[Show abstract][Hide abstract] ABSTRACT: Objective
. Women with infertility and recurrent miscarriages may have an overlapping etiology. The aim of this study was to compare the pregnancy loss in pregnancies after IVF treatment with spontaneous pregnancies in women with recurrent miscarriages and to assess differences related to cause of infertility.
. The outcome from 1220 IVF pregnancies (Group I) was compared with 611 spontaneous pregnancies (Group II) in women with recurrent miscarriages. Subgroup analysis was performed in Group I based on cause of infertility: tubal factor (392 pregnancies); male factor (610 pregnancies); and unexplained infertility (218 pregnancies).
. The clinical pregnancy loss rate in Group I (14.3%) was significantly lower than that of Group II (25.8%,
) and this was independent of the cause of infertility. However the timing of pregnancy loss was similar between Groups I and II. The clinical pregnancy loss rate in Group I was similar in different causes of infertility.
. The clinical pregnancy loss rate following IVF treatment is lower than that of women with unexplained recurrent miscarriages who conceived spontaneously. This difference persists whether the infertility is secondary to tubal factors, male factors, or unexplained cause.
Obstetrics and Gynecology International 11/2015; 2015(10):1-6. DOI:10.1155/2015/989454
[Show abstract][Hide abstract] ABSTRACT: A couple with a proband child of GJB2 (encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis (PGD), noninvasive prenatal testing (NIPT), and noninvasive prenatal diagnosis (NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a singleton pregnancy. At the 13th week of gestation, genomic DNA (gDNA) from the trio family and cell-free DNA (cfDNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the association of tissue inhibitor of metalloproteinase (TIMP) gene polymorphisms with unexplained recurrent spontaneous abortions (URSA) in a well-defined group of Han Chinese couples.
This is a case-control association study. Genomic DNA was extracted from peripheral blood samples from 84 couples with histories of three or more pregnancy losses and 69 age-matched healthy couples with at least one live birth and no histories of pregnancy loss. Polymerase chain reactions (PCRs) and sequencing with the fluorescent dye dideoxy-termination method were used to detect the rs4898 in TIMP-1, rs2277698 in TIMP-2, rs2234921 and rs5749511 in TIMP-3 and rs17035945 in TIMP-4 genotypes and allele frequencies.
Neither the allele frequencies nor any of the genetic model of the five TIMP gene SNPs (i.e., TIMP-1-rs4898, TIMP-2-rs2277698, TIMP-3-rs5749511 and rs2234921, and TIMP-4-rs7035945) were significantly differences between the URSA couples and the control group.
No evidence was found for any associations between the TIMP-1,-2,-3, or -4 genes SNPs with URSA in this Han Chinese Han.
European Journal of Obstetrics & Gynecology and Reproductive Biology 07/2014; 181C:84-88. DOI:10.1016/j.ejogrb.2014.07.013 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To investigate whether intracavitary physiotherapy is superior to endometrial scratching in patients with recurrent implantation failure (RIF) after in vitro fertilization/intracytoplasmic sperm injection- embryo transfer (IVF/ICSI-ET) cycles.
According to the inclusion criteria defined by our hospital, 63 patients with RIF were included in the retrospective study. 20 patients who received intracavitary physiotherapy were classified into Group A, 8 patients with both intracavitary physiotherapy and endometrial scratching were into Group B, and 35 patients who underwent endometrial scratching were into Group C. The primary outcome measures were implantation and clinical pregnancy rates. The secondary outcome measure was pregnancy outcome.
There were no statistical differences in implantation and clinical pregnancy rates between Groups A and C (29.41 vs 35.59 %, 45.00 vs 48.57 % respectively, P > 0.05), Groups B and C (36.36 vs 35.59 %, 50.00 vs 48.57 % respectively, P > 0.05). In addition, no statistical differences were discovered in pregnancy outcomes between Groups A and C (P > 0.05), Groups B and C (P > 0.05).
Intracavitary physiotherapy is not inferior to endometrial scratching on improving implantation and clinical pregnancy rates in patients with RIF after IVF/ICSI cycles.
Archives of Gynecology and Obstetrics 07/2014; 291(1). DOI:10.1007/s00404-014-3382-6 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the relationship between day 3 embryo quality and nucleus spreading rate/signal resolution rate in Fluorescence in situ hybridization (FISH) during the PGD procedure.
This study was a retrospective data analysis. 367 day-3 embryos were classified based on morphological scoring: grade 1 to grade 4 were defined from worse to better embryo quality. Day 3 embryos were classified as good quality when the number of blastomeres was between 6 and 10 and grade better than 2'. Nucleus spreading rate, signal rate and the full signal rate were compared between embryos with different morphological scoring.
Nucleus spreading rate of blastomeres from morphological high-quality embryos was significantly higher (86.25 %) than from poor-quality embryos (76.53 %) (p < 0.05). The rate of blastomeres with full signals was significantly higher (79.32 %) in the morphological high-quality group than in poor-quality group (64.54 %) (p < 0.05). Similar results were found from day 3 embryos with cell number between 6 cells and 10 cells (nucleus spreading rate 86.01 vs. 76.34 %, p < 0.05; full signal rate 78.72 vs. 62.71 %, p < 0.05). Both have no significant difference in the signal rate (82.67 vs. 89.66 %; 83.10 vs. 89.95 %).
Blastomeres from day 3 embryos with better morphological quality had higher nucleus spreading rate and higher full signal rate during FISH. Through this study, we speculate on whether it should reconsider the necessity of FISH application in embryos with poor quality.
Archives of Gynecology 03/2014; 290(1). DOI:10.1007/s00404-014-3189-5 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chromosomal abnormalities are an important cause of repeated miscarriage. Several studies have discussed the association between chromosomal abnormalities and repeated miscarriage. This study attempts to describe the pattern of miscarriage in this group of women and the eventual pregnancy outcome of couples with chromosomal abnormalities compared with couples with unexplained repeated pregnancy loss.
This was a retrospective study involving 795 couples with repeated miscarriages.
Out of 795 couples, 28 (3.52%) were found to have a chromosomal abnormality (carrier group). Over half (65.5%) of the chromosomal abnormalities were balanced reciprocal translocations. After referral, this carrier group had a total of 159 pregnancies, leading to 36 live births (22.6%) among 18 couples. The after referral miscarriage rate in the chromosomal anomaly group (55.6%) was significantly (P < 0.01) higher than that in the unexplained recurrent miscarriage group (28.1%). In couples with chromosomal anomaly, the miscarriages were more likely to occur between 6 and 12 weeks' gestation.
The encouraging cumulative live birth rate of 64.3% for couples with chromosomal anomaly and repeated miscarriage suggests that further attempts at natural conception are a viable option.
Journal of Obstetrics and Gynaecology Research 09/2013; 40(1). DOI:10.1111/jog.12133 · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This retrospective observational study was performed to determine the predictive value of midluteal serum progesterone measurement on the subsequent pregnancy outcome in women with unexplained recurrent miscarriage after referral. This study involved women with unexplained recurrent miscarriage attending the recurrent miscarriage clinic between January 1992 and March 2011. A total of 132 women with unexplained recurrent miscarriage who conceived again within 12 months of midluteal serum progesterone measurement were analysed. Midluteal serum progesterone concentrations were compared between miscarriage and live birth groups. Also live birth rates were compared between higher and lower progesterone groups. Among 132 women studied, the serum progesterone concentrations (mean +/- SE) in the live birth group (n = 86) and miscarriage group (n = 46) were 42.3 +/- 2.4 nmol/l and 42.5 +/- 3.2 nmol/l, respectively. In addition, using three different progesterone cut-off values (20, 30 and 40 nmol/l), the live birth and miscarriage rates were also not significantly different. The conclusion is that midluteal serum progesterone measurement does not predict the outcome of a subsequent pregnancy in women with unexplained recurrent miscarriage. RBMOnline
[Show abstract][Hide abstract] ABSTRACT: Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
[Show abstract][Hide abstract] ABSTRACT: This is a retrospective, observational study to evaluate the effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET). 11830 IVF-ET cycles from 10268 women were included. Four groups of different maternal age periods were compared. The groups were 21-30 years old group (4549 cycles), 31-35 years old group (4424 cycles), 36-40 years old group (2429 cycles), and over 40 years old group (428 cycles). The mean starting dose of Gn and mean total dose of Gn in each cycle were significantly higher (P<0.01), while the mean retrieved oocyte number was significantly lower (P<0.01) in groups of higher maternal age period than those in each of the lower groups. The biochemical pregnancy rate and the clinical pregnancy rate were significantly lower (P<0.01), while the miscarriage rate was significantly higher (P<0.01) in groups of higher maternal age period than those in the lower groups. No difference was found in two-pronuclear zygotes (2PN) rate and good quality embryo rate among different groups. Birth defect rate was also comparable in the born babies in different groups. In the group with patients' age over 40 years old, the pregnancy rate was 26.87%, the clinical pregnancy rate was 19.39%, while the miscarriage rate after clinical pregnancy was 36.14%. To draw the conclusion, patients with higher maternal age had worse IVF outcomes. In women of fertile age, patients between 20 and 30 years old have the best IVF outcomes. Patients over 40 years old have poor IVF outcome and high miscarriage rate, which suggested the necessity of preimplantation genetic screening (PGS).
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence, prognostic value, and response to thyroxine therapy of thyroid peroxidase antibody (TPOAb) in women with unexplained recurrent miscarriage (RM).
Observational, cohort study. The index cases included women with unexplained RM who tested positive for thyroid peroxidase antibody, and control cases included women with unexplained RM who tested negative for the antibodies; a second age-matched control group included women with RM who had a known cause for the repeated pregnancy loss.
Tertiary referral center for RM.
A total of 496 women with unexplained RM and 220 women with known diagnoses of RM who had a TPOAb test.
Thyroxine replacement (50 μg daily during pregnancy) was begun in some patients who tested positive for thyroid peroxidase antibody, irrespective of TSH level.
Miscarriage and live birth rates of a subsequent pregnancy.
A total of 496 women with unexplained RM who had a TPOAb test were included in the study. Of these, 10.7% of subjects tested positive for TPOAb. The prevalence of TPOAb in control subjects who had a known cause for RM was 11.8%. The live birth rate of the first pregnancies after referral was 64%, 53%, and 58% in TPOAb-negative, TPOAb-positive with thyroxine treatment, and TPOAb-positive without treatment subjects; there was no significant difference in the outcome between any two or three groups, or between those who tested positive or negative for TPOAb. Among women who tested positive for TPOAb, there was no difference in the antibody titer between women with unexplained RM and those with a known cause for the pregnancy loss. Women who tested positive for TPOAb were significantly more likely to have TSH levels above the normal range (≥4.2 mIU/L).
The prevalence of TPOAb-positive results in women with unexplained RM is not higher than in the general population, TPOAb-positive status does not have a prognostic value regarding the outcome of a subsequent pregnancy, and empirical thyroxine therapy in those who tested positive did not seem to improve outcome.
Fertility and sterility 05/2012; 98(2):378-82. DOI:10.1016/j.fertnstert.2012.04.025 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This is a retrospective, observational study to determine how often repeated consecutive miscarriages occur consistently in the same gestational period, including 1589 miscarriages among 543 women with recurrent miscarriage. In women who had two miscarriages only, 49.17% of both miscarriages occurred in the same gestational period, which was significantly higher than the expected probability of 34.54% (P<0.01). The proportions of all miscarriages occurring in the same gestational period in women with three, four and five or more miscarriages were 28.72%, 19.44% and 18.60%, compared with the expected probabilities of 14.36% (P<0.01), 6.57% (P<0.05) and <3.15% (P<0.05). The proportions of miscarriages occurring consistently in the same gestational period are higher than the theoretical probabilities calculated for the whole population.
[Show abstract][Hide abstract] ABSTRACT: Although uterine fibroids have been associated with spontaneous miscarriage, to our knowledge there have been no studies in the literature assessing their role in the recurrent miscarriage (RM) population. The aims of this study are to examine the impact of different types of fibroids on the pregnancy outcome of women with RM and to investigate to what extent resection of fibroids distorting the uterine cavity affects the outcome of a future pregnancy.
The study analysed retrospective and prospective data from a large tertiary referral RM clinic. Couples were investigated as per an established protocol. Fibroids were diagnosed using combined transvaginal ultrasound and hysterosalpingography. Fibroids distorting the uterine cavity were resected via hysteroscopy. Two study groups were subsequently examined: women with cavity-distorting fibroids who underwent surgery (n =25) and women with fibroids not distorting the cavity who did not undergo any intervention (n =54). The latter was compared with a control group of women with unexplained RM (n =285).
The prevalence of fibroids was found to be 8.2% (79/966). In total, 264 pregnancies of women with fibroids and 936 pregnancies of women with unexplained RM were analysed. Women with intracavitary distortion and undergoing myomectomy significantly reduced their mid-trimester miscarriage rates in subsequent pregnancies from 21.7 to 0% (P< 0.01). This translated to an increase in the live birth rate from 23.3 to 52.0% (P< 0.05). Women with fibroids not distorting the cavity behaved similarly to women with unexplained RM achieving a 70.4% live birth rate in their subsequent pregnancies without any intervention.
Fibroids are associated with increased mid-trimester losses amongst women with RM. Resection of fibroids distorting the uterine cavity can eliminate the mid-trimester losses and double the live birth rate in subsequent pregnancies. Women with fibroids not distorting the uterine cavity can achieve high live birth rates without intervention.
Human Reproduction 09/2011; 26(12):3274-9. DOI:10.1093/humrep/der293 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To find the association between recurrent spontaneous abortion (RSA)/early embryo growth arrest and Y chromosome polymorphism.
Peripheral blood samples of the male patients of big Y chromosome, small Y chromosome and other male patients whose partners suffered from unexplained RSA/early embryo growth arrest were collected. PCR and real-time fluorescent quantitative PCR were used to test the deletion and the copy number variation of DYZ1 region in Y chromosome of the patients. A total of 79 big Y chromosome patients (48 of whose partners suffered from RSA or early embryo growth arrest), 7 small Y chromosome patients, 106 other male patients whose partners had suffered from unexplained RSA or early embryo growth arrest, and 100 normal male controls were enrolled.
There was no fraction deletion of DYZ1 detected both in big Y patients and in normal men. Of RSA patients, 1 case showed deletion of 266bp from the gene locus 25-290bp, and 2 cases showed deletion of 773bp from 1347 to 2119bp. Of only 7 small Y chromosome patients, 2 cases showed deletion of 266bp from 25 to 290bp, and 4 cases showed deletion of 773bp from 1347 to 2119bp and 275bp from 3128 to 3420bp. The mean of DYZ1 copies was 3900 in normal control men; the mean in big Y patients was 5571, in RSA patients was 2655, and in small Y patients was 1059. All of the others were significantly different (P<0.01) compared with normal control men, which meant that DYZ1 copy number in normal control men was less than that of big Y chromosome patients, and was more than that of unexplained early RSA patients and small Y patients.
The integrity and copy number variation of DYZ1 are closely related to the Y chromosome length under microscope. The cause of RSA/early embryo growth arrest in some couples may be the increase (big Y patients) or decrease of DYZ1 copy number in the husbands' Y chromosome.
European journal of obstetrics, gynecology, and reproductive biology 08/2011; 159(2):371-4. DOI:10.1016/j.ejogrb.2011.07.033 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This first large-scale report of birth defects in 15,405 offspring conceived by assisted reproductive technologies in China found infants born after IVF alone to have a birth defect frequency comparable to that in the general Chinese population; rates were nonsignificantly higher in infants conceived with use of intracytoplasmic sperm injection compared with those conceived after IVF alone.
Fertility and sterility 01/2011; 95(1):458-60. DOI:10.1016/j.fertnstert.2010.08.024 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹⁹, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.
[Show abstract][Hide abstract] ABSTRACT: An association of polymorphism -1154G/A (rs1570360) in vascular endothelial growth factor (VEGF) gene with idiopathic recurrent spontaneous abortion (RSA) has been found in Caucasians. The aim of this study was to examine the association of VEGF -1154 with RSA in a well-defined group of Chinese Han patients.
The VEGF -1154G/A genotype was detected by real-time PCR with TaqMan probes. The products were also subjected to gene sequence analysis to validate the PCR results.
The allele frequencies of VEGF -1154G/A showed no significant difference between RSA patients and the normal controls (P = 0.183). The frequencies of VEGF -1154G/A genotypes were not significantly different between RSA patients and the normal controls (P = 0.228).
Our study revealed that VEGF -1154G/A polymorphism was not associated with the susceptibility to RSA in Chinese Han women.
American Journal Of Reproductive Immunology 10/2010; 65(5):521-5. DOI:10.1111/j.1600-0897.2010.00924.x · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The concerns over xenogeneic pathogens and immunogenic molecules derived from mouse embryonic fibroblasts (MEFs) trigger the development of human-derived feeder layers for human embryonic stem cell (hESC) maintenance. It is essential to evaluate the capability of these human feeder layers to retain the stemness and pluripotency of hESCs. In the present study, two Chinese hESC lines, SDU-hESCm-1 and SDU-hESCm-2, were continuously cultured on human adult uterine endometrial cells (hUEC), human fetal trophonema matrix cells (hFTMC), and MEFs for at least two month (up to 10 passages). A side-by-side comparison of the abilities to support: (1) self-renewal of the hESCs, (2) expression of undifferentiated markers, and (3) neural differentiation, was made between the human and mouse feeder layers. We demonstrated that the hESCs maintained on hUEC and hFTMC exhibited significantly higher growth rates and generated higher levels of DNA content than those on MEFs. Under neural differentiation-promoting conditions, greater neural differentiation was found in the hESCs maintained on human than on mouse feeder layers. These results suggest that human feeder layers derived from hUECs and hFTMCs are more efficient in supporting a long-term growth and neural differentiation of hESCs than MEFs.
[Show abstract][Hide abstract] ABSTRACT: To examine abnormal fertilization phenomena in blastomeres of embryos generated from conventional IVF and ICSI displaying a single pronucleus at the zygote stage.
132 embryos from monopronuclear zygotes (1PN) generated from conventional IVF and ICSI were examined by FISH (fluorescent in situ hybridization) with X, Y dual color centromere probes.
In the embryos that were obtained from conventional IVF, the percentage of diploid, monoploid and mosaic sex chromosome were 54.35, 23.91 and 21.74%, respectively. In the embryos from 1PN zygotes derived from ICSI, the percentage of diploid, monoploid and mosaic sex chromosomes were 31.51, 31.51 and 36.99%, respectively. For monoploid embryos, the ratio of XO was significantly higher than that of YO in both conventional IVF and ICSI groups.
The results demonstrated that the majority of embryos derived from 1PN zygotes generated with conventional IVF or ICSI have a high incidence of aneuploidy. Furthermore, the sex chromosome diploid ratio of embryos from 1PN zygotes derived from conventional IVF was significantly higher than those generated from ICSI procedure in Chinese women. Nevertheless, the high proportion of aneuploid embryos suggests that such embryos should not be utilized for embryo transfer.