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Background: Labial adhesions, a frequent gynecological condition in prepubertal girls, occur when the labia minora adhere along the midline. The prevailing hypothesis about their etiology suggests that labial adhesion may occur when the delicate and non-estrogenized labia minora undergo an inflammatory response, triggered by exposure to an irritant environment. Therefore, conservative treatment involves the application of topical estrogen or betamethasone cream. The role of androgens has not been considered yet in the pathophysiology or therapy of this condition. However, some studies have shown that androgen receptors are prevalent in the labia minora and vulvar vestibule., Case Summary: We present the case of a 29-month-old girl with symptomatic labial adhesions. She was first ineffectively treated with topical estriol, and then she was treated with a galenic cream containing both estriol and testosterone with complete recovery and without side-effects., Conclusions: Both androgens and estrogens play a significant role in maintaining the physiological trophic state of the vulva and vagina, even during childhood. Topical estriol+testosterone could be considered an alternative treatment for prepubertal labial adhesions refractory to standard topical therapy.

COVID-19 infection is associated with increased risk of pregnancy complications, making vaccination during pregnancy critical for mother-neonate dyads. Few data, often with an unrepresentative sample size, are available on SARS-CoV-2 vaccine-induced humoral and cell-mediated response. Here, we evaluated anti-S antibody and interferon-gamma (IFN-γ) production elicited by SARS-CoV-2 immunization in maternal and neonatal plasma. Pregnant women ( n = 230) were prospectively enrolled and classified as unvaccinated ( n = 103) and vaccinated ( n = 127); after serological screening for previous infections, assays were performed on 126 dyads, 15 mothers and 17 newborns. Positive anti-S antibodies were found in most of the vaccinated subjects, regardless of timespan between immunization and delivery (range: 7-391 days). A total of 89 of 92 vaccinated women showed a broad response to COVID-19 immunization and highly effective placental transfer, as attested by anti-S positive rates (maternal = 96.7%, cord = 96.6%). Most of our subjects had indeterminate results in an IGRA assay, preventing a conclusive evaluation of IFN-γ production. Indeed, pregnancy-related hormonal changes may influence T-cell response with an impact on IFN-γ production. Positive pregnancy and perinatal outcomes reinforce the evidence that the anti-SARS-CoV-2 immunization is effective and well-tolerated in pregnant women and also protective for the fetus/neonate, even though it was not possible to define the related IFN-γ production and role.

During female lifetime and pregnancy, inflammation and cellular senescence are implicated in physiological processes, from ovulation and menstruation, to placental homeostasis and delivery. Several lifestyles, nutritional, and environmental insults, as well as long-lasting pregestational inflammatory diseases may lead to detrimental effects in promoting and sustaining a chronic excessive inflammatory response and inflammaging, which finally contribute to the decay of fertility and pregnancy outcome, with a negative effect on placental function, fetal development, and future health risk profile in the offspring. Maladaptation to pregnancy and obstetric disease may in turn increase maternal inflammaging in a feedback loop, speeding up aging processes and outbreak of chronic diseases. Maternal inflammaging may also impact, through transgenerational effects, on future adult health. Hence, efficacious interventions should be implemented by physicians and healthcare professionals involved in prevention activities to reduce the modifiable factors contributing to the inflammaging process in order to improve public health., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Among 733 pregnant women with HIV followed between 2013 and 2021, only 8 (1.1%) had prior HPV vaccination. One had low-grade squamous intraepithelial lesions [LSIL], and none had HPV type information. Among the 725 non-vaccinated women, 578 (79.7%) had information on cervical cytology. Rate of cytologic abnormalities in this group was 20.6% (0.2% atypical glandular cells of undetermined significance [AGC], 1.7% atypical squamous cells of undetermined significance [ASC-US], 11.1% LSIL, and 7.6% high-grade squamous intraepithelial lesions [HSIL]). Among 56 women with HPV type information, 75.0% carried high risk types, with similar occurrence in women with and without cytologic abnormalities, 30.4% had multiple high-risk types, and 75.9% carried at least one of the types included in the currently recommended 9-valent vaccine., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV., Methods: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses., Results: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111-0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082-5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690-6.900)., Conclusion: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

SARS-CoV-2 infection has been related to adverse pregnancy outcomes. A placental role in protecting the fetus from SARS-CoV-2 infection has been documented. Nevertheless, it is still unclear how the placenta is affected in SARS-CoV-2 infection. Here we assessed placental mitochondrial (mt) and oxidative features in COVID-19 and healthy mothers. mtDNA levels, DNA oxidative damage, expression levels of genes involved in antioxidant defenses, mitochondrial dynamics and respiratory chain subunits were investigated in placentas from singleton pregnancies of 30 women with SARS-CoV-2 infection during the third trimester (12 asymptomatic, 18 symptomatic) and 16 controls. mtDNA levels decreased in COVID-19 placentas vs. controls and inversely correlated with DNA oxidative damage, which increased in the symptomatic group. Antioxidant gene expressions decreased in SARS-CoV-2 mothers ( CAT , GSS ). Symptomatic cases also showed a lower expression of respiratory chain ( NDUFA9 , SDHA , COX4I1 ) and mt dynamics ( DNM1L , FIS1 ) genes. Alterations in placental mitochondrial features and oxidative balance in COVID-19-affected mothers might be due to the impaired intrauterine environment, generated by systemic viral effects, leading to a negative vicious circle that worsens placental oxidative stress and mitochondrial efficiency. This likely causes cell homeostasis dysregulations, raising the potential of possible long-term effects.

Overweight and obesity during pregnancy have been associated with increased birth weight, childhood obesity, and noncommunicable diseases in the offspring, leading to a vicious transgenerational perpetuating of metabolic derangements. Key components in intrauterine developmental programming still remain to be identified. Obesity involves chronic low-grade systemic inflammation that, in addition to physiological adaptations to pregnancy, may potentially expand to the placental interface and lead to intrauterine derangements with a threshold effect. Animal models, where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS) resembling the obesity-induced immune profile, showed increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. Cytokine levels might be specifically important for the metabolic imprinting, as cytokines are transferable from maternal to fetal circulation and have the capability to modulate placental nutrient transfer. Maternal inflammation may induce metabolic reprogramming at several levels, starting from the periconceptional period with effects on the oocyte going through early stages of embryonic and placental development. Given the potential to reduce inflammation through inexpensive, widely available therapies, examinations of the impact of chronic inflammation on reproductive and pregnancy outcomes, as well as preventive interventions, are now needed.

Background: Breastfeeding has effects on health throughout the lives of mothers and babies. In 2014 in Italy, 10,976 babies were born through ART (assisted reproductive technology), accounting for 2.2% of annual births. The study aims to assess how both social and biological variables and the mode of conception influence breastfeeding., Methods: This observational study involves 161 pregnancies from three different modes of conception: homologous in vitro fertilization, ovum donation, and spontaneous pregnancies. Neonatal and maternal characteristics were collected from the hospital database, while breastfeeding outcomes were obtained through telephone interviews., Results: The mode of conception did not influence any of the breastfeeding outcomes. Breastfeeding duration was negatively affected by smoking. Vaginal delivery, birth weight > 2500 g, delivery > 37 gestational weeks, breastfeeding intention, and rooming-in are positively associated with the initiation of breastfeeding, while skin-to-skin contact and receiving information concerning breastfeeding are the most significant variables associated with its exclusivity and duration., Conclusions: The duration and exclusivity of breastfeeding are mainly related with information thereon, promotion, and breastfeeding support, but not with the mode of conception. It is essential to adequately support women from the outset in breastfeeding, as recommended by the World Health Organization (WHO) guidelines.

Obesity is becoming pandemic and is associated with impaired reproductive potential. Oxidative stress, low-grade chronic inflammation and mitochondrial dysfunctions, which characterize obesity, strongly affect oocyte environment and function. Supplementation with antioxidant and anti-inflammatory compounds has been suggested to improve fertility. Here we evaluated the effect of α-lipoic acid and myo-inositol supplementation on the oocyte environment of infertile obese women. Nineteen normal-weight and twenty-three obese women, infertile for non-ovarian reasons, were recruited. For two months before ovarian stimulation, all women received 400 μg/die folic acid, whereas 15 obese were additionally supplemented with 800 mg α-lipoic acid, 2 g myo-inositol/die. Antioxidant capacity was measured in follicular fluid by enzymatic assay; mitochondrial DNA (mtDNA) content and mRNA levels of two respiratory chain subunits were analyzed in granulosa cells by Real-time PCR. Pregnancy rate was similar between normal-weight and treated obese, and lower in untreated obese patients. Supplemented women showed significantly higher antioxidant levels in follicular fluid compared to the two groups taking only folic acid. Conversely, granulosa cells mtDNA content was decreased in treated and higher in untreated obese patients compared to normal-weight women, suggesting mtDNA increases to compensate for oxidative-stress damages. Reduced expression of respiratory subunits in untreated obese may confirm mitochondria impairment. Interestingly, mtDNA levels inversely correlated to both total and metaphase II oocyte number. In this preliminary study, combined supplementation of α-lipoic acid and myo-inositol in infertile obese women was associated with amelioration in the oxidative status of the oocyte environment, possibly contributing to a higher pregnancy rate., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Objectives: 1. To assess the performance of an extended questionnaire in identifying cases of SARS-CoV-2 infection among obstetric patients. 2. To evaluate the rate of infection among healthcare workers involved in women's care., Study Design: A prospective cohort study of obstetric patients admitted to MBBM Foundation and Buzzi Hospital (Lombardy, Northern Italy) from March 16th to May 22nd, 2020. Women were screened on admission by a questionnaire investigating major and minor symptoms of infection and high-risk contacts in the last 14 days. SARS-CoV-2 assessment was performed by RT-PCR on nasopharyngeal swabs. Till April 7th, a targeted SARS-CoV-2 testing triggered by a positive questionnaire was used; from April 8th, a universal testing approach was implemented., Results: There were 1,177 women screened by the questionnaire, which yielded a positive result in 130 (11.0%) cases. SARS-CoV-2 RT-PCR was performed in 865 (73.5%) patients, identifying 51 (5.9%) infections. During the first period, there were 29 infected mothers, 4 (13.8%) of whom had a negative questionnaire. After universal testing implementation, there were 22 (3%, 95% CI 1.94% - 4.04%) infected mothers, 13 (59.1%) of whom had a negative questionnaire; rate of infection among asymptomatic women was 1.9%. Six of the 17 SARS-CoV-2-positive women with a negative questionnaire reported symptoms more than 14 but within 30 days before admission. Isolated olfactory or taste disorders were identified in 15.7% of infected patients. Rate of infection among healthcare workers was 5.8%., Conclusions: An exhaustive triage questionnaire can effectively discriminate women at low risk of SARS-CoV-2 infection in the context of a targeted and a universal viral testing approach. In 15.7% of infected women, correct classification as a suspected case of infection was due to investigation of olfactory and taste disorders. Extension of the assessed time-frame to 30 days may be worth considering to increase the questionnaire's performance., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the clinical evolution of coronavirus disease 2019 (COVID-19) in hospitalized pregnant women and potential factors associated with severe maternal outcomes., Methods: We designed a prospective multicenter cohort study of pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were admitted to 12 Italian maternity hospitals between February 23 and March 28, 2020. Clinical records, laboratory and radiologic examinations, and pregnancy outcomes were collected. A subgroup of patients with severe disease was identified based on intensive care unit (ICU) admission, delivery for respiratory compromise, or both., Results: Seventy-seven patients were included, 14 of whom had severe disease (18%). Two thirds of the patients in the cohort were admitted during the third trimester, and 84% were symptomatic on admission. Eleven patients underwent urgent delivery for respiratory compromise (16%), and six were admitted to the ICU (8%). One woman received extracorporeal membrane oxygenation; no deaths occurred. Preterm delivery occurred in 12% of patients, and nine newborns were admitted to the neonatal intensive care unit. Patients in the severe subgroup had significantly higher pregestational body mass indexes (BMIs) and heart and respiratory rates and a greater frequency of fever or dyspnea on admission compared with women with a nonsevere disease evolution., Conclusion: In our cohort, one in five women hospitalized with COVID-19 infection delivered urgently for respiratory compromise or were admitted to the ICU. None, however, died. Increased pregestational BMI and abnormal heart and respiratory rates on admission were associated with severe disease.

This study investigated the associations between maternal adherence to a healthy diet, first trimester placental markers, and pregnancy outcome. Singleton spontaneous pregnancies were enrolled at 11 +0 -13 +6 gestational weeks in a prospective cohort study. A nutritional score (0-10) measuring the adherence to a healthy diet was calculated. A transabdominal ultrasound scan for placental marker assessment was performed (uterine artery (UtA) doppler, placental volume). Biochemical placental markers were recorded (Pregnancy Associated Plasma Protein A (PAPP-A), free β- Human Chorionic Gonadotropin (HCG)). Birth outcomes were obtained from medical records. Associations between the maternal nutritional score, first trimester placental markers, and pregnancy outcome were investigated by using multi-adjusted general linear models. In total, 112 pregnancies were enrolled with a median nutritional score of 7 (range 3-10). Median gestational age at birth was 277 days (range 203-296). The nutritional score was positively associated with PAPP-A concentrations, whereas a negative association was detected with the UtA mean pulsatility index and placental volume. A positive association was detected between nutritional score and gestational age at birth. This study demonstrates that a first trimester nutritional score as a measure of adherence to a healthy diet is significantly associated with early biochemical and ultrasound markers of placental development, with further association with gestational age at birth.

Background: No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes., Methods: Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses., Results: Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4 + T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65)., Conclusions: No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

Background: Few studies have evaluated in pregnant women with HIV the prevalence of smoking and its associations with maternal and neonatal outcomes. Objectives: to assess the prevalence of smoking among women with HIV in early pregnancy and the association between smoking and pregnancy outcomes in this particular population. Methods: We used data from a multicenter observational study to define the prevalence of smoking in women with HIV in early pregnancy, and the role of smoking status and intensity as risk factors for adverse maternal and neonatal outcomes. Main outcome measures were fetal growth restriction [FGR], preterm delivery [PD] and low birthweight [LB], evaluated in univariate and multivariate analyses. Results: The overall (2001-2018) prevalence of reported smoking (at least one cigarette/day) was 25.6% (792/3097), with a significant decrease in recent years (19.0% in 2013-2018). Women who smoked were less commonly African, had lower body mass index, older age, a longer history of HIV infection and higher CD4 counts. In univariate analyses, smokers were significantly more likely to have PD, LB, FGR and detectable HIV viral load at third trimester. Multivariable analyses confirmed for smokers a significantly higher risk of LB (adjusted odds ratio [AOR]: 1.69, 95%CI 1.22-2.34) and FGR (AOR 1.88, 95%CI 1.27-2.80), while the associations with detectable HIV and PD were not maintained. Conclusions: The common prevalence of smoking among pregnant women with HIV and its association with adverse outcomes indicates that smoking cessation programs in this population may have a significant impact on neonatal and maternal health.

Introduction: The role of ultrasound imaging in urogynecology is not defined. Significant developments in visualization techniques and interpretation of images allowed to study structures of the lower genitourinary tract and pelvic floor., Evidence Acquisition: PubMed and Scopus database were searched for publications on the following item: stress urinary incontinence, ultrasound, perineal ultrasound and preoperative and postoperative assessment., Evidence Synthesis: The role of ultrasound in urogynecology could be helpful in diagnosing of urinary incontinence and urethral hypermobility, to document pelvic floor anatomy and to assess anatomic and functional changes before and after surgery., Conclusions: Ultrasound could be an important step during preoperative and post-operative assessment of patients affected by stress urinary incontinence.

Background: Pregnancy hormonal milieu represents a crucial determinant of fetal outcome. We aim to determine 17β-estradiol (E 2 ) and progesterone (PGT) concentrations in spontaneous pregnancies during the first trimester. In addition, we aim to determine E 2 concentrations as a function of gestational age (GA) and PGT., Methods: Between November 2015 and March 2017, 104 healthy women of at least 18 years undergoing medical consultation for voluntary interruption of pregnancy were enrolled in an observational study at University Hospital ASST Fatebenefratelli Sacco, Milan, Italy. Only singleton pregnancies between 5 +0 and 13 +6 weeks of gestation were eligible. First trimester ultrasound scans were performed for dating and one fasting venous blood sample was collected for E 2 and PGT determinations., Results: E 2 and PGT concentrations steadily increased according to GA. The correlation between E 2 on a logarithmic scale and PGT concentrations was expressed by the following equation, explaining 12.6% of E 2 variance: logE 2  = 2.57 + 0.1 × PGT, (r = 0.34, p < 0.001). By performing a multivariable linear regression analysis adjusted for variables significantly correlated with E 2 concentrations, we obtained a model explaining the 53.5% of E 2 variance. The final equation to determine E 2 concentrations among Caucasian women was: logE 2  = 1.96 + 0.01 × GA + 0.004 × PGT., Conclusions: Gestational week-specific reference intervals are reported for maternal E 2 and PGT concentrations during early pregnancy, further providing a model for E 2 assessment in this period. This will represent a starting point for further evaluations between twin and ART pregnancies, as well as to potentially improve pregnancy outcome and future health of the offspring.

Pregnancy represents a period of major physiological and metabolic change, aiming to ensure proper fetal growth and development, as well as maternal preservation. This review focuses on maternal nutrition, and particularly on micronutrient deficiencies and supplementation during pregnancy. Nutrient deficiencies and consequences in pregnant women are presented, with an overview of current recommendations for dietary supplementation in pregnancy, even considering the risk of micronutrient overload. Appropriate universal supplementation and prophylaxis/treatment of nutritional needs currently appear to be the most cost-effective goal in low-income countries, thus ensuring adequate intake of key elements including folate, iron, calcium, vitamin D and A. In high-income countries, a proper nutritional assessment and counselling should be mandatory in obstetric care in order to normalize pregestational body mass index, choose a healthy dietary pattern and evaluate the risk of deficiencies.

Introduction: Metabolomics identifies phenotypical groups with specific metabolic profiles, being increasingly applied to several pregnancy conditions. This is the first preliminary study analyzing placental metabolomics in normal weight (NW) and obese (OB) pregnancies., Methods: Twenty NW (18.5 ≤ BMI< 25 kg/m 2 ) and eighteen OB (BMI≥ 30 kg/m 2 ) pregnancies were studied. Placental biopsies were collected at elective caesarean section. Metabolites extraction method was optimized for hydrophilic and lipophilic phases, then analyzed with GC-MS. Univariate and PLS-DA multivariate analysis were applied., Results: Univariate analysis showed increased uracil levels while multivariate PLS-DA analysis revealed lower levels of LC-PUFA derivatives in the lipophilic phase and several metabolites with significantly different levels in the hydrophilic phase of OB vs NW., Discussion: Placental metabolome analysis of obese pregnancies showed differences in metabolites involved in antioxidant defenses, nucleotide production, as well as lipid synthesis and energy production, supporting a shift towards higher placental metabolism. OB placentas also showed a specific fatty acids profile suggesting a disruption of LC-PUFA biomagnification. This study can lay the foundation to further metabolomic placental characterization in maternal obesity. Metabolic signatures in obese placentas may reflect changes occurring in the intrauterine metabolic environment, which may affect the development of adult diseases., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Magnesium (Mg) and calcium (Ca) are essential cations for women's preconception health. It is well known that, in blood, the concentration of ionized form of these two cations is temporally altered during menstrual cycle, suggesting a correlation between sex steroid hormones and serum calcium and magnesium levels. Evidence from literature suggests that in assisted reproductive technology increasing estrogens during ovarian hyperstimulation may also modulate serum magnesium and calcium levels. Therefore, we first examined total serum magnesium and calcium levels during follicular phase in a large population of infertile patients who underwent intrauterine insemination (IUI). The results were compared to a group of fertile women. Successively, we studied the total serum magnesium and calcium concentrations in infertile patients before and after ovarian hyperstimulation for in vitro fertilization (IVF). Results highlight that total serum concentration of magnesium and calcium does not seem altered in infertile women. During stimulation with gonadotropins, the values of the two cations do not change significantly in ovarian-stimulated women. However, we found a downward trend in the total magnesium and calcium levels in relation to the rising estrogens.

Background: Since the first successful use of donated oocytes in 1984, the number of oocyte donation cycles in Europe and the USA has dramatically increased. Consequently, there has been increasing interest in the impact of oocyte donation on maternal and fetal outcomes., Objective and Rationale: The aim of this review was to summarize the literature regarding maternal and fetal outcomes from pregnancies conceived through oocyte donation., Search Methods: Identification of relevant publications was through research within the Embase Medline and PubMed databases, the Google-indexed scientific literature and periodic specialized magazines from the on-line Library Service of the University of Milan., Outcomes: Oocyte donation seems to be independently associated with a higher rate of pregnancy-induced hypertension and pre-eclampsia. An explanatory hypothesis is that an immunological maladaptation causes placenta-mediated disorders in oocyte donation pregnancies. The risks are even higher in twin pregnancies. Oocyte donation also seems to be associated with lower fetal birthweight. However, after adjusting for obstetric complications, most studies report less pronounced differences in birthweight or no dissimilarities. The incidence of cesarean section is increased without clear clinical indications., Wider Implications: Oocyte donation pregnancies are associated with a higher rate of placental disorders of pregnancy, such as gestational hypertension and pre-eclampsia. The risk of poorer neonatal outcomes is increased in oocyte donation pregnancies compared to other in-vitro fertilization pregnancies. Poorer outcomes have been demonstrated especially for twin pregnancies and in association with previous chronic pathologies or the development of obstetrics complications., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: This study investigates the hypothesis that placenta works differently in oocyte donation (OD) compared to spontaneous pregnancies. To verify this hypothesis we examine the first trimester maternal serum levels of free β-hCG and pregnancy-associated plasma protein-A (PAPP-A). Then we evaluated for potential differences of Down syndrome screening between OD pregnancies, in vitro fertilization/intracytoplasmic sperm injection pregnancies with autologous oocytes (IVF/ICSI) and spontaneous pregnancies., Methods: We analyze 13624 spontaneously conceived pregnancies (Controls), 171 oocyte donation pregnancies (OD IVF/ICSI) and 76 IVF pregnancies with autologous oocytes (Autologous IVF/ICSI). Furthermore, we collect a cohort of 802 spontaneously conceived age-matched pregnancies, in order to evaluate how older uteri contribute to explain the changes in markers concentrations (Age-matched controls We compare the multiples of the median (MoM) of free β-hCG and PAPP-A and nuchal translucency., Results: Free β-hCG levels are significantly higher both in OD IVF/ICSI pregnancies (1.44 ± 1.06 MoM) and Autologous IVF/ICSI (1.48 ± 1.02 MoM) compared to Controls (1.15 ± 0.84 MoM; p < 0.05) and Age-matched Controls (1.18 ± 0.98 MoM; p < 0.05). PAPP-A levels do not significantly differ among the four groups. Significantly lower nuchal translucency is detected in Controls (1.41 ± 0.36 mm) compared to OD IVF/ICSI (1.46 ± 0.44 mm; p < 0.05), in Autologous IVF/ICSI (1.51 ± 0.34 mm; p < 0.05) and Age-matched Controls (1.44 ± 0.42 mm; p < 0.05)., Discussion: Oocyte donation pregnancies (OD IVF/ICSI) are significantly related to altered maternal serum placenta marker levels. These alterations might be due to the IVF technique., (Copyright © 2015 Elsevier Ltd. All rights reserved.)