Indications of invasive prenatal diagnosis in third trimester and pregnancy outcome / 中华围产医学杂志

Objective:To analyze the indications for invasive prenatal diagnosis in the third trimester and summarize the pregnant outcome.Methods:Clinical data of 121 women who underwent invasive prenatal diagnosis in the third trimester in the prenatal diagnostic center of the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020 was retrospectively analyzed. Different genetic diagnostic methods were used according to different indications. Indications and results of prenatal diagnosis, as well as the complications within two weeks after the invasive procedure, pregnancy outcome, and neonatal follow-up of all the participants were described.Results:Among the 121 cases, 107 cases underwent amniocentesis, seven underwent percutaneous umbilical blood sampling, and seven had both procedures performed at the same time (one underwent thoracocentesis at the same time). Newly identified ultrasound abnormalities in the second and third trimesters were the main indications for prenatal diagnosis, accounting for 99.2%(120/121), of which short limbs and fetal growth restriction accounted for 25.0% (30/120) and 20.0% (24/120), respectively. Genetic abnormalities and congenital diseases were detected in 20 cases with a detection rate of 16.5%(20/121). Among them, there were nine cases of achondroplasia, five cases of pathogenic copy number variations, one case of achondroplasia with pathogenic copy number variation, one trisomy 18, one 47,XXX, one tetrasome mosaicism of 12p, one de novo WTX c. 1072(Exon2) C>Tp.R358X heterozygous mutation, and one fetal hypoproteinemia. In addition, six cases with copy number variation of unknown significance (VUS) were detected, noting for a detection rate of 5.0%(6/121). Among the 20 cases with abnormal detection, 15 were terminated, two delivered prematurely before obtaining the prenatal diagnosis results, one underwent cesarean section before obtaining prenatal diagnostic results and two continued the pregnancies. In the six cases with VUS, one was terminated and the other five continued the pregnancy. Only one case had preterm premature rupture of membranes 2 d after amniocentesis and the incidence rate of complications after all kinds of invasive procedures was 0.8% (1/121). During the neonatal follow-up, postnatal whole exome sequencing revealed monogenetic disorder in two cases with normal prenatal diagnostic results; the patient with 12p chimerism had developmental delay; the one with WTX mutation deceased on the day of born; the rest newborns developed normally. Conclusions:As a relatively safe method, invasive prenatal diagnosis in the third trimester is of great importance and value in reducing the miss diagnostic rate of fetuses with severe genetic diseases and birth defects. The appropriate application of prenatal whole exome sequencing could further help to decrease the miss diagnostic rate of monogenetic disorder.

Study of genetic etiology in fetuses with severely short limbs in the first and second trimester using whole exome sequencing / 中华妇产科杂志

Objective To investigate pathogenic genes related to the phenotype of fetus with severely short limbs in the first and second trimester by whole exome sequencing (WES). Methods Thirteen fetuses with severely short limbs detected by ultrasonography in the first and second trimester admitted in Chinese PLA General Hospital from September 2016 to June 2018 were collected. All cases were performed induced abortion, 6 of which were carried out karyotype analysis of amniotic fluid at the same time. WES and copy number variations (CNV) were performed on specimens from fetal tissues after labor induction. The suspected pathogenic mutations were validated by Sanger sequencing reactions. Results No abnormal karyotypes or pathological CNV were found. In 10 fetuses, pathogenic or possibly pathogenic mutations were detected in the following genes: COL2A1, FGFR3, COL1A1, COL1A2, DYNC2LI1 and TRIP11, all of which were essential to skeletal development. The diagnostic yield of WES in the fetuses with severe short limbs was 10/13. Conclusions In the first and second trimester, most of the fetuses with extremely short limbs suffer from monogenic diseases. WES is likely to be a valuable diagnostic testing option for the fetuses with severe short limbs.

Prognosis and reproductive outcome of laparoscopic intracapsular myomectomy / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the prognosis and reproductive outcomes of laparoscopic intracapsular myomectomy.</p><p><b>METHODS</b>A total of 673 women received subserosal and intramural intracapsular laparoscopic myomectomy between March, 2007 and March, 2012, and their post-operative complications, the need for subsequent surgery, symptomatic relief and reproductive outcomes were analyzed.</p><p><b>RESULTS</b>Of these patients, 42.4% had subserosal myomas and 57.6% had intramural myomas. The mean total operative time was 96∓41 min with a mean blood loss of 128∓46.2 ml, and 82.3% of the patients were discharged 48 h after the operation without early complications. A small fraction (2.3%) of the patients had a second laparoscopic myomectomy for recurrent fibroids. Of the fertility-demanding women who underwent myomectomy, 71% achieved pregnancy, 49.8% underwent caesarean section, 8% had operative vaginal deliveries, and 42.2% had spontaneous deliveries; uterine rupture occurred in none of the cases.</p><p><b>CONCLUSION</b>Laparoscopic intracapsular myomectomy, by preserving the fibroid pseudocapsule and myometrial integrity, has no early postoperative complications and ensures good fertility rates and reproductive outcomes.</p>

Application of acellular allograft dermal tissue patch in the repair of transvaginal rectovaginal fistula / 中华妇产科杂志

Objective To investigate the clinical effect of acellular allograft dermal tissue patch used in transvaginal rectovaginal fistula repair.Methods From Jan.2008 to Dec.2011,22 patients with rectovaginal fistula undergoing treatment in Chinese People's Liberation Army General Hospital were studied retrospectively.Twelve patients treated by tissue patch were classified into study group matched with 10 patients with general surgery as controls.Results In study group,11 patients were successfully repaired by their first surgery; one patient was successfully fixed by the second surgery.The successful rate of first operation was 11/12 in study group and 4/5 in recurrent transvaginal rectovaginal fistula.In control group,7 patients were fixed successfully in their first surgeries,the successful rate of first surgery was 7/10.Two primary patients and 1 recurrent patient were successfully fixed by their second surgeries.All of the patients were followed up for (9.0 ± 2.0) months,and no recurrence diseases were observed.Conclusion The transvaginal rectovaginal fistula fixed using acellular allografi dermal tissue patch could get less trauma and higher cure rate.

Value of detection of cell-free fetal DNA in maternal plasma in the prenatal diagnosis of chromosomal abnormalities / 中华妇产科杂志

Objective To investigate the value of detection of fetal cell-free fetal DNA(cff-DNA)in maternal plasma in the prenatal diagnosis of chromosomal abnormalities.Methods The plasma from 3200 gravidas(singleton with 20.3 ± 3.8 gestational weeks)was collected from April 1st 2011 to May 30th 2012.They were divided into 3 groups:(1)To tally 1720 cases were included in the high-risk serological screening group,in which women were younger than 35 years and got high-risk results in serological screening;(2)To tally 1310 cases were included in the advanced age group,in which women's age was more than 35 years;(3)To tally 170 cases were included in the supplementary group,in which women were younger than 35 years and got low-risk results in serological screening,or women who didn't take serological screening tests.All the 3030 gravidas in group 1 and 2 didn't take invasive prenatal diagnosis because of fear of abortion or short of prenatal diagnosis.Cff-DNA were detected by next generation sequencing in Shenzhen BGI Genomics Center for clinical laboratory.Amniocentesis and karyotype analysis were provided to the positive cases and women with negative results were followed-up by telephone.Results(1)The 3200 cases took cff-DNA detection,and 31 cases got positive results,including 27 cases of trisomy 21 and 4 cases of trisomy 18.Sixteen cases of trisomy 21 and 1 case of trisomy 18 were in the high-risk serological screening group.7 cases of trisomy 21 and 2 cases of trisomy 18 were in the advanced age group.Four cases of trisomy 21 and 1 case of trisomy 18 were in the supplementary group.(2)And the 84％(26/31)cff-DNA detecting positive cases received amniocentesis.In the 27 trisomy 21 positive cases,23 received amnioeentesis and got karyotype of 47XN,+ 21,with the diagnostic accordance rate of 100％.In the 4 cases who didn't take karyotype analysis,fetal anomaly(ventricular septal defect,dextrocardia and choroid plexus cyst)was found in 1 case before 20 gestational weeks;intrauterine fetal demise happened in 1 case before getting the result;2 other cases who already had healthy children took abortion in the local hospital without taking amniocentesis.In the 4 trisomy 18 positive cases,3 took amniocentesis,2 of which were trisomy 18 and took abortion,the other was chimera(46,XN/47,XN,+ 18)with only 2％ cells of trisomy 18,with no malformation found after delivery.Hypoevolutism(3 weeks less than gestational week),general hydropsy and intrauterine fetal demise happened before the other case took amniocentesis.(3)Follow up of cff-DNA negative cases:until May 30th 2012,no Down's baby was found in the 1230 cases with cff-DNA test negative results.Conclusions(1)The non-invasive fetal trisomy test(NIFTY)by next generation sequencing is a safe,accurate and high throughput method for the prenatal diagnosis of trisomy-21.(2)Use NIFTY as a further screening for pregnant women with high-risk serological screening results could lower invasive prenatal diagnosis rate.(3)Cases with positive NIFTY test results should receive amniocentesis and karyotype analysis to confirm the diagnosis before abortion.