Objective To review systematically the literature on uterus-sparing surgical treatment options for adenomyosis. Design Systematic literature review. Setting Tertiary academic center. Patient(s) Women ...with histologically proven adenomyosis treated with uterus-sparing surgical techniques. Intervention(s) Conservative uterine-sparing surgery for adenomyosis classified as (1) complete excision of adenomyosis, (2) cytoreductive surgery or incomplete removal of the lesion, or (3) nonexcisional techniques, with studies selected if women with adenomyosis were treated surgically without performing hysterectomy. Main Outcome Measure(s) The cure rate after interventional strategies, the rate of symptom (dysmenorrhea and menorrhagia) control, and pregnancy rate in each group of intervention. Result(s) A quality assessment tool was used to assess the scientific value of each study. In total, 64 studies dealing with 1,049 patients were identified. After complete excision, the dysmenorrhea reduction, menorrhagia control, and pregnancy rate were 82.0%, 68.8%, and 60.5%, respectively. After partial excision, the dysmenorrhea reduction, menorrhagia control, and pregnancy rate were 81.8%, 50.0%, and 46.9%, respectively. Conclusion(s) Uterine-sparing operative treatment of adenomyosis and its variants appear to be feasible and efficacious. Well-designed, comparative studies are urgently needed to answer the multiple questions arising from this intriguing intervention.
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.
Abstract
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.
STUDY QUESTION
What classification system is more suitable for the accurate, clear, simple and related to the clinical management categorization of female genital anomalies?
SUMMARY ANSWER
The new ...ESHRE/ESGE classification system of female genital anomalies is presented.
WHAT IS KNOWN ALREADY
Congenital malformations of the female genital tract are common miscellaneous deviations from normal anatomy with health and reproductive consequences. Until now, three systems have been proposed for their categorization but all of them are associated with serious limitations.
STUDY DESIGN, SIZE AND DURATION
The European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE) have established a common Working Group, under the name CONUTA (CONgenital UTerine Anomalies), with the goal of developing a new updated classification system. A scientific committee (SC) has been appointed to run the project, looking also for consensus within the scientists working in the field.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The new system is designed and developed based on (i) scientific research through critical review of current proposals and preparation of an initial proposal for discussion between the experts, (ii) consensus measurement among the experts through the use of the DELPHI procedure and (iii) consensus development by the SC, taking into account the results of the DELPHI procedure and the comments of the experts. Almost 90 participants took part in the process of development of the ESHRE/ESGE classification system, contributing with their structured answers and comments.
MAIN RESULTS AND THE ROLE OF CHANCE
The ESHRE/ESGE classification system is based on anatomy. Anomalies are classified into the following main classes, expressing uterine anatomical deviations deriving from the same embryological origin: U0, normal uterus; U1, dysmorphic uterus; U2, septate uterus; U3, bicorporeal uterus; U4, hemi-uterus; U5, aplastic uterus; U6, for still unclassified cases. Main classes have been divided into sub-classes expressing anatomical varieties with clinical significance. Cervical and vaginal anomalies are classified independently into sub-classes having clinical significance.
LIMITATIONS, REASONS FOR CAUTION
The ESHRE/ESGE classification of female genital anomalies seems to fulfill the expectations and the needs of the experts in the field, but its clinical value needs to be proved in everyday practice.
WIDER IMPLICATIONS OF THE FINDINGS
The ESHRE/ESGE classification system of female genital anomalies could be used as a starting point for the development of guidelines for their diagnosis and treatment.
STUDY FUNDING/COMPETING INTEREST(S)
None.
Current proposals for classifying female genital anomalies seem to be associated with limitations in effective categorization, creating the need for a new classification system that is as simple as ...possible, clear and accurate in its definitions, comprehensive, and correlated with patients' clinical presentation, prognosis, and treatment on an evidence-based foundation. Although creating a new classification system is not an easy task, it is feasible when taking into account the experience gained from applying the existing classification systems, mainly that of the American Fertility Society.
Abstract The clinical implications of congenital uterine anomalies (CUA), and the benefits of hysteroscopic resection of a uterine septum, were evaluated. Studies comparing reproductive and obstetric ...outcome of patients with and without CUA and of patients who had and had not undergone hysteroscopic resection of a uterine septum, were evaluated. Meta-analysis of studies indicated that the pregnancy rate was decreased in women with CUA (RR 0.85, 95% CI 0.73 to 1.00; marginally significant finding, P = 0.05). The spontaneous abortion rate was increased in women with CUA (RR 1.68, 95% CI 1.31 to 2.15). Preterm delivery rates (RR 2.21, 95% CI 1.59 to 3.08), malpresentation at delivery (RR 4.75, 95% CI 3.29 to 6.84), low birth weight (RR 1.93, 95% CI 1.50 to 2.49) and perinatal mortality rates (RR 2.43, 95% CI 1.34 to 4.42) were significantly higher in women with CUA. Hysteroscopic removal of a septum was associated with a reduced probability of spontaneous abortion (RR 0.37, 95% CI 0.25 to 0.55) compared with untreated women. Presence of CUA might be associated with a detrimental effect on the probability of pregnancy achievement, spontaneous abortion and obstetric outcome. Hysteroscopic removal of a septum may reduce the probability of a spontaneous abortion.
Infertility and uterine fibroids Zepiridis, Leonidas I., MD, PhD; Grimbizis, Grigoris F., MD, PhD; Tarlatzis, Basil C., MD, PhD
Best practice & research. Clinical obstetrics & gynaecology,
07/2016, Volume:
34
Journal Article
Peer reviewed
Uterine fibroids are the most common tumors in women and their prevalence is higher in patients with infertility. At present, they are classified according to their anatomical location, as no ...classification system includes additional parameters such as their size or number. There is a general agreement that submucosal fibroids negatively affect fertility, when compared to women without fibroids. Intramural fibroids above a certain size (>4 cm), even without cavity distortion, may also negatively influence fertility. However, the presence of subserosal myomas has little or no effect on fertility. Many possible theories have been proposed to explain how fibroids impair fertility: mechanisms involving alteration of local anatomical location, others involving functional changes of the myometrium and endometrium, and finally endocrine and paracrine molecular mechanisms. Nevertheless, any of the above mentioned mechanisms can cause reduced reproductive potential, thereby leading to impaired gamete transport, reduced ability for embryo implantation, and creation of a hostile environment. The published experience defines the best practice strategy, as not many large, well-designed, and properly powered studies are available. Myomectomy appears to have an effect in fertility improvement in certain cases. Excision of submucosal myomas seems to restore fertility with pregnancy rates after surgery similar to normal controls. Removal of intramural myomas affecting pregnancy outcome seems to be associated with higher pregnancy rates when compared to non-operated controls, although evidence is still nοt sufficient. Treatment of subserosal myomas of reasonable size is not necessary for fertility reasons. The results of endoscopic and open myomectomy are similar; thus, endoscopic treatment is the recommended approach due to its advantages in patient's postoperative course.
Abstract
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.