Optimizing Performance of Transformer-based Models for Fetal Brain MR Image Segmentation.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To test transformer-based models' performance when manipulating pretraining weights, dataset size, input size and comparing the best-model with reference standard and state-of-the-art models for a resting-state functional (rs-fMRI) fetal brain extraction task. Materials and Methods An internal retrospective dataset (fetuses = 172; images = 519; collected from 2018-2022) was used to investigate influence of dataset size, pretraining approaches and image input size on Swin-UNETR and UNETR models. The internal and an external (fetuses = 131; images = 561) datasets were used to cross-validate and to assess generalization capability of the best model against state-of-the-art models on different scanner types and number of gestational weeks (GW). The Dice similarity coefficient (DSC) and the Balanced average Hausdorff distance (BAHD) were used as segmentation performance metrics. GEE multifactorial models were used to assess significant model and interaction effects of interest. Results Swin-UNETR was not affected by pretraining approach and dataset size and performed best with the mean dataset image size, with a mean DSC of 0.92 and BAHD of 0.097. The Swin-UNETR was not affected by scanner type. Generalization results on the internal dataset showed that Swin-UNETR had lower performances compared with reference standard models and comparable performances on the external dataset. Cross-validation on internal and external test sets demonstrated better and comparable performance of Swin-UNETR versus convolutional neural network architectures during the late-fetal period (GWs > 25) but lower performance during the midfetal period (GWs ≤ 25). Conclusion Swin-UNTER showed flexibility in dealing with smaller datasets, regardless of pretraining approaches. For fetal brain extraction of rs-fMRI, Swin-UNTER showed comparable performance with reference standard models during the late-fetal period and lower performance during the early GW period. ©RSNA, 2024.

Preterm birth in singleton pregnancies conceived by in vitro fertilization or intracytoplasmic sperm injection: an overview of systematic reviews.

BACKGROUND: The rate of preterm birth of singletons conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is increased, being as high as 15% to 16% across Europe and the United States. However, the underlying etiology, phenotype, and mechanisms initiating preterm birth (PTB) are poorly understood. OBJECTIVE: To quantify the PTB risk and examine supposed etiology in IVF/ICSI singleton pregnancies compared to naturally conceived. STUDY DESIGN: Overview of reviews including all available systematic reviews with meta-analysis comparing PTB risk in IVF/ICSI and naturally conceived singletons. A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases was performed up to December 31, 2023. Information available on etiology, phenotype, initiation of PTB, and relevant moderators was retrieved and employed for subgroup analyses. Random-effects meta-analysis models were used for pooling effect measures. Estimates were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The extent of overlap in the original studies was measured using the corrected covered area assessment. The quality of the included reviews was evaluated with the AMSTAR 2 tool. The Grading of Recommendations Assessment, Development and Evaluation approach was applied to rate evidence certainty. The protocol was registered on PROspective Register of Systematic Reviews (CRD42023411418). RESULTS: Twelve meta-analyses (16,522,917 pregnancies; ˃433,330 IVF/ICSI) were included. IVF/ICSI singletons showed a significantly higher PTB risk compared to natural conception (PTB ˂37 weeks: OR: 1.72, 95% CI: 1.57-1.89; PTB<32 weeks: OR: 2.19, 95% CI: 1.82-2.64). Influential analysis reinforced the strength of this association. Subgroup analyses investigating supposed etiology revealed a comparable risk magnitude for spontaneous PTB (OR: 1.79, 95% CI: 1.56-2.04) and a greater risk for iatrogenic PTB (OR: 2.28, 95% CI: 1.72-3.02). PTB risk was consistent in the subgroup of conventional IVF (OR: 1.95, 95% CI: 1.76-2.15) and higher in the subgroup of fresh only (OR: 1.79, 95% CI: 1.55-2.07) vs frozen-thawed embryo transfers (OR: 1.39, 95% CI: 1.34-1.43). There was minimal study overlap (13%). The certainty of the evidence was graded as low to very low. CONCLUSION: Singletons conceived through IVF/ICSI have a 2-fold increased risk of PTB compared to natural conception, despite the low certainty of the evidence. There is paucity of available data on PTB etiology, phenotype, or initiation. The greater risk increase is observed in fresh embryo transfers and involves iatrogenic PTB and PTB ˂32 weeks, likely attributable to placental etiology. Future studies should collect data on PTB etiology, phenotype, and initiation. IVF/ICSI pregnancies should undertake specialistic care with early screening for placental disorders, cervical length, and growth abnormalities, allowing appropriate timely follow-up, preventive measures, and therapeutic interventions strategies.

Etiologically Based Functional Taxonomy of the Preterm Birth Syndrome.

Preterm birth (PTB) is a complex syndrome traditionally defined by a single parameter, namely, gestational age at birth (ie, ˂37 weeks). This approach has limitations for clinical usefulness and may explain the lack of progress in identifying cause-specific effective interventions. The authors offer a framework for a functional taxonomy of PTB based on (1) conceptual principles established a priori; (2) known etiologic factors; (3) specific, prospectively identified obstetric and neonatal clinical phenotypes; and (4) postnatal follow-up of growth and development up to 2 years of age. This taxonomy includes maternal, placental, and fetal conditions routinely recorded in data collection systems.

The maternal-fetal neurodevelopmental groundings of preterm birth risk.

Background: Altered neurodevelopment is a major clinical sequela of Preterm Birth (PTB) being currently unexplored in-utero. Aims: To study the link between fetal brain functional (FbF) connectivity and preterm birth, using resting-state functional magnetic resonance imaging (rs-fMRI). Study design: Prospective single-centre cohort study. Subjects: A sample of 31 singleton pregnancies at 28-34 weeks assigned to a low PTB risk (LR) (n = 19) or high PTB risk (HR) (n = 12) group based on a) the Maternal Frailty Inventory (MaFra) for PTB risk; b) a case-specific PTB risk gradient. Methods: Fetal brain rs-fMRI was performed on 1.5T MRI scanner. First, directed causal relations representing fetal brain functional connectivity measurements were estimated using the Greedy Equivalence Search (GES) algorithm. HR vs. LR group differences were then tested with a novel ad-hoc developed Monte Carlo permutation test. Second, a MaFra-only random forest (RF) was compared against a MaFra-Neuro RF, trained by including also the most important fetal brain functional connections. Third, correlation and regression analyses were performed between MaFra-Neuro class probabilities and i) the GA at birth; ii) PTB risk gradient, iii) perinatal clinical conditions and iv) PTB below 37 weeks. Results: First, fewer fetal brain functional connections were evident in the HR group. Second, the MaFra-Neuro RF improved PTB risk prediction. Third, MaFra-Neuro class probabilities showed a significant association with: i) GA at birth; ii) PTB risk gradient, iii) perinatal clinical conditions and iv) PTB below 37 weeks. Conclusion: Fetal brain functional connectivity is a novel promising predictor of PTB, linked to maternal risk profiles, ahead of birth, and clinical markers of neurodevelopmental risk, at birth, thus potentially "connecting" different PTB phenotypes.

Effect of type III female genital mutilation on obstetric outcomes: A systematic review and meta-analysis.

Background: Controversial evidence suggests a potential association between female genital mutilation (FGM/C) and adverse obstetric outcomes, with type III FGM/C (infibulation) carrying the greatest risk. The aim of this systematic review and meta-analysis was to assess current rate of adverse obstetric outcomes in women with type III female genital mutilation and cutting (FGM/C; infibulation) delivering across different settings worldwide. Methods: We searched PubMed, Scopus, Embase, and ClinicalTrials.gov databases from inception to Jan 1, 2023. Studies were selected if they included the main outcome of postpartum haemorrhage (PPH) or secondary outcomes, which included major conditions affecting maternal-neonatal health during labour and delivery. DerSimonian-Laird random effects meta-analysis including pooled effect estimates with corresponding 95 % confidence intervals was performed. Heterogeneity was assessed using the I2 statistic. Meta regression for relevant covariates was performed when data on relevant confounders were available. The Newcastle-Ottawa scale (NOS) was used to assess quality of observational studies. The level of evidence was assessed with the GRADE method. Results: 14 observational studies including 15,320 type III FGM/C women and 59,347 controls were eligible. The risk for postpartum haemorrhage was significantly increased in type III FGM/C, in the main analysis (OR 1.83, 95 % CI 1.03 to 3.24, I2 = 93 %), in pooling of data adjusted for confounders (aOR 1.76, CI 1.42 to 2.17, I2 = 0 %), and in sensitivity analysis of higher quality studies with NOS≥7 (OR 2.76, CI 1.38 to 5.51, I2 = 95 %). Meta-regression showed that nulliparity was significantly and positively associated with postpartum haemorrhage. Similarly, analysis of data adjusted for confounders showed an increased risk of episiotomy in type III FGM/C (aOR 1.56, CI 1.03 to 2.35, I2 = 52 %). Sensitivity analysis of studies with NOS≥7 revealed a significant increase for episiotomy (OR 7.53, CI 1.19 to 47.54, I2 = 96 %), perineal tears (OR 4.24, CI 1.09 to 16.46, I2 = 66 %), prolonged second stage of labour (OR 5.19, 95 % CI 1.00 to 26.85, I2 = 66 %), and Apgar score less than 7 (OR 4.19, CI 1.64 to 10.70, I2 = 0 %). No difference was found regarding obstetric anal sphincter injuries and mode of delivery in these women. Deinfibulation achieved similar obstetric and neonatal outcomes to women who never had type III FGM. The overall quality of the studies was adequate (median NOS score: 7; IQR: 6-8), the level of evidence, according to the GRADE assessment, was low. Conclusions: These results consistently show an increased risk of adverse obstetric outcomes in women with FGM/C type III. Infibulation substantially increases the risk for PPH, particularly in nulliparae. Systematic Review registration: PROSPERO CRD42023421993.

The "arrhythmic" presentation of peripartum cardiomyopathy: case series and critical review of the literature.

Peripartum Cardiomyopathy (PPCM) is a polymorphic myocardial disease occurring late during pregnancy or early after delivery. While reduced systolic function and heart failure (HF) symptoms have been widely described, there is still a lack of reports about the arrhythmic manifestations of the disease. Most importantly, a broad range of unidentified pre-existing conditions, which may be missed by general practitioners and gynecologists, must be considered in differential diagnosis. The issue is relevant since some arrhythmias are associated to sudden cardiac death occurring in young patients, and the overall risk does not cease during the early postpartum period. This is why multimodality diagnostic workup and multidisciplinary management are highly suggested for these patients. We reported a series of 16 patients diagnosed with PPCM following arrhythmic clinical presentation. Both inpatients and outpatients were identified retrospectively. We performed several tests to identify the arrhythmic phenomena, inflammation and fibrosis presence. Cardiomyopathies phenotypes were reclassified in compliance with the updated ESC guidelines recommendations. Arrhythmias were documented in all the patients during the first cardiological assessment. PVC were the most common recorder arrhythmias, followed by VF, NSVT, AF, CSD.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Opportunistic salpingectomy at the time of vaginal hysterectomy: A systematic review and meta-analysis.

BACKGROUND: Despite the rising rates of opportunistic salpingectomy at the time of surgery for non-malignant conditions, salpingectomy is not widely adopted during vaginal hysterectomy (VH) and has not been extensively investigated. OBJECTIVES: The aim of the primary study was to determine the feasibility of bilateral opportunistic salpingectomy at the time of VH. Secondary aims included surgical outcomes, factors associated with patient selection, and the prevalence of incidental tubal malignancies. SEARCH STRATEGY: In this systematic review and meta-analysis we searched Pubmed, Embase and ClinicalTrials.gov databases from inception to September 1, 2023, using relevant keywords. SELECTION CRITERIA: Original articles with no language restriction reporting outcomes of women undergoing planned VH with opportunistic salpingectomy, were considered eligible. Studies including patients undergoing VH with and without opportunistic salpingectomy were also included. DATA COLLECTION AND ANALYSIS: The Newcastle-Ottawa scale was used to assess quality of observational studies. DerSimonian-Laird random effects meta-analysis was performed and pooled effect estimates and proportions with corresponding 95% confidence intervals were computed. Heterogeneity was assessed using the I2 statistic. RESULTS: Seven observational cohort studies including 4808 women undergoing opportunistic salpingectomy at the time of VH and 10 295 patients undergoing VH alone were selected. The pooled proportion of success was 81.83 per 100 observations (95% CI: 75.35-87.54). Opportunistic salpingectomy at the time of VH, when feasible, was associated with a significant reduction in intraoperative complications (OR 0.06, 95% CI: 0.01, -0.37, P = 0.03) and total operative time (95% CI: -17.80, -1.07, P = 0.03) compared to those where it failed. Successful salpingectomy was significantly hindered by nulliparity (OR 0.12, 95% CI: -17.69, -1.21, P < 0.001) and favored by pelvic organ prolapse (OR 3.20, 95% CI: 1.35, 7.55, P = 0.008). Immunohistochemical tubal abnormalities were found in 13/579 (2.1%) patients. The overall quality of the evidence, according to the GRADE assessment, was low. CONCLUSION: Opportunistic salpingectomy is safe, effective, and feasible at the time of VH. Nulliparity and pelvic organ prolapse are factors potentially influencing surgical outcomes.

First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia.

BACKGROUND: First-trimester screening for preeclampsia using a combination of maternal risk factors and mean arterial pressure, uterine artery pulsatility index, and placental growth factor, as proposed by the Fetal Medicine Foundation, provides effective prediction of preterm preeclampsia. Placental dysfunction is a potential precursor of spontaneous birth. OBJECTIVE: The objective of this study was to examine if the estimated risk of preeclampsia is associated with the gestational age at onset of spontaneous delivery in the absence of preeclampsia. STUDY DESIGN: This was a secondary analysis of the data from the Screening programme for pre-eclampsia trial in which there was a comparison of the performance of first-trimester screening for preterm preeclampsia using the Fetal Medicine Foundation model vs a traditional history-based risk scoring system. A subgroup of women from the trial with spontaneous onset of delivery (labor with intact membranes or preterm prelabor rupture of membranes) was included in this study and was arbitrarily divided into 3 groups according to the risk for preterm preeclampsia as determined by the Fetal Medicine Foundation model at 11 to 13 weeks' gestation as follows: group 1 low risk (˂1/100); group 2 intermediate risk (1/50 to 1/100); and group 3 high risk (˃1/50). A survival analysis was carried out using a Kaplan-Meier estimator and a Cox regression analysis with stratification by the 3 preeclampsia risk groups. Occurrence of spontaneous birth in the study groups was compared using log-rank tests and hazard ratios. RESULTS: The study population comprised 10,820 cases with delivery after spontaneous onset of labor among the 16,451 cases who participated in the Screening programme for pre-eclampsia trial. There were 9795 cases in group 1, 583 in group 2, and 442 in group 3. The gestational age at delivery was <28, <32, <35, <37, and <40 weeks in 0.29%, 0.64%, 1.68%, 4.52%, and 44.97% of cases, respectively, in group 1; 0.69%, 1.71%, 3.26%, 7.72%, and 55.23% of cases, respectively, in group 2; and 0.45%, 1.81%, 5.66%, 13.80%, and 63.12% of cases, respectively, in group 3. The curve profile of gestational age at spontaneous birth in the 3 study groups was significantly different overall and in pairwise comparisons (P values <.001). The Cox regression analysis showed that risks increased for spontaneous birth by 18% when the intermediate-risk group was compared with the low-risk group (P˂.001) and by 41% when the high-risk group was compared with the low-risk group (P˂.001). CONCLUSION: In this study that investigated birth after spontaneous onset of labor in women without preeclampsia, there were 2 major findings. First, the duration of pregnancy decreased with increasing first-trimester risk for preeclampsia. Second, in the high-risk group, when compared with the low-risk group, the risk for spontaneous birth was 4 times higher at a gestational age of 24 to 26 weeks, 3 times higher at 28 to 32 weeks, and 2 times higher at 34 to 39 weeks. These differences present major clinical implications for antepartum counselling, monitoring, and interventions in these pregnancies.

The kisspeptin system in and beyond reproduction: exploring intricate pathways and potential links between endometriosis and polycystic ovary syndrome.

Endometriosis and polycystic ovary syndrome (PCOS) are two common female reproductive disorders with a significant impact on the health and quality of life of women affected. A novel hypothesis by evolutionary biologists suggested that these two diseases are inversely related to one another, representing a pair of diametrical diseases in terms of opposite alterations in reproductive physiological processes but also contrasting phenotypic traits. However, to fully explain the phenotypic features observed in women with these conditions, we need to establish a potential nexus system between the reproductive system and general biological functions. The recent discovery of kisspeptin as pivotal mediator of internal and external inputs on the hypothalamic-pituitary-gonadal axis has led to a new understanding of the neuroendocrine upstream regulation of the human reproductive system. In this review, we summarize the current knowledge on the physiological roles of kisspeptin in human reproduction, as well as its involvement in complex biological functions such as metabolism, inflammation and pain sensitivity. Importantly, these functions are known to be dysregulated in both PCOS and endometriosis. Within the evolving scientific field of "kisspeptinology", we critically discuss the clinical relevance of these discoveries and their potential translational applications in endometriosis and PCOS. By exploring the possibilities of manipulating this complex signaling system, we aim to pave the way for novel targeted therapies in these reproductive diseases.

Commentary: Predicting adverse outcomes in pregnant patients positive for SARS-CoV-2 by a machine learning approach.

SARS-CoV-2 infection poses a significant risk increase for adverse pregnancy outcomes both from maternal and fetal sides. A recent publication in BMC Pregnancy and Childbirth presented a machine learning algorithm to predict this risk. This commentary will discuss potential implications and applications of this study for future global health policies.

Progesterone levels during ovarian stimulation in segmented ART cycles inversely correlate with normalized birthweight of neonates conceived through subsequent frozen-thawed embryo transfer.

PURPOSE: To evaluate the association between serum progesterone (P) at the day of ovulation trigger and neonatal birthweight in singletons born after frozen-thawed embryo transfer in segmented ART cycles. METHODS: A retrospective multicenter cohort study involving data from patients who achieved uncomplicated pregnancy and term delivery of ART-conceived singleton babies following a segmented GnRH antagonist cycle. The main outcome was birthweight's z-score of the neonate. Univariate and multivariate linear logistic regression analyses were made to investigate the relation of z-score with variables inherent to the patient and to the ovarian stimulation. The variable P per oocyte was created by dividing the value of progesterone at ovulation trigger by the number of oocytes retrieved at oocyte retrieval. RESULTS: A total of 368 patients were included in the analysis. At univariate linear regression, the birthweight z-score of the neonate appeared to be inversely related to both P levels at the ovulation trigger (- 0.101, p = 0.015) and P levels per oocyte at trigger (- 1.417, p = 0.001), while it was directly related to the height of the mother (0.026, p = 0.002) and to the number of previous live births (0.291, p = 0.016). In multivariate analysis, both serum P (- 0.1; p = 0.015) and P per oocyte (- 1.347, p = 0.002) maintained the significant inverse association with birthweight z-score after adjusting for height and parity. CONCLUSIONS: Serum progesterone level on the day of ovulation trigger inversely correlates with normalized birthweight of neonates in segmented GnRH antagonist ART cycles.

Maternal anxiety-driven modulation of fetal limbic connectivity designs a backbone linking neonatal brain functional topology to socio-emotional development in early childhood.

A link between maternal anxiety during pregnancy and adverse socio-emotional outcomes in childhood has been consistently sustained on the very early neurodevelopmental alteration of structural pathways between fetal limbic and cortical brain regions. In this study, we provide follow-up evidence for a feed-forward model linking (i) maternal anxiety, (ii) fetal functional neurodevelopment, (iii) neonatal functional network organization with (iv) socio-emotional neurobehavioral development in early childhood. Namely, we investigate a sample of 16 mother-fetus dyads and show how a maternal state-trait anxiety profile with pregnancy-specific worries can significantly influence functional synchronization patterns between regions of the fetal limbic system (i.e., hippocampus and amygdala) and the neocortex, as assessed through resting-state functional magnetic resonance imaging. Generalization of the findings was supported by leave-one-out cross-validation. We further show how this maternal-fetal cross-talk propagates to functional network topology in the neonate, specifically targeting connector hubs, and further maps onto socio-emotional profiles, assessed through Bayley-III socio-emotional scale in early childhood (i.e., in the 12-24 months range). Based on this evidence, we put forward the hypothesis of a "Maternal-Fetal-Neonatal Anxiety Backbone", through which neurobiological changes driven by maternal anxiety could trigger a divergence in the establishment of a cognitive-emotional development blueprint, in terms of the nascent functional homeostasis between bottom-up limbic and top-down higher-order neuronal circuitry.

Endometriosis increases the risk of gestational diabetes: a meta-analysis stratified by mode of conception, disease localization and severity.

To review the current evidence on the risk of gestational diabetes mellitus (GDM) in women with endometriosis, taking into account relevant confounders such as the higher frequency of Assisted Reproductive Technologies (ART) conceptions. Database searches on PubMed, Medline, Embase and Scopus through June 2022, using combinations of relevant keywords. A total of 18 studies, involving N = 4,600,885 women, were included. The overall risk of GDM in endometriosis patients was significantly higher than in controls (OR, 1.23; 95% CI 1.07-1.51). This significant association persisted in natural pregnancies (OR, 1.08; 95% CI 1.04-1.12) but not in pregnancies conceived through ART (OR, 0.93;95% CI 0.70-1.24). Based on the limited number of studies that examined this association in relation to endometriosis phenotype, an increased risk was found in more severe stages (OR, 3.20; 95% CI 1.20-8.54) but independently from localization of the lesions. Endometriosis increases the risk of GDM, with a possible progressive effect in more advanced stages of the disease. Although the effect magnitude may be limited in some subgroups, this finding has a clinically relevant impact due to both the strong biological plausibility and to the relatively high incidence of both endometriosis and GDM.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Obstetric, neonatal, and child health outcomes following embryo biopsy for preimplantation genetic testing.

BACKGROUND: Preimplantation genetic testing (PGT) of embryos developed in vitro requires a biopsy for obtaining cellular samples for the analysis. Signs of cell injury have been described in association with this procedure. Thus, the consequences of the biopsy on obstetric and neonatal outcomes have been the subject of some quantitative analyses, although the reliability of data pooling may be limited by important issues in the various reports. OBJECTIVE AND RATIONALE: The present review identifies evidence for whether pregnancies conceived after embryo biopsy are associated with a higher risk of adverse obstetric, neonatal, and long-term outcomes. Available evidence has been summarized considering manipulation at various stages of embryo development. SEARCH METHODS: We used the scoping review methodology. Searches of article databases were performed with keywords pertaining to the embryo biopsy technique and obstetric, neonatal, and postnatal outcomes. Studies in which embryos were biopsied at different stages (i.e. both at the cleavage and blastocyst stages) were excluded. We included data on fresh and frozen embryo transfers. The final sample of 31 documents was subjected to qualitative thematic analysis. OUTCOMES: Sound evidence is lacking to fully address the issues on the potential obstetric, neonatal or long-term consequences of embryo biopsy. For polar body biopsy, the literature is too scant to draw any conclusion. Some data, although limited and controversial, suggest a possible association of embryo biopsy at the cleavage stage with an increased risk of low birthweight and small for gestational age neonates compared to babies derived from non-biopsied embryos. An increase in preterm deliveries and birth defects in cases of trophectoderm biopsy was suggested. For both biopsy methods (at the cleavage and blastocyst stages), an increased risk for hypertensive disorders of pregnancy was found. However, these findings may be explained by confounders such as other embryo manipulation procedures or by intrinsic patient or population characteristics. WIDER IMPLICATIONS: Since there is inadequate evidence to assess obstetric, neonatal, and long-term health outcomes following embryo biopsy, an invasive PGT strategy should be developed with a cautious approach. A non-invasive approach, based on the analysis of embryo cell-free DNA, needs to be pursued to overcome the potential limitations of embryo biopsy.