Management of recurrent pregnancy loss associated with a parental carrier of a reciprocal translocation: a systematic review

This study reviews systematically the effectiveness of management strategies for carriers of a reciprocal translocation involving two chromosomes, ascertained on the basis of recurrent pregnancy loss. Subsequent pregnancy outcomes were tabulated based on whether management was medical or involved in vitro fertilization/preimplantation genetic diagnosis (IVF/PGD). A total of 129 cases from 13 articles met the criteria, of which 89% were managed medically. Before management, the overall live birthrate was 4% (19 of 484 pregnancies). Management was medical in 109 cases and IVF/PGD in 20 cases. Cumulative live birthrate was 74% (81 of 109 cases) in the medical management group and 35% (7 of 20) in the IVF/PGD group. Based on this systematic review, successful pregnancy outcomes are high following either medical management or IVF/PGD for carriers of a reciprocal translocation, ascertained on the basis of recurrent pregnancy loss. But it is difficult to compare outcomes directly for these two strategies because of the different end points reported. Understanding the differences is essential for effective counseling. Until a well-designed study comparing the two strategies is performed, or at least prospective cohort studies with strict entry criteria and definitions, the cumulative experience and success of both medical management and IVF/PGD must be used to counsel patients who are carriers of a reciprocal translocation, ascertained on the basis of recurrent pregnancy loss.     

Probability rates for different pregnancy outcomes in carriers of reciprocal chromosomal translocations involving chromosome 13

OBJECTIVES: The aim of study was to estimate the probability rates for unfavorable pregnancy outcomes in carriers of reciprocal chromosomal translocations involving 13 chromosome (RCT-13q). MATERIAL AND METHODS: We collected total empirical data about 232 pregnancies of 56 carriers coming from 28 pedigrees. RCT classification was based on classic cytogenetic methods for interpretation of breakpoint position. The probability rates of particular type of pathology related to the total number of pregnancies after ascertainment correction have been calculated with the help of Stengel-Rutkowski and Stene method. RESULTS: The risk figures for unbalanced offspring after 2:2 disjunction and adjacent-1 segregation for the whole group of pedigrees were calculated as 5.2 +/- 1.7% (9/173)--medium risk, for maternal (MAT) and paternal (PAT) carriers were about 6.2 +/- 2.3% (7/173) and 4.8 +/- 3.3% (2/42) respectively. Considering different segment lengths of 13q, similar values for shorter and longer segments were obtained [4.3 +/- 1.9% (5/115) for 13q21-->qter and 7.0 +/- 3.3% (4/58) for 13q12-->qter]. The risk figures for miscarriages as 36.4 +/-3.6% (63/173) and for stillbirths/early death as 4.6 +/- 31.6% (8/173) were obtained. The risk figures for unbalanced offspring after 3:1 disjunction were calculated as 7.7 +/- 7.45 (9/13). Conclusions: 1. Risk figures for different pregnancy outcomes are differ among particular forms of pathology. 2. Probability rate for unbalanced progeny at birth was calculated as a medium risk and similar values for carriers of different segments of 13q were obtained. 3. Probability rate for miscarriages was high but risk for stillbirths/early deaths of newborn was low. 4. No differences in values of rate for particular forms of pathology were found for maternal and paternal carriers of RCT-13q.     

Pedigree analysis of childless families of reciprocal chromosome translocation carriers

OBJECTIVES: Pedigree analysis of childless families of unique reciprocal chromosome translocation (RCT) carriers may be useful for clinical prognosis and genetic counselling. MATERIAL AND METHODS: The group 13 childless families of RCT carriers were detected. Cytogenetic analysis of RCT was performed on blood samples using GTG and RBG banding technique. RESULTS: Thirteen pedigrees were constructed on basis of 64 cytogenetic results and anamnestic data of 62 spontaneous abortions and 7 stillbirths. Familial RCT were found in ten families. In addition fourteen relatives of the RCT carriers have had healthy children. Further observations showed other three healthy children among progeny of eight families. Low risk for unbalanced progeny at birth were estimate in most families. CONCLUSION: Childless families of RCT carriers have possibility to have healthy offsprings. Spontaneous abortions are result of RCT carrierstrip.     

Pregnancy outcomes after recurrent pregnancy loss: a longitudinal cohort study on stress and depression

Published reports have indicated that rates of preimplantation embryo aneuploidy in a control donor population may vary between IVF centres. This suggests that location-specific conditions, in the clinic, IVF or genetics laboratory, may be influencing the chromosome dynamics or diagnosis. More recent reports suggest that rates of embryo mosaicism, representing mitotic errors, may vary between IVF centres. This would suggest perhaps a laboratory-controlled variable is influencing mitotic cell division during preimplantation embryo development. Various IVF laboratory-controlled factors may be impacting chromosome separation and segregation. Variables including type of culture media, pH, temperature, osmolality and oxygen concentration could all be possible factors influencing embryo aneuploidy. Furthermore, laboratory techniques, method of insemination, laser use or handling of biopsied cells may also influence genetic results. These IVF laboratory variables will be reviewed and literature suggesting a possible link to mitotic aneuploidy/mosaicism discussed.     

Meiotic segregation analysis of embryos from reciprocal translocation carriers in PGD cycles

Meiotic segregation patterns of 278 embryos from 41 preimplantation genetic diagnosis cycles of 34 reciprocal translocation carriers were analysed to investigate whether some characteristics of reciprocal translocation, including terminal breakpoints, acrocentric chromosome or carrier gender, are related to meiotic segregation patterns. The incidence of normal/balanced karyotypes in translocations with terminal breakpoints was significantly lower than those without terminal breakpoints (6.5% versus 14.4%, P = 0.005). The incidences of adjacent-1 (21.0% versus 29.6%), adjacent-2 (16.1% versus 11.1%) and 3:1 (41.9% versus 30.6%) segregation were not statistically significantly different in translocations with terminal breakpoints versus those without. Translocation with acrocentric chromosomes showed a significantly lower rate of 2:2 segregation (39.2% versus 60.2%, P = 0.001) and a higher rate of 3:1 segregation (43.1% versus 27.3%, P = 0.005) than those without acrocentric chromosomes. The incidence of 2:2 segregation was significantly higher in male than in female carriers (58.2% versus 45.0%, P = 0.019). This study suggested that reciprocal translocation involving terminal breakpoints resulted in a lower rate of normal/balanced karyotype in preimplantation embryos. Some characteristics of reciprocal translocation, such as terminal breakpoints, acrocentric chromosome and carrier gender, are related to the segregation patterns.     

Conventional ICSI improves the euploid embryo rate in male reciprocal translocation carriers

PurposeTo evaluate whether the morphologically normal spermatozoa selected for intracytoplasmic sperm injection (ICSI) under microscope had a higher rate of normal/balanced chromosome contents than that in the whole unselected sperm from reciprocal translocation carriers.MethodsFive hundred unselected spermatozoa from each of 40 male translocation carriers were performed with fluorescence in situ hybridization (FISH), to determine the rates of gametes with different meiotic contents of translocated chromosomes. Meanwhile, 3030 biopsied blastocysts from 239 male and 293 female reciprocal translocation carriers were detected with the microarray technique to analyze the rates of embryos with different translocated chromosome contents.ResultsThe D3 embryo rate, blastocyst formation rate, and euploid rate of blastocysts were remarkably higher in male carriers than those in female (p = 0.001, p = 0.004, and p = 0.035, respectively). In addition, the percentages of alternate products, which contained normal/balanced chromosome contents, in embryos from male carriers were markedly higher than those in sperm FISH (p = 2.48 × 10⁻⁵ and p = 2.88 × 10⁻¹⁰), while the percentages of adjacent-2 and 3:1 products were lower than those in sperm FISH (p = 0.003 and p = 5.28 × 10⁻⁴⁴). Moreover, consistent results were obtained when comparing the rates of products in embryos between male and female carriers. Specifically, the incidence of alternate products in male carriers was higher than those in female carriers (p = 0.022). However, no similar differences were seen between sperm and embryos of female carriers.ConclusionICSI facilitates the selection of spermatozoa with normal/balanced chromosome contents and improves the D3 embryo rate, blastocyst formation rate, and the euploid embryo rate in male carriers.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-020-02013-z.     

Preimplantation genetic diagnosis significantly improves the pregnancy outcome of translocation carriers with a history of recurrent miscarriage and unsuccessful pregnancies

Preimplantation genetic diagnosis (PGD) for translocations has been shown to significantly reduce the risk of recurrent miscarriage, but because the majority of embryos produced are unbalanced, pregnancy rate is relatively low since 20% or more cycles have no normal or balanced embryos to transfer. The purpose of this study was to evaluate whether PGD could improve pregnancy outcome in translocation carriers with a history of two or more consecutive miscarriages and no live births. PGD for translocations was offered to translocation carriers with two or more previous miscarriages (average 3.5) and no live births (0/117 pregnancies) using a combination of distal and proximal probes to the breakpoints. After PGD, only 18.3% of embryos were normal or balanced. Only 5.3% of pregnancies were lost after PGD compared with 100% before PGD (P < 0.001). The cumulative pregnancy rate was 57.6% and the cumulative ongoing pregnancy rate was 54.5% in the short period of time of 1.24 IVF cycles, or 46.3% and 43.9% respectively per cycle. In conclusion, PGD significantly reduced losses and increased the number of viable pregnancies (P < 0.001). IVF plus PGD are a faster method of conceiving a live child than natural conception, at least for translocation carriers with recurrent miscarriages and no previous live births.     

Pregnancy outcomes among chronic carriers of hepatitis B virus

Objective

To compare pregnancy outcomes of women with chronic HBV infection with those of HBV-negative women.

Methods

A retrospective cohort study was undertaken to analyze singleton pregnancies of women without medical/surgical disease and with known HBsAg status. Pregnancy outcome measures were compared among the control group, women with positive HBsAg status (case group), and those with positive HBeAg status.

Results

Among 26 350 enrolled pregnant women, 21 812 in the control group and 1446 in the case group were compared. Only the proportion of preterm births was significantly higher among pregnancies with positive HBsAg status (RR 1.013 [95% CI, 1.001–1.025]). Among women with positive HBsAg status who had been screened for HBeAg, GDM was significantly higher among women with positive HBeAg status (RR 1.434 [95% CI, 0.999–2.057]). Preterm births and low birth weight were also significantly higher among women with positive HBeAg status (RR 1.250 [95% CI, 1.000–1.563] and 1.258 [95% CI, 1.053–1.505], respectively).

Conclusion

Chronic carriers of HBV had a minimally increased risk of preterm birth and low birth weight but the risk was more pronounced in women with positive HBeAg status. Women with positive HBeAg status also had an increased risk of GDM.     

Evaluation of preimplantation genetic testing based on next-generation sequencing for balanced reciprocal translocation carriers

Research question

Can next-generation sequencing (NGS) based on copy number variation sequencing (CNV-Seq) identify normal/balanced embryos in balanced reciprocal translocation carriers and what are their reproductive outcomes?

Pregnancy and delivery outcomes in the women who have received adenomyomectomy: Performed by a single surgeon by a uniform surgical technique

ObjectiveAlthough adenomyomectomy for fertility-sparing is an expanding procedure worldwide, there is no guideline or consensus about how to manage the pregnant women who have previously received conservative surgery for adenomyosis. The aim of this study is to evaluate antenatal care and delivery outcomes in pregnant women after adenomyomectomy.Materials and methodsBetween May 2011 and May 2019, the medical record was reviewed in all delivery of pregnant women received adenomyomectomy performed by a single surgeon by a uniform surgical technique. The evaluating parameters consisted of antenatal care outcomes, delivery outcomes, intrapartum outcome, and neonatal outcomes.ResultsTwenty-two patients were evaluated to monitor pregnancy and delivery outcomes after the adenomyomectomy. Mean age of delivery was 37.0 years old (SD = 3.1, range 32–45, median 37). All were delivered by cesarean section. Mean gestational age was 36.2 weeks (SD = 3.6, range 27.4–39.4, median 37.3). The mean birth weight was 2560.9 g (SD = 771.8, range 1100–3920, median 2550) and the number of preterm births admitted for prematurity care was seven (31.8%, 7/22). Placental abnormality was found in the four cases, which included two placenta accreta and two previa. However, there were no cases of hysterectomy or intervention. We identified one case of uterine rupture during pregnancy (4.5%, 1/22) at 27 weeks of gestation. Except for preterm birth, adverse neonatal outcomes were not found in this study.ConclusionDelivery of pregnant women who received adenomyomectomy can obtain safe perinatal outcomes under close monitoring of preterm labor and surveillance of catastrophic pregnancy related complications.     

Embryoscopy and karyotype findings of repeated miscarriages in recurrent pregnancy loss and spontaneous pregnancy loss

Purpose

The aim of the study was to assess cytogenetic and embryoscopic characteristics in subsequent miscarriages of spontaneous pregnancy losses (SPL) and recurrent pregnancy losses (RPL).

Methods

A retrospective cohort of 75 women was affected by repeated pregnancy loss. Of those, 34 had SPL, 24 primary RPL, and 17 secondary RPL. Ploidy status and morphology was analyzed by transcervical embryoscopic examination of the embryo and cytogenetic analysis of the chorionic villi in subsequent miscarriages.

Results

Similar rates of recurrent ploidy status were observed between first and second miscarriage in SPL and RPL (82.4% recurrent ploidy status in SPL, p?>?0.999; 73% recurrent ploidy status in RPL, p?=?0.227). No difference was found regarding recurrent abnormal morphology between SPL and RPL (p?=?0.092). However, secondary RPL resulted significantly more often in recurrent abnormal morphology compared to primary RPL (p?=?0.004).

Conclusions

High rates of recurrent normal/abnormal karyotypes were observed in all groups with a majority of embryos presenting with recurrent abnormal morphology. Secondary RPL presented significantly more often with recurrent abnormal morphology compared to primary RPL. These findings offer prognostic information for the affected patient and might impact treatment choice.

     

Quadrivalent asymmetry in reciprocal translocation carriers predicts meiotic segregation patterns in cleavage stage embryos

The effect of quadrivalent geometry on meiotic behaviour was evaluated. Segregation patterns of 404 cleavage stage embryos from 40 reciprocal translocation carriers undergoing 75 PGD cycles were analysed according to the asymmetric degree of quadrivalent. The percentage of alternate products with severe asymmetric quadrivalents was significantly lower than patients with mild asymmetric quadrivalents (22.5% versus 38.7%, P = 0.001). The incidence of 3:1 products was significantly higher in patients with severe compared with mild asymmetric quadrivalents (23.1% versus 12.2%, P = 0.004). The incidence of adjacent 1 (25.8% versus 24.3%), 2 (11.5% versus 12.6%) and 4:0/other segregation products (17.0% versus 12.2%) were not statistically significantly different between embryos from patients with severe or mild asymmetric quadrivalents. After adjusting for the confounder of sex using a logistic regression model, the odds of alternate embryos is about one-half for carriers classified as severe (OR 0.456, 95% CI 0.291 to 0.705), and the odds of 3:1 embryos is 2.2 times higher for carriers with severe asymmetric quadrivalents (OR 2.235, 95% CI 1.318 to 3.846). Our results suggest that the meiotic segregation pattern is related to the degree of asymmetry of specific quadrivalents. Severe asymmetric quadrivalents increases the risk of abnormal embryos.     

Pregnancy outcomes after surgical treatment of ovarian pregnancy

Objective

To investigate pregnancy outcomes subsequent to ovarian pregnancy treated by surgery.

Methods

A retrospective analysis was conducted of ovarian pregnancies that were treated by surgery at a hospital in Korea between January 1996 and December 2009.

Results

Forty-nine women with ovarian pregnancies (1.6% of all ectopic pregnancies) were treated; 28 of these patients who were followed-up for more than a year were included in the study. The most common risk factor for ovarian pregnancy was endometriosis (42.9%). Accurate diagnosis of ovarian pregnancy was made preoperatively in 7 patients (25%). Of the 28 patients, 16 (57.1%) had subsequent pregnancies: 13 (46.4%) were intrauterine pregnancies and 3 (10.7%) were tubal pregnancies. However, no subsequent ovarian pregnancies occurred. In addition, only 1 patient had secondary infertility after surgery for ovarian pregnancy.

Conclusions

After an ovarian pregnancy treated by surgery, the outcome of a subsequent pregnancy is reasonable; there is a high rate of successful subsequent pregnancy and a low rate of subsequent ectopic pregnancy or of infertility.     

Clinical pregnancy following blastomere biopsy and PGD for a reciprocal translocation carrier: analysis of meiotic outcomes and embryo quality in two IVF cycles

A couple were referred for preimplantation genetic diagnosis (PGD) following diagnosis of a reciprocal translocation in the female partner: 46,XX,t(14;22)(q11.2;q13.3). PGD was carried out using fluorescence in situ hybridization (FISH) with probes specific for the translocated and centric segments of chromosome 22. An initial cycle was unsuccessful, producing 11 embryos for biopsy, only one of which, when followed up on day 4, yielded more than 10 nuclei (median 7.5, n=10). In addition, five of the embryos showed mosaic or chaotic chromosome constitutions; some of these embryos had fragmented or multilobed abnormal nuclei, hindering interpretation of the FISH signals. The single embryo transferred did not result in a pregnancy. A second cycle, using a revised protocol, produced 10 embryos, three of which were transferred, resulting in an ongoing singleton pregnancy. All the remaining embryos yielded 12 to 23 nuclei by day 4 (median 17, n=7). Apart from some tetraploid nuclei, only one embryo showed mosaicism. The significance of the changes in protocol leading to the successful outcome is discussed, and the pattern of meiotic segregation products is analysed and compared with other previous reports of reciprocal translocations.