Outcomes of dichorionic twin pregnancies with fused versus separate placentas.

PURPOSE: In a certain proportion of dichorionic twin pregnancies, the two placentas are fused. The clinical significance of this finding remains unclear. Our objective was to compare outcomes of dichorionic twin pregnancies with fused versus separate placentas as determined on first-trimester ultrasound. METHODS: Retrospective study of patients with dichorionic twins followed at a tertiary center between 2014 and 2022. The co-primary outcomes were fetal growth restriction and preeclampsia. Associations between fused placentas and the study outcomes were estimated using multivariable Poisson regression and were reported as adjusted relative risk (aRR) with a 95%-confidence interval (CI). RESULTS: Of the 328 eligible patients, 175 (53.4%) and 153 (46.6%) had fused and separate placentas, respectively. Compared with pregnancies with separate placentas, patients with fused placentas had a lower risk of preeclampsia [aRR 0.48 (95%-CI 0.24-0.97)] but a higher risk of fetal growth restriction [aRR 1.23 (95%-CI 1.02-1.48)] and admission to the neonatal intensive care unit [aRR 1.31 (95%-CI 1.01-1.71)]. In addition, pregnancies with fused placentas were more likely to have a total placental weight below the 10th percentile than those with separate placentas [aRR 1.93 (95%-CI 1.16-3.21)]. DISCUSSION: Dichorionic twin pregnancies with fused placentas have a lower risk of preeclampsia but are more likely to be complicated by fetal growth restriction, observations that may be attributed to the lower total placentas mass in pregnancies with fused compared with separate placentas. Fused placentas can be used as a potential biomarker for the prediction of pregnancy complications in dichorionic twin pregnancies.

Complex Gynecologic Fistulas Presenting 10 Years After Uterine Artery Embolization.

BACKGROUND: Uterine artery embolization (UAE) is a minimally invasive procedure for treatment of symptomatic uterine leiomyomas, but long-term complications are under-reported. CASE: This is the case of a healthy 51-year-old woman who had previously undergone UAE for symptomatic uterine leiomyomas. The patient presented with gross hematuria and pelvic pain 10 years later. She was found to have both a vesicouterine and a uteroduodenal fistula. The patient was successfully treated with hysterectomy, excision of the vesicouterine fistula, partial cystectomy, excision of the duodenal fistula, and primary duodenal repair. CONCLUSION: Complex gynecologic fistulas may occur as a long-term complication in symptomatic women with a history of UAE.

Should pregnant women with diabetes be counseled differently if nephropathy was detected? a population database study.

INTRODUCTION: The prevalence of diabetes mellitus has increased tremendously in the last two decades among women of reproductive age and this is mainly due to the pandemic of obesity. Diabetes mellitus is a well-known cause of maternal and neonatal complications in pregnancy. Diabetic nephropathy is a marker of severe diabetes and results in organ damage. However, only a small number of studies have evaluated the implications of diabetic nephropathy on pregnancy complications, with most having 50 to 100 nephropathy subjects. Our study aims to compare pregnant women with diabetes mellitus complicated by nephropathy or not and evaluate the relationship with obstetrical and perinatal morbidity and mortality, on a larger population. METHODS: This was a population-based study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) including women who delivered between 2004 and 2014. Multivariate logistic regression was used to control for confounding effects. RESULTS: Among 86,615 pregnancies that were complicated by diabetes mellitus, 1,241 (1.4%) had diabetic nephropathy. Diabetic nephropathy was strongly associated with preeclampsia (aOR 2.3, 95% CI 1.90-2.68), as well as chronic hypertension with superimposed preeclampsia or eclampsia (aOR 4.2, 95% CI 3.53-5.01), preterm birth (aOR 1.8, 95% CI 1.59-2.1), and blood transfusion (aOR 3.6 95% CI 2.82-4.46). Both groups were similar in age and income. CONCLUSION: Diabetic nephropathy is associated with increased obstetrical and perinatal morbidity compared to diabetes mellitus alone. These patients may benefit from a high dose of folic acid, more vigilant antenatal surveillance, delivery in a tertiary care center, and more rigorous screening and prevention methods for pregnancy-induced hypertension diseases at antenatal care visits.

Effect of double embryo transfer derived from autologous frozen oocytes on multiple pregnancy rates and presentation of success rates stratified by age at retrieval

Objective: To compare outcomes transferring one or two embryos in autologous frozen oocyte cycles. Material and Methods: A retrospective cohort study conducted at an academic fertility center between January 2012 and December 2018. One-hundred and fourteen patients underwent frozen oocyte transfers; 67 single embryo transfer (SET) and 47 double embryo transfer (DET). No subjects had more than two embryos transferred. Data were analyzed using t-test and chi-squared testing. Multivariate logistic regression was used to control for confounding effects. Power analysis suggested an 82% power with alpha of 5% and effect size of 27%. Results: Regarding the embryo stage, 72% were cleavage embryos and 28% were blastocyst embryos. Among those who had cleavage stage embryos, 48.8% underwent SET and 51.2% underwent DET. In the blastocyst embryos group these proportions were 84.4% and 15.6%, respectively. There were no difference in pregnancy rate for SET (40.3%) vs DET (36.2%) (p=0.78). Additionally, the live birth rate did not differ between SET and DET (28.4 vs 19.1%, respectively, p=0.26). The multivariate multilevel analysis provided adjusted odds ratios (95% confidence interval) of: 1.85 (0.46-7.44) for pregnancy; 0.497 (0.05-4.86) for clinical pregnancy; and 0.82 (0.11-6.29) for live birth when comparing SET and DET. Multiple pregnancy rates were significantly lower in the SET (0%), compared with DET group (44.4%) (p<0.002). Conclusion: SET results in excellent live birth outcomes in autologous frozen oocyte cycles. However DET results in significantly increased rates of multiple pregnancies. This suggests that SET is a viable option in autologous frozen oocyte cycles.

Association Between Bowel Obstruction or Intussusception and Endometriosis.

OBJECTIVE: To evaluate the association between endometriosis and bowel obstruction or intussusception using a large population database. METHODS: This was a population-based study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) from 2005 to 2014. We studied women aged 18 to 55 years without inflammatory bowel disease or cancer. Multivariate logistic regression was used to examine the association between endometriosis and bowel obstruction. RESULTS: Of the 18 427 520 women who met the criteria for inclusion, 96 539 had experienced bowel obstruction, for an overall prevalence of 52 per 10 000, and 3825 had experienced intussusception, for an overall prevalence of 2 per 10 000. When adjusted for sociodemographic characteristics, women with pelvic endometriosis had a consistently higher likelihood of bowel obstruction (odds ratio [OR] 2.6; 95% confidendence interval [CI] 2.3-3.00, P <0.01). In particular, intestinal endometriosis was associated with a 14.6-fold increased risk of bowel obstruction (95% CI 11.4-18.8, P <0.01), while rectovaginal endometriosis was associated with a 2.00-fold increased risk (95% CI 1.5-2.6, P <0.01). Pelvic endometriosis was significantly associated with adhesive bowel obstruction (adjusted OR: 3.2; 95% CI 2.6-3.9) and non-adhesive bowel obstruction (adjusted OR 2.4; 95% CI 2.0-2.8). The rates of endometriosis among women with or without intussusception were comparable. CONCLUSIONS: Pelvic endometriosis, in particular rectovaginal and intestinal endometriosis is strongly associated with bowel obstruction, independent of the presence of intra-abdominal adhesions. We did not find any association between pelvic endometriosis and intussusception.

What Are the Live Birth and Multiple Pregnancy Rates When 1 Versus 2 Low-Quality Blastocysts Are Transferred in a Cryopreserved Cycle? a Retrospective Cohort Study, Stratified for Age, Embryo Quality, and Oocyte Donor Cycles.

Outcomes among women who transferred only Gardner's grade BB or lower quality frozen embryos transferred (FET) are not well known. Our objective is to study whether transferring 2 versus 1 frozen low-quality blastocysts will increase the live birth rate (LBR) and the multiple pregnancy rate (MPR). This is a retrospective cohort study including 1104 FET cycles. Only day 5-6 blastocysts of grade BB or lower quality were included. Clinical pregnancy rate (CPR), MPR, and LBR per cycle were compared between single embryo transfer (SET) (n = 969) and double embryo transfer (DET) (n = 135). CPR and MPR were compared between SET and DET in grade BB, BC, CB, and CC individually. Among SET, BB blastocysts had higher CPR 34% (P = 0.0001) and a sub-significant increase in LBR 19% (P = 0.059) in comparison to other grade SET. Among all BB, MPR was significantly higher when transferring two versus one (5.9 vs. 1.9, P = 0.009). If age at egg collection ≥ 40 years (n = 97), no difference was found in CPR (11.1 vs. 11.7, P = 0.9), MPR (0 vs. 0), and LBR (6.3 vs. 0,P = 0.13) when SET or DET was performed. If age was < 40 years (n = 818), the MPR was significantly higher in DET than SET (6.7 vs. 1.63, P = 0.004). In egg donor cycles (n = 189), there was no difference in CPR, MPR, and LBR between SET and DET. Single embryo transfer should be offered even in women ≥ 40 years of age or transferring lower quality embryos since transferring more did not increase outcomes in this group, and SET is likely the safest path.

Dimercapto-1-propanesulfonic acid (DMPS) induces metaphase II mouse oocyte deterioration.

In light of the recent lead contamination of the water in Flint, Michigan and its potential adverse outcomes, much research and media attention has turned towards the safety profile of commonly used chelators. Dimercapto-1-propanesulfonic acid (DMPS) typically used in the treatment of lead, mercury and arsenic poisoning also displays a high affinity towards transition metals such as zinc and copper, essential for biological functioning. It is given in series of dosages (0.2-0.4g/day) over a long period, and has the ability to enter cells. In this work, we investigated the mechanism through which increasing concentrations of DMPS alter oocyte quality as judged by changes in microtubule morphology (MT) and chromosomal alignment (CH) of metaphase II mice oocyte. The oocytes were directly exposed to increasing concentration of DMPS (10, 25, 50, 100 and 300µM) for four hours (time of peak plasma concentration after administration) and reactive oxygen species (mainly hydroxyl radical and superoxide) and zinc content were measured. This data showed DMPS plays an important role in deterioration of oocyte quality through a mechanism involving zinc deficiency and enhancement of reactive oxygen species a major contributor to oocyte damage. Our current work, for the first time, demonstrates the possibility of DMPS to negatively impact fertility. This finding can not only help in counseling reproductive age patients undergoing such treatment but also in the development of potential therapies to alleviate oxidative damage and preserve fertility in people receiving heavy metal chelators.

Sonographic Measurement of Cervical Volume in Pregnant Women at High Risk of Preterm Birth Using a Geometric Formula for a Frustum Versus 3-Dimensional Automated Virtual Organ Computer-Aided Analysis.

OBJECTIVES: To compare cervical volume measurements by 3-dimensional (3D) sonography using Virtual Organ computer-aided analysis (VOCAL; GE Healthcare, Milwaukee, WI) versus a manual method using a geometric formula for a frustum. METHODS: We included 142 asymptomatic pregnant women at 16 to 24 weeks gestation at high risk for preterm birth. With a Voluson 730 Expert system (GE Healthcare), they underwent 2-dimensional (2D) transvaginal sonographic cervical length measurements and 3D cervical volume acquisition. The stored volumes were processed by VOCAL on a surface tablet. Cervical volume was manually calculated from the 2D images by using the formula V = 1/3 × π × h × (r12 + r22 + r1 × r2), where V represents cervical volume; π was approximated as 3.14159; h, cervical length; r1, radius at the internal os; and r2, radius at the external os. RESULTS: Cervical volume was lower when obtained manually than by VOCAL, with a coefficient of variation of 30%, a mean difference of 10.1 ± 14.9 cm3 (P < .0001), and a poor interclass correlation coefficient of 0.62 (95% confidence interval [CI], 0.31 to 0.78). Both methods had good reproducibility; however, VOCAL had wider limits of agreement. A positive correlation was found between both methods (r = 0.63; P < .0001). No correlation was found between cervical length by 2D transvaginal ultrasound and cervical volume by the VOCAL technique (r = 0.06; 95% CI, -0.10 to 0.22) or cervical volume by the manual method (r = 0.2; 95% CI, 0.08 to 0.39). CONCLUSIONS: The cervix represents a frustum (truncated cone, r1 is not equal to r2) in shape rather than a cylinder. Both methods are reproducible; VOCAL is less reliable but provides higher values of cervical volume.

Mesna (2-mercaptoethane sodium sulfonate) functions as a regulator of myeloperoxidase.

Myeloperoxidase (MPO), an abundant protein in neutrophils, monocytes, and macrophages, is thought to play a critical role in the pathogenesis of various disorders ranging from cardiovascular diseases to cancer. We show that mesna (2-mercaptoethanesulfonic acid sodium salt), a detoxifying agent, which inhibits side effects of oxazaphosphorine chemotherapy, functions as a potent inhibitor of MPO; modulating its catalytic activity and function. Using rapid kinetic methods, we examined the interactions of mesna with MPO compounds I and II and ferric forms in the presence and absence of chloride (Cl-), the preferred substrate of MPO. Our results suggest that low mesna concentrations dramatically influenced the build-up, duration, and decay of steady-state levels of Compound I and Compound II, which is the rate-limiting intermediate in the classic peroxidase cycle. Whereas, higher mesna concentrations facilitate the porphyrin-to-adjacent amino acid electron transfer allowing the formation of an unstable transient intermediate, Compound I*, that displays a characteristic spectrum similar to Compound I. In the absence of plasma level of chloride, mesna not only accelerated the formation and decay of Compound II but also reduced its stability in a dose depend manner. Mesna competes with Cl-, inhibiting MPO's chlorinating activity with an IC50 of 5µM, and switches the reaction from a 2e- to a 1e- pathway allowing the enzyme to function only with catalase-like activity. A kinetic model which shows the dual regulation through which mesna interacts with MPO and regulates its downstream inflammatory pathways is presented further validating the repurposing of mesna as an anti-inflammatory drug.

Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality.

Cyclophosphamide (CTX) is a chemotherapeutic agent widely used to treat ovarian, breast, and hematological cancers as well as autoimmune disorders. Such chemotherapy is associated with reproductive failure and premature ovarian insufficiency. The mechanism by which CTX and/or its main metabolite, acrolein, affect female fertility remains unclear, but it is thought to be caused by an overproduction of reactive oxygen species (ROS). Here, we investigated the effect of CTX on metaphase II mouse oocytes obtained from treated animals (120mg/kg, 24h of single treatment), and oocytes directly exposed to increasing concentrations of CTX and acrolein (n=480; 0, 5, 10, 25, 50, and 100µM) with and without cumulus cells (CCs) for 45min which correlates to the time of maximum peak plasma concentrations after administration. Oocytes were fixed and subjected to indirect immunofluorescence and were scored based on microtubule spindle structure (MT) and chromosomal alignment (CH). Generation of ROS was evaluated using the Cellular Reactive Oxygen Species Detection Assay Kit. Deterioration of oocyte quality was noted when oocytes were obtained from CTX treated mice along with CTX and acrolein treated oocytes in a dose-dependent manner as shown by an increase in poor scores. Acrolein had an impact at a significantly lower level as compared to CTX, plateau at 10µM versus 50µM, respectively. These variation is are associated with the higher amount of ROS generated with acrolein exposure as compared to CTX (p<0.05). Utilization of antioxidant therapy and acrolein scavengers may mitigate the damaging effects of these compounds and help women undergoing such treatment.

Galactose and its Metabolites Deteriorate Metaphase II Mouse Oocyte Quality and Subsequent Embryo Development by Disrupting the Spindle Structure.

Premature ovarian insufficiency (POI) is a frequent long-term complication of classic galactosemia. The majority of women with this disorder develop POI, however rare spontaneous pregnancies have been reported. Here, we evaluate the effect of D-galactose and its metabolites, galactitol and galactose 1-phosphate, on oocyte quality as well as embryo development to elucidate the mechanism through which these compounds mediate oocyte deterioration. Metaphase II mouse oocytes (n = 240), with and without cumulus cells (CCs), were exposed for 4 hours to D-galactose (2 µM), galactitol (11 µM) and galactose 1-phosphate (0.1 mM), (corresponding to plasma concentrations in patients on galactose-restricted diet) and compared to controls. The treated oocytes showed decreased quality as a function of significant enhancement in production of reactive oxygen species (ROS) when compared to controls. The presence of CCs offered no protection, as elevated ROS was accompanied by increased apoptosis of CCs. Our results suggested that D-galactose and its metabolites disturbed the spindle structure and chromosomal alignment, which was associated with significant decline in oocyte cleavage and blastocyst development after in-vitro fertilization. The results provide insight into prevention and treatment strategies that may be used to extend the window of fertility in these patients.

Uterine tachysystole in spontaneous labor at term.

OBJECTIVES: The objective of this study is to determine the incidence of uterine tachysystole and its association with spontaneous labor at term. METHODS: A retrospective cohort study of 8008 women in spontaneous labor (without prostaglandins or oxytocin). Fetal heart tracings and uterine activity were recorded every 15 min. PRIMARY OUTCOME: occurrence of tachysystole (> 5 uterine contractions /10 min over 30 min periods). SECONDARY OUTCOMES: non-reassuring fetal heart tracings (NRFHT), NICU admissions, and cesarean deliveries. RESULTS: About 890 patients (11.1 %) had at least one episode of tachysystole. Non-whites have higher incidence of uterine tachysystole; adjusted odds ratio (aOR) was 1.66 for Hispanics (95% CI 1.28-2.05), 1.58 for African Americans (95% CI 1.05-2.38), and 1.51 for Asians (95% CI = 1.13-2.0). The use of epidural analgesia was higher in the tachysystole group (62.2% versus 40.9%, aOR 1.89, CI 1.58-2.26; p < 0.001). Tachysystole was more frequent among nulliparous women and in women carrying higher weight fetuses. Oligohydramnios (aOR 1.62, CI 0.70-3.72; p < 0.004), and NRFHT were more common in the tachysystole group (4.2% versus 2.5%, p = 0.002). Newborns in the tachysystole group were two times more likely to be admitted to NICU (30 /890 [3.4%] versus 122 /7118 [1.7%], OR = 2, p=0.001). There was no difference in the frequency of meconium-stained amniotic fluid or Apgar scores <7 at 5 min. CONCLUSION: Uterine tachysystole occurs in more than 10% of spontaneous labors and is associated with NRFHR, increased rate of caesarean deliveries and NICU admissions. It is not associated with low Apgar scores or meconium-stained amniotic fluid.