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.

Lifestyle and dietary factors, iron status and one-carbon metabolism polymorphisms in a sample of Italian women and men attending a Transfusion Medicine Unit: a cross-sectional study.

Iron (Fe) status among healthy male and female blood donors, aged 18-65 years, is estimated. General characteristics and lifestyle factors, dietary habits and major one-carbon metabolism-related polymorphisms were also investigated. An explorative cross-sectional study design was used to examine a sample of blood donors attending the Transfusion Medicine Unit of the Verona University Hospital, Italy. From April 2016 to May 2018, 499 subjects were enrolled (255 men, 244 women, 155 of whom of childbearing age). Major clinical characteristics including lifestyle, dietary habits and Fe status were analysed. The MTHFR 677C > T, cSHMT 1420C > T, DHFR 19bp ins/del and RFC1 80G > A polymorphisms were also assayed. Mean plasma concentrations of Fe and ferritin were 16·6 µmol/l (95 % CI 16·0, 17·2) and 33·8 µg/l (95 % CI 31·5, 36·2), respectively. Adequate plasma Fe concentrations (> 10·74 µmol/l) were detected in 84·3 % and adequate ferritin concentrations (20-200 µg/l) was found in 72·5 % of the whole cohort. Among the folate-related polymorphisms analysed, carriers of the DHFR 19bp del/del mutant allele showed lower ferritin concentration when compared with DHFR 19bp ins/del genotypes. In a sample of Italian healthy blood donors, adequate plasma concentrations of Fe and ferritin were reached in a large proportion of subjects. The relationship of Fe status with lifestyle factors and folate-related polymorphisms requires more investigation to clarify further gene-nutrient interactions between folate and Fe metabolism.

B vitamin blood concentrations and one-carbon metabolism polymorphisms in a sample of Italian women and men attending a unit of transfusion medicine: a cross-sectional study.

PURPOSE: To define blood status of folate, vitamin B12, vitamin B6, homocysteine, and major one-carbon metabolism-related polymorphisms in healthy, males and females blood donors, aged 18-65 years were evaluated. General characteristics and lifestyle factors were also investigated. METHODS: An explorative cross-sectional study design was used to evaluate a sample of blood donors attending the Unit of Transfusion Medicine of the Verona University Hospital, Italy. From April 2016 to May 2018, 499 subjects were enrolled (255 men, 244 women of whom 155 of childbearing age). Major clinical characteristics including lifestyle and dietary habits, B vitamins and homocysteine were analyzed. The MTHFR 677 C>T, cSHMT 1420 C>T, DHFR 19 bp ins/del, RFC1 80 G>A polymorphisms were also determined. RESULTS: Mean plasma concentrations of folate, vitamin B12, vitamin B6 and homocysteine were 14.2 nmol/L (95% CI 13.7-14.8), 271.9 pmol/L (95% CI 262.6-281.5), 51.0 nmol/L (95% CI 48.7-53.4) and 13.5 µmol/L (95% CI 13.1-14.0), respectively. Plasma folate, was adequate (> 15 nmol/L) in 44.7% of all subjects, 39.0% of males and 42.5% of women < 45 years. Similarly, vitamin B12 was adequate (> 350 pmol/L) in 25.1% of all subjects and in 20.3% of men ≥ 45 years. The rare allele frequencies were 0.21 for MTHFR 677TT, 0.11 for cSHMT 1420TT, 0.18 for DHFR 19 bp del/del, 0.20 for RFC1 80AA, and a gene-nutrient interaction was confirmed for folate concentrations according to MTHFR 677C>T and DHFR 19 bp del/del. CONCLUSION: An Italian sample of healthy blood donors shows that an adequate concentration of plasma folate and vitamin B12 is reached only in a limited percentage of subjects, thus encouraging consideration for specific public health strategies.

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.

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.

Prevalence and risk factors for restless legs syndrome during pregnancy in a Northern Italian population.

The objective of the present study was to investigate the frequency and the risk factors for restless legs syndrome (RLS) during pregnancy in an Italian population rarely studied, in epidemiological studies on the syndrome. A total of 648 women (median age: 35 years; interquartile range: 32-38), who delivered on randomly selected days at the obstetric department of our hospital, were identified. One hundred and thirty-two women (20.4%, 95% confidence interval (CI): 17.3-23.5) met the criteria for a diagnosis of RLS. The odds ratio (OR) of RLS was, in comparison with women aged <35 years, 1.69 (95% CI 1.14-2.51) in women aged ≥35 years. Subjective insufficient sleep (OR: 2.35, 95% CI 1.27-4.35) and difficulty in initiating sleep (OR: 1.73, 95% CI 1.15-2.63) increased the risk of RLS. This study confirms the high frequency of RLS in pregnant women. The risk of the condition was increased in women aged ≥35 years and in the women reporting sleep-wake disturbances during pregnancy. Impact statement What is already known on this subject? Restless legs syndrome (RLS), a common neurological, sensorimotor disorder, is two/three times more frequent in pregnant women than in the general population. The prevalence of RLS during pregnancy ranges widely, showing differences among populations. What do the results of this study add? This study adds data about the frequency and the risk factors for RLS during pregnancy in a Northern Italian population, rarely considered in epidemiological studies on the syndrome. Older age and sleep-wake disturbances are the main factors associated with the condition. What are the implications of these findings for clinical practice and/or further research? Screening for RLS might be useful for pregnant women to manage the condition. Further research is needed to investigate and define the potential impact of RLS during pregnancy on foetal and maternal health.

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.

Recurrence of hypertensive disorders of pregnancy: an individual patient data metaanalysis.

OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. RESULTS: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1). CONCLUSION: Among women that experience hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively low, and the course of disease is milder for most women with recurrent disease. These reassuring data should be used for shared decision-making in women who consider a new pregnancy after a pregnancy that was complicated by hypertension.

Coffee and caffeine intake and risk of endometriosis: a meta-analysis.

PURPOSE: The potential association between endometriosis and coffee/caffeine consumption has been analysed in several epidemiological studies. In order to establish whether caffeine influences the risk of endometriosis, we provide to summarize the evidence from published studies on this issue. METHODS: We performed a meta-analysis of epidemiological studies published up to January 2013. We computed summary relative risks (RR) of endometriosis for any, high and low versus no coffee/caffeine consumption. RESULTS: We identified a total eight studies, six case-control and two cohort studies, including a total of 1,407 women with endometriosis. The summary RR for any versus non-consumption were 1.26 [95% confidence interval (CI) 0.95-1.66] for caffeine and 1.13 (95% CI 0.46-2.76) for coffee consumption; the overall estimate was 1.18 (95% CI 0.92-1.49). The summary RR were 1.09 (95% CI 0.84-1.42) and 1.09 (95% CI 0.89-1.33) for high and low caffeine consumption as compared to no consumption, respectively. CONCLUSION: The present meta-analysis provided no evidence for an association between coffee/caffeine consumption and the risk of endometriosis. Coffee/caffeine consumption, as currently used in diet, does not carry a health risk.

Histologic Subtypes in Endometriosis-Associated Ovarian Cancer and Ovarian Cancer Arising in Endometriosis: A Systematic Review and Meta-Analysis.

The definition of the association between ovarian cancer and endometriosis was first reported by Sampson in 1925. He identified the following criteria: (a) clear evidence of endometriosis in proximity to the tumour, (b) exclusion of a metastatic tumour to the ovary, (c) presence of tissue resembling endometrial stroma surrounding epithelial glands. The naming of these cancers is "endometriosis-associated ovarian cancer" (EAOC). Scott proposed an additional stringent criterion: evidence of histological transition from endometriosis to cancer is to define "ovarian cancer arising in endometriosis" (OCAE). The aim of this systematic review is to analyse the distribution of different ovarian cancer histotypes in EAOC and OCAE to understand their similarities and differences. A total of 31 studies were included. Four studies added data for both EAOC and OCAE. Twenty-three studies were selected for EAOC, with a total of 800 patients, and 12 studies were selected for OCAE, with a total of 375 patients. The results show no significant differences in the distribution of histotypes in the two populations analysed. Clear cell carcinoma (CCC) and endometrioid carcinoma (EC) were the most common subtypes and were less frequent in EAOC compared to OCAE; the odd ratios were 0.58 (0.26-1.29) and 0.65 (0.33-1.26) respectively, although the difference was not statistically significant. The other histotypes were present in small proportions. This analysis shows that the histological profiles of EAOC and OCAE are similar, suggesting a similar aetiopathological mechanism, which requires further research to investigate whether EAOC and OCAE may be in the same way but at different points of the process to malignancy or have different pathways of progression to malignancy.

Should I stay for local hormone therapy or should I go for radiofrequency to treat vulvovaginal atrophy? A patient preference trial.

OBJECTIVE: To compare patient satisfaction rate in postmenopausal women who chose dynamic quadripolar radiofrequency or topical estrogens as their preferred treatment for genitourinary syndrome of menopause. METHODS: Patients were divided into two groups according to their preference: one was treated with estrogen therapy (ET) and the other with dynamic quadripolar radiofrequency treatment (RF). All patients included fulfilled a series of validated questionnaires, at baseline and at the 6-mo follow-up, in order to evaluate the discomfort degree associated with the presence of vulvovaginal atrophy and the impact of the reported symptoms on QoL and sexuality. RESULTS: After propensity score matching, the proportion of women considering themselves satisfied with their genital health conditions was extremely small at study entry (5.2% of the RF group and 6.9% of the ET group), while at a 6-mo follow-up, it increased to 46.7% and 46.6%, respectively. No statistically significant between-group differences were found regarding mean numerical rating scale scores for dryness and dyspareunia at follow-up (5.6 ± 2.6 vs 5.3 ± 2.3, P = 0.5; and 2.9 ± 2.5 vs 3.0 ± 2.7, P = 0.46). At 6-mo follow-up, we observed no statistically significant differences between the two groups regarding the other items evaluated. RF treatment was overall well tolerated. CONCLUSION: The use of quadripolar radiofrequency devices seems effective, but it is not associated with better clinical outcomes compared with topical hormone treatment, which is a substantially cheaper and more convenient treatment for genitourinary syndrome of menopause. Therefore, we suggest limiting the use of dynamic quadripolar radiofrequency selectively when topical estrogens are not effective, not tolerated, or contraindicated.

A metaanalysis on alcohol consumption and risk of endometriosis.

OBJECTIVE: To offer a general figure of the available data on the relation between alcohol intake and risk of endometriosis, we conducted a systematic review and a metaanalysis of studies published up to May 2012. STUDY DESIGN: We carried out a literature search of all case-control and cohort studies published as original articles in English up to May 2012. Only those papers that were published as full-length articles were considered. Pooled estimates of the relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated using fixed or, when significant heterogeneity among estimates emerged, random effects models. A total of 15 studies were identified for the review. RESULTS: The summary estimate was 1.24 (95% CI, 1.12-1.36) for any alcohol intake vs no alcohol intake. Considering the results of the analyses of infrequent, moderate/regular, and heavy alcohol intake vs no alcohol intake, the summary RR estimates were, respectively, 1.14 (95% CI, 0.86-1.52), 1.23 (95% CI, 1.08-1.40), and 1.19 (95% CI, 0.99-1.43). Three studies reported separate results for current and former drinkers, and the summary RR were 1.42 (95% CI, 1.14-1.76) and 1.09 (95% CI, 0.83-1.43), respectively. CONCLUSION: The present metaanalysis provides evidence for an association between alcohol consumption and endometriosis risk. Further studies are needed to clarify whether alcohol consumption may exacerbate an existing disease or could be related to the severity of the disease.

Temporal trend in the frequency of ectopic pregnancies in Lombardy, Italy.

BACKGROUND: In recent years, epidemiological data showed that the incidence of ectopic pregnancies (EP) is decreasing, but few data are available on the time trend in Southern European populations. METHODS: Using data from the Lombardy Region Database, we calculated and standardized the EP rates/10,000 resident women and the ratios/1,000 pregnancies. RESULTS: Data regarding 1,777,011 pregnancies and 17,028 cases of EP were recorded among women resident in Lombardy between 1996 and 2010, aged 15-50 years old. The age-adjusted EP rates increased from 4.4 in 1996 to 5.8 in 2010. The age-adjusted EP ratio was 9.4/1,000 pregnancies in 1996 and 9.8 in 2010. Medical treatment increased over the period; the proportion of laparoscopic treatment increased from 25.9% in 1996 to 36.3% in 2010. CONCLUSION: The age-adjusted EP rate and ratio increased between 1996 and 2010, suggesting that the significance of EP as a public health problem has increased in the last years.

Temporal trends and determinants of peripartum hysterectomy in Lombardy, Northern Italy, 1996-2010.

PURPOSE: To analyze the temporal trends of peripartum hysterectomy (PH) in the period 1996-2010 in Lombardy, Italy. METHODS: Using data from the Regional Database, PH ratios/1,000 deliveries were calculated from 1996 to 2010, in strata of age and mode of delivery among women resident in Lombardy, Italy. PH cases were identified searching the database for the ICD-9 and ICD-10 codes for subtotal and total hysterectomy. PH ratios/1,000 deliveries in strata of age, mode of delivery and calendar year were computed. Poisson's regression analysis was used to test trend over time. RESULTS: A total of 905 PH and 1,289,163 deliveries were recorded between 1996 and 2010. The overall PH ratio was 0.70/1,000 deliveries. The PH ratio/1,000 deliveries increased over time, being 0.57 in 1996 and 0.88/1,000 deliveries in 2010 (P < 0.0001). After including calendar year, mode of delivery and maternal age in the Poisson's regression equation, no significant linear trend emerged in the PH ratio over time (P = 0.28). Women who underwent cesarean section (CS) (CS vs. vaginal delivery: OR 5.66, 95 % CI 4.91-6.54) and older women were at increased risk of PH (maternal age ≥40 vs. <30 years: OR 5.66, 95 % CI 4.48-7.15). The frequency of intractable peripartum hemorrhage and placenta praevia/accreta, the main indications for PH, significantly increased over the study period. CONCLUSIONS: In Lombardy, the PH ratio increased between 1996 and 2010. In our population, rising frequency of CS and older maternal age may explain this trend.

Temporal trends in adolescent pregnancies in Lombardy, Italy: 1996-2010.

OBJECTIVES: Data from southern European countries concerning teenage pregnancy have not been properly analysed so far. We provide the temporal trend of adolescent pregnancy rates in Lombardy, Northern Italy. METHODS: Using the hospital discharge register (1996-2010), teenage pregnancy-related admission rates per 1000 girls aged 13 to 19 years, residing in Lombardy, were computed. Miscarriage-, induced abortion-, and delivery ratios/100 pregnancies, and caesarean section ratio/100 deliveries, were calculated. RESULTS: The pregnancy rate increased from 9.07 in 1996-2000 to 10.20 in 2001-2005, and remained at that level (10.27) in 2006-2010. However, the rates by country of birth (native Italian and non-native Italian) showed a steady decline in 2003-2010, when data about residents in Lombardy, categorised by sex, age and country of birth, were available. The induced abortion rate rose from 5.38/1000 to 5.55/1000, then decreased slightly in 2006-2010. The abortion ratio/100 pregnancies diminished from 59.3 in 1996-2000 to 50.3 in 2006-2010. CONCLUSIONS: Between 1996 and 2010, the overall teenage pregnancy rate has risen in Lombardy. When the rates were calculated separately for adolescents born in Italy and immigrants, the trends reverted in the period 2003-2010: in both groups pregnancy- and birth rates steadily declined. Pregnancy-, abortion-, and birth rates in non-native Italians, after having dropped, are all still much higher than those among native Italians. Because the number of non-native Italian adolescent girls markedly increased over the last two decades, their group--with decreasing, but still higher, birth- and abortion rates--has caused the observed rise in those rates when all adolescents residing in Lombardy are considered indistinctly.

A systematic review on maternal and perinatal factors influencing breast development.

BACKGROUND: A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship between in utero and early life events and breast onset/development. METHODS: Eligible studies were identified in PubMed and Embase databases. We selected studies in which female human exposure during fetal or the first years of life was measured or estimated, and associations with breast onset or development were evaluated. RESULTS: Of the 49 cohort studies and 5 cross-sectional studies identified, 43 provided sufficient data to assess associations. High maternal weight, primiparity, and early weight gain, were related to an increased risk of early breast onset/development in most of the studies that analysed these associations, whereas late breast onset/development was associated with preterm birth. Results were inconsistent for smoking in pregnancy, maternal hypertensive disorders, breastfeeding, diabetes, and small for gestational age. No association emerged for maternal age at delivery, alcohol drinking, and selected drug use during pregnancy, and low birth weight. CONCLUSIONS: The results of this review show that high maternal weight, primiparity and early weight gain were associated with an increased risk of early breast onset/development. Late breast onset/development was associated with preterm birth. Breast development is a key physical marker of puberty onset, and early puberty development is linked to consequences that can reverberate throughout life. Answering the questions about the interconnections between pre/postnatal environmental exposures and their impact on puberty, represents an important area of multidisciplinary research.

Trend of change of sperm count and concentration over the last two decades: A systematic review and meta-regression analysis.

BACKGROUND: Since the 1970s, several studies found that sperm concentration (SC) and total sperm count (TSC) constantly worsened over time, mainly in high-income countries. OBJECTIVES: To evaluate whether the decreasing trend in sperm count is continuing in Western European countries and USA, we performed a systematic review and meta-regression analysis. MATERIALS AND METHODS: Embase and Pubmed/Medline were searched papers published in English in the 2000-2020 period limiting the search to data collected in the USA and Western European countries. RESULTS: We identified 62 articles and pooled information on 24,196 men (range 10-2,523), collected from 1993 to 2018. Considering all the studies, random-effects meta-regression analyses showed no significant trend for SC (slope per year -0.07 mil/mL, p-value = 0.86). Negative trends of SC were detected in Scandinavian countries (slope per year -1.11 mil/mL, 95% CI: -2.40 to +0.19; p-value = 0.09), but the findings were statistically not significant. No significant trends of SC were detected in Central Europe (slope per year +0.23, 95% CI -2.51 to +2.96; p-value = 0.87), the USA (slope per year +1.08, 95% CI -0.42 to +2.57; p-value = 0.16), and Southern Europe (slope per year +0.19, 95% CI -0.99 to +1.37; p-value = 0.75). We have analyzed separately findings from studies including sperm donors, fertile men, young unselected men (unselected men, study mean age < 25 years) and unselected men (unselected men, study mean age ≥ 25 years). No significant trends of SC were observed among sperm donors (slope per year -2.80, 95% CI -6.76 to +1.17; p-value 0.16), unselected men (slope per year -0.23, 95% CI -1.58 to +1.12; p-value 0.73), young unselected men (slope per year -0.49, 95% CI -1.76 to +0.79; p-value 0.45), fertile men (slope per year +0.29, 95% CI -1.09 to +1.67; p-value 0.68). DISCUSSION AND CONCLUSION: The results of this analysis show no significant trends in SC, in USA, and selected Western European countries.

Temporal trends in the frequency of hydatidiform mole in lombardy, northern Italy, 1996-2008.

OBJECTIVE: To analyze temporal trends of hospital admissions due to molar pregnancies in Italian and non-Italian women in Lombardy during the 1996-2008 period. METHODS: A standard form is used to register all discharges from public or private hospitals in Lombardy. Hydatidiform mole (HM) cases were identified when searching the database for code 630 of the International Classification of Diseases, Ninth Revision (ICD-9). Ratios of HM per 100,000 pregnancies in strata of age and nationality were computed. RESULTS: The estimated frequency of HM in Lombardy over the period 1996-2008 was 104.4 per 100,000 pregnancies (SE, 2.8) or 1 case in 935 pregnancies. The frequency of HM tended to decrease in the late 1990s, the crude ratio per 100,000 pregnancies being 127.3 in 1996, 89.3 in 2000, and 113.1 in 2008. The temporal trend analysis, adjusted for age class and geographical origin, showed a significant decrease (P = 0.025). The frequency of HM was 99.8/100,000 pregnancies among Italian women, 112.1/100,000 pregnancies among women from other European countries, 85.1/100,000 pregnancies among women from Africa, 176.9/100,000 pregnancies from South America, and 163.0/100,000 pregnancies among Asian women. Considering the periods 1996-2001 and 2002-2008 separately, the frequency of HMs was largely similar for all groups, except in Asian women: in this group, the frequency of HMs was 242.7/100,000 pregnancies and 120.1/100,000 pregnancies in 1996-2001 and 2002-2008, respectively. CONCLUSION: Between 1996 and 2008, the HM incidence in Lombardy showed a slight but significant decrease, mostly owing to the decrease of HM incidence among Asian women.