Donatella Caserta

Hysterosalpingo contrast sonography (HyCoSy): let's make the point!

IntroductionThe accurate evaluation of tubal patency as well of the morphologic characteristics of the uterine cavity is a fundamental step in the diagnostic work-up for infertility. Hysteroscopy and laparoscopy and dye have long been regarded as the reference methods to assess uterine morphology and tubal patency, respectively. However, their technical and clinical limitations have supported the introduction of an emerging technique: hysterosalpingo contrast sonography (HyCoSy), which has recently been improved with the use of modern contrast agents and three-dimensional resolution.MethodsA systematic literature search was performed in electronic databases (PubMed and Scopus). Key search terms included Hysterosalpingo contrast sonography (HyCoSy), Tubal patency, Infertility, Uterine cavity, Ultrasounds.ResultsHyCoSy has proved to be as reliable as laparoscopic techniques in the assessment of tubal patency and uterine morphology, and also it overcomes such major drawbacks as hospitalization, radiation exposure, anesthesia and use of iodinated contrast media. All in all, HyCoSy is considered as a safe and well tolerated outpatient procedure, which apparently favors the onset of spontaneous pregnancies.ConclusionThis paper provides a comprehensive overview of the literature dealing with HyCoSy to support its use as a first-line technique in standard infertility work-up.

Heavy metals in human amniotic fluid: A pilot study

Many heavy metals are essential nutrients for a healthy life. However, significant evidence supports prolonged prenatal exposure as a risk factor for several adverse health effects. The aim of this study is to evaluate the presence of heavy metals in human amniotic fluid (AF) to demonstrate that there is an early fetal in utero exposure.

Epigenetic modifications of primordial reproductive tract: A common etiologic pathway for Mayer-Rokitansky-Kuster-Hauser Syndrome and endometriosis?

http://dx.doi.org/10.1016/j.mehy.2016.02.015 0306-9877/ 2016 Published by Elsevier Ltd. Dear Editor, we read with great interest the paper by Alcolado [1], published in your prestigious Journal. This work conforms ‘‘the fetal basis of adult disease’’ hypothesis, which proposes that prenatal exposure to certain forms of environmental stress can cause increased susceptibility to clinical disorders, modulating the gene expression later in life (the so-called ‘‘epigenetic imprinting”). During embryogenesis, it was already shown that homeobox (Hox) genes are strictly involved in the differentiation of the paramesonephric duct into the mature female reproductive system [2]. Two weeks after birth, Hoxa9, Hoxa10, Hoxa11 and Hoxa13 develop their characteristic spatial distribution throughout the Müllerian ducts [3]. Moreover, it was demonstrated that the loss of Hoxa10 function provokes dysregulation during decidualization and implantation, resulting in female infertility [4]. Although clear data about the role of Hoxa gene clusters in infertility remain to be elucidated, we know that Hoxa10 specifically mediates the progesterone regulation of two prostaglandin E2 receptors (EP3 and EP4) in uterine stroma [5]. Moreover, another well-known family of genes that influence remarkably the organogenesis of the Müllerian reproductive tract is Wnt (wingless-type MMTV integration site family). Failures in Wnt signaling are associated with infertility, endometriosis, endometrial cancer and gestational trophoblastic disease such as choriocarcinomas [6]. Basing on these data, it is possible that epigenetic disturbance(s) during the Müllerian reproductive tract development may lead to modified intercellular communications, dysregulation of common downstream targets and, finally, to defect of organogenesis. Considering that the dysregulation of Wnt and/or Hox genes may affect cell migration during organogenesis and differentiation of Müllerian structures of the female reproductive tract, these altered pathways can underlie the well-known Mayer-Rokitansky-Kuster-Hauser Syndrome [7], clinically characterized by a physiological development of the secondary sexual characters and by a normal female karyotype 46 XX, with a congenital aplasia of the uterus and of 2/3 superior parts of vagina. A similar etiologic machinery was already hypothesized for endometriosis [8], a gynecological condition characterized by the breakdown of peritoneal immune homeostasis [9–11] and related symptoms and signs [12–14] due to the pro-inflammatory profile of pelvic as well as intrauterine microenvironment. Conflict of interest statement

Does supplementation with recombinant luteinizing hormone prevent ovarian hyperstimulation syndrome in down regulated patients undergoing recombinant follicle stimulating hormone multiple follicular stimulation for IVF/ET and reduces cancellation rate for high risk of hyperstimulation?

Aim of this study was to assess the efficacy of recombinant luteinizing hormone (rLH) supplementation in late follicular phase in multiple follicular stimulation with recombinant follicle stimulating hormone (rFSH) in Triptoreline down-regulated patients undergoing IVF, on preventing clinical OHSS and cycles cancellation for OHSS risk. Nine hundred ninety-nine patients aged ≤40 with basal FSH ≤12 mUI/Ml were down-regulated before starting rFSH stimulation for oocytes recovery. Patients were allocated in two groups: (A) (501 patients) treated with 150 IU of rFSH eventually adjusting rFSH dosage day 7 of stimulation until recombinant human chorionic gonadotropin (rhCG) administration, (B) (498 patients) treated with 150 IU of rFSH and 75 IU of rLH since day 7 of stimulation until rhCG administration and adjusting rFSH at the same day. E2 the day of rhCG was higher in group B (p < 0.0001); number of cycles cancelled in group A (42/8.3%) for risk of ovarian hyperstimulation syndrome (OHSS) was higher than group B (12/2.4%) (p < 0.000001). We observed an increase in pregnancies in group B compared with group A (16.8% vs 11.9%) (p < 0.05) and we observed also a larger number of clinical OHSS in group A than in group B (p < 0.05).

Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies

Background: Although exposure to endocrine disruptor compounds (EDCs) has been suggested as a contributing factor to a range of women’s health disorders including infertility, polycystic ovaries and the early onset of puberty, considerable challenges remain in attributing cause and effect on gynaecological cancer. Until recently, there were relatively few epidemiological studies examining the relationship between EDCs and endometrial cancer, however, in the last years the number of these studies has increased. Methods: A systematic MEDLINE (PubMed) search was performed and relevant articles published in the last 23 years (from 1992 to 2016) were selected. Results: Human studies and animal experiments are confirming a carcinogenic effect due to the EDC exposure and its carcinogenesis process result to be complex, multifactorial and long standing, thus, it is extremely difficult to obtain the epidemiological proof of a carcinogenic effect of EDCs for the high number of confusing factors. Conclusions: The carcinogenic effects of endocrine disruptors are plausible, although additional studies are needed to clarify their mechanisms and responsible entities. Neverthless, to reduce endocrine disruptors (ED) exposure is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as embryonic period and puberty.

Levels of Galectin-3 and Stimulation Expressed Gene 2 in the peritoneal fluid of women with endometriosis: a pilot study

Abstract Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease. This study analyzed the levels of two inflammatory factors – Galectin-3 and Stimulation Expressed Gene 2 – in the peritoneal fluid of 15 women affected by endometriosis and 8 controls. The peritoneal fluid was collected during laparoscopic surgery avoiding any form of contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were significantly higher in endometriosis group than in controls (64.7 ± 52.34 versus 21.05 ± 20.83 ng/ml, p = 0.044), whereas ST2 concentrations did not differ between the two groups. A significant positive correlation was found between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while ST2 levels were positively associated with VAS score. Our results suggest that Gal-3 and ST2 could be implicated in the inflammatory process of the disease. Further studies are needed to identify markers of early diagnosis and to open new therapeutic avenues in endometriosis. Chinese abstract 由于并未明确的发病机制,子宫内膜异位症成为一种令人困惑的疾病。一些研究认为腹腔液是子宫内膜异位发生和发展的关键炎症环境。本研究分析了两种炎症因子-- 半乳糖凝集素3及刺激表达基因2在15名患有子宫内膜异位症妇女和8名对照妇女腹腔液中的水平。腹腔液通过避免了任何污染的腹腔镜手术收集并妥善处理和保存，随后使用酶免疫分析法分析了浓缩腹腔液中的Gal-3和ST2。异位症组的Gal-3水平明显高于对照组(64.7 ± 52.34 比 21.05 ± 20.83 ng/ml,p=0.044)，而ST2水平在两组中并无明显差异。Gal-3与ST2水平存在明显的正相关，Gal-3水平与内异症的发展阶段、症状的持续时间、Marinoff及VAS评分正相关，而ST2与VAS评分呈正相关。我们的结果显示Gal-3和ST2或与内异症炎症发展过程有关。为确定子宫内膜异位症的早期诊断标记物及开展新的治疗方式仍需要进一步的研究。

Clinical factors and malignancy in endometrial polyps. Analysis of 1027 cases

STUDY OBJECTIVE To assess the prevalence of polyps carrying a malignancy and match association between clinical factors and oncologic progression. STUDY DESIGN A retrospective study (Canadian Task Force classification II-3) at a university hospital in Rome, Italy. We retrospectively analyzed data from 1027 women consecutively treated for endometrial polyps at our center in the period 2002-2011. The association of malignancy with hormonal status, tamoxifen, hypertension, symptoms, diabetes mellitus, obesity, and hormonal replacement therapy in pre- and post-menopausal women was assessed. RESULTS Mean age was 45.8±10.8 years. Benign polyps accounted for 95.8% of the total, pre-malignant for 2.67%, malignant for 1.54%. Our data showed that post-menopausal and older women (>60y) with endometrial polyps have a higher risk of developing a related endometrial cancer (OR: 3.05, 95% CI [1.54, 6.19], p<0.001 and OR: 2.8, 95% CI [1.38, 5.56], p≤0.003. Also we observed that women with AUB in the post-menopausal period displayed a risk of malignancy (OR: 31.1, 95% CI [10.3,111], p value <0.001). CONCLUSION Special attention should be drawn to symptomatic post-menopausal patients that appear to be at higher risk of malignancy. Symptomatic pre-menopausal women and asymptomatic post-menopausal women with polyps may be a group with intermediate-risk. These patients should undergo an individualized management plan, balancing both risks and benefits of surgical intervention after discussion with the patient.

Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients

Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.

Impact of 677C>T Mutation of the 5,10-Methylenetetrahydrofolate Reductase on IVF Outcome: Is Screening Necessary for All Infertile Women?

AIM Polymorphisms of genes connected to folate metabolism may alter the beneficial effect of folic acid on the methyl group cycle. The most common variation is the 677C>T polymorphism of the gene of the 5,10-methylentetrahydrofolate reductase (MTHFR). The aim of this study is to investigate of what influence, if any, does MTHFR 677C>T mutation have on female fertility and on the in vitro fertilization (IVF) outcome. PATIENTS AND METHODS Data of 273 patients were retrospectively analyzed. The study group (group A) consisted of 103 women, homozygous for the MTHFR 677C>T mutant genotype. The control group (group B) consisted of 170 patients without the mutation. RESULTS A longer stimulation duration was found in group A and the total amount of recombinant follicle-stimulating hormone (r-FSH) needed was appreciably higher. The fertilization rate was significantly higher in group B, although the implantation rate and clinical pregnancies were similar in both groups. CONCLUSIONS Alteration of inherited thrombophilic factors is connected with early pregnancy loss and IVF implantation failure. Our study showed an abortion rate higher, but not statistically significant, in group A. Based on these findings, our study suggests that MTHFR 677C>T mutation does not affect the IVF outcome and patients without thrombophilic risk factors undergoing an IVF cycle should not all be screened for thrombophilic disorders.

Poor responders in IVF: an update in therapy

Abstract Introduction: Assisted reproduction techniques are the frequent treatment of infertility. Despite the advances in science and technology, the management of poor responder patients is still considered as one of the most urgent problems. The lack of unified definition makes the management of the poor responder patients very difficult. The aim of this review is to examine and compare the different studies done about the problem of poor responder patients. Methods: On an online research of MEDLINE/PUBMED, we found several studies on pharmacological treatment for poor responders’ patients. Results: Our review shows that in the years numerous therapies for the management of these patients who do not respond to ovarian stimulation have been evaluated and studied, but the main problem is the large and still not well-defined meaning of poor responder women. Conclusion: The management of the poor responder patients is very difficult. Currently, there is no any standard treatment for poor responder patients. Considering the importance of the problem, it is important to identify a diagnostic and therapeutic target. Our review shows that there are many studies with different therapeutic approaches which deserve further in-depth study to standardize diagnostic and therapeutic target.