Pregnancy Outcomes in Women with Poorly Controlled Pregestational Diabetes Mellitus.

BACKGROUND: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications. OBJECTIVES: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM. METHODS: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared. RESULTS: The cohort included 89 women: 49 with HbA1c 6-8%, 29 with HbA1c 8-10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes. CONCLUSIONS: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Greater risk of type 2 diabetes progression in multifetal gestations with gestational diabetes: the impact of obesity.

BACKGROUND: The relationship between gestational diabetes mellitus and adverse outcomes in multifetal pregnancies is complex and controversial. Moreover, limited research has focused on the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus specifically in multifetal pregnancies, resulting in conflicting results from existing studies. OBJECTIVE: This study aimed to assess the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus between singleton and multifetal pregnancies in a large cohort of parturients with a 5-year follow-up. STUDY DESIGN: A retrospective study was conducted on a prospective cohort of pregnant individuals with pregnancies between January 1, 2017, and December 31, 2020, followed up to 5 years after delivery. Glucose levels during pregnancy were obtained from the Meuhedet Health Maintenance Organization laboratory system and cross-linked with the Israeli National Diabetes Registry. The cohort was divided into 4 groups: singleton pregnancy without gestational diabetes mellitus, singleton pregnancy with gestational diabetes mellitus, multifetal pregnancy without gestational diabetes mellitus, and multifetal pregnancy with gestational diabetes mellitus. Gestational diabetes mellitus was defined according to the American Diabetes Association criteria using the 2-step strategy. Univariate analyses, followed by survival analysis that included Kaplan-Meier hazard curves and Cox proportional-hazards models, were used to assess differences between groups and calculate the adjusted hazard ratios with 95% confidence intervals for progression to type 2 diabetes mellitus. RESULTS: Among 88,611 parturients, 61,891 cases met the inclusion criteria. The prevalence of type 2 diabetes mellitus was 6.5% in the singleton pregnancy with gestational diabetes mellitus group and 9.4% in the multifetal pregnancy with gestational diabetes mellitus group. Parturients with gestational diabetes mellitus, regardless of plurality, were older and had higher fasting plasma glucose levels in the first trimester of pregnancy. The rates of increased body mass index, hypertension, and earlier gestational age at delivery were significantly higher in the gestational diabetes mellitus group among patients with singleton pregnancies but not among patients with multifetal pregnancies. Survival analysis demonstrated that gestational diabetes mellitus was associated with adjusted hazard ratios of type 2 diabetes mellitus of 4.62 (95% confidence interval, 3.69-5.78) in singleton pregnancies and 9.26 (95% confidence interval, 2.67-32.01) in multifetal pregnancies (P<.001 for both). Stratified analysis based on obesity status revealed that, in parturients without obesity, gestational diabetes mellitus in singleton pregnancies increased the risk of type 2 diabetes mellitus by 10.24 (95% confidence interval, 6.79-15.44; P<.001) compared with a nonsignificant risk in multifetal pregnancies (adjusted hazard ratio, 9.15; 95% confidence interval, 0.92-90.22; P=.059). Among parturients with obesity, gestational diabetes mellitus was associated with an increased risk of type 2 diabetes mellitus for both singleton and multifetal pregnancies (adjusted hazard ratio, 3.66; [95% confidence interval, 2.81-4.67; P<.001] and 9.31 [95% confidence interval, 2.12-40.76; P=.003], respectively). CONCLUSION: Compared with gestational diabetes mellitus in singleton pregnancies, gestational diabetes mellitus in multifetal pregnancies doubles the risk of progression to type 2 diabetes mellitus. This effect is primarily observed in patients with obesity. Our findings underscore the importance of providing special attention and postpartum follow-up for patients with multifetal pregnancies and gestational diabetes mellitus, especially those with obesity, to enable early diagnosis and intervention for type 2 diabetes mellitus.

Flat Oral Glucose Tolerance Test During Pregnancy: Maternal Characteristics and Risk for Adverse Outcomes.

Flat oral glucose tolerance test (OGTT) curve is characterized by low glucose levels, seemingly nonresponsive to glucose load. Few studies have explored flat OGTT during pregnancy and have yielded conflicting results, some suggesting risk for fetal growth restriction. This study evaluated the characteristics and perinatal outcomes of women with a flat OGTT during pregnancy. We found that a flat OGTT curve occurs in younger, leaner pregnant women. Also, flat OGTT curve was significantly associated with a male fetus and higher levels of pregnancy-associated plasma protein A at the first-trimester screening. Although flat OGTT can possibly reflect some degree of hyperinsulinemia, it is generally not associated with adverse maternal or neonatal outcomes.

New reference values for biometrical measurements and sonographic estimated fetal weight in twin gestations and comparison to previous normograms.

Objective To construct new reference values for biometrical measurements and sonographic estimated fetal weight (sEFW) in twin gestations and compare them to previously published normograms. Methods A retrospective analysis of sEFW evaluations of twin gestations was performed between 2011 and 2016 in a single university-affiliated medical center. sEFW was calculated using the Hadlock 1985 formula. To avoid selection bias, one evaluation per pregnancy was randomly selected. Following mathematical transformation to obtain normality of values, normograms were constructed using a best-fit regression model for estimation of mean and standard deviation at each gestational age (GA). Normograms were validated by applying all observations to ensure equal distribution at parallel percentiles. Our normograms were then compared to previously published sEFW normograms for twin gestations. Results A total of 864 sEFW evaluations were performed on 195 twin pregnancies at 22-39 gestational weeks. Of them, 390 entered the primary analysis. The rest were left for validation. Seventy percent of the cohort were dichorionic-diamniotic twins (136/195), 16% (32/195) were monochorionic-diamniotic twins and three (1.5%) were monochorionic-monoamniotic twins. Twenty-four fetuses lacked data on chorionicity. The rest were monochorionic twins or were of unknown chorionicity. Values corresponding to the 2.5th, 10th, 50th, 90th and 97.5th percentiles for sEFW are presented for every GA. Validation by applying all 864 evaluations on constructed normograms was achieved. Comparison to previously published twins' sEFW normograms demonstrated wide variation between curves. Conclusion New reference values for biometrical measurements and sEFW in twin gestations are presented for clinical and research use. Comparison to other curves demonstrates the wide variability and need for further investigation on twin's normal growth.

Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia.

PURPOSE: To determine the molecular basis of familial, autosomal-recessive, non-obstructive azoospermia in a consanguineous Iranian Jewish family. METHODS: We investigated the genetic cause of non-obstructive azoospermia in two affected siblings from a consanguineous family. Homozygosity mapping in the DNA samples of the patients and their normospermic brother was followed by exome analysis of one of the patients. Other family members were genotyped for the mutation by Sanger sequencing. The mutation effect was demonstrated by immunostaining of the patients' testicular tissue. RESULTS: The two patients were homozygous for a splice site mutation in SYCE1 which resulted in retention of intron three in the cDNA and premature stop codon. SYCE1 encodes a Synaptonemal Complex protein which plays an essential role during meiosis. Immunostaining of patient's testicular tissue with anti-Syce1 antibody revealed an undetectable level of Syce1. Histological examination of the patients' tissue disclosed immature-stages spermatocytes without mature forms, indicating maturation arrest. CONCLUSION: The significance of most synaptonemal complex proteins was previously demonstrated in a mutant mouse model. The present report underscores the importance of synaptonemal complex proteins in spermatogenenesis in humans. Our new approach, combining homozygosity mapping and exome sequencing, resulted in one of the first reports of an autosomal-recessive form of NOA.

First-trimester fasting plasma glucose levels and progression to type 2 diabetes: A 5-year cohort study.

OBJECTIVE: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100-125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first-trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first- trimester fasting plasma glucose levels, as compared with gestational diabetes, a well-established risk factor for diabetes, in up to 5-year follow-up postpartum. METHODS: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post-delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic-area under the curve (ROC-AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status. RESULTS: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut-off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity. CONCLUSIONS: Increased first-trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first-trimester fasting plasma glucose has a more pronounced impact on progression to diabetes.

One abnormal value in oral glucose tolerance test during pregnancy and type 2 diabetes risk: Insights from a 5-Year Follow-Up study.

OBJECTIVES: To evaluate the risk of type 2 diabetes(T2D) following one abnormal value(OAbV) in an oral glucose tolerance test(oGTT) performed during pregnancy. STUDY DESIGN: A retrospective analysis of parturients between 01.01.2017 and 31.12.2020 with 5 years of follow-up after delivery. Glucose levels during pregnancy were extracted from the computerized laboratory system of Meuhedet HMO and cross-tabulated with the Israeli National Registry of Diabetes. Women with multiple gestations or pregestational diabetes were excluded. Maternal characteristics and risk of T2D were stratified and compared between 3 groups: normal glucose status, OAbV in oGTT, and gestational diabetes. Statistical analysis included univariate analysis followed by survival analysis. Further analysis was stratified to women with and without obesity. RESULTS: 58,693 women entered the analysis. Following an adjustment to maternal age, obesity, hypertension, and hyperlipidemia, OAbV in oGTT was associated with a 1.8-fold increased risk of T2D in a 5-year follow-up compared to normal glucose status. When stratified by obesity, OAbV was associated with a 3.7-fold increase in T2D in women without obesity, however, was no longer a statistically significant predictor of T2D among women with obesity. CONCLUSIONS: Women with OAbV oGTT during pregnancy are at increased risk for developing T2D over 5 years of follow-up.

External validation of vaginal birth after cesarean delivery calculator in Israeli cohort of parturients and construction of an improved model.

OBJECTIVE: To validate the Maternal Fetal Medicine Unit's (MFMU) vaginal birth after cesarean delivery (VBAC) calculator in an Israeli cohort, and to detect other variables associated with VBAC and construct an improved VBAC calculator. METHODS: A retrospective cohort study was performed at a single university-affiliated medical center. Women carrying a singleton, term, cephalic-presenting fetus, with previous one low transverse cesarean delivery who opted for trial of VBAC were included. Demographic and obstetric characteristics were incorporated into the MFMU's calculator, to predict probabilities of VBAC and compare prediction performance with the original publication utilizing receiver operating characteristic (ROC) statistics. Logistic regression analysis was used to investigate other variables and construct an improved model for success of VBAC. RESULTS: Of 490 parturients, 396 (80.8%) had a successful vaginal delivery. Compared to the original publication, the MFMU's calculator underperformed: area under the ROC curve (AUC) was 0.709 (95% confidence interval [CI] 0.652-0.766, P < 0.001). Sensitivity, specificity, positive and negative predictive values, and overall accuracy were 67.42%, 65.96%, 89.30%, 32.46%, and 32.46%, respectively. An improved model that included previous VBAC, prior vaginal delivery, spontaneous onset of delivery, and maternal diabetes resulted in improved prediction performance with an AUC of 0.771 (95% CI 0.723-0.82, P < 0.001). CONCLUSION: MFMU's VBAC calculator needs to be validated in different populations before implementation.

Oral Glucose Tolerance Test Performed after 28 Gestational Weeks and Risk for Future Diabetes-A 5-Year Cohort Study.

Gestational diabetes mellitus (GDM) is diagnosed by an oral glucose tolerance test (oGTT), preferably performed at 24 + 0-28 + 6 gestational weeks, and is considered a risk factor for type 2 diabetes (T2DM). In this study, we aimed to evaluate the risk of T2DM associated with abnormal oGTT performed after 28 weeks. We conducted a retrospective cohort study that included parturients with available glucose levels during pregnancy and up to 5 years of follow-up after pregnancy. Data were extracted from the computerized laboratory system of Meuhedet HMO and cross-tabulated with the Israeli National Registry of Diabetes (INRD). The women were stratified into two groups: late oGTT (performed after 28 + 6 weeks) and on-time oGTT (performed at 24 + 0-28 + 6 weeks). The incidence of T2DM was evaluated and compared using univariate analysis followed by survival analysis adjusted to confounders. Overall, 78,326 parturients entered the analysis. Of them, 6195 (7.9%) performed on-time oGTT and 5288 (6.8%) performed late oGTT. The rest-66,846 (85.3%)-had normal glucose tolerance. Women who performed late oGTT had lower rates of GDM and T2DM. However, once GDM was diagnosed, regardless of oGTT timing, the risk of T2DM was increased (2.93 (1.69-5.1) vs. 3.64 (2.44-5.44), aHR (95% CI), late vs. on-time oGTT, p < 0.001 for both). Unlike in oGTT performed on time, one single abnormal value in late oGTT was not associated with an increased risk for T2DM.

Factors Associated with Progression to Preeclampsia with Severe Features in Pregnancies Complicated by Mild Hypertensive Disorders.

In this retrospective cohort study, we aimed to investigate the variables associated with progression to preeclampsia with severe features in parturients already diagnosed with mild hypertensive disorders of pregnancy. The study was conducted in a single university-affiliated medical center between 2018 and 2020. All women admitted due to hypertensive disorders were included. Data collected was compared between parturients who progressed and did not progress to preeclampsia with severe features. Among 359 women presenting without severe features, 18 (5%) developed severe features, delivered smaller babies at lower gestational age, and with higher rates of cesarean delivery (p < 0.001 for all). Chronic hypertension, maternal diabetes, any previous gestational hypertensive disorder, gestational diabetes, number of hospitalizations, earlier gestational age at initial presentation, and superimposed preeclampsia as the preliminary diagnosis were all associated with preeclampsia progression to severe features. Previous delivery within 2-5 years was a protective variable from preeclampsia progression. Following regression analysis and adjustment to confounders, only gestational age at initial presentation and superimposed preeclampsia remained significant variables associated with progression to severe features (aOR 0.74 (0.55-0.96) and 34.44 (1.07-1111.85), aOR (95% CI), respectively, p < 0.05 for both) with combined ROC-AUC prediction performance of 0.89, 95% CI 0.83-0.95, p < 0.001. In conclusion, according to our study results, early gestational age at presentation and superimposed preeclampsia as the preliminary diagnosis are the only independent factors that are associated with progression to severe features in women already diagnosed with mild hypertensive disorders during pregnancy.

Hypoglycemia during the oral glucose tolerance test in pregnancy-maternal characteristics and neonatal outcomes.

OBJECTIVE: To evaluate maternal and neonatal outcomes in pregnancies complicated by hypoglycemia on 100-g oral glucose tolerance test (OGTT). METHODS: A retrospective cohort analysis of all live-born deliveries in a single medical center during 2018 and 2019 with available OGTT results and birth outcomes. Preterm deliveries (<34 weeks), multiple pregnancies and major anomalies were excluded. Hypoglycemia during OGTT was defined as at least one glucose value below 60 mg/dl. Maternal characteristics and perinatal outcomes were compared between three groups: Hypoglycemia on OGTT, Normal OGTT and Abnormal OGTT. Univariate followed by multivariate analyses were used to control for confounders. RESULTS: Overall, 2079 women were entered into the analysis. Of these, 216 (10.4%) had at least one hypoglycemic value, 1072 (51.6%) had normal OGTTs and 791 (38%) abnormal OGTTs. Hypoglycemia in OGTT was more prevalent in multiparous women and was associated with fetal male gender. Absolute birth weight, low birth weight and small for gestational age differed between groups; however, there was no difference between groups in overall birth weight centiles (60.1 ± 26.8 versus 63 ± 26 versus 60.9 ± 27; P > 0.05). Following adjustment of confounders, hypoglycemia was not associated with rates of low birth weight or small for gestational age (P < 0.05). There were no other differences in perinatal outcomes between groups. CONCLUSION: Hypoglycemia in OGTT is not associated with maternal or neonatal adverse outcomes.

[Fallopian tube torsion--a rare complication in the reproductive age].

Isolated fallopian tube torsion (ITT) is a rare condition defined as a total or partial rotation of the fallopian tube around its vascular axis. The torsion initiaLLy interferes with the venous and lymphatic circulation. If unrelieved in time, rapid progression occurs, occluding the arterial circulation and Leading to gangrene and hemorrhagic necrosis. The cLinicaL appearance usually includes sharp lower abdominal pain, with or without peritoneal signs. Urinary and gastrointestinal signs might also occur. isolated fallopian tube is a rare condition; the incidence s estimated to be 1:500,000 mostly in reproductive age women. ITT is most common in the right side, although several reports claim that there is no difference between the sides. The etiology is not completely understood, but tubal anomalies (anatomic or physiologic) as well as trauma or pelvic inflammation are predisposing factors. The clinical appearance and the imaging in these cases are not pathognomonic, and many cases are delayed by means of diagnosis and treatment. The treatment is surgical. Detorsion or salpingectomy is usually performed by laparoscopy. Three cases that were treated lately at the Department of Obstetrics and Gynecology at the Hadassah Medical Center are presented together with a review of the literature.

Using adhesive glue to repair first degree perineal tears: a prospective randomized controlled trial.

Our objective was to evaluate the effectiveness of adhesive glue in repairing first degree perineal tears. We conducted a noninferiority prospective, randomized, controlled trial comparing adhesive glue with traditional suturing. Each case was evaluated immediately after birth and after the puerperium. The two-sample t-test and the Mann-Whitney nonparametric test were applied to compare quantitative variables between the treatment groups. The chi-squared test and Fisher's exact test were used to assess the association between qualitative variables. A total of 102 women participated, 28 in the suture arm and 74 in the adhesive glue arm. While cosmetic and functional results of adhesive glue use were not inferior to suturing, the use of adhesive glue was associated with a shorter procedure, less need for local anesthetic, less pain, and greater satisfaction. Our results suggest a novel approach for the repair of common postpartum first degree lacerations. The use of adhesive glue achieves cosmetic and functional results equal to traditional suturing and offers some immediate advantages for the patient. While further clinical trials are needed to validate our results, it is important to inform obstetrician of the possible use of adhesive glue in these very common clinical scenarios. This trial is registered with NCT00746707.

Pilonidal cyst involving the clitoris in an 8-year-old girl--a case report and literature review.

Pilonidal disease is common among adolescents and adults, mainly located in the sacral area. Pilonidal disease involving the clitoris is extremely rare and has not been described in premenarcheal girls. We present a case of a recurrent pilonidal periclitoral cyst in an 8-year-old girl which was surgically treated.