to provide a comprehensive overview of the physiopathological mechanisms that type 3 UL may exert on fertility, and to present new perspectives that may help us to better understand both the need for and the methods of treating this unique type of fibroid.

Preventing Persistence of HPV Infection with Natural Molecules.

Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence.

Biological and clinical effects of a resveratrol-based multivitamin supplement on intracytoplasmic sperm injection cycles: a single-center, randomized controlled trial.

BACKGROUND: Resveratrol display's positive effects on follicle growth and development in preclinical studies while there is scantly information from clinical trials. The aim of this study was to evaluate the biological and clinical impact of a resveratrol-based multivitamin supplement on intracytoplasmatic sperm injection (ICSI) cycles. METHODS: A randomized, single-center controlled trial conducted at the University Center of Assisted Reproductive Technologies involving 101 women infertile women undergoing ICSI cycles was conducted. A pretreatment with a daily resveratrol based nutraceutical was administered to the Study Group; Control Group received folic acid. The primary outcomes were the number of developed mature follicles (>16 mm), total oocytes and MII oocytes recovered, the fertilization rate and the number of cleavage embryos/blastocysts obtained. Secondary endpoints were the duration and dosage of gonadotropins, the number of embryos for transfer, implantation, biochemical, clinical pregnancy rates, live birth and miscarriage rates. RESULTS: A significantly higher number of oocytes and MII oocytes were retrieved in the Study Group than in Control Group (p = .03 and p = .04, respectively). A higher fertilization rate (p = .004), more cleavage embryos/patient (p = .01), blastocytes/patients (p = .01) and cryopreserved embryos (p = .03) were obtained in the Study Group. No significant differences in biochemical or clinical pregnancy, live birth, and miscarriage rates were revealed, but a trend to a higher live birth rate was revealed in the Study Group. CONCLUSIONS: A 3 months period of dietary supplementation with a resveratrol-based multivitamin nutraceutical leads to better biological effects on ICSI cycles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registration identifier: NCT04386499.

Effects of Sodium Hyaluronate on Symptoms and Quality of Life in Women Affected by Pregnancy Rhinitis: A Pilot Study.

AIMS: To investigate sodium hyaluronate (SH) efficacy in the treatment of pregnancy rhinitis. METHODS: A single-center, prospective, open-label, 2 parallel-group study was carried out. Pregnant women affected by pregnancy rhinitis were randomly assigned to 1 of 2 groups: Group A was treated with SH, while Group B did not receive any treatment. Pregnancy rhinitis symptoms and quality of life (QOL) during pregnancy were investigated by administering a questionnaire and carrying out an otorhinolaryngoiatric visit. RESULTS: A significant reduction in the intensity of headache, snoring and insomnia in the Group A compared to the Group B were demonstrated. In the Group A, a significant lower presence of amount of secretions (Group A 0.88, 95% CI 0.57-1.18 vs. Group B 2.00, 95% CI 1.69-2.31, p < 0.001), turbinate hypertrophy (Group A 1.70, 95% CI 1.46-1.94 vs. Group B 2.53, 95% CI 2.29-2.77, p < 0.001), and mucosal congestion/hyperemia (Group A 1.41, 95% CI 1.14-1.68 vs. Group B 2.26, 95% CI 1.99-2.53, p < 0.001) was observed. No adverse events were reported in patients treated with SH. CONCLUSIONS: SH is a safe and effective therapeutic alternative for the treatment of pregnancy rhinitis symptoms, improving patients' QOL.

Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS.

In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).

An infertile couple suffering from oligospermia by partial sperm maturation arrest: can phytoestrogens play a therapeutic role? A case report study.

We describe the case of a 30-year-old man with severe oligospermia, caused by partial sperm maturation arrest at spermatidic stage, who was given phytoestrogens. The couple had been trying to conceive for 3 years. The woman was normal at the clinical and endocrinological examination. No other parameters except sperm count, motility and morphology were altered in the male subject. Semen analysis was performed at baseline and after 3 and 6 months of therapy, which consisted of phytoestrogens 80 mg/day for 6 months. An additional semen analysis was performed 6 months after the termination of therapy (wash-out period). During the third month semen parameters improved drastically; therefore a reproductive technique (intrauterine insemination) was performed. This treatment resulted in pregnancy, and a healthy baby weighing 3300 g was born. After 6 months of treatment, sperm parameters ameliorated further. Conversely, after the wash-out period, they returned to baseline values. The appealing results strongly suggest a therapeutic role for phytoestrogens in the treatment of oligospermia. However, it is evident that a validation stage and randomized, controlled studies are essential in order to confirm this observation and verify that phytoestrogens can play an important role in male infertility.

Phytoestrogens may improve the pregnancy rate in in vitro fertilization-embryo transfer cycles: a prospective, controlled, randomized trial.

OBJECTIVE: To compare the effectiveness of i.m. P and i.m. P plus oral phytoestrogens for luteal phase support in patients undergoing IVF-ET cycles. DESIGN: Prospective, controlled, randomized trial. SETTING: University Hospital, Perugia, Italy. PATIENT(S): Two hundred thirteen infertile patients undergoing IVF-ET were included in the study. The inclusion criteria were use of a GnRH agonist for pituitary down-regulation and age <40 years. The total number of cycles performed was 274. INTERVENTION(S): Patients were assigned to receive either i.m. P (50 mg daily) plus placebo or P (50 mg daily) plus phytoestrogen supplementation (1,500 mg daily) for luteal phase support starting from the evening of oocyte retrieval until either a serum pregnancy test result was negative or embryonic heartbeat was sonographically confirmed. MAIN OUTCOME MEASURE(S): The outcomes of IVF-ET were evaluated in both study groups in terms of implantation rate, biochemical pregnancy rate (PR), clinical PR, spontaneous abortion rate, and ongoing pregnancy/delivered rate. RESULT(S): Statistically significant higher values for implantation rate, clinical PR, and ongoing pregnancy/delivered rate were recorded in the patients who received P plus phytoestrogens for luteal phase support in comparison with patients receiving P and placebo. CONCLUSION(S): Although the results of this study encourage the use of phytoestrogens for luteal phase support in patients undergoing IVF-ET program, more studies are necessary to support the hypothesis that phytoestrogens have a beneficial effect in IVF cycles.

Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine the effects of 5 years of treatment with soy phytoestrogens on histological characteristics of endometrium in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Italy. PATIENT(S): Three hundred seventy-six postmenopausal healthy women, all with intact uterus. INTERVENTION(S): Women were distributed in two different groups using randomized criteria: group A (n = 179) patients received soy tablets (150 mg of isoflavones per day) for 5 years; group B (n = 197) patients received identical appearing placebo tablets for 5 years. MAIN OUTCOME MEASURE(S): Results of endometrial histology from biopsies obtained at baseline, 30 months, and 5 years after the beginning of the treatment. RESULT(S): Two hundred ninety-eight women completed the 5-year treatment. No cases of malignancy were detected during biopsy. Seventy percent of women undergoing treatment with soy phytoestrogens had an endometrium classified as atrophic or nonassessable versus 81% receiving placebo. The occurrence of endometrial hyperplasia was significantly higher in group A (3.37% vs. 0%). CONCLUSION(S): Long-term treatment (up to 5 years) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia. These findings call into question the long-term safety of phytoestrogens with regard to the endometrium.

High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial.

OBJECTIVE: To compare the effectiveness of clomiphene citrate (CC) alone or combined with phytoestrogens (PE) in ovulation induction in patients who had intrauterine insemination in a randomized, double-blind study. METHODS: A total of 134 women aged 25-35 years, who were infertile for at least 2 years and who had oligomenorrhea or amenorrhea associated with a positive menstrual response to the intramuscular progesterone-challenge test were enrolled. They were randomly treated with CC (100 mg daily for 5 days) and CC (100 mg daily for 5 days) in combination with PE (1500 mg daily for 10 days). We estimated the difference in uterine artery pulsatily index, number of preovulatory follicles, endometrial thickness, and pregnancy rate. RESULTS: Both treatments increased follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol plasma concentrations, but the differences were not statistically significant. However, the differences in endometrial thickness of the two groups were statistically significant. No significant differences in the pulsatility index values and in the number of preovulatory follicles were noted. CONCLUSION: A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates.