The natural evolution of untreated deep endometriosis and the effect of hormonal suppression: A systematic literature review and meta-analysis.

INTRODUCTION: Peritoneal infiltrating and fibrotic endometriosis, also known as deep endometriosis, is the most severe manifestation of the disease that can cause severe complications including bowel and ureteral stenosis. The natural history of these lesions and the possible effect of hormonal treatments on their progression are undefined. Therefore, we conducted a systematic review and meta-analysis to investigate whether and how frequently deep endometriosis progresses over time without or with ovarian suppression. This could inform management decisions in asymptomatic and mildly symptomatic patients. MATERIAL AND METHODS: For this pre-registered systematic review (CRD42023463518), the PubMed and Embase databases were screened, and studies published between 2000 and 2023 that serially evaluated the size of deep endometriotic lesions without or with hormonal treatment were selected. Data on the progression, stability, or regression of deep endometriotic lesions were recorded as absolute frequencies or mean volume variations. Estimates of the overall percentage of progression and corresponding 95% confidence intervals were calculated using a random-effect model. When studies reported lesion progression as pre- and post-treatment volume means, the delta of the two-volume means was calculated and analyzed using the inverse variance method. RESULTS: A total of 29 studies were identified, of which 19 studies with 285 untreated and 730 treated patients were ultimately selected for meta-analysis. The overall estimate of the percentage of lesion progression in untreated individuals was 21.4% (95% CI, 6.8-40.8%; I2 = 90.5%), whereas it was 12.4% during various hormonal treatments (95% CI, 9.0-16.1%; I2 = 0%). Based on the overall meta-analysis estimates, the odds ratio of progression in treated vs untreated patients was 0.52 (95% CI, 0.41-0.66). During hormonal suppression, the mean volume of deep endometriotic lesions decreased significantly by 0.87 cm3 (95% CI, 0.19-1.56 cm3; I2 = 0%), representing -28.5% of the baseline volume. CONCLUSIONS: Untreated deep endometriotic lesions progressed in about one in five patients. Medical therapy reduced but did not eliminate this risk. Given the organ function failure potentially caused by these lesions, the decision whether to use hormonal treatments in asymptomatic or mildly symptomatic women should always be shared, carefully weighing the potential benefits and harms of the two alternatives after extensive counseling.

Probability of second live birth after first natural and medically assisted reproduction-mediated live birth: A historical cohort study.

INTRODUCTION: Evidence on the role of medically assisted reproduction (MAR) in achieving the desired number of children is very limited. The aim of the current investigation was to assess the probability and the mode of conception of a second live birth according to the mode of conception of the first one. MATERIAL AND METHODS: This historical cohort study was based on administrative data from regional healthcare databases. Women hospitalized for childbirth in Lombardy between January 1, 2007 and December 31, 2017 were identified. The probability of a second live birth up to 2021 was estimated using the Kaplan-Meier method. We calculated this probability according to the mode of conception of the first birth, and the analysis was also performed in strata of maternal age at first birth. Cox proportional hazards models were fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between mode of conception at first live birth and the probability of having a second live birth. Mothers were right-censored if they moved out of the region, died, or did not have a second live birth by the end of follow-up. RESULTS: We identified 431 333 women who had their first live birth after a natural conception and 16 837 who had their first live birth after MAR. The probability of having a second live birth was 58.6% and 32.1%, respectively in the two groups (HR = 0.68, 95% CI: 0.66-0.70). Considering solely women who naturally conceived their first live birth, the probability to have a second child with MAR was 1.1% and to have a second child naturally 59.3%. The corresponding values were 11.5% and 25.2% in the group of women with a first MAR-mediated live birth. CONCLUSIONS: In our cohort, one woman out of 10 having a first MAR-mediated live birth underwent MAR programs again. Considering women who had a first natural live birth, this proportion was drastically reduced. In the field of MAR, more attention should be given to the capacity of a couple to achieve the number of desired children.

Adherence to the Mediterranean diet and the risk of unexpected poor response to ovarian stimulation in IVF cycles.

RESEARCH QUESTION: Can preconception adherence to a Mediterranean diet influence the rate of poor response to ovarian stimulation in IVF cycles? DESIGN: The impact of dietary habits on the success of IVF is controversial. Inconsistencies may be explained by confounders associated with the use of pregnancy as an outcome as well as by a reductionist view of diet that focuses on single components rather than on food patterns. This cross-sectional study analysed adherence to a Mediterranean diet in women with unexpected poor response to ovarian stimulation. Main inclusion criteria were: age 18-39 years, normal weight, preserved ovarian reserve and starting dose of gonadotrophins of 150-225 IU/day. Adherence to the Mediterranean diet was assessed through a Mediterranean diet score (MDS). Unexpected poor ovarian response was defined as the retrieval of ≤3 suitable oocytes. RESULTS: A total of 296 women were included, of whom 47 (15.9%) showed an unexpected poor response. A clear dose-related association with tertiles of MDS was not observed in the univariate analysis. However, in the multivariate analysis, the risk of unexpected poor response was significantly lower for women in the second tertile of MDS compared with the first tertile (adjusted odds ratio [OR] 0.29, 95% confidence interval [CI] 0.11-0.76) and for women in the second and third tertiles, grouped together, compared with the first tertile (adjusted OR 0.34, 95% CI 0.14-0.82). CONCLUSIONS: Low adherence to a Mediterranean diet could be a risk factor for unexpected poor ovarian response.

High-grade vaginal intraepithelial neoplasia and recurrence risk: analysis of an Italian regional referral center series.

PURPOSE: The main aim of this study was to investigate the long-term risk of disease recurrence in women treated for high-grade vaginal intraepithelial neoplasia (HG-VaIN). METHODS: We conducted a retrospective analysis on a cohort of 82 women diagnosed with HG-VaIN between 2010 and 2021 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. All women underwent either ablative treatment (CO2 laser ablation or electrocoagulation) or cold-knife excision. RESULTS: In our series, the recurrence rate following treatment was 17%. The 5-year cumulative probability of recurrence was 30.4% and the median time to recurrence was 15.5 months. None of the patients progressed to invasive vaginal cancer during follow-up. A concomitant cervical or vulvar intraepithelial lesion was significatively associated with an increased risk of recurrence (p = 0.006). CONCLUSIONS: The results of our study suggest that women with HG-VaIN are at high risk of developing disease recurrence after treatment, especially patients with a concomitant cervical or vulvar intraepithelial lesion. In these women strict monitoring is mandatory to obtain an early identification of recurrence.

Fat Grafting in Vulvar Lichen Sclerosus: Long Term Follow-Up.

OBJECTIVE: The rationale for the use of autologous fat grafting in the treatment of vulvar lichen sclerosus (VLS) consists in reduction of inflammation, regeneration of tissues, volume increase, and pain fiber control. The main outcome of this study was the evaluation of patients' satisfaction after treatment. Secondary outcomes included modifications in symptoms, psychosexual wellbeing, vulvar hydration, and histology after surgery. METHODS: Eligible for this study were women aged 18-85 years with a histological diagnosis of VLS who underwent at least one autologous vulvar fat grafting at the authors' center, between 2010 and 2019. In 2021, all women underwent a clinical reevaluation, comprehensive of vulvoscopy, vulvar biopsy, and handing out of validated questionnaires. RESULTS: Overall, 88.7% of patients declared themselves very satisfied/satisfied with the procedure. All symptoms were improved postsurgery; in particular, the difference was statistically significant for pruritus, burning, and dyspareunia ( p < .05). Sexual function was also improved at time of reevaluation, as were depressive and anxiety symptoms ( p < .05). No cases of vulvar intraepithelial neoplasia or cancer occurred during follow-up and vulvar architecture remained stable, although patients reported a significantly reduced need for topical steroids ( p < .0001). Lastly, in postoperative biopsies, inflammatory infiltrate was stable or reduced, and the distribution of elastic fibers was comparable or restored in most patients. CONCLUSIONS: Patient satisfaction with fat grafting is detectable up to 11 years after surgery, and as such, it may represent a valid therapeutic option in selected cases of VLS.

The role of maternal age on the risk of preterm birth among singletons and multiples: a retrospective cohort study in Lombardy, Norther Italy.

BACKGROUND: All over the world, especially in the developed countries, maternal age at birth is rising. This study aimed to assess the role of maternal age on the occurrence of preterm birth (PTB) in a large birth cohort of Lombardy Region, Northern Italy. METHODS: This population-based study used data from regional healthcare utilization databases of Lombardy to identify women who delivered between 2007 and 2017. PTBs were defined as births before 37 completed weeks of gestation and considered according to the gestational age (two categories: < 32 weeks and 32 to 36 weeks). Six maternal age groups were defined (< 20, 20-24, 25-29, 30-34, 35-39, ≥40 years). Logistic regression models were fitted to estimate the crude and adjusted odds ratio (aOR) and the corresponding 95% confidence interval (CI) for PTB among different maternal age groups. Analyses were separately performed according to type of pregnancy (singletons and multiples). Reference group was the age group with the lowest frequency of PTB. RESULTS: Overall, 49,759 (6.6%) PTBs were observed, of which 41,807 were singletons and 7952 were multiples. Rates of PTB were lowest in the women aged 25-29 years among singletons and in the 30-34 years old group among multiples. Our results described a U-shaped association between maternal age and risk of PTB. In particular, the risk of a singleton PTB between 32 and 36 weeks was significantly higher for women aged less than 20 years (aOR = 1.16, CI 95%: 1.04-1.30) and more than 40 years (aOR = 1.62 CI 95%: 1.54-1.70). The highest risk of a multiple delivery between 32 and 36 weeks was observed among women aged less than 25 years and more than 40 years (aOR = 1.79, CI 95%: 1.01-3.17, aOR = 1.47, CI 95%: 1.16-1.85 and aOR = 1.36, CI 95%: 1.19-1.55 respectively for < 20, 20-24 and > 40 age categories). PTB before 32 completed weeks occurred more frequently in the same age categories, except that among multiples no association with advanced maternal age emerged. CONCLUSION: Our study suggested that, after adjustment for potential confounders, both advance and young maternal age were associated with an increased risk of PTB.

Trends in Dizygotic and Monozygotic Spontaneous Twin Births During the Period 2007-2017 in Lombardy, Northern Italy: A Population-Based Study.

In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007-2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg's method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007-2010, 2011-2014 and 2015-2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.

Fatty acids intake and outcomes of assisted reproduction in women referring to an Italian Fertility Service: cross-sectional analysis of a prospective cohort study.

BACKGROUND: Infertility affects 15% of couples in Italy and approximately 10%-12% of couples worldwide. Focusing on female fertility, there are multiple causes, among which diet has a great influence. METHODS: We investigated whether the consumption of certain fatty acids affects four outcomes of the assisted reproduction techniques. From September 2014 to December 2016, women referring to our Italian fertility unit, eligible for assisted reproduction techniques, were invited to participate. Information on diet was recorded through a validated food frequency questionnaire. RESULTS: Four hundred and ninety-four women were included, of whom 95% achieved good quality oocytes, 87% achieved embryo transfer, 32.0% achieved clinical pregnancies and 24.5% achieved pregnancy at term. The fourth quartile of saturated fatty acids consumption, compared to the first one, showed an association with clinical pregnancy (adjusted relative risk 0.67, 95% confidence interval 0.45-1.00, p = 0.0491). Some associations emerge accounting for confounders. Age was associated with clinical pregnancy and pregnancy at term in the models considering all fatty intakes and food groups variables but was not associated with oocytes quality and embryo transfer. Physical activity was associated with clinical pregnancy. CONCLUSIONS: There is biological plausibility for the effect of omega-3 and omega-6 polyunsaturated fatty acids on oocyte development via synthesis of eicosanoids, even if only limited associations are shown in the present study. Future research should aim to measure the serum levels of fatty acids and investigate the outcomes of assisted reproduction techniques.

Endometriosis and irritable bowel syndrome: a systematic review and meta-analysis.

PURPOSE: Irritable bowel disease and endometriosis are two common diseases characterized by chronic inflammation state and recurrent abdominal pain. As a consequence of sharing of symptoms and chronic inflammation, endometriosis and IBS may coexist and be misdiagnosed and this leads to delays in diagnosis, mismanagement, and unnecessary testing. In recent years, some studies have found higher risk of IBS in women with endometriosis, compared to women without endometriosis. To provide a general overview, we performed a systematic review and a meta-analysis on published data on this issue. METHODS: By a systematic literature search selection process, 11 studies were identified for the current study: 2 prospective and 2 retrospective cohort studies, 4 case-control studies, 1 cross-sectional study and 2 clinical series. RESULTS: When we meta-analysed data about the prevalence of IBS in women with endometriosis, the overall OR (95%CI), compared to women without endometriosis was 3.26 (1.97-5.39) with no statistically significant heterogeneity. All three studies considering the incidence of IBS in women with a previous diagnosis of endometriosis showed about twofold greater risk among women with endometriosis than women without. Likewise, in the random effects model of the meta-analysis, the overall OR of history of IBS in women with endometriosis was 3.10 (95% CI 2.06-4.67), with no heterogeneity between three studies considered. CONCLUSION: This meta-analysis provides epidemiological evidence of a link between endometriosis and IBS, highlighting two or more times higher risk of IBS in women with endometriosis compared to women without the condition.

The "CIV Classification," a New Proposal for the Architectural Grading of Vulvar Lichen Sclerosus.

OBJECTIVES: The purpose of this cross-sectional study was to prepare a reliable and easy-to-use architectural classification for vulvar lichen sclerosus (VLS) aimed at defining the morphological patterns of this condition. MATERIALS AND METHODS: An expert panel composed by 7 physicians with expertise in clinical care of vulvar conditions outlined the architectural criteria for the definition of VLS severity (phimosis of the clitoris, involvement of the interlabial sulci, narrowing of the vulvar introitus), identifying 5 grades to build up a classification. Thirteen physicians with 2-30 years expertise in vulvar diseases (nonexpert group) were asked to evaluate 3-5 pictures from 137 patients. Each physician individually assigned a grade to each case, according to the previously mentioned criteria. Interrater reliability was analyzed by means of intraclass correlation coefficient (ICC). The reliability concerning the 2 classifications of each rater was analyzed by means of κ statistic. Intraobserver and interobserver reliability in vivo was analyzed by means of κ index. RESULTS: This study provides a new classification of VLS, based on defined anatomical criteria and graded into mutually exclusive progressive classes.The ICC analysis showed a substantial interrater reliability of the classification, ICC = 0.89 (0.87-0.91), both in the expert panel and in the nonexpert group (ICC = 0.92 and 0.87, respectively). An "almost perfect" intraobserver and interobserver reliability was achieved among physicians in vivo (κ = 0.93). CONCLUSIONS: Our classification showed a high reliability. It is easy to use, and it can be applied in clinical practice and eventually, in the evaluation of regenerative and cosmetic surgery.

The role of diet in unexpected poor response to ovarian stimulation: a cross-sectional study.

RESEARCH QUESTION: Is there an association between diet and poor ovarian response to ovarian stimulation in women with normal biomarkers of ovarian reserve? DESIGN: Women eligible for IVF at an Academic Fertility Center were invited to participate in this prospective cross-sectional study. The main inclusion criteria were age 18-39 years, body mass index 18-25 kg/m2, preserved ovarian reserve (antral follicle count 10-22 or anti-Müllerian hormone concentration 2-5 ng/ml) and a starting dose of gonadotrophins of 150-225 IU/day. Information on diet was obtained using a validated food frequency questionnaire. 'Unexpected poor ovarian response' was defined as the retrieval of three or fewer suitable oocytes. A logistic regression model was used to adjust for confounders. RESULTS: Out of the 303 women enrolled in the study, 48 (16%) showed an unexpected poor ovarian response. The frequency of poor responders increased with increasing glycaemic load, carbohydrate intake and fibre intake. When comparing the third with the first tertile (reference), the adjusted odds ratios for these were 3.91 (95% confidence interval [CI] 1.11-13.83, P = 0.04), 4.78 (95% CI 1.23-18.51, P = 0.02) and 6.03 (95% CI 1.18-30.77, P = 0.07), respectively. CONCLUSIONS: Elevated dietary glycaemic load as well as carbohydrate intake and fibre intake is significantly associated with unexpected poor ovarian response. Future interventional studies should clarify whether dietary modification might restore normal response.

Fatty acids, food groups and semen variables in men referring to an Italian Fertility Clinic: Cross-sectional analysis of a prospective cohort study.

Diet has been suggested as a factor affecting sperm quality, both in healthy and infertile men. To study whether specific food groups and fatty acids (FA) intake were associated with sperm parameters of men from couples referring to an Italian Fertility Clinic, we conducted a cross-sectional analysis. A semen sample was collected and analysed before proceeding with assisted reproduction. To evaluate food groups and fatty acids intake, we used a questionnaire of food frequency. We calculated odds ratios (OR) and 95% confidence intervals (CI) for abnormal semen parameters. Among 323 men, 19% had semen volume (SV) <1.5 ml, 31% sperm concentration (SC) <15 mil/mL, 33% total sperm count (TSC) <39 mil and 27% sperm progressive motility <32%. Low SC was more frequent in men with higher saturated FA (SFA) and polyunsaturated FA (PUFA) intake. Better SC and TSC were related to higher monounsaturated FA (MUFA)/SFA ratio. Monounsaturated FA and linoleic/linolenic acid ratio were not related to any considered parameters. Low TSC was associated with low vegetable intake. In conclusion, normal sperm parameters were more frequent in men with low intake of SFA and PUFA, and high vegetable intake. Higher MUFA/SFA ratio was associated with better sperm quality parameters.

Mediterranean diet and outcomes of assisted reproduction: an Italian cohort study.

BACKGROUND: Detrimental lifestyle habits have been indicated as potential causes of reduced fertility. Recently studies have suggested an association between healthy diets and increased live birth rates after assisted reproduction techniques. However, the issue remains under debate, and evidence is still accumulating. OBJECTIVE: The objective of the study was to study the relationship between a Mediterranean diet and outcomes of assisted reproduction techniques in subfertile couples in an Italian population. STUDY DESIGN: This was a prospective cohort study, conducted in an Italian fertility clinic. Couples undergoing in vitro fertilization were interviewed on the day of oocyte retrieval to obtain information on personal and health history, lifestyle habits, and diet. Adherence to a Mediterranean diet was evaluated using a Mediterranean diet score. Relative risks and 95% confidence intervals for embryo transfer, clinical pregnancy, and live birth were calculated. Potential confounders were included in the equation model. RESULTS: Among 474 women (mean age, 36.6 years, range, 27-45), 414 (87.3%) performed embryo transfer, 150 (31.6%) had clinical pregnancies, and 117 (24.7%) had live births. In a model including the potential confounders (age, leisure physical activity, body mass index, smoking, daily calorie intake, and previous failed in vitro fertilization cycles), findings showed that the Mediterranean diet score was not significantly associated with in vitro fertilization outcomes. Adjusted analyses were performed in strata of age, previous assisted reproduction technique cycles, and reasons for infertility, with consistent findings. The only exception was observed in women >35 years old with an intermediate Mediterranean diet score, who showed a lower risk of not achieving clinical pregnancy (adjusted relative risk, 0.84, 95% confidence interval, 0.71-1.00, P = .049). CONCLUSION: No clear association was observed between adherence to a Mediterranean diet and successful in vitro fertilization.

Semen quality and alcohol intake: a systematic review and meta-analysis.

Alcohol consumption is widespread in the Western world. Some studies have suggested a negative association between alcohol intake and semen quality although others have not confirmed this. MEDLINE and Embase were searched using 'alcohol intake' OR 'alcohol consumption' OR 'alcohol drinking' OR 'lifestyle' combined with 'semen quality' OR 'sperm quality' OR 'sperm volume' OR 'sperm concentration' OR 'sperm motility' for full-length observational articles, published in English. Reference lists of retrieved articles were searched for other pertinent studies. Main outcome measures were sperm parameters, if provided as means (standard deviation or standard error) or as medians (interquartile range). Fifteen cross-sectional studies were included, with 16,395 men enrolled. Main results showed that alcohol intake has a detrimental effect on semen volume (pooled estimate for no/low alcohol consumption 0.25 ml, 95% CI, 0.07 to 0.42) and normal morphology (1.87%, 95% CI, 0.86 to 2.88%). The difference was more marked when comparing occasional versus daily consumers, rather than never versus occasional, suggesting a moderate consumption did not adversely affect semen parameters. Hence, studies evaluating the effect of changes on semen parameters on the reproductive outcomes are needed in advance of providing recommendations regarding alcohol intake other than the advice to avoid heavy alcohol drinking.

Coffee and caffeine intake and male infertility: a systematic review.

BACKGROUND: Semen quality, a predictor of male fertility, has been suggested declining worldwide. Among other life style factors, male coffee/caffeine consumption was hypothesized to influence semen parameters, but also sperm DNA integrity. To summarize available evidence, we performed a systematic review of observational studies on the relation between coffee/caffeine intake and parameters of male fertility including sperm ploidy, sperm DNA integrity, semen quality and time to pregnancy. METHODS: A systematic literature search was performed up to November 2016 (MEDLINE and EMBASE). We included all observational papers that reported the relation between male coffee/caffeine intake and reproductive outcomes: 1. semen parameters, 2. sperm DNA characteristics, 3. fecundability. All pertinent reports were retrieved and the relative reference lists were systematically searched in order to identify any potential additional studies that could be included. RESULTS: We retrieved 28 papers reporting observational information on coffee/caffeine intake and reproductive outcomes. Overall, they included 19,967 men. 1. Semen parameters did not seem affected by caffeine intake, at least caffeine from coffee, tea and cocoa drinks, in most studies. Conversely, other contributions suggested a negative effect of cola-containing beverages and caffeine-containing soft drinks on semen volume, count and concentration. 2. As regards sperm DNA defects, caffeine intake seemed associated with aneuploidy and DNA breaks, but not with other markers of DNA damage. 3. Finally, male coffee drinking was associated to prolonged time to pregnancy in some, but not all, studies. CONCLUSIONS: The literature suggests that caffeine intake, possibly through sperm DNA damage, may negatively affect male reproductive function. Evidence from epidemiological studies on semen parameters and fertility is however inconsistent and inconclusive. Well-designed studies with predefined criteria for semen analysis, subject selection, and life style habits definition, are essential to reach a consistent evidence on the effect of caffeine on semen parameters and male fertility.

Nuchal translucency measurement, free ß-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 (m0 MoM) 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. © 2017 John Wiley & Sons, Ltd.

Risk of Monozygotic Twins After Assisted Reproduction: A Population-Based Approach.

BACKGROUND: Recent studies have suggested that ovarian stimulation and assisted reproductive techniques (ART) may increase the frequency of monozygotic twins. In this article, we present the analysis of the estimated frequency of twin deliveries following in vitro fertilization (IVF) in Lombardy during the period 2010-2014 for a total of 450,949 pregnancies. METHOD: This is a population-based study using data from the regional data base of Lombardy, a northern Italian region with a population of about 10 million inhabitants. During the considered period, a total of 461,424 single or multiple births were registered in Lombardy. After exclusion of triplets or more pregnancies, the total number of twin deliveries, in separate strata of like and unlike sex pregnancies twin deliveries, were obtained and the rate of twin deliveries was computed according to spontaneous and non-spontaneous conception and type of ART. Further, estimates of dizygotic or monozygotic twin births were calculated using Weinberg's methods. RESULTS: The frequency of twins deliveries was 1.24/100 deliveries after natural conception and 20.05 after assisted conception. The estimated rates of monozygotic twins was 0.45 and 0.72/100 (95% CI: 0.58-0.91) deliveries after natural and assisted conception, respectively. This difference was statistically significant (p < .05). CONCLUSION: the present population based study suggests that the risk of monozygotic twin is about 60% higher among assisted than after natural conception.

The risk of birth defects after assisted reproduction.

PURPOSE: Aim of this study was to investigate the association between congenital malformations and type of conception (spontaneous or medically assisted). METHODS: This is a population based study using data from the regional data base of Lombardy, a Northern Italian Region with a population of about 10 million inhabitants. Included in the study were 277,043 neonates born in Lombardy during the study period 2010-2012. Adjusted and unadjusted odds ratios (OR), and corresponding 95% confidence intervals (CI), of congenital abnormalities were calculated using unconditional multiple logistic regression. RESULTS: A total of 7057 births (2.5%) were reported after non spontaneous conception. Overall, the frequency of birth defects was 4.4% among births after spontaneous conception and 6.7% among births after non spontaneous ones (OR = 1.67, 95%CI = 1.5-1.9). The association disappeared after taking into account the confounding effect of maternal age and factors associated with non spontaneous conception. The crude OR of abnormalities was higher than unity for any defect (OR = 1.67, 95%CI = 1.5-1.9), multiple defects (OR = 1.76, 95%CI = 1.3-2.3), cardiovascular (OR = 2.05, 95%CI = 1.8-2.4), musculoskeletal (OR = 2.05, 95%CI = 1.7-2.5) and metabolic system abnormalities (OR = 1.97, 95%CI = 1.1-3.5). Almost all these associations, however, disappeared after taking into account potential confounding with the exception of musculoskeletal defects (adjusted OR = 1.31, 95%CI = 1.1-1.6). In this case also, if adjustment for multiple comparison is taking into account, results did not reach statistical significance. CONCLUSIONS: The results of this analysis confirm the recently emerging view that the increased frequency of birth defects observed after ART/medically induced ovulation only is largely due to confounders.

Intimate partner violence and repeat induced abortion in Italy: A cross sectional study.

OBJECTIVE: To investigate the impact of intimate partner violence (IPV) on the risk of repeat induced abortion (RIA), we compared IPV history among women with and without previous induced abortion (IA). METHODS: All consecutive women aged 18 years or more requiring IA in 12 Italian abortion clinics were eligible for inclusion in the study. They were asked to fill in an anonymous, self-developed questionnaire assessing sociodemographic data and their history of different types of violence and related risk factors. RESULTS: The analysis included 1030 women, 624 (60.6%) of whom reported a previous IA. Past or current IPV was reported by 19.3%: 7.0% reported sexual violence, 11.3% physical abuse and 12.1% psychological abuse. Past or current IPV was reported by 22.3% of women with RIA and 14.8% of those undergoing their first IA (adjusted odds ratio 1.57, 95% confidence interval 1.07-2.30; p = 0.02). When we considered sexual, psychological and physical abuse separately, we found that any kind of abuse was more frequent in women with RIA than in women with no previous IA. CONCLUSION: This study underlines the impact of IPV on the risk of RIA and suggests the need for screening for IPV among women requiring abortion, in order to identify women at risk of RIA and to improve their general and reproductive health.