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.

Medical treatment of ovarian endometriomas: a prospective evaluation of the effect of dienogest on ovarian reserve, cyst diameter, and associated pain.

The aim of the present study was to evaluate the effect of medical treatment of ovarian endometriomas on cyst diameter, associated pain, and ovarian reserve as measured with antral follicle count (AFC) and anti-Mullerian hormone (AMH). In this prospective study, 32 patients with unilateral endometrioma associated with pelvic pain, underwent 6-month medical treatment with dienogest. Before treatment, and at the end of 6 months of treatment, patients underwent evaluation of endometrioma diameter and AFC at transvaginal ultrasonography, measurement of AMH, and evaluation of associated pain. Mean cyst diameter was 4.0 ± 1.3 cm at baseline, and 2.4 ± 1.2 cm after 6 months of treatment (p < .0001), for a reduction in diameter of 40% and a reduction in volume of 79%. Mean visual analog scale score at enrollment was 6.3 ± 2.0, with a significant improvement at 6 months (0.9 ± 1.0, p < .0001). AFC for the affected ovary improved from 4.2 ± 2.8 at baseline, to 8.6 ± 4.2 cm after 6 months (+105%; p < .0001). AMH did not change significantly from baseline (3.40 ± 2.32 ng/mL) to end of treatment (2.80 ± 1.90 ng/mL, -18%, p = .27). Medical treatment with dienogest significantly reduces endometrioma diameter and associated pain, whereas the ovarian reserve appears to be preserved, with a significant improvement of AFC and no significant change in AMH.

Usefulness of Ospemifene in the treatment of urgency in menopausal patients affected by mixed urinary incontinence underwent mid-urethral slings surgery.

The aim of this study was to assess the effectiveness and safety of Ospemifene in the improvement of urgency component in women affected by mixed urinary incontinence (MUI) who underwent surgery with mid-urethral sling (MUS). Eighty-one patients with MUI underwent surgical intervention with MUS were enrolled. After surgical intervention 38 patients received Ospemifene 60 mg one tablet daily per os for 12 weeks. Physical examination, 3-day voiding diary, urodynamic testing were performed at the start and the follow-up after 12 weeks in the Trans-Obturator-Tape (TOT)-Alone group and TOT-Ospemifene. Patients completed the Overactive Bladder Symptom and Health-Related Quality of Life Short-Form (OAB-Q SF), International Consultation on Incontinence Questionnaire (ICIQ-UI-SF), and King' s Health Questionnaire (KHQ). A significant difference between the two groups was observed in peak flow (ml/s), in first voiding desire (ml), in maximum cystometric capacity (ml), and in detrusor pressure at peak flow (cmH2O) at urodynamic evaluation. A significative difference between the two groups at voiding diary was observed in the mean number of voids, urgent micturition episodes/24 h, urge urinary incontinence, and in nocturia events. The OAB-Q symptoms and OAB-Q (HRQL) scores after 12 weeks showed a significative difference between the two groups. Ospemifene is an effective potential therapy after MUSs in women with MUI improving urgency symptoms and quality of life.

Alpha lipoic acid in obstetrics and gynecology.

Alpha-Lipoic acid (ALA) is a natural antioxidant synthetized by plants and animals, identified as a catalytic agent for oxidative decarboxylation of pyruvate and α-ketoglutarate. In this review, we analyzed the action of ALA in gynecology and obstetrics focusing in particular on neuropathic pain and antioxidant and anti-inflammatory action. A comprehensive literature search was performed in PubMed and Cochrane Library for retrieving articles in English language on the antioxidant and anti-inflammatory effects of ALA in gynecological and obstetrical conditions. ALA reduces oxidative stress and insulin resistance in women with polycystic ovary syndrome (PCOS). The association of N-acetyl cysteine (NAC), alpha-lipoic acid (ALA), and bromelain (Br) is used for prevention and treatment of endometriosis. In association with omega-3 polyunsaturated fatty acids (n-3 PUFAs) with amitriptyline is used for treatment of vestibulodynia/painful bladder syndrome (VBD/PBS). A promising area of research is ALA supplementation in patients with threatened miscarriage to improve the subchorionic hematoma resorption. Furthermore, ALA could be used in prevention of diabetic embryopathy and premature rupture of fetal membranes induced by inflamation. In conclusion, ALA can be safely used for treatment of neuropatic pain and as a dietary support during pregnancy.

Prevention of recurrent lower urinary tract infections in postmenopausal women with genitourinary syndrome: outcome after 6 months of treatment with ospemifene.

Aim of this study was to evaluate the efficacy of ospemifene in the prevention of recurrent lower urinary tract infections in postmenopausal women with vulvovaginal atrophy. The study have a retrospective design. Thirty-nine patients were enrolled. Patients underwent clinical examination and urine culture. The urinary symptoms and the quality of life were evaluated with UTISA score, PUF and SF-36 questionnaires before and after treatment. All 39 patients received ospemifene 60 mg one tablet/daily for 6 months. Adverse effects and complications were assessed. Thirty-nine patients were enrolled in the study. Two patients experienced one new UTI episode and the mean number of positive urine culture decreased significantly after 6 months (3.65 ± 2.12 vs 0.25 ± 0.17, p < .0001). The mean number of urinary infection symptoms decreased significantly after treatment; dysuria reduced (4.76 ± 2.45 vs 0.89 ± 1.12). PUF score and SF-36 showed a statistically significant change (22.43 ± 5.89 vs 12.14 ± 3.21) and (52.86 ± 9.21 vs 83.43 ± 10.76). No adverse effects were reported and the total success rate was the 92.3% after 6 months at PGI-I. Ospemifene is a valid alternative with excellent tolerability for the UTIS prevention in postmenopausal patients.

Overactive bladder syndrome treatment with ospemifene in menopausal patients with vulvovaginal atrophy: improvement of sexuality?

The aim of this study was to assess the effectiveness of ospemifene in the improvement of sexual function in postmenopausal women with vulvovaginal atrophy (VVA) affected by overactive bladder syndrome (OAB) or urge urinary incontinence (UUI). One hundred five postmenopausal patients with VVA affected by OAB and/or UUI were enrolled for the study. All patients received ospemifene 60 mg for 12 weeks. Clinical examination, 3-d voiding diary and the vaginal health index (VHI) were performed at baseline and at 12 weeks. Patients completed the OAB-Q SF, FSFI, FSDS, and SF-36 questionnaires. The patient's satisfaction was also calculated. After 12 weeks, the reduction of urinary symptoms was observed. The OAB-Q symptoms, OAB-Q (HRQL) score were (55.34 ± 13.54 vs. 23.22 ± 9.76; p < .0001) and (22.45 ± 9.78 vs. 70.56 ± 15.49; p < .0001), before and after treatment. SF-36 questionnaire showed a significant improvement (p < .0001). VHI score increased and the women who regularly practice sexual activity increased after treatment. The total FSFI score increased significantly and the FSDS score changed after 12 weeks (p < .0001). The PGI-I after 12 weeks showed a total success rate of 90.5%. Ospemifene is an effective potential therapy for postmenopausal women with VVA affected by OAB or UUI improving sexual function and quality of life.

Retrospective analysis in 46 women with vulvovaginal atrophy treated with ospemifene for 12 weeks: improvement in overactive bladder symptoms.

AIMS: The aim of this study was to assess the effectiveness and safety of ospemifene in the improvement of overactive bladder (OAB) symptoms in postmenopausal women affected by vulvovaginal atrophy (VVA). METHODS: Forty-six postmenopausal patients affected by VVA with OAB syndrome were enrolled for the study. All patients received Ospemifene 60 mg for 12 weeks. Clinical examination, 3-day voiding diary, urodynamic testing, ultrasound measurement of endometrial and bladder wall thickness (BWT) and the Vaginal Health Index (VHI) were performed at baseline and 12 weeks. Patients completed the OAB-Q SF and UDI-6. RESULTS: After 12-weeks, the number of patients with detrusor overactivity decreased from 39% to 13% (p = 0.04). The reduction in the mean number in 24 h of voids (9.57 ± 2.12 vs. 6.63 ± 1.22, p < 0.0001), urgent micturition episodes/24 h (5.63 ± 1.46 vs. 1.44 ± 1.31, p < 0.0001), nocturia episodes (3.17 ± 0.85 vs. 1.11 ± 1.18, p < 0.0001), urinary incontinence episodes/24 h (0.85 ± 0.96 vs. 0.33 ± 0.64, p = 0.003) was observed. The UDI-6, OAB-Q symptoms, OAB-Q (HRQL) scores were 8.95 ± 0.91 vs. 5.56 ± 1.40, 62.60 ± 14.70 vs. 20.08 ± 10.83 and 18.71 ± 7.41 vs. 79.45 ± 14.47 (p < 0.001) before and after 12 weeks. CONCLUSION: Ospemifene is an effective potential therapy for postmenopausal women with VVA improving OAB symptoms and quality of life.

Continuous versus cyclic oral contraceptives after laparoscopic excision of ovarian endometriomas: a systematic review and metaanalysis.

In the lack of evidence consistently supporting the use of continuous vs cyclic oral contraceptives after surgery for endometriosis, we conducted a systematic review and metaanalysis with the objective of comparing a continuous vs a cyclic oral contraceptive schedule administered after surgical excision of ovarian endometriomas. A PubMed, MedLine, and Embase search through December 2014 was conducted, with the use of a combination of key words and text words related to endometrioma, endometriosis, oral contraceptives, oral estroprogestins, laparoscopy, and surgery. Studies directly comparing a continuous vs a cyclic schedule administered after surgical treatment of endometriomas were included, with pain and endometrioma recurrence rates as the primary outcomes. Three reviewers independently assessed methodology and extracted data from selected studies. The primary outcomes were considered pain recurrence (evaluated separately for dysmenorrhea, noncyclic chronic pelvic pain, and dyspareunia) and endometrioma recurrence evaluated at ultrasonography. Dichotomous outcomes from each study were expressed as risk ratio (RR) with a 95% confidence interval (CI). Three randomized clinical trials and 1 prospective controlled cohort study were included, for a total of 557 patients with endometriosis, 343 patients of whom had ovarian endometriomas completing the assigned treatment and follow-up. Lower recurrence rates for dysmenorrhea were obtained with a continuous schedule (RR, 0.24; 95% CI, 0.06-0.91; P = .04). Nonsignificant differences were present for chronic pelvic pain and dyspareunia. A continuous oral contraceptive schedule was associated with a nonsignificant reduction of cyst recurrence rates compared with a cyclic schedule (RR, 0.54; 95% CI, 0.28-1.05; P = .07). A continuous oral contraceptive regimen, as opposed to a cyclic regimen, may be suggested after surgery for endometriomas because of lower dysmenorrhea recurrence rates. Due to the small number and small sample sizes of the included studies, further randomized clinical trials are needed to confirm the findings of the present systematic review. Also, outcomes related to patient satisfaction and quality of life should be addressed.

The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis.

STUDY QUESTION: Does surgical treatment of endometriomas impact on the ovarian reserve as evaluated with antral follicle count (AFC)? SUMMARY ANSWER: This meta-analysis of published data shows that surgery for endometrioma does not significantly affect ovarian reserve as evaluated by AFC. WHAT IS KNOWN ALREADY: Surgical excision of an ovarian endometrioma significantly affects ovarian reserve evaluated with anti-Mullerian hormone (AMH) levels. Data for other reliable markers of ovarian reserve, such as AFC, have not been pooled in meta-analyses. STUDY DESIGN, SIZE, DURATION: A systematic review with electronic searches of PubMed, MEDLINE and Embase up to April 2014 was conducted to identify articles evaluating AFC before and after surgery for ovarian endometriomas, or before or after surgery for the affected versus the contralateral ovary. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 24 studies evaluated in detail, 13 were included for data extraction and meta-analysis, including a total of 597 patients. The primary outcome at pooled analysis was AFC (mean and SD) for affected ovaries before and after surgery. Secondary outcomes were AFC for the affected ovary versus the contralateral ovary before surgery, and AFC for the operated versus the contralateral ovary after surgery. The data were pooled using the RevMan software by the Cochrane Collaboration. Heterogeneity between studies was based on the results of the χ(2) and I(2) statistics. A random-effect model was used for the meta-analysis because of high heterogeneity between studies. MAIN RESULTS AND THE ROLE OF CHANCE: AFC for the operated ovary did not change significantly after surgery (mean difference 0.10, 95% CI -1.45 to 1.65; P = 0.90). Lower AFC for the diseased ovary compared with the contralateral one was present before surgery, although the difference was not significant (mean difference -2.79, 95% CI -7.10 to 1.51; P = 0.20). After surgery, the operated ovary showed a significantly lower AFC compared with the contralateral ovary (mean difference -1.40, 95% CI -2.27 to -0.52; P = 0.002). LIMITATIONS, REASONS FOR CAUTION: Heterogeneity among the selected studies was high; therefore, limiting the conclusions of the present systematic review. WIDER IMPLICATIONS OF THE FINDINGS: Ovarian reserve evaluated with AFC is not reduced after surgical treatment of an endometrioma. A lower AFC is present for the affected ovary both before and after surgery. Recently, concerns have been raised as to the reliability of AMH as a marker of ovarian reserve. Based on the present findings, surgical treatment of an endometrioma may be considered safer for the ovarian reserve than previously thought. STUDY FUNDING/COMPETING INTERESTS: No external funding was sought or obtained for this study. No conflicts of interest are declared.

Chronic Pelvic Pain, Vulvar Pain Disorders, and Proteomics Profiles: New Discoveries, New Hopes.

Chronic pelvic pain (CPP) is generally defined as non-cyclic pain perceived in the pelvic area that has persisted from three to six months or longer and is unrelated to pregnancy. The etiology of CPP is complex, multifactorial, with heterogeneous presentation, and includes several diseases such as endometriosis, adenomyosis, and interstitial cystitis/bladder pain syndrome. It may also be associated with sexual dysfunction, musculoskeletal disorders, and comorbid psychiatric symptoms. Vulvar pain disorders (VPDs) are typically categorized separately from chronic pelvic pain; among all VPDs, vulvodynia is a chronic vulvar pain of unknown etiology, lasting at least 3 months and that might be associated with other potentially linked factors. Proteomics represents a useful approach to study the proteome profiles of clinical samples. In this review, we have considered a selection of articles that have analyzed the protein abundance and novel protein species from various biological samples, including eutopic/ectopic endometrium, urine, serum, follicular, peritoneal fluid, and cervical mucus, potentially involved in the pathogenesis and progression of CPP and VPDs. These findings could represent valuable targets for paving the way for the differential diagnosis and therapeutic management of CPP and VDPs, thereby optimizing both the prevention and treatment of these conditions.

Immune-Onco-Microbiome: A New Revolution for Gynecological Cancers.

Despite significant advances in understanding the pathogenetic mechanisms underlying gynaecological cancers, these cancers still remain widespread. Recent research points to a possible link between microbiota and cancer, and the most recent attention is focusing on the relationship between the microbiome, the immune system, and cancer. The microbiome diversity can affect carcinogenesis and the patient's immune response, modulating the inflammatory cascade and the severity of adverse events. In this review, we presented the recent evidence regarding microbiome alterations in patients with gynaecological tumours to understand if the link that exists between microbiome, immunity, and cancer can guide the prophylactic, diagnostic, and therapeutic management of gynaecological cancers.

The Efficacy of Dienogest in Reducing Disease and Pain Recurrence After Endometriosis Surgery: a Systematic Review and Meta-Analysis.

The objective of this study is to determine whether dienogest therapy after endometriosis surgery reduces the risk of recurrence compared with placebo or alternative treatments (GnRH agonist, other progestins, and estro-progestins). The design used in this study is systematic review with meta-analysis. The data source includes PubMed and EMBASE searched up to March 2022. A systematic review and meta-analysis were performed in accordance with guidelines from the Cochrane Collaboration. Keywords such as "dienogest," "endometriosis surgery," "endometriosis treatment," and "endometriosis medical therapy" were used to identify relevant studies. The primary outcome was recurrence of endometriosis after surgery. The secondary outcome was pain recurrence. An additional analysis focused on comparing side effects between groups. Nine studies were eligible, including a total of 1668 patients. At primary analysis, dienogest significantly reduced the rate of cyst recurrence compared with placebo (p < 0.0001). In 191 patients, the rate of cyst recurrence comparing dienogest vs GnRHa was evaluated, but no statistically significant difference was reported. In the secondary analysis, a trend toward reduction of pain at 6 months was reported in patients treated with dienogest over placebo, with each study reporting a significantly higher reduction of pain after dienogest treatment. In terms of side effects, dienogest treatment compared with GnRHa significantly increased the rate of spotting (p = 0.0007) and weight gain (p = 0.03), but it was associated with a lower rate of hot flashes (p = 0.0006) and a trend to lower incidence of vaginal dryness. Dienogest is superior to placebo and similar to GnRHa in decreasing rate of recurrence after endometriosis surgery. A significantly higher reduction of pain after dienogest compared with placebo was reported in two separate studies, whereas a trend toward reduction of pain at 6 months was evident at meta-analysis. Dienogest treatment compared with GnRHa was associated with a lower rate of hot flashes and a trend to lower incidence of vaginal dryness.

Expectant, Medical, and Surgical Management of Ovarian Endometriomas.

Management options for ovarian endometriomas include expectant management, medical treatment, surgical treatment, in vitro fertilization (IVF), or a combination of the above. The choice of management depends on many clinical parameters that should be taken into consideration, the first of which is the main presenting symptom. Most patients are today referred to medical therapy as a first option in the case of associated pain, and to IVF in the case of associated infertility. When both symptoms are present, usually surgery is the preferred approach. Recently, however, surgical excision of an ovarian endometrioma has been associated with a postoperative reduction in the ovarian reserve, and recent guidelines suggest that the clinician should caution the patient as to the possible damage to the ovarian reserve in the case of surgery. However, evidence has been published as to a possible detrimental effect of the ovarian endometrioma on the ovarian reserve even if expectant management is followed. In this review, the current evidence on the conservative management of ovarian endometriomas, with particular focus on the issue of the ovarian reserve, is evaluated, and the different surgical techniques for the treatment of ovarian endometriomas are discussed.

Fertility after Cancer: Risks and Successes.

The incidence of cancer in reproductive-aged women is 7%, but, despite the increased number of cancer cases, advances in early diagnosis and treatment have raised the survival rate. Furthermore, in the last four decades, there has been a rising trend of delaying childbearing. There has been an increasing number of couples referred to Reproductive Medicine Centers for infertility problems after one partner has been treated for cancer. In these cases, the main cause of reduced fertility derives from treatments. In this review, we describe the effects and the risks of chemotherapy, radiotherapy, and surgery in women with cancer, and we will focus on available fertility preservation techniques and their efficacy in terms of success in pregnancy and live birth rates.

The role of microbiota in female fertility and infertility.

In recent years, the introduction of advanced technologies has led to a new scientific revolution: the discovery of the human microbiota. Next-generation sequencing allowed the identification of microbial communities in all districts of the human body and, among these, 9% are distributed in the genitourinary system. The microbiota plays a key role in controlling the homeostasis, therefore dysbiosis can lead to an alteration of the physiological state of health. An alteration of female reproductive microbial communities may affect fertility due to an alteration of the vaginal and endometrial ecosystem. A perturbation of the vaginal, cervical or endometrial flora may also have an impact on the outcome of assisted reproductive technology procedures, particularly in vitro fertilization and embryo transfer. This review examines the role of microbiota in human reproduction and its contribution to infertility. In addition we investigate the role of endometrial bacteria in recurrent implantation failure.

Reactive lymphoid hyperplasia of liver mimicking late ovarian cancer recurrence: case report and literature review.

Reactive lymphoid hyperplasia (RLH) is a rare, benign, lymphocytic tumour-like lesion reported in various organs. It has been previously identified in 18 cases in the English-language literature, but only 5 of them were related to oncological disease. No previous cases have been described of RLH occurring in ovarian cancer patients. We describe a case of hepatic RLH which developed in a patient treated for ovarian cancer 11 years previously. Radiological features on computed tomography (CT) scan and PET-CT (positron emission tomography-computed tomography) were strongly suggestive of oncological disease, in contrast to magnetic resonance imaging (MRI); the volume increment of the nodular lesion and the rise in carbohydrate antigen 125 corroborated the hypothesis of malignancy. The patient was subjected to resection of the 7th segment of the liver and the final histological report showed RLH. RLH should be considered in the presence of hepatic lesions in suspected ovarian cancer recurrence. Imaging techniques should be thoroughly investigated to exclude tumor recurrence promptly, in order to avoid unnecessary surgery.

Endometriosis-associated infertility: surgery or IVF?

Endometriosis is a chronic disease frequently associated with female infertility. The choice of treatment in case of endometriosis is one of the most discussed topics in Reproductive Medicine. The approach to the patient with endometriosis and infertility should be tailored based on different parameters. The localization of the disease, the severity of symptoms and the age of the patient are just some of them. Management options include surgery, in-vitro fertilization (IVF), or a combination of both. Data, mostly uncontrolled, would favor surgery at any stage of endometriosis, increasing the chances of natural conception compared to expectant management. Laparoscopic excision of the ovarian endometrioma should be the treatment of choice when there is associated pain. Surgery should be performed following appropriate techniques to reduce the possible damage to the ovarian reserve. Pregnancy rates around 50% have been consistently reported after surgery, which compare favorably with those obtained with IVF. IVF, on the other hand, may be preferred in case of associated male or tubal factor, in case of a reduced ovarian reserve, or if previous surgery has failed, particularly if there is no associated pain, and when the ultrasonographic features of the ovarian cyst are reassuring. Sometimes IVF may be preceded by surgery, when a difficult access to follicles at pick-up, due to the size and location of the ovarian cyst, or to severe adhesions, is anticipated. Due to the lack of solid evidence in the scenario of endometriosis-associated infertility, robust data from randomized clinical trials (RCTs) are strongly needed.

Vaginectomy: a minimally invasive treatment for cervical cancer vaginal recurrence.

OBJECTIVE: Radiotherapy and/or pelvic exenteration represent the treatment of vaginal recurrence, but the prognosis remains unsatisfactory and with long-term complications. We investigated the possible role of vaginectomy for isolated vaginal relapse (IVR) in cervical cancer (CC). METHODS: Patients with vaginal CC recurrence were evaluated for surgical treatment consisting in vaginectomy. Data were prospectively collected and analyzed to identify independent prognostic factors. RESULTS: Twenty-nine patients with IVR from CC were enrolled. Early and late complications were observed in 7 (24%) and 6 (21%) patients, respectively. After a median follow-up of 57.5 months (range, 8-100 months), 16 patients (55%) were disease-free. The 5-year overall survival and progression-free survival rates were 70.5% and 59.4%, respectively. CONCLUSIONS: In carefully selected patients, vaginectomy may be considered a therapeutic option for IVR. Older patients with long disease-free interval and small recurrences benefit the most from this bladder-sparing surgical technique.