Detection of copy number variants associated with late-onset conditions in ~16 200 pregnancies: parameters for disclosure and pregnancy outcome.

BACKGROUND: Copy number variants (CNVs) associated with late-onset medical conditions are rare but important secondary findings in chromosomal microarray analysis (CMA) performed during pregnancy. Here, we critically review the cases at two tertiary centres to assess the criteria which guide the disclosure of such findings and develop a disclosure decision tool (DDT) aimed at facilitating disclosure decision. Parental decisions on receiving CNVs associated with risks for late-onset conditions were also recorded. METHODS: Prenatal CMAs in Hadassah and Shaare Zedek Medical Centers from November 2013 to October 2021 were reviewed for CNVs associated with late-onset conditions. The DDT proposed uses a five-parameter scoring system, which considers the severity, median age of onset, penetrance, understanding of genotype-phenotype correlation and actionability of the finding. RESULTS: Out of 16 238 prenatal CMAs, 16 (0.1%) harboured CNVs associated with late-onset conditions, 15 of which were disclosed. Outcome information was available on 13 of the 16 pregnancies, all of which continued to delivery. CONCLUSIONS: Our suggested DDT will help clinicians to quantitatively weigh the variables associated with CNVs of this type and arrive at a well thought out clinical decision regarding disclosure. Although the prevalence of late-onset conditions as a major finding in the prenatal setup is low, it is expected to rise with the increasing use of non-invasive CMA testing and whole exome and genome sequencing.

Is it time for prenatal chromosomal-microarray analysis to all women? A review of the diagnostic yield in structurally normal fetuses.

PURPOSE OF REVIEW: Chromosomal-microarray analysis (CMA) is the first-tier test in pregnancies with structural malformations. Accumulating data show that pathogenic copy number variants (CNVs) can also be identified in structurally normal fetuses. We set out to summarize the published data on the diagnostic yield of CMA in structurally normal fetuses. RECENT FINDINGS: Six studies summarize a total of 29,612 prenatal CMAs performed in structurally normal fetuses. The incidence of highly penetrant pathogenic/likely pathogenic CNVs is 0.4-2.5%. Variability was demonstrated in the timing of CMA testing and type of CNVs classified as pathogenic. The incidence of variants of uncertain significance is 0.4-5.4%. The prevalence of susceptibility loci is 0.3-0.7% when specified, and the incidence of CNVs associated with late onset disease is 0.1%. SUMMARY: With a frequency of abnormal CNVs of 1:40 to 1:250 in structurally normal fetuses, it is recommended that all pregnant women be informed of the possibility to have CMA performed, even in the absence of malformations. Information should also be provided about uncertain and secondary findings.

Repair of uterine rupture following vaginal delivery: A comparison between minimally invasive and open repair.

OBJECTIVE: To compare operative data and patient satisfaction between open and laparoscopic surgery for postpartum-diagnosed uterine rupture. METHODS: In this questionnaire-based cohort study, the authors collected all cases of postpartum-diagnosed uterine rupture after vaginal delivery between 2016 and 2020 in a single academic tertiary center. The cohort was divided according to surgical method of repair, and demographic, clinical, operative and postoperative data were collected and compared between groups. A phone questionnaire on various satisfaction domains was conducted and satisfaction rates were compared between groups. RESULTS: Eight cases of uterine rupture following vaginal delivery were treated by laparoscopy and eight were treated by laparotomy. The median operative time was 103 min (interquartile range [IQR], 86.3-129.0 min) for the laparoscopy group and 61 min (IQR, 59.0-75.0 min) for the laparotomy group (P = 0.04). Blood transfusion was required in 25% of women who underwent laparoscopy, as compared with 88% of women who underwent laparotomy (P = 0.01 < 0.05). Median hospitalization time was 3 days (IQR, 3-4 days) in the laparoscopy group and 4 days (IQR, 4-4 days) in the laparotomy group (P = 0.2). Overall satisfaction, satisfaction from recovery, satisfaction from scars, satisfaction from ability to care for the neonate, and postoperative pain and mood were all improved in the laparoscopy group, as compared with the laparotomy group. CONCLUSION: Minimally invasive surgery is a viable surgical option for patients with uterine rupture diagnosed after vaginal delivery and may result in better patient recovery and satisfaction.

The effect of BNT162b2 SARS-CoV-2 mRNA vaccine on menstrual cycle symptoms in healthy women.

OBJECTIVE: To investigate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA BNT162b2 vaccine on women's menstrual cycle. METHODS: In this questionnaire-based cross-sectional study, we assessed menstrual pattern and changes in women who completed the SARS-CoV-2 mRNA BNT162b2 vaccine 3 months before and after receiving the vaccine. Included were women aged 18-50 years without known gynecologic comorbidities who regularly monitor their menstruation through electronic calendars. All participants competed a detailed questionnaire on their menstrual symptoms including information on any irregular bleeding. To minimize bias, each woman served as a self-control before and after vaccination. Primary outcome was rate of irregular bleeding following vaccination and secondary outcome was presence of any menstrual change, including irregular bleeding, mood changes, or dysmenorrhea following the vaccine. RESULTS: A total of 219 women met the inclusion critieria. Of them, 51 (23.3%) experienced irregular bleeding following the vaccine. Almost 40% (n = 83) of study participants reported any menstrual change following vaccination. Parity was positively asssociated with irregular bleeding with 26 (50%) of those suffering from irregular bleeding being multiparous compared with only 53 (31.5%) of women with no irregular bleeding (nulliparous 46% vs 60%, multiparous 50% vs 31%, rest 4% vs 8%, P = 0.049). The presence of medical comorbidities was also significantly higher among patients who experienced irregular bleeding (20.0% vs 6.0%, P = 0.003). CONCLUSION: Our study shows relatively high rates of irregular bleeding and menstrual changes after receiving the SARS-CoV-2 mRNA BNT162b2 vaccine. Further research is needed to confirm our findings and to better characterize the magnitude of change and any possible long-term implications.

Urinary tract injuries during cesarean delivery: long-term outcome and management.

OBJECTIVE: Urinary tract injury during cesarean delivery is a rare but severe complication. Due to the high prevalence of cesarean delivery, this injury may pose a high burden of morbidity. We reviewed the cases of lower urinary tract injuries identified during cesarean delivery in a tertiary medical center and identified diagnosis and treatment methods, as well as short and long-term outcomes, to establish a protocol of care for such cases. METHODS: We included women with urinary tract injury during cesarean delivery between 2004 and 2018. The cases were identified according to ICD-9 codes, as well as free text in the medical report and discharge letter. Data were collected retrospectively. Telephone interviews were conducted to obtain additional data regarding long-term outcomes. RESULTS: In14 years, a total of 17,794 cesarean deliveries were performed at our institution (17.5% of all deliveries), 14 cases of bladder injury, and 11 cases of ureteral injury were identified featuring an incidence of 0.08 and 0.06%, respectively. All bladder injuries were diagnosed and repaired intra-operatively. Six (55%) cases of ureteral injury were diagnosed in the post-operative period, and 3 of these patients required further surgery for definitive treatment. None of the patients suffered long-term adverse effects. Most bladder injuries occurred in women with previous cesarean delivery in the presence of abdominal adhesions. In contrast, most ureteral injuries occurred in women with emergency cesarean delivery during the second stage of labor, and were accompanied by an extension of the uterine incision. All women had normal kidney function in follow up and did not suffer from long term sequelae. CONCLUSION: Urinary tract injury is an uncommon complication of cesarean delivery. A high index of suspicion is recommended to avoid late diagnosis and complications. We propose a comprehensive protocol for the management of these injuries.

Repeat Kidney Transplant in a Patient With a Double Inferior Vena Cava and Difficult Venous Access: A Case Report.

Many obstacles may complicate renal transplant, the preferred treatment for end-stage renal disease. Anatomic anomalies are of special importance during surgery. Double inferior vena cava is a rare anomaly reported in 0.2% to 3% of the population and may complicate renal transplant in certain cases. We present a case of a 29-year-old man with end-stage renal disease who was scheduled for repeat kidney renal transplant from a living related donor. His transplant posed many challenges to the transplant team. These included (1) difficult access for dialysis, which required transhepatic insertion of a dialysis catheter, (2) anomalous inferior vena cava anatomy with a double inferior vena cava, (3) a blocked right inferior vena cava, and (4) a small blocked bridging vein connecting the right inferior vena cava to an additional left inferior vena cava. A stent was inserted into the bridging vein to allow venous drainage from the graft. During the transplant procedure, the donated kidney was transplanted into the left iliac fossa and anastomosed to the left external iliac vein. The surgery was successful, without major operative or postoperative complications. The patient was discharged with normal renal function and enjoys normal renal function 6 months after surgery. This case emphasizes the importance of pretransplant evaluation and preparation and the need for high index of suspicion for anatomic variants in donors and recipients.