Expanding the limits of vaginal surgery: Transvaginal vesicolithotomy for an incarcerated procidentia: A case report and literature review.

Bladder stones are rare in women. This report presents the case of a woman with a massive bladder stone and incarcerated procidentia. The 75-year-old woman presented to the outpatient clinic with procidentia and recurrent urinary tract infections. Preoperative imaging led to the diagnosis of cystolithiasis. After multidisciplinary counseling the patient underwent a vaginal hysterectomy with bilateral oophorectomy and transvaginal vesicolithotomy. A bladder biopsy was performed to rule out any malignancy. After three days, the patient was discharged with a Foley catheter; 15 days later, the bladder catheter was removed. She had an uncomplicated postoperative course. The presence of cystolithiasis and pelvic organ prolapse remains a challenge both in diagnosis and in treatment. The literature lacks solid evidence on the optimal management of these cases. Although there are no recommendations or consensus for their treatment, it seems that the one-step vaginal approach is preferable to the abdominal route.

Association of endometriosis with Sjögren's syndrome: Genetic insights (Review).

Patients with a history of endometriosis have an increased risk of developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is a potential association between endometriosis and an increased susceptibility for Sjögren's syndrome (SS). SS is a common chronic, inflammatory, systemic, autoimmune, multifactorial disease of complex pathology, with genetic, epigenetic and environmental factors contributing to the development of this condition. It occurs in 0.5­1% of the population, is characterized by the presence of ocular dryness, lymphocytic infiltrations and contributes to neurological, gastrointestinal, vascular and dermatological manifestations. Endometriosis is an inflammatory, estrogen­dependent, multifactorial, heterogeneous gynecological disease, affecting ≤10% of reproductive­age women. It is characterized by the occurrence of endometrial tissue outside the uterine cavity, mainly in the pelvic cavity, and is associated with pelvic pain, dysmenorrhea, deep dyspareunia and either subfertility or infertility. It is still unclear whether SS appears as a secondary response to endometriosis, or it is developed due to any potential shared mechanisms of these conditions. The aim of the present review was to explore further the biological basis only of the co­occurrence of these disorders but not their association at clinical basis, focusing on the analysis of the partially shared genetic background between endometriosis and SS, and the clarification of the possible similarities in the underlying pathogenetic mechanisms and the relevant molecular pathways.

Cuff meshoma post-laparoscopic sacrocolpopexy: vaginal-endoscopic mesh excision.

INTRODUCTION AND HYPOTHESIS: The objective was to present endoscopic images of a meshoma and describe the complete excision of a complicated mesh after sacrocolpopexy (SCP) using a combined vaginal-endoscopic technique. METHODS: We present a video documentation of an innovative technique. A 58-year-old woman was referred with painless, foul-smelling vaginal discharge and recurrent vaginal mesh erosions. She had undergone a laparoscopic SCP 12 years ago and her symptoms had begun 5 years ago. A pre-operative MRI scan revealed a cuff meshoma and an inflammatory sinus around the mesh extending from the cuff to the sacral promontory. Under general anesthesia, a 30° hysteroscope was inserted transvaginally into the sinus, where the retained mesh was seen in the form of a shrunken meshoma, and then the mesh arms were recognized extending cephalad into a sinus tract. Under direct endoscopic visualization, the mesh was carefully mobilized at its highest point with the use of laparoscopic grasping forceps. Then, the mesh was dissected with hysteroscopic scissors in close proximity to the bone. No peri-operative complications were recognized. RESULTS: A combined vaginal-endoscopic approach was successfully used to remove an eroded mesh and cuff meshoma after SCP. CONCLUSION: This procedure offers a minimally invasive, low-morbidity, and rapid-recovery approach.

Surgical results in POP/UI surgery after using PVDF compared to other materials. A systematic review and meta-analysis.

OBJECTIVES: Synthetic materials have been used for the surgical treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). During the last 25 years, these materials were composed mostly of polypropylene (PP), whereas recently the use of polyvinylidene difluoride (PVDF) is of increasing interest due to its characteristics. This study aimed to compare the results after SUI/POP surgery using PVDF versus PP materials by synthesizing the data of relevant existing literature. STUDY DESIGN: This systematic review and meta-analysis included clinical trials, case-control studies, or cohort studies written in the English language. The search strategy included the electronic databases MEDLINE, EMBASE, and Cochrane, and grey literature (congresses IUGA, EUGA, AUGS, FIGO). All studies have to provide numeric data or odds ratios (OR) of developing a specific outcome in surgeries with PVDF compared with outcomes of other used materials. No restrictions of race or ethnicity were applied, nor chronological restrictions. Exclusion criteria were studies that included patients with cognitive impairment, dementia, stroke, or central nervous system trauma. All studies were screened by two reviewers, initially by title and abstract, and afterward by full text. Disagreements were resolved through mutual consent. All studies were assessed for their quality and bias risk. Data were extracted using a data extraction form formulated in a Microsoft Excel spreadsheet. Our results were divided into studies dealing only with SUI patients, studies dealing only with POP patients, and cumulative analysis of variables expressed in both SUI and POP surgery. The primary outcomes were the rates of post-operative recurrence, mesh erosion, and postoperative pain after surgery with PVDF compared to PP. The secondary outcomes were post-operative sexual dissatisfaction, overall satisfaction rates, hematoma, urinary tract infection, de novo urge incontinence, and reoperation rate. RESULTS: No differences in the post-operative rates of SUI/POP recurrence, mesh erosion, and pain were found after surgery with PVDF vs surgery with PP. Patients after SUI surgery with PVDF tapes had statistically significant lower rates of de-novo urgency compared to the PP group [OR = 0.38 (0.18, 0.88), p = 0.01]; patients after POP surgery with PVDF materials had statistically significant lower rates of de-novo sexual dysfunction compared to the PP group [OR = 0.12 (0.03, 0.46), p = 0.002]. CONCLUSIONS: This study provided evidence that the use of PVDF in SUI/POP surgeries could be a valid alternative to PP. However our results are limited by uncertainty due to the overall low quality of the existent data. Further research and validation would contribute to better surgical techniques.

Higher live birth rate following transdermal testosterone pretreatment in poor responders: a systematic review and meta-analysis.

A systematic review and meta-analysis was performed aiming to identify good-quality randomized controlled trials (RCT) evaluating testosterone pretreatment in poor responders. Eight RCTs were analysed, evaluating 797 women. Transdermal testosterone gel was used in all studies, with a dose ranging from 10 to 12.5 mg/day for 10-56 days. The main outcome measure was achievement of pregnancy, expressed as clinical pregnancy or live birth. Testosterone pretreatment was associated with a significantly higher live birth (risk ratio [RR] 2.07, 95% confidence interval [CI] 1.09-3.92) and clinical pregnancy rate (RR 2.25, 95% CI 1.54-3.30), as well as a significant increase in the number of cumulus-oocyte complexes retrieved. Significantly fewer days to complete ovarian stimulation, a lower total dose of gonadotrophins, a lower cancellation rate due to poor ovarian response and a thicker endometrium on the day of triggering of final oocyte maturation were observed. No significant differences were observed in oestradiol concentration, the numbers of follicles ≥17 mm, metaphase II oocytes, two-pronuclear oocytes and embryos transferred, and the proportion of patients with embryo transfer. The current study suggests that the probability of pregnancy is increased in poor responders pretreated with transdermal testosterone who are undergoing ovarian stimulation for IVF.

Improvement in sperm quality by oral antioxidant supplementation in infertile men with varicocele who have not undergone surgical repair: Systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess whether oral antioxidant supplementation improves sperm quality in men with infertility and varicocele (VCL) who have not undergone surgical repair. In men with infertility and VCL who had not undergone surgical repair oral antioxidant supplementation significantly increased sperm concentration (WMD +5.86 × 106 /ml 95% CI: +1.47 to +10.24, p < 0.01; random effects model, six studies, 213 patients), total motility (WMD + 3.76%, 95% CI: +0.18 to +7.34, p = 0.04; random effects model, three studies, 93 patients), progressive motility (WMD + 6.38%, 95% CI: +3.04 to +9.71, p < 0.01; random effects model, three studies, 84 patients) and seminal volume (WMD +0.55 ml, 95%CI: +0.06 to +1.04, p = 0.03; random effects model, four studies, 120 patients). On the other hand, no significance difference was observed in sperm morphology (WMD +3.89%, 95% CI: -0.14 to +7.92, p = 0.06; random effects model, five studies, 187 patients). In conclusion, limited evidence suggests that the use of oral antioxidants in men with infertility and VCL, who have not undergone surgical repair improves their seminal volume, sperm concentration, total and progressive motility.

The use of urinary biomarkers in the diagnosis of overactive bladder in female patients. A systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and other proteins are related to overactive bladder (OAB) syndrome, as their urinary concentrations are significantly different from those of the general non-OAB population. This review aims to systematically assess whether NGF, BDNF, and other urinary by-products can be used as potential biomarkers to manage women with OAB. METHODS: This was a systematic review and metanalysis that was conducted according to PRISMA guidelines. Studies were identified by electronic search of Medline, Scopus, ScienceDirect, Embase, and Cochrane Register until October 2020. The included studies investigated the correlation of OAB with NGF, BDNF, and other potential biomarkers in symptomatic women and their controls. RESULTS: Twelve studies (581 female OAB patients and 394 female controls) were included. Urinary NGF, NGF/Cr, BDNF/Cr, ATP/Cr, and PGE2/Cr ratios were identified as potential biomarkers in female OAB patients. Results of the meta-analysis indicated that uNGF [standard mean difference (SMD) 1.45, 95% CI 0.53-2.36], NGF/Cr ratio (SMD 1.23, 95% CI 0.67-1.78), BDNF/Cr ratio (SMD 0.78, 95% CI 0.006-1.50), and BDNF/Cr ratio (RR 0.78, 95% CI 0.006-1.50) were increased in female OAB patients compared to healthy controls, whereas no difference was found for the PGE2/Cr and ATP/Cr ratios. Current data are inadequate to assess any other potential biomarkers, such as urinary MDA, ATP, and cytokines, in the management of OAB in female patients. CONCLUSIONS: uNGF, NGF/Cr, and BDNF/Cr ratio could be used in the assessment of female OAB patients. Further studies are needed to specify OAB urinary titer levels in OAB subgroups and healthy women and their potential as diagnostic and management tools in OAB women.

Functional and Reproductive Outcomes Following Surgical Management of Congenital Anomalies of the Cervix: A Systematic Review.

OBJECTIVE: The purpose of this systematic review was to evaluate surgical treatment for malformations of the cervix in terms of short- and long-term postoperative function and relevant reproductive outcomes. DATA SOURCES: International Prospective Register of Systematic Reviews (ID No CRD42019128899). Electronic databases were searched for eligible studies up to October 2019 on Medline/PubMed (1966-2019), Scopus/Elsevier (1950-2019), and Google Scholar (up to 2019). Search terms included "congenital cervical malformations/anomalies," "uterocervical aplasia/dysgenesis/agenesis," "cervical aplasia/dysgenesis/ agenesis," "müllerian anomalies/dysgenesis/agenesis," "utero-vaginal anastomosis," "cervical reconstruction," "uterocervical reconstruction/canalization," "cervical canalization," "reproductive/pregnancy/functional outcome," "menstruation," "pregnancy," and "regular periods." METHODS OF STUDY SELECTION: Studies were chosen and included with clear description of preoperative diagnosis via sonography, magnetic resonance imaging, and surgical confirmation; assessment and clear description of gynecologic anatomy and any concomitant anomalies; meticulous description of the operative technique; follow-up of at least 6 weeks postoperatively; and postoperative end points including menstrual and reproductive outcomes. We included randomized controlled trials, case-control studies (both prospective and retrospective), and case reports. Data registries, studies without clearly described primary or secondary outcomes, and studies not in the English language were excluded from the analyses. TABULATION, INTEGRATION, AND RESULTS: The literature search returned 745 studies; 546 records were initially excluded (397 not related to the topic, 15 not related to humans, 134 non-English language); 111 full-text articles were further excluded (patients underwent hysterectomy or no surgery); 88 studies with a total of 249 patients were suitable for analysis. Almost all patients had preoperative amenorrhea (248/249, 99.6%). Postoperatively, of 249 patients, resolution of menstruation occurred in 228 patients (91.6%), and hysterectomy was performed in 22 patients (8.8%); overall, there were 30 (12.0%) conceptions that resulted in 27 (10.8%) viable and 24 (9.6%) term pregnancies. Indications for hysterectomy were stenosis of the genital tract and sepsis. Coexisting vaginal agenesis and use of full thickness skin graft for creation of neocervix was associated with negative surgical outcomes. CONCLUSION: This review suggests that conservative surgical approaches result in better clinical and reproductive outcomes than more aggressive reconstructive surgeries for patients with malformations of the cervix.

Transperineal excision of a sizeable angiofibroma of the ischiorectal fossa. A case report.

Cellular angiofibroma is a recently described rare benign soft-tissue tumor more commonly presenting in middle-aged women, often mimicking malignancy. The vulva is most common location. Complete local excision is the best curative treatment and usually there is no recurrence after surgery. We describe a 49-year-old woman with a painless tumor in the left ischiorectal fossa. It was a random finding in a routine computed tomography (CT) scan after resection of ear melanoma 3 years previously. Ultrasonography showed a solid mass, and further magnetic resonance imaging (MRI) suggested a rhabdomyosarcoma. Altogether, these findings indicated malignant disease. An uncomplicated simple excision of the tumor was done in the operating theatre. The mass measured 7×5×5 cm and the histopathological examination found that it was a cellular angiofibroma, a benign lesion. There were no postoperative complications. This case report highlights the need for multidisciplinary team management of rare tumors such as cellular angiofibromas.

How frequent is severe ovarian hyperstimulation syndrome after GnRH agonist triggering in high-risk women? A systematic review and meta-analysis.

The aim of the present systematic review and meta-analysis was to assess the incidence of severe ovarian hyperstimulation syndrome (OHSS) after triggering of final oocyte maturation with gonadotrophin releasing hormone agonist (GnRHa) in high-risk women. The pooled incidence of severe OHSS in high-risk women who did not receive any form of luteal phase support was 0% (95% CI 0.0 to 0.0, I2 = 0%, random-effects model, 14 data sets, 983 women). The pooled incidence of severe OHSS in high-risk women in whom HCG was added to standard luteal phase support was 1% (95% CI 0.0 to 2.0, I2 = 27.02%, random-effects model, 10 data sets, 707 women). The incidence of severe OHSS in high-risk women triggered by a combination of GnRHa and HCG (dual triggering), who received standard luteal phase support, was 1% (95% CI 0.0 to 3.0, one study, 182 women). The incidence of severe OHSS in high-risk women, is not eliminated when HCG is administered either concomitantly with GnRHa (dual triggering), during the luteal phase after GnRHa triggering, or both. On the contrary, it is eliminated when no luteal support is administered.

Expression of genes that regulate follicle development and maturation during ovarian stimulation in poor responders.

RESEARCH QUESTION: Sex hormone-binding globulin (SHBG), androgen receptor (AR), LH beta polypeptide (LHB), progesterone receptor membrane component 1 (PGRMC1) and progesterone receptor membrane component 2 (PGRMC2) regulate follicle development and maturation. Their mRNA expression was assessed in peripheral blood mononuclear cells (PBMC) of normal and poor responders, during ovarian stimulation. DESIGN: Fifty-two normal responders and 15 poor responders according to the Bologna criteria were enrolled for IVF and intracytoplasmic sperm injection and stimulated with 200 IU of follitrophin alpha and gonadotrophin-releasing hormone antagonist. HCG was administered for final oocyte maturation. On days 1, 6 and 10 of stimulation, blood samples were obtained, serum hormone levels were measured, RNA was extracted from PBMC and real-time polymerase chain reaction was carried out to identify the mRNA levels. Relative mRNA expression of each gene was calculated by the comparative 2-DDCt method. RESULTS: Differences between mRNA levels of each gene on the same time point between the two groups were not significant. PGRMC1 and PGRMC2 mRNA levels were downregulated, adjusted for ovarian response and age. Positive correlations between PGRMC1 and AR (standardized beta = 0.890, P < 0.001) from day 1 to 6 and PGRMC1 and LHB (standardized beta = 0.806, P < 0.001) from day 1 to 10 were found in poor responders. PGRMC1 and PGRMC2 were positively correlated on days 6 and 10 in normal responders. CONCLUSIONS: PGRMC1 and PGRMC2 mRNA are significantly decreased during ovarian stimulation, with some potential differences between normal and poor responders.

Risk of gestational diabetes mellitus in women achieving singleton pregnancy spontaneously or after ART: a systematic review and meta-analysis.

BACKGROUND: Women who achieve pregnancy by ART show an increased risk of obstetric and perinatal complications compared with those with spontaneous conception (SC). OBJECTIVE AND RATIONALE: The purpose of this systematic review and meta-analysis was to synthesize the best available evidence regarding the association between ART and gestational diabetes mellitus (GDM) in women with singleton pregnancies. The research question asked was whether the risk of GDM is higher in women achieving singleton pregnancy by ART compared with those achieving singleton pregnancy spontaneously. SEARCH METHODS: A literature search, in MEDLINE, Scopus and Cochrane databases, covering the period 1978-2019, was performed aiming to identify studies comparing the risk of GDM in singleton pregnancies after ART versus after SC. Both matched and unmatched studies were considered eligible. Meta-analysis of weighted data was performed using the random effects model. Results were reported as risk ratio (RR) with 95% CI. Heterogeneity was quantified with the I2 index. OUTCOMES: The study reports on 63 760 women who achieved a singleton pregnancy after ART (GDM was present in 4776) and 1 870 734 women who achieved a singleton pregnancy spontaneously (GDM in 158 526). Women with singleton pregnancy achieved by ART showed a higher risk of GDM compared with those with singleton pregnancy achieved spontaneously (RR 1.53, 95% CI 1.39-1.69; I2 78.6%, n = 37, 1 893 599 women). The direction or the magnitude of the effect observed did not change in subgroup analysis based on whether the study was matched (n = 17) or unmatched (n = 20) (matched: RR 1.42, 95% CI 1.17-1.72; I2 61.5%-unmatched: RR 1.58, 95% CI 1.40-1.78; I2 84.1%) or whether it was prospective (n = 12) or retrospective (n = 25) (prospective studies: RR 1.52, 95% CI 1.27-1.83, I2 62.2%-retrospective studies: RR 1.53, 95% CI 1.36-1.72, I2 82.5%). Regarding the method of fertilization, a higher risk of GDM after ART versus SC was observed after IVF (n = 7), but not after ICSI (n = 6), (IVF: RR 1.95, 95% CI 1.56-2.44, I2 43.1%-ICSI: RR 1.42, 95% CI 0.94-2.15, I2 73.5%). Moreover, regarding the type of embryo transfer (ET), a higher risk of GDM after ART versus SC was observed after fresh (n = 14) but not after frozen (n = 3) ET (fresh ET: RR 1.38, 95% CI 1.03-1.85, I2 75.4%-frozen ET: RR 0.46, 95% CI 0.10-2.19; I2 73.1%). A higher risk of GDM was observed after ART regardless of whether the eligible studies included patients with polycystic ovary syndrome (RR 1.49, 95% CI 1.33-1.66, I2 75.0%) or not (RR 4.12, 95% CI 2.63-6.45, I2 0%), or whether this information was unclear (RR 1.46, 95% CI 1.22-1.75, I2 77.7%). WIDER IMPLICATIONS: The present systematic review and meta-analysis, by analysing 1 893 599 women, showed a higher risk of GDM in women achieving singleton pregnancy by ART compared with those achieving singleton pregnancy spontaneously. This finding highlights the importance of early detection of GDM in women treated by ART that could lead to timely and effective interventions, prior to ART as well as during early pregnancy.

Current knowledge about the management of congenital cervical malformations: a literature review.

The prevalence of congenital cervical agenesis or dysgenesis ranges from 1/80,000 to 1/100,000, and in about 50% of these cases it coexists with congenital vaginal agenesis. This narrative review summarizes the contemporary knowledge in the field of conservative surgical restoration of the reproductive tract. The management of congenital cervical malformations aims to [1] provide relief from the obstructive symptoms, [2] establish normal sexual function, and [3] preserve the uterus for future fertility. In cases of cervical agenesis and vaginal aplasia, the surgical approach involves the creation of neovagina, the creation of neocervix, and then subsequent restoration of the continuity of the genital tract. In cases where vagina is not congenitally absent, the surgical approach involves either a direct uterovaginal anastomosis or initial creation of neocervix and then subsequent restoration of the continuity of the genital tract. The neocervix can be surgically created with small intestinal submucosa, split-thickness skin graft, full-thickness skin graft, peritoneal flap, or vaginal mucosa lined with a polytetrafluoroethylene graft. Most of the published cases report long-term menstruation and sporadic pregnancies. Conservative surgery of cervical congenital malformations could serve as a first-line treatment. Sexual function and menstruation are established in the majority of patients. Extirpatory surgery may be preserved for surgical failures after initial restoration of the continuity of uterus-cervix-vagina or in cases with more complex anatomy.

Recommendations for the surgical treatment of endometriosis. Part 2: deep endometriosis.

STUDY QUESTION: How should surgery for endometriosis be performed? SUMMARY ANSWER: This document provides recommendations covering technical aspects of different methods of surgery for deep endometriosis in women of reproductive age. WHAT IS KNOWN ALREADY: Endometriosis is highly prevalent and often associated with severe symptoms. Yet compared to equally prevalent conditions, it is poorly understood and a challenge to manage. Previously published guidelines have provided recommendations for (surgical) treatment of deep endometriosis, based on the best available evidence, but without technical information and details on how to best perform such treatment in order to be effective and safe. STUDY DESIGN SIZE DURATION: A working group of the European Society for Gynaecological Endoscopy (ESGE), ESHRE and the World Endometriosis Society (WES) collaborated on writing recommendations on the practical aspects of surgery for treatment of deep endometriosis. PARTICIPANTS/MATERIALS SETTING METHODS: This document focused on surgery for deep endometriosis and is complementary to a previous document in this series focusing on endometrioma surgery. MAIN RESULTS AND THE ROLE OF CHANCE: The document presents general recommendations for surgery for deep endometriosis, starting from preoperative assessments and first steps of surgery. Different approaches for surgical treatment are discussed and are respective of location and extent of disease; uterosacral ligaments and rectovaginal septum with or without involvement of the rectum, urinary tract or extrapelvic endometriosis. In addition, recommendations are provided on the treatment of frozen pelvis and on hysterectomy as a treatment for deep endometriosis. LIMITATIONS REASONS FOR CAUTION: Owing to the limited evidence available, recommendations are mostly based on clinical expertise. Where available, references of relevant studies were added. WIDER IMPLICATIONS OF THE FINDINGS: These recommendations complement previous guidelines on management of endometriosis and the recommendations for surgical treatment of ovarian endometrioma. STUDY FUNDING/COMPETING INTERESTS: The meetings of the working group were funded by ESGE, ESHRE and WES. Dr Roman reports personal fees from ETHICON, PLASMASURGICAL, OLYMPUS and NORDIC PHARMA, outside the submitted work; Dr Becker reports grants from Bayer AG, Volition Rx, MDNA Life Sciences and Roche Diagnostics Inc. and other relationships or activities from AbbVie Inc., and Myriad Inc, during the conduct of the study; Dr Tomassetti reports non-financial support from ESHRE, during the conduct of the study; and non-financial support and other were from Lumenis, Gedeon-Richter, Ferring Pharmaceuticals and Merck SA, outside the submitted work. The other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: na.

The Outcome of Fertility-Sparing and Nonfertility-Sparing Surgery for the Treatment of Adenomyosis. A Systematic Review and Meta-analysis.

OBJECTIVE: The purpose of this systematic review was to identify the operative issues and specific dysmenorrhea and menorrhagia outcomes in women who had undergone fertility-sparing surgery, as well as determine the expected outcome for extirpative surgery. DATA SOURCES: PROSPERO (ID no. 125692). Search was conducted for eligible studies up to March 31, 2019, on MEDLINE/PubMed (1966-2019), Scopus/Elsevier (1950-2019), and Google Scholar (up to 2019). The search terms applied for the search strategy were as follows: adenomyosis, adenomyomas, uterus-sparing surgery, fertility-sparing surgery, pain, dysmenorrhea, menorrhagia, uterine volume, adenomyotic volume, case-control studies, cohort studies, and prospective studies. METHODS OF STUDY SELECTION: A total of 443 studies were initially identified. Exclusion criteria was as follows: (1) inadequate description of preoperative adenomyosis or absence of postoperative histology confirmation of adenomyosis, (2) no statement of use of a standardized instrument for measurement of pain, bleeding, or adenomyotic/uterine volume, (3) follow-up <12 months postoperatively, (4) study population <20 women, and (5) non-English language. TABULATION, INTEGRATION, AND RESULTS: Nineteen studies with a total of 1843 patients with adenomyosis were included. Twelve studies were further analyzed in the meta-analysis. Complete excision of adenomyosis was associated with improvement in pain, menorrhagia, and reduction of uterine volume by a factor of 6.2, 3.9, and 2.3, respectively; the partial excision of adenomyosis was associated with improvement in pain, menorrhagia, and reduction of uterine volume by a factor of 5.9, 3.0, and 2.9, respectively; the studies with a mixed volume of patients with complete and partial excision of adenomyosis reported improvement in pain, menorrhagia, and reduction of uterine volume by a factor of 4.0, 6.3, and 5.1, respectively. CONCLUSION: The surgical treatment of adenomyosis results in the satisfactory control of pain and bleeding, as well as in the reduction of uterine volume. Further research is warranted to investigate the long-term control of symptoms to identify any parameters related to the recurrence of adenomyosis, as well as to compare the conservative surgical treatment of adenomyosis with other treatment options.

In-utero stress and mode of conception: impact on regulation of imprinted genes, fetal development and future health.

BACKGROUND: Genomic imprinting is an epigenetic gene regulatory mechanism; disruption of this process during early embryonic development can have major consequences on both fetal and placental development. The periconceptional period and intrauterine life are crucial for determining long-term susceptibility to diseases. Treatments and procedures in assisted reproductive technologies (ART) and adverse in-utero environments may modify the methylation levels of genomic imprinting regions, including insulin-like growth factor 2 (IGF2)/H19, mesoderm-specific transcript (MEST), and paternally expressed gene 10 (PEG10), affecting the development of the fetus. ART, maternal psychological stress, and gestational exposures to chemicals are common stressors suspected to alter global epigenetic patterns including imprinted genes. OBJECTIVE AND RATIONALE: Our objective is to highlight the effect of conception mode and maternal psychological stress on fetal development. Specifically, we monitor fetal programming, regulation of imprinted genes, fetal growth, and long-term disease risk, using the imprinted genes IGF2/H19, MEST, and PEG10 as examples. The possible role of environmental chemicals in genomic imprinting is also discussed. SEARCH METHODS: A PubMed search of articles published mostly from 2005 to 2019 was conducted using search terms IGF2/H19, MEST, PEG10, imprinted genes, DNA methylation, gene expression, and imprinting disorders (IDs). Studies focusing on maternal prenatal stress, psychological well-being, environmental chemicals, ART, and placental/fetal development were evaluated and included in this review. OUTCOMES: IGF2/H19, MEST, and PEG10 imprinted genes have a broad developmental effect on fetal growth and birth weight variation. Their disruption is linked to pregnancy complications, metabolic disorders, cognitive impairment, and cancer. Adverse early environment has a major impact on the developing fetus, affecting mostly growth, the structure, and subsequent function of the hypothalamic-pituitary-adrenal axis and neurodevelopment. Extensive evidence suggests that the gestational environment has an impact on epigenetic patterns including imprinting, which can lead to adverse long-term outcomes in the offspring. Environmental stressors such as maternal prenatal psychological stress have been found to associate with altered DNA methylation patterns in placenta and to affect fetal development. Studies conducted during the past decades have suggested that ART pregnancies are at a higher risk for a number of complications such as birth defects and IDs. ART procedures involve multiple steps that are conducted during critical windows for imprinting establishment and maintenance, necessitating long-term evaluation of children conceived through ART. Exposure to environmental chemicals can affect placental imprinting and fetal growth both in humans and in experimental animals. Therefore, their role in imprinting should be better elucidated, considering the ubiquitous exposure to these chemicals. WIDER IMPLICATIONS: Dysregulation of imprinted genes is a plausible mechanism linking stressors such as maternal psychological stress, conception using ART, and chemical exposures with fetal growth. It is expected that a greater understanding of the role of imprinted genes and their regulation in fetal development will provide insights for clinical prevention and management of growth and IDs. In a broader context, evidence connecting impaired imprinted gene function to common diseases such as cancer is increasing. This implies early regulation of imprinting may enable control of long-term human health, reducing the burden of disease in the population in years to come.

Clinical presentation and management of atypical polypoid adenomyomas: Systematic review of the literature.

The aim of this study is to investigate clinical behavior of Atypical Polypoid Adenomyomas (APAs) and to describe the rates of (i) recurrences, (ii) their association with endometrial hyperplasia and (iii) with endometrial cancer. All studies that reported the outcome of the clinical management of patients with histologically proven APAs were included. A review of the English literature since 1970 was systematically performed (PROSPERO No CRD42018080003). A quality assessment tool was used to assess the scientific value of all the studies. Main contribution of this review is the proposal of new definitions regarding the clinical behaviour of APAs: Cure, Residual or persistent APA, Recurrent APA, Synchronous endometrial hypeprasia, Subsequent endometrial hyperplasia, Synchronous endometrial cancer, and Subsequent endometrial cancer, are terms elucidated in the context of this review. Their rates after initial diagnosis and treatment of APAs are presented as the main outcome measures. 63 studies and 350 patients were included in the systematic review. Fifteen studies that reported 208 patients who did not have hysterectomy as initial treatment were included for further quantitative assessment. The cure rate of APAs in cases where uterus was preserved was 51.0% (106/208), the residual rate of APA was 20.2% (42/208), the recurrence rate of APA was 35.1% (73/208), the concurrent endometrial hyperplasia rate was 7.2% (15/208), the concurrent endometrial cancer rate was 4.8% (10/208), the subsequent endometrial hyperplasia rate of was 6.7% (14/208), and the subsequent endometrial cancer rate of was 10.1% (21/208). Moreover, 56.4% of the patients with APA who opted for uterine sparing treatment and wished to conceive they had a viable pregnancy. The use of hysteroscopic techniques at the initial management of APAs is related with significantly decreased residual rate, and signicantly increased cure rates. In this review, the recurrence rate and the association of APAs with cancer appeared to be higher compared to the previously reported in the literature rates. APAs comprise an intriguing clinical entity that needs individualized treatment, considering the increased association to serious gynecological diseases. Hysterectomy is the appropriate treatment, however uterus-sparing surgery can be offered to selected patients.

Surgical management of congenital uterine anomalies (including indications and surgical techniques).

The prevalence of congenital uterine anomalies (CUA) is reported to be 4.3-6.7% in the general population, 3.4%-8% in the infertile population, and 12.6-18.2% of those with recurrent miscarriages. They are the result of abnormal formation, differentiation, and fusion of the Müllerian or paramesonephric ducts during fetal life. To date, various classification systems have been proposed for the categorization of CUA, but the recently introduced ESHRE/ESGE classification seems to be a new, clear, and systematic categorization, which could be the basis for clinicians to rely on when they refer to CUA and their clinical impact either generally or concerning pregnancy outcomes. CUA are apparently related to an impaired reproductive outcome, while their exact clinical impact as well as the effectiveness of their treatment remain considered controversial. Surgery is indicated in women presenting with symptoms related to specific uterine anomalies, especially in those with fertility problems. In this review, indications, surgical techniques for the repair of CUA according to their classification, and fertility and pregnancy outcomes before and after surgery will be thoroughly reviewed.