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.

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.

The Promise and Pitfalls of AI-Generated Anatomical Images: Evaluating Midjourney for Aesthetic Surgery Applications.

BACKGROUNDS: The rapid advancement of generative artificial intelligence (AI) systems, such as Midjourney, has paved the way for their use in medical training, producing computer-generated images. However, despite clear disclosures stating that these images are not intended for medical consultations, their accuracy and realism are yet to be thoroughly examined. METHODS: A series of requests were addressed to the Midjourney AI tool, a renowned generative artificial intelligence application, with a focus on depicting appropriate systemic anatomy and representing aesthetic surgery operations. Subsequently, a blinded panel of four experts, with years of experience in anatomy and aesthetic surgery, assessed the images based on three parameters: accuracy, anatomical correctness, and visual impact. Each parameter was scored on a scale of 1-5. RESULTS: All of images produced by Midjourney exhibited significant inaccuracies and lacked correct anatomical representation. While they displayed high visual impact, their unsuitability for medical training and scientific publications became evident. CONCLUSIONS: The implications of these findings are multifaceted. Primarily, the images' inaccuracies render them ineffective for training, leading to potential misconceptions. Additionally, their lack of anatomical correctness limits their applicability in scientific articles. Although the study focuses on a single AI tool, it underscores the need for collaboration between AI developers and medical professionals. The potential integration of accurate medical databases could refine the precision of such AI tools in the future. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. METHODS: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. RESULTS: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. CONCLUSIONS: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

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.

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.

Forty-two normomenstruating adolescents with Müllerian obstructive anomalies: Presentation, pitfalls in the dagnosis and surgical management.

INTRODUCTION: We analyzed the frequency, presentation and pitfalls in the diagnosis and surgical management of a large group of normomenstruating adolescents with obstructive reproductive tract anomalies. MATERIAL AND METHODS: Retrospective analysis of prospectively collected data. Of the 143 outpatients referred for severe dysmenorrhea and persistent pelvic pain, 42 (29.3%) young women with obstructive Müllerian anomalies and regular menstrual flow were identified. These patients were divided into four groups: (1) patients with duplicate uterine cavities, obstructed hemivagina and ipsilateral renal agenesis (n = 34); (2) patients with unicornuate uterus and noncommunicating cavitated rudimentary horn (n = 5); (3) patients with accessory cavitated uterine mass (n = 2); (4) patients with partially obstructed transverse vaginal septum (n = 1). All 42 patients were conservatively treated via laparoscopy and 35/42 patients had also vaginal surgery. RESULTS: Of the four groups, patients in groups 2 and 3 (n = 7) were conservatively managed by laparoscopy alone; for patients in groups 1 and 4 (n = 35), laparoscopy and the vaginal approach were used. Patients of group 1 were treated by resecting the obstructed vaginal septum with drainage of retained collections. In patients in group 2, surgery consisted of the removal of the rudimentary horn. Patients of group 3 were treated by the removal of myometrial neoformations. In the patient in group 4, treatment consisted of removal of the septum. All surgical procedures were successful and no major complications were recorded. Follow-up reports highlighted the disappearance of obstruction and clear improvement in pain symptoms. CONCLUSIONS: Unilateral obstructive anomalies of the female genital tract are difficult to identify. Early diagnosis allows the preservation of reproductive activity and avoids potential complications.

Rokitansky Syndrome or Cervicovaginal Atresia?

STUDY OBJECTIVE: To investigate the possibility of conservative management of rudimentary uterine horns associated with vaginal agenesis. DESIGN: Observational study on cohort of consecutive cases treated with the same criteria from 2008 to 2021. SETTING: Two academic institutions and teaching hospitals in Milan, Italy. PATIENTS: Eight patients with vaginal agenesis associated with rudimentary cavitated uterine horns treated by the same team and postoperatively followed. INTERVENTIONS: All the subjects underwent the same standardized surgical procedure: laparoscopy, intraoperative ultrasound, and horn-vestibular direct anastomosis. Postoperatively vaginoscopy was performed every 6 months. MEASUREMENTS AND MAIN RESULTS: The postoperative course was generally uneventful and the mean hospital stay was 4.3 ± 2.5 (SD) days. All the patients began to menstruate a few months after the operation. Menstrual flows were light but regular. All patients had a neovaginal length > 4 cm at 1 year postoperatively, reaching approximately 6 cm at 2 years. During the follow-up period, 5 patients were sexually active without dyspareunia. In all cases, surgery restored the continuity of the neovagina and uterine horn through the creation of a "vaginal-horn fistula tract." CONCLUSION: In patients with vaginal agenesis associated with the presence of a uterine cavitary horn, it is possible to recover not only sexual activity but also menstrual function. The horn-vestibular anastomosis may be considered a valid, safe, and effective therapeutic option but requires accurate preoperative and intraoperative evaluation of rudimentary uterine structures.

How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

Delayed blastocyst development is influenced by the level of progesterone on the day of trigger.

PURPOSE: To evaluate the association between progesterone (P) level on the day of trigger and time to blastulation in IVF cycles. METHODS: This was a retrospective cohort study with autologous IVF cycles performed at our Institution from January 2019 to December 2021. A total of 1109 IVF cycles were included. The primary outcome was to compare time to blastulation in terms of percentage of expanded (grade 3) blastocysts on day 5 according to progesterone level at trigger. RESULTS: A total of 3517 blastocysts were analyzed. After dividing progesterone level in quartiles (Q1, P < 0.50 ng/ml; Q2 0.50 ng/ml ≤ P ≤ 0.78 ng/ml; Q3, 0.79 ng/ml ≤ P ≤ 1.15 ng/ml; Q4, P > 1.15 ng/ml), we observed a delay in blastocyst development according to the increasing level of progesterone at trigger (analysis by rank, P-value = 0.01). After adjusting for confounding factors at the multivariate analysis, the percentage of day 5 blastocysts was reduced for Q3 (- 13.8%, 95% CI from - 20.5 to - 7.0%, p < 0.001) and Q4 (- 7.7%, 95% CI from - 15.5 to 0.0%, p = 0.05) compared to Q1 (reference). CONCLUSIONS: Progesterone levels on day of trigger correlate to the percentage of expanded (grade 3) blastocysts on day 5 and a delayed blastocyst development day 5 is expected for high progesterone levels.

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.

The cumulative incidence of neonatal metabolic acidemia after terminal bradycardia in the 2nd stage of labor: a survival-based model.

PURPOSE: The aim of the study was to estimate by a survival analysis model the hazard function (HF) for neonatal metabolic acidemia (MA) throughout the 2nd stage of labor (2STG) at the time of occurrence of a terminal bradycardia ≥ 10 min requiring expedited delivery, and the cumulative incidence function (CIF) for MA according with the duration of bradycardia stratified in 10-12 min and > 12 min. METHODS: Singleton pregnancies experiencing terminal fetal bradycardia requiring expedited delivery in the 2STG at 38 + 0-41 + 3 weeks and delivering in the year 2019, were identified. The presence of MA (pH < 7 and/or BE ≤ - 12 mmol/L) was determined based on the acid-base status in the umbilical artery cord blood. Survival analysis was used to assess the hazard function (HF) and the cumulative incidence function (CIF) for MA occurring after terminal fetal bradycardia, at the 2STG. RESULTS: Out of a non-consecutive population of 12,331 pregnancies, there were 52 cases that fit the inclusion criteria. Twenty-four (46.2%) of those develop MA. Abnormal quantitative pH values and the HF for MA correlated with the duration of 2STG at the time of bradycardia onset, but not with bradycardia duration. After 60 min of duration of 2STG, the HF (or instantaneous rate of failure) increased dramatically (from 1.2 to 20 about at 120 min). At paired duration of 2STG, a higher CIF was observed for the terminal bradycardia > 12 min. CONCLUSION: Forty-six percent of term fetuses with terminal bradycardia had MA at birth. Despite the low sensitivity and a non-significant association with quantitative pH values, the duration of terminal bradycardia in the 2STG is associated with a higher CIF for MA.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

Pre- versus Post-Menopausal Onset of Overactive Bladder and the Response to Vaginal Estrogen Therapy: A Prospective Study.

Background and Objectives: This study examined the utility of local estrogen therapy for improving urinary symptoms in women diagnosed with Overactive Bladder allied to the time of onset of urinary symptoms whether pre- or post-menopausal. Materials and Methods: Subject to informed consent, menopausal women diagnosed with Overactive Bladder (OAB) and Genitourinary Syndrome of Menopause (GSM) were enrolled at three urogynecological units. OAB symptoms were scored using the Global Pelvic Floor Symptoms Bother Questionnaire (GPFSBQ), with explicit attention to question number 3 that specifically addresses the presence or absence of urgency and the Patient Perception of Intensity of Urgency Scale (PPIUS). The Vaginal Health Index (VHI) was used to assess the vaginal mucosa trophism. Exclusion criteria included: Pelvic organ prolapse (POP) ≥ stage II, urinary tract infection or disease, diabetes, inflammatory diseases, use of diuretics, alcohol or drug addictions, neurological and/or psychiatric disorders, and other precluding conditions. Women were treated with local estrogens for 3 months and re-evaluated. Results: Forty-three post-menopausal women were enrolled. Of these, ten women developed OAB symptoms before menopause (Group I) and 33 developed symptoms after menopause (Group II). Following local estrogen therapy, based on the Global Pelvic Floor Symptoms Bother Questionnaire, improvement of OAB symptoms was reported by 20% of patients in Group I (p = 0.414) and 64% of patients in Group II, (p = 0.002). Based on the PPIUS scale, diminution in urinary urgency was experienced by 20% of patients in Group I (p = 0.68) and 66% of patients in Group II (p = 0.036). Improved VHI scores were graded statisticaly significant in both groups (Group I in 100% of women, p = 0.005 vs. 76% in Group II, p = 0.004). Conclusions: Our results indicate that local estrogen therapy is more effective in women who develop OAB after menopause.

Endometrioid Borderline Ovarian Tumor: Clinical Characteristics, Prognosis, and Managements.

BACKGROUND: Endometrioid borderline ovarian tumor (EBOT) is a rare subtype of borderline ovarian malignancies. This study was designed to determine the prognosis of a series of EBOT. METHODS: This is a retrospective review of patients with EBOT treated in or referred to our institutions and a centralized, histological review by a reference pathologist. Data on the clinical characteristics, management (surgical and medical), and oncologic outcomes of patients were required for inclusion. RESULTS: Forty-eight patients were identified. Median age was 52 years (range 14-89). Fourteen patients underwent a conservative surgery and 32 a bilateral salpingo-oophorectomy (unknown in 2 cases). Two patients had bilateral tumors. Forty-three patients had stage I disease, and five patients had stage II disease (10%). Stromal microinvasion and intraepithelial carcinoma was observed in 6 (12%) and 13 (27%) patients respectively. Endometriosis was histologically associated in 12 patients (25%). Synchronous endometrial disease was found in 7 (24%) of 29 patients with endometrial histological evaluation. The median follow-up was 72 months (range 6-146). Two patients developed a recurrence after cystectomy in form of borderline disease (5%). No death related to EBOT occurred. CONCLUSIONS: Peritoneal restaging surgery should be performed if not realized initially, because 5% of EBOTS are diagnosed at stage II-III. Fertility-sparing surgery seems a safe option in selected patients. Because synchronous endometrial diseases, including endometrial carcinoma are frequent, systematic hysterectomy (or endometrial sampling in case of fertility-sparing surgery) is mandatory. Prognosis is generally excellent. Recurrence is a rare event (6%), but it can occur in the form of invasive disease.

Clear Cell Borderline Ovarian Tumor: Clinical Characteristics, Prognosis, and Management.

BACKGROUND: Clear cell borderline ovarian tumor (CCBOT) is one of the rarest subtypes of borderline ovarian malignancies. The aim of this study was to determine the prognosis of a series of CCBOT. PATIENTS AND METHODS: A retrospective review of patients with CCBOT treated or referred to our institutions. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion. RESULTS: Nineteen patients were identified. Median age was 62 (range 36-83) years. Four patients underwent a conservative surgery and 14 a bilateral salpingo-oophorectomy +/- hysterectomy (unknown in 1 case). One patient had bilateral tumor, and all cases were stage-I disease. All CCBOTs showed an adenofibromatous pattern. Stromal microinvasion was observed in seven cases and intraepithelial carcinoma in two cases. Endometriosis was histologically associated in one case. The median follow-up was 76 (range 6-231) months. No recurrence occurred. Two patients died of intercurrent disease. CONCLUSIONS: Peritoneal staging procedures should always be associated, but restaging surgery could be omitted if there was no suspicious lesion in the peritoneum during initial surgery, since all patients reported had stage-I disease. Fertility-sparing surgery appears to be a safe alternative in young patients. Synchronous endometrial disorders with atypia are infrequent. Prognosis is generally excellent, and long-term risk of recurrence is low. The two recurrences described in literature occurred in stage-IC diseases, highlighting the importance of avoiding perioperative rupture.

The effect of vitrified-warmed blastocyst transfer on postnatal growth: a 1-year follow-up questionnaire study.

RESEARCH QUESTION: Is postnatal growth of singletons aged 12 months born after vitrified-warmed blastocyst transfer (frozen embryo transfer [FET]) different from children born after fresh blastocyst transfer? DESIGN: A retrospective cohort study conducted at a single university-affiliated obstetrics and fertility centre between 2014 and 2016. Women who underwent fresh transfer or FET at blastocyst stage and obtained a singleton live birth were included. Propensity score inverse probability weighting was used to balance baseline maternal characteristics between fresh and FET cycles. RESULTS: Of the 382 women with singleton live births, 124 underwent a fresh blastocyst transfer and 258 underwent a FET. Significantly higher birth weight and length z-scores were observed after FET (P = 0.01 and P = 0.002, respectively) compared with the fresh transfer group. At 12 months of age, the fresh and FET groups showed no significant effect on the weight z-score, but the FET was associated with a higher height z-score (P = 0.001) compared with fresh blastocyst transfer. The comparison between males and females from the same study group showed higher birth weight z-score for males in the FET group (P < 0.001). During the first 12 months, however, males in the FET group showed a slower growth trajectory in terms of weight (P = 0.007). CONCLUSIONS: At 12 months of postnatal life, an increased height and sex-dependent differences in growth trajectories were observed in singletons born after FET compared with those born after fresh embryo transfer.

Anti-Müllerian hormone concentration as an indicator of female general health status: a cross-sectional study.

RESEARCH QUESTION: To evaluate the correlation between clinical and hormonal parameters and comorbidity burden in Caucasian women presenting for fertility treatment. DESIGN: Monocentric cross-sectional study including a cohort of 3163 Caucasian women seeking medical care for fertility treatment. All patients underwent centralized laboratory testing for hormonal assessment. Complete clinical and laboratory data from the entire cohort were retrospectively analysed. Comorbidity burden score was assessed by the Charlson Comorbidity Index (CCI; categorized as 0 versus 1 versus ≥2). RESULTS: Descriptive statistics and regression models tested the associations between clinical and laboratory parameters and CCI. Among the entire cohort of patients, a CCI = 0 was found in 2977 women (94.1%), and CCI = 1 and CCI ≥2 were found in 113 (3.6%) and 73 (2.3%) patients, respectively. Age (P = 0.009), gravidity (P = 0.001), anti-Müllerian hormone (AMH, P < 0.001) and TSH (P = 0.003) values were significantly different among CCI groups. In regression models, age at presentation and AMH emerged as independent indicators of CCI ≥ 1. Age at presentation <36 years (odds ratio [OR] 1.742, 95% confidence interval [CI] 1.284-2.364) and an AMH concentration ≤2.3 ng/ml (OR 1.864, 95% CI 1.29-2.69) were the most informative cut-off values for CCI ≥ 1 in the study population. CONCLUSIONS: A younger age at presentation and lower AMH concentrations are significant independent indicators of decreased general health in women requiring clinical evaluation for fertility treatment. As observed for sperm parameters in men, AMH might serve as a proxy of women's general health status.

Pregnancy outcome of confined placental mosaicism: meta-analysis of cohort studies.

OBJECTIVE: This study aimed to assess the rate of adverse obstetrical and neonatal outcomes in pregnancies diagnosed with confined placental mosaicism relative to that of unaffected controls. DATA SOURCES: Web-based databases were searched using relevant key words, and articles published from 1980 to February 2022 were retrieved. STUDY ELIGIBILITY CRITERIA: Observational studies in English language including ≥10 cases of singleton pregnancies with diagnosis of confined placental mosaicism were included. The diagnosis was established after detection of any chromosomal abnormality at chorionic villus sampling for any indication, followed by normal karyotype from amniotic fluid or neonatal leukocyte culture. METHODS: Two authors independently screened the references for eligibility, data extraction, and assessment of methodological quality using the Newcastle-Ottawa scale. All available obstetrical and neonatal outcomes were recorded. Random-effect meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals of available outcomes in pregnancies with and without confined placental mosaicism. Statistical heterogeneity was evaluated with I2 statistics (International Prospective Register of Systematic Reviews registration number: CRD42021260319). RESULTS: Of the 80 articles reviewed, 8 retrospective matched-cohort studies (708 cases of confined placental mosaicism and 11,599 unaffected controls) compared cases with and without confined placental mosaicism and were included in the meta-analysis. The risk of delivering small-for-gestational-age neonates was significantly increased in confined placental mosaicism pregnancies according to crude analysis (odds ratio, 2.45; 95% confidence interval, 1.23-4.89; I2=72%) and to sensitivity analysis of high-quality studies (odds ratio, 3.65; 95% confidence interval, 2.43-5.57; I2=0%). Similarly, confined placental mosaicism resulted in an increased risk of birthweight below the third centile (odds ratio, 5.33; 95% confidence interval, 1.19-24.19; I2= 83%). Subgroup analysis revealed that the risk of delivering small-for-gestational-age neonates was 3-fold higher for confined placental mosaicism excluding trisomy 16, and 11-fold higher for cases including trisomy 16 only vs unaffected controls, respectively. No difference was found in the risk of low birthweight and preterm birth (at <37 weeks' gestation). Other outcomes were insufficiently reported, therefore they were not analyzed. CONCLUSION: Pregnant women prenatally diagnosed with confined placental mosaicism have an increased risk of impaired fetal growth, suggesting the need for intensified antenatal surveillance.

Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.

BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSION: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.