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 ◽  
...  

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

2007 ◽  
Vol 88 ◽  
pp. S85-S86 ◽  
Author(s):  
S. Munne ◽  
J. Garrisi ◽  
F. Barnes ◽  
L. Werlin ◽  
W. Schoolcraft ◽  
...  

2021 ◽  
Vol 10 (17) ◽  
pp. 3895
Author(s):  
Wei-Hui Shi ◽  
Zi-Ru Jiang ◽  
Zhi-Yang Zhou ◽  
Mu-Jin Ye ◽  
Ning-Xin Qin ◽  
...  

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.


2018 ◽  
Vol 26 (6) ◽  
pp. 806-811 ◽  
Author(s):  
Samer Tannus ◽  
Yoni Cohen ◽  
Sara Henderson ◽  
Weon-Young Son ◽  
Togas Tulandi

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.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Vaiarelli ◽  
D Cimadomo ◽  
S Colamaria ◽  
M Giuliani ◽  
C Argento ◽  
...  

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


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
R. Sainte-Rose ◽  
C. Petit ◽  
L. Dijols ◽  
C. Frapsauce ◽  
F. Guerif

AbstractThe aim of this study was to determine the effectiveness of extended embryo culture in advanced maternal age (AMA) patients (37–43 years). In this retrospective analysis, 21,301 normally fertilized zygotes from 4952 couples were cultured until the blastocyst stage. Blastocyst development, including kinetics and morphology, transfer rate, implantation and live birth rates, were measured. In AMA patients, the blastocyst rate was significantly decreased as compared to that in younger women. On day 5, blastocysts underwent growth retardation in AMA patients, which was highlighted by a decreased rate of full/expanded blastocysts. Organization of the cells (trophectoderm and inner cell mass) was unaffected by age. However, in AMA patients, a ‘good’ morphology blastocyst had a decreased probability to implant compared with an ‘average’ morphology blastocyst in younger women. While the rates of blastocyst transfer and useful blastocysts were similar to younger patients, in AMA patients, both implantation and live birth rates were significantly reduced. Our results support the idea that extended embryo culture is not harmful for AMA patients. However, embryo selection allowed by such culture is not powerful enough to avoid chromosomal abnormalities in the developed blastocysts and therefore cannot compensate for the effect of a woman’s age.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
H Yoshihara ◽  
M Sugiura-Ogasawara ◽  
T Kitaori ◽  
S Goto

Abstract Study question Can antinuclear antibody (ANA) affect the subsequent live birth rate in patients with recurrent pregnancy loss (RPL) who have no antiphospholipid antibodies (aPLs)? Summary answer ANA did not affect the pregnancy prognosis of RPL women. What is known already The prevalence of ANA is well-known to be higher in RPL patients. Our previous study found no difference in the live birth rates of ANA-positive and -negative patients who had no aPLs. Higher miscarriage rates were also reported in ANA-positive patients compared to ANA-negative patients with RPL. The RPL guidelines of the ESHRE state that “ANA testing can be considered for explanatory purposes.” However, there have been a limited number of studies on this issue and sample sizes have been small, and the impact of ANA on the pregnancy prognosis is unclear. Study design, size, duration An observational cohort study was conducted at Nagoya City University Hospital between 2006 and 2019. The study included 1,108 patients with a history of 2 or more pregnancy losses. Participants/materials, setting, methods 4D-Ultrasound, hysterosalpingography, chromosome analysis for both partners, aPLs and blood tests for ANA and diabetes mellitus were performed before a subsequent pregnancy. ANAs were measured by indirect immunofluorescence. The cutoff dilution used was 1:40. In addition, patients were classified according to the ANA pattern on immunofluorescence staining. Live birth rates were compared between ANA-positive and ANA-negative patients after excluding patients with antiphospholipid syndrome, an abnormal chromosome in either partner and a uterine anomaly. Main results and the role of chance The 994 patients were analyzed after excluding 40 with a uterine anomaly, 43 with a chromosome abnormality in either partner and 32 with APS. The rate of ANA-positive patients was 39.2 % (390/994) when the 1: 40 dilution result was positive. With a 1:160 dilution, the rate of ANA-positive patients was 3.62 % (36/994). The live birth rate was calculated for 798 patients, excluding 196 patients with unexplained RPL who had been treated with any medication. With the use of the 1 40 dilution, the subsequent live birth rates were 71.34 % (219/307) for the ANA-positive group and 70.67 % (347/491) for the ANA-negative group (OR, 95%CI; 0.968, 0.707-1.326). After excluding miscarriages with embryonic aneuploidy, chemical pregnancies and ectopic pregnancies, live birth rates were 92.41 % (219/237) for the ANA-positive group and 92.04 % (347/377) for the ANA-negative group (0.951, 0.517-1.747). Using the 1:160 dilution, the subsequent live birth rates were 84.62 % (22/26) for the ANA-positive group, and 70.47 % (544/772) for the ANA-negative group (0.434, 0.148-1.273). Subgroup analyses were performed for each pattern on immunofluorescence staining, but there was no significant difference in the live birth rate between the two groups. Limitations, reasons for caution The effectiveness of immunotherapies could not be evaluated. However, the results of this study suggest that it is not necessary. Wider implications of the findings The measurement of ANA might not be necessary for the screening of patients with RPL who have no features of collagen disease. Trial registration number not applicable


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