scholarly journals Different Strategies of Preimplantation Genetic Testing for Aneuploidies in Women of Advanced Maternal Age: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (17) ◽  
pp. 3895
Author(s):  
Wei-Hui Shi ◽  
Zi-Ru Jiang ◽  
Zhi-Yang Zhou ◽  
Mu-Jin Ye ◽  
Ning-Xin Qin ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Live Birth ◽  
Maternal Age ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Advanced Maternal Age ◽  
Controlled Trials ◽  
Preimplantation Genetic Testing ◽  
Randomized Controlled ◽  
Blastocyst Biopsy

Background: Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in women of advanced maternal age (AMA). However, the effectiveness remains controversial. Method: We conducted a comprehensive literature review comparing outcomes of IVF with or without PGT-A in women of AMA in PubMed, Embase, and the Cochrane Central Register of Controlled Trials in January 2021. All included trials met the criteria that constituted a randomized controlled trial for PGT-A involving women of AMA (≥35 years). Reviews, conference abstracts, and observational studies were excluded. The primary outcome was the live birth rate in included random control trials (RCTs). Results: Nine randomized controlled trials met our inclusion criteria. For techniques of genetic analysis, three trials (270 events) performed with comprehensive chromosomal screening showed that the live birth rate was significantly higher in the women randomized to IVF/ICSI with PGT-A (RR = 1.30, 95% CI 1.03–1.65), which was not observed in six trials used with FISH as well as all nine trials. For different stages of embryo biopsy, only the subgroup of blastocyst biopsy showed a higher live birth rate in women with PGT-A (RR = 1.36, 95% CI 1.04–1.79). Conclusion: The application of comprehensive chromosome screening showed a beneficial effect of PGT-A in women of AMA compared with FISH. Moreover, blastocyst biopsy seemed to be associated with a better outcome than polar body biopsy and cleavage-stage biopsy.

scholarly journals Analysis of IVF live birth outcomes with and without preimplantation genetic testing for aneuploidy (PGT-A): UK Human Fertilisation and Embryology Authority data collection 2016–2018

2021 ◽  
Author(s):  
Kathryn D. Sanders ◽  
Giuseppe Silvestri ◽  
Tony Gordon ◽  
Darren K. Griffin
Keyword(s):  
Genetic Testing ◽  
Data Collection ◽  
Live Birth ◽  
Maternal Age ◽  
Birth Rate ◽  
Treatment Cycle ◽  
Cohort Analysis ◽  
Live Birth Rate ◽  
Traffic Light ◽  
Preimplantation Genetic Testing

Abstract Purpose To examine the live birth and other outcomes reported with and without preimplantation genetic testing for aneuploidy (PGT-A) in the United Kingdom (UK) Human Embryology and Fertilization Authority (HFEA) data collection. Methods A retrospective cohort analysis was conducted following freedom of information (FoI) requests to the HFEA for the PGT-A and non-PGT-A cycle outcomes for 2016–2018. Statistical analysis of differences between PGT-A and non-PGT-A cycles was performed. Other than grouping by maternal age, no further confounders were controlled for; fresh and frozen transfers were included. Results Outcomes collected between 2016 and 2018 included total number of cycles, cycles with no embryo transfer, total number of embryos transferred, live birth rate (LBR) per embryo transferred and live birth rate per treatment cycle. Data was available for 2464 PGT-A out of a total 190,010 cycles. LBR per embryo transferred and LBR per treatment cycle (including cycles with no transfer) were significantly higher for all PGT-A vs non-PGT-A age groups (including under 35), with nearly all single embryo transfers (SET) after PGT-A (significantly more in non-PGT-A) and a reduced number of transfers per live birth particularly for cycles with maternal age over 40 years. Conclusion The retrospective study provides strong evidence for the benefits of PGT-A in terms of live births per embryo transferred and per cycle started but is limited in terms of matching PGT-A and non-PGT-A cohorts (e.g. in future studies, other confounders could be controlled for). This data challenges the HFEA “red traffic light” guidance that states there is “no evidence that PGT-A is effective or safe” and hence suggests the statement be revisited in the light of this and other new data.

Reduced spontaneous abortion and increased live birth rate after PGD for advanced maternal age

2007 ◽  
Vol 88 ◽  
pp. S85-S86 ◽  
Author(s):  
S. Munne ◽  
J. Garrisi ◽  
F. Barnes ◽  
L. Werlin ◽  
W. Schoolcraft ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Live Birth ◽  
Maternal Age ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Advanced Maternal Age

P–093 The use of donor sperm improves post-ICSI live birth rates in advanced maternal age women

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M R Mignin. Renzini ◽  
M Da. Canto ◽  
M C Guglielmo ◽  
D Garcia ◽  
E. D Ponti ◽  
...  
Keyword(s):  
Live Birth ◽  
Maternal Age ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Advanced Maternal Age ◽  
Sperm Donation ◽  
Donor Sperm ◽  
Live Birth Rates ◽  
Oocyte Yield ◽  
Icsi Outcomes

Abstract Study question Can the use of donor sperm improve post-ICSI live birth rate in advanced maternal age (AMA) patients? Summary answer The use of donor sperm increases post-ICSI live birth rate while substantially reducing abortion occurrence in AMA patients. What is known already Oocyte DNA repair capacity decreases with maternal age, when sperm DNA integrity is particularly important to avoid the transfer of gene truncations and de novo mutations to the zygote. Optimal DNA repair activity in the zygote requires paternal inheritance of 8-oxoguanine DNA glycosylase (OGG1), a rate-limiting enzyme in the base excision repair pathway. However, the involvement of paternal aging and sperm quality in the severe drop in fertility observed in AMA patients has not been addressed. While strategies to mitigate the impact of AMA on fertility have exclusively targeted oocyte quality, the sperm contribution in this scenario remains somehow neglected. Study design, size, duration Retrospective, multicentric, international study including 755 first ICSI cycles with patients’ own oocytes achieving a fresh ET between 2015 and 2019, 337 of which using normozoospermic partner semen and 418 using donor sperm. The association of sperm origin (partner vs. donor) with live birth was assessed by univariate/multivariate analysis in non-AMA (<37 years, n = 278) and AMA (≥37 years, n = 477) patients. ICSI outcomes were compared between partner and donor sperm in non-AMA and AMA patients. Participants/materials, setting, methods The study was conducted in 3 fertility clinics including 755 Caucasian patients aged 24 to 42 years. Univariate/multivariate analyses were performed to test the association of sperm origin with live birth; infertility factor, maternal age, oocyte yield and number of embryos transferred were included in the model as confounding variables. In addition, ICSI outcomes were compared between donor and partner sperm groups with the Chi-square (percentages) or with the Wilcoxon sum rank (continuous variables) tests. Main results and the role of chance The multivariate analysis revealed that the use of donor sperm was positively and independently associated with live birth occurrence in AMA [1.82 OR (1.08–3.07) 95% IC; p = 0.024], but not in non-AMA patients [1.53 (0.94–2.51); p = 0.090]. Maternal age [0.75 (0.64–0.87); p < 0.001], number of MII oocytes recovered [1.14 (1.05–1.23); p = 0.001] and number of embryos transferred [1.90 (1.27–2.86); p = 0.002] were also independently associated with live birth in AMA patients. Live birth and delivery rates were 70–75% higher, while miscarriage rate was less than half in donor sperm compared to partner sperm AMA cycles (LBR: 25.4% vs. 14.5%, p = 0.003; DR: 22.5% vs. 13.5%, p = 0.008; MR: 18.0% vs. 39.5%; p = 0.009). Implantation (17.4% vs. 13.5%; p = 0.075) and clinical pregnancy rates (27.5% vs. 22.3%; p = 0.121) did not significantly differ between sperm donation and partner sperm AMA cycles. Male age was substantially lower (23.6 ± 5.2 vs. 41.4 ± 5.0; p < 0.0001) and oocyte yield was higher (5.1 ± 3.1 vs. 4.3 ± 2.6; p < 0.0001) in sperm donation compared to partner sperm AMA cycles, while maternal age did not vary (39.8 ± 1.6 vs. 39.6 ± 1.7; p = 0.348). Limitations, reasons for caution This study is limited by its retrospective nature and by differences in patients’ profiles between sperm donation and homologous cycles, although this variation has been controlled for in the statistical analysis. Wider implications of the findings: The findings suggest that donor sperm can improve live birth rates by drastically reducing miscarriage occurrence in AMA patients. Therefore, the present results may influence AMA treatment decisions and, above all, contribute for AMA patients to achieve a healthy birth. Trial registration number Not applicable

The Effect of Assisted Hatching on Live Birth Rate Following Fresh Embryo Transfer in Advanced Maternal Age

2018 ◽  
Vol 26 (6) ◽  
pp. 806-811 ◽  
Author(s):  
Samer Tannus ◽  
Yoni Cohen ◽  
Sara Henderson ◽  
Weon-Young Son ◽  
Togas Tulandi
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Live Birth ◽  
Maternal Age ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Advanced Maternal Age ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Assisted Hatching

Objective: Assisted hatching (AH) was introduced 3 decades ago as an adjunct method to in vitro fertilization (IVF) and embryo transfer (ET) to improve embryo implantation rate. Limited data are available on the effect of AH on live birth rate (LBR) in advanced maternal age. The objective of this study is to investigate the effect of AH on LBR in women aged 40 years and older. Materials and Methods: A retrospective study conducted at a single academic reproductive center. Women aged ≥40 years, who were undergoing their first IVF cycle were included. Laser-assisted hatching was the method used for AH and single or double embryos were transferred. Embryo transfer was performed at the cleavage or blastocyst stage. Separate analysis was performed on each ET stage. Live birth rate was the primary outcome. Results: A total of 892 patients were included. Of these, 681 women underwent cleavage ET and 211 underwent blastocyst ET. The clinical pregnancy rate in the entire group was 15.3% and the LBR was 10.2%. Baseline and cycle parameters between the AH group and the control group were comparable. Assisted hatching in the cleavage stage was associated with lower clinical pregnancy rate (odds ratio [OR], 0.52; confidence interval [CI], 0.31-0.86; P = .012) and lower LBR (OR, 0.36; CI, 0.19-0.68; P = .001). Assisted hatching did not have any effect on outcomes in blastocyst ET. Conclusion: Assisted hatching does not improve the reproductive outcomes in advanced maternal age. Performing routine AH for the sole indication of advanced maternal age is not clinically justified.

P–606 A second stimulation in the same ovarian cycle rescues advanced-maternal-age patients obtaining ≤ 3 blastocysts after the conventional approach by preventing treatment-discontinuation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Vaiarelli ◽  
D Cimadomo ◽  
S Colamaria ◽  
M Giuliani ◽  
C Argento ◽  
...  
Keyword(s):  
Live Birth ◽  
Maternal Age ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Advanced Maternal Age ◽  
Ovarian Cycle ◽  
Treatment Discontinuation ◽  
Control Group ◽  
Cumulative Live Birth Rate ◽  
Cumulative Live Birth

Abstract Study question Is double stimulation in the same ovarian cycle (DuoStim) a valuable strategy to rescue advanced-maternal-age patients obtaining ≤ 3 blastocysts for chromosomal-testing after conventional stimulation? Summary answer DuoStim is effective to prevent treatment discontinuation thereby increasing the 1-year cumulative-live-birth-rate among advanced-maternal-age patients obtaining 0–3 blastocysts after a first conventional stimulation. What is known already Folliculogenesis is characterized by continuous waves of follicular growth. DuoStim approach exploits these dynamics to conduct two stimulations in a single ovarian cycle and improve the prognosis of advanced-maternal-age and/or reduced-ovarian-reserve women. Independent groups worldwide successfully adopted DuoStim with various regimens reporting similar oocyte/embryo competence after both stimulations. Recently, we have demonstrated the fruitful adoption of DuoStim in patients fulfilling the Bologna criteria, especially because of the prevention of treatment discontinuation. Here we aimed at investigating whether DuoStim can be adopted to rescue poor prognosis patients obtaining 0–3 blastocysts after the conventional approach. Study design, size, duration Proof-of-concept matched case-control study. All patients obtaining 0–3 blastocysts after conventional-stimulation between 2015–2018 were proposed DuoStim. The 143 couples who accepted were matched for maternal age, sperm factor, cumulus-oocyte-complexes and blastocysts obtained after the first stimulation to 143 couples who did not. The primary outcome was the 1-year cumulative-live-birth-rate. If not delivering, the control group had 1 year to undergo a second attempt with conventional-stimulation. All treatments were concluded (live-birth achieved or no euploid left). Participants/materials, setting, methods Only GnRH-antagonist with recombinant-gonadotrophins and agonist trigger stimulation protocols were adopted. All cycles entailed ICSI with ejaculated sperm, blastocyst culture, trophectoderm biopsy, comprehensive-chromosome-testing and vitrified-warmed euploid single-embryo-transfer(s). Cumulative-live-birth-rate was calculated per patient considering both stimulations in the same ovarian cycle (DuoStim group) or up to two stimulations in 1 year (control group). Treatment discontinuation rate in the control group was calculated as patients who did not return for a second stimulation among non-pregnant ones. Main results and the role of chance Among the 286 couples included (41.0±2.9yr;4.9±3.1 cumulus-oocytes-complexes and 0.8±0.9 blastocysts), 126 (63 per group), 98 (49 per group), 52 (26 per group) and 10 (5 per group) obtained 0,1,2 and 3 blastocysts after the first stimulation, respectively. The cumulative-live-birth-rate was 9% in the control group after the first attempt (N = 13/143). Among the 130 non-pregnant patients, only 12 returned within 1-year (165±95days later;discontinuation rate=118/130,91%), and 3 delivered. Thus, the cumulative-live-birth-rate from two stimulations in 1-year was 11% (N = 16/143). In the DuoStim group, the cumulative-live-birth-rate was 24% (N = 35/143; Fisher’s-exact-test< 0.01,power=80%). The odds-ratio of delivering in the DuoStim versus the control group adjusted for all matching criteria was 3.3,95%CI:1.6–7.0,p<0.01. This difference (0%,22%,15% and 20% in the control versus 10%,31%,46% and 40% in the DuoStim group among patients obtaining 0,1,2 and 3 blastocysts at the first stimulation, respectively) is mainly due to treatment discontinuation in the control group (98%,65%,77% and 80% among patients obtaining 0,1,2 and 3 blastocysts at the first stimulation, respectively) and the further increased maternal age at the time of second retrieval (∼6 months). Notably, 2 patients delivered 2 live-births after DuoStim (none in the control) and 14 patients with a live-birth have euploid blastocysts left (2 in the control). Limitations, reasons for caution Randomized-controlled-trials and cost-effectiveness analyses are desirable to confirm these data. Moreover, 75% of the patients included were >39yr and 44% obtained no blastocyst after the first stimulation. Therefore future studies among younger women and/or more women obtaining ≥1 blastocyst are advisable to set reasonable cut-off values to apply this strategy. Wider implications of the findings: A second stimulation in the same ovarian cycle might be envisioned as a rescue strategy for poor IVF outcomes after a first stimulation, so to prevent treatment discontinuation and increase the cumulative-live-birth-rate. This is feasible since 6–7 days span the first and the second stimulation in the DuoStim protocol. Trial registration number none

scholarly journals CUMULATIVE LIVE BIRTH RATE IN WOMEN 37 YEARS OF AGE OR LESS WHO UTILIZE PREIMPLANTATION GENETIC TESTING-ANEUPLOIDY (PGT-A) VERSUS UNTESTED EMBRYOS

2020 ◽  
Vol 114 (3) ◽  
pp. e417-e418
Author(s):  
Rachel B. Mejia ◽  
Karen M. Summers ◽  
Abigail C. Mancuso ◽  
Emily A. Capper ◽  
Patrick Ten Eyck ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Live Birth ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Cumulative Live Birth Rate ◽  
Preimplantation Genetic Testing ◽  
Cumulative Live Birth

scholarly journals The Pregnancy Outcome of Mosaic Embryo Transfer: A Prospective Multicenter Study and Meta-Analysis

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 973
Author(s):  
Ying Xin Zhang ◽  
Jang Jih Chen ◽  
Sunanta Nabu ◽  
Queenie Sum Yee Yeung ◽  
Ying Li ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Pregnancy Outcome ◽  
Live Birth ◽  
Birth Rate ◽  
Meta Analysis ◽  
Live Birth Rate ◽  
Miscarriage Rate ◽  
Prenatal Genetic Testing ◽  
Preimplantation Genetic Testing ◽  
Mosaic Embryo

Chromosomal mosaicism is at high occurrence in early developmental-stage embryos, but much lower in those at prenatal stage. Recent studies provided evidence on the viability of mosaic embryos by reporting pregnancy outcomes. Expanded research is warranted to evaluate its clinical significance. This is a multi-center prospective cohort study on 137 mosaic, 476 euploid and 835 non-preimplantation genetic testing (non-PGT) embryos from three in vitro fertilization (IVF) providers of three countries in Asia, applying the same preimplantation genetic testing for aneuploidies (PGT-A) reporting criteria. Mosaic embryo transfers (METs) resulted in a significantly lower clinical pregnancy rate (40.1% versus 59.0% versus 48.4%), lower ongoing/live birth rate (27.1% versus 47.0% versus 35.1%) and higher miscarriage rate (33.3% versus 20.5% versus 27.4%) than euploid and non-PGT transfers, respectively. Pregnancy losses after METs were different between embryos carrying numerical and segmental chromosomal abnormalities (p = 0.04). Our meta-analysis concluded that METs gave rise to pregnancies but were associated with a reduced ongoing/live birth rate and a higher miscarriage rate. All 37 MET live births were confirmed viable, among which 8 completed prenatal genetic testing with normal results. Longitudinal investigation on one MET pregnancy evidenced the aneuploidy depletion hypothesis. This is the first multi-center prospective study reporting a full MET pregnancy outcome with complementary information from prenatal genetic testing as compared to euploid and non-PGT cohorts.

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