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Fertility Sparing Procedure using Carbon Dioxide Fiber Laser Vaporization of Ovarian Endometrioma

The surgical management of endometrioma is still a matter of debate. Cystectomy, which is recognized as the standard technique, seems to be associated ...

San Raffaele Scientific Institute

Endometriosis is an inflammatory disease affecting 7-10% of women throughout their reproductive life. Few data are available regarding the age at menopause of women affected by this disease. Most of the available evidence, although scanty, would indicate that both ovarian surgery for endometriomas and endometriosis per se appear to influence age at menopause. Other factors might interfere with the age at menopause of women affected by endometriosis. The purpose of this review was to examine the age at menopause in women with a history of endometriosis and to identify factors that might affect the timing of menopause.

Does endometriosis influence the age of menopause?

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG.

Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms.

Over the past few years, a new topic in the field of endometriosis has emerged: the potential impact of the disease on pregnancy outcomes. This review aims to summarize in detail the available evidence on the relationship between endometriosis, particularly deep endometriosis (DE), and obstetrical outcomes. Acute complications of DE, such as spontaneous hemoperitoneum, bowel perforation, and uterine rupture, may occur during pregnancy. Although these events represent life-threatening conditions, they are rare and unpredictable. Therefore, the current literature does not support any kind of prophylactic surgery before pregnancy to prevent such complications. Results on the impact of DE on obstetrical outcomes are debatable and characterized by several limitations, including small sample size, lack of adjustment for confounders, lack of adequate control subjects, and other methodologic flaws. For these reasons, it is not possible to draw conclusions on this topic. The strongest evidence shows that DE is associated with higher rates of placenta previa; for other obstetrical outcomes, such as miscarriage, intrauterine growth restriction, preterm birth and hypertensive disorders, results are controversial. Although it is unlikely that surgery of DE may modify the impact of the disease on the course of pregnancy, no study has yet investigated this issue.

Obstetrical complications of endometriosis, particularly deep endometriosis.

To assess postoperative recurrence rates in patients with endometriomas managed by either "one-step" CO fiber laser vaporization or cystectomy.

Recurrence Rate after "One-Step" CO Fiber Laser Vaporization versus Cystectomy for Ovarian Endometrioma: A 3-Year Follow-up Study.

Endometriosis-related fibrosis represents a complex phenomenon with underlying mechanisms yet to be clarified. Fibrosis is consistently present in all disease forms and contributes to classic endometriosis-related symptoms of pain and infertility. The purpose of this literature review was to examine the role of various cellular populations and biologic mechanisms and signaling pathways in inducing fibrogenesis of endometriotic lesions. A search was performed through PubMed and MEDLINE for animal and human studies published in English in the last 23 years that examined fibrosis in superficial, ovarian, and deep infiltrating endometriosis. The main cell types found to be involved in the development of fibrosis were platelets, macrophages, ectopic endometrial cells, and sensory nerve fibers. Interactions among each of the cell types contribute to the production of fibrosis through the production of soluble factors, mostly transforming growth factor-β but also other cytokines and neuropeptides. Cell types known to be critical to the pathophysiology of endometriosis also contribute to fibrogenesis, thus supporting the theory that fibrosis is an inherent part of endometriosis.

Cellular Components Contributing to Fibrosis in Endometriosis: A Literature Review.

This meta-analysis aimed to offer a general picture of the available data on the effects of early-life factors on the risk of developing endometriosis in adult life. An advanced, systematic search of the online medical databases PubMed, EMBASE and CINAHL was limited to full-length manuscripts published in English in peer-reviewed journals up to February 2019. Log of relative risk (RR) was employed to calculate the pooled effect sizes using both fixed and random effects modelling and I-squared tests to assess heterogeneity. Funnel plots were used to investigation publication bias. The meta-analysis was registered in PROSPERO (ID CRD42019138668). Six studies that included a total of 2360 women affected by endometriosis were analysed. The pooled results showed that the risk of developing endometriosis in adult life was significantly increased by being born prematurely (logRR 0.21, 95% CI -0.03 to 0.40), having a low birthweight (logRR 0.35, 95% CI -0.15 to 0.54), being formula-fed (logRR 0.65, 95% CI -0.35 to 0.95) and having been exposed to diethylstilbestrol (DES) in utero (logRR 0.65, 95% CI 0.26 to 1.04. Among intrauterine and early neonatal exposures, prematurity, birthweight, formula feeding and DES were risk factors for the development of endometriosis in adult life.

Early-life factors, in-utero exposures and endometriosis risk: a meta-analysis.

Data about endometrioma ablation using energies with little thermal spread reported good results in terms of ovarian reserve and postoperative pregnancy rates. The aim of the present study was to assess the impact of one step CO<inf>2</inf> fiber laser vaporization for endometrioma on subsequent controlled ovarian stimulation.

Ovarian responsiveness in assisted reproductive technology after CO2 fiber laser vaporization for endometrioma treatment: preliminary data.

To assess the postoperative likelihood of conception in patients with endometriomas managed by either CO laser vaporization or cystectomy.

Fertility Outcome after CO Laser Vaporization versus Cystectomy in Women with Ovarian Endometrioma: A Comparative Study.

The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database prospectively collected from January 2017 to February 2020 including  = 572 women who underwent laparoscopic surgery for endometriosis (cases,  = 324) or other benign gynecologic diseases (controls,  = 248). Inflammatory markers and coagulation parameters were determined. An advanced systematic search of the literature on the same parameters was conducted up to April 2020. A significantly higher neutrophil count was found in endometriosis patients. Patients with endometriomas and stage III-IV disease had a significantly lower absolute lymphocyte count and shortened activated partial thromboplastin time (aPTT) values. In the final regression model, aPTT retained significant predictive value for stage III-IV endometriosis (odds ratio (OR) = 0.002, 95% confidence interval (CI) = 0.00-0.445;  = 0.024). Results from the  = 14 included studies in the systematic review are characterized by a high variability, but some consistency has been found for alterations in thrombin time, platelet-to-lymphocyte ratio, and neutrophil count associated with endometriosis. Modest systemic changes of some inflammatory and coagulation parameters are associated with endometriosis. Indeed, all the modifications detected are still within the normal reference intervals, explaining the high heterogeneity among studies.

Assessment of Coagulation Parameters in Women Affected by Endometriosis: Validation Study and Systematic Review of the Literature.

Gestational diabetes mellitus (GDM) is a metabolic complication associated with adverse outcomes for mother and fetus. Arsenic (As) exposure has been suggested as a possible risk factor for its development. The aim of this meta-analysis was to provide a comprehensive overview of published evidence on the association between As and GDM. The systematic search from PubMed, MEDLINE, and Scopus was limited to full-length manuscripts published in peer-reviewed journals up to April 2020, identifying fifty articles. Ten studies met the inclusion criteria, nine for quantitative synthesis with a total of  = 1984 GDM cases. The overall pooled risk was 1.56 (95% Confidence Interval - CI = 1.23, 1.99) with moderate heterogeneity (χ = 21.95; I% = 64). Several differences among the included studies that may account for heterogeneity were investigated. Stratification for exposure indicator confirmed a positive association for studies assessing urine As. A slightly higher risk was detected pooling studies based in Asia rather than in North America. Stratification for GDM diagnostic criteria showed higher risks when diagnosis was made according to the Canadian Diabetes Association (CDA-SOGC) or World Health Organization (WHO) criteria, whereas a lower risk was observed when adopting the American Diabetes Association (ADA) criteria. These results provide additional evidence for a possible association between As exposure and GDM, although the data need to be interpreted with caution due to heterogeneity.

Maternal Arsenic Exposure and Gestational Diabetes: A Systematic Review and Meta-Analysis.

The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.

Endometriosis and Phytoestrogens: Friends or Foes? A Systematic Review.

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed  = 40 studies eligible for inclusion in this systematic review. Of these,  = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.

Article	Year
Does endometriosis influence the age of menopause? Minerva ginecologica\| PubMed ID: 28891281	2018
Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms. International journal of molecular sciences\| PubMed ID: 28930160	2017
Obstetrical complications of endometriosis, particularly deep endometriosis. Fertility and sterility\| PubMed ID: 29202964	2017
Recurrence Rate after "One-Step" CO Fiber Laser Vaporization versus Cystectomy for Ovarian Endometrioma: A 3-Year Follow-up Study. Journal of minimally invasive gynecology\| PubMed ID: 31377455	2020
Cellular Components Contributing to Fibrosis in Endometriosis: A Literature Review. Journal of minimally invasive gynecology\| PubMed ID: 31785417	2020
Early-life factors, in-utero exposures and endometriosis risk: a meta-analysis. Reproductive biomedicine online\| PubMed ID: 32532666	2020
Ovarian responsiveness in assisted reproductive technology after CO2 fiber laser vaporization for endometrioma treatment: preliminary data. Minerva endocrinologica\| PubMed ID: 32638581	2020
Fertility Outcome after CO Laser Vaporization versus Cystectomy in Women with Ovarian Endometrioma: A Comparative Study. Journal of minimally invasive gynecology\| PubMed ID: 32712323	2021
Assessment of Coagulation Parameters in Women Affected by Endometriosis: Validation Study and Systematic Review of the Literature. Diagnostics (Basel, Switzerland)\| PubMed ID: 32784640	2020
Maternal Arsenic Exposure and Gestational Diabetes: A Systematic Review and Meta-Analysis. Nutrients\| PubMed ID: 33050632	2020
Endometriosis and Phytoestrogens: Friends or Foes? A Systematic Review. Nutrients\| PubMed ID: 34444692	2021
A Systematic Review of Atypical Endometriosis-Associated Biomarkers. International journal of molecular sciences\| PubMed ID: 35457244	2022

Matteo Schimberni

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