Annalisa Inversetti

A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes

BACKGROUND Traditionally, pregnancy was considered to have a positive effect on endometriosis and its painful symptoms due not only to blockage of ovulation preventing bleeding of endometriotic tissue but also to different metabolic, hormonal, immune and angiogenesis changes related to pregnancy. However, a growing literature is emerging on the role of endometriosis in affecting the development of pregnancy and its outcomes and also on the impact of pregnancy on endometriosis. The present article aims to underline the difficulty in diagnosing endometriotic lesions during pregnancy and discuss the options for the treatment of decidualized endometriosis in relation to imaging and symptomatology; to describe all the possible acute complications of pregnancy caused by pre-existing endometriosis and evaluate potential treatments of these complications; to assess whether endometriosis affects pregnancy outcome and hypothesize mechanisms to explain the underlying relationships. METHODS This systematic review is based on material searched and obtained via Pubmed and Medline between January 1950 and March 2015. Peer-reviewed, English-language journal articles examining the impact of endometriosis on pregnancy and vice versa were included in this article. RESULTS Changes of the endometriotic lesions may occur during pregnancy caused by the modifications of the hormonal milieu, posing a clinical dilemma due to their atypical appearance. The management of these events is actually challenging as only few cases have been described and the review of available literature evidenced a lack of formal estimates of their incidence. Acute complications of endometriosis during pregnancy, such as spontaneous hemoperitoneum, bowel and ovarian complications, represent rare but life-threatening conditions that require, in most of the cases, surgical operations to be managed. Due to the unpredictability of these complications, no specific recommendation for additional interventions to the routinely monitoring of pregnancy of women with known history of endometriosis is advisable. Even if the results of the published studies are controversial, some evidence is suggestive of an association of endometriosis with spontaneous miscarriage, preterm birth and small for gestational age babies. A correlation of endometriosis with placenta previa (odds ratio from 1.67 to 15.1 according to various studies) has been demonstrated, possibly linked to the abnormal frequency and amplitude of uterine contractions observed in women affected. Finally, there is no evidence that prophylactic surgery would prevent the negative impact of endometriosis itself on pregnancy outcome. CONCLUSIONS Complications of endometriosis during pregnancy are rare and there is no evidence that the disease has a major detrimental effect on pregnancy outcome. Therefore, pregnant women with endometriosis can be reassured on the course of their pregnancies although the physicians should be aware of the potential increased risk of placenta previa. Current evidence does not support any modification of conventional monitoring of pregnancy in patients with endometriosis.

HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population.

Abstract Background: Pre-eclampsia (PE) is a hypertensive multisystem disorder, causing significant fetal-maternal mortality and morbidity worldwide. This study aims to define possible longitudinal predictive mRNA markers involved in the main pathogenic pathways of PE: inflammation [macrophage migration inhibitory factor (MIF)], hypoxia and oxidative stress [hypoxia inducible factor 1-α subunit (HIF1A) and β-site APP-cleaving enzyme-2 (BACE2)] and endothelial dysfunction [endoglin (ENG), fms-related tyrosine kinase-1 (FLT1) and vascular endothelial growth factor (VEGF)]. Methods: Peripheral blood was collected from 33 singleton pregnancies characterized by a high cardiovascular profile risk sampled consecutively at 6–16; 17–23; 24–30; 31–34; ≥35 weeks followed by the Obstetrics and Gynecology Unit of the San Raffaele Hospital in Milan. A real-time quantitative PCR reaction was performed on plasma RNA. Results: Of the 33 women enrolled, nine developed PE. Until 23 weeks HIF1A was significantly higher in women who later developed PE compared to women who did not (p=0.049 and p=0.012 in the first and second blood collection). In the third time interval MIF (p=0.0005), FLT1 (p=0.024), ENG (p=0.0034) and BACE2 (p=0.044) appeared to be significantly increased while HIF1A was elevated even from 24 week onwards but not reaching the statistical significance. In the fourth time interval ENG mRNA still remained increased (p=0.037). Conclusions: HIF1A, marker of hypoxia and oxidative stress, and MIF, marker of inflammation, seemed to be the most promising RNA markers, suggesting that hypoxia, principally, and inflammation may play an important role in PE pathogenesis.

Risk of spontaneous preterm birth in singleton pregnancies conceived after IVF/ICSI treatment: meta‐analysis of cohort studies

Preterm birth (PTB) is more common in pregnancies conceived by in‐vitro fertilization (IVF) as compared with those conceived naturally. However, the extent to which this is attributed to spontaneous labor or to iatrogenic indications has not been determined. The aim of this study was to quantify the risk of spontaneous PTB (sPTB) in singleton pregnancies resulting from IVF or intracytoplasmic sperm injection (ICSI) treatment as compared with that in spontaneously conceived pregnancies.

Nuchal translucency measurement, free β-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis.

So far, data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal translucency, free beta‐human chorionic gonadotrophin and pregnancy‐associated plasma protein‐A measurements. Moreover, a meta‐analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m0MoM) were performed. Free beta‐human chorionic gonadotrophin test showed slightly higher values in the ICSI group than controls (RR = 1.09, 95%CI: 1.03–1.16) but not in the IVF group (RR = 1.03, 95%CI: 0.94–1.12). Pregnancy‐associated plasma protein‐A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80–0.90; 0.82, 0.74–0.89 and 0.83, 0.79–0.86, respectively). The nuchal translucency measurement did not show any statistical differences between study groups (IVF and ICSI) and controls (RR = 1.00, 95%CI: 0.94–1.08 and RR = 1.01, 95%CI: 0.97–1.05, respectively). These results may be due to alterations in the placentation of ART pregnancies. Differentiating further subgroups of ART pregnancies may explain the differences in biomarker concentrations, in prenatal behavior and in obstetric outcomes between ART and spontaneous pregnancies.

Predictive biomarkers of pre-eclampsia and effectiveness of preventative interventions for the disease.

Introduction: Pre-eclampsia (PE) is one of the most common pregnancy complication characterized by placental and maternal vascular dysfunction. It affects about 3 – 8% of women during the second half of pregnancy and represents one of the major causes of neonatal morbidity and mortality. The etiology of PE largely remains unknown. Areas covered: PE is considered a syndrome with multisystem involvement, so the ideal predictive test for it should utilize a combination of many predictors. Measurement in early pregnancy of a variety of biophysical and biochemical markers implicated in the pathophysiology of PE associated with clinical risk factors has been proposed to predict the development of the syndrome, thereby mitigating an adverse outcome. Expert opinion: The identification of reliable indicators is a clinically relevant issue that could result in early therapeutic intervention and leading to the prevention of maternal and fetal injuries before the manifestation of clinical signs. Many factors complicate the prevention of PE cases. Most are attributed to unknown etiology, the low predictive value of current screening tests and the several presentations of the disease. Although preventative treatments have been studied extensively, an effective intervention to avoid the development of PE has not yet been discovered.

Severe Hypothyroidism Causing Pre-Eclampsia-Like Syndrome

Objective. Analyzing and managing pre-eclampsia-like syndrome due to severe hypothyroidism. Methods. Presentation of a case of severe hypothyroidism due to Hashimotos syndrome, associated with a severe early-onset preeclampsia-like syndrome, managed in our Gynecology Department. Results. Severe pre-eclampsia led to miscarriage at 24 weeks of gestational age in a 42-year-old woman, although we attempted to correct hypothyroidism with increasing doses of levothyroxine and liothyronine sodium. Conclusion. Recognizing pre-eclampsia-like syndrome caused by overt hypothyroidism from other forms of pregnancy-induced hypertension is essential for choosing the correct treatment.

Congenital heart defects in IVF/ICSI pregnancy: systematic review and meta‐analysis

There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously.

Uterine artery Doppler pulsatility index at 11–38 weeks in ICSI pregnancies with egg donation

Abstract Background: Uterine artery Doppler pulsatility index (UtA-PI) may be different in pregnancies with egg donation (ICSI-ED) as compared to conceptions with autologous intra-cytoplasmatic sperm injection (autologous ICSI) and to spontaneous conceptions (SC). Methods: One hundred and ninety-four pregnant women with different modes of conception (MC) were prospectively evaluated: 53 ICSI-ED, 36 autologous ICSI and 105 SC. To evaluate the effects of different MC on PI, multivariable linear regression (MLR) models predicting UtA-PI were fitted after adjustment for maternal age, body mass index, race, parity, smoking status and gestational age. Results: In the first trimester, at MLR, autologous ICSI was not associated with a significantly different UtA-PI [estimate (EST) 0.01; 95% confidence interval (CI) −0.19, 0.2; P=0.9] when compared to SC. Conversely, MC by ICSI-ED was associated with lower first trimester UtA-PI (EST −0.32; CI −0.55, −0.08; P=0.01) when compared to SC. At MLR, MC by autologous ICSI and by ICSI-ED were not associated with significant differences in the second and third trimester UtA-PI when compared to SC. Conclusion: ICSI-ED conception presented lower UtA-PI when compared to SC at 11+0–13+6 weeks but not at later assessments. Correction of UtA-PI measurement specifying the origin of oocyte may be useful in first trimester screening.

A case of pre-eclampsia and foetal growth restriction after embolisation for a postmolar uterine arteriovenous malformation

Introduction Arteriovenous malformations (AVMs) of the uterus are rare vascular lesions that may be congenital or more commonly acquired aft er medical or surgical abortion, spontaneous miscarriage, dilation and curettage (DC) and gestational trophoblastic neoplasia (GTN) (Timmerman et al. 2000). Uterine artery embolisation (UAE) is the most common treatment option in symptomatic women: it appears to be eff ective with few complications and it may allow the preservation of fertility (Badawy et al. 2001). Th e actual risk of possible complications during pregnancy aft er uterine AVM embolisation is unknown. Th e most frequent pregnancy-related complications reported in a few cases are placental abnormalities, such as placenta accreta and increta, uterine atony, uterine rupture and foetal growth restriction (FGR) (Chow et al. 1995, Delotte et al. 2006). In this article, we report the fi rst case of pre-eclampsia and FGR aft er UAE for AVM in a woman treated for GTN.

OP23.02: Percutaneous transvesical chorionic villus sampling: an alternative method for difficult procedures

Objectives: Cervical cerclage is performed in patients with cervical insufficiency to reduce risks of abortion/extreme prematurity. Severe complications can occur if performed in patients with intra-amniotic infection. High levels of intraamniotic interleukin-6 (IL-6) are associated with histological chorioamnionitis. In expert hands amniocentesis is considered a safe procedure which we use routinely in management of PPROM. The aim of our study is to validate our strategy diagnostic amniocentesis prior to cerclage. Methods: Prospective cohort study in Centre of Fetal Medicine in 2014-16. We included 29 patients with cervical insufficiency eligible for emergency cerclage. In all cases we performed transabdominal amniocentesis. Amniotic fluid was tested for IL-6 (Roche Diagnostics) and bacterial DNA (PCR Mycoplasma, Ureaplasma). In patients with IL-6 <2000 ng/l McDonald transvaginal cerclage with Mersilene tape (Ethicon) was performed. Between 2000–4999 ng/l therapeutic dose of IV antibiotics was administered (Clarithromycin or Clindamycin) and amniocentesis was repeated in one week. If IL-6 lower, we performed cerclage. Patients with IL-6 >5000 ng/l were ruled out and managed conservatively. Results: We performed 29 amniocenteses. 21 patients were tested negative and proceeded with cerclage. 4 intermediate received antibiotics, had second amniocentesis (all with lower IL-6) and a cerclage afterwards. 4 patients were ruled out and managed expectantly. We performed cerclage in 25 cases. Mean gestational age at surgery was 22.1 (min 16.2, max 26.0). Mean IL-6 was 1046 ng/l (min 215, max 4254). In 1 case there was an abortion after cerclage. In all other 24 cases (96%) live fetuses were born. Mean gestational age at delivery 33.1 (min 24.5, max 41.1), mean birth weight 2072g (min 542, max 3770). Out of the 4 ruled out patients: 3 had a septic abortion within 1 week, 1 patient had an emergency Caesarean at 26 weeks for sepsis and bleeding. Conclusions: Invasive diagnostic to rule out intra-amniotic infection seems beneficial before emergency cerclage.