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Role of preimplantation genetic screening in effectiveness of programs of assisted reproductive technologies in women with recurrent miscarriage (a review)
Introduction. Failures and defects of implantation after IVF are to high extent determined by maternal factors, which are manageable. However, until now, medical tactics have not been clearly defined in identifying the most significant of them among patients who have failures and defects in implantation in previous IVF programs.Objective. To summarize research literature and results of many years of our own research to determine medical tactics in patients with failures and defects in implantation in previous IVF programs when identifying significant maternal risk factors.Material and methods. The analysis and collation of data have been performed on the basis of 80 literature sources with a focus on the papers of domestic authors, including publications with regard to their own study results.Results. The most significant maternal risk factors for failures and defects of implantation after IVF were identified: chronic endomyometritis and thrombophilia. The pregravid preparation algorithm has been determined in patients with chronic endometritis and with previous failures and defects in implantation after IVF, including the use of antibacterial, antiviral, anti-inflammatory, immunomodulating and physiotherapy. We show the necessity for the prescription of low molecular weight heparins in patients with thrombophilia since the establishment of pregnancy after IVF has been shown.Conclusion. Carrying out pregravid preparation in patients with chronic endometritis and prescribing low molecular weight hepa-rins from early pregnancy in patients with thrombophilia can increase the percentage of women who have become pregnant after IVF and have passed the embryonic threshold.
Only a few years ago the American Society of Assisted Reproductive Medicine (ASRM), the European Society for Human Reproduction and Embryology (ESHRE) and the British Fertility Society declared preimplantation genetic screening (PGS#1) ineffective in improving in vitro fertilization (IVF) pregnancy rates and in reducing miscarriage rates. A presumably upgraded form of the procedure (PGS#2) has recently been reintroduced, and is here assessed in a systematic review. PGS#2 in comparison to PGS#1 is characterized by: (i) trophectoderm biopsy on day 5/6 embryos in place of day-3 embryo biopsy; and (ii) fluorescence in-situ hybridization (FISH) of limited chromosome numbers is replaced by techniques, allowing aneuploidy assessments of all 24 chromosome pairs. Reviewing the literature, we were unable to identify properly conducted prospective clinical trials in which IVF outcomes were assessed based on "intent to treat." Whether PGS#2 improves IVF outcomes can, therefore, not be determined. Reassessments of data, alleged to support the efficacy of PGS#2, indeed, suggest the opposite. Like with PGS#1, the introduction of PGS#2 into unrestricted IVF practice again appears premature, and threatens to repeat the PGS#1 experience, when thousands of women experienced reductions in IVF pregnancy chances, while expecting improvements. PGS#2 is an unproven and still experimental procedure, which, until evidence suggests otherwise, should only be offered under study conditions, and with appropriate informed consents.
Preimplantation genetic diagnosis and screening improves the chances of achieving a viable pregnancy, not only free of undesired single-gene defects but also aneuploidy. In addition, improvements in vitrification provide an efficient means of preserving embryos (blastocysts). By combining trophectoderm biopsy with recent improvements in vitrification methods, only those embryos that have proved themselves viable and potentially more competent are tested. Using array comparative genomic hybridization (aCGH) to assess all 24 chromosomes, aneuploidy rates were compared between day-3 blastomere biopsy and day-5 trophectoderm biopsy. Of those 1603 embryos, 31% were euploid, 62% were aneuploid and 7% not analysable. A significantly larger proportion of embryos were euploid on day-5 biopsy (42%) compared with day-3 biopsy (24%, P < 0.0001). The number of euploid embryos per patient was not significantly different. Combining extended culture, trophectoderm biopsy and aneuploidy assessment by aCGH and subsequent vitrification can provide a more efficient means of achieving euploid pregnancies in IVF.
To determine any beneficial effects of preimplantation genetic screening (PGS) of all chromosomes by array comparative genomic hybridization (aCGH), with either day 3 or blastocyst biopsy, for idiopathic recurrent pregnancy loss (RPL) patients compared with their expected loss rate.
Case series report.
Multiple fertility centers.
A total of 287 cycles of couples with idiopathic RPL (defined as two or more losses).
PGS was done with day 3 biopsy (n = 193) or blastocyst biopsy (n = 94), followed by analysis with aCGH.
Spontaneous abortion rate, euploidy rate.
A total of 2,282 embryos were analyzed, of which 35% were euploid and 60% were aneuploid. There were 181 embryo transfer cycles, of which 100 (55%) became pregnant with an implantation rate of 45% (136 sacs/299 replaced embryos) and 94 pregnancies (92%) were ongoing (past second trimester) or delivered. The miscarriage rate was found to be only 6.9% (7/102), compared with the expected rate of 33.5% in an RPL control population and 23.7% in an infertile control population.
Current PGS results with aCGH indicate a significant decrease in the miscarriage rate of idiopathic RPL patients and high pregnancy rates. Furthermore, this suggests that idiopathic recurrent miscarriage is mostly caused by chromosomal abnormalities in embryos.
Examination of fetal tissue from spontaneous miscarriages shows that 50-70% of them were caused by abnormal karyotype. The most frequent genetic abnormalities include abnormal number of chromosomes, aberration of chromosomes structure and chromosome mosaic anomalies.
The aim of the study was to find out whether there is any difference in the frequency of chromosomal aberrations in patients who miscarried for the first time comparing to patients with recurrent miscarriages.
Examination was performed on 129 miscarriage material samples from 128 women. Fluorescent hybridization in-situ (FISH) was used for genetic examination.
We received 120 results in which 45 (37,5%) were abnormal. The most frequent chromosomal aberration was trisomy followed by triploidy and monosomy of chromosome X. Among 59 samples from first miscarriage we found 25 abnormal karyotypes. In the 61 samples from the second, third and the next miscarriages we found 20 chromosomal abnormalities.
Frequency of chromosomal aberrations in the tissue from the first miscarriage is significantly higher than in samples from second or following miscarriages, which means that genetic factors are less likely to induce recurrent miscarriages. Genetic results confirm that most chromosomal abnormalities arise de-novo.
It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate. Therefore, advanced maternal age (AMA) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) on the outcome after assisted reproductive technology (ART).
A prospective randomized controlled clinical trial (RCT) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization (FISH) for the chromosomes X, Y, 13, 16, 18, 21 and 22 in AMA couples (aged > or =37 years) with a control group without PGD-AS. From the 400 (200 for PGD-AS and 200 controls) couples that were allocated to the trial, an oocyte pick-up was performed effectively in 289 cycles (148 PGD-AS cycles and 141 control cycles).
Positive serum HCG rates per transfer and per cycle were the same for PGD-AS and controls: 35.8% (19.6%) [%/per embryo transfer (per cycle)] and 32.2% (27.7%), respectively (NS). Significantly fewer embryos were transferred in the PGD-AS group than in the control group (P<0.001). The implantation rate (with fetal heart beat) was 17.1% in the PGD-AS group versus 11.5% in the control group (not significant; P=0.09). We observed a normal diploid status in 36.8% of the embryos.
This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred.
Preimplantation genetic screening (PGS) is used to determine the chromosome status of human embryos from patients with advanced maternal age (AMA), recurrent miscarriage (RM) or repeated implantation failure (RIF).
Embryos from 47 such couples were investigated for chromosomes 13, 15, 16, 18, 21 and 22 using fluorescence in situ hybridization with two rounds of hybridization. The investigation included parental lymphocyte work-up, the screening of blastomeres on day 3 and full follow-up on day 5/6 of untransferred embryos.
The outcome of 60 PGS cycles is described, in which 523 embryos were biopsied; 91% gave results, of which 18% were diploid for all the chromosomes tested and 82% were abnormal. The pregnancy rate per cycle that reached the biopsy stage was 27%, and 30% per embryo transfer. Satisfactory follow-up was obtained from 353 embryos; all those diagnosed as abnormal were confirmed as such, although two false-positives were detected in relation to specific chromosome abnormalities. Meiotic errors were identified in 16% of embryos. Between the RM, AMA and RIF groups, there was a significant difference in the distribution of embryos that were uniformly abnormal and of those with meiotic errors; with an almost 3-fold increase in meiotic errors in the first two groups compared with the RIF group.
This complete investigation has identified significant differences between referral groups concerning the origin of aneuploidy in their embryos.
Chromosomal abnormalities are an important cause of spontaneous abortion and recurrent miscarriage (RM). Therefore, we have analysed the incidence of chromosomal abnormalities and embryo development in patients with RM.
Preimplantation genetic diagnosis (PGD) was performed on 71 couples with RM and 28 couples undergoing PGD for sex-linked diseases (control group). Chromosomes 13, 16, 18, 21, 22, X and Y were analysed by fluorescence in-situ hybridization.
The implantation rate in RM patients was 28% and three patients (13%) miscarried. The percentage of abnormal embryos was significantly increased (P < 0.0001) in RM patients compared with controls (70.7 versus 45.1%). All of the embryos were abnormal in 19 cycles (22.1%) and repeated PGD cycles yielded similar rates of chromosomal abnormalities in 14 couples. Anomalies for chromosomes 16 and 22 were significantly higher (P < 0.01) in RM cases. In the RM population, euploid embryos reached the blastocyst stage more frequently than abnormal embryos (61.7 versus 24.9%; P < 0.0001).
RM is associated with a higher incidence of chromosomally abnormal embryos, of which some are able to develop to the blastocyst stage. IVF plus PGD is an important step in the management of these couples, but the technique has to move towards a full chromosome analysis.
Advanced maternal age (AMA) is an important parameter that negatively influences the clinical pregnancy rate in IVF, in particular owing to the increased embryo aneuploidy rate. It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate. The purpose of this study was to test whether employing preimplantation genetic screening (PGS) in AMA patients would increase the clinical pregnancy rate.
We conducted a two-center, randomized controlled trial (RCT) to analyze the outcome of embryo transfers in AMA patients (>or=38 years of age) after PGS using FISH analysis for chromosomes X, Y, 13, 16, 18, 21 and 22. The PGS group was compared with a control group. The primary outcome measure was clinical pregnancy rate after 6-7 weeks of gestation per randomized patient.
The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome. Of the 320 patients calculated to be included in the study, 56 and 53 patients were randomized into the PGS and control groups, respectively. The clinical pregnancy rate in the PGS group was 8.9% (95% CI, 2.9-19.6%) compared with 24.5% (95% CI, 13.8-38.3%) in the control group, giving a difference of 15.6% (95% CI, 1.8-29.4%, P = 0.039).
Although the study was terminated early, this RCT study provides evidence against the use of PGS for AMA patients when performing IVF. Trial registration number: ISRCTN38014610.
All agree that in hindsight the rapid adoption of preimplantation genetic screening (PGS) using cleavage stage biopsy and
fluorescence in situ hybridization (FISH) in routine clinical practice without proper evaluation of (cost-)effectiveness basically resulted in
couples paying more money for a less effective treatment. Now, almost 20 years later, we are on the verge of a new era of
PGS. But have things really changed or are we simply going back to the future?
Preimplantation Genetic Screening (PGS) has been used in clinical practice for more than 15 years with the goal of increasing live birth rates after IVF. In this thesis it is shown that PGS in its current form instead decreases live birth rates after IVF. Reasons for its inefficacy are provided and new forms of PGS and the role of embryo selection in the near future of IVF are being discussed.
Objective:
To evaluate the usefulness of preimplantation genetic screening (PGS) using fluorescence in situ hybridization (FISH) for two different indications: repetitive implantation failure (RIF) and advanced maternal age (AMA).
Design:
Two prospective, randomized controlled trials with patients allocated in two arms: blastocyst transfer on day 5 (group A) or PGS with transfer on day 5 (group B).
Setting:
University-affiliated private clinics.
Patient(s):
The RIF study included women <40 years with three or more failed IVF cycles without other known causal factors (91 patients). The AMA study included intracytoplasmic sperm injection patients aged between 41 and 44 (183 patients).
Intervention(s):
In the PGS group, single-cell day 3 biopsy was performed with aneuploidy screening for chromosomes 13, 15, 16, 17, 18, 21, 22, X, and Y. In both the blastocyst transfer group and the PGS group, ET was performed on day 5.
Main outcome measure(s):
Live-birth rate per patient and per started cycle.
Result(s):
A significant increase in live-birth rates per patient was found in the PGS group compared with the blastocyst group for the AMA study (30/93 patients [32.3%] vs. 14/90 patients [15.5%]; odds ratio, 2.585; confidence interval, [1.262-5.295]). In the RIF study no significant differences were observed (23/48 patients [47.9%] vs. 12/43 patients [27.9%]).
Conclusion(s):
PGS with FISH was shown to be beneficial for the AMA group.
The objective of this systematic review was to assess live birth rates and miscarriage rates after preimplantation genetic screening or natural conception for unexplained recurrent miscarriage. There were no randomized controlled trials or comparative studies found on this topic. Until data from randomized controlled trials become available, this review summarizes the best available evidence of the efficacy of preimplantation genetic screening vs. natural conception.
To evaluate a new strategy for comprehensive chromosome screening at the blastocyst stage.
Clinical research study.
An IVF clinic and a specialist preimplantation genetic diagnosis laboratory.
Forty-five infertile couples participated in the study. The mean maternal age was 37.7 years, and most couples had at least one previous unsuccessful IVF treatment cycle (mean 2.4).
This study used a novel chromosome screening approach, combining biopsy of several trophectoderm cells on day 5 after fertilization and detailed analysis of all 24 types of chromosome using comparative genomic hybridization.
Proportion of embryos yielding a diagnostic result, aneuploidy rate, implantation rate, and pregnancy rate.
A diagnosis was obtained from 93.7% of embryos tested. The aneuploidy rate was 51.3%. The probability of an individual transferred embryo forming a pregnancy reaching the third trimester/birth was 68.9%, an implantation rate 50% higher than contemporary cycles from the same clinic. The pregnancy rate was 82.2%.
The comprehensive chromosome screening method described overcomes many of the problems that limited earlier aneuploidy screening techniques and may finally allow preimplantation genetic screening to achieve the benefits predicted by theory. The high embryo implantation rate achieved is particularly encouraging and, if confirmed in subsequent studies, will be of great significance for IVF clinics attempting to reduce the number of embryos transferred or to implement single embryo transfer.
One of the most important factors in increasing the screening potential of preimplantation genetic diagnosis (PGD) for aneuploidy is to increase the number of chromosomes analysed. Inclusion of chromosomes 8, 14 and 20 to the standard set of chromosomes X, Y, 13, 15, 16, 17, 18, 21 and 22 allows the analysis of 12 chromosomes in three rounds of fluorescent in-situ hybridization (FISH) without decreasing the efficiency of the technique. Pregnancy rate was significantly increased when only embryos that had been diagnosed as normal for the 12 chromosomes analysed were transferred compared with transfer of embryos with any abnormality for chromosomes 8, 14 or 20 (P < 0.05). This study proves that the high efficiency and practical feasibility of FISH analysis of 12 chromosomes in PGD for aneuploidy is a superior approach than the standard nine-chromosome analysis in order to screen for abnormalities.
The objective of this study was to identify specific subgroups of recurrent pregnancy loss (RPL) patients of unknown aetiology in whom the selection of chromosomally normal embryos for transfer improves reproductive outcome in preimplantation genetic screening (PGS). A total of 428 PGS cycles were included and chromosomes 13, 15, 16, 18, 21, 22, X and Y were evaluated. In RPL patients < or =37 years, a lower incidence of chromosomal abnormalities (P = 0.0004) and miscarriages (P = 0.0283) was observed, and there were significantly higher pregnancy (P < 0.0384) and implantation (P < 0.0434) rates than in patients >37 years. In the former subset, results showed: (i) significantly higher implantation rates (P = 0.0411) in couples that had experienced a previous aneuploid miscarriage; (ii) similar aneuploidy, pregnancy and implantation rates in couples suffering previous miscarriages during fertility treatments and in those with previous spontaneous pregnancies; (iii) no miscarriages after PGS in couples in whom a fluorescence in-situ hybridization assay showed the male partner's sperm to be abnormal; and (iv) lower implantation rates in couples with > or =5 previous miscarriages, associated with a lower percentage of chromosomally abnormal embryos. It is concluded that PGS is to be strongly recommended when RPL is associated with miscarriages during infertility treatments, chromosomopathy in a previous miscarriage, up to five previous miscarriages and a high incidence of chromosomal abnormalities in spermatozoa.
To test the hypothesis that patients with advanced maternal age (AMA) have a higher implantation rate (IR) after embryo transfer of embryos with a normal chromosomal pattern for the chromosomes studied with preimplantation genetic screening (PGS) compared with patients who had an embryo transfer without PGS.
Prospective randomized controlled trial (RCT).
Academic tertiary setting.
Patients with AMA (> or =35 years).
In an RCT, the clinical IR per embryo transferred was compared after embryo transfer on day 5 or 6 between the PGS group (analysis of chromosomes 13, 16, 18, 21, 22, X, and Y) and the Control group without PGS.
No differences were observed between the PGS group and the Control group for the clinical IR (15.1%; 14.9%; rate ratio 1.01; exact confidence interval [CI], 0.25-5.27), the ongoing IR (at 12 weeks) (9.4%; 14.9%), and the live born rate per embryo transferred (9.4%; 14.9%; rate ratio 0.63; exact CI, 0.08-3.37). Fewer embryos were transferred in the PGS group (1.6 +/- 0.6) than in the Control group (2.0 +/- 0.6). A normal diploid status was observed in 30.3% of the embryos screened by PGS.
In this RCT, the results did not confirm the hypothesis that PGS results in improved reproductive outcome in patients with AMA.
To determine whether the routine use of preimplantation genetic screening (PGS) in "good prognosis" women improves in vitro fertilization (IVF) cycle outcome.
Randomized, controlled, prospective clinical study.
Private infertility clinic.
Infertile women predicted to have a good prognosis as defined by: age <39 years, normal ovarian reserve, body mass index <30 kg/m(2), presence of ejaculated sperm, normal uterus, <or=2 previous failed IVF cycles.
Patients were randomized to the PGS group or the control group on day 3 after oocyte retrieval; 23 women underwent blastomere biopsy on day 3 after fertilization (PGS group), and 24 women underwent routine IVF (control group). All embryos were transferred on day 5 or 6 after fertilization.
Pregnancy, implantation, multiple gestation, and live birth rates.
No statistically significant differences were found between the PGS and control groups with respect to clinical pregnancy rate (52.4% versus 72.7%). However, the embryo implantation rate was statistically significantly lower for the PGS group (31.7% versus 62.3%) as were the live birth rate (28.6% versus 68.2%) and the multiple birth rate (9.1% versus 46.7%).
In a "good prognosis" population of women, PGS does not appear to improve pregnancy, implantation, or live birth rates.
To determine whether preimplantation genetic diagnosis (PGD) would decrease spontaneous abortion rates in patients with idiopathic recurrent pregnancy loss (RPL).
Controlled clinical study.
IVF center and PGD reference laboratory.
Patients with RPL with no known etiology.
Preimplantation genetic diagnosis by fluorescence in situ hybridization analyzing nine chromosomes.
The spontaneous abortion rate after PGD was compared to the patients' own expected risk of abortion. Patients were evaluated according to the number of previous losses, fertility, and maternal age.
Preimplantation genetic diagnosis significantly reduced spontaneous abortions in patients with RPL, especially for patients with more than two previous losses (12.8% vs. 35.9% expected). The PGD significantly reduced the rate of spontaneous abortion in both fertile (15.2% vs. 33.8% expected) and infertile patients (13.0% vs. 29.5%), which also achieved similar delivery rates (37% and 34%, respectively). The beneficial effect of PGD was less pronounced in patients <35 years than in patients > or =35 years old (13.6% vs. 34.0% expected). Overall, the PGD reduced the miscarriage rate to a similar baseline of 14%-16% across all maternal ages.
Preimplantation genetic diagnosis improves pregnancy outcome for women with idiopathic RPL, especially those with more than two previous losses, and >35 years of age, and that improvement is not affected by fertility status.
To assess the potential benefit of preimplantation aneuploidy testing on the outcome of in vitro fertilization (IVF) for women of advanced maternal age (AMA).
Prospective randomized clinical trial.
Private IVF clinic.
Sixty-two infertile AMA couples undergoing fertility treatment.
Fluorescent in situ hybridization (FISH) for chromosomes X, Y, 13, 15, 16, 17, 18, 21, and 22.
Preimplantation aneuploidy testing of biopsied blastomeres on day 3 of development.
Fertilization and blastocyst developmental rates were similar for the test and control groups: 80% versus 77.4% and 49% versus 48.2%, respectively. The average number of embryos transferred was comparable at 2.2 for the test group and 2.7 for the control group. Implantation rates were also equivalent across the two groups: 37.3% in the control group versus 36.5% in the test group. Nevertheless, the spontaneous abortion rate was observed to be lower for the test group: 25.9% versus 32.26% in the control group. This resulted in an observed increase in delivery rates for the test group: 78% versus 67.74% in the control group.
Preimplantation aneuploidy testing does not appear to statistically significantly improve outcome parameters in infertile AMA patients; however, a trend toward a decrease in the spontaneous abortion rate with a subsequent higher delivery rate was observed.
To compare the frequency of chromosomal abnormalities in products of conception from women with and without a history of recurrent spontaneous abortion.
Retrospective analysis of prospectively collected material.
Private practice at the Genetics and IVF Institute, Fairfax, Virginia and Grupo de Reproducción AGY Asociados, México City, México.
Women with (n = 94) and without (n = 130) a history of recurrent spontaneous abortion who had a spontaneous abortion between January 1, 1992 and November 1, 1994.
Chromosomal analysis performed on products of conception using standard G-banding technique.
The percentage of chromosomal abnormalities among products of conception from women with and without recurrent spontaneous abortion was compared.
Among products of conception from women with recurrent spontaneous abortion, 57% (54/94) had abnormal and 43% (40/94) had normal chromosome analyses. Products of conception from women without recurrent spontaneous abortion had abnormal chromosome analyses in 57% (74/130) and normal results in 43% (56/130).
No differences in frequency of abnormal karyotype were observed in products of conception from women with recurrent spontaneous abortion compared with women without recurrent spontaneous abortion.
To examine the frequency of chromosomal abnormalities in products of conception from patients with recurrent miscarriages in relation to the number of previous miscarriages.
Retrospective analysis.
Nagoya City University Medical Hospital.
A total of 1,309 women with a history of 2-20 consecutive first-trimester abortions.
Chromosomal analysis performed on products of conception with use of a standard G-banding technique.
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.
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.
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.
Embryos that are transferred after in vitro fertilization frequently fail to implant in the uterus; in many cases, this failure is due to chromosomal abnormalities in the embryo. The current methods of diagnosis of aneuploidy cannot detect many chromosomal abnormalities. This report on the case of a 38-year-old woman with a long history of infertility describes the use of comparative genomic hybridization to determine that all the chromosomes of a single embryo were free of aneuploidy, resulting in the birth of a healthy infant.
To apply preimplantation genetic diagnosis (PGD) for the treatment of patients with a history of failed IVF-ET or habitual aborters.
Prospective clinical study.
Tertiary center for assisted reproduction.
Ninety-four couples with failed IVF-ET after >2 IVF cycles and 64 couples with >2 spontaneous abortions.
Patients were prepared for oocyte retrieval using standard controlled ovarian hyperstimulation protocols after standard laboratory techniques. Blastomeres from 6- to 8-cell embryos were analysed using fluorescence in situ hybridization with commercial chromosomal probes, and normoploid embryos were transferred on day 3 after fertilization.
Pregnancy and implantation rates and live births.
Both 3- and 5-probe PGD resulted in a significantly higher outcome than controls for failed IVF-ET. Five-probe PGD appeared to be more suitable for habitual aborters.
This pilot study suggests that 3-probe PGD is a valid option for failed IVF-ET patients. The use of five or more probes is indicated for habitual aborters.
To determine the aneuploidy rate in embryos of women with idiopathic recurrent miscarriages and to evaluate whether preimplantation genetic diagnosis for aneuploidy screening could be a feasible approach to improve the possibility of successful pregnancy in these couples.
Prospective cohort study.
Tertiary university referral center.
Women (n = 49) with recurrent idiopathic miscarriages.
In vitro fertilization with preimplantation genetic diagnosis for aneuploidy screening.
Ongoing pregnancy rate (PR) and aneuploidy rate.
The aneuploidy rate was, respectively, 43.85% and 66.95% in the younger and older group. The ongoing PR per cycle was 25.71% in the younger and 2.94% in the older patients.
There is no therapeutic evidence to prescribe IVF with or without preimplantation genetic diagnosis for aneuploidy screening for this heterogeneous group of patients.
To determine whether preimplantation genetic diagnosis (PGD) and transfer of euploid embryos would decrease spontaneous abortion rates in recurrent miscarriage (RM) patients.
Controlled clinical study.
In vitro fertilization centers and PGD reference laboratory.
Recurrent-miscarriage patients with three or more prior lost pregnancies with no known etiology.
Biopsy of a single blastomere from each day 3 embryo, followed by fluorescence in situ hybridization analysis.
The rate of spontaneous abortions in RM subjects undergoing PGD were compared with [1] their own a priori expectations and [2] a comparison group of women undergoing PGD for advanced maternal age (> or =35 years).
Before PGD, RM patients had lost 87% (262/301) of their pregnancies, with an expected loss rate of 36.5%. After, they only lost 16.7% pregnancies. This difference was mostly due to reduction in pregnancy loss in the > or =35-years age subgroup, to 12% from an expected 44.5%.
Preimplantation genetic diagnosis aneuploidy screening has a beneficial effect on pregnancy outcome in RM couples, especially those in which the woman is aged > or =35 years. Our data indicate that PGD reduces the risk of miscarriage in RM patients to baseline levels.
The clinical impact of PGD was evaluated through the analysis of the reproductive outcome before and after PGD in the same group of poor prognosis IVF patients, undergoing PGD for chromosomal abnormalities. Based on a series of 2359 PGD cycles, resulting in the establishment of 498 chromosomal abnormality-free clinical pregnancies, the reproductive history prior to PGD was analysed. Of 483 previous pregnancies analysed in patients with 432 pregnancies generated after PGD for aneuploidies, 328 (68%) ended in spontaneous abortions, in contrast to 28.4% after PGD, with only 155 (32%) resulting in deliveries, compared with 71.9% take-home baby rates after PGD. The patients experienced 315 previous IVF attempts, resulting in the transfer of 706 embryos in 308 cycles, of which only 49 (6.9%) implanted, compared with a 34.9% implantation rate observed in the same patients after PGD. Similar analysis of the previous reproductive outcomes of 45 carriers of balanced translocations achieving pregnancies following PGD, showed even stronger clinical impact, with a reduction of spontaneous abortions from 87.8% to 17.8%, and improvement of take-home baby rate from 11.5% to 81.4% after PGD. The results demonstrate a strong clinical impact of PGD, resulting in improvement of implantation rate, reduction of spontaneous abortions and increase in the take-home baby rate.
The inicidence of miscarriage is correlated with maternal age. The majority of miscarriages are chromosomally abnormal. The purpose of this study was to determine in a large population of infertility patients (>2000 cycles) if preimplantation genetic diagnosis (PGD) reduced the rate of spontaneous abortions.
Multicenter retrospective controlled study.
One hundred IVF centers referring samples to a reference PGD laboratory.
Infertile women.
The spontaneous abortion rate after PGD was retrospectively compared to non-PGD cycles from the 2002 American Society for Reproductive Medicine-Society for Assisted Reproduction Technology report on IVF cycles.
Spontaneous abortions and trisomic offspring rates.
The study included 2,279 cycles of PGD. The pregnancy rate per retrieval was 26.7% (average age 39.6). The mean pregnancy loss for the PGD group (0.167) was significantly lower than for the general IVF group (0.215) (P<.001). After PGD, the spontaneous abortion rate was 14.1% for ages 35-40, and 22.2% for women over 40, compared to 19.4% (P=.03) and 40.6% (P<.001), respectively, in controls. The clinical error rate of PGD (1.2%) was significantly lower than expected (4.7%) (P<.001).
The data suggests that PGD significantly reduces the risk of spontaneous abortions in women undergoing IVF and PGD, particularly in women over 40. In addition, PGD may also reduce the risk of trisomic offspring.
Recurrent pregnancy loss is a devastating health problem that affects many couples who are trying to establish a family. Evaluation depends on a number of factors, including the pattern of pregnancy loss, underlying medical disease and life-style issues. A detailed obstetric history, including gestational age at the time of death, ultrasound, pathology and cytogenetic results, is key in the evaluation and management of recurrent pregnancy loss. This complex reproductive disorder requires a multidisciplinary approach since genetic, endocrinologic, anatomic, immunologic, infectious, thrombophilic and iatrogenic factors may require evaluation and management. Monitoring of subsequent pregnancies requires close supportive care.
Recurrent pregnancy loss affects up to 5% of couples trying to establish a family. Evaluation classically begins after 3 consecutive miscarriages of less than 10 weeks of gestation but may be warranted earlier if a prior miscarriage was found to be euploid, or if there is concomitant infertility and/or advancing maternal age. The evaluation begins with an extensive history and physical, followed by a diagnostic screening protocol. Management must be evidence-based; unproven treatments should be avoided. If no factor is identified, many couples will still eventually have a successful pregnancy outcome with supportive therapy alone.
Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of recurrent miscarriages
- S Munné
- S Chen
- J Fischer
Munné S, Chen S, Fischer J, et al. Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older
with a history of recurrent miscarriages. Fertil Steril. 2005;84(2):331335.
doi: 10.1016/j.fertnstert.2005.02.027
Prognostic factors for preimplantation genetic screening in repeated pregnancy loss
- C Rubio
- P Buendía
- L Rodrigo
RubIo C, Buendía P, Rodrigo L, et al. Prognostic factors for preimplantation genetic screening in repeated pregnancy loss. Reprod
Biomed Online. 2009;18(5):687-693.
doi: 10.1016/S1472-6483(10)60015-6
Proportion of aneuploidy does not impact live birth rate or Проблемы репродукции
- J M Franasiak
- R Barnett
- K H Hong
- M D Werner
- R T Scott
Franasiak JM, Barnett R, Hong KH, Werner MD, Scott RT.
Proportion of aneuploidy does not impact live birth rate or
Проблемы репродукции, 2, 2017