Abnormal Embryonic Karyotype Research Articles

Chromosomal analysis of pregnancy tissue from women with recurrent early pregnancy loss

Purpose: This study aimed to determine the cytogenetical distribution of chromosomal disorders in couples after recurrent early pregnancy loss. Background: One of the most important causes of pregnancy loss found in around half of the first trimester miscarriages is fetal chromosomal abnormalities, the role of fetal chromosomal disorders needs to be better evaluated. Method: This study was conducted at two hospital and private clinics in Duhok, Iraqi Kurdistan from February 2017 to February 2022, and reviewed retrospectively The study included 150patients with history of Recurrent Early Pregnancy Loss were admitted for curettage because of miscarriage in early pregnancy Patients were divided in two group. Results: The study population included a total of 150 fetal tissue specimens obtained during dilation and curettage after the diagnosis of spontaneous miscarriage. Patients were divided in two groups. Group 1 included 95patients with an abnormal embryonic karyotype in the aborted material. Group 2 comprised 55 patients with a normal embryonic karyotype in the aborted products. Patients with a normal embryonic karyotype in the aborted products were significantly younger (p=0.0147). Conclusion: Young patients suffering from repeated miscarriages have a low probability to find chromosomal disorders in the embryonic tissue. Chromosomal analysis should be offered after previous miscarriages before further diagnostic methods are performed.

P–383 Cytogenetic analysis of products of conception from miscarriages following natural conception and IVF pregnancy: a comparative study

Abstract Study question Do cytogenetic results from products of conception from miscarriages differ from patients conceiving by natural conception versus IVF? Summary answer: Cytogenetic results were similar, with no statistical difference from miscarriages following natural conception and assisted conception. What is known already Cytogenetic sampling of products of conception (POC) following recurrent miscarriages (RM) are recommended to rule out parental chromosomal rearrangements. The RCOG recommends cytogenetic testing in cases of recurrent miscarriages (3 consecutive miscarriages). However some units routinely request cytogenetic analysis following a single miscarriage following an IVF pregnancy. There is no evidence to support the routine sampling of POCs following assisted conception. Study design, size, duration: Retrospective cohort study of 117 cytogenetic samples, followed up by the outcome of parental karyotyping if applicable. Patients were categorised based on mode of conception into natural conception (NC) with recurrent miscarriages (≥3) or one miscarriage following IVF. Data collected between 2018–2020. Primary Outcome measure: Presence and type of cytogenetic abnormality; individual parental targeted G-band karyotyping result. Participants/materials, setting, methods: A total of 117 cytogenetic results were reviewed, of which 35 were unsuitable for analysis due to contamination (Total n = 79: NC = 60, IVF = 19). Main results and the role of chance: Cytogenetic analysis showed abnormal results in 59% of miscarriages following natural conception and 53% of miscarriages from IVF pregnancy (p = 0.46). Abnormal cytogenetic results were mainly sporadic. Trisomy 16 was the commonest abnormality in both groups. Others included Trisomy 15, 22, 21, 8, 13, 5, 9, 10, 14, 18, single X (Turner’s), all occurring in the same frequency in both groups. As expected 35 out of 45 abnormal cytogenetic results occurred with a maternal age greater than 35 years. One couple from the NC group were referred to a geneticist for a Trisomy 9 imbalance. All other parental karyotyping results were normal. Limitations, reasons for caution This study contains a small sample size, and would benefit from further data collection to account for a percentage of samples being inadequate for analysis. Wider implications of the findings: Cytogenetic results were similar from miscarriages following natural conception and assisted conception. IVF does not increase the risk of miscarriage from abnormal embryonic karyotype. Routine cytogenetic testing following one miscarriage in patients undergoing IVF is not cost effective. Trial registration number Not applicable

Lower chromosomal abnormality frequencies in miscarried conceptuses from frozen blastocyst transfers in ART.

Are blastocyst culture and cryopreservation in ART associated with chromosomal abnormalities in miscarried products of conception (POC)? Frozen blastocyst transfer in women aged 35 years or older and frozen embryo transfer (ET) (including both cleavage-stage embryo and blastocyst) in women aged <35 years are associated with decreased frequencies of embryonic chromosomal abnormalities in miscarried POC. Blastocyst culture and embryo cryopreservation have been previously associated with favorable ART treatment outcomes and widely applied in clinical practice. However, the association between these embryo manipulation procedures and embryonic chromosomal abnormalities has not been evaluated to the best of our knowledge. This retrospective study included a total of 720 patients who underwent IVF/ICSI, and the retained POC were obtained. A single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) of all miscarried conceptuses was performed. This study was based on the Clinical Reproductive Medicine Management System/Electronic Medical Record Cohort Database (CCRM/EMRCD) at our center. In total, 720 miscarried POCs were collected from patients undergoing ART (including fresh cleavage-stage ET, fresh blastocyst transfer, frozen cleavage-stage ET and frozen blastocyst transfer), and the incidences and profiles of cytogenetic abnormalities in the miscarried conceptuses were measured via SNP-based CMA. The chromosomal abnormality rate in POC varied from 33.7% to 66.7% among the different ET strategies. In the patients aged ≥35 years, frozen blastocyst transfer was significantly associated with a lower incidence of chromosomal aberrations in the POCs (adjusted odds ratio (aOR): 0.171 (95% CI: 0.040-0.738); P = 0.018) than fresh blastocyst transfer. In the patients aged <35 years, frozen ET was significantly associated with a lower incidence of chromosomal aberrations than fresh ET in both cleavage-stage ET cycles and blastocyst transfers cycles (aOR: 0.545 (0.338-0.879), P = 0.013; and aOR: 0.357 (0.175-0.730), P = 0.005, respectively). Trisomy was the most frequent abnormal embryonic karyotype in the different ET strategies, and its frequency significantly differed among strategies (P < 0.05). This study was retrospectively designed, and we cannot draw any definite conclusions from our results regarding the adequate safety of embryo cryopreservation in ongoing pregnancy. To our knowledge, this is the first study assessing the associations of ET strategies with the probability of miscarriage associated with embryonic chromosomal abnormalities. However, the underlying mechanism of these associations is unknown; this study may promote research concerning ET strategies and promote comprehensive consultations and recommendations for patients. This work was supported by the Natural Science Foundation of China (Grant No.81571409), Science and Technology Research Project of Henan (Grant No. 172102310009) and Medical Science and Technology Research Project of Henan (Grant No. 201701005). The authors declare no competing interests. N/A.

Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure

Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)? PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups. PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40-50% and 5-25% in patients with RPL, respectively. A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35-36, 37-38, 39-40 or 41-42years) were selected for PGT-A groups. All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted. There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16-13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28-10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02-0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03-0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients. The sample size was too small to find any significant advantage for improving the live birth rate and reducing the clinical miscarriage rate per patient. Further study is necessary. A large portion of pregnancy losses in the RPL group might be due to aneuploidy, since PGT-A reduced the overall incidence of pregnancy loss in these patients. Although PGT-A did not improve the live birth rate per patient, it did have the advantage of reducing the number of embryo transfers required to achieve a similar number live births compared with those not undergoing PGT-A. This study was supported by the Japan Society of Obstetrics and Gynecology and grants from the Japanese Ministry of Education, Science, and Technology. There are no conflicts of interest to declare. N/A.

Comparison of the etiological constitution of two and three or more recurrent miscarriage

Objective: To compare the etiological constitution of recurrent miscarriage (RM) between patients with consecutive two and three or more miscarriages through combining the routine examination results and embryonic karyotype. Methods: Patients with a history of two or more consecutive clinical miscarriages (≤12 weeks of gestation) consulting in the RM clinic of the First Affiliated Hospital of Sun Yat-sen University from March 2011 to January 2016 were collected. Six hundred and ninety-six with detailed history recorded, routine clinical examinations of RM and at least once embryonic karyotype were ultimately enrolled in this study. Their etiological constitution of RM were analyzed in groups of consecutive two and three or more miscarriage. The etiologies of RM in analysis consisted of women age, body mass index (BMI) , chromosome abnormalities of couples, uterine abnormalities, endocrinology abnormalities and antiphospholipid syndrome (APS) . Results: (1) Among 696 patients, the abnormal embryonic karyotypes was 60.6% (422/696) and routine RM etiologies was 32.2% (224/696) , leaving the ratio of unexplained RM was only 29.0% (202/696). (2) A total of 717 embryo karyotype were found in 696 patients, included21 cases with twice embryo karyotype results the percentage of normal embryo was 39.7% (285/717) , while abnormal ones was 60.3% (432/717). Among the types of abnormal karyotype, the most common ones (>10%) were trisomy 16 (19.2%, 83/432) , monosome X (11.3%, 49/432) and trisomy 22 (10.9%, 47/432). (3) Among the 696 RM patients, the number of two and three or more miscarriages were respectively 446 (64.1%, 446/696) and 250 (35.9%, 250/696). Comparing groups of three or more miscarriages with two miscarriages, there were significant differencein older age as well as uterine adhesion (P<0.05). But no difference was found in body mass index (BMI) , the rates of chromosome abnormalities of couples, uterine abnormalities except uterine adhesion, endocrinology abnormalities and APS (all P>0.05) between two groups. Conclusions: The abnormal embryonic karyotype is the most common cause of first-trimester RM. The etiological constitution of two and three or more recurrent miscarriages is accordant, suggesting that routine clinical examination and the embryonic karyotype should be started following two consecutive clinical early miscarriages.

Chromosomal karyotype in chorionic villi of recurrent spontaneous abortion patients.

Recurrent spontaneous abortion (RSA) is a multifactorial disease of which the exact causes are still unknown. In the current study, we aimed to analyze the distribution of abnormal embryonic karyotypes in RSA. 781 RSA patients of 17 hospitals in Shanghai from January 2014 to September 2016 were enrolled. Fetal villus tissues were collected during uterine curettage and then cultured in situ for karyotyping. All of the 781 cases were successfully cultured. There were 393 cases of abnormal karyotypes, accounting for 50.3% of the total cases. Women with abnormal embryonic karyotype were significantly older compared to those with normal karyotype (P < 0.001). The majority of patients with abnormal karyotype fell among age groups of 25-29 and 30-34. There were 247 cases of aneuploidy, accounting for 62.8% of the total abnormal karyotype cases. Autosomal trisomy was the primary form of aneuploidy (189/247, 76.5%), and the most common types were trisomy-16 (n = 69), trisomy-22 (n = 28), trisomy-21 (n = 21), trisomy-15 (n = 15), and trisomy-13 (n = 10). Abnormal karyotype is a major factor related to RSA. Further studies are needed to elucidate the etiology of RSA in order to achieve more effective prevention and treatment.

Genotyping analysis of protein S-Tokushima (K196E) and the involvement of protein S antigen and activity in patients with recurrent pregnancy loss

ObjectivePreston et al. indicated that Protein S (PS) deficiency was associated with stillbirths but not miscarriages. The PS-Tokushima missense variant was reported to serve as a genetic risk factor for deep vein thrombosis in the Japanese population. A previous cross-sectional study showed no increase in the prevalence of PS-Tokushima in patients with recurrent early pregnancy loss or in patients with intra uterine fetal death and/or fetal growth restriction. There has been limited number of prospective studies examining the pregnancy outcome in patients with both a PS deficiency and recurrent pregnancy loss (RPL). We examined the association between PS deficiency, PS-Tokushima and RPL. Study designThe study group consisted of 355 Japanese women with two or more consecutive pregnancy losses and 101 parous women. The frequency of PS-Tokushima and the subsequent live birth rate in relation to a PS deficiency defined as low PS-specific activity (total PS activity/total PS antigen) and the carriage of PS-Tokushima were examined. Results and conclusionsThere was no significant difference in the frequency of PS-Tokushima between patients and controls. The 8 patients carriers of PS-Tokushima variant were capable of a subsequent live birth without the use of heparin. There was no significant difference in subsequent live birth rates between patients with low or normal PS-specific activity/PS activity without heparin prophylaxis after excluding miscarriages caused by an abnormal embryonic karyotype using multivariate logistic regression analysis. There was no association between PS-Tokushima and RPL and a PS deficiency or low PS activity was shown not to serve as a reliable clinical predictor of subsequent miscarriage.

The frequencies of the presence of embryonic pole and cardiac activity in early miscarriages with abnormal karyotypes

Aims: The objective of this study was to compare the frequencies of the presence of an embryonic pole and cardiac activity in miscarriages with normal and abnormal embryonic karyotypes. Materials and Methods: From January 2008 to December 2012, 405 patients with early miscarriage were evaluated during pregnancy by regular ultrasound, and karyotyping was performed on chorionic villus tissue after curettage. The frequencies of the presence of an embryonic pole and cardiac activity were compared between patients with a normal embryonic karyotype and patients with an abnormal embryonic karyotype. Results: Of the 405 samples, 224 cases (55.3%) had an abnormal karyotype, and 181 cases (44.7%) had a normal karyotype. The frequencies of the presence of an embryonic pole and cardiac activity in miscarriages with normal embryonic chromosomes (71.8% and 57.5%, respectively) were similar to those of miscarriages with abnormal embryonic chromosomes (74.1% and 62.1%, respectively). The frequencies of the presence of an embryonic pole and cardiac activity were higher in miscarriages with viable autosomal trisomies (trisomies 21, 13, and 18), monosomy X, and triploidy than in miscarriages with a normal karyotype or other abnormal karyotypes. Conclusions: The frequencies of the presence of an embryonic pole and cardiac activity are higher in miscarriages with viable autosomal trisomies, monosomy X, and triploidy than in miscarriages with a normal karyotype or other abnormal karyotypes.

Recurrent pregnancy loss and obesity

Recurrent pregnancy loss (RPL) was defined as two or more miscarriages. Antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities, particularly translocation and abnormal embryonic karyotype, are identifiable causes of RPL. Obesity may increase the risk of sporadic miscarriage in pregnancies conceived spontaneously. Obesity with body mass index (BMI)>30 kg/m2 is an independent risk factor for further miscarriage with odds ratio 1.7-3.5 in patients with early RPL. Obesity is associated with euploid miscarriage. Unexplained RPL with euploid embryo might be a common disease caused by both polymorphisms of multiple susceptibility genes and lifestyle factors such as women's age, obesity, and smoking. Patients with a history of RPL were found to have a higher risk of cardiovascular disease, celiac disease, gastric ulcer, gastritis, and atopic dermatitis. No study has examined the effect of weight loss on the prevention of further miscarriage in patients with RPL.

Genotyping analysis for the 46 C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss.

BackgroundEstablished causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations and abnormal embryonic karyotype. A systematic review concluded that coagulation factor XII (FXII) deficiency was associated with RPL. However, it could not be established whether the 46 C/T SNP of FXII or low activity of FXII was a risk factor for RPL, because of the small sample size.Methods and FindingsWe conducted a cross-sectional and cohort study in 279 patients with two or more unexplained consecutive pregnancy losses and 100 fertile women. The association between the lupus anticoagulant (LA) activity and FXII activity was examined. The frequency of the CC, CT and TT genotypes and the FXII activity were also compared between the patients and controls. Subsequent miscarriage rates among the CC, CT, TT genotypes and according to the FXII activity was examined. LA was associated with reduced FXII activity. The CT, but not the TT, genotype was confirmed to be a risk factor for RPL in the cross-sectional study using multivariate logistic regression analysis (OR, 2.8; 95% CI, 1.37–5.85). The plasma FXII activity in the patients was similar to that in the controls. Neither low FXII activity nor the CT genotype predicted the subsequent pregnancy outcome in the cohort study. On the other hand, and intermediate FXII activity level of 85–101% was predictive of subsequent miscarriage.ConclusionsLow FXII activity was not associated with RPL. The FXII gene was found to be one of the significant susceptibility genes for RPL, similar to the FV Leiden mutation. However, the clinical influence of the CT genotype might be relatively small, because the presence/absence of this genotype did not have any predictive value for the subsequent pregnancy outcome. This was the first study indicating the influence of FXII 46C/T on further pregnancy outcomes.

A comparative cytogenetic study of miscarriages after IVF and natural conception in women aged under and over 35 years

To compare the frequency and the spectrum of karyotype abnormality in the first trimester miscarriages in women aged under and over 35 years, who conceived naturally (NC) and who conceived through in vitro fertilization (IVF). Comparative analysis of cytogenetic data obtained by karyotyping of miscarriages in patients who conceived naturally, and who conceived through IVF. Patients were subcategorized by their age: <35 years (NC, n = 173; IVF, n = 108) and ≥ 35 years (NC, n = 107; IVF, n = 111). A total of 499 miscarriage karyotypes was analyzed. The spectrum and the relative proportions of different cytogenetic categories in karyotypically abnormal miscarriages differed neither between the NC and IVF patients aged <35 years, nor between the NC and IVF patients aged ≥ 35 years. In the patients aged <35 years, the incidence of abnormal miscarriage karyotype was lower in the IVF group (37.04 % vs 62.43%). In the patients aged ≥ 35 years, the incidence of miscarriages with cytogenetic pathology did not differ between the NC and the IVF group (75.70 % vs 58.56%). The lowest frequency of karyotypically abnormal miscarriages (29.82%) was detected in the young IVF-treated patients at <7 weeks of gestation. IVF does not increase the risk of a pregnancy loss because of abnormal embryonic karyotype, nor does it increase the preponderance for any specific type of cytogenetic abnormality in both patients aged under and over 35 years. In young IVF-treated women early pregnancy loss is generally caused by non-cytogenetic factors. Identification of a cytogenetically normal spontaneous abortion is clinically significant and reinforces the importance of developing an appropriate diagnosis and treatment strategies for IVF patients in order to reduce the risk of euploid pregnancy loss.

Genotyping analyses for polymorphisms of ANXA5 gene in patients with recurrent pregnancy loss

To investigate whether polymorphisms at the promoter or 5'-untranslated region of annexin A5 gene (ANXA5) influence miscarriage. Case-control study and nested case-control study. Hospitals. A total of 264 patients with two to nine recurrent pregnancy losses (RPLs) and 195 fertile control subjects. None. The frequency of six single-nucleotide polymorphisms (SNPs) of the ANXA5 gene in RPL patients versus control subjects, and subsequent live birth rate with and without risk alleles in RPL patients. The minor allele was significantly more frequent in RPL patients than in control subjects for SNP5 (rs1050606). The live birth rates of patients with and without risk alleles of SNP5 were 84.0% and 84.3%, respectively, after excluding cases with abnormal embryonic karyotype, with no significant difference. The variations with the ANXA5 gene upstream region, especially SNP5, were confirmed to be risk factors of RPL. However, presence/absence of the ANXA5 risk allele did not have any predictive effect for subsequent pregnancy outcome. This was the first study indicating the influence of ANXA5 SNP5 for pregnancy outcome.

Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage

We previously found that a normal karyotype in a previous miscarriage is a predictor of subsequent miscarriage. However, the prevalence of recurrent miscarriage caused by an abnormal embryonic karyotype has not yet been reported, since embryonic karyotype is not typically analyzed during conventional examinations. A total of 482 patients who underwent both embryonic karyotype determination and conventional examinations for recurrent miscarriage were enrolled in this study. The distribution of the causes and the live birth rate for each cause were examined. The total percentage of subjects in whom conventional causes of recurrent miscarriage could be detected was 29.5%. The prevalence of the abnormal embryonic karyotype was 41.1% in the subjects in whom no conventional causes of miscarriage could be identified. The prevalence of recurrent miscarriage of truly unexplained cause, that is, of subjects without conventional causes in whom the embryonic karyotype was ascertained to be normal, was 24.5%. Among the patients in whom the first determination revealed an abnormal embryonic karyotype, 76.2% (32/42) showed an abnormal embryonic karyotype in the repeat determination as well. The cumulative live birth rate (71.9%) in women with recurrent miscarriages caused by the abnormal embryonic karyotype was significantly higher than that (44.7%) in women with recurrent miscarriages associated with the embryonal euploidy. An abnormal embryonic karyotype was found to represent the commonest cause of recurrent miscarriage, and the percentage of cases with recurrent miscarriage of truly unexplained cause was limited to 24.5%.The two groups should be distinguished for both clinical and research purposes.

Genetic Factors as a Cause of Miscarriage

Aneuploidy in the conceptus or fetus, occurs in 5-10% of all pregnancies and is a common reproductive problem in humans. Most aneuploid conceptuses die in utero, resulting in early pregnancy loss. Causes of recurrent miscarriage may include abnormal chromosomes in either partner, particularly translocations, antiphospholipid antibodies and uterine anomalies. Chromosomal aberrations in parents are a major pre-disposing factor and causative of abortion if carried over to the embryo. The transmission rate in the embryo can be speculated to be about 50%. Embryo morphology, developmental rates, and maternal age are correlated with chromosomal abnormalities. Translocation in either partner is one of the most important causes of recurrent miscarriage and the prognosis of subsequent pregnancy in couples with abnormal embryonic karyotype is poorer than that in couples with normal chromosome karyotypes. As for parents whose karyotypes are normal, the frequency of normal embryonic karyotypes significantly increases with the number of previous abortions and a normal karyotype in a previous pregnancy is a predictor of subsequent miscarriage. Recently, many kinds of genetic polymorphisms have also been found to be associated with recurrent miscarriages. In contrast, preimplantation genetic diagnosis for aneuploidy screening is sometimes performed in patients with unexplained recurrent miscarriages. We review genetic factors as a cause of miscarriage.

Diagnosis and treatment methods for recurrent miscarriage cases.

Recurrent miscarriage is classically defined as three or more consecutive pregnancy losses. Established causes of recurrent miscarriage are antiphospholipid antibodies, uterine anomalies and abnormal chromosomes in either partner, particularly translocations. Embryonic aneuploidy is the most important cause of miscarriage before 10 weeks' gestation. It can be speculated that about 51% of patients with a history of three miscarriages experienced these because of abnormal embryonic karyotypes. It is not necessary to give any medication for such cases caused by an abnormal embryonic karyotype. Psychological tender loving care might be the most important requirement to continue conceiving till live birth results.

ORIGINAL ARTICLE: Occasional Antiphospholipid Antibody Positive Patients with Recurrent Pregnancy Loss Also Merit Aspirin Therapy: A Retrospective Cohort‐Control Study

ProblemIt is well known that treatment with aspirin plus heparin is effective for patients with antiphospholipid syndrome (APS) to prevent pregnancy loss. However, it is unclear if occasional antiphospholipid antibodies (aPL) are a risk factor and whether patients with aPL at one time point but not diagnosed as APS should be treated.Method of studyWe therefore studied whether aspirin alone is effective in patients with occasional aPL who did not meet the criteria for APS. We compared live birth rates between 52 patients with occasional aPL treated with aspirin and 672 unexplained patients with no medication. Patients in both group had a history of two or three pregnancy losses.ResultsIn all, 44 of 52 patients (84.6%) with occasional aPL could experience live birth when treated with aspirin alone. 509 of 672 patients (75.7%) with unexplained pregnancy losses could have babies. When miscarriage cases caused by an abnormal embryonic karyotype were excluded, the success rates were 95.7% (44/46) and 81.2% (509/621), respectively. The live birth rate in patients with occasional aPL treated with aspirin was significantly higher than that in unexplained patients with no medication (P = 0.008).ConclusionWe therefore conclude that aspirin is also useful in patients with occasional aPL but not APS.

Endometrial factors in recurrent miscarriage.

Recurrent pregnancy loss may be a consequence of an abnormal embryonic karyotype, or maternal factors affecting the endometrium resulting in defective implantation. In order to study the endometrial factors responsible for recurrent pregnancy loss, endometrial biopsy samples should be precisely timed according to the LH surge, and the investigation should be carried out in a non-conception cycle, prior to the next pregnancy. The various methods of studying the endometrium including morphological studies, morphometry, immunohistrochemistry, measurement of endometrial protein in plasma and uterine flushings, cytokine expression in endometrial cells, leukocyte populations in the endometrium and ultrasonographic and hysteroscopic studies, were reviewed. The clinical relevance of the observed abnormality depends on whether or not the abnormality is persistent in subsequent cycles, and if the observed abnormality is of significant prognostic value. Very little is known about the treatment of endometrial defect associated with recurrent pregnancy loss, but preliminary data suggest that the use of HMG may be of benefit.

Embryonic karyotype of abortuses in relation to the number of previous miscarriages

Objective: To examine the frequency of chromosomal abnormalities in products of conception from patients with recurrent miscarriages in relation to the number of previous miscarriages. Design: Retrospective analysis. Setting: Nagoya City University Medical Hospital. Patient(s): A total of 1,309 women with a history of 2–20 consecutive first-trimester abortions. Intervention(s): Chromosomal analysis performed on products of conception with use of a standard G-banding technique. Main Outcome Measure(s): The frequencies of abnormal and normal embryonic karyotypes for each number of previous abortions were studied. The subsequent pregnancy outcome of patients whose previous miscarriages were karyotyped were studied along with the predictive value of karyotyping of previous miscarriages for subsequent miscarriages. Result(s): The miscarriage rate increased with the number of previous spontaneous abortions. The frequency of abnormal embryonic karyotypes significantly decreased and that of normal embryonic karyotypes significantly increased with the number of previous abortions. Among 71 patients whose embryonic karyotypes were normal, 44 aborted subsequently, and 23 of 60 patients whose embryonic karyotypes were abnormal aborted subsequently. Patients with a previous normal embryonic karyotype aborted more frequently than those with an abnormal karyotype. Conclusion(s): The frequency of normal embryonic karyotypes significantly increases with the number of previous abortions, and a normal karyotype in a previous pregnancy is a predictor of subsequent miscarriage.