Can pelvic organ prolapse in postmenopausal women be treated with laser therapy?

PURPOSE: This study aims to assess the effectiveness of the non-ablative photothermal erbium laser (Er:YAG laser) for managing anterior and/or posterior vaginal compartment prolapse. METHODS: A randomized, single-blind, 1:1 trial was performed comparing Er:YAG laser treatment to watchful waiting in postmenopausal women with symptomatic cystocele and/or rectocele stage 2 or 3 who opted to undergo surgery due to bothersome prolapse symptoms. Three Er:YAG laser treatments at monthly intervals were applied for the Er:YAG laser group, while there was no treatment for the watchful-waiting group. The primary outcome was the proportion of patients with stage 0 or 1 following laser treatment, while secondary outcomes included the Pelvic Organ Prolapse Quantification System (POP-Q points), Pelvic Floor Distress Inventory Questionnaire short-form, Pelvic Floor Impact Questionnaire short-form, and Patients Global Impression of Improvement (PGI-I). All outcomes were evaluated at baseline and 4 months post baseline. RESULTS: Thirty women (15 vs. 15) were eligible to be included. No participants (0%) in either group had POP-Q stage 0 or 1 at 4 months. Moreover, no change was present in the secondary outcomes. In the PGI-I, 2/15 (14%) and 0/15 (0%) participants declared much better/very much better in the laser and watchful-waiting group, respectively. CONCLUSIONS: The findings of this study do not support use of the intravaginal Er:YAG laser for treatment of the anterior/posterior vaginal wall. Clinical trial identification number: NCT03714607.

Safety of non-steroidal anti-inflammatory drugs in postpartum period in women with hypertensive disorders of pregnancy: systematic review and meta-analysis.

OBJECTIVE: To assess the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure when administered for postpartum analgesia in women with hypertensive disorders of pregnancy. METHODS: MEDLINE, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were searched systematically from inception to 5 December 2019 for studies evaluating the safety of postpartum NSAIDs in women with any gestational hypertensive disorder. Randomized controlled trials (RCTs) and cohort studies were eligible for inclusion. Case-control studies, case series and case reports were excluded. The primary outcomes of interest were the incidence of severe hypertension and systolic, diastolic and mean arterial blood pressure. Pooled estimates were obtained by fitting a random-effects statistical model. The quality of evidence was assessed according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: Ten studies were included, comprising five RCTs and five retrospective cohort studies and involving a total of 1647 women. All studies were evaluated qualitatively and eight of them were included in the quantitative meta-analysis. Administration of NSAIDs was not associated with a significantly higher risk of severe postpartum hypertension (odds ratio, 1.52 (95% CI, 0.77-3.01)). Similarly, no significant differences were found in postpartum systolic blood pressure (mean difference (MD), -3.03 mmHg (95% CI, -6.21 to 0.15 mmHg)) and mean arterial pressure (MD, -0.38 mmHg (95% CI, -1.88 to 1.11 mmHg)) between women who received NSAIDs and those who did not, whereas postpartum diastolic blood pressure was marginally lower in women treated with NSAIDs (MD, -2.28 mmHg (95% CI, -4.44 to -0.13 mmHg)). The same effects were observed when studies with a large sample size, RCTs, women with severe pre-eclampsia and studies using ibuprofen as the study drug and acetaminophen as the control treatment were examined separately. The credibility of evidence was judged to be very low according to GRADE, owing to concerns about study limitations, inconsistency and imprecision. CONCLUSIONS: This meta-analysis suggests that postpartum administration of NSAIDs is not associated with elevated blood pressure in women with hypertensive disorders of pregnancy. However, the existing evidence is of very low quality, thus future large-scale RCTs are warranted to verify the safety of postpartum NSAIDs in this population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

A study protocol of vaginal laser therapy in gynecological cancer survivors.

Objectives: Sexual dysfunction and radiation cystitis are common adverse events following radiotherapy for gynecological cancer (GC). This study aims to assess the efficacy of intravaginal CO2 laser on GC survivors with dyspareunia following pelvic radiation and/or brachytherapy.Methods: This is the study protocol of a randomized double-blind placebo-controlled trial. All participants will receive five therapies (active or placebo) at monthly intervals. Outcomes will include a 10-cm visual analog scale measuring dyspareunia, vaginal dryness, and other symptom intensity, 3-day voiding diary, Day-to Day Impact of Vaginal Aging questionnaire, Female Sexual Function Index, European Organization for Research and Treatment of Cancer Quality of Life questionnaire cervical cancer module, Urogenital Distress Inventory short form, King's Health Questionnaire, International Consultation on Incontinence Questionnaire short form/female lower urinary tract symptoms, patient perception of improvement, sexual satisfaction of male partners, vaginal maturation value, and Vaginal Health Index. Differences between groups will be assessed at baseline and 1, 3, 6, 9, and 12 months following the five laser therapies.Results: As this is a study protocol, the study is ongoing with an expected end of recruitment and analysis date of 2021.Conclusion: Pelvic radiotherapy for GC increases the 5-year survival rate but with a negative impact on women's quality of life due to sexual dysfunction and radiation cystitis onset. With this study, CO2 laser therapy will be evaluated for the first time in GC survivors treated with radiotherapy. ClinicalTrials.gov registration number: NCT03714581.

Maternal fetal loss history and increased acute leukemia subtype risk in subsequent offspring: a systematic review and meta-analysis.

PURPOSE: History of fetal loss including miscarriage and stillbirth has been inconsistently associated with childhood (0-14 years) leukemia in subsequent offspring. A quantitative synthesis of the inconclusive literature by leukemia subtype was therefore conducted. METHODS: Eligible studies (N = 32) were identified through the screening of over 3500 publications. Random-effects meta-analyses were conducted on the association of miscarriage/stillbirth history with overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150 cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia. Sensitivity and subgroup analyses by age and ALL subtype, as well as meta-regression were undertaken. RESULTS: Fetal loss history was associated with increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04-1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in sensitivity analyses. Notably, stillbirth history was significantly linked to ALL risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL and AML with previous miscarriage reached marginal significance. The association of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60). CONCLUSIONS: In this meta-analysis involving >50,000 children, we found noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia type; namely, of stillbirth with ALL and miscarriage history with infant ALL. Elucidation of plausible underlying mechanisms may provide insight into leukemia pathogenesis and indicate monitoring interventions prior to and during pregnancy.

Addition of low-dose hCG to rFSH during ovarian stimulation for IVF/ICSI: is it beneficial?

PURPOSE: The aim of the study was to assess the eftect ot the addition or iow-cose numan cnononic gonauoiropm (hCG) to ovarian stimulation with recombinant follicle stimulating hormone (rFSH) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome. MATERIALS AND METHODS: This retrospective clinical study was conducted on 141 women undergoing ICSI through a short GnRH-agonist protocol with rFSH and the addition of low-dose (100 IU/day) hCG. The control group consisted of 124 women undergoing ovarian stimulation with a similar protocol devoid of hCG. Statistical analysis in the study population along with a subgroup analysis for age 35 years and 36 years was performed. RESULTS: Women in hCG group were statistically significant older and with higher basal FSH compared to control group. This can be attributed to the Centre's latent tendency to add hCG in the stimulation protocol in poor prognosis patients. Despite this fact and the fact that several ovarian stimulation parameters, such as peak estradiol levels, number of oocytes retrieved, number of mature oocytes, and fertilization rates were in favor of the control group, the quality of transferred embryos and pregnancy rates were in favor of hCG group. Similar results were obtained in the subgroup analyses apart from peak estradiol levels, which did not differ among the study groups. CONCLUSIONS: The addition of hCG to rFSH may be associated with better quality embryos and higher pregnancy rates, even in women of advanced reproductive age with higher basal FSH levels, which are often considered to have poorer ovarian reserve.

HNF1A gene mutations and premature ovarian failure (POF): evidence from a clinical paradigm combining MODY 3 and POF.

Premature ovarian failure (POF) defines the occurrence of ovarian failure prior to the age of 40. It occurs in one out of 100 women but is very rare before age 20 (1:10,000). Maturity-onset diabetes of the young (MODY), caused by mutations in the HNF1A gene, is also a rare disorder; all types of MODY account for 1-2% of adult diabetic cases. These two rare nosologic entities coexisted in an adolescent girl evaluated for delayed puberty. Although this combination could represent a chance association, an interrelation might exist. We examined HNF1A expression in human fetal and adult ovaries by immunohistochemistry using a polyclonal HNF1A antibody. HNF1A protein was expressed in both the fetal and adult human ovaries. Based on these findings, we hypothesize that HNF1A participates in ovarian organogenesis and/or function and that mutations in the HNF1A gene might represent another molecular defect causing POF, possibly in combination with other genetic factors. The study underlines the importance of rare clinical paradigms in leading the way to elucidation of the pathogenetic mechanisms of rare diseases.

Causes of infertility in men with Down syndrome.

Men with Down syndrome are considered as infertile although the causes of infertility are not known in detail yet. Although this constitutes a general rule there are three confirmed cases of parenting by fathers with Down syndrome. Many investigators have addressed the causes of infertility and their studies indicate that the causes may be hormonal deficits, morphological alterations of the gonads, abnormal spermatogenesis, psychological and social factors related to the mental retardation. It is obvious that the extra chromosome 21 has a detrimental direct and indirect effect on the reproductive capacity of the affected male patient. But the definite cause of the insufficient and inadequate spermatogenesis remains to be discovered.

Erectile function and male reproduction in men with spinal cord injury: a review.

Spinal cord injury (SCI) in men results in defects in erectile function, ejaculatory process and male reproductive potential. There are alterations in the capacity of men with SCI to achieve reflexogenic, psychogenic and nocturnal erections. The sexual function in different stages after SCI and the types of erections depend mainly on the completeness of the injury and the level of neurological damage. Furthermore, most of the SCI men demonstrate defects concerning the entrance of semen into the posterior urethra and the expulsion of the semen through the penile urethra and the urethral orifice. In addition, SCI men develop defects in the secretory function of the Leydig cells, Sertoli cells and the male accessory genital glands. The overall result is a decreased quality of the semen is recovered either with penile vibratory stimulation (PVS) or with electroejaculation. Nowadays the therapeutic andrological approach of SCI men focuses on achievement of erectile function, recovery of spermatozoa and assisted reproductive technology. The first line of therapy recommended for infertility in SCI men is collection of semen via PVS with concomitant evaluation of total motile sperm yields for assisted conception which may include intravaginal insemination, intrauterine insemination, or in vitro fertilisation/intracytoplasmic sperm injection. Patients failing PVS may be referred for electroejaculation or surgical sperm retrieval.

Hysteroscopy for training residents using uterine post-hysterectomy specimens with a mobile hysteroscope.

BACKGROUND: Training in hysteroscopy can be challenging, especially in conscious women as an office procedure. OBJECTIVE: To develop a realistic hysteroscopy training model for residents using human uteri. METHODS: Human uterine specimens were acquired immediately after hysterectomy, before they were sent for histological analysis and were used as a training model for hysteroscopy. RESULTS: We describe this new technique, which we have used for one year in our resident training programme. Each resident performs at least 20 simulated diagnostic hysteroscopies in extirpated uteri, before performing procedures on women in the operating room. CONCLUSIONS: Simulating hysteroscopy on human uterine models offers a novel and realistic way of training novices prior to conducting procedures under supervision on live patients. WHAT IS NEW: This is a novel model for training and offers a much more realistic training opportunity.

Adenomyosis: Disease, uterine aging process leading to symptoms, or both?

For many decades adenomyosis has been a histological diagnosis in hysterectomy specimens. Traditionally, it has been considered a disease of late reproductive and premenopausal years causing uterine enlargement, dysmenorrhoea and menorrhagia. Recent advances in pelvic and uterine imaging techniques including transvaginal sonography and magnetic resonance imaging were responsible for a shift towards a non-invasive diagnosis and made a significant contribution to a better understanding of its pathogenesis, epidemiology, histological spectrum, and clinical symptomatology. With these non-invasive tools it has been shown that adenomyosis is probably a condition affecting much younger populations and is frequently asymptomatic at an early stage of its development. Regarding symptomatic disease, the distribution and extent of adenomyotic lesions do not correlate consistently with the various symptoms that are considered typical of adenomyosis. More importantly, accurate diagnosis of adenomyosis suffers from a lack of consensus among experts on imaging and even histological diagnostic criteria. Several pathogenetic theories have attempted to shed light on the establishment, evolution and distribution of adenomyotic lesions within the uterine wall, including the tissue injury and repair (TIAR) mechanism, metaplasia, and the more recent genetic-epigenetic theory. So far, none of these can adequately and independently explain the appearance of all types of adenomyosis. This review paper attempts a correlation between the proposed pathogenetic theories and the clinical and histological spectrum of adenomyosis, in an effort to give a plausible explanation of the evolution of this condition from an asymptomatic state to a disease, through synthesis of the existing data.

Alexithymia is positively associated with the outcome of in vitro fertilization (IVF) treatment.

The goal was to examine prospectively the relation of psychological factors to the outcome after in vitro fertilization (IVF) in a sample of Greek women. Previous studies investigating the relation of IVF outcome to anxiety and depression have yielded contradictory results; other psychological dimensions have not been studied. 81 women who followed an IVF program during a 6-mo. period were prospectively evaluated. Demographic and gynecological data were assessed and women completed questionnaires measuring anxiety, depression, narcissistic traits, over-dependency, self-esteem, hostility, and alexithymia. Multiple logistic regression analysis showed that successful IVF outcome correlated with more alexithymic characteristics and younger age. Correlation between alexithymia and successful IVF outcome is demonstrated. This might be explained by the "operational" nature of IVF techniques, to which alexithymic individuals would respond better.

Changing the way we train surgeons in the 21th century: A narrative comparative review focused on box trainers and virtual reality simulators.

The traditional method of acquiring surgical skills by observing and assisting in surgical procedures involving human beings has been challenged during the past several years. Lessons obtained from aviation suggested that the use of simulators is related to reduced costs, increased efficiency in performing certain tasks and above all safety. A shift in paradigm is also required in modern surgical training. The development of endoscopic surgery allowed for the incorporation of medical simulators into training programmes. A review of the literature was conducted using specific inclusion and exclusion criteria, for articles published up to July 31th, 2018. Relevant studies were identified using computerized bibliographic searches of MEDLINE database. The keywords that were used in various combinations were: "Medical Simulators", "Surgical Training", "Laparoscopy", "Surgical Skills", "Box trainers", "Virtual reality simulators", "Surgical Education". Surgical training with box trainers and/or virtual reality simulators confers a significant benefit in terms of surgical skills development, increases patient safety and reduces costs. Nevertheless, the use of virtual reality simulators was significantly more expensive. Simulation training allows trainees to learn from their mistakes, to repeat surgical tasks multiple times so as to establish muscle memory, and enhance skill competency with the aid of informative feedback. Simulators are necessary for the development of the skills required to meet the specific needs of endoscopic surgery in the 21st century. Teaching hospitals should introduce simulation training programmes in order to increase efficiency, reduce costs and improve patient safety. As medical advancements continue to transform the way we perform surgery day by day, simulation training will play a pivotal role in every surgical specialty.

Paving the way for changing perceptions in breast surgery: a systematic literature review focused on oncological and aesthetic outcomes of oncoplastic surgery for breast cancer.

BACKGROUND: The emphasis on aesthetic outcomes and quality of life after breast cancer surgery has motivated breast surgeons to develop oncoplastic breast conserving surgery (OPS). Training programs are still rare in most countries, and there is little standardization, which challenges the scientific evaluation of these techniques. This systematic review aims to assess oncological and cosmetic outcomes of OPS. METHODS: After a strict selection process with precise inclusion and exclusion criteria, oncologic and aesthetic outcomes of oncoplastic surgery were searched, using the MEDLINE database up to September 30th, 2017. Available published literature was classified in levels of evidence. After a thorough screening process, only studies with the best level of evidence were included on selection. Systematic reviews and meta-analyses were not included for methodological reasons. RESULTS: Titles and abstracts of 2.854 citations were identified and after screening 15 prospective studies including 1.391 patients were reviewed and scored in detail. Local relapse was found in 2.8% of cases with a wide range of follow-up (from 6 to 74 months). Close margins were retrieved in 11% of cases and positive margins in 9.4% of cases. Mastectomy was implemented in 6.9% of breast cancer patients to whom OPS was performed. Good cosmetic outcomes were detected in 90.2% of patients undergoing OPS, leaving open issues for who should perform cosmetic evaluation and which method should be used. CONCLUSION: Tumor margins, mastectomy rates, and cosmetic outcomes of OPS have to be further improved by standardizing various aspects of OPS. Research efforts should focus on level I evidence assessing both oncological and aesthetic outcomes of OPS and survival rates.

Pharmacogenetics in ovarian stimulation--current concepts.

Ovarian response to follicle-stimulating hormone (FSH) action differs considerably among women; this has prompted researchers to determine which factors modify this response. The challenge is to identify the genes that affect the response to FSH stimulation by the application of pharmacogenetics to assisted reproduction techniques (ARTs). Recently, new insights have been gained in the investigation of the variability in the gene that encodes the FSH receptor (FSHR) gene or genes of the estrogen pathway. Several polymorphisms of the FSHR gene have been discovered, but Ser680Asn and Thr307Ala are the two most studied. The Ser680Asn polymorphism of the FSHR gene has been found to influence the ovarian response to FSH stimulation in women undergoing in vitro fertilization (IVF), and in women with the genotype Ser/Ser, the FSHR appears to be more resistant to FSH action. The clinical implications of this finding are highly important; the ultimate goal is to apply genetic markers as routine diagnostic tests before ovarian stimulation to predict ovarian response, determine the required FSH dose, and avoid the possible complications related to FSH stimulation.

MRI investigation for neurofibromatosis type 1 lesions during pregnancy--a case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder of the nervous system that causes tumor growth on the nerves, skin changes and bone deformities, and it is reported to be associated with adverse perinatal outcome in pregnant women. CASE: We report a case of MRI investigation of a pregnant woman with a known NF1 disease who showed exacerbation of skin lesions during pregnancy. No dangerous lesions that could compromise pregnancy outcome were detected, thus allowing the pregnancy to continue to term uneventfully. CONCLUSION: MRI has strong indications for the follow-up of pregnant patients with neurofibromatosis as it can detect lesions that can serve as risk factors for pregnancy complications.

Comparison between "short" and "long" protocols in an ICSI programme.

In the present retrospective study we compare the efficacy of gonadotropin-releasing hormone (GnRH) agonist in a long protocol and a GnRH agonist in a short protocol administration for controlled ovarian hyperstimulation (COH) in an ICSI program. A total of 424 consecutive patients with a history of male factor were included in the present study. Three hundred and three patients were included in the long protocol and 121 in the short protocol. Patients treated with the short protocol were stimulated in a shorter time and achieved lower estradiol levels. A significantly higher percentage of oocytes transferred were found in the long protocol. The clinical pregnancy rate per embryo transfer was 39.3% in the long protocol and 19.2% in the short protocol (p=0.001).

Small doses of LH activity are needed early in ovarian stimulation for better quality oocytes in IVF-ET.

OBJECTIVE: To examine whether exogenous LH administration has a beneficial effect on the quality of oocytes, fertilization potential, as well as pregnancy rate in IVF-ET cycles. A randomized trial comparing r-FSH versus r-FSH and LH was employed. STUDY DESIGN: Forty-six infertile couples entering IVF-ET for the first time (either tubal or male factor) were divided after prospective randomization into two groups. In both groups the long protocol with GnRH-analogs was used. In group A, ovarian stimulation started with r-FSH (200 IU/day) for the first four days. In group B, the stimulation protocol started with one amp hMG (75 IU FSH + 75 IU LH activity) daily for four days, with simultaneous administration of r-FSH (150 IU/day). The outcome was compared. RESULTS: Statistical difference was observed in the number of mature oocytes, the number of fertilized oocytes as well as the number of transferable embryos. In all cases, results were statistically significantly better (p < 0.05) in group B. Clinical pregnancy rate, finally, was similar in the two groups. CONCLUSION: The relatively small sample size does not allow a definitive conclusion for the important role of LH during early oocyte maturation. Our results, however, indicate a beneficial effect when small doses of LH are used for ovarian stimulation in IVF-ET cycles. This effect may be more important in cases in which few embryos are available for transfer.