Preimplantation Genetic Diagnosis Group Research Articles

A blastocyst biopsy approach for preimplantation genetic diagnosis technique that affects the expression of SNAP-α in mice

Preimplantation genetic diagnosis (PGD) is a technique that is commonly used during assisted reproduction in the clinics to eliminate genetically abnormal embryos before implantation. The blastomere biopsy technique has risks related to the embryo, but blastocyst biopsy has not been systematically evaluated in relation to effects after birth, and the resulting offspring have not been followed up on. We designed a series of experiments to evaluate the risk of blastocyst biopsy on the resulting progeny. Mice were divided into a PGD group and a control group. The former was the progeny of mice that underwent blastocyst biopsy and the latter was delivered through a normal pregnancy without blastocyst biopsy. Each group consisted of 15 animals. We found no effects of blastocyst biopsy on reproductive capacities and weight gain. As for neurobehavioral evaluation between both groups, there were no significant differences in tail suspension test, sucrose preference test, the open field test and the elevated plus maze. Western blotting, immunohistochemistry and quantitative RT-PCR results showed that the expression levels of MBP, PRDX5 and UCHL1 in the PGD group were not significantly different compared to the control group, but SNAP-α expression in the PGD group was lower than that in control group. In summary, we concluded that blastocyst biopsy had no adverse effect on the general growth and behavior in mice. However, blastocyst biopsy effected the expression of SNAP-α. Therefore, the safety of blastocyst biopsy requires further evaluation.

Growth, health, and motor development of 5-year-old children born after preimplantation genetic diagnosis

To evaluate the growth, health, and motor development of children born after preimplantation genetic diagnosis (PGD). Observational cohort study and comparison of 5-year-old children born after PGD to similar aged children born after IVF/intracytoplasmic sperm injection (ICSI) and children from families with a genetic disorder born after natural conception (NC). University hospital. One hundred three children were included in the PGD group. The two control groups consisted of 90 children born after IVF/ICSI and 58 children born after NC. PGD. We measured height, weight, body circumferences, body mass index, and blood pressure and performed a dysmorphological and neurological examination. We also collected data about the children's medical history, health care consultations, and motor milestones. The mean height, weight, and body mass index were comparable for all groups. Six (5.8%) PGD, four (4.4%) IVF/ICSI, and five (8.6%) NC children had a major congenital abnormality. The incidence of acute and chronic illnesses was similar in all groups. Motor milestones were achieved on time, but the IVF/ICSI group had a slightly younger mean sitting age. None of the children had severe neurological problems. Five-year-old children born after PGD show normal growth, health, and motor development when compared with children born after IVF/ICSI and NC children from families with a genetic disorder. NCT02149485.

Obstetrical and Neonatal Outcome after Pre Implantation Genetic Diagnosis; Eight Year Experience at King Faisal Specialized Hospital & Research Center

Objectives: To determine if there is any observable effect of pre implantation genetic diagnosis (PGD) on obstetrical outcome and perinatal morbidity and mortality, birth defects, neonatal outcome in addition, finding the rate of misdiagnosis. Setting: King Faisal Specialist Hospital and Research Center (Reproductive Medicine & Perinatology Sections) at Riyadh, Saudi Arabia. Design: A retrospective chart review of PGD patients from Jan 2001- Dec 2009. Materials and Methods: A total of 70 PGD pregnancies and 70 matching spontaneously conceived pregnancies were reviewed. The main outcome measures were rate of multiple pregnancies, gestational age (GA) at delivery, mode of delivery, sex, apgar score (A/S), birth weight, presence of birth defects, misdiagnosis and perinatal and neonatal mortalities. Results: Data were collected from 79 children born after PGD and compared to 72 children born after spontaneous pregnancies. PGD group had significantly more multiple pregnancies. However, there was no statistically significant difference between other outcomes in terms of: birth weight, GA at delivery, sex distribution, perinatal mortality and presence of congenital malformations. The misdiagnosis rate was 1.4%. Conclusion: PGD does not add risk factors to the health of babies born after the procedure. The perinatal death rate and rate of congenital malformations were not higher for PGD group in this study.

Risk factors for depression and anxiety among men and women planning for pre-implantation genetic diagnosis

Background: Previous studies have shown that women planning for in vitro fertilisation (IVF) show more distress than do men. Most studies about distress and pre-implantation genetic diagnosis (PGD) are based on women’s experiences. Little is known about what are the risk factors for men and women to experience anxiety or depression when planning for PGD.Objective: The first aim was to investigate presence of symptoms of depression and anxiety in men (n = 17) and women (n = 19) planning for PGD and compare this to men (n = 23) and women (n = 24) who were planning their first IVF. The second aim was to investigate if specified risk factors could predict the presence of anxiety and depression in the PGD group.Method: Anxiety and depression were measured with the questionnaire, the Hospital Anxiety and Depressions Scale (HADS). The Swedish version of the short Sense of Coherence scale was used to measure individuals’ sense of coherence. An index was created for six risk factors tested in the PGD group.Results: Low Sense of Coherence and history of miscarriage or termination were predictors of symptoms of depression among women in the PGD group. Socioeconomic risk and having a child with the genetic disease were predictors for anxiety in men.Conclusion: Women planning for PGD and IVF reported similar levels of anxiety or depression while men in the PGD group reported significantly more anxiety than men planning for IVF. Risk factors indicating depression or anxiety were found in the PGD group. The results of the present study are relevant for pre PGD counselling.

Does early cleavage correlate with chromosome constitution in human preimplantation embryos?

IntroductionThe purpose of this study is to analyze the correlation between the occurrence of early cleavage and chromosome constitution of embryos from preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). Material and methodsA total of 595 embryos from 96 cycles were included in this retrospective study. ResultsWhen clinical pregnancy rates per transfer were compared, statistically significant differences were observed between patients that had at least one early cleavage (ECpos) embryo and patients no EC (ECneg) (35.7% vs. 6.7%; p<.001). Statistically significant differences were found between EC, No PN and 2PN embryos at 26h, good embryo quality at day 2 (71.4%, 55.6% and 40.7%, respectively; p<.05) and in blastocyst rate (43.3% EC vs. no early cleavage embryos (NEC) 27.1%; p<.001) in PGS cycles. These differences were not found in the PGD group. Early-cleaved embryos exhibited less chromosome abnormalities than No PN and 2PN group in PGS (61%, 69.4% and 77.2%; p<.05) and differences in PGD group (69.8%, 76.2% and 66.7%; p<.05). DiscussionEarly cleavage has shown to correlate with embryo quality, with the capacity to develop up to blastocyst stage, as well as with euploid chromosome constitution.

The uptake and outcome of prenatal and pre‐implantation genetic diagnosis for Huntington's disease in the Netherlands (1998–2008)

We aimed to study reproductive behaviour of couples opting for prenatal diagnosis (PND) and pre-implantation genetic diagnosis (PGD) for Huntington's disease (HD). In the Netherlands, exclusion PND is available for persons at 50% risk, whereas exclusion PGD is not allowed. All 162 couples who underwent PND or PGD for HD between 1998 and 2008 and referrals for exclusion PGD to Belgium were included. Couples' reproductive information was collected until December 2010; 132 couples (81.5%) underwent PND in 262 pregnancies, 54 (33.3%) started PGD, and 25 used both. Sixteen percent of PND couples used exclusion PND and 6% used exclusion PGD. The outcomes were 76.5% of PND couples delivered ≥1 unaffected child(ren) after PND, and 44.4% of PGD couples delivered ≥1 PGD child(ren) (mean 2.5 cycles/couple). Couples opting for PGD secondarily (after a previous pregnancy) had more frequently terminated a pregnancy for HD (87.0%) compared with couples secondarily opting for PND (55.2%; p = 0.015). At-risk or HD expansion carrier males were underrepresented in the group of couples primarily opting for PGD (25%) and overrepresented in the secondary PGD group (64%). We conclude that couples reconsider their choices in every subsequent pregnancy based on their previous experience, personal beliefs and the gender of the at-risk partner.

A comparison of decisions about prenatal diagnosis and pre-implantation genetic diagnosis

Background: The development of pre-implantation genetic diagnosis (PGD) means that it is possible to avoid the birth of a child with a genetic condition without a termination. Objectives: Three issues were addressed. (1) Do decisions to terminate pregnancy following prenatal diagnosis (PND) differ from decisions not to implant embryos following PGD? (2) Do differences vary according to the condition diagnosed? (3) We performed a preliminary exploration of factors that might influence differences. Method: In Study 1, 216 participants were randomly assigned to two conditions and were asked whether they would terminate a pregnancy (PND group) or avoid implantation (PGD group) following diagnosis of five genetic conditions. In Study 2, 11 women completed a questionnaire prior to an interview. Results: In Study 1, there was interaction between the technology (PND or PGD) and the severity of the genetic condition diagnosed. For the most and least severe conditions, the number of women choosing to terminate/avoid implantation was similar in both groups. For conditions in the middle range of severity significantly more women said that they would avoid implantation. In Study 2, thematic analysis identified a number of themes that might influence decision-making. Conclusion: The technology used to test plays an important factor in decision-making for some conditions.

Human embryonic development after blastomere removal: a time-lapse analysis

Blastomere biopsy of human embryos is performed for preimplantation genetic diagnosis (PGD). The impact on further development is largely unexplored, though studies on mice suggest an influence on the hatching process. The objective of this study was to evaluate the effect of blastomere biopsy on early human embryonic development using time-lapse analysis. Embryos from couples undergoing PGD treatment or IVF/ICSI were included. In the PGD group, 56 human embryos had one blastomere biopsied. As controls, 53 non-biopsied IVF/ICSI embryos were selected. All embryos were cultured until 5 days after fertilization in a time-lapse incubator (EmbryoScope™). Images of embryos were acquired every 20 min. Time-points of key embryonic events were registered, and development in the two groups was compared. Duration of the biopsied cell-stage in the PGD group was longer than in the control group (P < 0.001), causing biopsied embryos to reach subsequent embryonic stages until hatching at significantly later time-points (P(compaction) < 0.001; P(morula) < 0.001; P(earlyblast) < 0.001; P(fullblast) = 0.01), but with unchanged intervals. Embryos in the PGD group started hatching at the same time-point as the control group, but had a smaller diameter (P < 0.001), and a thicker zona pellucida (P < 0.001) when hatching. Time-lapse videos revealed that in the control group, expansion of the blastocyst caused continuous thinning of zona pellucida until the blastocyst hatched, whereas in the PGD group the blastocyst hatched through the opening in zona pellucida artificially introduced prior to the biopsy. We find that blastomere biopsy prolongs the biopsied cell-stage, possibly caused by a delayed compaction and alters the mechanism of hatching.

Does blastomere biopsy in preimplantation genetic diagnosis affect early serum β-hCG levels?

ObjectiveTo determine whether the serum β-human chorionic gonadotropin (hCG) profile following preimplantation genetic diagnosis (PGD) is lower than that of intracytoplasmic sperm injection (ICSI) cycles.MethodsA total of 129 PGD cycles and 1,161 age-matched ICSI cycles, which resulted in pregnancy (serum β-hCG≥5 mIU/mL) on post-ovulation day (POD) 12 were included. We compared the mean serum β-hCG levels on POD 12, 14, 21, and 28, doubling time of serum hCG, and created a cut-off value for predicting a singleton pregnancy in each group.ResultsThe mean serum β-hCG concentration of the PGD group was significantly lower than that of the control group on POD 12, 14, and 21. The doubling time of serum β-hCG at each time interval showed no significant difference. The cut-off-value of serum β-hCG for predicting a single viable pregnancy was 32.5 mIU/mL on POD 12 and 113.5 mIU/mL on POD 14 for the PGD group, which was lower than that for the control group.ConclusionBlastomere biopsy may decrease the β-hCG-producing activity of the trophoblasts, especially in early pregnancy. Setting a lower cut-off value of serum β-hCG for predicting pregnancy outcomes in PGD may be needed.

Outcomes of vitrified–warmed day-4 embryos after day-3 cleavage-stage biopsy

The objective of this study was to compare the post-warming survival rates of biopsied and non-biopsied day-3 embryos vitrified on day 4 and to evaluate the clinical outcomes of following transfers. This study included 18 preimplantation genetic diagnosis (PGD) patients and 18 non-PGD patients treated between January 2005 and January 2009 who had not achieved live births during their fresh embryo-transfer cycles and whose surplus embryos were cryopreserved on day 4. The embryo survival rate after warming in the PGD and non-PGD groups was similar (53/59, 89.8% versus 55/64, 85.9%, respectively; difference of 3.9% 95% CI -7.3 to 13.4). Vitrified embryo-transfer cycles yielded no significant differences between PGD and non-PGD groups in implantation rates (12/46, 26.1% versus 9/47, 19.1%, respectively; difference of 6.9%, 95% CI -9.7 to 22.2), clinical pregnancy rates (11/18, 61.1% versus 9/18, 50%, respectively; difference of 11.1%, 95% CI -20.6 to 40.6) and live birth rates (9/18, 50% versus 6/18, 33.3%, respectively; difference of 16.7%, 95% CI -15.1 to 44.8). These results showed that, in PGD cycles, embryos can be vitrified effectively on day 4 after biopsy on day 3. The objective of this study was to compare the post-warming survival rates of biopsied and non-biopsied day-3 embryos that vitrified on day 4 and to evaluate the clinical outcomes of following transfers. This retrospective study included 18 preimplantation genetic diagnosis (PGD) and 18 non-PGD patients treated between January 2005 and January 2009 who had not achieved live births during their fresh embryo transfer cycles and whose surplus were frozen on day 4. After warming in frozen embryo-transfer cycles, embryo survival with respect to embryo grades, implantation, clinical pregnancy and live birth rates were compared. The embryo survival rate after warming in the PGD group was similar to the survival rate in the non-PGD group (53/59, 89.8% versus 55/64, 85.9%, respectively; difference of 3.9%, 95% CI -7.3 to 13.4, P=0.701). Frozen embryo transfer yielded no significant differences between PGD and non-PGD groups in implantation rates (12/46, 26.1% versus 9/47, 19.1%, respectively; difference of 6.9%, 95% CI -9.7 to 22.2, P=0.581), clinical pregnancy rates (11/18, 61.1% versus 9/18, 50%, respectively; difference of 11.1%, 95% CI -20.6 to 40.6, P=0.737) or live birth rates (9/18, 50% versus 6/18, 33.3%, respectively; difference of 16.7%, 95% CI -15.1 to 44.8, P=0.499). These results showed that, in PGD cycles, embryos can be vitrified effectively on day 4 after biopsy on day 3.

Preimplantation genetic diagnosis in Saudi Arabia: parents' experience and attitudes

Preimplantation genetic diagnosis (PGD) has been proposed as an alternative to prenatal diagnosis (PND). This study compares the attitudes towards PGD of four groups of parents in Saudi Arabia: two groups at genetic risk for different conditions but with no experience of PGD procedures and two groups who had experience, either of PGD or of in vitro fertilisation (IVF) for infertility. One hundred and eighty four participants attending the King Faisal Specialist Hospital and Research Centre (KFSH&RC) in Riyadh were interviewed using a semi-structured questionnaire: 49 had children affected by a haemoglobin disorder, 48 had children with non-syndromic deafness, 37 were attending the PGD service and 50 were attending IVF services for infertility. Opinions in the two genetic groups were very similar: families were enthusiastic about PGD and relatively unconcerned about its technical limitations or the desirability of a confirmatory PND. The technical limitations of PGD and the moral status of embryos were of greatest concern to the PGD group. Waiting for the pregnancy result was the most commonly mentioned concern in the PGD and IVF groups. PGD might be considered for a range of conditions in Saudi Arabia. However, it is not an easy option, and couples must be selected and counselled appropriately.

O-138: Preimplantation genetic diagnosis (PGD) is indicated for recurrent miscarriage even in cycles producing five or fewer embryos

PGD is indicated for patients suffering from infertility or recurrent miscarriage when sufficient numbers of embryos are available. We have studied PGD in groups of patients with low egg yields and varying etiologies. Here we focus on patients with recurrent miscarriages. Previous studies have shown that couples with a history of idiopathic recurrent pregnancy loss (RPL) have a high incidence of chromosomally abnormal embryos. PGD for this indication has proven to significantly reduce the risk of miscarriage while producing high pregnancy rates. However, PGD is a selection tool, and when an IVF cycle produces as many or fewer embryos as the number expected to be replaced, the selection power of PGD is diminished; the same number of normal embryos may be replaced with or without PGD. The objective of this study was to determine whether PGD is indicated in patients producing 5 or fewer embryos. This study is a retrospective analysis of PGD patients with recurrent pregnancy loss in an IVF program. Patients with two or more consecutive miscarriages scheduled for PGD were included in the study. Patients with 5 or fewer embryos that were suitable for biopsy on Day 3 were asked whether or not they wished to continue with PGD analysis. Embryos were determined to be suitable for biopsy if there were at least 4 cells, with fewer than 30% fragmentation. Those who cancelled PGD were considered the “control” group, and those who decided to proceed were the ”test“ group. For the test group, single-cell biopsy was performed on Day 3, followed by fixation and PGD using FISH with probes for 9 chromosomes. Embryo replacement occurred on Day 4 for the test group. Replacement was performed on Day 3 for patients in the control group. Implantation and pregnancy rates were determined by fetal cardiac activity/number of embryos transferred or the number of retrievals. A total of 70 RPL couples produced 5 or fewer embryos that were suitable for biopsy. Of those, 47 decided to continue with the PGD procedure. The implantation and delivery rates were significantly higher in the group that received PGD (p<0.05; see Table 1). Although the spontaneous abortion rate was lower in the PGD group (4/22, 18.1% vs. 3/6, 50%), this difference was not statistically significant.Tabled 1 Even when 5 or fewer embryos were produced, the utilization of PGD was effective in increasing the delivery rate. PGD is therefore indicated for patients with idiopathic RPL irrespective of the number of embryos produced in the cycle. This finding may not be applicable to other poor responder patient groups; the effect of embryo number on other types of poor responders is under active investigation.

Preimplantation genetic diagnosis significantly reduces pregnancy loss in infertile couples: a multicenter study

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.

Outcome of preimplantation genetic diagnosis in frozen-thawed embryos

Cryopreservation of embryos is widely applied in ART. And it is also useful for efficient preimplantation genetic diagnosis (PGD) in cases with supernumerary embryos or with collected embryos through several cycles in poor responders. The aim of this study is to evaluate the feasibility of FISH or PCR in the blastomeres biopsied from frozen-thawed embryos and the outcome of PGD, and to determine whether frozen- thawing process affect the embryo development after blastomere biopsy. Retrospective clinical study. In 86 patients, 319 PGD cycles were performed between Jan. 2000 and Dec. 2003. Patients were divided into 2 groups: thawed PGD group − PGD cycle was performed in frozen-thawed embryos (33 patients, 40 cycles, age = 34.2±4.7yrs. (mean±SD)), fresh PGD group − PGD cycle was performed in fresh embryos (patients=53, cycles=279, mean age = 31.8±4.3yrs.). In 20 cycles, supernumerary embryos were frozen and thawed, and in 19 cycles, embryos were collected through several cycles in poor responders and then thawed altogether. PGD was performed for translocation carriers or aneuploidy screening and some single gene diseases were included. Ovarian stimulation was done using GnRH agonist/FSH long protocol or clomifen citrate/GnRH antagonist protocol in poor responders. Oocytes were inseminated by ICSI and the fertilized embryos were cryopreserved at PN stage or cleaving embryo stage. In thawed embryo transfer cycles, estradiol was administrated from day 2 of menstrual cycle and progesterone injection was started from 1 day before 2PN thawing. The cryopreserved embryos were thawed and blastomeres were biopsied in survived embryos developed to 6–10 cell stage. PGD was performed by using FISH or PCR and the embryos were replaced 3 days after PN thawing. The survival rate of the thawed embryos, the rate of successful diagnosis for FISH or PCR, embryo development and pregnancy rate were compared between thawed and fresh PGD cycles. The survival rate of thawed embryos was 71.2±29.8% (mean±SD). The FISH or PCR analysis was successful in 88.1±22.0 % in thawed PGD group and 95.2±10.3% in fresh PGD group (P>0.05). The proportion of transferable embryos in thawed PGD group was similar to fresh PGD group (21.6±19.7% vs. 27.4±18.8%; P>0.05). The rate of embryos developed cleavage after biopsy was also similar in both groups (62.0±26.5% vs. 66.4±26.1%; P>0.05). The clinical pregnancy rate per transfer was 11.4 % (4/35) in thawed PGD group and 21.3% (57/267) in fresh PGD group. Although it was not statistically significant, the pregnancy rate tends to be lower in thawed PGD group. Our data suggest that blastomere biopsy and analysis with FISH or PCR is feasible in frozen-thawed embryos if the embryos survive well. The embryo development was not affected by biopsy in thawed embryos, but the pregnancy rate was lower in thawed PGD cycles. Therefore PGD in thawed embryos could be applied usefully in cycles with supernumerary embryos or collected cyropreserved embryos, and optimization of freezing-thawing condition might be important.

Do patients who undergo Preimplantation Genetic Diagnosis have higher pregnancy rates and should fewer embryos be transferred?

Do patients who undergo Preimplantation Genetic Diagnosis have higher pregnancy rates and should fewer embryos be transferred?

Einschätzung der Eizellspende und der Leihmutterschaft - Abhängigkeit von eigenen Erfahrungen

The aim of the study was to find out the attitudes of different groups towards technologies which are prohibited by the German Embryo Protection Law. We evaluated by using a questionnaire, in how far oocyte donation and surrogate motherhood were accepted in Germany in different groups of the population. 34 infertile patients, 74 patients who asked for preimplantation genetic diagnosis (PID), 29 women, who had finished family planning, and 59 medical students were asked for their opinion in a standardized and closed questionnaire. Overall the different groups, especially medical students, were very critical towards oocyte donation and surrogate motherhood. However, to help another couple to conceive a child 68.6 % of PID patients, 62.1 % of infertile patients, 43.2 % of women with finished family planning, and 47.6 % of students were prepared to donate oocytes. On the other hand, only 40.9 %, 40.0 %, 25.9 %, and 13.2 % of PID patients, infertile patients, women with finished family planning and medical students, respectively, would accept oocyte donation for themselves. Regarding surrogate motherhood, the PID group and students were strictly against the idea to be a surrogate mother by themselves. Members of the infertile group as well as those women with finished family planning were more indifferent regarding this question. Students and women with finished family planning, however, would prefer adoption, whilst PID- and infertility groups are more indifferent. Men are more positive towards both techniques as compared to women. As compared to known data from other countries, the acceptance of oocyte donation in all groups and surrogate motherhood is comparable to other European countries, when only PID patients and infertile patients are respected. The other two groups are more critical against surrogate motherhood. To conclude, it becomes apparent how opinions regarding these techniques are influenced by the own situation and experiences.

Effect of PGD on implantation and ongoing pregnancy rates in cases with predominantly macrocephalic spermatozoa

Although its occurrence is rare, the presence of large headed or macrocephalic spermatozoa and increased chromosomal abnormality has recently been reported by several groups. Moreover, when intracytoplasmic sperm injection (ICSI) was performed with samples containing macrocephalic spermatozoa, lower fertilization and implantation rates result in poor clinical outcome. In order to evaluate the impact of preimplantation genetic diagnosis (PGD) on implantation and ongoing pregnancy rates in these couples, the results of 23 PGD cycles were compared with non-PGD cycles ( n = 60) as well as cycles with absolute teratozoospermia (having zero normal morphology) with ( n = 14) or without PGD ( n = 66). Out of 82 embryos biopsied in the macrocephalic sperm group, abnormalities were detected in 46.4% of the embryos analysed. Most of the abnormalities were trisomies (37.0%) and complex aneuploidies (51.9%). A 33.3% pregnancy rate was achieved by selectively transferring euploid embryos after PGD with the statistically higher implantation rate of 25.0% compared with non-PGD cycles (IR: 12.3%, P < 0.01). Moreover, only one missed abortion (14.3%) was observed in the PGD group, whereas seven of the 15 pregnancies resulted in abortion in the non-PGD group (46.7%). Preliminary results indicate that patients should be counselled for increased chromosomal abnormality and a possible beneficial effect of eliminating chromosomally abnormal embryos with PGD on abortion rates.

Preimplantation genetic diagnosis as both a therapeutic and diagnostic tool in assisted reproductive technology

Preimplantation genetic diagnosis as both a therapeutic and diagnostic tool in assisted reproductive technology

Improved implantation after preimplantation genetic diagnosis of aneuploidy

The objective of this study was to assess the improvement in implantation rates after preimplantation genetic diagnosis (PGD) of numerical abnormalities for the sole indication of advanced maternal age when compared with a control group. Each PGD patient was matched to a control patient according to several parameters prior to obtaining pregnancy results. The diagnosis was based on the analysis of chromosomes X, Y, 13, 15, 16, 18, 21 and 22 plus a ninth probe (1, 7, 14 or 17) on a single cell per embryo. The results were also analysed in relation to the previous number of IVF cycles and the number of dipronucleated zygotes obtained, when replacing presumptively chromosomally normal embryos on day 4 of development. It was found that women of advanced reproductive age (average age 40 years) had a higher implantation rate (18%) than their matched controls treated with standard IVF (11%) ( P < 0.05). This increase was not observed in patients with two or more previous IVF cycles or patients with fewer than eight zygotes. Patients with eight or more 2PN zygotes and one or no previous cycles showed the greatest improvement in implantation rate, from 8.8% in controls to 19.2% in the PGD group (average age 40 years) ( P < 0.025).

Preimplantation genetic diagnosis (PGD) as both a diagnostic and therapeutic tool in assisted reproductive technology (ART)

Objective: To evaluate the role of PGD as both a diagnostic and therapeutic tool in ART. Design: An IRB approved, multicenter, randomized prospective study was initiated with 60 patients. Three high-risk groups were identified: 1. Group I: Women with recurrent pregnancy loss (RPL) 2. Group II: Women with advanced maternal age (AMA) 3. Group III: Women who have failed >2 IVF cycles (FC) Materials/Methods: All patients entered into the study met all inclusion criteria and were then randomized into PGD or control in one of the 3 groups. All stimulation protocols utilized Follistim/Antagon and Pregnyl. Oocyte recovery was performed by ultrasound guided transvaginal approach. On day #3 post oocyte recovery all 6–8 cell embryos in the PGD group underwent blastomere biopsy and fixation. Slides were then federal expressed to St. Barnabas Hospital in Livingston, New Jersey. FISH was performed utilizing the following probes: x, y, 13, 15, 16, 17, 18, 21, 22. On day #5 post oocyte recovery results were obtained and embryo transfer of no more than 3-chromosomally normal embryos was performed. Medications including corticosteroids, antibiotics, low dose aspirin (80–81mg) and progestational supplementation were utilized. Serum B-HCG levels were obtained 12 days post embryo transfer. Results: See table TableResultsRPLAMAFCTOTAL# of patients enrolled11161441# of patients PGD77620# of embryos biopsied33411892# of abnormal embryos23/33 (69.7%)22/41 (53.6%)15/18 (83.3%)60/92 (65.2%)# of no transfer2/7 (28.6%)1/7 (14.3%)3/6 (50%)6/20 (30%)# of pregnancies PGD5/7 (71.4%)3/7 (42.8%)08/20 (40%)# of pregnancies control2/4 (50%)3/9 (33%)05/21 (23.8%) Open table in a new tab Conclusions: A number of preliminary comments can be made: 1. PGD does appear to be beneficial in the RPL group. 2. PGD does appear to confirm that aneuploidy is a common cause of RPL. 3. PGD does not appear to be beneficial in either the AMA or FC groups. 4. In view of the large number of abnormal embryos in each group, couples may consider alternative options earlier such as donor oocytes or donor embryos. Supported by: Education Grant funded by Organon Inc. West Orange, New Jersey.